Medicine and Health Sciences Commons^™

Promoting Differentiation And Survival Of Human C-Kit+ Cardiac Progenitor Cells Ex Vivo., Tareq Al-Maqtari

Electronic Theses and Dissertations

c-kit+ cardiac progenitor cells (CPCs) have recently gained much attention due to the therapeutic effects they exert on cardiac function following their administration into the infarcted heart as evidenced by animal studies and by a recent clinical trial (SCIPIO). However, injecting these cells in the heart is associated with poor differentiation into specialized cardiac cell types and with rapid death of the engrafted cells. With the ultimate goal of advancing cardiac stem cell therapy, we sought to facilitate the differentiation of human CPCs into cardiac cell types (e.g. cardiomyocytes, smooth muscle cells, endothelial cells and cardiac fibroblasts) by overexpressing selected …

Amphiphilic Tobramycin Analogues As Antibacterial And Antifungal Agents, Sanjib K. Shrestha, Marina Y. Fosso, Keith D. Green, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

In this study, we investigated the in vitro antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6″-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C₁₂ and C₁₄ chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg/liter …

Health Literacy Impact On National Healthcare Utilization And Expenditure, Rafia S. Rasu, Walter Agbor Bawa, Richard Suminski, Kathleen Snella, Bradley Warady

Pharmacy Faculty Publications and Presentations

Background: Health literacy presents an enormous challenge in the delivery of effective healthcare and quality outcomes. We evaluated the impact of low health literacy (LHL) on healthcare utilization and healthcare expenditure. Methods: Database analysis used Medical Expenditure Panel Survey (MEPS) from 2005-2008 which provides nationally representative estimates of healthcare utilization and expenditure. Health literacy scores (HLSs) were calculated based on a validated, predictive model and were scored according to the National Assessment of Adult Literacy (NAAL). HLS ranged from 0-500. Health literacy level (HLL) and categorized in 2 groups: Below basic or basic (HLS <226) and above basic (HLS ≥226). Healthcare utilization expressed as a physician, nonphysician, or emergency room (ER) visits and healthcare spending. Expenditures were adjusted to 2010 rates using the Consumer Price Index (CPI). A P value of 0.05 or less was the criterion for statistical significance in all analyses. Multivariate regression models assessed the impact of the predicted HLLs on outpatient healthcare utilization and expenditures. All analyses were performed with SAS and STATA® 11.0 statistical software. Results: The study evaluated 22 599 samples representing 503 374 648 weighted individuals nationally from 2005- 2008. The cohort had an average age of 49 years and included more females (57%). Caucasian were the predominant racial ethnic group (83%) and 37% of the cohort were from the South region of the United States of America. The proportion of the cohort with basic or below basic health literacy was 22.4%. Annual predicted values of physician visits, nonphysician visits, and ER visits were 6.6, 4.8, and 0.2, respectively, for basic or below basic compared to 4.4, 2.6, and 0.1 for above basic. Predicted values of office and ER visits expenditures were $1284 and $151, respectively, for basic or below basic and $719 and $100 for above basic (P<.05). The extrapolated national estimates show that the annual costs for prescription alone for adults with LHL possibly associated with basic and below basic health literacy could potentially reach about $172 billion. Conclusion: Health literacy is inversely associated with healthcare utilization and expenditure. Individuals with below basic or basic HLL have greater healthcare utilization and expenditures spending more on prescriptions compared to individuals with above basic HLL. Public health strategies promoting appropriate education among individuals with LHL may help to improve health outcomes and reduce unnecessary healthcare visits and costs.

Mechanisms Of Activation Of Nucleus Accumbens Neurons By Cocaine Via Sigma-1 Receptor-Inositol 1,4,5-Trisphosphate-Transient Receptor Potential Canonical Channel Pathways., Jeffrey L. Barr, Elena Deliu, Gabriela Cristina Brailoiu, Pingwei Zhao, Guang Yan, Mary E. Abood, Ellen M. Unterwald, Eugen Brailoiu

