Pharmacy and Pharmaceutical Sciences Commons^™

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 …

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.

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Mala Lā’Au Lapa’Au: Preserving The Hawaiian ‘Āina And Mo’Omehue, Sandra Fogg

Senior Honors Projects

The study of medicinal plants in the western world tends to focus on the isolation and elucidation of natural products that have bioactive characteristics and potential for pharmaceutical formulation. However, the utilization of medicinal plants in cultures that still practice ancient medicine, such as Hawai’i and other Pacific Island nations, involves the use of whole plant parts in conjunction with spiritual rituals to heal illnesses and ailments. In order to gather a different perspective of the use of plants in medicine, a diverse investigation of “Lā’au Lapa’au,” or the Hawaiian art of healing through the use of plants and spiritual …

Analyzation Of Metabolic Reprogramming In Drug-Resistant Mcf-7 Cells, Derick Han, Ho Leung, Andrew Vo

Student Scholar Symposium Abstracts and Posters

The Warburg effect states that cancer cells mainly receive their energy from anaerobic glycolysis. Thus, mitochondria play a different role in the metabolism of cancer cells as opposed to normal, healthy cells. In chemotherapy, there is always a chance of the cancer regressing. Making drug-resistant cancer cells to analyze their metabolism may change how cancer is treated. This study aimed to create drug-resistant MCF-7 cell lines with doxorubicin in order to determine the metabolic changes that have occurred in the process of becoming resistant to drug treatments.

Clinical Applications Of A Combination Chemotherapy Using 8-Chloro Camp And 8-Chloro Adenosine, Erik Munoz, Andrea Saich, Andrew Cox, Yu-An Peter Chang

Student Scholar Symposium Abstracts and Posters

Dr. Cho-Chung from the NIH first thought to use halogenated cAMP derivatives as competitive inhibitors of cAMP to slow down cancer cell mitosis. While the iodine and bromine substituted versions showed very little therapeutic actions, 8-Chloro cAMP has been shown to have strong anti-cancer effects. This has been shown in the phase II clinical trials this drug has undergone. However, these trials have had issues with solubility and toxicity. The drug is similar to vitamin C and is excreted quickly. Scientists tried to overcome this by using a peristaltic pump to give patients a continuous dosage, but this proved too …

Swosu Research And Scholarly Activity Fair 2015, Jason L. Johnson

SWOSU Research and Scholarly Activity Fair Programs

Welcome to the Twenty-Second SWOSU Research and Scholarly Activity Fair! On display today are 103 presentations involving 169 student researchers, writers, performers, and artists, and 40 faculty sponsors encompassing scholarly activity from the Departments of: Accounting, Computer Science, and Entrepreneurship; Art, Communication, and Theatre; Biological Sciences; Chemistry and Physics; Education; Engineering Technology; Finance, Management, and Marketing; Language and Literature; Music; Nursing and Allied Health; Pharmaceutical Sciences; Psychology; and Social Sciences.

Beta-Lactam Antimicrobial Dosing Optimization In Obese Patients Compared To Non-Obese Patients Using Population Pharmacokinetic/Pharmacodynamic Approach, Eun Kyoung Chung

Open Access Dissertations

Obesity is a significant global health problem and has been associated with altered pharmacokinetics and pharmacodynamics of many drugs. However, little is known regarding the effect of obesity on the pharmacokinetics and pharmacodynamics of many broad-spectrum, beta-lactam antibiotics such as piperacillin/tazobactam, meropenem, and cefepime. The objective of this study is to evaluate the population pharmacokinetics and pharmacodynamics of piperacillin/tazobactam, meropenem, and cefepime in hospitalized obese patients in order to determine dosing regimens that provide similar exposures between obese and non-obese patients. ^ For piperacillin/tazobactam, a retrospective analysis was conducted using prospectively collected serum concentration-time data from two previous studies (Study …

Histopathology And Oxidative Stress Analysis Of Concomitant Misoprostol And Celecoxib Administration, Derek E. Murrell, James W. Denham, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Nonsteroidal anti-inflammatory drugs (NSAIDs), non-selective or selective inhibitors of cyclooxygenase (COX-1 and -2), reduce pain and inflammation associated with arthritic diseases. Celecoxib, a COX-2-selective inhibitor providing decreased gastric injury relative to on-selective NSAIDs, is commonly prescribed. Misoprostol, a prostaglandin analog, supplements NSAID-inhibited prostaglandin levels. As concomitant celecoxib and misoprostol administration has been shown to intensify renal adverse effects, this article examined the influence of concomitant administration on hepatic histopathology, oxidative stress, and celecoxib concentration. On days 1 and 2, rat groups (n = 6) were gavaged twice daily (two groups with vehicle and two groups with 100 μg/kg misoprostol). From …

