Master of Science, The Ohio State University, 2007, Graduate School

Committee: Not Provided (Other) Subjects:

Doctor of Philosophy, The Ohio State University, 2023, Veterinary Preventive Medicine

Rotavirus (RV) is a double stranded RNA virus that infects mature enterocytes of the villi causing acute gastroenteritis in the young of many mammalian species including humans. Diarrhea associated with RV in young piglets leads to major losses in the pork industry due to mortality, morbidity, and reduced weight gain. In humans, diarrheal disease accounts for 1 in 9 childhood deaths worldwide, with RV species A (RVA) responsible for approximately 1.5 million hospitalizations with ~200,000 deaths in children annually, mainly in the low- and middle- income countries (LMIC). High mortality rates associated with RVA diarrhea in LMIC is partially attributed to nutritional inadequacies such as vitamin A (VA). VA is one of the key regulators of immunity in the gastrointestinal tract. VA deficiency (VAD) affects ~30% of children ˂5 years of age in LMIC making them highly susceptible to opportunistic pathogens. The main objective of our study was to determine the effects of VAD and VA supplementation on innate, adaptive, and lactogenic immune responses using RV conventional swine model. We hypothesized that dietary VAD would compromise innate and adaptive immune responses against RVA inoculation (immunization) in pregnant and lactating sows leading to impaired lactogenic protection of their piglets against RVA. In addition, we hypothesized that VA supplementation to VAD, RVA inoculated sows would restore compromised immune responses. To test our hypothesis, pregnant sows were placed on VAD and VA sufficient (VAS) diets starting on gestation day (GD)~30.. A subset of VAD sows was supplemented with VA (VAD+VA) from GD ~76 (third trimester) to the end of experiment. Experimental sows were inoculated with porcine RVA G5P[7] (OSU strain) at GD~90. Sow fecal samples were collected and analyzed for RVA RNA shedding and fecal consistency after RVA inoculation at GD~90. Blood, milk (post-partum) samples were collected pre- and post-partum [GD ~90, GD~109, day post-partum (DPP0 (col (open full item for complete abstract)

Committee: Anastasia Vlasova (Advisor); Scot Kenney (Committee Member); Qiuhong Wang (Committee Member); Linda Saif (Advisor) Subjects: Immunology; Virology

MPH, University of Cincinnati, 2022, Medicine: Epidemiology

Background. Vitamin D is commonly understood to be involved in the regulation of bone density and calcium homeostasis which also regulate parathyroid hormone activity. Many studies also discuss the impact of vitamin D deficiency on neuropsychological conditions such as depression, multiple sclerosis, and dementia. This study seeks to examine the relationship between age, serum vitamin D levels, and risk for dementia. Methods. This study was a retrospective cohort study of patients seen at the University of Cincinnati Academic Health Center. 21264 subjects contributed to 50268 total observations. Observations were included if they contained serum vitamin D levels, as well as values for predictors of interest such as dementia status, age, race, gender, and UV status at the time of the visit. A mixed methods approach was used to conduct multiple linear regression using vitamin D level as the primary outcome variable, dementia status, age, race, gender, UV status, and an interaction term between dementia status and age. Results and Conclusions. Patients who eventually develop dementia were shown to have reduced vitamin D values compared to their counterparts in the never dementia group. Race, gender, and UV status of the visit were all statistically significant. Belonging to black or African American race, and male gender patient groups contributes to having lower serum vitamin D levels. Age alone was not statistically significant; however, the interaction term between age and dementia group was (t= 3.99, F=15.94, p<0.0001). This supports the hypothesis that the rate of change in serum vitamin D values would be different between patients who go on to develop dementia and those who do not. Of specific interest, mean serum vitamin D values in each group were relatively close to 32 ng/ml of vitamin D which has been reported to be a threshold about which parathyroid hormone activity is modulated. Further research to better understand the role of parathyroid (open full item for complete abstract)

