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Dissertations / Theses on the topic 'Cardiovascular system – Diseases – Treatment'

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1

Cho, Jinsoo. "Velocity-based cardiac segmentation and motion-tracking." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180106/unrestricted/cho%5Fjinsoo%5F200312%5Fphd.pdf.

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2

Lam, Lap-fung, and 林立峰. "Flow cytometric analysis of intra-platelet VASP for evaluation of clopidogrel resistance in ischemic heart disease patients undergoingpercutaneous coronary intervention." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2012. http://hub.hku.hk/bib/B48421200.

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Ischemic heart disease (IHD) is the most common cause of death around the world. The underlying cause of IHD is myocardial ischemia as a result of progressive narrowing of coronary arteries due to atherosclerosis with potential thrombotic complications mediated by platelets. In addition to the role in hemostasis, platelets are increasingly recognized as an important mediator in this atherothrombotic disease. Basic management of IHD lies on medical therapy and coronary revascularization procedures. Percutaneous coronary intervention (PCI) is a commonly used revascularization procedure in the treatment of IHD especially for relief and reduction of symptoms. On the other hand, antiplatelet therapy is often administrated to patients undergoing PCI in an attempt to prevent major adverse cardiac events (MACE) following the procedures. However not all patients respond to the same degree of the antiplatelet therapy and some still develop MACE or stent thrombosis in the presence of the treatment with antiplatelet drugs. Recently a flow cytometric-based assay has been developed to monitor the effect of the antiplatelet drug, particularly the P2Y12 receptor antagonist, in patients treated with this kind of drug. This assay measures the activity of platelets as platelet reactivity index (PRI) based on the phosphorylation state of an intracellular platelet protein called vasodilator stimulated phosphoprotein (VASP). The measured value of PRI is inversely related to the response of patient to the antiplatelet drug. In this study, the response of patients to the P2Y12 receptor antagonist Clopidogrel was investigated following PCI. The PRI of patients was found to be significantly lower than normal subjects without taking this drug, indicating the therapeutic effect of this drug on the patients. However nearly one-third of patients (17 out of 59) studied were found to be non-responsive to clopidogrel treatment based on a cut-off established in this study for classifying patients into responders or non-responders. Furthermore, significant difference between the two types of stents used in PCI procedure, namely bare metal stent (BMS) and drug eluting stent (DES), was observed in the study. Patients receiving DES had nearly three times higher percentage of being non-responsive to clopidogrel than the BMS counterpart (45% vs. 16%, p<0.028). This study provides evidence that DES may be implicated in the non-responsiveness or drug resistance of clopidogrel in patient undergoing PCI.
published_or_final_version
Pathology
Master
Master of Medical Sciences
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3

陳潔兒 and Kit-yee Brenda Chan. "Making it a practice: a pre-admission pre-operation education programme for patients on elective CABG." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40720111.

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4

Lai, Wing-hon Kevin, and 黎永漢. "Generation of vasculogenic progenitor cells from human induced pluripotent stem cells for the treatment of cardiovascular diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197112.

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Pluripotent stem cells hold great promise in regenerative medicine. Theoretically, a variety of tissues can be generated from this progeny. The production of tailor-made stem cells for individualized patient treatment is the ultimate goal of stem cell based therapy. Human induced pluripotent stem cells (iPSCs) hold the precious key to success and promote the clinical application of stem cells. By reprogramming somatic cells, pluripotent stem cells can be generated in a patient-specific manner and subsequently differentiated into specific tissue for regeneration. Nonetheless exposure of hiPSCs to animal feeder cells and serum during generation and maintenance imposes a risk of transmitting animal pathogens to human subjects, thus hindering their potential therapeutic application. In addition, the efficacy of iPSC generation is < 1% of total somatic cells used. The first part of the study focused on the development of improved methods to produce a more efficient xenogen-free culture system to produce more clinically compatible iPSCs. Specific tissue or cells derived from stem cells may offer a solution and cell therapy using endothelial cells and their progenitors may be possible in treatment of severe cardiovascular diseases. In theory, endothelial cells can be generated from different sources of progenitor cells although no direct comparison of these various derived endothelial cells (ECs) has been reported. Thus in the second part of the study, the functional and physiological properties of BM, ESC and iPSC-ECs will be evaluated to determine their therapeutic potential in ischemic disease. A mouse hind limb ischemia model was used to assess and monitor neovascularization by the derived ECs. The results can provide further insight to evaluate the possibility of using iPSCEC as the cell source for patient-specific treatment. Use of pluripotent stem cells is a promising approach in therapeutic angiogenesis although numerous hurdles continue to hamper their widespread clinical use. Conditioned medium derived from progenitor cells may be another possible strategy in the treatment of ischemic diseases such that direct cell transplantation is avoided. Conditioned media produced from ex vivo culture of endothelial cells contain a combination of angiogenic factors that can be applied to promote neovascularization in ischemic tissue. Nonetheless the efficacy of this angiogenic application is unknown. The third part of the study focused on the potential application of EC-derived conditioned media in the treatment of ischemic disease using a mouse hind limb ischemia model. Some cardiovascular risk factors such as diabetes might affect endothelial cell function such that autologous application of ECs and their conditioned media is not feasible. A human embryonic stem cell line may offer and alternative means to obtain stable quality ECs and conditioned medium for therapeutic use. In summary, advances in stem cell technology hold great promise for the treatment of cardiovascular disease, further improved by the generation of patient-specific stem cells using iPSC technology. Vascular cells can be generated from different sources of stem cells with similar angiogenic properties and may be used in the treatment of ischemic diseases.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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5

Stewart, Simon. "Optimising therapeutic efficacy in acute and chronic cardiac disease states /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phs851.pdf.

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6

Wang, Kai, and 王凱. "Structure-function and physiological properties of HCN-encoded pacemaker channels." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557273.

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7

Saikus, Christina Elena. "Towards mri-guided cardiovascular interventions." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/44912.

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Imaging guidance may allow minimally invasive alternatives to open surgical exposure and help reduce procedure risk and morbidity. The inherent vascular and soft-tissue contrast of MRI make it an appealing imaging modality to guide cardiovascular interventional procedures. Advances in real-time MRI have made MRI-guided procedures a realistic possibility. The MR environment, however, introduces additional challenges to the development of compatible, conspicuous and safe devices. The overall goal of this work was to enable selected MRI-guided cardiovascular interventional procedures with clearly visible MR devices. In the first part of this work, we developed actively visualized devices for three distinct MRI-guided interventional procedures and techniques to assess their signal performance. We then investigated factors influencing complex device safety in the MR environment and evaluated a technique to better determine and monitor potential device heating. This input contributed to the development of a system to further improve device safety with continual device monitoring and dynamic scanner feedback control. In the final part of this work, we demonstrated the utility of MRI guidance and actively visualized devices to enable traditional and complex cardiovascular access. Together these provide important elements to bring MRI-guided cardiovascular interventional procedures closer to clinical implementation.
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8

Anchala, Raghupathy. "Management of hypertension and prevention of cardiovascular diseases in India : the role of decision support systems." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648283.

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9

Chiu, Sin-ming, and 趙善明. "Absence of Nucks1 enhances mesenchymal stem cells mediated cardiac protection." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/197087.

