Abstract not available

Microbial contamination of contact lenses is a significant risk factor leading to adverse responses. Adhesion of microorganisms to a contact lens is the first step in a series of events that leads to contact lens-related infections or inflammation. Recently, some of the non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to have the ability to interfere with microbial biofilm formation. In this project, antibacterial properties of commonly used NSAIDs (salicylic acid, sodium diclofenac and ketorolac) were assessed and characterised using biological assays and molecular biological techniques. Salicylic acid, ketorolac and diclofenac reduced adhesion of a range of bacterial species isolated from corneal infection and inflammatory events to contact lenses in a dose-dependent manner. Salicylic acid also decreased the adhesion of Pseudomonas aeruginosa and Staphylococcus epidermidis to human corneal epithelial cells in a dose-dependent manner. Results further demonstrated that NSAIDs had a significant impact on the production of virulence factors such as Type IV pili mediated (twitching) motility, flagella mediated swimming, elastase, protease IV and alkaline protease and affected the production of acylated homoserine lactones of P. aeruginosa. Salicylic acid and ketorolac affect the expression of P. aeruginosa outer membrane proteins. In the presence of the salicylic acid and ketorolac more than 85% of all detectable outer membrane proteins changed and most were down-regulated. Moreover, in the presence of salicylic acid at least five gene products, including Na+ - translocating NADH (Nrq1), choline dehydrogenase (CHDH), a hypothetical protein of unknown function, a gene product with no similarity to any known sequence in the database and a sequence similar to 23S rRNA of P. aeruginosa, were down-regulated. The results of this study clearly demonstrated that NSAIDs have a significant impact on virulence factors and the expression of acylated homoserine lactones by P. aeruginosa. This thesis has illustrated the potential of NSAIDs for preventing bacterial contamination of contact lenses by ocular pathogens and highlights the potential for NSAIDs as antibacterial agents. Therefore, this class of compound should be investigated further for their therapeutic efficacy in vivo.

This thesis describes a project to produce controlled release ketoprofen beads for capsules, both at Oregon State University and in an industrial scale-up operation, that are bioequivalent to the commercial product Oruvail. A bead formulation was produced by layering drug and binders in water onto nonpareil sugar seeds in a spray coating apparatus. Ketoprofen beads manufactured in this manner will immediately release their drug content in either an in vitro or an in vivo environment. Industrially produced beads were non-homogeneous in size. Large beads in a coating batch sweep up a disproportional amount of coating material leading to a thicker coating layer and decreased drug release rates. In order to predict the effects of coating modifications, an equation was developed to accurately predict the coating thickness of any material applied to spherical particles of any size. The equation developed is suggested as a replacement for one that has been in published and cited for over 20 years, but overestimates coating thickness. The bulk of this thesis details the process of altering the drug release characteristics of the beads through application of diffusional and enteric barrier coatings, and testing for bioequivalence with Oruvail through biostudy data gathered from human volunteers. Urinary drug excretion rates were measured as a substitute for timed blood sampling of the subjects. Validity of the substitution was shown. Fed state biostudies involved beads manufactured and coated at Oregon State University. Fasted state biostudies involved beads that were industrially manufactured in a scale-up operation and coated both industrially and at Oregon State University. Deconvolution, a mathematical tool, was used to determine in vivo dissolution rates and the need for further coating modification. Statistical testing using a Two 1-Sided T test was the final arbiter of whether or not bioequivalence was concluded. Bioequivalence was achieved in subjects under a fed state and finally under fasting conditions, as required by the Food and Drug Administration, with drug beads coated with ethylcellulose to slow drug release and overcoated with an enteric bather to retard early drug release. Deconvolved in vivo dissolutions originating from biostudy data were used to develop In Vitro / In Vivo Correlations (IVIVC's). IVIVC's were used to predict in vivo biostudy data from in vitro dissolution results following coating formulation modification. A practical guide for the development and use of an IVIVC was written for pharmaceutics practitioners who have an understanding of pharmacokinetics, but may lack sufficient expertise in pharmacokinetics to develop an IVIVC. / Graduation date: 1998

Thesis (Ph. D.)--University of Hong Kong, 2005. / Title proper from title frame. Also available in printed format.

Thesis (Ph. D.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most frequently prescribed classes of drugs worldwide. Due to their excellent effects for analgesic, anti-inflammatory and antipyretic, most elder population used frequently for osteoarthritis. Gastrointestinal symptoms and ulceration associated with NSAIDs are common. Such ulcers may cause pain, bleeding, or perforation. It leads to other medical problems. The aim of this study was to examine the utilizations of medical resources associated with inpatients with NSAID related peptic ulcer disease and compared to non-NSAID related peptic ulcer disease. The study used the database from a teaching hospital in southern Taiwan. Inpatients who were identified ICD-9 CM codes as peptic ulcer diseases from January 1st of 2008 to December 31 of 2008 were included in this study. We also examined the indications for usage of NSAIDs, the date of prescription before the index date. The results showed 17.6% of inpatients with peptic ulcer disease related to NSAIDs. Inpatients with NSAIDs related peptic ulcer disease compared with inpatients with non-NSAIDs related peptic ulcer disease had significant difference in age and comorbidity. Although rapid urease test positive rate for Helicobacter pylori was higher in group of non-NSAID related peptic ulcer disease, it seemed underestimate because of the test number of patients was low. The average total direct medical cost of inpatients with NSAID related peptic ulcer was NT$ 36,491 and non-NSAID related peptic ulcer was NT$ 37,266.1. There were no significant difference in medical costs of standard care , intensive care , blood products,endoscopy, endoscopic hemostasis, surgery, CT scan , ultrasound, laboratory tests,medications, doctor¡¦s service between the two groups. Diagnostic and therapeutic procedures were no statistically significant difference, including blood transfusion,CT scan, endoscopic hemostasis, surgery, symptoms presentations, and intensive care. In this study, the duration for using NSAID was within 30 days for inpatients associated with NSAID related peptic ulcer, which had a substantial excess numbers of ulcer hospitalization. Since the common disease for using NSAID is osteoarthritis,which is very popular in elderly, therefore, we suggested that the policy makers of the National Health Insurance should be aware that preventive usage of proton pump inhibitors for the elder population who need frequent use of NSAIDs might decrease NSAID related ulcer complications.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Thesis (Ph. D.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xii, 150 p. : ill. Includes abstract. Includes bibliographical references (p. 124-128).

Thesis (M. Sc.)--University of Toronto, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Med. Sc.)--University of Hong Kong, 2004. / Also available in print.