Lead exposure poses as a risk factor for various adverse health effects including intellectual delays, reduced IQ, and behavioural problems in children, as well as cognitive decline in adults. Lead enters drinking water through corrosion of leaded materials such as lead pipes, solder, and brass devices. Three rounds of residential and non-residential lead monitoring were conducted to evaluate the corrosion control implemented by Halifax Water, and to identify sites with elevated lead concentrations. Follow-up testing was conducted at several sites to determine the sources of lead, and the factors that contributed to high lead release. Finally, a bench scale experiment was conducted to determine the impacts of plumbing flux on metal release. The lead action level for residential testing was exceeded only in the round that was conducted during the winter. Lead concentrations were also higher in the winter rounds than the fall round of non-residential sampling. The seasonal lead variation was likely caused by fluctuations in aluminum residuals in the water leaving the plant. Frequency of use, age, and outlet manufacturer were factors that were associated with elevated lead levels. Follow-up studies were conducted at several fountains to determine the source of elevated lead levels. These fountains typically contained several leaded components and received infrequent use. Fountains with leaded components that received high, regular usage had often provided samples with low lead levels. Drinking fountains that were banned and recalled in the US for potentially containing lead lined cooling tanks were found at eight locations throughout the study area. It was found that three of the eight likely contained the lined cooling tanks. High lead levels were present in samples collected from these fountains, even at sites with frequent usage. Low-use sites with the lead lined tank produced the highest lead levels in this study. Fountains suspected of containing lead lined tanks were removed and replaced, and the lead levels were significantly reduced at these sites. The impact of plumbing flux on metal concentrations was relatively short in duration, lasting only a week for most metals, with the exception of tin. Lead levels were found to stabilize under all flux conditions following roughly 40 L of flushing. Flux type was the main factor contributing to the elevated metals. The traditional petroleum flux was much more resistant to flushing than the water soluble flux, as it caused elevated tin levels for several weeks and a tacky flux deposition in the copper pipe remained even three months after the start of the experiment. The high amount of chloride from the flux was aggressive towards the copper corrosion, but it is unclear if this would have led to copper pitting corrosion.

Inflammatory bowel disease (IBD) alters neuronal regulation of the gastrointestinal (GI) tract. The superior mesenteric ganglia (SMG) contain sympathetic neurons that modulate GI functions such, as motility and blood flow. IBD reduces the release of noradrenaline, a sympathetic neurotransmitter. We hypothesized that the reduction in NA release is due to inhibition of voltage-gated calcium current (ICa), as calcium influx is a regulator of neurotransmitter release. We also hypothesized that tumor necrosis factor α (TNFα), a proinflammatory cytokine elevated during IBD, can also inhibit the ICa of SMG neurons. Therefore, we compared ICa amplitude in neurons from normal mice and mice with dextran sulphate sodium (DSS; 5% w/v)-induced colitis. Neurons dissociated from the SMG were cultured overnight and changes to ICa were investigated using electrophysiological, Ca2+ imaging, PCR and neurotransmitter release techniques. Colitis significantly reduced ICa of SMG neurons by selectively inhibiting N-type Ca2+ channels. This was accompanied by a reduction in mRNA encoding the N-type channel alpha subunit (CaV 2.2) and a rightward shift in the voltage dependence of activation of ICa. Colitis reduced the NA release from the colon and jejunum. Depolarization-induced release of tritiated-NA was inhibited by ω-Conotoxin GVIA (300 nM). These results suggest that the changes in VGCC observed at the cell bodies of SMG neurons were also occurring at the nerve terminals during colitis. Similar experimental techniques were performed using SMG neurons incubated overnight in TNFα (1nM). TNFα decreased ICa and depolarization-induced Ca2+ influx in SMG neurons. Similar to DSS-induced colitis, the reduction in ICa was limited to N-type Ca2+ channels. Preincubation of neurons with SC 514 (20μM) and Bay 11 7082 (1µM), inhibitors of nuclear factor kappa B signaling, prevented the reduction in ICa. Preincubation with the p38 MAPK inhibitor, PD 169316 (30µM), recovered a smaller portion of the reduction in Ca2+ influx. These data suggest that DSS colitis and TNFα inhibit N-type VGCC ICa in sympathetic neurons and identify a novel role for NF-κB and p38 MAPK in the regulation of neurotransmitter release. These findings also suggest that DSS colitis inhibits NA release by altering sympathetic N-type VGCC in the colon and jejunum. / Thesis (Master, Physiology) -- Queen's University, 2008-09-02 12:06:20.438

No description available.

