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Description
Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D.

Cardiovascular disease (CVD) is the number one cause of death in the United States and type 2 diabetes (T2D) and obesity lead to cardiovascular disease. Obese adults are more susceptible to CVD compared to their non-obese counterparts. Exercise training leads to large reductions in the risk of CVD and T2D. Recent evidence suggests high-intensity interval training (HIT) may yield similar or superior benefits in a shorter amount of time compared to traditional continuous exercise training. The purpose of this study was to compare the effects of HIT to continuous (CONT) exercise training for the improvement of endothelial function, glucose control, and visceral adipose tissue. Seventeen obese men (N=9) and women (N=8) were randomized to eight weeks of either HIT (N=9, age=34 years, BMI=37.6 kg/m2) or CONT (N=8, age=34 years, BMI=34.6 kg/m2) exercise 3 days/week for 8 weeks. Endothelial function was assessed via flow-mediated dilation (FMD), glucose control was assessed via continuous glucose monitoring (CGM), and visceral adipose tissue and body composition was measured with an iDXA. Incremental exercise testing was performed at baseline, 4 weeks, and 8 weeks. There were no changes in weight, fat mass, or visceral adipose tissue measured by the iDXA, but there was a significant reduction in body fat that did not differ by group (46±6.3 to 45.4±6.6%, P=0.025). HIT led to a significantly greater improvement in FMD compared to CONT exercise (HIT: 5.1 to 9.0%; CONT: 5.0 to 2.6%, P=0.006). Average 24-hour glucose was not improved over the whole group and there were no group x time interactions for CGM data (HIT: 103.9 to 98.2 mg/dl; CONT: 99.9 to 100.2 mg/dl, P>0.05). When statistical analysis included only the subjects who started with an average glucose at baseline > 100 mg/dl, there was a significant improvement in glucose control overall, but no group x time interaction (107.8 to 94.2 mg/dl, P=0.027). Eight weeks of HIT led to superior improvements in endothelial function and similar improvements in glucose control in obese subjects at risk for T2D and CVD. HIT was shown to have comparable or superior health benefits in this obese sample with a 36% lower total exercise time commitment.
ContributorsSawyer, Brandon J (Author) / Gaesser, Glenn A (Thesis advisor) / Shaibi, Gabriel (Committee member) / Lee, Chong (Committee member) / Swan, Pamela (Committee member) / Buman, Matthew (Committee member) / Arizona State University (Publisher)
Created2013
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Description
Nationally, African Americans suffer disproportionately from diabetes; with 13.2% of African Americans diagnosed with diabetes compared to 7.6% of non-Hispanic whites (CDC, 2014). Nearly one-half of all people with diabetes are non-adherent to their oral medications; adherence to insulin therapy was 60%-80% (Brunton et al., 2011; Cramer, 2004; Rubin, 2005).

Nationally, African Americans suffer disproportionately from diabetes; with 13.2% of African Americans diagnosed with diabetes compared to 7.6% of non-Hispanic whites (CDC, 2014). Nearly one-half of all people with diabetes are non-adherent to their oral medications; adherence to insulin therapy was 60%-80% (Brunton et al., 2011; Cramer, 2004; Rubin, 2005). This study explored the question, "What mechanisms are associated with adherence to diabetes medication, including insulin, for African Americans in the Southwest?" Twenty-three people participated in the study; 17 participated in interviews and six participated in gendered focus groups. A community-based participatory research (CBPR) approach engaged the African American community as partners in research.

Major themes emerging from the data included illness perception, support, and the process of medication adherence. Acceptance of the diabetes diagnosis was imperative for medication adherence. Stigmatization of diabetes was salient in the recruitment process and as it related to mechanisms for adherence. Furthermore, many informants were not aware of a family history of diabetes before their own diagnosis. Four gendered emerging typologies were identified, which further illuminated major themes. Moreover, an eight-step process of medication adherence model is discussed. The researcher was able to identify culturally compatible strategies that may be extended to those struggling with medication adherence. The implications section suggests a set of strategies that healthcare providers can present to people with diabetes in order to increase medication adherence.
ContributorsWardian, Jana (Author) / Marsiglia, Flavio F (Thesis advisor) / Sun, Fei (Committee member) / Shaibi, Gabriel (Committee member) / Arizona State University (Publisher)
Created2015
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Description
This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be

