Treatments aimed at modifying cardiac substrate utilisation are designed to improve metabolic efficiency. In the fasting state, the heart mainly relies on fatty acid oxidation for its energy production. The heart can adapt to metabolise glucose, lactate and amino acids depending on the predominate milieu and demands placed upon it. A shift from fatty acid oxidation to carbohydrate oxidation leads to a lower oxygen consumption per unit of adenosine triphosphate produced. It is this concept of improving cardiac efficiency by a reduction in oxygen demand that underpins the use of metabolic manipulating agents as a therapeutic strategy in heart failure. Cardiac energy starvation is increasingly recognised as playing a central role in the pathophysiology of heart failure. Alterations in substrate utilisation thus underlie the hope that metabolic manipulating agents will be of benefit in heart failure of both ischaemic and non-ischaemic origin. This metabolic shift is achieved by promoting glucose utilisation and reducing the utilisation of fatty acids. This leads to a greater production of adenosine triphosphate per unit of oxygen consumed. With an ongoing demand for treatment options in ischaemic heart disease and the growing burden of chronic heart failure, new treatment modalities beyond contemporary therapy warrant consideration. This thesis aims to investigate the short term effects of metabolic manipulation on changes in cardiac energetic status, cardiac function, efficiency and substrate utilisation.

published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

This study deals with the role that 'failure' plays in the lives of people, as seen from a pastoral-theological perspective. In this respect, a number of questions presented themselves, including; How the phenomenon known as 'failure' is viewed within the community of the secular sciences? How is the phenomenon known as 'failure' viewed from a Biblical point of view? Can 'failure' be reversed and turned into something beneficial? In the secular world, a 'failure' is seen as someone who does not live up to expectations, or to a person who continually make mistakes and who does not learn from the experience. There is scant room in the secular world for 'failure', and there is an enormous amount of pressure on individuals in society to be 'successful.' This peer pressure to conform to certain expectations carries with it a corresponding fear of 'failure', and therefore being rejected by society. Scripture would appear to view 'failure' in a more lenient light, but at the same time, carries a wider connotation to 'failure' than society does. The purpose of this study is to investigate what is meant by 'failure', both from a basis-theoretical and a meta-theoretical perspective, in accordance with Zerfass's model, in order to develop a counselling model, designed to assist counsellors in the counselling of people who suffer from the effects of 'failure'. The basis-theoretical part of this study found that Scripture does not recognise the phenomenon we call 'failure', apart from man missing God's mark, and sinning. The greatest, or worst form of 'failure' encountered in Scripture is indicative of the sinner not accepting the redemptive work of Christ, and being condemned to perish in eternal damnation. What is colloquially known as 'failure', Scripture treats as stepping stones to success and sanctification. The meta-theoretical part of this investigation brought up an interesting thought: that 'failure' was learned behaviour, a negative set of values that society impresses upon individuals to they must conform to. Where 'failure' is experienced, society teaches the person to cope with 'failure' by utilizing inherent strengths and negating weaknesses, rather than exploring the 'failure' in an endeavour to mine the salient values that are present. From an empirical research, using hermeneutic-phenomenological principles, a model was developed that is intended to assist the counsellor in reversing counselee 'failure' into success. The conclusion of this research is that while broader society may not have an answer to 'failure', pastoral-theology is perfectly positioned to assist with the counselling of people who deem themselves to be 'failures’. / Thesis (Ph.D. (Pastoral))--North-West University, Potchefstroom Campus, 2005.

after vibration endurance testing involves manual inspection only after the test is completed. An adaptable, reliable and low cost real time monitoring and diagnostic system that would interrupt the testing operation at the first onset of a failure is desired. This thesis describes accelerometer based, microphone (single and dualmicrophone) based and acoustic emission sensor based monitoring systems for automotive light assembly failure detection during endurance testing. Preliminary results from accelerometer based and dual-microphone based diagnostic systems show that significant differences between healthy and faulty fog light assemblies can be detected. Based on these initial testing results, subsequent testing and data analysis were conducted for accelerometer based and dual microphone based systems. Four data analysis methods have been used: (1) Averaging signals in the time domain, (2) FFT of time domain waveforms over a specified time, (3) Averaging frequency spectra, and (4) Statistical methods for time domain signals. Individual frequency spectra (from FFT) and the average of multiple frequency spectra have shown potential to distinguish between signals from faulty and healthy light assemblies. Statistical measures, such as, Arithmetic mean (μ) and Kurtosis (K) can also be used to differentiate healthy and faulty light assemblies. In general, this work has shown the good potential to develop methods for adaptable, reliable and low cost real time monitoring and diagnostic systems that would interrupt the testing operation at the first onset of a failure. / Thesis (Master, Mechanical and Materials Engineering) -- Queen's University, 2007-09-28 16:13:47.511

No description available.

No description available.

