Matching Items (11)
Description
It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be linked with dysfunctional complexes in the mitochondrial respiratory chain, increased oxidative stress, and potential cell death. Increased understanding of the pathophysiology of this disease has enabled the development of various therapeutic strategies aimed at restoring mitochondrial respiration. This thesis contains an analysis of the biological activity of several classes of antioxidants against oxidative stress induced by diethyl maleate in Friedreich's Ataxia lymphocytes and CEM leukemia cells. Analogues of vitamin E α-tocopherol have been shown to protect cells under oxidative stress. However, these same analogues show various levels of inhibition towards the electron transport chain complex I. Bicyclic pyridinols containing a ten carbon substituent provided favorable cytoprotection. N-hydroxy-4-pyridone compounds were observed to provide little protection. Similarly, analogues of CoQ10 in the form of pyridinol and pyrimidinol compounds also preserved cell viability at low concentrations.
ContributorsJaruvangsanti, Jennifer (Author) / Hecht, Sidney (Thesis advisor) / Woodbury, Neal (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2012
Description
Throughout time, compounds from natural sources have provided humans with medicines, and recently become the structural inspiration for semisynthetic drugs. One arena that has benefited greatly from the use of these natural products is the discovery of novel antibacterial agents. Methicillin-resistant Staphylcoccus aureus (MRSA) continues to plague the United States as well as throughout the world, at least in part because of increasing antibiotic resistance. Therefore, scientists continue to scour natural products as potential leads, either directly or indirectly, for antibiotics to treat MRSA. The structure of the indole sesquiterpene, polyalthenol, was discovered in 1976 and recent work shows a 4µg/mL minimum inhibitory concentration (MIC) against a variety of strains of MRSA. Given the unique framework of this natural product and its biological activity against MRSA, the total synthesis becomes the next logical step. Presently a racemic synthesis has successfully afforded an indole ketone with the correct relative stereochemistry of polyalthenol, however, the completion of the total synthesis of polyalthenol presents several challenges. Herein, the work towards the synthesis is described in addition to the proposed completion of the synthesis.
ContributorsReichenberg, Erynn Wright (Author) / Madar, David J (Thesis advisor) / Skibo, Edward (Committee member) / Miller, William (Committee member) / Arizona State University (Publisher)
Created2012
Description
Combretastatin A-4 (CA-4) represents one of the most promising antineoplastic and cancer vascular targeting stilbenes that have been isolated from the South African bush willow, Combretum Caffrum Kuntze. In order to further explore the bioactivity of this molecule, a diiodo derivative of CA-4, as well as its phosphate prodrug, was synthesized and analyzed for its biological activity; although only a scale up synthesis of this compound was performed herein for ongoing analysis. In general, no increased specificity was noted for the human cancer cell lines. Antiangiogenic properties were similar to the untreated control. The diiodocombstatin was active against M. luteus, and its phosphate prodrugs were very active against N. gonorrhoeae. Combretastain A-2 is another biologically active stilbene isolated from Combretum Caffrum Kuntze. In an attempt to increase biological activity of this molecule both mono-iodo and diiodo derivatives have been partially synthesized. The initial step involving the iodination of piperonal utilizes a novel, cost effective and mild reaction. The iodo stilbenes were obtained via a Wittig reaction using phosphonium salts 25 and 27 along with 2,3-Bis-[tert-butyldimethylsiloxy]-4-methoxy benzaldehyde 29. Deprotection of the subsequent z-stilbenes, non-isolated mono-iodo stilbene and the diiodo 30 produced two synthetic objective z-stilbenes 16 and 17. Synthesis as well as biological analysis is ongoing.
ContributorsTrickey-Platt, Brindi Brooks (Author) / Pettit, George R. (Thesis advisor) / Moore, Ana (Committee member) / Skibo, Edward (Committee member) / Arizona State University (Publisher)
Created2011
Understanding the Current State of Vaccination Coverage in Arizona Schools: A Correlational Analysis
Description
The purpose of this study was to investigate what correlations exist between the immunization and personal belief exemption (PBE) rates and selected characteristics of Arizona schools. The demographic information of a school's student body, the percentage of student who are on free or reduced lunch, the presence of a Title I program at the school, the median household income of the zip code the school resides in, and the presence of a school nurse were all compared with immunization and PBE rates. Using data provided by the Arizona Department of Health Services (AZDHS), the National Center for Education Statistics (NCES), and the United States Census Bureau, these factors were investigated for kindergarten and 6th grade students. It was found that a higher percentage of white students in a student body was correlated with an higher rate of PBE and a lower immunization rate for measles, mumps, and rubella (MMR), polio, and hepatitis B. A higher percentage of Hispanic students in a student body was correlated with a lower rate of PBE and a higher immunization rate for measles, mumps, rubella (MMR), polio, and hepatitis B. There was little to no correlation between the percentage of students on free or reduced lunch and immunization or PBE rates. A higher median household income was correlated with a higher rate of PBE in public and private schools. Additionally, the immunization rates at schools with a nurse were significantly higher and the rate of PBE was significantly lower than at schools without a nurse. Finally, schools with a Title I program had mean immunization rates that were significantly higher and a mean PBE rate that was significantly lower than schools that did not have a Title I program.