College of Pharmacy Faculty Papers

Cocaine promotes addictive behavior primarily by blocking the dopamine transporter, thus increasing dopamine transmission in the nucleus accumbens (nAcc); however, additional mechanisms are continually emerging. Sigma-1 receptors (σ1Rs) are known targets for cocaine, yet the mechanisms underlying σ1R-mediated effects of cocaine are incompletely understood. The present study examined direct effects of cocaine on dissociated nAcc neurons expressing phosphatidylinositol-linked D1 receptors. Endoplasmic reticulum-located σ1Rs and inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) were targeted using intracellular microinjection. IP3 microinjection robustly elevated intracellular Ca(2+) concentration, [Ca(2+)]i. While cocaine alone was devoid of an effect, the IP3-induced response was σ1R-dependently enhanced by cocaine co-injection. Likewise, …

Computational Modeling Of Rna-Small Molecule And Rna-Protein Interactions, Lu Chen

Dissertations and Theses (Open Access)

The past decade has witnessed an era of RNA biology; despite the considerable discoveries nowadays, challenges still remain when one aims to screen RNA-interacting small molecule or RNA-interacting protein. These challenges imply an immediate need for cost-efficient while predictive computational tools capable of generating insightful hypotheses to discover novel RNA-interacting small molecule or RNA-interacting protein. Thus, we implemented novel computational models in this dissertation to predict RNA-ligand interactions (Chapter 1) and RNA-protein interactions (Chapter 2).

Targeting RNA has not garnered comparable interest as protein, and is restricted by lack of computational tools for structure-based drug design. To test the potential …

Overcoming Acquired Resistance To Braf Inhibitors By Novel Synergistic Drug Combination And Discovery Of Novel Smac Mimetics As Selective Survivin Inhibitors, Jin Wang

Theses and Dissertations (ETD)

The first part (Chapter 1 and 2) of this dissertation presents a novel combination study of melanoma therapy. Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short term chemotherapy. Since the inhibitions of targets in the RAFMEK-ERK pathway result in G0/G1 cell cycle arrest, vemurafenib-resistant cancer cells are expected to escape this cell cycle arrest and progress to subsequent G2/M phase. We hypothesized that a combined therapy using vemurafenib with a G2/M phase blocking agent will trap resistant cells and overcome vemurafenib resistance. To test this hypothesis, we first determined the combination index (CI) values of …

Chemically Related 4,5-Linked Aminoglycoside Antibiotics Drive Subunit Rotation In Opposite Directions, Michael R. Wasserman, Arto Pulk, Zhou Zhou, Roger B. Altman, John C. Zinder, Keith D. Green, Sylvie Garneau-Tsodikova, Jamie H. Doudna Cate, Scott C. Blanchard

Pharmaceutical Sciences Faculty Publications

Dynamic remodelling of intersubunit bridge B2, a conserved RNA domain of the bacterial ribosome connecting helices 44 (h44) and 69 (H69) of the small and large subunit, respectively, impacts translation by controlling intersubunit rotation. Here we show that aminoglycosides chemically related to neomycin-paromomycin, ribostamycin and neamine-each bind to sites within h44 and H69 to perturb bridge B2 and affect subunit rotation. Neomycin and paromomycin, which only differ by their ring-I 6'-polar group, drive subunit rotation in opposite directions. This suggests that their distinct actions hinge on the 6'-substituent and the drug's net positive charge. By solving the crystal structure of …

Hybrid Nanocrystals For Treatment And Bioimaging Of Disease, Tonglei Li

Pharmaceutical Sciences Faculty Patents

Hybrid nanocrystals able to reach specific targets in the body for treatment and biological imaging are provided, as well as methods of making and administering same for treatment of disease conditions and for bioimaging and radiotherapy. The hybrid nanocrystals and methods can be used alone or in combination with other treatment and imaging modalities.

Patent No. Us 9,090,589 B2: Specific Nnos Inhibitors For The Therapy And Prevention Of Human Melanoma, Richard B. Silverman, Frank L. Meyskens Jr., Sun Yang, Haitao Ji, Fengtian Xue, Thomas L. Poulos

Pharmacy Faculty Articles and Research

Methods for melanoma treatment and prevention with selective nitric oxide synthase inhibitor compounds and related pharmaceutical compositions, alone or in conjunction with one or more other melanoma therapies.

