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Permanent link (DOI): https://doi.org/10.7939/R3FT8DQ31

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Liposome-based therapy: An alternative approach to treat Helicobacter pylori infection in high prevalence communities such as Aklavik, NWT Open Access

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Other title
Subject/Keyword
Helicobacter pylori
Liposome
Aklavik
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Mahmoud, Maysoon
Supervisor and department
Keelan, Monika (Laboratory Medicine and Pathology)
Examining committee member and department
Holovati, Jelena (Laboratory Medicine and Pathology)
Goodman, Karen (Medicine)
Thomson, Alan (Medicine)
Turner, Justine (Pediatrics)
Tyrrell, Gregory (Laboratory Medicine and Pathology)
Department
Medical Sciences-Laboratory Medicine and Pathology
Specialization

Date accepted
2015-12-08T09:14:53Z
Graduation date
2016-06
Degree
Doctor of Philosophy
Degree level
Doctoral
Abstract
Helicobacter pylori infects about half of the world population causing chronic gastritis, peptic ulcer or gastric cancer. The Aboriginal people in Aklavik, NWT, Canada are concerned about gastric cancer because of the high prevalence of H. pylori infection (58%) in their community. H. pylori colonization of the acidic stomach environment is dependent on the production of urease enzyme and bacterial adhesins such as BabA. Toxins produced by H. pylori, CagA and VacA, contribute to the development of stomach diseases. Standard therapies often fail due to antimicrobial resistance and lack of compliance. Liposomes are lipid vehicles that have wide therapeutic applications in enhancing the delivery of drugs and genes into different cells. This thesis characterizes H. pylori isolated from residents of Aklavik for major virulence genes, describes the prevalence of gastric biopsy histopathology outcomes, and estimates the effect of H. pylori virulence genotype on the prevalence of gastric biopsy histopathology outcomes. In addition, liposome-based treatment approaches are investigated as alternative treatment approaches for H. pylori eradication. This thesis is the first report on the frequencies of H. pylori genotype and histopathology outcomes for the community of Aklavik, NWT, and identifies the association of virulence genes cagA and vacA subtypes with gastritis and/or intestinal metaplasia. Cationic liposome-enhanced delivery of urease antisense DNA inhibited urease expression by 40%, which may interfere with H. pylori survival in acidic conditions. Alterations in liposome composition to improve liposome stability did not improve delivery of antisense DNA to H. pylori. However, cationic liposomes themselves were previously reported to have antimicrobial activity against some bacteria and protozoans at concentrations that are nontoxic to mammalian cells. This thesis is the first demonstration of the enhanced effect of liposomes on the delivery of urease antisense DNA to H. pylori resulting in impaired urease expression and activity, and also the first report on the antimicrobial activity of stearylamine-containing cationic liposomes against H. pylori. The novel findings presented in this thesis provide the potential for alternative treatment approaches for the eradication of H. pylori infections, important strategies for communities where there is a high prevalence of H. pylori infection.
Language
English
DOI
doi:10.7939/R3FT8DQ31
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
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