Saudi Cultural Missions Theses & Dissertations
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Item Restricted The impact of Dairy- free diet on the management of Hypertension- A systematic review.(University of Nottingham, 2024) Alzubidi, Fatimah; McCullough, FionaIntroduction: Hypertension is a significant risk factor for chronic diseases, and its prevalence is increasing globally. The development of hypertension is influenced by genetic predisposition, environmental factors, age-related changes, and immunological influences. Dietary management plays a key role in managing hypertension, with the DASH diet being an effective intervention. Calcium intake through diet, particularly from dairy products, has been shown to help lower blood pressure. Previous studies have demonstrated a link between dairy consumption and decreased blood pressure. Aim: This paper aimed to systematically review the existing literature by comparing diets without dairy to those that include dairy, focusing on the effect of dairy exclusion on hypertension, which was the primary outcome, as well as on secondary outcomes, such as changes in lipid profile, weight, waist circumference, and glucose levels. Methods: PubMed, Scopus, Embase, and Web of Science were used to search for relevant articles that study the impact of dairy food exclusion on the management of hypertension. Only records that met the following inclusion criteria were considered: published between 2000 and June 2024, full text, and in English, focusing on adults aged ≥18 years of either gender, with or without health conditions. The Cochrane Collaboration quality assessment tool was employed to assess the included studies. Results: The results of six randomised clinical trials involving 462 adult participants indicated that a dairy-free diet did not have any discernible effect on both systolic and diastolic blood pressure measurements (in mmHg). Conclusion: This review indicates that eliminating dairy products from one's diet has no apparent impact on the incidence or management of hypertension despite the limitations of the included studies. Moreover, it emphasises the need for additional research to explore the effects of fat content and micronutrients on the management of hypertension.16 0Item Restricted INVESTIGATING CHANGES IN ANGIOTENSIN II SIGNALLING, RESPIRATORY VARIABILITY AND CAROTID BODY FUNCTION IN RESPONSE TO CHRONIC HYPOXIA(University of Birmingham, 2024-08-05) Aldossary, Hayyaf Saad; Holmes, Andrew; Coney, AndrewChronic hypoxia (CH) and rises in circulating angiotensin II (Ang II) are key features of chronic obstructive pulmonary disease (COPD), an illness associated with respiratory dysfunction. Hypertension is an important co-morbidity in COPD. It has recently been suggested that the carotid body (CB) has an important role in causing vascular dysfunction in COPD patients. In response to CH, the CB undergoes extensive structural and functional adaptation, leading to hyperactivity. It is proposed that CB hyperactivity contributes to hypertension development in CH/COPD. The CB serves as a peripheral chemoreceptor located at the common carotid artery bifurcation, sensing and reacting to alterations in arterial O2, CO2, and pH levels. Previous studies have suggested the involvement of Ang II and its G Protein-Coupled Receptor (GPCR) member, AT1R, in mediating CB activity. It is currently unknown if the membrane arrangement of AT1Rs is altered by CH. It is not clear if Ang II stimulation involves activation of TRPC channels. Furthermore, a role for heightened Ang II-AT1R-TRPC signalling in mediating CB hyperactivity in response to CH remains uncertain. Key aims of this thesis were to: 1. Assess if AT1R membrane protein expression is increased in CH, 2. Explore how single molecule organisation of AT1R is modified by CH, 3. Provide a detailed evaluation of respiratory changes induced by CH, 4. Identify if CB Ang II-TRPC signalling is upregulated in CH and 5. Determine if targeting Ang II-TRPC signalling in vivo decreases the blood pressure in CH animals. In Chapter 2 and 3, utilizing the PC12 cell line as a surrogate for CB type I cells, it was revealed that AT1R protein expression was elevated by CH, accompanied by modifications in cell size, suggesting adaptive responses to prolonged hypoxia. Subsequent investigations utilising super-resolution microscopy demonstrated that AT1Rs form distinct clusters in the cell membrane. Furthermore, the maximum cluster size is increased under CH, indicating enhanced supercluster formation. In Chapter 4, expanding beyond cellular responses, the impact of CH on respiratory variables was evaluated using whole body plethysmography. It revealed key alterations, such as rises in respiratory frequency, shortening of respiratory timings and elevations in inspiratory and expiratory drive. Furthermore, a decrease in breath to breath interval variability was observed after CH exposure. In Chapter 5, carotid sinus nerve (CSN) activity measurements showed augmented, more consistent responses to Ang II that were apparent in a greater proportion of fibres in the CH group, suggesting increased Ang II sensitivity. In the presence of Ang II, the TRPC channel blocker, specifically 2-APB, produced exaggerated inhibition of CB activity in the CH