Samhd1 Is A Single-Stranded Nucleic Acid Binding Protein With No Active Site-Associated Nuclease Activity., Kyle J. Seamon, Zhiqiang Sun, Luda S. Shlyakhtenko, Yuri L. Lyubchenko, James T. Stivers

Journal Articles: Pharmaceutical Sciences

The HIV-1 restriction factor SAMHD1 is a tetrameric enzyme activated by guanine nucleotides with dNTP triphosphate hydrolase activity (dNTPase). In addition to this established activity, there have been a series of conflicting reports as to whether the enzyme also possesses single-stranded DNA and/or RNA 3'-5' exonuclease activity. SAMHD1 was purified using three chromatography steps, over which the DNase activity was largely separated from the dNTPase activity, but the RNase activity persisted. Surprisingly, we found that catalytic and nucleotide activator site mutants of SAMHD1 with no dNTPase activity retained the exonuclease activities. Thus, the exonuclease activity cannot be associated with any …

Crystal Structure Of O-Methyltransferase Calo6 From The Calicheamicin Biosynthetic Pathway: A Case Of Challenging Structure Determination At Low Resolution, Oleg V. Tsodikov, Caixia Hou, Christopher T. Walsh, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Calicheamicins (CAL) are enedyine natural products with potent antibiotic and cytotoxic activity, used in anticancer therapy. The O-methyltransferase CalO6 is proposed to catalyze methylation of the hydroxyl moiety at the C2 position of the orsellinic acid group of CAL.

RESULTS: Crystals of CalO6 diffracted non-isotropically, with the usable data extending to 3.4 Å. While no single method of crystal structure determination yielded a structure of CalO6, we were able to determine its structure by using molecular replacement-guided single wavelength anomalous dispersion by using diffraction data from native crystals of CalO6 and a highly non-isomorphous mercury derivative. The structure …

Modeling Of Mpges-1 Three-Dimensional Structures: Applications In Drug Design And Discovery, Chang-Guo Zhan, Xiaoqin Huang, Adel Hamza

Pharmaceutical Sciences Faculty Patents

This invention relates to representations of prostaglandin synthase three-dimensional structures. Such representations are suitable for designing agents that modulate the activity of the enzyme by binding to the substrate binding domain.

A Modified Potency Test Strategy For Iv Admixtures Prepared By Robotic Systems, Fang Zhao, Vivek S. Dave, Susan E. Hughes

Pharmacy Faculty/Staff Publications

Introduction:

Robotic systems are increasingly used for compounding sterile IV admixtures (1-5). In addition to routine gravimetric checks, initial and periodic drug potency analysis by high-performance liquid chromatography (HPLC) is desired to verify the system accuracy. However, the conventional HPLC test procedures often result in unexpected failures (1-2).

This study was initiated to develop a modified HPLC test strategy to eliminate the common source of variability and focus the effort on the accuracy of robotic system.

Formulation And In Vivo Evaluation Of Aliskiren-Loaded Poly(Lactic-Co-Glycolic) Acid Nanoparticles, Derek E. Murrell, Jessica M. Coleman, Stacy D. Brown, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Aliskiren (ALS) is a direct renin inhibitor with low bioavailability and high drug cost. The goal of this study was to increase the bioavailability of ALS through nanoformulation. The optimized formulation was then evaluated in spontaneously hypertensive rats (SHRs). We developed an ALS poly(lactic-co-glycolic) acid nanoparticle (ALS-NP) through the emulsion–diffusion–evaporation method with various solvents, stabilizer concentrations, and centrifugation speeds. SHRs were orally dosed with 30 mg/kg ALS or dose equivalent ALS-NP. Several parameters were assayed in plasma and/or urine at baseline and 24 h post-dose, while pharmacokinetic analysis included serial sampling. The optimum formulation was found with ethyl acetate, a …

Low And Moderate Prenatal Ethanol Exposure Of Mice During Gastrulation Or Neurulation Delays Neurobehavioral Development, Uta B. Schambra, Jeff Goldsmith, Kevin Nunley, Yali Liu, Sam Harirforoosh, Heidi M. Schambra

Pharmacy Faculty Articles and Research

Human and animal studies show significant delays in neurobehavioral development in offspring after prolonged prenatal exposure to moderate and high ethanol doses resulting in high blood alcohol concentration (BECs). However, none have investigated the effects of lower ethanol doses given acutely during specific developmental time periods. Here, we sought to create a mouse model for modest and circumscribed human drinking during the 3rd and 4th weeks of pregnancy.