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Despite major advances in diagnosis and prevention of coronary artery disease (CAD), the development of therapies to regenerate functional cardiomyocytes after myocardial infarction (MI) is very challenging. Studies have demonstrated that bone marrow derived mesenchymal stem cells (BM-MSCs) secrete a panel of growth factors and anti-inflammatory cytokines to activate resident cardiomyocytes and cardiac stem cells in myocardial repair after MI. However, the mechanisms of modulating BM-MSC secretions are not well understood. Recently, molecular candidates in regulating BM-MSCs paracrine secretion to improve cardiac protection have been explored. Amongst the molecular candidates, Nuclear casein kinase and cyclin-dependent kinase substrate 1 (Nucks1) is suggested as a regulatory protein in nuclear factor-kappa B (NF-κB) signaling pathway by interacting with TANK-binding kinase 1 (TBK1). TBK1 is a non-canonical I kappa B (IκB) kinase that can activate the NF-κB transcription factor and its transcriptional response. NF-κB signaling pathway controls many cellular responses such as cell survival, proliferation and cytokine productions. We hypothesizes Nucks1 may have potential roles in regulating mouse BM-MSCs secretion of growth factors and cytokine profiles in heart repairs after MI. To test our hypothesis, the cardiac protection efficacy of acute infarcted mouse myocardium was measured after the transplantation of WT versus Nucks1 KO BM-MSCs. To this end, we developed a mouse model of acute myocardial infarction (AMI) induced by ligation of left descendant coronary artery. Acute infarcted mouse myocardium receiving WT or Nuck1 KO BM-MSCs transplantation, demonstrated a significant improvement of left ventricular ejection fraction (LVEF), ESP, +dP/dt, ESPVR and vessel density, and reduced infarction size in comparison with PBS control group post-4 weeks of transplantation. Furthermore, acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs transplantation provided better cardioprotective effects than those receiving WT BM-MSCs transplantation. Immunostaining disclosed CD31 and smooth muscle actin (SMA) expression in acute infarcted mouse myocardium receiving Nucks1 KO BM-MSCs were relatively higher than those receiving WT BM-MSCs transplantation. Additionally, a distinct secretion profile of growth factors and cytokines between Nucks1 KO BM-MSCs versus WT BM-MSCs under in vitro ischemia was studied. Expression of vascular endothelial growth factor alpha (VEGFα) in Nucks1 KO BM-MSCs under hypoxia/ serum deprivation was significantly higher than that of WT BMMSCs. Taken together, our data suggested BM-MSCs provide cardiac protection in acute infarcted myocardium. Transplantation of Nucks1 KO BMMSCs may further enhance the cardiac repair of the acute infracted myocardium through an induction of VEGFα.
published_or_final_version
Medicine
Master
Master of Philosophy
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10

Chan, Hoi Huen. "The vascular modulation effect of Panax ginseng." HKBU Institutional Repository, 2013. http://repository.hkbu.edu.hk/etd_ra/1518.

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11

Xie, Lixia. "Effects of salvianolic acid B against apoptosis and adhesion molecules expression in the vascular endothelial cells." HKBU Institutional Repository, 2009. http://repository.hkbu.edu.hk/etd_ra/1082.

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12

MacInnes, J. "Illness representations, treatment beliefs and the relationship to self-care in heart failure." Thesis, Canterbury Christ Church University, 2011. http://create.canterbury.ac.uk/10332/.

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Purpose The purpose of this study was to explore the beliefs people with heart failure hold about their illness and its treatment and to determine any relationships between these beliefs and self-care using the Common Sense Model (CSM) of illness cognitions and behaviour as the theoretical framework (Leventhal et al, 1980). Methods Using a mixed methodology (Creswell and Plano Clark, 2007), findings from patient interviews were used to adapt the Revised Illness Perception Questionnaire (IPQ-R) (Moss-Morris et al, 2002) and the Beliefs about Medicines Questionnaire (BMQ) (Horne et al, 1999) in order to make them illness-specific. A questionnaire assessing self-care was developed based on the European Heart Failure Self-care Behaviour Scale (EHFScBS) (Jaarsma et al, 2003), the interview findings and a nominal group technique with specialist heart failure nurses. These questionnaires were used to determine beliefs and the relationship to behaviour in a cross-sectional survey of 169 patients with heart failure. Results A number of statistically significant correlations were found between beliefs and self-care. Most notably, perceived medication knowledge (r = 0.51, p ≤ 0.01), beliefs about the necessity of medication (r = 0.45, p ≤ 0.01) and illness coherence (r = 0.39, p ≤ 0.01). Multiple regression analysis revealed that 46% of the variance in self-care could be explained by illness representations and treatment beliefs (Adj. R2 = 0.46, F = 9.93, p = 0.00). Three factors were significant predictors of self-care - medication knowledge (β = 0.319, p = 0.003), a belief in the illness having serious consequences (β = 0.258, p = 0.008) and the impact of medication use on lifestyle (β = -0.231, p = 0.03). Discussion The exploration of illness representations revealed a realistic picture of heart failure with a cluster of beliefs around a chronic illness with serious consequences and a high number of symptoms. There was a strong belief in the necessity of medication but for some, medication use had a negative impact on daily life. Patients were confident in their knowledge of medication but this was reduced when family members took control of medication management. A number of beliefs were predictive of self-care, suggesting that interventions designed to maximise these beliefs and correct any misconceptions may enhance self-care and potentially improve clinical outcomes in this population.
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13

Awotedu, Kofoworola Olajire. "Functional changes of the vasculature in HIV/AIDS patients on Haart and Haart Naïve HIV participants." Thesis, Walter Sisulu University, 2013. http://hdl.handle.net/11260/185.

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The present study sought to explore the functional changes that occur in the vasculature of HIV positive participants of African origin in Mthatha district of South africa which might lead to increased risk in their cardiovascular system. Available literature shows that arterial stiffness plays an important role in cardiovascular events such as stroke, vasculitis and myocardial infarction. Measurement of (aortic pulse wave velocity; PWV) provides some of the strongest evidence concerning the prognostic significance of large artery stiffening. This study was aimed at investigating the relationship between anthropometry, age, E-Selectin level, cytokine levels, haemodynamic variables, blood counts and blood lipid profile with pulse wave velocity. Some traditional cardiovascular risk factors such as alcohol, and smoking were also taken into account. This was a cross-sectional study comprising of 169 participants (62 males and 107 females). 63 were HIV negative (group A), 54 HIV positive on treatment (group B), and 52 were HIV positive not on treatment (group C). Pulse wave velocity (PWV) was assessed using the Sphygmocor Vx. Statistically, ANOVA was used for variables with normal distribution and non parametric tests were used for variables with skewed distribution. Notable significant differences were seen in the means of the following variables across all the 3 groups. Conclusion: This study showed that HIV infected patients with or without antiretroviral therapy have increase arterial stiffness which is associated with an increased cardiovascular risk. The sphygmocor is an accurate, non invassive and useful tool in the evaluation of arterial stiffness and its use in clinical practice should be encouraged. PWV and the augmentation index (AIx) are the two major non- iv invasive methods of assessing arterial stiffness. Life style modification should be incorporated into the management of HIV patients so as the continuous monitoring of their haematological and lipid profile.
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14

Tarapués, Román Mónica Natalie. "Monitoring and analysis of adverse reactions associated with medicines recently approved for treatment of cardiovascular disease collected through the spontaneous reporting system." Doctoral thesis, Universitat Autònoma de Barcelona, 2015. http://hdl.handle.net/10803/325418.

