Medicine and Health Sciences Commons^™

Discovery Of Small-Molecule Natural Products That Target Cellular Bioenergetics, Sandipan Datta

Electronic Theses and Dissertations

Molecular-targeted antitumor therapy has found favor in antitumor drug discovery programs. Hypoxia (< 5% oxygen) is a comfeature of solid tumors and hypoxia-inducible factor-1 (HIF-1) represents an important antitumor target. Bioenergetic homeostasis is typically altered in tumor cells and HIF-1 plays an important role to produce a glycolytic phenotype. Glycolysis inhibitors are an emerging class of potential tumor-selective adjuvant therapeutic agents. Natural product aerobic glycolysis inhibitors may enhance the effectiveness of current therapies. Mitochondrial oxidative phosphorylation inhibitors in botanical dietary supplements (BDS) possess a potential health hazard which should be identified and appropriately regulated. Chapter one briefly reviews the molecular-targeted natural product antitumor drug discovery process. Descriptions of tumor hypoxia, HIF-1, HIF-1 regulatory pathways and the effect of HIF-1 on tumor cell bioenergetics are presented. Cellular bioenergetic pathways and natural products that inhibit HIF-1 by interfering with cellular bioenergetics are discussed. Mitochondriotoxic small-molecule natural products reported previously are further reviewed. Chapter two discusses the effect of chromatographic media on molecular-targeted antitumor drug discovery. A panel of crude extracts was eluted through columns of various chromatographic media using a step gradient method. Total recoveries from the various columns and various elution protocols were compared and statistically analyzed. The crude extracts and column eluates were evaluated for HIF-1 inhibitory activity. Chapter three discusses the development of a bioenergetics-based screening method to screen crude extracts for glycolysis inhibitors. Crude extracts (10,648) were screened and seven hits (hit rate 0.72%) were identified. Bioassay-guided isolation of Moronobea coccinea crude extract resulted in isolation of a protonophoric compound moronone (1) (false positive). The structure of 1 was determined by a combination of spectroscopic and spectrometric means. The protonophoric compounds must be rapidly dereplicated for successful discovery of glycolysis inhibitors. Chapter four discusses the screening of BDS products and pure compounds for mitochondrial uncouplers or electron transport chain inhibitors. The blue cohosh (Caulophyllum thalictroides) extract and three saponins cauloside A (3), saponin PE (4) and cauloside C (5) permeabilize the mitochondrial membrane. Sesamin (6) and guggulsterol III (7) and guggul (Commiphora wightii) extract inhibit mitochondrial complex I. These extracts and compounds are cytotoxic in nature.

Impaired Object Tracking In Children With Chromosome 22q11.2 Deletion Syndrome, Margarita H. Cabaral, Elliott A. Beaton, Joel Stoddard, Tony J. Simon

Psychology Faculty Publications

Background:

Chromosome 22q11.2 Deletion Syndrome (22q11.2DS) occurs in approximately 1:4,000 live births with a complex and variable presentation that includes medical, socioemotional and psychological symptoms with intellectual impairment. Cognitive impairments in spatiotemporal and visuospatial attention have also been reported. However, maintenance of selective attention to dynamic and interacting objects has not been systematically investigated in children with 22q11.2DS.

Methods:

We used a multiple object tracking task to assay capacity and resolution performance of children with 22q11.2DS aged 7 to 14 years versus age-matched typically developing (TD) peers.

Results:

Children with 22q11.2DS but not TD children demonstrated impaired performance when task …

Development Of Novel Thermosensitive Polymers For Bioresponsive Drug Delivery, Vivek Kumar Garripelli

Electronic Theses and Dissertations

Stimuli-responsive polymers have already shotremendous promise in controlled and self-regulated drug delivery. Successful construction of responsive polymers requires amalgamation of chemical, physical and biological principles. For careful therapy, a great deal of advantages offered by stimuli-responsive polymers is essential. A small or modest change in the environmental condition (e.g. temperature, pH, light) brings a sharp change in the properties of the responsive polymers. 'Smart' drug delivery systems utilize these principles to mimic the biological response behavior to a certain extent. Synthetic polymers incorporated with stimuli-responsive behavior would be amenable to overcome some of the systemic and intracellular delivery barriers. Development …

Metabolism And Pharmacokinetics In The Development Of New Therapeutics For Cocaine And Opioid Abuse, Pradeep Kumar Vuppala

Electronic Theses and Dissertations

Cocaine and opioid abuse are a major public health concern and the cause of significant morbidity and mortality worldwide. The development of effective medication for cocaine and opioid abuse is necessary to reduce the impact of this issue upon the individual and society. The pharmacologic treatment for drug abuse has been based on one of the following strategies: agonist substitution, antagonist treatment, or symptomatic treatment. This dissertation is focused on the role of metabolism and pharmacokinetics in the development of new pharmacotherapies, CM304 (sigma-1 receptor antagonist), mitragynine and 7-hydroxymitragynine (μ-opioid receptor agonists), for the treatment of drug abuse. The affinity …

Virginia Dental Journal (Vol. 89, No. 1, 2012)

Virginia Dental Journal

No abstract provided.

