Therapeutics Commons^™

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

The Importance Of Managing Psychosocial Health: A Case Study, Mary Insana Fisher, Harold L. Merriman

Physical Therapy Faculty Publications

Managing the physical aspects of lymphedema requires an individual to be committed to daily treatment of this chronic condition. Performing manual lymph drainage, using compression bandaging or compression garments, exercising, and caring for the skin all take time and a high level of dedication. This commitment to self-care can be emotionally and psychologically exhausting.

When coupled with other emotional stressors in a patient’s life, successful treatment of lymphedema is challenging. We present a case demonstrating how the physical and psychological aspects of care interplay, and, when well-managed, can positively affect the outcome.

Breast Cancer Edge Task Force Outcomes - Clinical Measures Of Strength And Muscular Endurance: A Systematic Review, Mary Insana Fisher, Claire Davies, Christine Beuthin, Genevieve Colon, Brittany Zoll, Lucinda Pfalzer

Physical Therapy Faculty Publications

Background: Muscular strength deficits are a common morbidity following treatment for breast cancer. Accurate assessment of strength and muscular endurance following breast cancer treatments is essential in identifying deficits and planning rehabilitation strategies.

Purpose: The purpose of this systematic review was to identify strength and muscular endurance outcome measures for use with women treated for breast cancer that possess strong psychometric properties and are clinically useful.

Methods: Multiple electronic databases were searched between February and June 2013. Included studies of tools used to assess strength and muscular endurance met the following criteria: reported psychometric properties, clinically feasible methods, adults (preferably …

Test Items In The Complete And Short Forms Of The Bot-2 That Contribute Substantially To Motor Performance Assessments In Typically Developing Children 6-10 Years Of Age, Kadi Carmosino, Ashley Grzeszczak, Kaylie Mcmurray, Ali Olivo, Bo Slutz, Brittany Zoll, Betsy Donahoe-Fillmore, C. Jayne Brahler

Physical Therapy Faculty Publications

Objectives: Determine the magnitude of association between individual subtest items of the Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), and the respective total subtest scores and to review items on the BOT-2 Short Form.

Background: The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2), is a test used to measure gross motor proficiency in both typically developing children and children with developmental disabilities between the ages of four and twenty-one. The BOT-2 Short Form consists of fourteen test items proportionally selected from the subtests of the Complete Form. It can be used as a screening tool and takes less …

In Vitro Propagation Of Gentiana Scabra Bunge – An Important Medicinal Plant In The Chinese System Of Medicines, Shih-Hung Huang, Dinesh Chandra Agrawal, Fang-Sheng Wu, Hsin-Sheng Tsay

Biology Publications

Background: Gentiana scabra Bunge commonly known as `Long dan cao' in China has been used in traditional Chinese medicines for more than 2000 years. Dry roots and rhizome of the herb have been used for the treatment of inflammation, anorexia, indigestion and gastric infections. Iridoids and secoiridoids are the main bioactive compounds which attribute to the pharmacological properties of this plant. The species is difficult to mass propagate by seed due to the low percentage of germination and limited dormancy period. Wild populations in some locations are considered to be in the endangered category due to over exploitation.

Results: In …

Oncology Section Task Force On Breast Cancer Outcomes: An Introduction To The Edge Task Force And Clinical Measures Of Upper Extremity Function, Pamela K. Levangie, Mary Insana Fisher

Physical Therapy Faculty Publications

With the proliferation of outcome measures in the literature, many of which lack documentation of sufficient psychometric properties to justify use, it is difficult to document patient change or demonstrate effectiveness of interventions. The goal of the Section on Research’s EDGE (Evaluation Database to Guide Effectiveness) Task Force is to facilitate identification of valid and reliable tests and measures that reflect clinically important outcomes and are responsive to change for standard use across selected patient groups. This paper lays the groundwork for understanding the work of the Oncology Section’s Breast Cancer EDGE Task Force on clinical measures of shoulder function …

Oncology Section Task Force On Breast Cancer Outcomes: Scapular Assessment, Mary Insana Fisher, Pamela K. Levangie

Physical Therapy Faculty Publications

Background: Functional deficits and changes in scapular mechanics following breast cancer (BC) treatments have been documented. Scapular assessment is important when examining the shoulder in survivors of breast cancer to document the need for or effectiveness of physical therapy intervention. The Oncology Section Task Force on Breast Cancer Outcomes sought to identify scapular examination tools that can be recommended for routine use in individuals treated for BC.