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Existen varios medicamentos disponibles para el tratamiento de la patología cardiovascular, así como para otras enfermedades consideradas factores de riesgo cardiovasculares, como son; diabetes, hipertensión y dislipidemia. Cuando un medicamento es comercializado por primera vez, su perfil de seguridad debe considerarse provisional debido a limitaciones propias de los ensayos clínicos pre-comercialización. Para los nuevos medicamentos, la información relevante sobre su seguridad en la población se genera durante los primeros años post-comercialización. El objetivo de esta tesis es contribuir al conocimiento del perfil de seguridad de nuevos medicamentos cardiovasculares mediante el uso de las notificaciones espontáneas recolectadas por el sistema Español de Farmacovigilancia. Se incluyeron en el análisis de esta tesis todos los medicamentos cardiovasculares comercializados en España entre 2007 y 2011. Se seleccionaron y analizaron todas las notificaciones espontáneas que incluyeron alguno de los medicamentos cardiovasculares objetos de estudio hasta final de 2014. Además, en aquellas reacciones adversas relevantes se realizaron revisiones bibliográficas de casos publicados, análisis de información científica relevante, y también, análisis estadísticos de desproporcionalidad. Los principales resultados fueron publicados en dos estudios. El estudio I analizó la asociación entre uso de gliptinas y reacciones musculoesqueléticas. Las gliptinas son una nueva clase de antidiabéticos orales que inhiben la acción de la enzima dipeptidil peptidasa-4 para controlar el nivel de sérico de glucosa en pacientes con diabetes tipo 2. En mayo del 2012 en el sistema Español se encontraron treinta y cuatro notificaciones espontáneas que describían molestias musculoesqueléticas con gliptinas; veintisiete con sitagliptina, seis con vildagliptina y una con saxagliptina. Estos casos representaron el 10% de todas las notificaciones con gliptinas. Además, en dos casos se reportó re-exposición positiva. En la literatura médica poco esta descrito en relación a estas reacciones adversas y el uso de las gliptinas. A pesar de ser leves, estas molestias musculoesqueléticas podrían afectar la adherencia al tratamiento antidiabético. El estudio II analizó la posible asociación entre el uso de dronedarona y falla renal. Dronedarona, es un nuevo antiarrítmico derivado de la amiodarona indicado para el tratamiento de la fibrilación auricular. A pesar de sus ventajas, existe limitada información respecto al potencial daño renal asociado a su uso. En Mayo 2014, se identificaron 18 casos, diez casos en el sistema Español y ocho en la literatura médica. Estos dieciocho pacientes desarrollaron falla renal durante el tratamiento con dronedarona. En todos los casos se observó una secuencia temporal plausible, aunque las enfermedades concomitantes podrían ser factores de confusión. Sin embargo, la falla renal asociada con dronedarona podría complicar la clínica de los pacientes con fibrilación auricular, en especial de aquellos que también presentan insuficiencia cardíaca. Para analizar y estudiar las reacciones musculoesqueléticas con gliptinas y la falla renal asociada a dronedarona, otros estudios observacionales son necesarios, mientras tanto los médicos deben estar atentos ante estas potenciales reacciones adversas en su práctica clínica diaria. El conocimiento sobre la seguridad de los medicamentos es un proceso que se construye constantemente. La notificación espontánea fue el primer método de vigilancia post-comercialización y a pesar de sus inherentes limitaciones (falta de información, infranotificación), todavía contribuye con los principales objetivos de la vigilancia de medicamentos: aumentar la información para la seguridad de los pacientes y disminuir la euforia de los prescriptores ante los nuevos medicamentos en el mercado.
Several medicines for treatment of cardiovascular disease and other risk factors such as diabetes, dyslipidemia, and hypertension are available in the market. However, at the moment of drug approval, the safety profile should be considered provisional due to the limitations of the pre-marketing clinical trials. Also, relevant safety information about newly launched medicines usually arises in the first post-marketing years. The aim of this thesis is to contribute to the knowledge regarding safety profile of new marketed cardiovascular drugs using reports collected in the Spanish spontaneous reporting system. A group of cardiovascular drugs launched in Spain between 2007 and 2011 was selected. All the spontaneous reports involving the study drugs until the end of 2014 were retrieved and carefully analysed. Also, a review of case reports published and other scientific information was done. Statistical methods were applied to strengthen the potential ADR-drug associations. The main results were described in two original studies. In study I, an association between gliptins use and musculoskeletal reactions was found in the Spanish database. Gliptins are a new antidiabetic class that inhibits the action of dypeptidil peptidase-4 enzyme for controlling the glucose blood level in type 2 diabetic patients. In May 2012, thirty-four reports describing musculoskeletal complaints with gliptins were found in the database; twenty-seven for sitagliptin, six for vildagliptin and one for saxagliptin. These cases represented the 10% of all gliptins reports. Moreover, in two of them positive re-exposure was described. These adverse reactions were hardly described with gliptins use. Despite not being serious, these symptoms may impair the treatment adherence in patients with type 2 diabetes. In study II, the potential association between the use of dronedarone and renal impairment was analysed. The effect of dronedarone on renal function was supported by limited information. Dronedarone, a new antiarrhythmic drug, is a noniodinated amiodarone derivative indicated for the treatment of atrial fibrillation. In the Spanish database ten cases were found and, in addition, eight cases were identified in medical literature. These eighteen cases described renal impairment during dronedarone treatment. All cases showed a plausible temporal association, although the baseline conditions could be considered as potential confounder. Renal impairment associated with this drug could seriously aggravate the clinical condition of patients with atrial fibrillation, especially in those who also suffer from heart failure. Despite the fact that, either in musculoskeletal reactions associated with gliptins or renal impairment with dronedarone, further observational studies are needed in order to verify these potential safety signals, in the meantime clinicians should be aware of these potential reactions in clinical practice. The knowledge of safety information of marketed medicines is a constant process that is built-up over time. Pharmacovigilance was the first method for post-marketing surveillance and despite its inherent limitations such as lack of information or underreporting, it still contribute to the main objectives of post-marketing surveillance: to increase patients’ safety and to decrease the prescribers’ euphoria in front of new medicines.
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15

Ng, Fook-hong, and 吳福康. "Management of adverse gastrointestinal events in patients with anti-platelet therapy." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290963.

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16

Hu, Guang. "Pharmacological characterization of angiogenesis effect of Astragali Radix." Thesis, University of Macau, 2012. http://umaclib3.umac.mo/record=b2586303.

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17

Woodman, Richard John. "The independent effects of purified EPA and DHA supplementation on cardiovascular risk in treated-hypertensive type 2 diabetic individuals." University of Western Australia. School of Medicine and Pharmacology, 2003. http://theses.library.uwa.edu.au/adt-WU2003.0028.