The Effects Of Stress-Reducing Interventions On Perceived Test Anxiety And Achievement Of Nursing Students, Julie Mcdaniel

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Isolation Of L4 Ribo-Protein Mutants That Affect The Expression Of Tna Operon Of Escherichia Coli, Soniykha Dhevi Murukan

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Patterns Of Cancer Genetic Testing : A Randomized Survey Of Oregon Clinicians, Summer Cox, Amy I. Zlot, Kerry Silvey, Debi Elliot, Tara Horn, Amber Johnson, Richard F. Leman

OHSU-PSU School of Public Health Faculty Publications and Presentations

Introduction. Appropriate use of genetic tests for population-based cancer screening, diagnosis of inherited cancers, and guidance of cancer treatment can improve health outcomes. We investigated clinicians’ use and knowledge of eight breast, ovarian, and colorectal cancer genetic tests. Methods. We conducted a randomized survey of 2,191 Oregon providers, asking about their experience with fecal DNA, OncoVue, BRCA, MMR, CYP2D6, tumor gene expression profiling, UGT1A1, and KRAS. Results. Clinicians reported low confidence in their knowledge of medical genetics; most confident were OB-GYNs and specialists. Clinicians were more likely to have ordered/recommended BRCA and …

The Impact Of Literacy Through Movement In A 3rd Grade Hispanic Classroom, Daniel Peregrino

Open Access Theses & Dissertations

This case study examines the effects of a kinesthetic literacy-training program on the complexity of narrative production and performance on the Garfield Motivation to Read Survey in a group of four 3rd grade elementary students. The 3rd grade teacher attended a Literacy Through Movement workshop to learn a range of movement-based literacy activities and methods for the classroom. The LITMO program was then implemented as part of a language arts poetry module for 3 weeks in her classroom. Changes in four students' performance on the Garfield Survey and narrative samples were measured before and after the LITMO intervention. Results suggest …

Simulating Molecular Mechanisms Of The Mdm2-Mediated Regulatory Interactions: A Conformational Selection Model Of The Mdm2 Lid Dynamics, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Diversity and complexity of MDM2 mechanisms govern its principal function as the cellular antagonist of the p53 tumor suppressor. Structural and biophysical studies have demonstrated that MDM2 binding could be regulated by the dynamics of a pseudo-substrate lid motif. However, these experiments and subsequent computational studies have produced conflicting mechanistic models of MDM2 function and dynamics. We propose a unifying conformational selection model that can reconcile experimental findings and reveal a fundamental role of the lid as a dynamic regulator of MDM2-mediated binding. In this work, structure, dynamics and energetics of apo-MDM2 are studied as a function of posttranslational modifications …

Whole Body Vibration Training Is Osteogenic At The Spine In College-Age Men And Women, Todd C. Shoepe, Hawley C. Almstedt, Gianna C. Ligouri

Health and Human Sciences Faculty Works

Osteoporosis is a chronic skeletal disease characterized by low bone mass which is currently challenging the American health care system. Maximizing peak bone mass early in life is a cost-effective method for preventing osteoporosis. Whole body vibration (WBV) is a novel exercise method with the potential to increase bone mass, therefore optimizing peak bone and decreasing the risk for osteoporotic fracture. The aim of this investigation was to evaluate changes in bone mineral density at the hip, spine, and whole body in college-age men and women who underwent a WBV training protocol. Active men (n=6) and women (n=4), ages 18-22 …

Physical Activity In Childhood May Be The Key To Optimizing Lifespan Skeletal Health, Hawley C. Almstedt, Katherine B. Gunter, Kathleen F. Janz

Health and Human Sciences Faculty Works

Physical activities undertaken in childhood, particularly activities which apply large forces quickly convey optimal benefits to bone mass, size, and structure. Evidence is accumulating that benefits persist well beyond activity cessation. This review examines the potential for early childhood activity to improve bone mineralization and structure and explores childhood activity as prevention for osteoporosis in later life.

