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Description
Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and

Doxorubicin (DOX) is a cardiotoxic, anthracycline-based, anti-neoplastic agent that causes pathological cardiac remodeling due to altered protein expression associated with cardiotoxicity. DOX cardiotoxicity causes increased Akt phosphorylation, blunted AMPK phosphorylation and upregulated mTOR phosphorylation. Akt is activated by cellular stress and damage. AMPK is activated by increases in AMP and ADP concentrations and decreased ATP concentration. mTOR is active in cellular growth and remodeling. These proteins are cellular kinases with cascades that are influenced by one another. Exercise preconditioning may diminish the cardiotoxic effects on these proteins. Female, Ovariectomized Sprague-Dawley rats (N=33) were randomized to: Exercise+DOX (EX+DOX, n=9); Exercise+Vehicle (EX+VEH, n=8); Sedentary+DOX (SED+DOX, n=8); and Sedentary+Vehicle (SED+VEH, n=8) groups. DOX (4mg/kg) or VEH (saline) intraperitoneal injections were administered bi-weekly (cumulative dose of 12mg/kg). VEH animals received body weight matched volumes of saline based on dosing in animals receiving DOX. Exercise (EX) animals underwent high intensity (85-95% VO2 peak) interval training (HIIT) (4x4 min bouts) separated by low intensity (50-60% VO2max) intervals (2 min bouts) 5 days per week. Exercise began 1 week prior to the first injection and was continued throughout the study. Rats were euthanized 5 days after the last injection. Left ventricular tissue was isolated, processed into lysate and used for western blot analyses [2x2 ANOVA; (α=0.05)]. DOX induced significant phosphorylation of Akt and mTOR (p=0.035; p=0.032) only in SED+DOX rats, but unchanged in EX+DOX rats. No significant differences (p=0.374) in AMPK phosphorylation were observed between groups. Exercise Preconditioning prevents some DOX-induced changes in the cardiac mTOR signaling pathway implicated in pathological remodeling.
ContributorsPanknin, Timothy M (Author) / Angadi, Siddhartha (Thesis director) / Sweazea, Karen (Committee member) / Dickinson, Jared (Committee member) / School of Nutrition and Health Promotion (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
This creative thesis project aimed to create career development resources that School of Life Sciences majors could use to enhance their college experience, expand the breadth of relevant career options for School of Life Sciences majors, and confront and divert career problems through the implementation of these career development resources.

This creative thesis project aimed to create career development resources that School of Life Sciences majors could use to enhance their college experience, expand the breadth of relevant career options for School of Life Sciences majors, and confront and divert career problems through the implementation of these career development resources. Students encounter career problems when their intention and action diverge. These career problems may cause a student to stop their pursuit of a given career, change majors, or even stop schooling completely. It is the objective of this project to help resolve these career problems by introducing a career development resource flyer that educates the student about a given career, provides coursework to guide a student towards this career path, familiarize students with extracurricular efforts necessary for this position, propose valuable resources that the student can utilize to learn more about the career, and offer a question and answer portion for further career and professional understanding. In order to create these career development resource flyers a variety of professionals, both with and without relationships with Arizona State University were contacted and interviewed. The answers gathered from these interviews were then utilized to create the career flyers. The project was successful in creating five distinct career development resource flyers, as well as a blank template with instructions to be used in the future by the School of Life Sciences. The career development resource flyers will be utilized by the School of Life Sciences advising staff for future exploratory majors, but is not limited to just these students. Aspirations are set to create an expansive reservoir of these resources for future generations of students to access in hopes that they will be better suited to find a career path that they are passionate about and be better prepared to attain.
ContributorsGallegos, Darius Sloan (Author) / Wilson Sayres, Melissa (Thesis director) / Downing, Virginia (Committee member) / DeNardo, Dale (Committee member) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
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Description
The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is

The anthracycline drug Doxorubicin (DOX) is a highly effective treatment for breast cancer, but its clinical utility is limited by dose-dependent cardiovascular toxicity. The toxic effects are partly attributed to DOX-induced generation of reactive oxygen species, which may impair nitric oxide-mediated vasodilation. Exercise training activates antioxidant defense mechanisms and is thus hypothesized to counteract oxidative stress when initiated prior to DOX administration. Adult 8-week old, ovariectomized female Sprague-Dawley rats were divided into 4 groups: sedentary + vehicle (Sed+Veh); Sed+DOX; exercise + veh (Ex+Veh); and Ex+DOX. Rats in the exercise groups were preconditioned with high intensity interval training consisting of 4x4 minute bouts of exercise at 85-95% of VO2peak separated by 2 minutes of active recovery performed 5 days per week. Exercise was implemented one week prior to the first injection and continued throughout the study. Animals received either DOX (4mg/kg) or veh (saline) intraperitoneal injections bi-weekly for a cumulative dose of 12 mg/kg per animal. Five days following the final injection, animals were anesthetized with isoflurane, decapitated and aortas and perivascular adipose tissue (PVAT) were removed for western blot analyses. No significant differences in aortic protein expression were detected for inducible nitric oxide synthase (iNOS) or the upstream activator of endothelial nitric oxide synthase (eNOS), Akt, across groups (p>0.05), whereas eNOS protein expression was significantly downregulated in Sed+DOX (p=0.003). In contrast, eNOS expression was not altered in Ex+DOX treated animals. Protein expression of iNOS in PVAT was upregulated with exercise in the DOX-treated groups (p=0.039). These findings suggest that exercise preconditioning may help mitigate vascular effects of DOX by preventing downregulation of eNOS in the aorta.
ContributorsO'Neill, Liam Martin (Author) / Sweazea, Karen (Thesis director) / Angadi, Siddhartha (Committee member) / Dickinson, Jared (Committee member) / School of Human Evolution and Social Change (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-12
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Description

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing

2D fetal echocardiography (ECHO) can be used for monitoring heart development in utero. This study’s purpose is to empirically model normal fetal heart growth and function changes during development by ECHO and compare these to fetuses diagnosed with and without cardiomyopathy with diabetic mothers. There are existing mathematical models describing fetal heart development but they warrant revalidation and adjustment. 377 normal fetuses with healthy mothers, 98 normal fetuses with diabetic mothers, and 37 fetuses with cardiomyopathy and diabetic mothers had their cardiac structural dimensions, cardiothoracic ratio, valve flow velocities, and heart rates measured by fetal ECHO in a retrospective chart review. Cardiac features were fitted to linear functions, with respect to gestational age, femur length, head circumference, and biparietal diameter and z-scores were created to model normal fetal growth for all parameters. These z-scores were used to assess what metrics had no difference in means between the normal fetuses of both healthy and diabetic mothers, but differed from those diagnosed with cardiomyopathy. It was found that functional metrics like mitral and tricuspid E wave and pulmonary velocity could be important predictors for cardiomyopathy when fitted by gestational age, femur length, head circumference, and biparietal diameter. Additionally, aortic and tricuspid annulus diameters when fitted to estimated gestational age showed potential to be predictors for fetal cardiomyopathy. While the metrics overlapped over their full range, combining them together may have the potential for predicting cardiomyopathy in utero. Future directions of this study will explore creating a classifier model that can predict cardiomyopathy using the metrics assessed in this study.

ContributorsNumani, Asfia (Co-author) / Mishra, Shambhavi (Co-author) / Sweazea, Karen (Thesis director) / Plasencia, Jon (Committee member) / School of Mathematical and Statistical Sciences (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05