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[Formulae and special characters can only be approximated here. Please see the pdf version of the Abtract for an accurate reproduction.] Type 2 diabetes at least doubles the risk of cardiovascular disease. This can partly be explained by the increased prevalence of risk factors such as hypertension, dyslipidaemia and obesity. However, the underlying abnormality of insulin resistance and the presence of more recently identified risk factors including endothelial dysfunction, increased inflammation, and increased oxidative stress might also contribute towards the heightened cardiovascular risk. Fish oil, which contains eicosapentaenoic acid (EPA, 20:5 n-3), has wide-ranging beneficial effects on these and other abnormalities, and has reduced cardiovascular mortality in secondary prevention studies. Animal and human studies have recently established that in addition to EPA, docosahexaenoic acid (DHA, 22:6 n-3) also has beneficial effects, and furthermore, may have less detrimental effects than EPA on glycaemic control which has worsened in some fish and fish oil studies involving Type 2 diabetic subjects. Study 1 : This intervention study aimed to determine the independent effects of EPA and DHA on cardiovascular risk factors and glycaemic control in individuals with Type 2 diabetes receiving treatment for hypertension. In a double-blind placebo-controlled trial of parallel design, 59 subjects in good to moderate glycaemic control (HbA1c < 9%) were recruited from media advertising and randomised to 4 g/day of EPA, DHA or olive oil (placebo) for 6 weeks. Thirty-nine men and 12 post-menopausal women aged 61.2±1.2 yrs completed the study. Relative to placebo, and with Bonferroni adjustments for multiple comparisons, serum triglycerides fell by 19% (p=0.022) and 15% (p=0.022) in the EPA and DHA groups respectively. There were no changes in serum total cholesterol, or LDL- and HDL-cholesterol, although HDL2-cholesterol increased 16% with EPA (p=0.026) and 12% with DHA (p=0.05). HDL3-cholesterol fell by 11% (p=0.026) with EPA supplementation and LDL particle size increased by 0.26±0.10 nm (p=0.02) with DHA. Urinary F2-isoprostanes, an in-vivo marker of oxidative stress was reduced by 19% following EPA (p=0.034) and by 20% following DHA. DHA but not EPA supplementation reduced collagen-stimulated platelet aggregation (16.9%, p=0.05) and thromboxane release (18.8%, p=0.03), but there were no significant changes in PAF-stimulated platelet aggregation. Fasting glucose rose by 1.40±0.29 mmol/l (p=0.002) following EPA and 0.98±0.29 mmol/l (p=0.002) following DHA. Neither EPA nor DHA had any significant effect on HbA1c, fasting serum insulin or C-peptide, insulin sensitivity, stimulated insulin secretion, 24-hr ambulatory blood pressure and heart rate, markers of inflammation, and fibrinolytic or vascular function. Study 2 : This study aimed to examine the influence and causes of increased inflammation on vascular function in subjects recruited for Study 1. Compared with healthy controls (n=17), the diabetic subjects (n=29) had impaired flow-mediated dilatation (FMD) (3.9±3.0% vs 5.5±2.4%, p=0.07) and glyceryl-trinitrate mediated dilatation (GTNMD) (11.4±4.8% vs 15.4±7.1%, p=0.04) of the brachial artery. They also had higher levels of the inflammatory markers C-reactive protein (2.7±2.6 mg/l vs 1.4±1.1 mg/l, p=0.03), fibrinogen (3.4±0.7 g/l vs 2.7±0.3 g/l, p<0.001) and tumor necrosis factor-alpha (20.9±13.4 pg/l vs 2.5±1.7 pg/l, p<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD (p=0.02), accounting for 17% of total variance. Similarly, leukocyte count accounted for 23% (p<0.001) and IL-6 for 12% (p=0.03) of variance in GTNMD. Von Willebrand factor, a marker of endothelial cell activation was correlated with leukocyte count (r=0.38, p=0.04), FMD (r=-0.35, p=0.06) and GTNMD (r=-0.47, p=0.009), whilst P-selectin, a marker of platelet activation was correlated with fibrinogen (r=0.58, p=0.001). Conclusion : EPA and DHA have similar beneficial effects on triglycerides, HDL2 cholesterol and oxidative stress in individuals with Type 2 diabetes and hypertension. However, DHA also increases LDL particle size and reduces collagen-stimulated platelet aggregation and thromboxane release, thus offering more potential than EPA as an anti-thrombotic agent. The beneficial effects of both oils were potentially offset by deterioration in glycaemic control. Neither oil affected blood pressure or vascular function. Longer-term studies with major morbidity and mortality as the primary outcome measures are required to assess the overall benefits and risks of EPA and DHA. The cross-sectional observations from Study 2 are consistent with the hypothesis that impaired vascular function in individuals with Type 2 diabetes and hypertension is at least in part secondary to increased inflammation, with associated endothelial and platelet activation.
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18

楊瀟. "野黃芩素納米混懸液製備及其作為野黃芩苷活性前體的體內研究 Formulation development of scutellarein nanosuspensions as an in-vivo active, rapidly absorbed precursor of its glycoside scutellarin / by Xiao Yang." Thesis, University of Macau, 2014. http://umaclib3.umac.mo/record=b3132957.

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19

Nelson, Mark 1957. "Aspects of pharmacological management of hypertension in general practice." Monash University, Dept. of Epidemiology and Preventive Medicine, 2002. http://arrow.monash.edu.au/hdl/1959.1/7923.

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20

Fontaine, David. "Analyse pharmacologique comparative de l'action vasculaire du ramipril et d'inhibiteurs de l'HMG-COA réductase sur l'aorte isolée de rat: perspectives d'applications cliniques." Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211194.

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La prévention des maladies cardiovasculaires constitue actuellement une approche capitale dans la diminution de la mortalité au sein de nos pays industrialisés. Tous les facteurs de risques étant associés à une dysfonction endothéliale, nous nous sommes intéressés à deux classes de médicaments dont l’action bénéfique se situe, du moins en partie, au niveau de l’endothélium vasculaire :les inhibiteurs de l’enzyme de conversion de l’angiotensine (IECA) et les inhibiteurs de l’hydroxy-3-méthyl-3-glutaryl-Coenzyme A (HMG-CoA) réductase (statines).

Le présent travail contribue à l’étude in vitro des effets protecteurs vasculaires de l’administration chronique, chez le rat, de deux statines (la pravastatine et l’atorvastatine) vis-à-vis de la toxicité aiguë des LDL humaines oxydées et vis-à-vis de la tolérance à la nitroglycérine. Une comparaison est menée par rapport au ramipril dans ces deux modèles expérimentaux.

Les effets de ces médicaments se manifestent au niveau vasculaire par une amélioration de la disponibilité du NO. Toutefois, dans nos modèles, des mécanismes singulièrement différents ont été identifiés entre les agents étudiés :alors que le ramipril engendre une augmentation de l’expression de la eNOS, enzyme synthétisant le NO, les statines permettent une meilleure disponibilité de ce radical par un mécanisme post-traductionnel. Outre cette action, elles semblent agir directement sur des enzymes oxydatives comme les NAD(P)H oxydases.

Une action antioxydante des statines pourrait expliquer tous les effets observés, ce qui n’est pas le cas pour le ramipril. Vu que le stress oxydatif intervient dans tous les facteurs de risques cardiovasculaires, diverses perspectives cliniques sont envisagées afin d’améliorer l’approche thérapeutique de la maladie athéroscléreuse.


