Therapeutics Commons^™

Sources Of Intravascular Atp During Exercise In Humans: Critical Role For Skeletal Muscle Perfusion, Brett S. Kirby, Anne R. Crecelius, Jennifer C. Richards, Frank A. Dinenno

Health and Sport Science Faculty Publications

Exercise hyperemia is regulated by several factors and one factor known to increase with exercise that evokes powerful vasomotor action is extracellular ATP. The origination of ATP detectable in plasma from exercising muscle of humans is, however, a matter of debate and ATP has been suggested to arise from sympathetic nerves, blood sources (e.g. erythrocytes), endothelial cells, and skeletal myocytes, among others. Therefore, we tested the hypothesis that acute augmentation of sympathetic nervous system activity (SNA) results in elevated plasma ATP draining skeletal muscle, and that SNA superimposition during exercise further increases ATP vs exercise alone. We show that increased …

Oxidative Stress Based Strategies For Enhancing The Efficacy Of Histone Deacetylase Inhibitors (Hdaci), Nilsa Rivera-Del Valle

Dissertations and Theses (Open Access)

Histone deacetylase inhibitors (HDACi) are anti-cancer drugs that primarily act upon acetylation of histones, however they also increase levels of intracellular reactive oxygen species (ROS). We hypothesized that agents that cause oxidative stress might enhance the efficacy of HDACi. To test this hypothesis, we treated acute lymphocytic leukemia cells (ALL) with HDACi and adaphostin (ROS generating agent). The combination of two different HDACi (vorinostat or entinostat) with adaphostin synergistically induced apoptosis in ALL. This synergistic effect was blocked when cells were pre-treated with the caspase-9 inhibitor, LEHD. In addition, we showed that loss of the mitochondrial membrane potential is the …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

A Home-Based Exercise Program For The Foot And Ankle To Improve Balance, Muscle Performance And Flexibility In Community Dwelling Older Adults: A Pilot Study, Laurel Long, Kurt Jackson, Lloyd L. Laubach

Physical Therapy Faculty Publications

Background and purpose: Strength and range of motion of the foot and ankle have been shown to be related to measures of balance and fall risk in older adults. The primary purpose of this pilot investigation was to evaluate the feasibility of a 6-week home-based exercise program focusing on the foot and ankle and any associated changes in balance, muscle performance and range of motion in older adults. Methods: This single-group repeated measures study involved a convenience sample of 21 healthy communitydwelling older adults age 60-90. Nineteen participants completed all phases of the testing and training. The intervention was a …

A Comparison Of Upper Extremity Function Between Female Breast Cancer Survivors And Healthy Controls: Typical Self-Report Of Function, Motion, Strength, And Muscular Endurance, Mary Insana Fisher

Physical Therapy Faculty Publications

Many women who have experienced breast cancer (BC) report continued impairments in upper extremity (UE) function beyond the time required for normal healing after surgical treatment. Most research supporting this has not made comparisons between survivors of breast cancer (BCS) to a sample of healthy women. This lack of comparison to a healthy cohort prevents an understanding of whether continued deficits in UE function are due to normal aging or the BC treatment.

The purpose of this research was to compare quality of life (QOL) and UE function among long term breast cancer survivors and similar aged women without cancer. …

Whole-Body Vibration Improves Functional Mobility, Flexibility, And Relative Risk For Falling In The Assisted Living Elderly: A Case Series, Christina Garrity, Harold L. Merriman, C. Jayne Brahler

Physical Therapy Faculty Publications

Study design: A randomized double blind repeated measures, case series study of whole body vibration (WBV) in the assisted living elderly.

Background: A single exposure to WBV has been shown to have benefit with respect to muscle activity, strength, balance, and power in some studies while other studies have found no benefit. Its overall effectiveness is unknown due to the conflicting findings reported in the literature.

Case description: Six subjects (5 female, 1 male; mean age = 85.4) in an assisted living community volunteered to participate. Subjects were exposed to a single bout of WBV at 0, 2, 20, and …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

What Is The Role Of Incretin Mimetics In The Treatment Of Type 2 Diabetes?, Isaac Silberstein

The Science Journal of the Lander College of Arts and Sciences

Type 2 diabetes mellitus (DM) is an intricate disorder defined by insulin resistance, impaired insulin secretion, hyperglycemia, and both microvascular and macrovascular complications. Standard antidiabetic agents like metformin, insulin, sulfonylureas and thiazolidinediones are often insufficient at glucoregulation and do not address the decline in beta cell function that characterizes type 2 diabetes. Moreover, the adverse effects of some of these pharmaceuticals, such as hypoglycemia and weight gain, are disappointing and further limit their clinical utility. Research demonstrates that the actions of two potent incretins. Glucagon-like peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), address these concerns as they stimulate beta …

