Pharmacy and Pharmaceutical Sciences Commons^™

An Investigation Into The Use Of An Herbal Labor Induction Tincture Containing Black Cohosh, Cramp Bark, Partridgeberry, And Motherwort On Contractile Responses Produced From Isolated Strips Of Mouse Uterine Tissues, Clayton Neuenschwander, Katrina Wu, Teresa F. Degolier

Biological Sciences Faculty Publications

Introduction: Alternative solutions in the form of herbal remedies meant to ease or expedite the process of labor have often been pursued and administered but have seldom been quantitatively tested for efficacy. Published research has shown some validation for some commonly used herbs such as blue cohosh (Caulophyllum thalictroides), red raspberry (Rubus idaeus), castor bean (Ricinus communis) and evening primrose (Oenothera biennis) on isolated mouse uterine strips. Methods: This study tested an array of herbs used by midwives in a labor induction tincture, which included black cohosh (Actaea racemosa), cramp bark (Viburnum opulus), partridgeberry (Mitchella repens), and motherwort (Leonurus cardiaca). …

Kshv Susceptibility And Transmission Within Tonsillar Specimens, Farizeh Aalam

Pharmaceutical Sciences (PhD) Dissertations

Despite nearly three decades of research, not much is known regarding the early stages of development for KSHV lymphoproliferative disorders, hindering our ability to develop prophylactic measures or effective treatments. This dissertation will focus on the host and viral factors influencing the magnitude and dynamics of KSHV infection in the human tonsil to pave the way for future interventions directed at limiting person-to-person transmission of KSHV.

To understand the contribution of host factors to KSHV susceptibility in B lymphocytes, we generated a library of 40 tonsillar specimens. Our results indicate that the immunological composition of tonsillar lymphocytes varies across our …

Modulating The Tumor Microenvironment To Improve Immunotherapy Treatments, Lleayem Nazario-Johnson, David Rowley

Senior Honors Projects

Advances in immunotherapy are revolutionizing the treatments of certain cancers, especially those in the blood. However, wider applications for eradicating solid tumors have been slow to emerge. A likely reason is the presence of myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment that secrete immunosuppressive molecules which attenuate the attack of immune cells. We hypothesize that small molecule Wnt/Beta- Catenin inhibitors can be used to modulate the immunosuppressive actions of MDSCs and increase the effectiveness of immunotherapy treatments, such as with chimeric antigen receptor (CAR) T-cells. The Wnt/Beta-Catenin Pathway has been shown to be a crucial driving force behind the …

Comparative Metabolism Of Aflatoxin B1 In Two Quail Genera Coturnix Japonica And Callipepla Californica, Sean Moody

All Graduate Plan B and other Reports, Spring 1920 to Spring 2023

Avian species are highly susceptible to the hepatotoxic mycotoxin aflatoxin B₁ (AFB₁). Domesticated turkeys are exquisitely sensitive, due to a combination of highly-efficient hepatic cytochrome P450 (CYP)-mediated bioactivation, and to dysfunctional alpha-class glutathione S-transferases (GSTAs) which typically detoxify the bioactivated electrophilic metabolite exo-AFB₁-8,9-epoxide (AFBO). Wild turkeys are relatively resistant to AFB₁ in large part due to expression of functional GSTAs. Quail, a related Galliforme, are slightly less sensitive in vivo to AFB₁, but whether this is related to the hepatic metabolic profiles of these two critical enzymes has not been rigorously evaluated. …

Development Of Novel Peptide-Doxorubicin Conjugates For Targeting Triple-Negative Breast Cancer, Azam Saghaeidehkordi

Pharmaceutical Sciences (PhD) Dissertations

Triple-negative breast cancer (TNBC) is the most aggressive and difficult to treat subtype of breast cancer. Chemotherapy is an active treatment option in combination with other treatments; however, the side effects limit the effective therapeutic dose. To selectively target the cancer cells, I have synthesized three peptide-drug conjugates (PDCs) to specifically target the TNBC cells. The first PDC contains peptide 18-4 with an additional cysteine in the N-terminal (NH2- CWxEAAYQrFL-CONH2) linked to aldoxorubicin (Aldox), a modified version of a common chemotherapy drug doxorubicin (Dox). The cytotoxicity of the PDC and free Dox (positive control) were assessed against MDA-MB-231, MDA-MB-468, and …

