Introduction: Hypertension is a complex disease that affects about 40% of adults worldwide, and is a major risk factor for cardiac hypertrophy and heart failure. Abnormal calcium handling plays a key role in hypertension and cardiovascular disease. In order to function normally cells of the cardiovascular system need to keep intracellular Ca2+ levels under tight control. This is achieved by a number of Ca2+ handling proteins including the plasma membrane Ca2+-ATPase (PMCA). Recent genome wide association studies have shown that single nucleotide polymorphisms in ATP2B1, the gene encoding PMCA1, are strongly linked with hypertension risk. Hypothesis: PMCA1 plays an important role in regulation of blood pressure and protection against hypertension and cardiac hypertrophy. Aims: This thesis aims to examine whether there is a link between PMCA1 and blood pressure regulation, and the development of hypertension. It also aims to determine the impact this link may have on cardiac structure and function. Methods and Results: To study the role of PMCA1, a global PMCA1 heterozygous knockout mouse (PMCA1Ht) was used. Under basal conditions, 3 month old PMCA1Ht mice had about 50% reduction in PMCA1 protein expression compared to the wild type (WT) mice. PMCA1Ht and WT mice had similar blood pressure as measured by tail-cuff method. To study the mice under hypertensive stress conditions, 3 month old PMCA1Ht and WT mice were infused via minipump with angiotensin II. Upon angiotensin II treatment, PMCA1Ht mice showed a significantly greater increase in systolic and diastolic pressure compared to WT mice. Angiotensin II also induced vascular remodelling, with PMCA1Ht mice having greater media thickness and cross sectional area than WT mice. Moreover, PMCA1Ht mice showed a significantly greater cardiac hypertrophic response than WT mice. On the other hand, cardiac function and heart rate were similar in PMCA1Ht and WT mice. While angiotensin II had no effect on PMCA1 expression in the heart, it significantly increased PMCA1 expression in the aortas of both WT and PMCA1Ht mice. More importantly, WT mice had significantly higher PMCA1 expression level than the PMCA1Ht mice treated with the same dose of angiotensin II. This suggests that PMCA1 plays a pivotal role in Ca2+ extrusion in the vasculature and that under stressful conditions PMCA1Ht mice are less able to respond to stress through a compensatory increase in PMCA1 expression, leading to increased intracellular Ca2+ concentration, which in turn leads to increased vascular contractility and increased blood pressure. Conclusion: This work provides evidence that PMCA1 is involved in blood pressure regulation and protects against the development of hypertension and cardiac hypertrophy.

No description available.

Binary element-hydride systems have become a pertinent topic for high pressure research, following the measurement of record high temperature superconductivity in the dense hydrogen-sulfur system. The experimental study followed predictions of superconductivity with high transition temperature (Tc) in (H2S)2H2 at high pressures, leading to the current consensus that the high Tc phase is H3S, produced from the decomposition and recombination of H2S at high pressures. However, conjecture over the behaviour of hydrogen sulfide upon compression, and experimental limitations, cast significant ambiguity over interpretations of the structure and mechanism of the superconducting phase. Nonetheless, theory also predicts high Tc superconductivity in the dense hydrogen selenide and telenide systems; both experimentally uncharted at high pressures prior to this study. This thesis explores and maps the phase diagrams of hydrogen-chalcogen (S, Se, Te) systems using a combination of high pressure Raman spectroscopy and x-ray diffraction techniques. Gaining a comprehensive understanding of the behaviour of these systems under pressure is crucial to the eventual elucidation of the true nature of high Tc superconductivity. Hydrogen sulfide (H2S) and hydrogen selenide (H2Se) are appreciably toxic. A simple in situ synthesis technique is reported for producing hydrogen-chalcogenides directly from their constituent elements within diamond anvil cells, circumventing the need to condense toxic gases. This technique is also utilised to provide excess hydrogen, in order to produce the hydrogen-rich cocrystals thought to be vital to the formation of the high Tc phase. The hydrogen-sulfur system is most thoroughly investigated, and first presented. High quality Raman spectroscopic data provides an experimental review of pure H2S. Studies of (H2S)2H2 evaluate the current known ambient temperature phases and reveal three novel low temperature phases. Phase II0 is identified on cooling of phase I to 173 K (10 GPa), via splitting of both the single S-H stretching mode and low-frequency H2 vibron; sharp stretching modes indicate a significant reduction in orientational disorder. Successive splitting of the low-frequency H2 vibrons indicates two additional phase changes at 29 GPa (phase III0) and 53 GPa (phase- IV0) respectively, at 80 K. Phase IV0 is associated with an overall increase in symmetry. Evidence is also presented for a tentative fourth novel low temperature phase at ~160 GPa (20 K) and for the formation of an exceptionally stable hydrogen-sulfur compound with potentially novel stoichiometry. The behaviour of the H2S and (H2S)2H2 mixed molecular system is also reported; demonstrating that the coexistence of (H2S)2H2 and H2S can influence the hydrogen-bonding within both systems at high pressures. The first high pressure studies of the hydrogen-selenium system at ambient temperature are reported. The high pressure phase sequence of H2Se (I { I0 - IV) is identified by Raman spectroscopy, mirroring that of H2S. The isothermal boundaries for phases I0 and IV are found at 7 and 12 GPa respectively, at 300 K. Phase IV may have higher symmetry than phase IV H2S. X-ray diffraction and Raman spectroscopy demonstrate that the H2Se:H2 mixtures form cocrystals of (H2Se)2H2 from 4.2 GPa, with tetragonal space group I4=mcm, analogous to (H2S)2H2. Both H2Se and (H2Se)2H2 are shown to decompose into their constituent elements above 24 GPa. Attempts to synthesise the elusive H2Te directly from hydrogen and tellurium are reported. No reaction occurs upon heating Te in H2 at 0.2 GPa to 573 K. No visible reaction occurs between H2 and the high-pressure phases of Te, upon laser-heating. No photoreaction occurs upon exposure of tellurium in hydrogen to intense laser light (532 nm) at 0.2 GPa and 300 K, but formation may be stabilised at lower temperatures.