We acutely treated mice during embryo gastrulation on gestational day (GD) 7 or neurulation on GD8 with a low or moderate ethanol dose given via gavage that resulted in BECs of 107 …

Molecular Overlap In The Regulation Of Sk Channels By Small Molecules And Phosphoinositides, Miao Zhang, Xuan-Yu Meng, Ji-Fang Zhang, Meng Cui, Diomedes E. Logothetis

Pharmacy Faculty Articles and Research

Phosphatidylinositol 4,5-bisphosphate (PIP2) directly interacts with the small-conductance Ca2+-activated K+ 2-a (SK2-a) channel/calmodulin complex, serving as a critical element in the regulation of channel activity. We report that changes of protein conformation in close proximity to the PIP2 binding site induced by a small-molecule SK channel modulator, NS309, can effectively enhance the interaction between the protein and PIP2 to potentiate channel activity. This novel modulation of PIP2 sensitivity by small-molecule drugs is likely not to be limited in its application to SK channels, representing an intriguing strategy to develop drugs controlling the activity of the large number of PIP2-dependent proteins.

Editorial: Phosphoinositides And Their Phosphatases: Linking Electrical And Chemical Signals In Biological Processes, Susy C. Kohout, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

No abstract provided.

The College Of Pharmacy, South Dakota State University

Jackrabbits Script and Scope (Formerly called College of Pharmacy and Allied Health Professions Magazine)

[Page] 2 Master of Public Health College of Pharmacy joins forces with other colleges and USD to offer Master of Public Health degree.
[Page] 4 Father of Tamoxifen V. Craig Jordan visits State as Francis Miller Distinguished Lecturer.
[Page] 6 Hometown satisfaction Dedication to hometown and residents earns Travis Anderberg ’04 the 2015 South Dakota Retailer of the Year.
[Page] 10 Excellence Tadd Hellwig named college’s outstanding scholar while Debra Farver chosen college’s teacher of the year.
[Page] 12 Building better mouse models Markl Faculty Scholar Wenfeng An’s research using mouse models lands two National Institutes of Health grants.
[Page] …

Research News. Grants, 2015. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Grants (2015-)

No abstract provided.

Research News. Publications, 2015. Volume 1, University Of Mississippi. School Of Pharmacy, Soumyajit Majumdar

Publications (2015-)

Publications that appeared during the period January 1 through June 30, 2015

The Role Of Community Pharmacy-Based Vaccination In The Usa: Current Practice And Future Directions, Albert Bach, Jeffery A. Goad

Pharmacy Faculty Articles and Research

Community pharmacy-based provision of immunizations in the USA has become commonplace in the last few decades, with success in increasing rates of immunizations. Community pharmacy-based vaccination services are provided by pharmacists educated in the practice of immunization delivery and provide a convenient and accessible option for receiving immunizations. The pharmacist's role in immunization practice has been described as serving in the roles of educator, facilitator, and immunizer. With a majority of pharmacist-provided vaccinations occurring in the community pharmacy setting, there are many examples of community pharmacists serving in these immunization roles with successful outcomes. Different community pharmacies employ a number …

Nanoformulation For Anticancer Drug Delivery: Enhanced Pharmacokinetics And Circulation, Gaurav Parekh

Doctoral Dissertations

In this study, we have explored the application of the Layer-by-Layer (LbL) assembly technique for improving injectable drug delivery systems of low soluble anticancer drugs (e.g. Camptothecin (CPT), Paclitaxel (PTX) or Doxorubicin (DOX)). For this study, a polyelectrolyte shell encapsulates different types of drug nanocores (e.g. soft core, nanomicelle or solid lipid nanocores).The low soluble drugs tend to crystallize and precipitate in an aqueous medium. This is the reason they cannot be injected and may have low concentrations and low circulation time in the blood. Even though these drugs when present in the cancer microenvironment have high anti-tumor inhibition, the …

Intractable Delay And The Need To Amend The Petition Provisions Of The Fdca, Diana R. H. Winters

Indiana Law Journal

Private party oversight has proven to be ineffective at countering inaction by the Food and Drug Administration (FDA). Inaction when regulation is warranted can put the public at continued and increasing risk of harm, but the failure of private enforcement to compel action reverberates beyond this harm to the interests of individuals. It also diminishes the transparency of agency decision making, lessens the opportunity for public participation, and reduces the interaction between the institutions that oversee agencies. Moreover, the benefits afforded to the administrative process by judicial review are weakened.