group, suggestive of a rise in Ang II-TRPC signalling. Lastly, in Chapter 6, cardiovascular measurements showed that single bolus injection of 2-APB did not successfully decrease the mean arterial pressure (MAP) or heart rate (HR) in CH animals. This is likely due to it not reaching a high enough concentration in the CB. These investigations provide comprehensive information regarding AT1R, CB and respiratory adaptations to CH. The findings should help guide the development of novel therapeutic interventions, based on targeting Ang II-AT1R-TRPC signalling, to treat CB hyperactivity in conditions such as COPD.11 0Item Restricted Socioeconomic inequalities in cardiovascular diseases risk factors: Analysis of the Health Survey of England(Saudi Digital Library, 2023-11-01) Abideen, Raseel; Douiri, AbdelIntroduction: Cardiovascular diseases present a significant global health challenge, contributing substantially to morbidity and mortality. This complex issue arises from a confluence of genetic, lifestyle, and environmental factors. Despite medical advancements, socioeconomic determinants persist as formidable barriers to achieving equitable health outcomes. Addressing these inequalities is pivotal in mitigating the impact of cardiovascular diseases on public health. Aim: The primary aim of this research is to investigate the association between socioeconomic factors and the prevalence of three cardiovascular risk factors: hypertension, obesity, and smoking. By delving into the Health Survey of England dataset for 2019, this study seeks to unravel the complex web of associations that link demographic and socioeconomic strata with the prevalence of these risk factors. Methodology: This research adopts a cross-sectional design, leveraging the comprehensive Health Survey of England dataset. Analyzing a range of demographic and socioeconomic variables, the study employs rigorous statistical methods, including chi-square tests, logistic regression, and descriptive analysis. This approach offers a comprehensive examination of the relationships between socioeconomic factors and cardiovascular risk profiles. Results: The study offers nuanced insights into the interplay of age and hypertension, revealing a significant surge in prevalence and odds beyond the age of 45. Distinct ethnic disparities in hypertension prevalence highlights higher rates among Black individuals, signifying their increased susceptibility. Socioeconomic status emerges as an important factor, with lower income groups displaying elevated odds of hypertension. Exploring obesity patterns uncovers the influence of gender and culture, with males at higher risk and Asian ethnic groups displaying lower odds. Socioeconomic status is again noteworthy, as higher standing correlates with decreased obesity risk. Smoking behaviors exhibit age-related variation, with young adults aged 25-34 displaying the highest prevalence and likelihood of being current smokers. Ethnic disparities in smoking behaviors underscore cultural influences, while income and deprivation complexities link with smoking behaviors. Conclusion: This dissertation underscores the interconnected nature of age, gender, ethnicity and socioeconomic status in shaping cardiovascular risk profiles. Recommendations include targeted interventions for hypertension among older adults and ethnic minority populations, culturally sensitive obesity interventions, and comprehensive antismoking initiatives. Findings emphasize the significance of addressing health disparities and fostering equitable health outcomes in the pursuit of a healthier future for all.17 0Item Restricted EFFICACY OF ANTIDIABETIC DRUGS IN NORMALIZING BLOOD PRESSURE IN HYPERTENSIVE DIABETIC ANIMALS AND NOVEL MECHANISMS IN THE DISTAL NEPHRON(Saudi Digital Library, 2023) Gholam, Mohammed Fawzi A; Alli, AbdelHypertension associated diabetes is a highly prevalent disease and a major risk factor for DN, the most common cause of end stage renal disease in the US. The regulation of salt balance by the kidney is a major player for blood pressure regulation by adjusting blood volume in response to changes in systemic pressure. NCC and ENaC are expressed mainly in the late DCT and play a crucial role in blood pressure regulation. The cytoskeleton of eukaryotic cells provides structural support for the plasma membrane and regulates numerous epithelial transport proteins. Multiple antidiabetic drugs including, dapagliflozin and metformin, have shown a positive effect on the kidney. However, less is known about their mechanisms of action in terms of blood pressure regulation. The goals of this project are to define the mechanistic link between NCC and ENaC and the actin cytoskeleton proteins in the diabetic hypertensive db/db mice, furthermore, to investigate the effects of the antidiabetic agents including dapagliflozin and metformin on sodium reabsorption and blood pressure. We found that NCC interacts with the actin cytoskeleton filamin A and is dependent on CaMKII activity, which may serve as a feedback mechanism to maintain basal levels of NCC activity in the distal nephron. Moreover, we identified a novel blood pressure reducing role of metformin in diabetic nephropathy by regulating the cathepsin B-ENaC axis. Besides, we found the augmentation of cathepsin