This project details the synthesis and analysis of five analogs of model compound NEt-4IB (6-[ethyl(4-isobutoxy-3-isopropylphenyl)amino]nicotinic acid), that target the retinoid-X-receptor (RXR). These molecules were synthesized by substituting, adding, or removing substituents in the nitrogen-containing ring of NEt-4IB. The parent compound is a RXR partial agonist and has proven to be effective in the treatment of type II diabetes without the unwanted side effects seen with full agonists. Many of the current drugs used to treat type II diabetes are accompanied by adverse effects including increased triglyceride levels, weight gain, and hypoglycemia. Biological evaluation with KK-Ay (obese diabetic) model mice indicates that NEt-4IB may even be more effective than current drugs on the market, like pioglitazone. As a result, it is predicted that due to such structural similarity, the analogs synthesized for this work will perform equally, if not better than, NEt-4IB.
ContributorsMaiorella, Emma Lauren (Author) / Wagner, Carl (Thesis director) / Marshall, Pamela (Committee member) / School of Mathematical and Natural Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
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Description
Background: The prevalence of childhood obesity has disproportionately affected Latino youth. This increase in obesity is seen with an increased incidence of Type 2 Diabetes. Objective/Hypothesis: The objective of this study was to determine the effects of a community based lifestyle intervention, which encompassed nutrition education and physical activity, on

Background: The prevalence of childhood obesity has disproportionately affected Latino youth. This increase in obesity is seen with an increased incidence of Type 2 Diabetes. Objective/Hypothesis: The objective of this study was to determine the effects of a community based lifestyle intervention, which encompassed nutrition education and physical activity, on diabetes risk in pre-diabetic Latino adolescents. Diabetes risk was assessed using pancreatic beta cell function as measured by proinsulin: insulin ratio. It was hypothesized that reductions in added sugar intake and reductions in saturated fat intake will be associated with improved beta cell function as measured by proinsulin: insulin ratio. Study Design/Participants: In this quasi-experimental study design, n=17 pre-diabetic Latino adolescents between the ages of 14-16 participated in a lifestyle intervention. Methods: Anthropometric measurements (weight, height, waist circumference, BMI) and body composition (body %) were determined for all participants at baseline and post intervention. Fasting proinsulin (PI), fasting insulin (I) and 2hr-OGTT were also determined. Dietary intake was measured using the Block Kids Food Screener for kids ages 2-17y (2007). The intervention consisted of nutrition education classes and physical activity sessions for 12 weeks. Results: We found significant decreases in body fat % following the intervention. There were no significant decreases in fasting insulin. Proinsulin significantly decreased. However we did no see a significant change in PI/I (p= 0.003). Dietary behaviors of added sugar (p=0.03) and saturated fat (p=0.04) showed significant decreases. No significant associations were found between changes in added sugar to improvements in beta cell function, r=0.072, p-value= 0.7. We also did not observe significant associations between reductions in saturated fat intake and improvements in beta cell function, r=0.152, p-value =0.6. Conclusions: We concluded that a 12-week lifestyle intervention resulted in significant changes in dietary behaviors. These changes were not however associated with improvements in beta cell function.
ContributorsKaur, Manroop (Author) / Shaibi, Gabriel (Thesis director) / Bruening, Meredith (Committee member) / Barrett, The Honors College (Contributor) / School of Nutrition and Health Promotion (Contributor)
Created2015-05
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Description
Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective

Bexarotene is a commercially produced drug commonly known as Targetin presecribed to treat cutaneous T-cell lymphoma (CTCL). Bex mimics the actions of natural 9-cis retinoic acid in the body, which are derived from Vitamin A in the diet and boost the immune system. Bex has been shown to be effective in the treatment of multiple types of cancer, including lung cancer. However, the disadvantages of using Bex include increased instances of hypothyroidism and excessive concentrations of blood triglycerides. If an analog of Bex can be developed which retains high affinity RXR binding similar to the 9-cis retinoic acid while exhibiting less interference for heterodimerization pathways, it would be of great clinical significance in improving the quality of life for patients with CTCL. This thesis will detail the biological profiling of additional novel (Generation Two) analogs, which are currently in submission for publication, as well as that of Generation Three analogs. The results from these studies reveal that specific alterations in the core structure of the Bex "parent" compound structure can have dramatic effects in modifying the biological activity of RXR agonists.
ContributorsYang, Joanna (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Hibler, Elizabeth (Committee member) / Barrett, The Honors College (Contributor)
Created2012-05
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Description
Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor

Bexarotene (Targretin®) is an FDA approved drug used to treat cutaneous T-cell lymphoma (CTCL), as well as off-label treatments for various cancers and neurodegenerative diseases. Previous research has indicated that bexarotene has a specific affinity for retinoid X receptors (RXR), which allows bexarotene to act as a ligand-activated-transcription factor and in return control cell differentiation and proliferation. Bexarotene targets RXR homodimerization to drive transcription of tumor suppressing genes; however, adverse reactions occur simultaneously when bound to other nuclear receptors. In this study, we used novel bexarotene analogs throughout 5 iterations synthesized in the laboratory of Dr. Wagner to test for their potency and ability to bind RXR. The aim of our study is to quantitatively measure RXR homodimerization driven by bexarotene analogs using a yeast two-hybrid system. Our results suggests there to be several compounds with higher protein activity than bexarotene, particularly in generations 3.0 and 5.0. This higher affinity for RXR homodimers may help scientists identify a compound that will minimize adverse effects and toxicity of bexarotene and serve as a better cancer treatment alternative.
ContributorsSeto, David Hua (Author) / Marshall, Pamela (Thesis director) / Wagner, Carl (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor) / School of Social and Behavioral Sciences (Contributor)
Created2015-05
Description
The purpose of this study was to examine the association between VLDL and diabetes risk factors, and the impact of a lifestyle intervention on VLDL levels in obese Latino youth. Participants (N=160) in this study were taken from a lager diabetes prevention program for Latino adolescents (Age=14.8±0.8 years, BMI=98.2±1.4). Youth

The purpose of this study was to examine the association between VLDL and diabetes risk factors, and the impact of a lifestyle intervention on VLDL levels in obese Latino youth. Participants (N=160) in this study were taken from a lager diabetes prevention program for Latino adolescents (Age=14.8±0.8 years, BMI=98.2±1.4). Youth participated in a 12-week lifestyle intervention that included physical activity (60 minutes, 3x/week) and nutrition education sessions (60 minutes, 1x/week) that were delivered to families at the downtown Phoenix YMCA. Primary outcomes included VLDL and diabetes risk factors including fasting and 2-hour glucose and insulin which were measured at baseline and 12-weeks post-intervention. Baseline VLDL levels were significantly correlated with fasting insulin (r =.270, P<0.01) and youth who were more insulin resistant displayed higher VLDL levels compared to youth who were less insulin resistant derived from fasting insulin levels (M=29.8±14.7 mg/dl vs. M=21.6±9.6 mg/dl, P<0.01). In total, 77 participants completed the lifestyle intervention. At post-intervention, VLDL levels were significantly reduced (M=26.0±13.3 mg/dl to M=23.3±11.6 mg/dl, P=0.02). Culturally-grounded, community-based, family-focused lifestyle interventions are a promising approach for reducing cardiovascular disease risk factors in high-risk youth at risk for diabetes.
ContributorsNavabi, Neeku Ariana (Author) / Shaibi, Gabriel (Thesis director) / Soltero, Erica (Committee member) / Ryder, Justin (Committee member) / School of Nutrition and Health Promotion (Contributor) / Arizona State University. College of Nursing & Healthcare Innovation (Contributor) / Barrett, The Honors College (Contributor)
Created2018-12
Description

This project aimed to identify barriers to participation and develop strategies to increase the accessibility of a diabetes prevention program in the Latino community. Surveys were administered to past participants of a randomized control trial at a community event where study results were shared. The top concerns expressed by respondents

