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- All Subjects: Cellular Biology
- All Subjects: Asthmatics
- Genre: Academic theses
- Creators: Sweazea, Karen
Description
ABSTRACT
Asthma is a high-stress, chronic medical condition; 1 in 12 adults in the United States combat the bronchoconstriction from asthma. However, there are very few strong studies indicating any alternative therapy for asthmatics, particularly following a cold incidence. Vitamin C has been proven to be effective for other high-stress populations, but the asthmatic population has not yet been trialed. This study examined the effectiveness of vitamin C supplementation during the cold season on cold incidence and asthmatic symptoms. Asthmatics, otherwise-healthy, who were non-smokers and non-athletes between the ages of 18 and 55 with low plasma vitamin C concentrations were separated by anthropometrics and vitamin C status into two groups: either vitamin C (500 mg vitamin C capsule consumed twice per day) or control (placebo capsule consumed twice per day). Subjects were instructed to complete the Wisconsin Upper Respiratory Symptom Survey-21 and a short asthma symptoms questionnaire daily along with a shortened vitamin C Food Frequency Questionnaire and physical activity questionnaire weekly for eight weeks. Blood samples were drawn at Week 0 (baseline), Week 4, and Week 8. Compliance was monitored through a calendar check sheet. The vitamin C levels of both groups increased from Week 0 to Week 4, but decreased in the vitamin C group at Week 8. The vitamin C group had a 19% decrease in plasma histamine while the control group had a 53% increase in plasma histamine at the end of the trial, but this was not statistically significant (p>0.05). Total symptoms recorded from WURSS-21 were 129.3±120.7 for the vitamin C and 271.0±293.9, but the difference was not statistically significant (p=0.724). Total asthma symptoms also slightly varied between the groups, but again was not statistically significant (p=0.154). These results were hindered by the low number of subjects recruited. Continued research in this study approach is necessary to definitively reject or accept the potential role of vitamin C in asthma and cold care.
Asthma is a high-stress, chronic medical condition; 1 in 12 adults in the United States combat the bronchoconstriction from asthma. However, there are very few strong studies indicating any alternative therapy for asthmatics, particularly following a cold incidence. Vitamin C has been proven to be effective for other high-stress populations, but the asthmatic population has not yet been trialed. This study examined the effectiveness of vitamin C supplementation during the cold season on cold incidence and asthmatic symptoms. Asthmatics, otherwise-healthy, who were non-smokers and non-athletes between the ages of 18 and 55 with low plasma vitamin C concentrations were separated by anthropometrics and vitamin C status into two groups: either vitamin C (500 mg vitamin C capsule consumed twice per day) or control (placebo capsule consumed twice per day). Subjects were instructed to complete the Wisconsin Upper Respiratory Symptom Survey-21 and a short asthma symptoms questionnaire daily along with a shortened vitamin C Food Frequency Questionnaire and physical activity questionnaire weekly for eight weeks. Blood samples were drawn at Week 0 (baseline), Week 4, and Week 8. Compliance was monitored through a calendar check sheet. The vitamin C levels of both groups increased from Week 0 to Week 4, but decreased in the vitamin C group at Week 8. The vitamin C group had a 19% decrease in plasma histamine while the control group had a 53% increase in plasma histamine at the end of the trial, but this was not statistically significant (p>0.05). Total symptoms recorded from WURSS-21 were 129.3±120.7 for the vitamin C and 271.0±293.9, but the difference was not statistically significant (p=0.724). Total asthma symptoms also slightly varied between the groups, but again was not statistically significant (p=0.154). These results were hindered by the low number of subjects recruited. Continued research in this study approach is necessary to definitively reject or accept the potential role of vitamin C in asthma and cold care.