<p>The focus of this study is to synthesize a novel hinged polymer actuator. The linking molecule (hinge) is phenazine with interconnected dipyrrole units.</p>

The aim of the present study was to formulate oral modified release matrices of diclofenac sodium, using the Eudragit® polymers. In addition to the formulation processes, numerous variables had to be investigated, which included dissolution variables, formulation variables, and processing variables. The application of the tabletting technique as well as the use of Eudragit® polymers to modify the release of diclofenac sodium is motivated at the outset. A comprehensive review of modified drug release, the use of the tabletting methodologies and the application of Eudragit® polymers are presented. In-process quality control tests as well as the mechanisms and interpretation of the dissolution process are outlined. Diclofenac sodium, a potent nonsteroidal anti-inflammatory drug, was used in the present study, hence a brief review of this drug is also presented. The direct compression as well as the wet granulation tabletting methods were investigated. The major limitation of the direct compression method was found to be the lack of suitable flow properties of the powder blend. The wet granulation technique however, was successfully employed to prepare various diclofenac sodium Eudragit® matrix tablets. All tablets were prepared to contain 100 mg diclofenac sodium. The optimisation process was shown to be an integral procedure in influencing the matrix characteristics. In addition, it was shown that drug release was significantly influenced by different types and concentrations of Eudragit® polymers. A specific formulation was selected to investigate the integrity of the matrices produced by the wet granulation technique. The drug release profile of a commercially available modified release preparation containing diclofenac sodium viz. Veltex® 100 CR (reference standard) was also obtained. A comparison of the drug release profiles of Veltex® 100 CR capsules and the selected formulation showed them to be markedly dissimilar. Hence, a strong motivation is provided for rationalising the selection of the particular formulation in the present study, that was shown to release diclofenac sodium optimally. The selected formulation was prepared using a combination of the Eudragit® RL and Eudragit® RS polymers. In vitro dissolution studies on the selected as well as various other formulations demonstrated the wet granulation method to be both predictable and reproducible. However, absolute drug release independency of dissolution methods, media and agitation rates was unattainable. Furthermore, drug release was shown to be pH dependent. The selected formula was subjected to certain formulation and processing variables. An increase in the concentrations of lactose and starch was shown to increase drug release. Different types of diluents were also shown to influence drug release from the tablets. The method of incorporation of the lubricant, magnesium stearate, was investigated. Compression studies demonstrated the susceptibility of the tablets to changes in drug release behaviour and morphological characteristics as the hardness was varied. X-ray diffraction studies demonstrated that the processes of granulation and compression did not promote any atomic rearrangement of the drug and Eudragit® polymers. Scanning electron microscopy was useful in investigating the integrity and surface morphology of newly formulated as well as stored samples, while energy dispersive x-ray microprobe analysis adequately revealed the elemental composition of the tablets. The selected formulation was shown to be stable at room temperature (21 ±1°C) and low temperature (5± 1°C), while storage at 37°C with 80% relative humidity and 40°C demonstrated significantly decreased drug release behaviour during short term (3 months) stability testing. Tablet hardness evaluated during the stability testing showed that there were virtually no differences in tablet hardness between the room temperature and low temperature samples, while tablets stored at 37°C with 80% relative humidity and 40°C hardened considerably. However, tablet potencies and the moisture content of the samples were not significantly influenced during the storage period. In addition to usual observations and mathematical manipulation, some of the data generated from this study were also evaluated statistically. / Thesis (M.Sc.)-University of Durban-Westville, 1998.