Committee: Kelly Brunst Ph.D. (Committee Member); Jeffrey Welge Ph.D. (Committee Member); Robert Krikorian Ph.D. (Committee Member) Subjects: Epidemiology

Doctor of Philosophy, The Ohio State University, 1974, Graduate School

Committee: Not Provided (Other) Subjects: Health Sciences

Doctor of Philosophy, The Ohio State University, 1963, Graduate School

Committee: Not Provided (Other) Subjects: Biology

MS, University of Cincinnati, 2011, Allied Health Sciences: Nutrition

Purpose: To assess the prevalence of vitamin D deficiency in patients on hemodialysis upon admission to a long term acute care hospital, as well as to examine characteristics of these individuals, with the purpose of identifying possible risk factors for vitamin D deficiency in kidney failure. Subjects: 56 hemodialysis patients who were admitted on or began treatment with hemodialysis and were under the care of Dr. Patrick McCullough at the Drake Rehabilitation Center in Cincinnati, OH between June 2009 and December 2010 were included in this study. Study Design and Methods: Data for this study were obtained as part of a retrospective observational cohort study of patients on hemodialysis who received vitamin D supplementation as standard of care while admitted to a LTACH. Patient data for this study were collected pre-supplementation at the baseline assessment visit. Biochemical data included 25(OH) D levels, 1, 25(OH)2 D levels, Parathyroid hormone (PTH), serum calcium, and serum albumin. Demographic information and medical history were collected retrospectively from chart review. For analysis, patients were categorized into three groups based on widely used cutoffs for serum 25(OH) D in Chronic Kidney Disease; vitamin D sufficient (>30 ng/mL), vitamin D insufficient (<30 ng/mL but >10 ng/mL) and vitamin D deficient (<10 ng/mL). Differences were then explored between the groups for biochemical data, demographic information, and medical history. Results: Seven percent (n=4) of the patients in the cohort were vitamin D sufficient, 48% (n=27) were vitamin D insufficient and 45% (n=25) were vitamin D deficient upon admission. No patients were diagnosed with a vitamin D deficiency prior to admission. As expected, vitamin D supplementation upon admission was related to vitamin D group assignment with a greater number of sufficient patients being supplemented with vitamin D than in the other groups. The vitamin D deficient group was significantly younger than the (open full item for complete abstract)

Committee: Sarah Couch PhD (Committee Chair); Kari Dunning PhD (Committee Member) Subjects: Nutrition

Doctor of Philosophy, The Ohio State University, 2004, Ohio State University Nutrition

Oxidative and nitrative stress play pivotal roles in the etiology of chronic diseases such as cancer and heart disease. Therefore, investigations to determine the effects of oxidative and nitrative stress on dietary antioxidant utilization are critical for our understanding of chronic disease prevention. To date, the impact of these stressors on vitamin E utilization in humans is controversial. Therefore, for this dissertation, we hypothesized that oxidative and nitrative stress from cigarette smoking will alter vitamin E utilization such that smokers have higher dietary requirements for vitamin E than nonsmokers. Using novel analytical techniques in liquid chromatography/mass spectrometry, we determined that the increased reactive nitrogen species associated with cigarette smoking caused a doubling of plasma nitro-gamma-tocopherol. Furthermore, using deuterium labeled alpha-tocopherols, we observed that smokers, compared with nonsmokers, had a 13% faster plasma alpha-tocopherol disappearance, suggesting that alpha-tocopherol functions in vivo as an antioxidant. Further, smokers' alpha-tocopherol disappearance rates correlated with plasma ascorbic acid concentrations, suggesting that higher plasma ascorbic acid concentrations could prevent the rapid alpha-tocopherol disappearance. Therefore, we conducted a double-blind, placebo-controlled, cross-over investigation in smokers and nonsmokers who were provided supplemental ascorbic acid (2-weeks, twice daily, 500 mg) or placebo prior to evaluating vitamin E disappearance kinetics. Plasma ascorbic acid concentrations doubled in both groups in response to the supplement compared to the placebo. In smokers during placebo treatment, vitamin E disappearance kinetics were again faster than in nonsmokers. However, during vitamin C supplementation, smokers' vitamin E disappearance was normalized. Plasma F2alpha-isoprostanes, a marker of lipid peroxidation, remained 34% higher than nonsmokers and vitamin E metabolite production (open full item for complete abstract)

