Medicine and Health Sciences Commons^™

Pharmaceutics Ii Bps 315, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Halogenated Diarylacetylenes And Methods Of Treating Cancer, Vitaliy M. Sviripa, Wen Zhang, Chunming Liu, David S. Watt

Pharmaceutical Sciences Faculty Patents

Halogenated diarylacetylenes, e.g., diarylacetylenes having at least one halo substituent in one aryl ring and an amine in the opposing aryl ring, can inhibit the proliferation of LSI 74T colon cancer cells through the inhibition of c-myc and induction of the cyclin-dependent kinase inhibitor-I (i.e., p21(Wifl/Cipl)). Such compounds are useful as antineoplastic agents.

Phaeophleospora Vochysiae Savi & Glienke Sp. Nov. Isolated From Vochysia Divergens Found In The Pantanal, Brazil, Produces Bioactive Secondary Metabolites, Daiani C. Savi, Khaled A. Shaaban, Francielly M. W. Gos, Larissa V. Ponomareva, Jon S. Thorson, Chirlei Glienke, Jürgen Rohr

Pharmaceutical Sciences Faculty Publications

Microorganisms associated with plants are highly diverse and can produce a large number of secondary metabolites, with antimicrobial, anti-parasitic and cytotoxic activities. We are particularly interested in exploring endophytes from medicinal plants found in the Pantanal, a unique and widely unexplored wetland in Brazil. In a bio-prospecting study, strains LGMF1213 and LGMF1215 were isolated as endophytes from Vochysia divergens, and by morphological and molecular phylogenetic analyses were characterized as Phaeophleospora vochysiae sp. nov. The chemical assessment of this species reveals three major compounds with high biological activity, cercoscosporin (1), isocercosporin (2) and the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone (3). …

Microscopic Allies: Examining And Tackling Legal And Regulatory Barriers To The Development Of Phage Therapy, Jacob Zent

William & Mary Environmental Law and Policy Review

No abstract provided.

Outcomes Of A Pharmacist-Managed Clinic For Underserved Persons With Unmanaged Type 2 Diabetes Mellitus, Ashley L. Lefebvre, Andrew R. Zullo, Ruth Dapaah-Afriyie, Christina M. Collins, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background

A multidisciplinary approach is recommended for the management of type 2 diabetes mellitus (DM).

Aim

To evaluate the impact of a pharmacist intervention on haemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), and diabetes-related hospitalisations in an underserved cohort with unmanaged type 2 DM.

Methods

This analysis was a retrospective cohort study. Criteria for inclusion were persons with unmanaged type 2 DM defined as HbA1c values ≥8% at time of enrolment, ≥18 years old, and enrolment in a pharmacist-managed clinic for ≥12 months. Pre- and post-intervention differences in HbA1c, SBP and DBP values were assessed using …

February 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

A Novel Mir-375-Hoxb3-Cdca3/Dnmt3b Regulatory Circuitry Contributes To Leukemogenesis In Acute Myeloid Leukemia, Laixi Bi, Bin Zhou, Haiying Li, Licai He, Chunjing Wang, Zhonggai Wang, Liqing Zhu, Mengqian Chen, Shenmeng Gao

Faculty Publications

Background: Acute myeloid leukemia (AML) is a heterogeneous group of hematopoietic malignancies due to sophisticated genetic mutations and epigenetic dysregulation. MicroRNAs (miRNAs), a class of small non-coding RNAs, are important regulators of gene expression in all biological processes, including leukemogenesis. Recently, miR-375 has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-leukemia activity in AML is largely unknown. Methods: Quantitative reverse transcriptase PCR (qRT-PCR) was used to measure the expression of miR-375 and HOXB3 in leukemic cells and normal controls. Targets of miR-375 were confirmed by western blot and luciferase assay. Phenotypic effects …

Relationship Between The Dimerization Of Thyroglobulin And Its Ability To Form Triiodothyronine, Cintia E. Citterio, Yoshiaki Morishita, Nada Dakka, Balaji Veluswamy, Peter Arvan

Pharmacy Faculty Articles and Research

Thyroglobulin (TG) is the most abundant thyroid gland protein, a dimeric iodoglycoprotein (660 kDa). TG serves as the protein precursor in the synthesis of thyroid hormones tetraiodothyronine (T₄) and triiodothyronine (T₃). The primary site for T₃ synthesis in TG involves an iodotyrosine acceptor at the antepenultimate Tyr residue (at the extreme carboxyl terminus of the protein). The carboxyl-terminal region of TG comprises a cholinesterase-like (ChEL) domain followed by a short unique tail sequence. Despite many studies, the monoiodotyrosine donor residue needed for the coupling reaction to create T₃ at this evolutionarily conserved …

