Browsing by Subject "hyperbaric oxygen"
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Item Characterization of a Novel Extracellular Superoxide Dismutase Allele Discovered in Mouse Models of Atherosclerosis(2004-07-01) Pierce, Anson; Dory, Lad; Easom, Robert; Basu, AlakanandaAnson Pierce, Characterization of a Novel Extracellular Superoxide Dismutase Allele Discovered in Mouse Models of Atherosclerosis. Doctor of Philosophy (Biochemistry and Molecular Biology), July 2004, 128 pp., 3 tables, 22 illustrations, references, 230 titles. Many diseases display some involvement with oxidative mechanisms and could potentially benefit from antioxidant therapy designed to restore the balance between reductive and oxidative factors. Data presented in this dissertation explore and establish the protective effect hyperbaric oxygen (HBO) has on the development of atherosclerosis, an oxidation-driven inflammatory disease mediated through low-density lipoproteins in the vasculature. Atherosclerosis in the apolipoprotein E-/- (apoE-/-) mouse is drastically reduced after 10 weeks of HBO treatment. Macrophages in HBO treated mice have an increased antioxidant capacity and reduced ability to generate oxidants. From this work, a new polymorphism of a key antioxidant enzyme, extracellular superoxide dismutase (ecSOD), is identified and characterized in mice. The new polymorphism is termed the “short” allele, and has the potential to alter the regulation of ecSOD mRNA and protein, as well as enzyme activity. Examination of its effect on the ecSOD phenotype in mice shows dramatic changes in enzyme levels and activity. In the plasma compartment ecSOD activity and mass are elevated, and indicate based on heparin injection studies that a change in ecSOD distribution results in tissues of mice expressing the short allele. Systematic examination of ecSOD in tissues of mice shows that its distribution is altered such that it is more accessible to heparin; this is most evident in the liver and kidney of mice expressing the short allele. The finding that HBO is protective against atherosclerosis highlights a potentially promising approach to treatment for this devastating disease, sheds light on the role oxidative processes play in atherosclerosis, and identifies potential targets for antioxidant therapy. This study also shows for the first time that two alleles for a major antioxidant enzyme exist in mice that display markedly different effects on the ecSOD phenotype, a finding that underlines the importance of genetic homogeneity in mouse models and adds to our knowledge concerning the role antioxidants play in human health and disease.Item EFFECTS OF HYPERBARIC OXYGEN TREATMENT ON IRRITABLE BOWEL DISEASE(2013-04-12) Shaygan, LidaPurpose: Irritable bowel diseases (IBD), including Crohn's disease and ulcerative colitis, are idiopathic inflammatory disorders of the gastrointestinal tract that lead to chronically inappropriate immune responses against normal flora in the gut. Among other factors, oxidative stress and increased intestinal tissue injury have been indicated in patients with IBD. Hyperbaric oxygen treatment (HBOT) has been successfully used in humans to treat different conditions such as decompression sickness in scuba diving (Gill et al., 2004), carbon monoxide poisoning, and poor wound healing in diabeteic patients (Tiaka et al., 2011). The purpose of this experiment was to determine the effect of hyperbaric oxygen treatment on colon inflammation in irritable bowel disease. Methods: Colitis was induced in mice using dextran sodium sulfate (DSS), according to a previous described model (Wirtz et al., 2007), and one of the groups was treated with hyperbaric oxygen. 24 eight-week old male C57-BL/6 mice (Jackson Laboratories) were divided into 3 groups: a control group, which was only given distilled water; a second group in which IBD was induced through a 14 day DSS (3%) in drinking water, and a third group also induced with a 14 day DSS (3%) in drinking water and simultaneously treated with HBO daily for two hours. Daily weight loss for all mice was recorded, colons were measured, and colon tissue was histologically analyzed. Results: Hyperbaric oxygen treatment of DSS induced mice led to a significant (P <.05) increase in body weight and colon weight/length ratio measurements compared to DSS induced mice that did not undergo hyperbaric oxygen treatment. Conclusions: Hyperbaric oxygen treatment (HBOT) of colitis induced mice does not appear to decrease colon weight/length ratio, a reliable marker of inflammatory responses in IBD (Galvez et al., 2000). However, HBOT does improve survival and maintains body weight at better levels than DSS-induced mice without treatment. Histological analysis of colon tissues is pending and will provide a better indication of the degree of inflammation in DSS induced mice treated with HBOT.