Committee: Tammy Bray (Advisor) Subjects: Health Sciences, Nutrition

Master of Science in Biomedical Sciences (MSBS), University of Toledo, 2010, College of Medicine

Gastrointestinal (GI) carcinoids are slow growing malignancies of neuroendocrine phenotype that can behave aggressively. To date, there are no effective therapies for metastatic carcinoid cancer. Previous work by our lab and others has shown that carcinoids express variety of voltage-operated (VOCCs) and non-voltage-operated Ca2+ channels to allow Ca2+ to enter the cell. Although, the role of Ca2+ entry in these tumors is not well understood, previous work by our group and others has shown that mitochondria are important regulators of voltage-operated and non-voltage-operated Ca2+ entry. In addition, cancer cells typically exhibit mitochondrial dysfunction and poor anti-oxidant status. These observations and the central role that mitochondria play in metabolism, Ca2+ homeostasis and cell death pathways make mitochondria an appealing potential target for anti-cancer treatment in carcinoid tumors. We used an spectrum of human cancer cell lines and a variety of microfluorescence methods including wide-field, confocal, and total internal reflection (TIRF) microscopy to assess Ca2+ signaling and mitochondrial function in combination with pharmacological interventions to assay whether mitochondria are a potential target for anti-cancer therapy. To this end, we tested the effectiveness of an oxidant therapy approach in carcinoid cells.

Committee: David Giovannucci Ph.D. (Committee Chair); Andrew Beavis Ph.D. (Committee Member); Vazquez Guillermo Ph.D. (Committee Member) Subjects: Biomedical Research; Molecular Biology; Scientific Imaging

Doctor of Philosophy, Case Western Reserve University, 2010, Chemistry

Hydroperoxy endoperoxides, the singlet oxygen cycloadducts of hydroperoxy diene,are likely to be generated in the retina owing to the presence of photosensitizers that can generate singlet oxygen. We speculated that these endoperoxides would undergo fragmentation reactions to give toxic aldehydes, e.g., γ-hydroxyl alkenals. A simple model hydroperoxy endoperoxide and its linoleate derivatives were prepared and were found to undergo fragmentations. The reactions are catalyzed by metal ions and promoted by vitamin (Vit) E. Thus, the hydroperoxy endoperoxides readily give γ-hydroxy alkenals and their oxidation products, butenolides. Vit E converts metal ions to their reduced forms that react with hydroperoxy endoperoxides, causing fragmentation to aldehydes. We also examined the influence of a membrane environment on the fate of hydroperoxy endoperoxides. In the membrane, further oxidation of the initially formed γ-hydroxyalkenal to a butenolide is disfavored. A conformational preference for the γ-hydroxyalkenal, to protrude like a whisker from the membrane into the aqueous phase,may protect it from oxidation induced by lipid hydroperoxides that remain buried in the lipophilic membrane core. We prepared a simple model β-hydroxy hydroperoxide, through disproportionation of a hydroperoxy endoperoxide, and investigated mechanisms of its fragmentation. We found that antioxidants, e.g., Vit E and Vit C, in the presence of catalytic amounts of transition metal ions (Fe3+ or Cu2+), can strongly promote the fragmentation of β-hydroxy hydroperoxides to deliver toxic aldehyde products. These findings further demonstrated the potential for some “antioxidants” to exhibit pro-oxidant effects. The fragmentation mechanism for a linoleate-derived hydroperoxy epoxide (13-HP-Epo-Acid) was investigated. The pseudosymmetric formation of toxic aldehydes during the Fe2+-promoted fragmentation of 13-HP-Epo-Acid implies the existence of a pseudosymmetric diepoxycarbinyl radical intermediate. (open full item for complete abstract)