Doctorat en sciences pharmaceutiques
info:eu-repo/semantics/nonPublished

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21

Sandén, Per. "Efficacy and safety of warfarin treatment in venous thromboembolic disease." Doctoral thesis, Umeå universitet, Institutionen för folkhälsa och klinisk medicin, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-133618.

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Background As a major cause of morbidity and mortality treatment of venous thromboembolism is important, with the correct use of anticoagulants it is possible to greatly reduce both mortality and morbidity. Warfarin is among the most widely used anticoagulants being effective in treatment and prevention of venous thromboembolism with few negative side effects other than bleeding complications. With a narrow therapeutic window warfarin treatment requires constant monitoring and adjustments to stay effective without an increased bleeding risk. The aim of this thesis was to study the efficacy and safety of warfarin treatment in venous thromboembolic disease. Methods Using AuriculA, the Swedish national quality register for atrial fibrillation and anticoagulation, a cohort was created of patients registered with warfarin treatment during the study time January 1st 2006 to December 31th 2011, including all different indications for anticoagulation. In all four studies the study design was retrospective with information added to the cohort from the Swedish national patient register about background data and endpoints in form of bleeding complications in all studies and thromboembolic events in study 1 and 2. In study 3 and 4 information was added from the cause of death register about occurrence of death and in study 3 cause of death. In study 3, information from the prescribed drugs register about retrieved prescriptions of acetylsalicylic acid was added. Results In study 1 the mean TTR was found to be high both among patients managed at primary healthcare centres and specialised anticoagulation clinics at 79.6% and 75.7%. There was no significant difference in rate of bleeding between the two types of managing centres being 2.22 and 2.26 per 100 treatment years. In study 2 no reduction in complication rate with increasing centre TTR was seen for patients with atrial fibrillation with few centres having centre TTR below 70% (2.9%), in contrast to previous findings by Wan et al(1). For those with warfarin due to VTE where a larger proportion of the centres had centre TTR below 70% (9.1%) there was a reduction in complication rate with increasing centre TTR. Among the 13859 patients with treatment for VTE in study 3 age (HR 1.02, CI 95% 1.01-1.03), hypertension (HR 1.29, CI 95%1.02-1.64), Cardiac failure (HR 1.55, CI 95% 1.13-2.11), chronic obstructive pulmonary disease (HR 1.43, CI 95% 1.04- 1.96), alcohol abuse (HR 3.35, CI 95% 1.97-5.71), anaemia (HR 1.77, CI 95% 1.29-2.44) and a history of major bleeding (HR 1.75, CI 95% 1.27-2.42) increased the risk of bleeding during warfarin treatment. In study 4 both those with high iTTR and those with low INR variability had a low rate of bleedings at 1.27 (1.14-1.41) or 1.20 (0.94-1.21) per 100 treatment years compared to those with low iTTR and high INR variability having a rate of bleeding at 2.91 (2.61-3.21) or 2.61 (2.36-2.86) respectively. Those with the combination of both low iTTR and high INR variability had an increased risk of bleeding, hazard ratio HR 3.47 (CI 95 % 2.89-4.17). The quartile with both the lowest iTTR and the highest INR variability had an increased risk of bleeding with a hazard ratio 4.03 (3.20-5.08) and 3.80 (CI 95%, 3.01-4.79) compared to the quartile with the highest iTTR and lowest INR variability. Conclusion It is possible to achieve a safe warfarin treatment both in specialised anticoagulation centres and in primary health care. At initiation of treatment some of the patients at high risk of bleeding can be identified using knowledge about their background. With the use of quality indicators as TTR and INR variability during treatment those at high risk of complications can be identified and analysing treatment quality on centre level gives an opportunity to identify improvement areas among managing centres. With the addition of new treatment options warfarin can still be the most suitable option for some patients, being safe and effective when well managed.
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22

Qu, Wenlong. "The multiprocessor SAS framework for modeling and cost-effectiveness analysis of treatments for cardiovascular disease." Thesis, University of Ottawa (Canada), 2004. http://hdl.handle.net/10393/26748.

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This thesis provides an economic and mathematical framework, and the computing tools to compare the effects, costs and incremental cost-effectiveness of acute or preventative interventions for cardiovascular disease. A Finite Space Markov Chain Decision Analysis Model is designed by integrating a Decision Trees Model and a Markov Chain Model. The model and Cost-Effectiveness Analysis are implemented by using SAS/IML both on a PC with one processor and on a machine with multiple processors of the High Performance Computing Virtual Laboratory. A sample case with four states and eight intervention policies is studied to illustrate the framework, which is composed of (1) life path simulation, (2) cost and effectiveness estimation, (3) cost-effectiveness analysis, (4) sensitivity analysis, and (5) performance analysis on different platforms. Solution of delay effects, correlation among risk factors, and fluctuation in discount rate are viewed as limitations of the thesis and rewarding areas for further research.
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23

Slee, Deborah Helen. "Synthetic approaches to oxabicyclic ring systems of potential importance in the treatment of cardiovascular disease." Thesis, University of Exeter, 1993. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.535915.

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24

Mahmood, Dler Faieeq Darweesh. "Thioredoxin-1 (Trx1) : a new target in the treatment of cardiovascular diseases." Phd thesis, Université Pierre et Marie Curie - Paris VI, 2014. http://tel.archives-ouvertes.fr/tel-01069096.

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The cardiovascular diseases (CVDs), resulting from complications of atherosclerosis, remain the leading cause of morbidity and death worldwide. Atherosclerosis as a chronic inflammatory disease, involves both innate and adaptive arms of immunity in which macrophages play the orchestral role in modulating lesion initiation, progression, and potentially devastating thrombotic complications. Available evidences support the notion of a central role of oxidative stress, due mainly to the imbalance between antioxidants and reactive oxygen species (ROS) in CVDs. Furthermore, the pathology is frequently associated with dynamic changes in macrophage activation, with classically activated M1 cells implicated in initiating and sustaining inflammation and M2 or M2-like cells associated with resolution or smoldering chronic inflammation. Among endogenous antioxidants, the thiordoxine-1 (Trx1) plays a central role in several diseases including CVD. Thus, the ubiquitous Trx1 has been reported to exert a myriad of beneficial roles. Indeed, it regulates not only cellular redox homeostasis and acts as a principal antioxidant defense system, but it also affects energy metabolism, modulates the immunological and inflammatory responses, and controls cell growth and survival. In contrast, its truncated form (Trx-80), exerts an opposite effects. However, several studies reported the beneficial role of Trx system in CVDs but the detailed molecular mechanism is not addressed yet. Therefore, the present study aims to investigate the role of both Trx1 and Trx80 in the biology of atherosclerosis through the modulation of macrophage polarization and the implicated signaling pathways as well. Our in vitro major findings, using human macrophages and murine peritoneal macrophages, revealed that Trx1 on one hand promoted the polarization of anti-inflammatory M2 macrophages through downregulation of p16INK4a and suppressing nuclear translocation of activator protein-1 (AP-1) and Ref-1 as evidenced by the expression of the CD206 and IL-10 markers. On the other hand Trx1 also reduced the lipopolysaccharide (LPS)-induced differentiation of inflammatory M1 macrophages, as indicated by the decreased expression of the M1 cytokines, tumor necrosis factor-α (TNF-) and monocyte chemoattractant protein-1 (MCP¨-1). By contrast, Trx80 treatment attenuated the polarization of anti-inflammatory M2 macrophages induced by IL-4 or IL-4/IL-13 even it potentiated LPS-induced M1 activation. To validate our obtained in vitro results, hyperlipoproteinemic C57Bl/6.ApoE2.ki mice and human atherosclerotic vessel specimens from patients undergoing vascular surgery were used. Consistently, Trx1 and Trx80 affected macrophage phenotype in thymus, liver and atherosclerotic lesions. As a consequence, Trx1 reduced whereas Trx80 increased the aortic lesion area in mice. Plasma levels of cholesterol and triglycerides did not changed by the treatment. To further explore our results, the implicated signaling pathways has been studied and it was found that both Trx1 and Trx80 activated Akt. Furthermore, Trx80 uses mTOR signaling pathway to exert its effect in polarizing macrophages toward M1 phenotype since it activated mTOR in a dose-dependent manner as demonstrated by the increased phosphorylation of P70S6K. Based on our results, Trx1 antagonizes whereas Trx80 potentiates atherosclerosis through changing M1/M2 phenotypes. Therefore, Trx1 represents a promising target for therapeutic interventions.
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25