ContributorsSellers, Abigail Leigh (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / School of International Letters and Cultures (Contributor) / School of Molecular Sciences (Contributor) / Sandra Day O'Connor College of Law (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
With the new independence of adulthood, college students are a group susceptible to adopting unsupported, if not harmful, health practices. A survey of Arizona State University undergraduate students (N=200) was conducted to evaluate supplement use, trust in information sources, and beliefs about supplement regulation. Of those who reported using supplements, college students most frequently received information from friends and family. STEM majors in fields unrelated to health who were taking a supplement were found to be less likely to receive information about the supplement from a medical practitioner than those in health fields or those in non-STEM majors (-26.9%, p=0.018). STEM majors in health-related fields were 15.0% more likely to treat colds and/or cold symptoms with research-supported methods identified from reliable sources, while non-health STEM and non-STEM majors were more likely to take unsupported cold treatments (p=0.010). Surveyed students, regardless of major, also stated they would trust a medical practitioner for supplement advice above other sources (88.0%), and the majority expressed a belief that dietary supplements are approved/regulated by the government (59.8%).
ContributorsPerez, Jacob Tanner (Author) / Hendrickson, Kirstin (Thesis director) / Lefler, Scott (Committee member) / College of Liberal Arts and Sciences (Contributor) / School of Molecular Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2018-05
Description
Continuing work has been done on a novel class of anti-cancer drugs employing a vinylogous extended amidine system functionalized into benzimidazole ring. Three new derivatives, utilizing a true sugar mimic at the N1-position, have been synthesized. Compounds 6-amino-1-[2-(2-hydroxyethoxy)ethyl-4-imino-2,5-dimethyl-1H-benzimidazole- 7-one (5), 6-amino-1-[2-(2-hydroxysulfonoethoxy)ethyl-4-imino-2,5-dimethyl-1H-benzimidazole-7-one (6), and 6-amino-1-[2-(2-hydroxysulfonoethoxy)ethyl-4-methylimino-2,5-dimethyl-1H-benzimidazole-7-one (7) have been synthesized utilizing similar protocols used in the synthesis of previously screened anti-tumor drugs produced by this laboratory. Compounds (5) and (6) have undergone screening similar to the National Cancer Institute’s (NCIs) Developmental Therapeutic Program (DTP), performed by Dr. Dan LaBarbera at the University of Boston. Both compounds show high cytotoxicity, with complete cell death at 5 µM and bioactive concentrations in the low nanomolar concentrations; more complete data is forthcoming. The proposed mechanism of action is through inhibition of p90RSK 1-2 which is responsible for the phosphorylation of Bcl-2 associated death promoter (BAD), a key metabolite in directing the onset of apoptosis. Future directions of next generation derivatives include modifying the 2-position of the benzimidazole ring into a halogenating or alkylating agent and possibly replacing the methanesulfonate with a phosphate group. This research is being published in the Journal of Medicinal Chemistry.
ContributorsMorrison, Zachary Tyler (Author) / Skibo, Edward (Thesis director) / Lefler, Scott (Committee member) / Barrett, The Honors College (Contributor) / Department of Chemistry and Biochemistry (Contributor)
Created2014-05
Description
Spending time outdoors can have a positive impact on the physical and mental health of individuals. These physiological and psychological benefits were comprehensively reviewed, accompanied by a brief history of these views in American society and how modern programs are promoting outdoor activity. Some of the populations targeted in this research include children, veterans, the elderly, and the clinically ill. A guidebook for Arizona outdoor adventures \u2014 containing original landscape photography \u2014 was created to encourage ASU students to explore local hikes, campsites, and other outdoor opportunities near the city of Phoenix. Each entry contained a brief description of the area or trail, along with the distance from the ASU Tempe campus and information on the length and difficulty of the hike, if applicable. A section at the end of the book was aimed at education readers on basic outdoor survival protocol, as many people venture into the wild with very little understanding of the dangers associated with their activities. A website was made that mirrors the guidebook, but was intended to be a more accessible method of sharing our information. The final component of the project involved maintaining a social media account over the course of the year, allowing us to expand our reach to people beyond ASU and this community. Over the course of the project, the account gained a large following, and several posted photos went on to be featured on prominent regional accounts. By combining the four components described previously, several resources were created for people, particularly students attending ASU, to gain a better understanding of the outdoor adventures available to them, and the benefits that spending time surrounded by nature can have.