Computational Design Of Β-Fluorinated Morphine Derivatives For Ph-Specific Binding, Makena Augenstein, Nayiri Alexander, Matthew Gartner

Student Scholar Symposium Abstracts and Posters

Molecular extension and dissection techniques are used to design a morphine derivative that promotes selective binding in inflamed tissue due to its lower pH while avoiding dangerous activation in the brain. Morphine is used to treat pain associated with inflammation. While being effective analgesics, opioids carry the risk of central side effects, including addiction, respiratory depression, and sedation. Opioids are agonists that bind to the μ-opioid peptide receptor (MOR) within central and peripheral nerves and act via a G-protein coupled receptor pathway.

Deprotonation of the tertiary amine induces a negative charge on the nitrogen, discouraging binding at physiological pH (pH=7.4). …

Siderophore-Mediated Zinc Acquisition Enhances Enterobacterial Colonization Of The Inflamed Gut, Judith Behnsen, Hui Zhi, Allegra T. Aron, Venkateswaran Subramanian, William Santus, Michael H. Lee, Romana R. Gerner, Daniel Petras, Janet Z. Liu, Keith D. Green, Sarah L. Price, Jose Camacho, Hannah Hillman, Joshua Tjokrosurjo, Nicola P. Montaldo, Evelyn M. Hoover, Sean Treacy-Abarca, Benjamin A. Gilston, Eric P. Skaar, Walter J. Chazin, Sylvie Garneau-Tsodikova, Matthew B Lawrenz, Robert D Perry, Sean-Paul Nuccio, Pieter C. Dorrestein, Manuela Raffatellu

Pharmacy Nuclear Magnetic Resonance Center Faculty Publications

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. However, the probiotic bacterium Escherichia coli Nissle 1917 (or “Nissle”) exhibits appreciable growth in zinc-limited media even when these transporters are deleted. Here, we show that Nissle utilizes the siderophore yersiniabactin as a zincophore, enabling Nissle to grow in zinc-limited media, to tolerate calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. We also show that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with increased relative zinc binding as the …

November / December 2021, Cindy Brooks, Randy Curry

RURAL ROCKS

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

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

In Vitro Activity Of Non-Antibiotic Drugs Against Staphylococcus Aureus Clinical Strains, Natalie K. Boyd, Grace C. Lee, Chengwen Teng Pharm.D., Ph.D., Christopher R. Frei

Faculty Publications

Objectives: We hypothesised that one or more of the non-antibiotic candidates selected for this study would demonstrate antibiotic activity against Staphylococcus aureus.

Methods: We determined minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) for non-antibiotic drugs (amlodipine, azelastine, ebselen and sertraline) against five clinical S. aureus isolates and one quality control strain using the Microplate Alamar Blue Assay (MABA). Our research group selected clinical isolates obtained from nasal and wound swab cultures of patients with skin and soft-tissue infections who were seen at primary care clinics in the South Texas Ambulatory Research Network (STARNet).

Results: Three of the non-antibiotic …

Characterizing And Overcoming Resistance To Aminomethylspectinomycins In Gram-Negative Bacteria, Nisha Das

Theses and Dissertations (ETD)

Spectinomycin (SPC) is a broad-spectrum aminocyclitol antibiotic. Its use in agriculture has led to widespread resistance in enteric bacteria, necessitating the development of more effective analogs. Aminomethyl spectinomycins (amSPC) are modified spectinomycins with increased potency against many bacterial species. These species include Legionella pneumophila, which harbors a chromosomally encoded aminoglycoside modifying enzyme (AME). In this study, we follow up on this observation and examine the extent to which the amSPCs are substrates for AMEs through adenylation (ANTs) and phosphorylation (APH). APH(9)-Ia and ANT(3")(9) were expressed in E. coli BL21(DE3) and purified using the Ni-affinity chromatography. The ability of AMEs to …