Li, Wai-sum Rachel, and 李蕙琛. "Effects of abacavir on cardiovascular system." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46330288.

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26

劉巨基 and Kui-kai Gary Lau. "Surrogate markers of atherosclerosis and cardiovascular disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40733749.

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27

Wong, Chun-kit Arthur, and 黃俊傑. "Serum uric acid and its relationship with cardiovascular diseases." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/208600.

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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
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28

Gobin, Reeta Rukmini Devi. "Metabolic syndrome and cardiovascular disease." Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.610102.

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29

Barker, Ann Elizabeth. "Wild Blueberry Consumption and Risks for Cardiovascular Disease." Fogler Library, University of Maine, 2006. http://www.library.umaine.edu/theses/pdf/BarkerAE2006.pdf.

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30

Willeit, Peter. "Natriuretic peptides and cardiovascular disease." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648533.

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31

Chan, Hiu-ting, and 陳曉庭. "The effect of diet intake on vascular function and therapeutic effect of cardiovascular medicine in patients with cardiovascular disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hub.hku.hk/bib/B50434342.

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Cardiovascular diseases (CVDs) remain to be the leading causes of morbidity and mortality in Hong Kong and worldwide. Among different modifiable risk factors, dietary pattern is on the major determinant for CVD and overall mortality. Other than pharmacological therapies for cardiovascular risk factors, such as hypertension, hyperlipidemia and diabetes, maintaining a healthy diet is a more sustainable method in general population to prevent CVDs. Current lifestyle intervention in the West countries focus on high intake of fruit and vegetables with more than 400g per day and limited saturated fats with less than 10% of energy, there is very limited data on impact of dietary pattern on CVDs in Chinese. Prior studies among Chinese in Hong Kong have shown that only half of the local population fell within these recommended ranges for fat, saturated fatty acid and cholesterol intakes. Several different dietary patterns have been recommended for CVDs prevention based on: i) food groups, such as Mediterranean diet, the Dietary Approaches to Stop Hypertension (DASH) diet; ii) macronutrients: the low-carbohydrate diet, low glycemic index diet, very-low- fat diet and iii) nutrition or vitamin supplement. However, the effect of different dietary patterns based on modulations of food group, macronutrients and particular micronutrients on vascular structure and function in Chinese subjects is unclear. In the first part of this thesis, the relationships between different dietary pattern and surrogate markers of subclinical atherosclerosis and vascular function in different high risk populations for CVDs were investigated. In Chapter 3, we compared the assessment of dietary pattern in Chinese using different tool, including Food Frequency Questionnaire (FFQ); Dietary Record; and Dietitian assessment. In this study, we demonstrated that suitable dietary assessments tools should be chosen for the assessment of different dietary pattern, according to characteristics of assessments. In Chapter 4, the relationship between the fruit intake and subclinical atherosclerosis as measured by carotid intimal thickness (IMT) was investigated in patient with type II diabetes mellitus (DM). Our results showed that high fruit intake was associated with lower burden of carotid atherosclerosis, independent of level of vitamin intake in patients with type II DM. In Chapter 5, we compared the impact of high carbohydrate diet on arterial stiffness between control subjects without CVDs and patients with high risk for CVDs. Our findings showed that high carbohydrate diet mainly affected patients with established CVDs, and their increased arterial stiffness was associated with an elevation of blood pressure. In Chapter 6, we determined the effect of dietary vitamin intake on oxidative stress in patients with high risk of CVDs. In those high risk patients for CVDs, we demonstrated that increased dietary intake of vitamin A, beta-carotene and alpha tocopherol were associated with decreased oxidative stress, but these relationships were not observed in those control subjects without CVDs. It is likely attributed to the higher systemic oxidative stress levels in patients with high risk of CVDs. On the other hand, food intake may also affect the clinical efficacy of cardiovascular therapies. In particularly, it has been well established that herbal intake which is commonly used by Chinese can affect the anticoagulant effect of warfarin on patients with non-valvular atrial fibrillation (AF). Thus, in this second part of the thesis, we investigated the effect of concomitant herbal intake on anticoagulation control in patients with non-valvular AF treated with warfarin. Our results showed that patients with AF treated with warfarin had limited knowledge on potential interaction between herbal substances in foods and warfarin, in which increased herbal substances intake significantly reduced the percentage time of anticoagulant effect within the therapeutic range. Moreover, a single section of education on knowledge of herbal ingredients did not improve their percentage time of therapeutic range for these patients. In conclusion, these findings suggest that dietary pattern in Chinese might have significant impact of vascular function in patients with type II DM and high risk for CVDs. Moreover, the herbal substances in the diet among Chinese could have significant impact of the therapeutic effects in some of the cardiovascular medications, such as warfarin. Future clinical studies will be needed to confirm these potential beneficial effects of particular diet intake on vascular function in patients with high risks of CVDs as well as potential interaction between herbal substances in Chinese diet and cardiovascular medications.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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32

Zeng, Ke Han. "Innovative cuboid method to attenuate noises from site-measured heart sound signals." Thesis, University of Macau, 2015. http://umaclib3.umac.mo/record=b3335275.

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33

Li, Sin Wan. "Development of immunoassays for prognosis and diagnosis of cardiovascular diseases /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202007%20LI.

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34

毛皚炘 and Yee-yan Mo. "Effects of dietary soy isoflavones for cardiovascular disease (Review)." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42997525.

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35

Loke, Wai Mun. "Cardiovascular protective effects of dietary polyphenols." University of Western Australia. School of Biomedical and Chemical Sciences, 2008. http://theses.library.uwa.edu.au/adt-WU2009.0051.