Committee: Robert Salomon (Advisor); Anthony Pearson (Committee Chair); Rajesh Viswanathan (Committee Member); Michael Zagoski (Committee Member); Paul Carey (Committee Member) Subjects: Chemistry

Doctor of Philosophy, Case Western Reserve University, 2010, Chemistry

Hydroperoxy endoperoxides, the singlet oxygen cycloadducts of hydroperoxy diene, are likely to be generated in the retina owing to the presence of photosensitizers that can generate singlet oxygen. We speculated that these endoperoxides would undergo fragmentation reactions to give toxic aldehydes, e.g., γ-hydroxyl alkenals. A simple model hydroperoxy endoperoxide and its linoleate derivatives were prepared and were found to undergo fragmentations. The reactions are catalyzed by metal ions and promoted by vitamin (Vit) E. Thus, the hydroperoxy endoperoxides readily give γ-hydroxy alkenals and their oxidation products, butenolides. Vit E converts metal ions to their reduced forms that react with hydroperoxy endoperoxides, causing fragmentation to aldehydes. We also examined the influence of a membrane environment on the fate of hydroperoxy endoperoxides. In the membrane, further oxidation of the initially formed γ- hydroxyalkenal to a butenolide is disfavored. A conformational preference for the γ- hydroxyalkenal, to protrude like a whisker from the membrane into the aqueous phase, may protect it from oxidation induced by lipid hydroperoxides that remain buried in the lipophilic membrane core. We prepared a simple model β-hydroxy hydroperoxide, through disproportionation of a hydroperoxy endoperoxide, and investigated mechanisms of its fragmentation. We found that antioxidants, e.g., Vit E and Vit C, in the presence of catalytic amounts of transition metal ions (Fe3+ or Cu2+), can strongly promote the fragmentation of β-hydroxy hydroperoxides to deliver toxic aldehyde products. These findings further demonstrated the potential for some “antioxidants” to exhibit pro-oxidant effects. The fragmentation mechanism for a linoleate-derived hydroperoxy epoxide (13-HP- Epo-Acid) was investigated. The pseudosymmetric formation of toxic aldehydes during the Fe2+-promoted fragmentation of 13-HP-Epo-Acid implies the existence of a pseudosymmetric diepoxycarbinyl radical interm (open full item for complete abstract)

Committee: Robert Salomon PhD (Advisor); Anthony Pearson PhD (Committee Chair); Paul Carey PhD (Committee Member); Rajesh Viswanathan PhD (Committee Member); Michael Zagorski PhD (Committee Member) Subjects: Chemistry

Master of Science, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2006, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 1971, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2008, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2007, Graduate School

Committee: Not Provided (Other) Subjects:

Master of Science, The Ohio State University, 2024, Food Science and Technology

Vitamin D is a secosteroid with numerous benefits for human health, including its effects in skeletal health, immunomodulation, cell proliferation, and cellular differentiation. Despite these benefits, vitamin D deficiency is a global health concern. While supplementation is common in many countries and is commonly conducted by oral delivery, individuals with fat malabsorption face challenges with vitamin D absorption. Thus, transdermal delivery is therefore considered a suitable alternative for these individuals. However, the stability of vitamin D in most commercially available cosmetic products is questionable due to its sensitivity to temperature, light, pH, and oxygen. Therefore, this study aims at developing a vitamin D3 delivery system using hemp seed oil for enhanced transdermal delivery and Maillard reacted lecithin conjugates. Further the study focuses on characterizing and optimizing the encapsulation method to achieve thermal and oxidative stability of hemp seed oil and vitamin D3. Hemp seed oil was chosen as the carrier for vitamin D3 due to its excellent skin permeation ability and rich polyunsaturated fatty acid profile, which provides additional health benefits. According to results, moisture and water activity data conform with recommended values for low moisture food products whereas the p-anisidine test indicated good lipid quality during the period of storage. Thermogravimetric analysis and differential scanning calorimetry results demonstrate that the proposed wall matrix provides adequate thermal and oxidative stability for the encapsulated vitamin D3. The study did not identify a significant difference (p < 0.05) in retention of vitamin D3 based on the temperature treatment provided. Moreover, 50 °C heat treatment achieved the best encapsulation efficiency of 59.5 % compared to 100 °C and the control. Overall, the use of Maillard-reacted glycated lecithin wall matrix appears to be a promising approach for protecting vitamin D3 from external st (open full item for complete abstract)