Evaluation Of The Effectiveness Of Continuing Professional Development In The Pharmaceutical Workplace: A Cross-Sectional Study In Lebanon, Georges Hatem, Mathijs Goossens, Diana Ghanem, Roula Bou Assi

BAU Journal - Creative Sustainable Development

The objective of this study is to evaluate the effectiveness of Continuous Professional Development in the pharmaceutical workplace and the direct impact on the pharmacists’ personal and professional progression and to assess their perceptions toward various CPD methods and their incorporation into this recent learning pathway. Methods: A cross-sectional descriptive study was conducted in Lebanon within three months from July 2017 till September 2017 using a survey as a tool. Overall 142 participants were conveniently selected frequency matching national government estimates of pharmacists’ work location and gender . Results: Among the respondents, 38.7% reported that they have learnt through CD/DVD, …

Mutants Of The White Abcg Transporter In Drosophila Melanogaster Have Deficient Olfactory Learning And Cholesterol Homeostasis, Jennifer L. Myers, Maria Porter, Nicholas Narwold, Krishna Bhat, Brigitte Dauwalder, Gregg Roman

Faculty and Student Publications

Drosophila’s white gene encodes an ATP binding cassette G-subfamily (ABCG) half transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w¹¹¹⁸ mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w¹¹¹⁸ learning phenotype is also found in the w^apricot and w^coral alleles, is dominant, and is …

Assessing Potentiation Of The (Α4)3(Β2)2 Nicotinic Acetylcholine Receptor By The Allosteric Agonist Cmpi, Farah Deba, Kemburli Munoz, Eloisa Peredia, Gustav Akk, Ayman K. Hamouda

Pharmacy Faculty Publications and Presentations

The extracellular domain of the nicotinic acetylcholine receptor isoforms formed by three α4 and two β2 subunits ((α4) 3(β2)2 nAChR) harbors two high-affinity “canonical” acetylcholine (ACh)-binding sites located in the two α4:β2 intersubunit interfaces and a low-affinity “noncanonical” AChbinding site located in the α4:α4 intersubunit interface. In this study, we used ACh, cytisine, and nicotine (which bind at both the α4:α4 and α4:β2 interfaces), TC-2559 (which binds at the α4:β2 but not at the α4:α4 interface), and 3-(2-chlorophenyl)-5- (5-methyl-1-(piperidin-4-yl)-1H-pyrrazol-4-yl)isoxazole (CMPI, which binds at the α4:α4 but not at the α4:β2 interface), to investigate the binding and gating properties of CMPI …

Biocompatible Fepo4 Nanoparticles: Drug Delivery, Rna Stabilization, And Functional Activity, Sagar Rayamajhi, Sarah Wilson, Santosh Aryal, Robert Delong

Pharmacy Faculty Publications and Presentations

FePO4 NPs are of special interest in food fortification and biomedical imaging because of their biocompatibility, high bioavailability, magnetic property, and superior sensory performance that do not cause adverse organoleptic effects. These characteristics are desirable in drug delivery as well. Here, we explored the FePO4 nanoparticles as a delivery vehicle for the anticancer drug, doxorubicin, with an optimum drug loading of 26.81%±1.0%. This loading further enforces the formation of Fe3+ doxorubicin complex resulting in the formation of FePO4-DOX nanoparticles. FePO4-DOX nanoparticles showed a good size homogeneity and concentration-dependent biocompatibility, with over 70% biocompatibility up to 80 µg/mL concentration. Importantly, cytotoxicity …

Arrhythmogenic Hearts In Pkd2 Mutant Mice Are Characterized By Cardiac Fibrosis, Systolic, And Diastolic Dysfunctions, Farideh Amirrad, Rajasekharreddy Pala, Kiumars Shamloo, Brian S. Muntean, Surya M. Nauli

Pharmacy Faculty Articles and Research

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b₁ signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2^wt/wt (control or wild-type) and MyH6 …