Lee, Shun Hang = 密度泛函理論計算的壓力修正 / 李信恆. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (p. 67-69). / Abstracts in English and Chinese. / Lee, Shun Hang = Mi du fan han li lun ji suan de ya li xiu zheng / Li Xinheng. / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Theoretical backgrounds --- p.4 / Chapter 2.1 --- Density Functional Theory --- p.4 / Chapter 2.2 --- Pseudopotential approximation --- p.6 / Chapter 2.3 --- Car-Parrinello Molecular Dynamics --- p.8 / Chapter 3 --- Simulation details --- p.10 / Chapter 3.1 --- Simulation overview --- p.10 / Chapter 3.2 --- Electronic minimization --- p.11 / Chapter 3.2.1 --- The need and setting of electronic minimization --- p.11 / Chapter 3.2.2 --- Results and convergence of electronic minimization --- p.13 / Chapter 3.3 --- Atomic minimization --- p.13 / Chapter 3.4 --- CPMD runs and parameter settings --- p.14 / Chapter 3.4.1 --- The NVE ensemble --- p.14 / Chapter 3.4.2 --- The NVT ensemble --- p.14 / Chapter 3.5 --- Taking the average --- p.20 / Chapter 3.6 --- Check for valid stress tensors and pressure --- p.22 / Chapter 3.7 --- Check for the structure --- p.24 / Chapter 3.7.1 --- The need for structure checks --- p.24 / Chapter 3.7.2 --- Methods to check the structures --- p.24 / Chapter 4 --- Pressure Correction --- p.30 / Chapter 4.1 --- Theoretical Basis for the Correction --- p.30 / Chapter 4.2 --- CPMD Calculation Results --- p.32 / Chapter 4.2.1 --- E(V) at different T --- p.34 / Chapter 4.2.2 --- Results of stress tensor checks --- p.35 / Chapter 4.2.3 --- The EOS's found in this study --- p.38 / Chapter 4.2.4 --- Comparisons with others´ة work --- p.39 / Chapter 4.2.5 --- Difference between LDA and GGA results --- p.42 / Chapter 5 --- Magnesium Silicate (MgSiO3) --- p.45 / Chapter 5.1 --- Simulations for MgSiO3 perovskite --- p.47 / Chapter 5.1.1 --- Simulation parameters and various check --- p.47 / Chapter 5.1.2 --- Results for MgSiO3 perovskite --- p.50 / Chapter 5.2 --- Simulations for MgSiO3 post-perovskite --- p.53 / Chapter 5.2.1 --- Simulation parameters and various check --- p.53 / Chapter 5.2.2 --- Results of MgSiO3 post-perovskite --- p.55 / Chapter 6 --- Discussions --- p.58 / Chapter 6.1 --- Other thermodynamic quantities --- p.58 / Chapter 6.2 --- Asymptotic behaviour of ΔP(V) --- p.59 / Chapter 6.3 --- Applications to the exact XC functional --- p.60 / Chapter 7 --- Conclusion --- p.61 / Chapter 8 --- Appendix --- p.62 / Chapter 8.1 --- Efficient method to perform electronic minimization --- p.62 / Chapter 8.2 --- Efficient method to perform atomic minimization --- p.63 / Chapter 8.3 --- Other related settings --- p.64 / Chapter 8.4 --- Typical input files for CPMD calculations using Quantum-Espresso --- p.65 / Bibliography --- p.67