Efficacy Of Phosphatidic Acid Ingestion On Lean Body Mass, Muscle Thickness And Strength Gains In Resistance-Trained Men, William Mccormack

Health and Human Sciences Faculty Works

Background: Phosphatidic acid (PA) has been reported to activate the mammalian target of rapamycin (mTOR) signaling pathway and is thought to enhance the anabolic effects of resistance training. The purpose of this pilot study was to examine if oral phosphatidic acid administration can enhance strength, muscle thickness and lean tissue accruement during an 8-week resistance training program. Methods: Sixteen resistance-trained men were randomly assigned to a group that either consumed 750 mg of PA (n = 7, 23.1 ± 4.4 y; 176.7 ± 6.7 cm; 86.5 ± 21.2 kg) or a placebo (PL, n = 9, 22.5 ± 2.0 y; …

L-Alanyl-L-Glutamine Ingestion Maintains Performance During A Competitive Basketball Game, William Mccormack

Health and Human Sciences Faculty Works

Background: The purpose of this study was to examine the efficacy of L-alanyl-L-glutamine (AG) ingestion on basketball performance, including jump power, reaction time, shooting accuracy and fatigue. Methods: Ten women (21.2 ± 1.6 years; height: 177.8 ± 8.7 cm; body mass: 73.5 ± 8.0 kg), all scholarship NCAA Division I basketball players, volunteered for this study. Subjects participated in four trials, each consisting of a 40-min basketball game with controlled time-outs for rehydration. During the first trial (DHY) subjects were not allowed to rehydrate, and the total weight lost during the contest was used to determine fluid replenishment during the …

The Effect Of A Dietary Supplement (N-Oleyl-Phosphatidyl-Ethanolamine And Epigallocatechin Gallate) On Dietary Compliance And Body Fat Loss In Adults Who Are Overweight: A Double-Blind, Randomized Control Trial, William Mccormack

Health and Human Sciences Faculty Works

Background: A dietary supplement containing a blend of 170mg of N-oleyl-phosphatidylethanolamine (NOPE) and 100mg of epigallocatechin-3-gallate (EGCG) has been shown to improve compliance to low caloric diets. Considering the cost of dietary ingredients, many manufacturers attempt to determine the lowest efficacious dose. Thus, the purpose of this study was to evaluate the efficacy of 8-weeks of supplementation with a daily intake of 120mg of NOPE and 105mg of EGCG in conjunction with a low caloric diet and regular, moderate exercise on dietary compliance in healthy, overweight adults. An additional purpose was to examine the effect of this supplement/diet/exercise paradigm on …

Body Mass Index Change In Adulthood And Lung And Upper Aerodigestive Tract Cancers, Heather Tarleton

Health and Human Sciences Faculty Works

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population-based case-control study conducted in Los Angeles County. Adulthood BMI change was measured as the proportional change in BMI between age 21 and 1 year before interview or diagnosis. Five categories of BMI change were included, and individuals with no more than a 5% loss or gain were defined …

The Effect On Colon Visualization During Colonoscopy Of The Addition Of Simethicone To Polyethylene Glycol-Electrolyte Solution: A Randomized Single-Blind Study., Rebecca Matro, Keegan Tupchong, Constantine Daskalakis, Victoria Gordon, Leo Katz, David Kastenberg

Division of Gastroenterology and Hepatology Faculty Papers

OBJECTIVES: Colonic bubbles associated with polyethylene glycol-electrolyte solution (PEG-ELS) are common and obscure mucosal visualization. This study aimed to determine whether adding simethicone decreases the incidence of bubbles.

METHODS: Prospective, single-blind, randomized comparison of split dose PEG-ELS vs. PEG-ELS+simethicone (PEG-S) for outpatient colonoscopy. Bubble severity for colonic segments was assessed on withdrawal as A=no/minimal bubbles, B=moderate bubbles/interfere with detecting 5 mm polyp, C=severe bubbles/interfere with detecting 10 mm polyp. Primary end point was Grade B or C bubbles in any colon segment. Secondary end points were cleansing quality, incidence and severity of side effects, and polyp detection.

RESULTS: One hundred …

Service Learning In Higher Education Exercise Science Programs, Wendy Bjerke Ph.D.

Journal of Sustainable Social Impact

Service Learning in Higher Education Exercise Science Programs

ABSTRACT

Research Category

INTRODUCTION: Service Learning (SL) describes teaching methods that incorporate student service activities with specific learning objectives. SL has been applied to allied health higher education programs.

PURPOSE: To determine the applicability of SL to exercise science courses. SL data associated with an undergraduate course in exercise physiology serving a local fire department is examined.