The motivation for the present study is systematically presented and the aims and objectives of the study are clearly defined. A comprehensive review on modified release drug delivery has been presented to provide the basis for the meltable aqueous dispersion technique as an approach to the formulation of a multiple-unit oral modified release drug delivery system. In addition, a brief discussion on the theory of dissolution testing and the mechanisms and interpretation of the dissolution process has been presented. Naproxen sodium, a potent non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic activity employed in the study, has been briefly discussed. In the present study, the coacervation phase separation technique utilizing ethylcellulose was initially investigated but proved unsuccessful in producing a formulation displaying suitable drug release characteristics. Subsequently, the meltable aqueous dispersion technique utilizing cetostearyl alcohol was successfully employed to formulate a multipleunit modified release naproxen sodium preparation containing 550 mg of naproxen sodium. The use of cetosteary!alcohol, as·a·retarding material, generated modified ·drug release characteristics as a function of its content. Magnesium stearate (anti-tackiness agent) and Span 20 and Tween 60· (surfactants) were incorporated in the formulation to optimize particle size and sphericity. The influence. of various formulation variables on drug release characteristics were investigated: An optimized formulation displaying a desirable modified release profile of naproxen sodium was achieved employing a 1:1 ratio of naproxen sodium:cetostearyl alcohol, 2% m/m .. .. magnesium stearate, and 1%m/m Span 20 dispersed in a liquid manufacturing vehicle of pH 0.6 containing 2% m/m Tween 60. In vitro dissolution studies on the selected formulation showed drug release to be predictable and reproducible, dependent on the dissolution method, agitation rate, and the pH of the dissolution media (i.e. pH-dependent drug release). The density of the microspheres was shown to decrease as the concentration of cetostearyl alcohol increased whilst the mean specific surface area increased with increasing concentrations of cetostearyl alcohol. Differential scanning calorimetric studies reveals a change in the thermograms which is suggestive of eutectic formation. Scanning electron microscopy proved useful in evaluating the integrity and surface morphology of the microspheres as well as in elucidating the drug release characteristics of the formulation. Energy dispersive x-ray microprobe analysis revealed the elemental composition of the microspheres to be a composite of the pure ingredients. X-ray mapping and the line scan depicted the homogenous distribution of drug within the microspheres and confirmed that the formulation is a matrix-type modified release I' preparation. Stability studies were performed on the selected formulation at room temperature (21 :t 1°C), 40°C, 37°C with 80% relative humidity, and at low temperature (5 :t 1°C). The shelf-life of the selected formulation was determined to be 1.29 years. Applying the data to five different kinetic models to investigate the drug release mechanisms showed that first order and cube-root release characteristics were exhibited by the microspheres. / Thesis (M.Sc.)--University of Durban-Westville, 1997.

This dissertation examines two main research questions: Why do firms deviate from their predicted level of toxic emissions, and how do these differences relate to financial performance? The objective is threefold: (1) to understand deviation in corporate environmental performance by looking at both industry and firm level variables, (2) to see how this deviation relates to both profitability and fluctuations in financial performance, and (3) to see if, and how, corporate environmental legitimacy affects the relationship between corporate environmental deviation and corporate financial performance. To achieve this objective the construct “corporate environmental performance deviation” is developed. It is defined as the extent to which a firm’s environmental performance deviates from its predicted performance, and is used to capture within-firm strategic choices in environmental management. Predicted environmental performance is calculated based on certain firm characteristics such as size and industry. Actual environmental performance is calculated using a weighted score of air emissions obtained from the Toxic Release Inventory (TRI) database. The difference between these two values represents a corporation’s environmental performance deviation. Corporate environmental performance deviation focuses on strategic choices related to environmental management, while recognizing that environmental management is the result of both institutional pressures and within-firm strategic decisions. Aligned with this focus, variables 2 related to this strategic choice are used to explain deviation in environmental management, including an environmental integration capability, firm strategy, and industry munificence and dynamism. Associated with the internal and external organizational analysis, institutional theory and the resource-based view (RBV) are used to explore the tension between deviation to increase competitiveness versus isomorphism to attain legitimacy. The sample is composed of 311 U.S. firms who have reported their toxic air releases to the TRI from 1998-2007. The sample is broken down into two subsets, those that exceed (positive deviation) or fail to meet (negative deviation) predicted environmental performance. Results of a longitudinal analysis show that positive environmental deviation is related to a greater capacity to strategically integrate environmental issues into a firm’s existing business approach, less munificence and dynamism in the task environment, and reduced financial fluctuations. Negative environmental deviation is decreased through a demonstrated capacity to strategically integrate environmental issues into a firm’s existing strategic approach, and related to greater munificence and dynamism in the task environment, reduced profitability and increased financial fluctuations. Lastly, although there are no significant main effects for corporate environmental legitimacy, the paradoxical combination of negative deviation and environmental legitimacy can reduce the severity of the negative financial results to negative deviation, both in terms of profitability and financial fluctuations.