Prospective, Open-Label Trial Measuring Satisfaction And Convenience Of Two Formulations Of Lamotrigine In Subjects With Mood Disorders, Martha Sajatovic

Faculty Scholarship

Background: Lamotrigine is an anticonvulsant drug indicated for the maintenance treatment of bipolar I disorder and for various types of epilepsy. An orally disintegrating tablet (ODT) of lamotrigine was developed to provide a formulation option that might increase patient convenience and satisfaction. Methods: Subjects with mood disorders who reported difficulty swallowing currently prescribed lamotrigine immediate-release medication (baseline) were enrolled and treated with lamotrigine ODT for three weeks (end of treatment). Subject satisfaction and convenience were measured using the Treatment Satisfaction Questionnaire for Medication (TSQM). Also measured were global psychopathology using the Clinical Global Impression severity index (CGI-S) and depressive symptoms …

Are Oncolytic Viruses A Cure For Cancer? A Look At Reovirus, Adenovirus, And Hsv-1 In Cancer Treatment, Yehuda Rosenberg

The Science Journal of the Lander College of Arts and Sciences

This paper aims to evaluate the option of utilizing Oncolytic Viruses as a viable treatment in fighting cancer. However, due to the broad nature of the subject, a more limited purview is necessary. With that in mind, the focus will be on a few of the more researched ones: Reovirus, Adenovirus, and HSV-1. In each case, we will examine what makes each of these potential options. This will include an examination of each one's tumor-specificity. Cancer and viral physiology will be discussed as necessary to examine the distinct protein expressions in tumor cells, so that the virus's method of battling …

Efficacy Of Probiotics Lactobacillus Rhamnosus Gg And Saccharomyces Boulardii In The Treatment Of Antibiotic-Associated Diarrhea And Clostridium Diffiicile-Associated Disease, Estie Klugmann

The Science Journal of the Lander College of Arts and Sciences

Antibiotic therapy may cause serious side effects. Two disturbing effects of antibiotic administration are antibiotic-associated diarrhea and Clostridium difficile-associated disorder. Antibiotic-associated diarrhea occurs as a direct result of the normal flora destruction due to the antibiotics - which do not discriminate against pathogens or healthy forms of bacteria. C. diff disorder also occurs as an indirect result of antibiotic administration, because the destruction of the normal flora prevents people from having healthy bacteria to prevent disease. There have been studies conducted to determine if replacing the destroyed normal flora with probiotics, or beneficial microorganisms will prevent or treat these conditions. …

Is Modafinil (Provigil®) Effective In Improving Cognitive Function In Adults With Narcolepsy?, Stephanie V. Bui

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not modafinil (Provigil®) is effective in improving cognitive function in adults with narcolepsy.

STUDY DESIGN: Review of all English language primary randomized controlled trials from 1996 to 2010.

DATA SOURCES: Double-blind, randomized controlled trials that compared modafinil (Provigil®) to a visually matched placebo were found using OVID, MEDLINE, and Cochrane Databases.

OUTCOME(S) MEASURED: Each of the three trials assessed the effect of modafinil on cognitive and executive function by Low-Resolution Brain Electromagnetic Tomography (LORETA), and the following assessment tools: Epworth Sleepiness Scale (ESS), Multiple Sleep …

Is Yoga An Effective Management Strategy For Disordered Eating?, Patricia G. Byrne

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether yoga is an effective management strategy for disordered eating.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials that evaluated yoga as a treatment intervention for disordered eating found using Medline@OVID and PubMed.

OUTCOME MEASURED: Outcomes were interpreted by eating disorder severity as measured on the Eating Disorder Examination, Eating Disorder Diagnostic Scale, and Binge Eating Scale. Secondarily, there was an assessment of associated attitudes and behaviors towards eating, including body satisfaction, physical activity level, …

What Is The Effectiveness Of Onabotulinumtoxina (Botox®) In Reducing The Number Of Chronic Migraines (Cm) In Patients 18-65 Years Old?, Kristin A. Beddingfield

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not onabotulinumtoxinA (Botox®) is effective in reducing the number of chronic migraines (CM) in patients 18-65 years old? Study Design: Review of three published, double blind randomized controlled trials were used for this review, which were found on PubMed; were selected based on their relevance to the clinical question and if they included patient oriented outcomes.

