Class of 2012 Abstract / Specific Aims: To assess the chemical stability of ampicillin for injection in normal saline at pH values ranging from 5 to 6. Methods: A stability-indicating high performance liquid chromatography (HPLC) method was developed and used to determine the stability of ampicillin for injection in normal saline following buffering with sodium acetate and acid adjustment with HCl at pH values of 5, 5.5, and 6. To confirm that the assay was stability-indicating, ampicillin trihydrate reference standard (1 mg/mL) was exposed to alkali, acid, and oxidative stress conditions and analyzed by HPLC for the presence of degradation products. Analysis was performed on a reverse-phase (C-18) column with a mobile phase consisting of water, acetonitrile, 1 M monobasic potassium phosphate, and 1 N acetic acid (909:80:10:1). Other HPLC parameters were: flow rate 1 mL/min; detection wavelength 254 nm; injection volume 20 µL; column temperature 30˚C. The method was evaluated for linearity, precision, and accuracy. The chemical stability of ampicillin for injection (18 mg/mL) in normal saline and sodium acetate (pH adjusted at values of 5, 5.5, and 6) was assessed at baseline (t=0), 7, 11, 17, 31, and 44 hours and compared to a control solution (no pH adjustment). Measurements at each time interval were performed in triplicate. Main Results: Ampicillin trihydrate reference standard (1 mg/mL) was adequately separated from degradation products following exposure to alkali, acid, and oxidative stress conditions. After 16 hours, a precipitate was observed in the solution at pH 6, and therefore stability is not reported. All other solutions (pH 5, pH 5.5, and control) were stable for at least 24 hours at room temperature and yielded t90 values of 110, 64.2, and 27.5 hours, respectively. Conclusions: Adjustment of intravenous ampicillin solutions to pH values of 5 or 5.5 significantly increased stability. Ampicillin appears to be most stable at a pH near its isoelectric point (pH 5).

The brain microcirculation plays a key role in cerebral physiology and neuronal activation. In the case of degenerative diseases such as Alzheimer’s, severe deterioration of the microvascular networks (e.g. vascular occlusions) limit blood flow, thus oxygen and nutrients supply, to the cortex, eventually resulting in neurons death. In addition to functional neuroimaging, modelling is a valuable tool to investigate the impact of structural variations of the microvasculature on blood flow and mass transfers. In the brain microcirculation, the capillary bed contains the smallest vessels (1-10 μm in diameter) and presents a mesh-like structure embedded in the cerebral tissue. This is the main place of molecular exchange between blood and neurons. The capillary bed is fed and drained by larger arteriolar and venular tree-like vessels (10-100 μm in diameter). For the last decades, standard network approaches have significantly advanced our understanding of blood flow, mass transport and regulation mechanisms in the human brain microcirculation. By averaging flow equations over the vascular cross-sections, such approaches yield a one-dimensional model that involves much fewer variables compared to a full three-dimensional resolution of the flow. However, because of the high density of capillaries, such approaches are still computationally limited to relatively small volumes (<100 mm3). This constraint prevents applications at clinically relevant scales, since standard imaging techniques only yield much larger volumes (∼100 cm3), with a resolution of 1-10 mm3. To get around this computational cost, we present a hybrid approach for blood flow modelling where the capillaries are replaced by a continuous medium. This substitution makes sense since the capillary bed is dense and space-filling over a cut-off length of ∼50 μm. In this continuum, blood flow is characterized by effective properties (e.g. permeability) at the scale of a much larger representative volume. Furthermore, the domain is discretized on a coarse grid using the finite volume method, inducing an important computational gain. The arteriolar and venular trees cannot be homogenized because of their quasi-fractal structure, thus the network approach is used to model blood flow in the larger vessels. The main difficulty of the hybrid approach is to develop a proper coupling model at the points where arteriolar or venular vessels are connected to the continuum. Indeed, high pressure gradients build up at capillary-scale in the vicinity of the coupling points, and must be properly described at the continuum-scale. Such multiscale coupling has never been discussed in the context of brain microcirculation. Taking inspiration from the Peaceman “well model” developed for petroleum engineering, our coupling model relies on to use analytical solutions of the pressure field in the neighbourhood of the coupling points. The resulting equations yield a single linear system to solve for both the network part and the continuum (strong coupling). The accuracy of the hybrid model is evaluated by comparison with a classical network approach, for both very simple synthetic architectures involving no more than two couplings, and more complex ones, with anatomical arteriolar and venular trees displaying a large number of couplings. We show that the present approach is very accurate, since relative pressure errors are lower than 6 %. This lays the goundwork for introducing additional levels of complexity in the future (e.g. non uniform hematocrit). In the perspective of large-scale simulations and extension to mass transport, the hybrid approach has been implemented in a C++ code designed for High Performance Computing. It has been fully parallelized using Message Passing Interface standards and specialized libraries (e.g. PETSc). Since the present work is part of a larger project involving several collaborators, special care has been taken in developing efficient coding strategies.