Methods: A systematic review of the literature on scapular measures was conducted. Relevant studies were examined for psychometric properties and clinical usefulness. Each method was given a recommendation score based on the Breast …

High Dose, Variable Length, N-Acetylcysteine (Hinac) Therapy For Late-Presenting Acetaminophen Poisoning, Jessica K. Eygnor Do, Suprina Dorai Md, Philip W. Moore Do, J Ward Donovan Md, Keith K. Burkhart Md

Department of Emergency Medicine

No abstract provided.

Chhs July E-Newsletter, Dr. John Bonaguro, Dean, Vashon S. Wells, Editor, Wku College Of Health & Human Services

College of Health & Human Services Publications

No abstract provided.

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 …

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 …

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, …

Muscle Contraction Duration And Fibre Recruitment Influence Blood Flow And Vo2 Independent Of Contractile Work During Steady-State Exercise In Humans, Jennifer C. Richards, Anne R. Crecelius, Brett S. Kirby, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

We tested the hypothesis that, among conditions of matched contractile work, shorter contraction durations and greater muscle fibre recruitment result in augmented skeletal muscle blood flow and oxygen consumption (O2) during steady-state exercise in humans. To do so, we measured forearm blood flow (FBF; Doppler ultrasound) during 4 minutes of rhythmic handgrip exercise in 24 healthy young adults and calculated forearm O2 via blood samples obtained from a catheter placed in retrograde fashion into a deep vein draining the forearm muscle. In Protocol 1 (n = 11), subjects performed rhythmic isometric handgrip exercise at mild and moderate intensities under conditions …

Novel Use Of Dual Anti-Inflammatory Therapy To Overcome Drug Resistance And Improve Functional Recovery Following Spinal Cord Injury, Jennifer Dulin

Dissertations and Theses (Open Access)

Over 1.2 million Americans are currently living with a traumatic spinal cord injury (SCI). Despite the need for effective therapies, there are currently no proven effective treatments that can improve recovery of function in SCI patients. Many therapeutic compounds have shown promise in preclinical models of SCI, but all of these have fallen short in clinical trials.

P-glycoprotein (Pgp) is an active transporter expressed on capillary endothelial cell membranes at the blood-spinal cord barrier (BSCB). Pgp limits passive diffusion of blood-borne drugs into the CNS, by actively extruding drugs from the endothelial cell membrane. Pgp can become pathologically up-regulated, thus …

Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein

Pharmacy Faculty Articles and Research

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …

Neuroprotective Effects Of Bilobalide Are Accompanied By A Reduction Of Ischemia-Induced Glutamate Release In Vivo, Dorothee Lang, Cornelia Kiewert, Alexander Mdzinarishvili, Tina Maria Schwarzkopf, Rachita K. Sumbria, Joachim Hartmann, Jochen Klein

Pharmacy Faculty Articles and Research

Neuroprotective properties of bilobalide, a specific constituent of Ginkgo extracts, were tested in a mouse model of stroke. After 24 h of middle cerebral artery occlusion (MCAO), bilobalide reduced infarct areas in the core region (striatum) by 40–50% when given at 10 mg/kg 1 h prior to MCAO. Neuroprotection was also observed at lower doses, or when the drug was given 1 h past stroke induction. Sensorimotor function in mice was improved by bilobalide as shown by corner and chimney tests. When brain metabolism in situ was monitored by microdialysis, MCAO caused a rapid disappearance of extracellular glucose in the …

Systematically Controlling For The Influence Of Age, Sex, Hertz And Time Post-Whole-Body Vibration Exposure On Four Measures Of Physical Performance In Community-Dwelling Older Adults: A Randomized Cross-Over Study, Harold L. Merriman, C. Jayne Brahler, Kurt Jackson