This Article analyzes two examples of FDA inertia and compares …

New Approach To Develop Ultra-High Inhibitory Drug Using The Power Function Of The Stoichiometry Of The Targeted Nanomachine Or Biocomplex, Dan Shu, Fengmei Pi, Chi Wang, Peng Zhang, Peixuan Guo

Pharmaceutical Sciences Faculty Publications

AIMS: To find methods for potent drug development by targeting to biocomplex with high copy number.

METHODS: Phi29 DNA packaging motor components with different stoichiometries were used as model to assay virion assembly with Yang Hui's Triangle [Formula: see text], where Z = stoichiometry, M = drugged subunits per biocomplex, p and q are the fraction of drugged and undrugged subunits in the population.

RESULTS: Inhibition efficiency follows a power function. When number of drugged subunits to block the function of the complex K = 1, the uninhibited biocomplex equals q(z), demonstrating the multiplicative effect of stoichiometry on inhibition with …

Influence Of Linker Length And Composition On Enzymatic Activity And Ribosomal Binding Of Neomycin Dimers, Derrick Watkins, Sunil Kumar, Keith D. Green, Dev P. Arya, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by …

Inhibition Of Aminoglycoside Acetyltransferase Resistance Enzymes By Metal Salts, Yijia Li, Keith D. Green, Brooke R. Johnson, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn²⁺ metal ions displayed an inhibitory effect on the resistance enzyme AAC(6')-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we explore a wide array of metal salts (Mg²⁺, …

Research Proposal: Emrs Changing Patient Medication Errors, Kerry Moore

Applied Research Projects

In 2009 the federal government initiated the American Recovery and Reinvestment Act (ARRA) in efforts to improve timely and quality health care. This new initiative promised to provide great incentives to health care providers who took advantage of the program by implementing electronic medical records (EMRs) within their facilities, clinics, and practices. Coupled with tight deadlines and the incentive of reimbursement, the health care world has been witness to an influx of EMRs being developed by vendors and implemented at health care facilities. The rate at which these EMRs have been implemented has been astounding. So fast, the health care …

Effective Use Of Team Based Learning In A Flipped Classroom, Nabila Ahmed-Sarwar

Pharmacy Faculty/Staff Publications

This roundtable presentation highlighted the components of team based learning activities in a flipped classroom. The instructional techniques to maximize knowledge application and critical thinking are described. Additional student performance and level of satisfaction with this course design in comparison to lecture based course design in previous years is evaluated.

Behavioral And Pharmacological Investigation Of Anxiety And Maternal Responsiveness Of Postpartum Female Rats In A Pup Elevated Plus Maze, Yu Yang, Jingxue Qin, Weihai Chen, Hong Chen, Ming Li

Department of Psychology: Faculty Publications

The present study investigated the validity of a novel pup-based repeated elevated plus maze task to detect reduced anxiety and increased maternal responsiveness in postpartum female rats and explored the roles of dopamine D2, serotonin transporter and GABA/benzodiazepine receptors in the mediation of these processes. Sprague–Dawley postpartum or nulliparous female rats were tested 4 times every other day on postpartum days 4, 6 and 8 in an elevated plus maze with 4 pups or 4 pup-size erasers placed on each end of the two open arms. When tested with erasers, untreated postpartum mother rats entered the open arms proportionally more …

Examining Pharmacy Students’ Perceptions Of Clinical Faculty Mentoring Characteristics Influencing Students’ Decision To Pursue A Pharmacy Residency, Kin S. Ly

All Theses And Dissertations

The field of pharmacy is changing from a drug-distribution-centered model to a patient-centered integrated model whereby pharmacists are actively involved in patient care as part of an interdisciplinary team. To address the estimated pharmacy leadership crisis in the future and to prepare pharmacists to work in the changing healthcare landscape, national pharmacy organizations such as the American Society of Health-System Pharmacists (ASHP) and the American College of Clinical Pharmacy (ACCP) have stated that postgraduate pharmacy residency should be mandatory by 2020. Past pharmacy research literature has shown that while many factors influence students to pursue a pharmacy residency, there is …