METHODS: Among 90 firefighters, resting heart rate, blood pressure, estimated relative VO2 max, body composition, lower extremity power, upper body strength, flexibility, and perceived stress was assessed pre and post an education and physical …

Agenda-Building Influences On The News Media's Coverage Of The U.S. Food And Drug Administration's Push To Regulate Tobacco, 1993-2009, Caroline D. Foster, James F. Thrasher, Sei-Hill Kim, India Rose, John C. Besley, Ashley Navarro

Faculty Publications

Citing agenda-building theory, this article examines the influence of three key factors on the news media's coverage of the process of placing tobacco and tobacco products under regulation of the U.S. Food and Drug Administration between 1993 and 2009. We analyzed data from a content analysis of 570 news articles from The New York Times and Washington Post and found that the media published significantly more FDA regulation articles during the Clinton administration than during the Bush administration. Our analysis links that imbalance of media coverage to the influence of the president of the United States (Clinton and Bush, during …

Rating Scale Analysis And Psychometric Properties Of The Caregiver Self-Efficacy Scale For Transfers, Daniel Cipriani, Francine E. Hansen, Danielle L. Mcpeck, Gina L.D. Kubec, Julie J. Thomas

Physical Therapy Faculty Articles and Research

Parents and caregivers faced with the challenges of transferring children with disability are at risk of musculoskeletal injuries and/or emotional stress. The Caregiver Self-Efficacy Scale for Transfers (CSEST) is a 14-item questionnaire that measures self-efficacy for transferring under common conditions. The CSEST yields reliable data and valid inferences; however, its rating scale structure has not been evaluated for utility. The aims of this study were to evaluate the category response structure of the CSEST, test the utility of a revised rating scale structure, and confirm its psychometric properties. The Rasch Measurement Model was used for all analyses. Subjects included 175 …

Investigation Into The Functional Mobility Difference Between Obese And Non-Obese Elderly, Xuefang Wu, Han T. Yeoh, Rahul Soangra, Thurmon Lockhart

Physical Therapy Faculty Articles and Research

Obese aging population is increasing in the United States, and obese elderly experience fall twice as frequent as their lean counterparts. However, the mechanisms of older obese adults fall are still not clear. It is not known whether the obese elderly has more functional mobility impairments than their lean counterparts, and consequently have increased risks of falls. It was hypothesized that obese elderly have more functional mobility impairments compared with their healthy weight counterparts. Six lean and six obese community-dwelling elderly participated in the study. “Timed up & go” test was used to quantify the functional mobility for both lean …

A Comparative Study For Performance Evaluation Of Sit-To-Stand Task With Body Worn Sensor And Existing Laboratory Methods, Rahul Soangra, Thurmon E. Lockhart

Physical Therapy Faculty Articles and Research

Human movement such as sit-to-stand (STS) is one of the most fundamental and essential movement among daily living activities. Elderly who are unable to stand are severely limited in daily activities and rely on others for their care. In the coming next two decades about 20% of US population will be above the age of 65 years, and considering ever-increasing elderly population and health care expenses, the rehabilitation of functionally limited elderly is becoming a topic of greater concern. Clinically STS movement is looked upon with great interest, such as its analysis is meaningful in order to evaluate motor control …

Explaining Benefit Utilization Variability In Fmnp In Kentucky: An Application Of Pierre Bourdieu’S Theory, Stephanie M. Holcomb-Kreiner

Theses and Dissertations--Sociology

Research has demonstrated the crucial role fresh fruit and vegetable consumption plays in maintaining good health. However, most Americans do not consume adequate amounts, and low-income Americans consume the lowest quantities of fresh fruits and vegetables. The Farmers’ Market Nutrition Program (FMNP) and Senior Farmers’ Market Nutrition Program (SFMNP) attempts to rectify this situation by providing vouchers to low-income women, children, and elders that can be used only at farmers’ markets for the purchase of locally grown, fresh fruits and vegetables. Unfortunately, FMNP and SFMNP exhibit variable and often low benefit utilization. This variable and often low benefit utilization is …

Proteasome Regulation Of Caspase-8: Significance In Cancer, Michael Vincent Fiandalo