Phenylpropanolamine (PPA), a sympathomimetic amine, has been widely used over the past 40 years as a decongestant and, in much larger dosages, as an appetite suppressant. Considerable interest has recently been shown in this drug due to its increasing popularity as an over-the-counter anorectic agent. Much controversy exists concerning the unfavourable side-effects of PPA resulting from the higher doses required for appetite suppression and the potential of this drug for abuse. A literature search revealed a paucity of information concerning the determination of PPA in biological fluids and, most noticeably, on the pharmacokinetics of this drug. An original method for determining PPA in serum and urine using high performance liquid chromatography (HPLC) which has increased sensitivity over other published HPLC methods is presented here. The simplicity of the extraction from biological fluids and subsequent determination by HPLC, enables concentrations of PPA to be monitored after a single dose of the drug. This method is therefore readily applicable to bioavailability and pharmacokinetic studies. The dissolution profiles of 4 sustained-release formulations of PPA were determined in a modified USP rotating paddle apparatus and the samples analysed using HPLC. A mathematical equation was applied to these data which are expressed in terms of dissolution parameters. Oral test dosage forms and solutions of PPA were investigated in bioavailability trials using the developed HPLC method to analyse the urine and serum samples. Linear one body compartment kinetics were assumed and the WagnerNelson method used to transform in vivo serum data to absorption plots which were then fitted to the well known Weibull equation. In order to more appropriately characterize the kinetic processes of absorption, distribution and elimination, a more complex model was utilized which involved numerical integration of a series of differential equations. The data were fitted to these models using nonlinear regression techniques. The pharmacokinetics of PPA are shown to exhibit some evidence of nonlinearity. The absorption of the drug appears to be di scontinuous and PPA seems to favour a two body compartment model.

Master of Science / Department of Electrical and Computer Engineering / Don M. Gruenbacher / The method for communicating within an interconnection network, or fabric of connections between nodes, can be as diverse as are the applications which utilize them. Because of dynamic traffic loads on these interconnection networks, fully-adaptive routing algorithms have been shown to exploit locality while balancing loads and softening the effects of hot-spots. One issue which has been overlooked is the impact of data traveling along the periphery of a selected minimal routable quadrant (MRQ) within these fully-adaptive algorithms. As data aligns with the destination in the x, y, and z dimensions for instance, the data then traverses the periphery of an MRQ. For each dimension that this occurs, the data is given one less choice for routing around hotspots which could appear later along the path. By weighting the decision of selecting a next-hop by avoiding the periphery of the selected MRQ, the data then has more options for avoiding hotspots. One hybridized routing algorithm which borrows heavily from CQR (an efficient and stable fully-adaptive algorithm), is introduced within this work. Enhanced CQR with Periphery Avoidance, attempts to weight the routing decision for a next hop using both output queues and the proximity to the periphery of the MRQ. This fully-adaptive algorithm is tested using simulations and a laboratory research cluster using a USB interconnect in the hypercube topology. It is also compared against other static, oblivious, and adaptive algorithms. Thor's Tack Hammer, the Kansas State University research cluster, is also benchmarked and discussed as an inexpensive and dependable parallel system.

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No description available.

Magister Artium (Sport, Recreation and Exercise Science) - MA(SRES) / This study is motivated by the growing need for South African sport competitions (such as the Olympic Games and various other sport-specific world championships) to be transformed into quality and profitable events, noting that they need to be managed professionally, with well organised and sophisticated athlete preparation with excellent management systems. New pressures have emerged from within South Africa from key stakeholders that require sport organisations to become more performance orientated, and to build their capacity in order to improve or better manage their organisational performance. The primary focus of the research, therefore, is on quality management practices in high performance sport at a programme management level while the research also reviews substantial literature concerning the study in order to explain the dynamics surrounding the high performance management practices of Swimming Centres of Excellence at the two selected universities in South Africa. The study is qualitative and unpacks two theoretical frameworks namely, Total Quality Management practices and a conceptual framework of high performance management structures and processes. The overarching findings and recommendations are that the implementation of the Quality Management Practices (QMPs) require that the principles and philosophy of excellence are shared and understood by all stakeholders. To implement QMPs successfully, there is a need to radically transform conventional practices to achieve radical and pervasive change. The research shows evidence that QMPs involve the redesign of organisational structures, the re-design of work and the re-definition of management style. The swimming high performance environment must be willing to take this into consideration for successful implementation of QMPs at the Centres of Excellence to ensure its future performance