Thesis (M Med (Family Medicine))--University of Limpopo, 2010. / Background: The state of Hypertension disease is universally under diagnosed and/or inadequately treated resulting in extensive target-organ damage and premature deaths. Therefore, sustainable and aggressive population-based programs for hypertension awareness, prevention, treatment, and control are keys of success in limiting this epidemic. The study aims to determine the Kang Adult population’s hypertension prevalence and the relationship between high blood pressure, anthropometric measures and their life style factors such as diet, use of tobacco products and alcohol consuming habits. Methodology: The study, a population based cross-sectional trial, was conducted on adult residents of Kang (18 year-old and above) from November to December 2008. Data was collected using the questionnaire, through physical measurements of weight, height and BP using a modified protocol based on World Health Organization (WHO) STEP wise instruments on chronic disease (Bonita, 2001). The sample consisted of 161 participants between 20 and 82 years of age. Results: Hypertension was observed in 31.6% of participants (95% CI: 24.6%-39.5%). With regard to the hypertension prevalence rate, no significant differences were observed between males and females (males 28.3% versus females 33.6%, p = 0.59). An elevated blood pressure was seen with significantly higher frequency in overweight group compared with the normal weight group (p = 0.029), in obese group compared x with the normal weight group (p = 0.002), and in obese group compared with the overweight group (p = 0.045). The study found no significant association between hypertension and use of tobacco products (p=0.46) or alcohol consumption (p=0.73), went in vigorous-intensity activity (p=0.22) and moderate-intensity activity that causes large increases in breathing, or heart rate for at least 10 minutes continuously (p=0.70). Conclusions: It is concluded that hypertension is a common problem in adult Kang population, with a prevalence of 31.6%. Hypertension prevalence was found to be associated with anthropometric measurements such as overweight and obesity. No significant association between hypertension and use of tobacco products, alcohol consumption, vigorous-intensity and moderate-intensity activities that cause increases in breathing or heart rate for at least 10 minutes continuously. However, the present study had the limitation of a small sample size. Further studies are needed to clarify the hypertension magnitude throughout the country, with large samples.

Thesis (Family Medicine)-- University of Limpopo, 2010. / Summary not available

Cellular responses to changes in pressure are implicated in numerous disease processes. In glaucoma apoptosis of retinal ganglion cells (RGCs) is associated with elevated intra-ocular pressure (IOP), however the exact cellular basis of this link remains unclear. This research aimed to examine the direct response of neuronal cells to elevated hydrostatic pressure in terms of apoptosis. We developed an in vitro model consisting of a pressure chamber to adjust ambient hydrostatic pressure, a source of neuronal cells and methods to measure apoptosis in these cells. The neural cells examined were primary retinal cultures, four neuronal cell lines (B35, PC12, C17, NT2), and the RGC-5 cell line. Pressure conditions selected were within physiological limits; 100 mmHg above atmospheric pressure (as seen clinically in severe acute glaucoma) and extended in RGC-5 neurons to 30 mmHg (chronic glaucoma) and 15 mmHg (normal IOP). Apoptosis was detected by cell morphology and specific immunochemical markers: TUNEL and Annexin V. Caspase-3 activation, a known pathway of apoptosis, was also investigated in RGC-5 neurons. These fluorescent markers were detected and quantified by automated Laser Scanning Cytometry. Negative controls were treated identically except for the application of pressure, while positive controls were generated by treatment with a known apoptotic stimulus. The results showed that neurons responded to elevated hydrostatic pressure directly and that an apoptotic process was induced. There was a greater level of apoptosis in pressurised cells compared to the negative controls. This apoptotic effect at high pressures was seen in primary rat retinal cultures and in both undifferentiated (B35, C17, NT2, RGC-5) and differentiated (PC12, RGC-5) neuronal cell lines. RGC-5 neurons showed a graded response, proportionate to the level of pressure elevation, representative of the severity of analogous clinical settings (acute, chronic glaucoma & normal). RGC-5 neurons also showed increased activation of Capsase-3. Thus this pathway may play a role in pressure induced apoptosis. Our findings indicate that pressure alone may act as a stimulus for apoptosis in neuronal cells. We suggest the possibility of novel mechanisms of pressure related mechanotransduction and cell death, relevant to the pathogenesis of glaucoma.

Thesis (Ph. D.)--Washington State University, December 2007. / Includes bibliographical references (p. 198-231).

Thesis (M.S.)--University of Delaware, 2007. / Principal faculty advisor: David G. Edwards, Dept. of Health, Nutrition, and Exercise Sciences. Includes bibliographical references.

Thesis (Ph. D.)--Landbouwhogeschool te Wageningen, 1981. / Summary in Dutch. Includes bibliographical references (p. 170-176).