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Polyphenols are naturally-occurring phytochemicals, which form an integral part of the human diet. Results from epidemiological studies have associated polyphenol intake with reduced risk of cardiovascular diseases. Previous human intervention studies suggested that dietary polyphenols exert their cardioprotective effects through their antioxidant and anti-inflammatory effects. While most in vitro experiments have not accounted for the bioavailability and metabolism of these polyphenols, our work has provided direct evidence, using quercetin, that metabolic transformation, together with bioavailability, exert profound effects on bioactivity. We examined the effect of quercetin and its major metabolites on the production of pro-inflammatory eicosanoids by human leukocytes. Studies comparing free radical scavenging, antioxidant activity and eicosanoid production demonstrate that there are different structural requirements for antioxidant and anti-inflammatory activity. We also investigated the effect of metabolic transformation on flavonoid bioactivity by comparing the activity of quercetin and its major metabolites to inhibit inflammatory eicosanoid production from human leukocytes. Quercetin was a potent inhibitor of leukotriene B4 formation in leukocytes (IC50 ~ 2µM), and its activity was dependent on specific structural features, particularly the 2,3 double bond of the C ring. Functionalisation of the 3'-OH group with either methyl or sulfate reduced inhibitory activity up to 50% while a glucuronide substituent at the 3-OH effectively removed the leukotriene B4 inhibitory activity. The major quercetin metabolite quercetin-3'-O-sulfate retained considerable lipoxygenase inhibitory activity (IC50 ~ 7 µM) while quercetin-3-O-glucuronide maintained antioxidant activity but had no lipoxygenase inhibitory activity at physiologically relevant concentrations. We conclude that structural modification of quercetin due to metabolic transformation had a profound effect on bioactivity, and that the structural features required for antioxidant activity of 8 quercetin and related flavonoids were unrelated to those required for inhibition of inflammatory eicosanoids.
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36

Zhang, Yuelin, and 張月林. "Mesenchymal stem cells derived from pluripotent stem cells for cardiovascular repair and regeneration." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196438.

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Despite major advances in pharmacological and surgical treatments of cardiovascular diseases (CVDs), clinical outcomes of patients with severe CVDs remain very poor. Most of medication and interventions currently available are only playing roles of preventing further damage to myocardium, declining the risk of on-going cardiovascular events, lifting the cardiac pumping efficiency and lower early mortality rates, none of these treatments can regenerate or repair damaged cardiac tissue or restore heart function. As a result, several new strategies have been explored to overcome limitations of current therapeutic approaches. One prospective is to replace dead cardiac vascular cells with young and green cells to repair or regenerate damaged heart myocardium. Several types of stem cells, including bone marrow hematopoietic stem cells, mesenchymal stem cells (MSCs), embryonic stem cell (ESCs)and induced pluripotent stem cells (iPSCs),have been tested as the candidates for treatment of CVDs. Among a myriad of types of stem cells, bone marrow derived MSCs(BM-MSCs) has received great attention based on several unique properties such as easy isolation and expansion, stable genetic background and low immunogenicity. However, the therapeutic efficacy of BM-MSCs derived from aging or diseased donors is impaired. The differentiation potential of BM-MSCs is gradually reduced with the increased culture time. Thus, it is urgent to identify some novel alternative sources for MSCs. Moreover, the potential mechanisms of MSCs therapy have not been understood totally. This thesis is designed to investigate the therapeutic efficacy and potential mechanisms of several novel types of MSCs, including hESC-MSCs and hiPSC-MSCs and Rap1-/--BM-MSCson several types of CVDs, including pulmonary arterial hypertension (PAH), dilated cardiomyopathy (DCM)and myocardial infarction (MI). In Chapter 4, it disclosed that hESC-MSCs have a better therapeutic efficacy than BM-MSCs in attenuation of PAH induced by monocrotaline in mice. The greater therapeutic potential of hESC-MSCs on PAH was not only attributed to the higher capacity of differentiation into de-novo vascular cells, but also attributed to higher cell survival rate and greater paracrine effects post-transplantation. In Chapter 5, it demonstrated that compared with BM-MSCs, iPSC-MSCs have a better therapeutic effect on doxorubicin-induced cardiomyopathy. Several potential mechanisms of action were involved in iPSC-MSCs-based therapy for cardiomyopathy. It demonstrated that iPSC-MSCs transplantation not only attenuated the generation of reactive oxygen species(ROS)and the level of inflammation, but also restored depletion of cardiac progenitor cells and promoted endogenous myocardial regeneration against doxorubicin induced cardiomyopathy. Moreover, mitochondrial transfer and paracrine actions of iPSC-MSCs played critical roles in the rescue for doxorubicin-induced cardiomyopathy. In Chapter 6, it uncovered that compared with wild type BM-MSCs,Rap1-/--BM-MSCs transplantation achieved a better benefit to MI induced by ligation of left anterior descending (LAD)coronary artery. Rap1-mediated NF-κB activity plays a key role in regulation MSCscytokine secretion profiles. The absence of Rap1 in MSCs leads to reduced pro-inflammatory cytokines secretion and enhanced MSCs survival capacity, thus yielding a better therapeutic efficacy. In conclusion, findings presented in this thesis provide important new insights regarding different novel types of MSCs, including those derived from ESC and iPSC. They have distinct mechanisms of action from BM-MSCs and provide superior therapeutic efficacy in various form of severe CVDs, including PAH and DCM. The safety and efficacy of these novel types of MSCs for treatment of CVDs deserve further investigations.
published_or_final_version
Medicine
Doctoral
Doctor of Philosophy
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37

Leung, Yiu-por, and 梁耀波. "Coping strategies of cardiovascular disease patients." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 1996. http://hub.hku.hk/bib/B31978125.

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38

Ostertag, Luisa Martha. "The impact of dietary polyphenols on human platelets : integrating functional and nutrigenomic analyses." Thesis, University of Aberdeen, 2011. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=185749.

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This thesis aims to integrate functional and nutrigenomics analyses to examine how dietary polyphenols affect human platelet function and thus may contribute to the prevention of cardiovascular diseases. Initially, 26 low molecular weight phenolic compounds were screened for their effects on platelet aggregation and P-selectin expression in vitro. Only high, non-physiological concentrations of some phenolics showed anti-platelet effects. In parallel we conducted a systematic review of the literature to assess how polyphenol-rich foodstuffs, beverages, or extracts affect platelet function in humans. Cocoa-derived flavan-3-ols were the only class of dietary polyphenols that consistently showed anti-platelet effects in both, acute and chronic settings. Consequently we conducted an acute randomised-controlled human intervention study in which healthy volunteers consumed three different types of chocolates containing different amounts of flavan-3-ols. We found that flavan-3-ol-enriched dark chocolate beneficially affected ex vivo bleeding time, platelet aggregation and P-selectin expression. These effects were gender-dependent. Bioavailability of cocoa-derived flavan-3-ols, as assessed by a targeted metabolomics approach, was also gender-dependent. Using a platelet proteomics approach, we found subtle changes in platelet protein levels 2 h after consumption of flavan-3-ol-enriched chocolate in men, which may partly explain the observed anti-platelet effects. Finally, we assessed whether flavan-3-ols are internalised in platelets after consumption of dark chocolate. No internalisation could be found up to 2.5 h after chocolate ingestion, despite these compounds appearing in plasma. In conclusion, flavan- 3-ol-enriched dark chocolate beneficially affects platelet function in a gender-dependent way, but underpinning mechanisms are still unknown. Furthermore, current insights into their bioavailability cannot fully explain the ability of flavan-3-ols to affect platelet function. Successful future progress of research into the bioavailability and mechanisms of flavan-3- ols in vitro and in vivo will depend on the availability of pure standards for the major human metabolites of flavan-3-ols.
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39

Assomull, Ravi Gulab. "Cardiovascular magnetic resonance in dilated cardiomyopathy." Thesis, University of Cambridge, 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607644.