Physical Therapy Faculty Publications

Though popular, there is little agreement on what whole-body vibration (WBV) parameters will optimize performance. This study aimed to clarify the effects of age, sex, hertz, and time on four physical function indicators in community-dwelling older adults (N = 32). Participants were exposed to 2 minutes WBV per session at either 2 Hz or 26 Hz, and outcome measures were recorded at 2-, 20-, and 40-minute post-WBV. Timed get-up-and-go and chair sit-and-reach performances improved post-WBV for both sexes, were significantly different between 2 Hz and 26 Hz treatments (P ≤ 0.05), and showed statistically significant interactions between age and gender …

Unifying The Mathematical Modeling Of In Vivo And In Vitro Microdialysis, Peter M. Bungay, Rachita K. Sumbria, Ulrich Bickel

Pharmacy Faculty Articles and Research

A unifying approach is presented for developing mathematical models of microdialysis that are applicable to both in vitro and in vivo situations. Previous models for cylindrical probes have been limited by accommodating analyte diffusion through the surrounding medium in the radial direction only, i.e., perpendicular to the probe axis, or by incomplete incorporation of diffusion in the axial direction. Both radial and axial diffusion are included in the present work by employing two-dimensional finite element analysis. As in previous models, the nondimensional clearance modulus (Θ) represents the degree to which analyte clearance from the external medium influences diffusion through the …

Knee Range Of Motion: Reliability And Agreement Of 3 Measurement Methods, Paul G. Peters, Michael A. Herbenick, Philip A. Anloague, Ronald J. Markert, L. Joseph Rubino

Physical Therapy Faculty Publications

We conducted a study to compare 3 methods of measuring knee range of motion: visual estimation by physicians, hand goniometry by physical therapists, and radiographic goniometry. We hypothesized that reliability would be high within and across all techniques. We found intrarater and interrater reliability to be satisfactory for visual estimation, hand goniometry, and radiographic goniometry. Interrater reliability across methods did not agree satisfactorily. Between-methods differences in estimating knee range of motion may result from variations in technique among physicians and physical therapists.

A Comparison Of Two Pelvic Floor Muscle Training Programs In Females With Stress Urinary Incontinence: A Pilot Study, Betsy Donahoe-Fillmore, Wendy Chorny, C. Jayne Brahler, Ashley Ingley, Jennifer Kennedy, Valerie Osterfeld

Physical Therapy Faculty Publications

Background: Stress urinary incontinence (SUI) is a condition affecting millions of Americans. Few studies have assessed the benefits of different exercises involved in pelvic floor muscle training (PFMT). Purposte: The purpose of this study was to compare the effects of a traditional PFMT program to an assisted pelvic floor muscle training (APFMT) program that included contraction of hip musculature.

Investigating The Associations Between Core Strength, Postural Control And Fine Motor Performance In Children, Rachel Burnett, Nicole Cornett, Gina Rekart, Betsy Donahoe-Fillmore, C. Jayne Brahler, Susan Aebker, Megan Kreill

Physical Therapy Faculty Publications

Study design: Quantitative design including statistical analysis.

Objectives: The objective of this study was to determine if there is an association between core strength, postural control, fine motor precision and integration, specifically in typical children in the first and third grades, ages 6-10. The secondary purpose of this study was to determine if there was an association between BMI and fine and gross motor ability in this same population.

Background: The relationship between core strength, postural control and fine motor skills in children is not well understood. The assumption that trunk stability and control are necessary for the maturation of …

Ruthenium Complexes As Dna Photonucleases In Treatment Of Malignant Skin Carcinoma, Devi Kalyan Karumanchi

All Capstone Projects

A variety of Ruthenium complexes possessing terpyridine complexes as ligands in their coordination sphere have been investigated extensively as DNA photo nucleases in vitro. This work has led to the realization that compounds of Ruthenium bind to DNA purines and that the interactions are of an unprecedented bridging variety. Owing to the molar absorptivity of these complexes in the visible region, direct cleavage of duplex DNA by these complexes requires irradiation in the range of 400-500 nm.

Although the observation of DNA photo cleavage in vitro makes these systems good candidates for further investigation, it does not provide any information …

Mechanism-Based Strategies To Enhance The Actions Of A, Fabiola C. Gomez

Dissertations and Theses (Open Access)

Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due …