Committee: Osvaldo Campanella (Advisor); Rafael- jimenez Flores (Committee Member); Monica Giusti (Committee Member) Subjects: Food Science; Nutrition

Doctor of Philosophy, Case Western Reserve University, 2023, Pharmacology

Vitamin A is an essential nutrient that is distributed within the body to support chromophore synthesis in the eyes and retinoid signaling in most other tissues. Vertebrates possess specialized protein machinery mediating vitamin A uptake, metabolism, and distribution. Disruptions in those processes are implicated in ophthalmological, dermatological, and immune disorders. The body of work herein uses mouse models to genetically dissect mechanisms governing vitamin A homeostasis, especially in the context of the eyes. Abundant expression of the retinol-binding protein (RBP4) receptor STRA6 in the retinal pigment epithelium and homeostatic blood levels of RBP4 delay vitamin A deprivation in the eyes. The ocular vitamin A status of STRA6-deficient mice is therefore susceptible to nutritional manipulation. The outer tissue separating the retina from the blood flow was subjected to RNA-sequencing to understand responses in mild and severe ocular vitamin A deficiency. Both deficient states shared symptoms of visual impairment, but significant alterations in morphology and function of the outer blood retinal barrier were unique to severe vitamin A deficiency. Though existing vitamin A rejuvenation treatments improve clinical outcomes, our findings have reinforced that such therapies would be otherwise futile without intact STRA6 expression. The basis for reliance on a RBP4-dependent system has not been fully understood. At the core, the setup has evolved to protect vertebrates during times of fasting or dietary vitamin A insufficiency. However, vitamin A can also be delivered through lipoproteins, independent of RBP4. By relieving ISX's control of beta-carotene (BC) absorption and conversion in the gut, I tested whether circumventing the RBP4 pathway is possible. BC-fed Isx; Stra6 double-knockout mice exhibited favorable outcomes for cone photoreceptors that fare poorly in Stra6 knockout mice. Despite this apparent advantage, a comprehensive assessment of extraocular peri (open full item for complete abstract)

Committee: Johannes von Lintig (Advisor); Marcin Golczak (Committee Chair); Jason Mears (Committee Member); Danny Manor (Committee Member); Beata Jastrzebska (Committee Member); Eckhard Jankowsky (Other) Subjects: Biochemistry; Nutrition; Ophthalmology; Pharmacology; Physiology

Doctor of Philosophy (PhD), Ohio University, 2023, Chemistry and Biochemistry (Arts and Sciences)

Stroke and heart attack are among the leading causes of death in the United States and worldwide. The high mortality rate is alarming given the wide availability of therapies for these illnesses. The mechanisms of action of these two diseases are remarkably similar, despite the fact that they are linked to two quite distinct organs in our body; in both, there is significant oxygen deprivation at the cellular level. Nitorooxidative stress occurs in physiological system due to the imbalance between Nitric Oxide (NO) and peroxynitrite (ONOO-). Using electrochemical nanosensors1,2 and a hypoxic chamber (which can control O2 from 21% to 0%), nitrooxidative stress in the endothelial and neural systems was studied, as well as two potential treatments (L-arginine and vitamin D3). Additionally, a connection was made between the protein HIF-1α and nitrooxidative stress. According to experimental data, L-arginine and vitamin D3 treatments can restore the [NO]/[ONOO-] balance in the endothelial system by up to 73 % and 69%, respectively. L-arginine and vitamin D can help the neural system's balance by up to 61% and 8%, respectively. Both L-arginine and vitamin D3 were also found to be effective in downregulation of HIF-1α in severe hypoxic conditions.