Kaposi Sarcoma Herpesvirus Induces Ho-1 During De Novo Infection Of Endothelial Cells Via Viral Mirna-Dependent And -Independent Mechanisms, Sara Botto, Jennifer Totonchy, Jean K. Gustin, Ashlee V. Moses

Pharmacy Faculty Articles and Research

Kaposi sarcoma (KS) herpesvirus (KSHV) infection of endothelial cells (EC) is associated with strong induction of heme oxygenase-1 (HO-1), a stress-inducible host gene that encodes the rate-limiting enzyme responsible for heme catabolism. KS is an angioproliferative tumor characterized by the proliferation of KSHV-infected spindle cells, and HO-1 is highly expressed in such cells. HO-1 converts the pro-oxidant, proinflammatory heme molecule into metabolites with antioxidant, antiinflammatory, and proliferative activities. Previously published work has shown that KSHV-infected EC in vitro proliferate in response to free heme in a HO-1-dependent manner, thus implicating virus-enhanced HO-1 activity in KS tumorigenesis. The present study investigated …

Role Of 5'Tg3'-Interacting Factors (Tgifs) In Vorinostat (Hdac Inhibitor)-Mediated Corneal Fibrosis Inhibition, Ajay Sharma, Nishant R. Sinha, Saad Siddiqui, Rajiv R. Mohan

Pharmacy Faculty Articles and Research

Purpose: We have previously reported that vorinostat, an FDA-approved, clinically used histone deacetylase (HDAC) inhibitor, attenuates corneal fibrosis in vivo in rabbits by blocking transforming growth factor β (TGFβ). The 5′TG3′-interacting factors (TGIFs) are transcriptional repressors of TGFβ1 signaling via the Smad pathway. The present study was designed to explore the expression of TGIFs in human corneal fibroblasts and to investigate their role in mediating the antifibrotic effect of vorinostat.

Methods: Human corneal fibroblast cultures were generated from donor corneas. RNA isolation, cDNA preparation, and PCR were performed to detect the presence of TGIF1 and TGIF2 transcripts. The cultures were …

Elaboration And Design Of Α7 Nachr Negative Allosteric Modulators, Osama I. Alwassil

Theses and Dissertations

α7 Neuronal nicotinic acetylcholine receptors are one of two major classes of receptors responsible for cholinergic neurotransmission in the central nervous system. The existence of α7 neuronal nAChRs in different regions of the nervous system suggests their involvement in certain essential physiological functions as well as in disorders such as Alzheimer’s disease (AD), drug dependence, and depression. This project was aimed toward the discovery and development of small–molecule arylguanidines that modulate α7 nAChR function with improved subtype-selectivity through an allosteric approach. Identifying the required structural features of these small molecules allowed optimization of their negative allosteric modulator (NAM) actions at …

Expression Of The Nkcc2a Cotransporter In Mouse Central Nervous System, Katherine E. Fahy, James B. Lucot, Hayo Castrop, Mauricio Di Fulvio

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The …

Nosh-Aspirin (Nbs-1120), A Dual Nitric Oxide And Hydrogen Sulfide-Releasing Hybrid, Reduces Inflammatory Pain, Miriam D. Fonseca, Fernando Q. Cunha, Khosrow Kashfi, Thiago M. Cunha

Publications and Research

The development of nitric oxide (NO)- and hydrogen sulfide (H2S)-releasing nonsteroidal anti-inflammatory drugs (NSAIDs) has generated more potent anti-inflammatory drugs with increased safety profiles. A new hybrid molecule incorporating both NO and H2S donors into aspirin (NOSH-aspirin) was recently developed. In the present study, the antinociceptive activity of this novel molecule was compared with aspirin in different models of inflammatory pain. It was found that NOSH-aspirin inhibits acetic acid-induced writhing response and carrageenan (Cg)-induced inflammatory hyperalgesia in a dosedependent (5–150 lmol/kg, v.o.) manner, which was superior to the effect of the same doses of aspirin. NOSH-aspirin’s antinociceptive effect was also …

Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown

Theses and Dissertations--Neuroscience

The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Celecoxib Or Diclofenac Hepatic Status In The Presence Or Absence Of Rebamipide, Derek E. Murrell, Yuyun Rahmasari, James W. Denham, Peter C. Panus, Sam Harirforoosh

Pharmacy Faculty Articles and Research

OBJECTIVE: Utilization of nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, can produce gastrointestinal ulceration. Thus, cyclooxygenase-2-selective inhibitors, such as celecoxib, and protective agents (e.g. rebamipide) have been employed to alleviate harmful NSAID effects. This study sought to explore the influence of rebamipide on the hepatic outcomes following administration of two commonly prescribed NSAIDs.