The Winding Road To Relapse: Forging A New Understanding Of Cue-Induced Reinstatement Models And Their Associated Neural Mechanisms, Mark D. Namba, Seven E. Tomek, M. Foster Olive, Joshua S. Beckmann, Cassandra D. Gipson

Psychology Faculty Publications

In drug addiction, cues previously associated with drug use can produce craving and frequently trigger the resumption of drug taking in individuals vulnerable to relapse. Environmental stimuli associated with drugs or natural reinforcers can become reliably conditioned to increase behavior that was previously reinforced. In preclinical models of addiction, these cues enhance both drug self-administration and reinstatement of drug seeking. In this review, we will dissociate the roles of conditioned stimuli as reinforcers from their modulatory or discriminative functions in producing drug-seeking behavior. As well, we will examine possible differences in neurobiological encoding underlying these functional differences. Specifically, we will …

Semi-Synthesis Of A Novel Library Of Alkaloids As Potential Selective Analgesics, Brittany M. Gallagher

Theses and Dissertations

Semi-synthetic compounds are an important part of the therapeutic drug discovery process. The goals of the project were to synthesize different generations of matrine analogues in order to gain many opportunities to manipulate the core structure. The long-term goal was, by manipulating the structure, the possibility to increase the biological activity of the original compound while also decreasing the toxicity. The first-generation matrine analogue allows for a synthesis similar to the Striker reaction producing aminonitriles. An alkyne coupling reaction was also possible with the modification, producing propargyl-amines. Both of the reactions resulted in the addition of a triple bond substituent …

Prevalence Of Infection-Competent Serogroup 6 Legionella Pneumophila Within Premise Plumbing In Southeast Michigan, Brenda G. Byrne, Sarah Mccolm, Shawn P. Mcelmurry, Paul E. Kilgore, Joanne Sobeck, Rick Sadler, Nancy G. Love, Michele S. Swanson

Department of Pharmacy Practice

Coinciding with major changes to its municipal water system, Flint, MI, endured Legionnaires’ disease outbreaks in 2014 and 2015. By sampling premise plumbing in Flint in the fall of 2016, we found that 12% of homes harbored legionellae, a frequency similar to that in residences in neighboring areas. To evaluate the genetic diversity of Legionella pneumophila in Southeast Michigan, we determined the sequence type (ST) and serogroup (SG) of the 18 residential isolates from Flint and Detroit, MI, and the 33 clinical isolates submitted by hospitals in three area counties in 2013 to 2016. Common to one environmental and four …

Ciprofloxacin For The Treatment Of Cardiobacterium Hominis Prosthetic Valve Endocarditis, Lisa M. Avery, Catherine B. Felberbaum, Muhammad Hasan

Pharmacy Faculty/Staff Publications

Prosthetic valve endocarditis due to Cardiobacterium hominis is rare and recommended therapy includes a third generation cephalosporin. We report a case of Cardiobacterium hominis endocarditis post transcatheter aortic valve replacement in a patient with significant beta-lactam antimicrobial sensitivities who was successfully treated with ciprofloxacin monotherapy in conjunction with surgery.

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

The Effect Of Grapefruit Intake On Endogenous Serum Estrogen Levels In Postmenopausal Women, Kristine R. Monroe, Frank Z. Stanczyk, Kathleen Hill-Besinque, Malcolm C. Pike

Pharmacy Faculty Articles and Research

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study …

Novel Combination Bmp7 And Hgf Gene Therapy Instigates Selective Myofibroblast Apoptosis And Reduces Corneal Haze In Vivo, Suneel Gupta, Michael K. Fink, Arkasubhra Ghosh, Ratnakar Tripathi, Prashant R. Sinha, Ajay Sharma, Nathan P. Hesemann, Shyam S. Chaurasia, Elizabeth A. Giuliano, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

PURPOSE. We tested the potential of bone morphogenic protein 7 (BMP7) and hepatocyte growth factor (HGF) combination gene therapy to treat preformed corneal fibrosis using established rabbit in vivo and human in vitro models.

METHODS. Eighteen New Zealand White rabbits were used. Corneal fibrosis was produced by alkali injury. Twenty-four hours after scar formation, cornea received topically either balanced salt solution (BSS; n ¼ 6), polyethylenimine-conjugated gold nanoparticle (PEI2-GNP)-naked plasmid (n ¼ 6) or PEI2-GNP plasmids expressing BMP7 and HGF genes (n ¼ 6). Donor human corneas were used to obtain primary human corneal fibroblasts and myofibroblasts for mechanistic studies. …

Cost-Effectiveness Analysis Of Metformin+Dipeptidyl Peptidase-4 Inhibitors Compared To Metformin+Sulfonylureas For Treatment Of Type 2 Diabetes, Christina S. Kwon, Enrique Seoane-Vazquez, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

Background: Patients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D.