Committee: Tadeusz Malinski (Advisor); Michael Held (Committee Member); Katherine Cimatu (Committee Chair); Krisanna Machtmes (Committee Member); Howard Dewald (Committee Member) Subjects: Biochemistry; Chemistry

Master of Science, Miami University, 2022, Kinesiology, Nutrition, and Health

Weight loss in older adults can lead to bone mineral density losses and frailty if adequate calcium and vitamin D are not consumed. The purpose of this secondary data analysis was to examine the effect of a 6-month calorically restricted dietary weight loss intervention tailored to include calcium and vitamin D-containing dairy products on calcium and vitamin D intake in older adults. A sample of 35 older (≥58 years), overweight (BMI≥27kg/m2), adults were randomly assigned to a dietary intervention or non-diet group. The dietary intervention included a structured meal plan, nutrition counseling, and monthly 3-day dietary recalls using the NDSR software. Two-way repeated measures ANOVAs were performed using GraphPad to compare differences in calcium and vitamin D intake. The dietary intervention group had significantly higher intakes of vitamin D compared to the control group across the 6-month intervention, F(1, 211) = 8.331, p = 0.0043. However, the effect of the dietary intervention on both average calcium intake, F(6, 224) = 0.08425, p = .552, and average vitamin D intake, F(6, 211) = 0.3516, p = .908, between groups was non-significant. Further research is needed surrounding strategies to achieve and maintain nutrient increases during weight loss in older adults.

Committee: M. Elizabeth Miller PhD (Advisor); Kevin Ballard PhD (Committee Member); Kyle Timmerman PhD (Committee Member) Subjects: Kinesiology; Nutrition

PhD, University of Cincinnati, 2021, Medicine: Cancer and Cell Biology

The mammalian host continuously interacts with trillions of commensal microbes, collectively termed the microbiota. Signals from the microbiota are critical for facilitating normal development and physiology in the host including digestion, metabolism, and, importantly, regulation of mucosal immunity. Studies employing germ-free models or antibiotics demonstrate that disruption of the microbiota significantly impairs host defense against invading pathogens. However, the mechanistic underpinnings of this protective relationship remain unclear. Intestinal epithelial cells (IECs) reside directly at the host-microbiota interface and represent the first point of entry for various pathogens. Here, we report that the microbiota suppresses adherence of the intestinal pathogen Citrobacter rodentium to IECs by transcriptionally and epigenetically downregulating expression of the pathogen-binding cell surface glycoprotein Clec2e. Functional studies demonstrate that this microbiota-sensitive regulation was dependent on the expression and recruitment of the histone deacetylase, HDAC3. Secondly, we uncovered a novel mechanism through which the IEC-associated commensal bacteria, Segmented Filamentous Bacteria (SFB), promote early protection against the same pathogen. SFB-induced histone modifications in IECs at sites enriched for retinoic acid receptor motifs, suggesting SFB may enhance defense through retinoic acid (RA). Consistent with this, inhibiting RA signaling suppressed SFB-induced protection. Intestinal RA levels were elevated in SFB mice despite inhibition of mammalian RA production, indicating that SFB modulate RA. Interestingly, RA was produced by intestinal bacteria and loss of bacterial-intrinsic aldehyde dehydrogenase activity decreased RA levels and increased infection. Thus, these data reveal RA as an unexpected microbiota-derived metabolite that primes innate defense against an enteric pathogen. Collectively, these findings expand our understanding of microbi (open full item for complete abstract)

Committee: Theresa Alenghat Ph.D. (Committee Chair); David Haslam M.D. (Committee Member); Daniel Starczynowski (Committee Member); Satoshi Namekawa Ph.D. (Committee Member); Tatiana Kalin M.D. Ph.D. (Committee Member) Subjects: Cellular Biology