Magister Artium (Sport, Recreation and Exercise Science) - MA(SRES) / Despite government’s formation of financial support grants such as the Operational Excellence Programme to provide much needed assistance, South African elite athletes have not been performing to expectation at recent international championships, such as the Olympic Games. International experiences demonstrate the importance of a well-structured and implemented funding support system to improve elite athlete performance at international levels. This has led to questions of how to improve this situation for elite South African athletes who receive funding support from the South Africa Sports Confederation and Olympic Committee and to revisit the implementation of the funding support for elite athletes. This study will take, experiences of South African elite athletes as well as sport managers into consideration and will also look at international lessons of experience of the funding support of elite sport to provide improved options for financial support and elite athlete development. Using qualitative research methods, this study explored the underlying factors regarding funding support of elite athletes in South Africa based on experiences and perceptions of elite athletes. Within the context of the study, elite athletes would refer to senior track and field athletes and senior swimmers who had been a part of Team South Africa and represented the nation at international competitions. Data was collected in three ways: a) A literature review in the form of an analysis of the high performance policies of: the National Olympic Committee of South Africa and the South African Sports Confederation and Olympic Committee that has governed elite sport in South Africa post 1994 and the policies that govern high performance funding support within Athletics South Africa and Swimming South Africa; b) interviews with eight preselected elite athletes to discuss career performances and funding support received and c) interviews with four coaches/managers of the preselected elite athletes to discuss their perspectives on the funding support their athletes received. Strict ethics considerations were also adhered to insofar as written consent was obtained from all participants beforehand, as the intended interviews would be either audio recorded or video recorded. Pseudonyms were also used for participants with the assurance that participation was voluntary. The eventual findings of the study brought to light that the implementation of the funding support provided by the South African Sports Confederation and Olympic Committee was good in theory but not necessarily so in practice. Overall, participants were grateful for the support received but felt that certain changes needed to be considered going forward for the improvement of future performances.

The process of investigating plants to identify chemical substances is of great interest to natural product scientists because there is a need to discover new drugs for treating diseases. In our study, plant extracts were prepared from the bulbs of Crinum macowanii, Boophane disticha as well as Eucomis autumnalis and further experiments were made on the extracts. High performance liquid chromatography with other instruments (ultra-violet detector, mass spectrometer) coupled to it, were used in the search for the active ingredients in the extracts prepared. Old methods of separation and identification such as flash column chromatography and thin layer chromatography also played an important role in the investigation of these extracts. Other techniques such as nuclear magnetic resonance (NMR), helped in the structural elucidation once the compounds had been purified. The use of analytical techniques (HPLC-MS, NMR) was found to be important in the process of investigating the extracts and the presence of various active ingredients was confirmed. The methods used traditionally for extract preparation (boiling plants in water for certain amount of time) were investigated and the important relationship between the boiling time and concentration of the active components was established. It was found that the increase in boiling time of the plants during preparation decreases the concentrations of the active components. The experiments conducted provide some scientific evidence which motivates that the traditional preparations of the plants are related to the dosage. / Dissertation (MSc (Chemistry))--University of Pretoria, 2008. / Chemistry / unrestricted

Erythromycin is a macrolide antibiotic with a spectrum similar to penicillin and is used mainly in the treatment of infections caused by gram-positive organisms. Since its discovery in 1952, erythromycin has achieved wide-spread clinical use. Susceptibility of erythromycin base to inactivation by acid results in decreased availability following exposure to acidic gastric fluids. Formulation of acid resistant dosage forms and the preparation of acid stable chemical derivatives have been attempted to improve absorption and subsequent clinical efficacy . Two of the most commonly used erythromycin derivatives are the stearic acid salt (erythromycin stearate) and the lauryl sulphate salt of the propionyl ester (erythromycin estolate). Although it has been known for many years that erythromycin is susceptible to acid degradation, very few reports on the stability of erythromycin in aqueous solutions appear in the literature. In this study, a high-performance liquid chromatographic system using electrochemical detection was employed for a kinetic study of erythromycin degradation. The effect of varying acid pH on the degradation rate of both erythromycin base and erythromycin stearate, and the effect on the hydrolysis rate of erythromycin estolate is presented. In addition, the effect of temperature on erythromycin degradation was also investigated. Until recently, the majority of pharmacokinetic and bioavailability studies have utilized relatively non-specific microbiological assay procedures. However, in this study a solid phase extraction, followed by the use of a high-performance liquid chromatographic system using electrochemical coulometric detection was employed for the determination of erythromycin in biological fluids. Human volunteers each received enteric coated erythromycin base pellets in capsule dosage form and also film coated erythromycin stearate tablets on separate occasions. Results from the clinical trials revealed the enteric coated erythromycin base pellets had a greater bioavailability than the film coated erythromycin stearate tablets. Computer fitting of data revealed no intra-volunteer variability in elimination rate constants, suggesting differences in serum levels following administration of both dosage forms are due to variation in absorption. Results from the clinical trials were also compared with those obtained from a further trial, during which the same volunteers received erythromycin estolate