Landomycins As Glutathione-Depleting Agents And Natural Fluorescent Probes For Cellular Michael Adduct-Dependent Quinone Metabolism, Alessio Terenzi, Mery La Franca, Sushilla Van Schoonhoven, Rostyslav Panchuk, Álvaro Martínez, Petra Heffeter, Redding Gober, Christine Pirker, Petra Vician, Christian R. Kowol, Rostyslav Stoika, Luca Salassa, Jürgen Rohr, Walter Berger

Pharmaceutical Sciences Faculty Publications

Landomycins are angucyclines with promising antineoplastic activity produced by Streptomyces bacteria. The aglycone landomycinone is the distinctive core, while the oligosaccharide chain differs within derivatives. Herein, we report that landomycins spontaneously form Michael adducts with biothiols, including reduced cysteine and glutathione, both cell-free or intracellularly involving the benz[a]anthraquinone moiety of landomycinone. While landomycins generally do not display emissive properties, the respective Michael adducts exerted intense blue fluorescence in a glycosidic chain-dependent manner. This allowed label-free tracking of the short-lived nature of the mono-SH-adduct followed by oxygen-dependent evolution with addition of another SH-group. Accordingly, hypoxia distinctly stabilized the fluorescent mono-adduct. While …

Insulin-Like Growth Factor-1 Differentially Modulates Glutamate-Induced Toxicity And Stress In Cells Of The Neurogliovascular Unit, Cellas A. Hayes, Brandon G. Ashmore, Akshaya Vijayasankar, Jessica P. Marshall

Faculty and Student Publications

The age-related reduction in circulating levels of insulin-like growth factor-1 (IGF-1) is associated with increased risk of stroke and neurodegenerative diseases in advanced age. Numerous reports highlight behavioral and physiological deficits in blood-brain barrier function and neurovascular communication when IGF-1 levels are low. Administration of exogenous IGF-1 reduces the extent of tissue damage and sensorimotor deficits in animal models of ischemic stroke, highlighting the critical role of IGF-1 as a regulator of neurovascular health. The beneficial effects of IGF-1 in the nervous system are often attributed to direct actions on neurons; however, glial cells and the cerebrovasculature are also modulated …

Aberrant Crosstalk Between Insulin Signaling And Mtor In Young Down Syndrome Individuals Revealed By Neuronal-Derived Extracellular Vesicles, Marzia Perluigi, Anna Picca, Elita Montanari, Riccardo Calvani, Federico Marini, Roberto Matassa, Antonella Tramutola, Alberto Villani, Giuseppe Familiari, Fabio Di Domenico, D. Allan Butterfield, Kenneth J. Oh, Emanuele Marzetti, Diletta Valentini, Eugenio Barone

Chemistry Faculty Publications

INTRODUCTION: Intellectual disability, accelerated aging, and early-onset Alzheimer-like neurodegeneration are key brain pathological features of Down syndrome (DS). Although growing research aims at the identification of molecular pathways underlying the aging trajectory of DS population, data on infants and adolescents with DS are missing.

METHODS: Neuronal-derived extracellular vesicles (nEVs) were isolated form healthy donors (HDs, n = 17) and DS children (n = 18) from 2 to 17 years of age and nEV content was interrogated for markers of insulin/mTOR pathways.

RESULTS: nEVs isolated from DS children were characterized by a significant increase in pIRS1^Ser636, a marker of …

Rapid-Onset Anti-Stress Effects Of A Kappa-Opioid Receptor Antagonist, Ly2795050, Against Immobility In An Open Space Swim Paradigm In Male And Female Mice, Caroline Baynard, Thomas E. Prisinzano, Eduardo R. Butelman

Pharmaceutical Sciences Faculty Publications

The kappa-opioid receptor (KOR) / dynorphin system is implicated with behavioral and neurobiological effects of stress exposure (including heavy exposure to drugs of abuse) in translational animal models. Thus some KOR-antagonists can decrease the aversive, depressant-like and anxiety-like effects caused by stress exposure. The first generation of selective KOR-antagonists have slow onsets (hours) and extremely long durations of action (days-weeks), in vivo. A new generation of KOR antagonists with rapid onset and shorter duration of action can potentially decrease the effects of stress exposure in translational models, and may be of interest for medication development. This study examined the …