Methods: …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

The Future Direction Of Inter-Professional Education In Ireland: Insights From Focus Groups With Key Stakeholders, Cathal Cadogan, Cristin Ryan, Paul Gallagher, Helena Kelly, Catriona Bradley, Wilsie Bishop, Brian Cross, Larry Calhoun, Mckenzie Calhoun, Debbie C. Byrd, Reid B. Blackwelder, Judith Strawbridge

ETSU Faculty Works

Rationale: An inter-professional education (IPE) masterclass symposium titled, ‘The journey to team-based healthcare’, was jointly hosted by the School of Pharmacy, Royal College of Surgeons in Ireland (RCSI), the Irish Institute of Pharmacy and the Bill Gatton College of Pharmacy in East Tennessee State University in May 2017. The masterclass provided a comprehensive overview of IPE initiatives based on the extensive experience of senior academics from the host institutions, which included staff from pharmacy, nursing and medicine. The masterclass was attended by healthcare professionals, policy makers and educationalists working in Ireland. As part of the symposium, focus groups were conducted …

Telepharmacy And The Law, Hailey Button, Karl Williams

Doctoral External Publications

Recently, an "Advisory Notice" was placed on the website of the New York State Board of Pharmacy entitled "Automated Dispensing Machines" that provide "drugs for sale to customers outside of their respective registered pharmacy areas", and that it "considers this to be a violation of state law"¹. In support, the Notice cited the Education Law relating to the profession of pharmacy² and Regulations of the Commissioner of Education³. Finally, ownership of the pharmacy and the Supervising Pharmacist are responsible for compliance and "may be subject to disciplinary and unprofessional conduct action". The Notice did not …

Bacterial Lps At The Immune Modulating Component In Juzen-Taiho-To, Diego Montenegro

Dissertations, Theses, and Capstone Projects

Juzen-taiho-to (JTT) is an immune-boosting herbal formulation with an ideal balance of safety and efficacy. For example, JTT is clinically used in Japan to stimulate the immunological functions of cancer patients undergoing chemotherapy and radiation. Although the clinical effects of JTT are recognized, the active compounds and mechanism of action are unknown. The studies conducted previously in our laboratory associated several phytosterols and plant glycolipids with the potent immunostimulatory activity of JTT: namely, β-sitosteryl β-D-glucoside (BSSG), glucocerebroside (GluCer), digalactosyldiacylglycerol (DGDG) and monogalactosyldiacylglycerol (MGDG). However, these compounds, when further purified, exhibited little or no immunostimulatory activity. This suggested that the immunostimulatory …

Chronic Voluntary Oral Methamphetamine Induces Deficits In Spatial Learning And Hippocampal Protein Kinase Mzeta With Enhanced Astrogliosis And Cyclooxygenase-2 Levels, Jorge A. Avila, Roseanna M. Zanca, Denis Shor, Nicholas Paleologos, Amber A. Alliger, Maria E. Figueiredo-Pereira, Peter A. Serrano

Publications and Research

Methamphetamine (MA) is an addictive drug with neurotoxic effects on the brain producing cognitive impairment and increasing the risk for neurodegenerative disease. Research has focused largely on examining the neurochemical and behavioral deficits induced by injecting relatively high doses of MA [30 mg/kg of body weight (bw)] identifying the upper limits of MA-induced neurotoxicity. Accordingly, we have developed an appetitive mouse model of voluntary oral MA administration (VOMA) based on the consumption of a palatable sweetened oatmeal mash containing a known amount of MA. This VOMA model is useful for determining the lower limits necessary to produce neurotoxicity in the …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …

Synthesis Of Non-Natural Cofactor Analogs Of S-Adenosyl-L-Methionine Using Methionine Adenosyltransferase, Jon S. Thorson, Tyler Huber, Jianjun Zhang, Shanteri Singh

Pharmaceutical Sciences Faculty Patents

The present disclosure relates to the synthesis of non-natural analogs of S-adenosyl-L-methionine (SAM) and/or of Se-adenosyl- L-methionine (SeAM) by reacting a methionine analog and adenosine triphosphate (ATP) in the presence of at least one methionine adenosyltransferase (MAT), and to use thereof with downstream SAM and/or SeAM utilizing enzymes.

To see the remainder of this abstract, please download this patent.