The present studies investigated the relationship between altered renal carbohydrate intermediary metabolism and kidney functional and structural changes in the adult Spraque-Dawley rat. Both the acute (upto 28 days) and chronic (60-120 days) diabetic states were invstigated. The single intraperitoneal injection of streptozotocin at a dose of 45mg/kg body weight produced a stable, non-ketotic, non-insulin dependent and reproducible diabetic state. Compared to age matched control animals (AMC), diabetic animals (DA) demonstrated a progressive increase in mean UFR, plasma glucose, creatinine, glycosuria values and urea clearance rate over the experimental course while creatinine clearance (CCR) fell from day 21 onwards reaching 50% of AMC values by day 120. Changes in renal and hepatic metabolite concentrations were apparent after 4 days of diabetes and two patterns emerged. Renal and hepatic glucose, glocuse-1-phosphate and β-hydroxybutyric acid concentrations progressively increased over the 120 days experimental period while reduced concentrations of glycolytic and other metabolic intermediates, namely, glucose-60-phosphate, fructose-6-phosphate, fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone 3- phosphate and malonyl-CoA concentrations were present. Increased concentrations of BHBA in both the liver and kidney was accompanied by the progressive reduction of malonyl-CoA. Since gluconeognesis is favoured at the expense of glycolysis in these diabetic animals, the absence of phosphofructokinase activity may be explained by a decreased concentration of fructose-6-phosphate. Renal gluconeogenic enzymes such as fructose-1,6-phosphatase were mainly located in the kidney cortex, predominantly located in the proximal tubular epithelium and that glycolytic enzymes such as hexokinase occurred mainly in the kidney medulla, restricted essentially in distal segments. Histological examination demonstrated an increasing degree of renal clear cell changes affecting from 5-20% of cells noted from day 10 to day 120, respectively in the cortical renal tubules. In addition acute pyelonephritis was also observed in all diabetic animals on days 90 and 120.

My studies have investigated the possible involvement of the plasminogen activator/plasmin system in glomerular physiology and pathology. Urokinase plasminogen activator and its cellular receptor are not found immunocytochemically within the normal or diseased glomerulus in vivo. Plasminogen activator inhibitor-1, an inhibitor of urokinase plasminogen activator was, however, identified in crescents from cases of crescentic glomerulonephritis, but not within the glomerular tuft proper. Culture of human glomerular cells initially revealed urokinase plasminogen activator and plasminogen activator-1 proteins within the supernatant of epithelial cells and mesangial cells, as measured by ELISA. However, immunocytochemical characterisation of each of the cell cultures showed that there was contamination of some of the mesangial cell cultures by epithelial cells. Pure cultures of both types of cell produced plasminogen activator inhibitor-1. However, measurement of urokinase plasminogen activator activity by zymography confirmed that this molecule was not present within supernatants obtained from pure mesangial cell cultures. Furthermore, the use of combined non-isotopic in situ hybridisation and immunocytochemistry allowed identification of urokinase plasminogen activator mRNA only within human cultured glomerular epithelial cells and not within mesangial cells. This finding proved that contaminating epithelial cells were responsible for urokinase plasminogen activator production in cultures thought to be made up of pure mesangial cells. Thus there is excellent evidence for synthesis of this molecule only by epithelial cells. Non-isotopic and radioactive in situ hybridisation were unsuccessful in identifying urokinase plasminogen activator within human kidney sections and the difficulties involved in the methodology of this technique, and the implications of the culture cell work for the role of the plasminogen activator/plasmin system in the glomerulus, are discussed.

Chronic renal failure (CRF) is associated with loss of lean body mass, a high incidence of malnutrition, and with insulin resistance. CRF is often complicated by metabolic acidosis. Metabolic acidosis is known to alter both protein and carbohydrate metabolism. A series of studies have been undertaken to investigate the effect of metabolic acidosis on protein metabolism in both normal and CRF human subjects, and to study whether metabolic acidosis in CRF affects insulin sensitivity. Protein turnover was studied using the technique of primed constant infusions of L-[1-¹³C]leucine. Normal subjects were studied before and after ammonium chloride induced metabolic acidosis. Acidosis was associated with increased protein turnover and amino acid oxidation. In CRF subjects, correction of acidosis with sodium bicarbonate decreased protein turnover and amino acid oxidation. The effect of acidosis in CRF on insulin mediated carbohydrate metabolism was studied using the technique of the hyperinsulinaemic euglycaemic clamp. Insulin sensitivity increased with correction of acidosis. By combining L-[1-¹³C]leucine infusions with hyperinsulinaemic euglycaemic clamps, the response of protein metabolism to hyperinsulinaemia was measured before and after correction of acidosis. The presence of acidosis did not impair the ability of insulin to modulate protein metabolism. There is therefore, dissociation between the effects of acidosis in CRF on insulin mediated carbohydrate metabolism and insulin mediated protein metabolism. In summary, metabolic acidosis increases protein catabolism in both normal and CRF man and may contribute to the loss of lean body mass characteristic of CRF. Insulin resistance in CRF improves with correction of acidosis. However the effects of acidosis on protein metabolism are not mediated via alterations in insulin sensitivity.

No description available.