This project aimed to identify barriers to participation and develop strategies to increase the accessibility of a diabetes prevention program in the Latino community. Surveys were administered to past participants of a randomized control trial at a community event where study results were shared. The top concerns expressed by respondents were related to the use of personal information. Primary barriers to participation included work/school commitments and transportation issues. Strategies to increase accessibility included providing flexible class times, having bilingual research staff, and using multiple forms of community outreach such as flyers, health events, phone calls, texts, and social media. Expanding community partners was also identified as a primary strategy for increasing program reach. Researchers should focus on addressing confidentiality concerns, providing financial compensation for attendance, flexible scheduling, and utilizing diverse outreach methods to enhance access to diabetes prevention programs in the Latino community

ContributorsHouck, Kassidy (Author) / Shaibi, Gabriel (Thesis director) / Williams, Allison (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2023-05
Description

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application

The ever-increasing importance of cancer and neurodegenerative diseases continues to grow as populations across the world are affected by death and aging. The vitamin A (RXR) and vitamin D (VDR) receptor pathways offer promising potential to aid in treatment of cancer and Alzheimer’s disease. This thesis discusses the potential application of novel analogs of Bexarotene (RXR agonist), MeTC7 (a new potent VDR antagonist), and vitamin D as possible therapeutics for cancer and Alzheimer’s disease.

ContributorsHong, Jennifer (Author) / Jurutka, Peter (Thesis director) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Barrett, The Honors College (Contributor) / School of Mathematical and Natural Sciences (Contributor)
Created2023-05
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Description
Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. More

Bexarotene is a Food and Drug administration (FDA)-approved therapeutic used in the treatment of cutaneous T-cell lymphoma (CTCL). However, bexarotene therapy causes significant side effects like hyperlipidemia and hypothyroidism due to crossover activity with retinoic acid receptor (RAR), thyroid hormone receptor (TR), and liver X receptor (LXR) signaling, respectively. More recently bexarotene has shown promise to reverse neurodegeneration, improve cognition and decrease levels of amyloid- β in transgenic mice expressing familial Alzheimer’s disease (AD) mutations. Bexarotene is a high affinity ligand for the retinoid X receptor (RXR) that heterodimerizes with the liver- X- receptors (LXR) and with peroxisome proliferator-activated receptor-gamma (PPARϒ) to control cholesterol efflux, inflammation, and transcriptionally upregulates the production of apolipoprotein (ApoE) in the brain. Enhanced ApoE expression may promote clearance of soluble Aβ peptides from the brain and reduce Aβ plaques, thus resolving both amyloid pathology and cognitive deficits. The present study assessed the potential of bexarotene and a group of 62 novel rexinoids to bind and activate RXR using a series of biological assays and screening methods, including: 1) a mammalian two-hybrid system (M2H) and an 2) Retinoid X Receptor response element (RXRE)-mediated reporter assays in cultured human cells. Moreover, Liver X Receptor response element (LXRE)-mediated luciferase assays were performed to analyze the ability of the novel analogs to activate LXRE - directed transcription, and to induce ApoE messenger ribonucleic acid (mRNA) in U87 glial cells. Furthermore, the most potent analogs were analyzed via quantitative polymerase chain reaction (qPCR) to determine efficacy in modulating expression of two critical tumor suppressor genes, activating transcription factor 3 (ATF3) and early growth response 3 (EGR3). Results from these multiple assays indicate that the panel of RXR ligands contains compounds with a range of activities, with some analogs capable of binding to RXR with higher affinity than others, and in some cases upregulating ApoE expression to a greater extent than bexarotene. The data suggests that minor modifications to the bexarotene core chemical structure may yield novel analogs possessing an equal or greater capacity to activate RXR and may be useful as therapeutic agents against CTCL and Alzheimer’s disease.
ContributorsReshi, Sabeeha Mushtaq (Author) / Jurutka, Peter (Thesis advisor) / Wagner, Carl (Committee member) / Marshall, Pamela (Committee member) / Arizona State University (Publisher)
Created2023