High Activity Mutants Of Cocaine Esterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Lei Fang

Pharmaceutical Sciences Faculty Patents

The Bacterial cocaine esterase (CocE) mutants disclosed herein each have enhanced catalytic efficiency for ( -)cocaine, as compared to CocE mutants in the prior art, including CocE mutant E172-173. The presently-disclosed subject matter further includes a pharmaceutical composition including a mutant of bacterial cocaine hydrolase, as described herein, and a suitable pharmaceutical carrier. The presently-disclosed subject matter further includes a method of treating a cocaine-induced condition comprising administering to an individual an effective amount of a mutant of bacterial cocaine hydrolase variant, as disclosed herein, to accelerate cocaine metabolism and produce biologically inactive metabolites.

The Challenged Brain Bps 205g, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Regulation Of Kv2.1 Channel Inactivation By Phosphatidylinositol 4,5-Bisphosphate., Mayra Delgado-Ramírez, José J De Jesús-Pérez, Iván A Aréchiga-Figueroa, Jorge Arreola, Scott K Adney, Carlos A. Villalba-Galea, Diomedes E Logothetis, Aldo A Rodríguez-Menchaca

School of Pharmacy Faculty Articles

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a membrane phospholipid that regulates the function of multiple ion channels, including some members of the voltage-gated potassium (Kv) channel superfamily. The PIP2 sensitivity of Kv channels is well established for all five members of the Kv7 family and for Kv1.2 channels; however, regulation of other Kv channels by PIP2 remains unclear. Here, we investigate the effects of PIP2 on Kv2.1 channels by applying exogenous PIP2 to the cytoplasmic face of excised membrane patches, activating muscarinic receptors (M1R), or depleting endogenous PIP2 using a rapamycin-translocated 5-phosphatase (FKBP-Inp54p). Exogenous PIP2 rescued Kv2.1 channels from rundown and partially …

Pharmacists' Role In Harm Reduction: A Survey Assessment Of Kentucky Community Pharmacists' Willingness To Participate In Syringe/Needle Exchange, Amie Goodin, Amanda Fallin-Bennett, Traci Green, Patricia R. Freeman

Nursing Faculty Publications

Background: Pharmacists' role in harm reduction is expanding in many states, yet there are limited data on pharmacists' willingness to participate in harm reduction activities. This study assessed community pharmacists' willingness to participate in one harm reduction initiative: syringe/needle exchange.

Methods: In 2015, all Kentucky pharmacists with active licenses were emailed a survey that examined attitudes towards participation in syringe/needle exchange. Response frequencies were calculated for community pharmacist respondents. Ordinal logistic regression estimated the impact of community pharmacist characteristics and attitudes on willingness to provide clean needles/syringes to people who inject drugs and to dispose of used syringes/needles, where both …

Informing Efforts To Develop Nitroreductase For Amine Production, Anne-Frances Miller, Jonathan T. Park, Kyle L. Ferguson, Warintra Pitsawong, Andreas S. Bommarius

Chemistry Faculty Publications

Nitroreductases (NRs) hold promise for converting nitroaromatics to aromatic amines. Nitroaromatic reduction rate increases with Hammett substituent constant for NRs from two different subgroups, confirming substrate identity as a key determinant of reactivity. Amine yields were low, but compounds yielding amines tend to have a large π system and electron withdrawing substituents. Therefore, we also assessed the prospects of varying the enzyme. Several different subgroups of NRs include members able to produce aromatic amines. Comparison of four NR subgroups shows that they provide contrasting substrate binding cavities with distinct constraints on substrate position relative to the flavin. The unique architecture …

Hydrochloric Acid Infusion For The Treatment Of Metabolic Alkalosis In Surgical Intensive Care Unit Patients, Jason D. Guffey, Curtis E. Haas, Amber Crowley, Kathryn A. Connor, David C. Kaufman

Pharmacy Faculty/Staff Publications

Background: Older reports of use of hydrochloric acid (HCl) infusions for treatment of metabolic alkalosis document variable dosing strategies and risk. Objectives: This study sought to characterize use of HCl infusions in surgical intensive care unit patients for the treatment of metabolic alkalosis. Methods: This retrospective review included patients who received a HCl infusion for >8 hours. The primary end point was to evaluate the utility of common acid-base equations for predicting HCl dose requirements. Secondary end points evaluated adverse effects, efficacy, duration of therapy, and total HCl dose needed to correct metabolic alkalosis. Data on demographics, potential causes of …

Pharmacy Practice And Research: The Development Of A University Collaboration In Colombia, Ellen Schellhase

Engagement & Service-Learning Summit

No abstract provided.