MATERIALS AND METHODS: Rats were given either vehicle or rebamipide (30 mg/kg) orally twice daily for two days, then on the third day respective groups were dosed with either vehicle, celecoxib (40 mg/kg), or diclofenac (10 mg/kg) in addition to a respective dose of vehicle …

Redesign Of Trans-Splicing Molecules For The Correction Of Dystrophia Myotonica Type 1 Toxic Rna Transcripts, Eleanor G. Harrison

Undergraduate Honors Theses

Dystrophia myotonica (DM1), one of the most common forms of muscular dystrophy, is caused by a repeated trinucleotide expansion in the DMPK gene. This mutation results in the accumulation of toxic cellular RNA transcripts. Spliceosome-mediated RNA trans-splicing (SMaRT) technology is a form of gene therapy that possesses the potential to correct these toxic RNA transcripts and thus cure the disease. Despite its promise, prior research applications of SMaRT technology to DM1 have been hampered by poor efficiency and have not been validated in a relevant model of the disease. In order to improve the efficiency of trans-splicing, this study examined …

Considerations For The Use Of Dietary Or Herbal Supplements, Samantha Morrison, Mary Menezes, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

The Impact Of An Omega-3 Enriched Diet On Hyperactivity And Biochemistry In An Animal Model For Attention-Deficit/Hyperactivity Disorder, Nadine M. Hammoud

Open Access Theses

Attention-deficit/hyperactivity disorder (ADHD) is the most diagnosed behavioral disorder in children. It affects around 5% of children worldwide and 11% of children in the United States, with rates increasing. Pharmaceutical treatments, such as amphetamines and methylphenidates, are not effective for everyone and are known to have unwanted side effects. While the etiology of the disorder is not yet fully understood, there are clear genetic and environmental components. Nutritional insufficiencies have recently become a popular environmental risk factor under investigation. Essential fatty acids (EFA), omega-3 polyunsaturated fatty acids (PUFA) in particular, are needed for proper brain development and function. Our lab …

The Effect Of Pomegranate Juice Extract On The Hedgehog Signaling Pathway In Pancreatic Cancer, Veronica Gomez, Talia Shackelford, Autumn Tocchi, Melissa Rowland-Goldsmith

e-Research: A Journal of Undergraduate Work

Pancreatic cancer is the fourth leading cause of cancer death in the United States. There have been several reports indicating that phytochemicals in fruits can reduce the risk of cancer due to the anti-oxidant and anti-inflammatory effects of the polyphenols. Our lab has shown that pomegranate juice extract (PJE) has anti-proliferative and pro-apoptotic effects in human pancreatic cancer cells. In the past, we have shown that cells adhere more strongly to the plate when treated with PJE. This observation prompted an investigation of how PJE regulates cell adhesion proteins. Previously, our lab investigated E-cadherin, a cell adhesion protein. Upon activation …

Investigating Propargyl-Linked Antifolates In Inhibiting Bacterial And Fungal Dihydrofolate Reductase, Joshua Andrade

Honors Scholar Theses

Antimicrobial agents have been invaluable in reducing illness and death associated with bacterial infection. However, over time, bacteria have evolved resistance to all major drug classes as a result of selective pressure. The advancement of new drug compounds is therefore vital. The Anderson-Wright Lab has focused on developing potent and selective inhibitors of dihydrofolate reductase (DHFR), an enzyme key in cell proliferation and survival, in several pathogenic species. The lab has found that a set of compounds, known as propargyl-linked antifolates, are DHFR inhibitors that are both biologically effective and have strong pharmacokinetic properties.

The efficacy of novel propargyl-linked antifolates …

Effects Of Pde4 Pathway Inhibition In Rat Experimental Stroke, Fan Yang, Rachita K. Sumbria, Dong Xue, Chuanhui Yu, Dan He, Shuo Liu, Annlia Paganini-Hill, Mark J. Fisher

Pharmacy Faculty Articles and Research

PURPOSE: The first genomewide association study indicated that variations in the phosphodiesterase 4D (PDE4D) gene confer risk for ischemic stroke. However, inconsistencies among the studies designed to replicate the findings indicated the need for further investigation to elucidate the role of the PDE4 pathway in stroke pathogenesis. Hence, we studied the effect of global inhibition of the PDE4 pathway in two rat experimental stroke models, using the PDE4 inhibitor rolipram. Further, the specific role of the PDE4D isoform in ischemic stroke pathogenesis was studied using PDE4D knockout rats in experimental stroke. METHODS: Rats were subjected to either the …

The Role Of Ape/Ref-1 In Hepatocellular Carcinoma Progression, Zhen Yang, Sun Yang, Bobbye J. Misner, Feng Liu-Smith, Frank L. Meyskens