Theses and Dissertations--Molecular and Cellular Biochemistry

Anti-tumor therapeutic strategies based on combinations of chemotherapeutic agents with a death inducing ligand such as TNF-α Related Apoptosis Inducing Ligand (TRAIL), are directed towards selective and effective cancer cell apoptosis and enhanced therapeutic response. We previously demonstrated that proteasome inhibition sensitizes TRAIL resistant prostate cancer cells to TRAIL-mediated apoptosis via stabilization of the active p18 subunit of initiator caspase-8. The present study investigated the functional link between caspase-8 and the proteasome, by analyzing the impact of caspase-8 ubiquitination and proteasomal degradation on the outcomes of the extrinsic apoptosis pathway in cancer cells. Caspase-8 ubiquitination status was assessed by polyubiquitin …

The Cellular Nucleic Acid Binding Protein Regulates The Alzheimer’S Disease Β-Secretase Protein Bace1, Christopher J. Holler

Theses and Dissertations--Molecular and Cellular Biochemistry

Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting the elderly population and is believed to be caused by the overproduction and accumulation of the toxic amyloid beta (Aβ) peptide in the brain. Aβ is produced by two separate enzymatic cleavage events of the larger membrane bound amyloid precursor protein, APP. The first, and rate-limiting, cleavage event is made by beta-secretase, or BACE1, and is thus an attractive therapeutic target. Our lab, as well as many others, has shown that BACE1 protein and activity are increased in late-stage sporadic AD. We have extended these findings to show that BACE1 …

Hiv Rna Suppression And Immune Restoration: Can We Do Better?, Marilia Rita Pinzone, Michelino Di Rosa, Bruno Cacopardo, Giuseppe Nunnari

Department of Microbiology and Immunology Faculty Papers

HAART has significantly changed the natural history of HIV infection: patients receiving antiretrovirals are usually able to control viremia, even though not all virological responders adequately recover their CD4+ count. The reasons for poor immune restoration are only partially known and they include genetic, demographic and immunologic factors. A crucial element affecting immune recovery is immune activation, related to residual viremia; indeed, a suboptimal virological control (i.e., low levels of plasma HIV RNA) has been related with higher levels of chronic inflammation and all-cause mortality. The sources of residual viremia are not yet completely known, even though the most important …

Evidence That The Density Of Self Peptide-Mhc Ligands Regulates T-Cell Receptor Signaling., Nadia Anikeeva, Dimitry Gakamsky, Jørgen Schøller, Yuri Sykulev

Department of Microbiology and Immunology Faculty Papers

Noncognate or self peptide-MHC (pMHC) ligands productively interact with T-cell receptor (TCR) and are always in a large access over the cognate pMHC on the surface of antigen presenting cells. We assembled soluble cognate and noncognate pMHC class I (pMHC-I) ligands at designated ratios on various scaffolds into oligomers that mimic pMHC clustering and examined how multivalency and density of the pMHCs in model clusters influences the binding to live CD8 T cells and the kinetics of TCR signaling. Our data demonstrate that the density of self pMHC-I proteins promotes their interaction with CD8 co-receptor, which plays a critical role …

The Career Support Network (Csn): Workforce Programming Through A New Lens, Rickie Brawer, Mph, Phd, James D. Plumb Md, Mph, Stephen Kern, Phd, Otr/L, Faota

Department of Family & Community Medicine Faculty Papers

Challenges:

Loss of Earn center as referral source

Multiple IRB submissions

Training/orientation at Philadelphia Prison System for working with pre-release prisoners

Service team organization/scheduling

Coordinating of cohorts at various stages of enrollment

Sepa-Reads: Cardiovascular Health Literacy Coalition, Rickie Brawer, Mph, Phd, James D. Plumb Md, Mph, Rob Simmons Drph,Mph,Ches, Martha Romney Rn,Ms,Jd,Mph, Patricia Yurchick, Rn, Mba, Cphq, Leslie Stearns

Department of Family & Community Medicine Faculty Papers

Poster includes:

Health literacy definition

Factors that contribute to health literacy

Extent of the literacy problem

What do we know from a decade of research?

Readmission rates

Evaluation: long and short term outcomes

And much more.

Passive Stretching And Its Effect On Spasticity And Range Of Motion In Children With Cerebral Palsy: A Systematic Review, Mallory Groppe, Katrin Baxter, Todd E. Davenport

School of Pharmacy Faculty Articles

Study Design: Only research studies published in peer-reviewed journals in the last two decades and published in the English language were included. Studies centered on surgical or pharmacological interventions were not included. To examine the strengths and weaknesses of these studies, the Physiotherapy Evidence Database (PEDro) scale and Sackett’s levels of evidence were used. Objectives: The aim of this paper is to analyze literature published in the past two decades, which explores the effects of stretching when used to reduce spasticity and increase range of motion in children with spastic cerebral palsy (CP), as well as to address the effects …