OUTCOMES MEASURED: The outcomes measured were headache/migraine free days measured by >50% responder rate analysis, the Treatment Responder Rate based on Physician Global Assessment, and total adverse events reported by …

Pilot Study Of A Kinect-Based Video Game To Improve Physical Therapy Treatment, Jacob Samuel Brown

Department of Computer Graphics Technology Degree Theses

Burnie is an exergame being developed at Purdue University and is used in this study. Burnie was developed using the Unity3D engine and OpenNI to interface with the Xbox Kinect. This study looked at how gesture intensity affected perceived enjoyment and perceived fatigue of the game. The results of the study could not reject the null hypothesis. Gesture intensity does not have a significant relationship to perceived enjoyment and perceived fatigue. This result means that future studies can alter the gesture intensity of the game Burnie without adversely affecting the player’s enjoyment and fatigue levels.

Raman Micro Spectroscopy Study Of The Interaction Of Vincristine With A549 Cells Supported By Expression Analysis Of Bcl-2 Protein, Haq Nawaz, Amaya Garcia, Aidan Meade, Fiona Lyng, Hugh Byrne

Articles

Understanding the interaction of anticancer drugs with model cell lines is important to elucidate the mode of action of these drugs as well as to develop cost effective and rapid screening methods. Raman spectroscopy has been demonstrated to be a valuable technique for high throughput, noninvasive analysis. The interaction of vincristine with a human lung adenocarcinoma cell line (A549)was investigated using Raman micro spectroscopy. The results were correlated with parallel measurements from the MTT cytotoxicity assay, which yielded an IC₅₀ value of 0.10 ± 0.03 μM. The Raman spectral data acquired from vincristine treated A549 cells was analysed to …

Impaired Skeletal Muscle Blood Flow Control With Advancing Age In Humans: Attenuated Atp Release And Local Vasodilation During Erythrocyte Deoxygenation, Brett S. Kirby, Anne R. Crecelius, Wyatt F. Voyles, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Skeletal muscle blood flow is coupled with the oxygenation state of hemoglobin in young adults, whereby the erythrocyte functions as an oxygen sensor and releases ATP during deoxygenation to evoke vasodilation. Whether this function is impaired in humans of advanced age is unknown.

Objective: To test the hypothesis that older adults demonstrate impaired muscle blood flow and lower intravascular ATP during conditions of erythrocyte deoxygenation.

Methods and Results: We showed impaired forearm blood flow responses during 2 conditions of erythrocyte deoxygenation (systemic hypoxia and graded handgrip exercise) with age, which was caused by reduced local vasodilation. In young adults, …

Pharmacokinetics And Brain Uptake In The Rhesus Monkey Of A Fusion Protein Of Arylsulfatase A And A Monoclonal Antibody Against The Human Insulin Receptor, Ruben J. Boado, Jeff Zhiqiang Lu, Eric Ka-Wai Hui, Rachita K. Sumbria, William M. Pardridge

Pharmacy Faculty Articles and Research

Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder of the brain caused by mutations in the gene encoding the lysosomal sulfatase, arylsulfatase A (ASA). It is not possible to treat the brain in MLD with recombinant ASA, because the enzyme does not cross the blood-brain barrier (BBB). In the present investigation, a BBB-penetrating IgG-ASA fusion protein is engineered and expressed, where the ASA monomer is fused to the carboxyl terminus of each heavy chain of an engineered monoclonal antibody (MAb) against the human insulin receptor (HIR). The HIRMAb crosses the BBB via receptor-mediated transport on the endogenous BBB insulin receptor, …

The Effect Of Pre-Operative Coumadin Therapy On Patients Who Develop Hemorrhagic Events Post Bariatric Surgery, Richard Boorse Md, Peter J. Bechtel Md, Cathleen Webber Rn, Mshs, Suzanne L. Smith Mba, Rrt, Tas, Cathy Fuhrman Rn, Msn

Department of Surgery

No abstract provided.

Evaluation Of A Surgical Intervention To Experimentally Compare Co2 Laser To Scalpel Incisions, Added Growth Factor, And Suture Material To Reduce Cutaneous Scarring, Rhian E. Davies

PCOM Biomedical Studies Student Scholarship

Introduction The goal of this study was to determine if the repair of full thickness skin incisions in an animal model could be improved by using a CO2 laser vs. scalpel, commercial vs. swine intestinal submucosa (SIS) sutures, and addition of exogenous nerve growth factor (NGF).

Materials and Methods A rat model was used to evaluate the following tissue components: prevalence of mast cell granules, thickness of epidermis, organization of collagen, infiltration of tissue into SIS, neutrophil presence around suture holes, and granulation tissue production around suture holes.

Results Added NGF led to a significant decrease in the number of …