Pharmacy Faculty Articles and Research

Hepatocellular carcinoma (HCC) is responsible for a third of the estimated cancer-caused deaths worldwide. To deeply understand the mechanisms controlling HCC progression is of primary importance to develop new approaches for treatment. Apurinic/apyrimidinic endonuclease-1/redox effector factor 1 (APE/Ref-1) has been uncovered elevated in various types of cancer, including HCC. Additionally, HCC progression is always correlated with elevated copper (Cu). Our previous data demonstrated that Cu treatment initiated APE/Ref-1 expression and its downstream targets. Therefore, we hypothesized that APE/Ref-1 may be involved in HCC progression through mediating the effect of Cu to its signaling cascades. Following different treatments, human HCC cell …

Antidepressant Effects Of The Nts1 Agonist Pd149163 In The Forced Swim Test, Lawrence Carey Iv

All NMU Master's Theses

Neurotensin is a neuropeptide that influences monoaminergic neurotransmission in areas of the brain involved in the pathophysiology of depression. The forced swim test is a commonly used screening model for putative antidepressant medications. Drugs that have antidepressant effects in humans reliably decrease the time animals spend in an immobile posture in the forced swim test without increasing general locomotor activity as measured in an open field test. The present study sought to examine the effects of the neurotensin NTS₁ receptor agonist PD149163 and the tricyclic antidepressant drug imipramine on immobility in the forced swim test and on locomotor activity …

Production Of Recombinant Human Coagulation Factor Ix By Transgenic Pig, Weijie Xu

Department of Chemical and Biomolecular Engineering: Dissertations, Theses, and Student Research

Hemophilia B is the congenital bleeding disorder caused by deficiency in functional coagulation factor IX (FIX) and about 28,000 patients worldwide in 2012. And current treatment is restricted to protein-replacement therapy, which required FIX concentrates for patients’ life-time. Approximately 1 billion units FIX were consumed in 2012. However, still about 70-80% patients, mostly in developing countries, received inadequate or no treatment because of the unavailable and/or unaffordable FIX concentrates. Considering safety reasons, e.g. transmission of blood-borne diseases, the recombinant human FIX (rFIX) is recommended other than the plasma-derived FIX. However, only one rFIX is currently available on the market. The …

Neuroinflammation And Neurodegeneration In Adult Rat Brain From Binge Ethanol Exposure: Abrogation By Docosahexaenoic Acid, Nuzhath Tajuddin, Kwan-Hoon Moon, Simon Alex Marshall, Kimberly Nixon, Edward J. Neafsey, Hee-Yong Kim, Michael A. Collins

Pharmaceutical Sciences Faculty Publications

Evidence that brain edema and aquaporin-4 (AQP4) water channels have roles in experimental binge ethanol-induced neurodegeneration has stimulated interest in swelling/edema-linked neuroinflammatory pathways leading to oxidative stress. We report here that neurotoxic binge ethanol exposure produces comparable significant effects in vivo and in vitro on adult rat brain levels of AQP4 as well as neuroinflammation-linked enzymes: key phospholipase A2 (PLA2) family members and poly (ADP-ribose) polymerase-1 (PARP-1). In adult male rats, repetitive ethanol intoxication (3 gavages/d for 4 d, ∼ 9 g/kg/d, achieving blood ethanol levels ∼ 375 mg/dl; "Majchrowicz" model) significantly increased AQP4, Ca+2-dependent PLA2 GIVA (cPLA2), phospho-cPLA2 GIVA …

A Simple High Performance Liquid Chromatography Method For Determination Of Rebamipide In Rat Urine, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Rebamipide is a mucoprotective agent commonly used to prevent nonsteriodal anti-inflammatory drug-induced gastrointenstinal side effects [1]. Human plasma and urine analysis of rebamipide utilizing high performance liquid chromatography (HPLC) have been reported [2]. Recently, we reported on the plasma levels of rebamipide in presense or absence of celecoxib or diclofenac in rats [3] using a modified HPLC method of detection developed by Jeoung et al. [4]. To tailor the method towards use in urinary rebamipide extraction and analysis, the following modifications were made:

• To compensate for high concentrations of rebamipide found in urine, a new rebamipide stock solution was prepared …

Chemical Profiling And Biological Activity Of Two Tunicate-Associated Marine Bacteria, Lyubina Yankova

Honors Scholar Theses

Marine natural products have recently been an increasingly abundant source of novel antibiotics. Given that there is an increasing resistance to current drug therapies, finding new sources such as marine natural products is essential. Tunicate-associated marine bacteria can be a significant source of antibacterial compounds. Two tunicates of the species Eudistoma were collected from Portobelo National Park on the Salmedina Reef of Panama in the Caribbean Sea. Bacteria associated with the tunicate were isolated, cultured, extracted, and fractionated. Fractions were tested against an array of clinically relevant bacterial pathogens in the BioMAP assay. Two fractions MB0086E and MB0088E demonstrated activity …