isoforms in the diabetic db/db mouse kidney is associated with an increase in renal MARCKS expression and proteolysis. On the other hand, NCC and the actin cytoskeleton linker protein ezrin interacts at the DCT in the hypertensive diabetic kidney. Dapagliflozin reduced NCC and ezrin interaction and alleviated blood pressure, blood glucose, urine osmolality, and promoted urinary sodium. Furthermore, some bioactive lipids in diabetic kidney membranes were altered after dapagliflozin treatment. Taken together, metformin and dapagliflozin may have the potential to normalize blood pressure in diabetics and reduce the risk of developing diabetic nephropathy.18 0Item Restricted Do Respiratory Influences on Cardiovascular Regulation Provide Early Markers of Hypertension in Young Adults with Family History of Hypertension?(2023-05-05) Al Enazi, Fahad; Marshall, Janice; Coney, AndrewBackground: Hypertension is well-known leading cause of the majority of cardiovascular diseases. Individuals with a parental history of hypertension (FH+) have a two-fold greater risk of developing hypertension than those without parental hypertension (FH-). Objective: This PhD project had three main aims. First, to elucidate whether young normotensive adult FH+ already have disturbed autonomic regulation of arterial blood pressure (ABP) relative to FH- at rest and in response to everyday stressors such as postural manoeuvres and environmental stressors. Second, to investigate whether slow breathing normalises autonomic dysregulation in FH+. Third, to assess whether slow breathing acutely or following training reduces ABP and restores autonomic regulation in normotensives and hypertensives. Methods: The first and second aims were explored by recording arterial blood pressure (ABP), a range of haemodynamic variables, heart rate variability (HRV) and baroreceptor reflex sensitivity (BRS), in young normotensive FH+ and FH- men and women at rest, during and following acute mental stress (Stroop colour-word test) and during acute slow breathing at 6 breaths/minute. The third aim was evaluated by a systematic review and meta-analysis on the effects of device- and non-device guided slow breathing acutely and by training for ≥4 weeks on ABP and autonomic regulation of ABP in normotensives and hypertensives. Results and Conclusion: The experimental studies showed no differences between FH+ and FH- at rest. However, FH+ showed exaggerated increases in ABP and total peripheral resistance to mental stress relative to FH-. On the other hand, HRV, which mainly reflects vagal influences on the heart, was reduced during mental stress in FH+ and FH- and consistent with inhibition of the baroreceptor reflex being a characteristic of the defence response, vagal BRS was also reduced in FH+ and FH-. However, sympathetic BRS to a fall in ABP assessed by the squat to stand test was depressed by mental stress in FH- but not FH+. These findings provide novel evidence that sympathetic control of ABP is disturbed in young adult FH+ such that repeated exposure to mental stressors would be expected to increase their risk of hypertension. Acute slow breathing reduced ABP in both FH+ and FH- but reduced TPR in FH- only. Concomitantly, HRV was increased in both groups, while vagal BRS was increased in FH+ only. Theses novel results suggest that FH+ are more resistant to the ability of slow breathing to reduce sympathetic tone, but that vagal influence are normalised. Importantly, the systematic review and meta-analysis, demonstrated that slow breathing is effective in both hypertensives and normotensives in lowering ABP, enhancing HRV, and improving BRS, at least in normotensives. Thus, collectively the results indicate that slow breathing training should help to reduce abnormal autonomic regulation in young FH+ by increasing vagal regulation of the heart and decreasing sympathetic activity to the heart and vasculature, so lowering their future risk of hypertension.26 0Item Restricted MECHANISMS OF COGNITIVE IMPAIRMENT DEVELOPMENT IN AGED HYPERTENSIVE RATS: FOCUS ON MACROPHAGES(ProQuest, 2023) Alshammari, Abdulkarim; Fagan, Susan; Zhang, DuoStroke survivors have an increased risk of developing long-term disability and dementia. Hypertension and aging are major contributing factors to vascular dementia, stroke, and the development of PSCI. Most animal models fail to capture the complex interplay between these pathophysiologic processes. The purpose of this dissertation is to investigate the impact of aging and hypertension on cognitive function, prior to, and following stroke. We utilized aged hypertensive rats to study the trajectory of vascular cognitive impairment, and to investigate the impact of delayed and chronic stimulation of Angiotensin II type 2 receptor on stroke outcomes. Sixty SHRs were housed (in pairs) for 18 months with cognitive assessments every six months and post-surgery. Multiple MRI scans were performed at baseline and throughout the study. At day 3 after stroke, rats were randomized to receive either an angiotensin receptor agonist, Compound 21, or plain drinking water and followed up for 8 weeks. Additionally, we examined the ability of C21 to mediate anti- inflammatory and neurotrophic effects in mouse microglial cell line, C8-B4, and RAW 264.7 macrophages.19 0