ContributorsEarhart, Kathryn Michelle (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Lespron, Christy (Committee member) / Arizona State University (Publisher)
Created2015
Description
The common cold is a significant cause of morbidity world-wide, with human rhinovirus infections accounting for a majority colds suffered each year. While the symptoms of the common cold are generally mild and self-limiting, vulnerable populations such as individuals with asthma can experience severe secondary complications including acute asthma exacerbation which can result in severe morbidity. Most human rhinovirus types utilize Intercellular Adhesion Molecule-1 (ICAM-1) as a receptor to enter cells and initiate infection. Expression of this cell-surface protein is elevated in the respiratory tract of asthma patients. The theoretical basis for this research is the observation that plasma measures of the soluble form of Intercellular Adhesion Molecule-1 (sICAM-1) decrease in response to vitamin C supplementation. As rhinovirus infection occurs in the upper respiratory tract, the primary aim of this study was to evaluate change in sICAM-1 concentration in nasal lavage of asthmatic individuals in response to vitamin C supplementation. Otherwise healthy asthmatic adults between the ages of 18-65 years who were not currently using steroidal nasal sprays, smoking, or actively training for competitive sports were recruited from a university community and surrounding area to participate in an 18-day double-blind randomized placebo-controlled supplement study with a parallel arm design. 13 subjects were stratified based on age, gender, BMI and baseline plasma vitamin C level to receive either 500 mg vitamin C twice daily (VTC, n=7) or placebo (PLC, n=6). Biochemical measures included nasal lavage sICAM-1, plasma sICAM-1, plasma histamine, and plasma vitamin C. Survey measures included Wisconsin Upper Respiratory Symptom Survey-21 to assess colds, Daytime Symptom Diary Scale to assess asthma symptoms, and measures of diet quality including a vitamin C food frequency questionnaire and Rapid Eating Assessment for Participants. No between group comparison of means reached significance (Mann-Whitney U test, p>0.05). Nasal lavage sICAM-1 levels were decreased in VTC group by 37% at study day 4, although this finding did not reach significance. Findings in this study can be used to develop future investigations into the response of nasal lavage sICAM-1 to vitamin C supplementation.
ContributorsGnant, Lindsay (Author) / Johnston, Carol (Thesis advisor) / Sweazea, Karen (Committee member) / Chang, Yung (Committee member) / Arizona State University (Publisher)
Created2014
Description
Male reproductive dysfunction accounts for almost half of male infertility cases, yet the signaling mechanisms involved in the male reproductive system remain unclear. Although the exact cause of male reproductive dysfunction varies, obtaining a better understanding of the modulators of smooth muscle contractions may provide new targets for the treatment of male reproductive conditions. The male reproductive tract, consisting of the testes, epididymis, vas deferens, and penis, is lined with innervated smooth muscle fibers that transport spermatozoa through the system. Contractions of these smooth muscle fibers can be modulated by neurotransmitters and hormones, like dopamine and norepinephrine, as well as biogenic amines. The focus of this study is on the biogenic amine tyramine, which is produced by the breakdown of tyrosine via decarboxylation. Tyramine has been shown to modulate vasoconstriction and increase blood pressure due to its effect on smooth muscle contractions. This study has found that tyramine localizes in male reproductive tissues and modulates smooth muscle contractions. Age and environment were also found to play a significant role in the expression of tyramine and its associated receptor, TAAR1.
ContributorsSteadman, Solange (Author) / Baluch, Debra (Thesis advisor) / Roberson, Robert (Committee member) / Sweazea, Karen (Committee member) / Arizona State University (Publisher)
Created2023
Description
Type 1 diabetes (T1D) is the result of an autoimmune attack against the insulin-producing β-cells of the pancreas causing hyperglycemia and requiring the individual to rely on life-long exogenous insulin. With the age of onset typically occurring in childhood, there is increased physical and emotional stress to the child as well as caregivers to maintain appropriate glucose levels. The majority of T1D patients have antibodies to one or more antigens: insulin, IA-2, GAD65, and ZnT8. Although antibodies are detectable years before symptoms occur, the initiating factors and mechanisms of progression towards β-cell destruction are still not known. The search for new autoantibodies to elucidate the autoimmune process in diabetes has been slow, with proteome level screenings on native proteins only finding a few minor antigens. Post-translational modifications (PTM)—chemical changes that occur to the protein after translation is complete—are an unexplored way a self-protein could become immunogenic. This dissertation presents the first large sale screening of autoantibodies in T1D to nitrated proteins. The Contra Capture Protein Array (CCPA) allowed for fresh expression of hundreds of proteins that were captured on a secondary slide by tag-specific ligand and subsequent modification with peroxynitrite. The IgG and IgM humoral response of 48 newly diagnosed T1D subjects and 48 age-matched controls were screened against 1632 proteins highly or specifically expressed in pancreatic cells. Top targets at 95% specificity were confirmed with the same serum samples using rapid antigenic protein in situ display enzyme-linked immunosorbent assay (RAPID ELISA) a modified sandwich ELISA employing the same cell-free expression as the CCPA. For validation, 8 IgG and 5 IgM targets were evaluated with an independent serum sample set of 94 T1D subjects and 94 controls. The two best candidates at 90% specificity were estrogen receptor 1 (ESR1) and phosphatidylinositol 4-kinase type 2 beta (PI4K2B) which had sensitivities of 22% (p=.014) and 25% (p=.045), respectively. Receiver operating characteristic (ROC) analyses found an area under curve (AUC) of 0.6 for ESR1 and 0.58 for PI4K2B. These studies demonstrate the ability and value for high-throughput autoantibody screening to modified antigens and the frequency of Type 1 diabetes.