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40

Butlin, Mark Graduate School of Biomedical Engineering Faculty of Engineering UNSW. "Structural and functional effects on large artery stiffness: an in-vivo experimental investigation." Awarded by:University of New South Wales. Graduate School of Biomedical Engineering, 2007. http://handle.unsw.edu.au/1959.4/29479.

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Large artery stiffness is predictive of adverse cardiovascular events and all cause mortality. Artery structure and function are determinants of artery stiffness. This thesis presents a series of in-vivo experimental studies of effect of structural and functional changes on large artery stiffness. Improved analysis methods were developed for measurement of arterial stiffness indexes, Pulse Wave Velocity (PWV) and pressure wave re ection. These were applied in studies of acute in ammation, active and passive changes in systemic pressures, aortic elastic laminae defects, and aortic calcification in rats using a novel, high fidelity, dual pressure sensing technique of measuring aortic rat PWV. Findings indicated that acute in ammation does not increase large artery stiffness, and that localised effects altering arterial structure do not manifest in in-vivo changes in large artery stiffness. The functional component of stiffness was investigated using graded systemic infusion of vasoconstrictor agents (angiotensin-II, noradrenaline, and Endothelin-1 (ET-1)) in the in-vivo ovine iliac artery. There was a markedly greater dose dependency of pressure independent change in PWV (angiotensin-II) compared to direct endothelial effects (ET-1), although blocking of ET-1 receptors produced marked changes in iliac blood ow. A similar experiment in the human iliac artery found that the B-antagonist and nitric oxide (NO) donor, x Structural and functional effects on large artery stiffness nebivolol, potentially causes a decrease in regional functional stiffness. An additional study in human subjects directly measured the decrease in forearm arterial stiffness during reactive hyperaemia following different periods of ischaemia. The findings precluded the use of this method in measuring brachial artery structural stiffness with maximal smooth muscle relaxation. Increasing periods of ischaemia had a bi-phasic relationship with changes in arterial stiffness, the first phase linked to endogenous nitric oxide release. This finding is of importance in the clinical quantification of endothelial dysfunction. These findings in basic research of arterial haemodynamics provide new quantitative contributions to the in-vivo experimental investigation of the aetiology of large artery stiffness related to structure and function of endothelial and medial wall properties. This can lead to potential clinical applications and techniques for assessment of cardiovascular risk.
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41

Heys, Michelle. "Life course determinants of cognitive function and cardiovascularrisk." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2010. http://hub.hku.hk/bib/B46448160.

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42

McCain, Wilfred C. "Cardiovascular components of organophosphorus-induced delayed neuropathy." Thesis, Virginia Tech, 1991. http://hdl.handle.net/10919/41691.

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The focus of this study was to assess the cardiovascular effects in hens of a single 2.5 mg/kg intramuscular injection of phenyl saligenin phosphate (PSP) into the breast muscle. Parameters were measured at 1, 3, 7, and 20 days post treatment. All hens developed clinical signs of delayed neuropathy by day 10 and these signs were maximal by day 20. Alterations of measured parameters were observed prior to the onset of clinical signs of organophosphorus-induced delayed neuropathy (OPIDN) (days 1, 3, and 7) as well as when maximal clinical signs were evident (days 15-21). Significant decreases in the activities of brain NTE and plasma cholinesterase as well as decreases in weight and the level of pcO2 and an increase in peripheral resistance were observed prior to evidence of clinical signs of OPIDN. When maximal signs of OPIDN were present, brain NTE and plasma cholinesterase were at control levels but brain cholinesterase was significantly increased. Significant decreases in body weight and arterial pCO2 and significant increases in limb venous flow, arterial blood pressure, and hematocrit were seen at this time.
Master of Science
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43

Huang, Jie. "Whole-genome sequencing-based association studies of cardiovascular biomarkers." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708994.

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44

Cheung, Yiu-fai, and 張耀輝. "An analysis of the determinants of peripheral conduit arterial stiffness in children and teenagers in health and disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B29761815.

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Ng, Kuen-to, and 伍權韜. "The gender difference and association between social position and cardiovascular risk factors in Hong Kong." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B45012775.

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46

Wang, Siqi. "NONINVASIVE ASSESSMENT AND MODELING OF DIABETIC CARDIOVASCULAR AUTONOMIC NEUROPATHY." UKnowledge, 2012. http://uknowledge.uky.edu/cbme_etds/5.

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Abstract:
Noninvasive assessment of diabetic cardiovascular autonomic neuropathy (AN): Cardiac and vascular dysfunctions resulting from AN are complications of diabetes, often undiagnosed. Our objectives were to: 1) determine sympathetic and parasympathetic components of compromised blood pressure regulation in patients with polyneuropathy, and 2) rank noninvasive indexes for their sensitivity in diagnosing AN. Continuous 12-lead electrocardiography (ECG), blood pressure (BP), respiration, regional blood flow and bio-impedance were recorded from 12 able-bodied subjects (AB), 7 diabetics without (D0), 7 with possible (D1) and 8 with definite polyneuropathy (D2), during 10 minutes supine control, 30 minutes 70-degree head-up tilt and 5 minutes supine recovery. During the first 3 minutes of tilt, systolic BP decreased in D2 while increased in AB. Parasympathetic control of heart rate, baroreflex sensitivity, and baroreflex effectiveness and sympathetic control of heart rate and vasomotion were reduced in D2, compared with AB. Baroreflex effectiveness index was identified as the most sensitive index to discriminate diabetic AN. Four-dimensional multiscale modeling of ECG indexes of diabetic autonomic neuropathy: QT interval prolongation which predicts long-term mortality in diabetics with AN, is well known. The mechanism of QT interval prolongation is still unknown, but correlation of regional sympathetic denervation of the heart (revealed by cardiac imaging) with QT interval in 12-lead ECG has been proposed. The goal of this study is to 1) reproduce QT interval prolongation seen in diabetics, and 2) develop a computer model to link QT interval prolongation to regional cardiac sympathetic denervation at the cellular level. From the 12-lead ECG acquired in the study above, heart rate-corrected QT interval (QTc) was computed and a reduced ionic whole heart mathematical model was constructed. Twelve-lead ECG was produced as a forward solution from an equivalent cardiac source. Different patterns of regional denervation in cardiac images of diabetic patients guided the simulation of pathological changes. Minimum QTc interval of lateral leads tended to be longer in D2 than in AB. Prolonging action potential duration in the basal septal region in the model produced ECG and QT interval similar to that of D2 subjects, suggesting sympathetic denervation in this region in patients with definite neuropathy.
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Luke, Baw D. "Educational attainment and cardiovascular disease related mortality a retrospective cohort evaluation of Chinese elderly population in Hong Kong /." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41711373.

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Norton, Cynthia Ann. "The Effect of Whole Wild Blueberries on Endothelial Function of the Sprague-Dawley Rat as Related to Cardiovascular Disease." Fogler Library, University of Maine, 2003. http://www.library.umaine.edu/theses/pdf/NortonCA2003.pdf.

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Jones, Daryl Rhys. "Treatment of prion diseases with camelid antibodies." Thesis, Royal Veterinary College (University of London), 2013. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.618290.

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Khan, Hassan. "Markers of glycaemia and risk of cardiovascular disease." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648585.

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