Cancer remains a leading cause of death in the United States. The most common treatment options include chemotherapy, but poor solubility, adverse side effects and differential drug sensitivity hamper clinical applications. Current chemotherapy generally aims to deliver drugs at the limit of toxicity, assuming that higher dosage increases efficacy, with little attention paid to potential benefits of tunable release. Growing evidence suggests that releasing drugs at a constant rate will be as effective as a single bolus dose. To test this hypothesis, it is critical to develop drug delivery systems that fine-tune drug release and elucidate the impact of tunable drug release rates on chemotherapeutic efficacy. Block copolymer micelles, spherical nanoassemblies with a core-shell structure, are widely used in recent research. Micelles for this study were engineered to release a model drug (doxorubicin: DOX) at differential rates under acidic conditions, corresponding to tumor tissue (pH < 7). Three specific aims were pursued: to develop drug carriers capable of tuning drug release rates; to determine activity of developed carriers in vitro; and to elucidate effects of tunable drug release rates in vivo. Block copolymers with covalently linked DOX were synthesized and self-associated, forming micelles. Drug binding linkers (glycine, aminobenzoate, or hydrazide) were used to tune release of DOX. Micelles were characterized to determine physicochemical properties such as particle size, drug entrapment yields, and drug release parameters. Characterization revealed that drug release profiles were modulated by interchanging drug binding linkers. Micelles were evaluated in vitro to elucidate the effect of tunable drug release. Micelles delivered drugs at a slower, prolonged rate compared to free DOX. Cytotoxicity and cellular internalization analysis revealed that by slowing release rates, micelles kill cells more efficiently. Biodistribution studies showed that micelles decrease DOX accumulation in peripheral tissue while increasing the maximum tolerated dose. Antitumor activity studies verified that micelles with slower release rates better suppressed tumor growth. This further confirms that release rates play a key role in chemotherapeutic efficacy. Therefore, this thesis provides better insights into the effects of tunable drug release in tumors, leading the way for improved chemotherapy treatments in the future.

Spinal fusion is used to treat diseases or disorders of the spine by fusing together two or more vertebrae. Two associated risks with spinal fusion are infection and blood loss. Administration of tranexamic acid is used to prevent blood loss, and transfusions are given following blood loss. Surgical site infections are prevented with vancomycin powder spread into the surgical wound, while established infections are treated by debridement and delivery of antibiotics for 4 to 6 weeks. The present research explored an alternate method to prevent and treat blood loss or infection in spinal fusion. Poly(lactic-co-glycolic acid) (PLGA) microspheres was used to encapsulate vancomycin for 42 days to treat infection. Vancomycin encapsulated in gelatin microspheres had a controlled release of 7 days to prevent infection. Tranexamic acid was dissolved into phosphate-buffered saline or carboxymethylcellulose to provide a release of 6 hours to prevent blood loss after surgery. The microspheres and tranexamic acid were delivered to a target region using a water based spray system. The spray system demonstrated the delivery and distribution of drugs to a target region. The microsphere spray system is capable of spraying drugs onto a target region to prevent or treat blood loss and infection over time.

The goal of the proposed study is to understand the morphology, physical, and responsive properties of synthetic polymer and biopolymer layer-by-layer (LbL) arrays using the inkjet printing and stamping technique, in order to develop patterned encapsulated thin films for controlled release and biosensor applications. In this study, we propose facile fabrication processes of hydrogen-bonded and electrostatic LbL microscopic dot arrays with encapsulated target organic and cell compounds. We study encapsulation with the controllable release and diffusion properties ofpoly(vinylpyrrolidone) (PVPON), poly(methacrylic acid) (PMAA), silk-polylysine, silk-polyglutamic acid, pure silk films, and E-coli cells from the multi-printing process. Specifically, we investigate the effect of thickness, the number of bilayers, and the hydrophobicity of substrates on the properties of inkjet/stamping multilayer films such as structural stability, responsiveness, encapsulation efficiency, and biosensing properties. We suggest that a more thorough understanding of the LbL assembly using inkjet printing and stamping techniques can lead to the development of encapsulation technology with no limitations on either the concentration of loading, or the chemical and physical properties of the encapsulated materials. In addition, this study offers new encapsulation concepts with simple, cost effective, highly scalable, living cell-friendly, and controllable patterning properties.