ContributorsSwitzer, Hannah (Co-author) / Weinstein, Casey (Co-author) / Smith, Andrew (Thesis director) / Lefler, Scott (Committee member) / Kozakiewicz, Scott (Committee member) / Harrington Bioengineering Program (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05
Description
A potential new class of cancer chemotherapeutic agents has been synthesized by varying the 2 position of a benzimidazole based extended amidine. Compounds 6-amino-2-chloromethyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1A) and 6-amino-2-hydroxypropyl-4-imino-1-(2-methansulfonoxyethyl)-5-methyl-1H-benzimidazole-7-one (1B) were assayed at the National Cancer Institute's (NCI) Developmental Therapeutic Program (DTP) and found to be cytotoxic at sub-micromolar concentrations, and have shown between a 100 and a 1000-fold increase in specificity towards lung, colon, CNS, and melanoma cell lines. These ATP mimics have been found to correlate with sequestosome 1 (SQSTM1), a protein implicated in drug resistance and cell survival in various cancer cell lines. Using the DTP COMPARE algorithm, compounds 1A and 1B were shown to correlate to each other at 77%, but failed to correlate with other benzimidazole based extended amidines previously synthesized in this laboratory suggesting they operate through a different biological mechanism.
ContributorsDarzi, Evan (Author) / Skibo, Edward (Thesis advisor) / Gould, Ian (Committee member) / Francisco, Wilson (Committee member) / Arizona State University (Publisher)
Created2011
Description
Peer-reviewed literature on the effects of sound and music on babies ranging from the prenatal period to the postnatal period, called the perinatal period moving forward, is vast. Substantial research has been directed towards the neural connections they make with sound, musical therapy, audio learning, and much more. The primary focus of this thesis was to review the current literature on how the father's voice affects the fetus during the perinatal period. During the preliminary research of the topic, the process faced an immediate problem as this concept had very little substantial sources. The number of relevant articles or documents with the term “father” in the title can be counted on one hand. In some cases, research that explored the father’s voice did so only as a supporting statistic or comparison to the main goal of exploring the mother’s voice. The mother’s voice has been prioritized as a research topic because of the immediate physical connection between the mother and the child throughout the entire pregnancy. The third semester of pregnancy is often a period of study since what the mother senses, says or does will somehow translate into an experience for the child’s developing brain. On the other hand, the father’s voice has been considered an environmental sound, a position justified by some researchers due to phenomena such as differing levels of fetal attention and observed “preference” of a newborn. The scarcity of research regarding the father’s voice, or the voice of a non-parental male, can be explained in several ways. These include the father’s potential absence due to work, inherited ideologies and biases against active parenting for the father, parental roles, and their unwillingness to utilize infant-directed speech and singing for psychological reasons, during the perinatal period, compared to that of the mother. Researching ways to deepen the relationship between the father and baby during the perinatal period, along with developing new biotechnologies for different kinds of evaluative tests, will help advance the subject matter of how the father’s voice impacts a baby to a larger scale.
ContributorsNguyen, Justin Dinh Huy (Author) / Norton, Kay (Thesis director) / Lefler, Scott (Committee member) / School of Music, Dance and Theatre (Contributor) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
Every year, Inflammatory Bowel Disease (IBD) is diagnosed in a growing number of the Americans. Consequently, an extensive amount of research has been dedicated to understanding this disease, and identifying which factors contribute to its symptoms. A large portion of this research has been focused on diet. This paper outlines some of the common diets that are recommended to help those with IBD. The diets discussed are the specific carbohydrate diet, IBD-AID, enteral/parenteral nutrition, low – FODMAP diet, and exclusion diet. It was found that there is a lot of overlap between these diets. Several foods such as corn, dairy, and processed meats were on the avoidance list for more than one diet. Additionally, several diets recommend including probiotic and prebiotic foods each day. From the research gathered in this paper, it is recommended to create an individualized diet with a team of healthcare professionals, using the diets discussed as a guide. While diet is only one of many lifestyle choices that can affect the symptoms of IBD, it is an important one to consider, and can greatly impact the quality of life for patients.
ContributorsAllred, Brandon (Author) / Don, Rachael (Thesis director) / Lefler, Scott (Committee member) / Barrett, The Honors College (Contributor) / Dean, W.P. Carey School of Business (Contributor) / Department of Information Systems (Contributor) / School of Molecular Sciences (Contributor)
Created2023-05