ContributorsHesterman, Jennifer (Author) / LaBaer, Joshua (Thesis advisor) / Borges, Chad (Committee member) / Sweazea, Karen (Committee member) / Mangone, Marco (Committee member) / Arizona State University (Publisher)
Created2022
Description
Lipolysis or hydrolysis of triglyceride (TG) stored within intracellular lipid droplets (LD), is vital to maintaining metabolic homeostasis in mammals. Regulation of lipolysis and subsequent utilization of liberated fatty acids impacts cellular and organismal functions including body fat accumulation and thermogenesis. Adipose triglyceride lipase (ATGL) is the intracellular rate-limiting enzyme responsible for catalyzing hydrolysis of TG to diacylglycerol (DAG), the initial step of the lipolytic reaction. G0/G1 switch gene-2 (G0S2) and hypoxia-inducible gene-2 (HIG2) are selective inhibitors of ATGL. G0S2 facilitates accumulation of TG in the liver and adipose tissue, while HIG2 functions under hypoxic conditions. Sequence analysis and mutagenesis were used to confirm the presence of conserved domains between these proteins, and that these domains are required for efficient binding and inhibition of ATGL. Further analysis revealed a Positive sequence (Pos-Seq)-LD binding motif in G0S2 but not HIG2. The Pos-Seq mediated ATGL-independent localization to LD and was required for achieving maximal inhibition of ATGL activity by G0S2. Identification and mutational analysis of this motif revealed distinct mechanisms for HIG2 and G0S2 LD association. In addition to molecular characterization of known protein inhibitors of lipolysis, an intracellular member of the apolipoprotein L (ApoL) family, ApoL6, was also identified as a LD and mitochondria associated protein expressed in adipose tissue. Brown adipose tissue uses fatty acids as fuel for increasing its energy output as heat during acute responses to cold exposure. A Comprehensive Lab Animal Monitoring System was used to compare heat production at room temperature (RT) and 4oC in transgenic animals overexpressing ApoL6 in brown adipose tissue. Overexpression of ApoL6 delayed utilization of long-chain fatty acids (LCFAs) as a fuel source while promoting an enhanced thermogenic response during initial cold exposure. ApoL6 mediated inhibition of LCFA utilization results from binding of ApoL6 to Mitochondrial Trifunctional Protein (MTP/TFP), which catalyzes mitochondrial β-oxidation. Indirect calorimetry and fasting acute cold exposure experiments suggest the augmented thermogenic profile of ApoL6 transgenic animals is a result of enhanced utilization of medium-chain fatty acids (MCFAs), glucose, and amino acids as fuel sources. Cumulatively these results indicate multiple mechanisms for regulation lipolysis and fatty acid utilization.
ContributorsCampbell, Latoya E (Author) / Lake, Douglas (Thesis advisor) / Liu, Jun (Committee member) / Folmes, Clifford (Committee member) / Sweazea, Karen (Committee member) / Baluch, Debra (Committee member) / Arizona State University (Publisher)
Created2021