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 …

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.

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 …

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 …

Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

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 …

Bridging The Location Gap: Physician Perspectives Of Physician-Pharmacist Collaboration In Patient Care (Bridge Phase Ii), Keri D. Hager, Donald Uden, Daniel M. Tomaszewski

Pharmacy Faculty Articles and Research

Background: To optimize patient outcomes, the patient-centred medical home model emphasizes comprehensive team-based care. Pharmacists are qualified to enhance appropriate medication use and help improve patient outcomes through provision of medication therapy management (MTM) services. To optimally provide MTM, pharmacists must effectively collaborate with physicians. This study explored factors that influence pharmacist-physician collaboration.

Methods and Findings: A convenience sample of five physicians participated in semi-structured interviews and the resulting data were analyzed using qualitative methods. Transcripts of the interviews were independently coded for themes by two researchers. Five themes emerged: trustworthiness, role specification, relationship initiation, effects on practice, …

Utilization Of Rxoutcome™ (Core Compms) To Develop Curricular Integration Content Mapping, Siu Fun Wong, Jason Yamaki

Pharmacy Faculty Posters and Presentations

The establishment of curricular integration requires intricate and elaborate planning of the course content. This education development model outlines the use of an electronic learning management system, RxOutcome™, to develop a comprehensive course content mapping and tracking system to monitor and manage the development and delivery of the didactic curriculum at CUSP.

Applying The Pharmacists’ Patient Care Process To Immunization Services: A Resource Guide For Pharmacists, Albert Bach, Jeff Goad, Mitchel Rothholz, Brian Wall, Anne Burns, Liza Chapman, Jean-Venable “Kelly” R. Goode, Sheila Seed, Rebecca Snead

Pharmacy Faculty Articles and Research

"This guidance document has been written and formatted to align comprehensive components of a pharmacy-based immunization patient encounter Collect Assess Plan Implement Follow-Up 6 American Pharmacists Association and recommendations from the National Vaccine Advisory Committee (NVAC) the Standards for Adult Immunization Practice with the original framework of the PPCP.5 The colored columns to the right throughout this document are the PPCP steps as they have been published by JCPP, and the main document text describes how to integrate each PPCP step into immunization services."

Compliance To The Consort Statement On Participant Flow Diagrams In Infectious Disease Randomized Clinical Trials, Onyeka P. Godwin, Brandon Dyson, Paul S. Lee, Soon Park, Euni Lee

Pharmacy Faculty Articles and Research

Background: The Consolidated Standard of Reporting Trials (CONSORT) Guidelines were developed to support adequate reporting of randomized controlled trials (RCTs).

Method: A systematic review was conducted including RCTs of infectious diseases published in the top general medical and infectious disease journals in 2010. The level of compliance to flow diagram and its association with the CONSORT endorsement by the journals were evaluated.

Results: A total of 67 studies were included in the analysis and a half of the studies were HIV/AIDS RCTs. About 78% of the studies included the flow diagram and 66% of the studies described …

Drug-Induced Cardiotoxicity Of Oncological Agents: Monitoring Parameters, Prevention, And Future Chemotherapy, Sarah Nguyen, Mary Nguyen, Laura Tsu

Pharmacy Faculty Articles and Research

The goal of this article is to educate pharmacists of the impact of cardiotoxicity on chemotherapy regimens including key cancer agents, monitoring parameters, prevention, and the future of chemotherapy.

Formulation And In Vitro Evaluation Of Niacin-Loaded Nanoparticles To Reduce Prostaglandin Mediated Vasodilatory Flushing, Dustin L. Cooper, Jennifer A. Carmical, Peter C. Panus, Sam Harirforoosh

Pharmacy Faculty Articles and Research

OBJECTIVE: Niacin, activating G-protein coupled receptor (GPR) 109A, stimulates release of vasodilatory prostaglandins (PGs) such as PGE2 which can elicit niacin-associated flushing side effects. Poly-lactic-co-glycolic acid (PLGA) and poly-lactic acid (PLA) are used in nanoparticle (NP) drug delivery to reduce adverse effects and modulate drug release. Our study evaluated the in vitro effects of niacin-loaded PLGA or PLA-NPs on PGE2 expression in whole human blood as a model for niacin-induced flushing.

MATERIALS AND METHODS: NPs were formulated using a solvent evaporation process and characterized by size, polydispersity, zeta potential, drug entrapment, morphology, and drug release. NP in vitro …

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 …

Stribild: A Review Of Component Characteristics And Combination Drug Efficacy, Derek E. Murrell, Jonathan P. Moorman, Sam Harirforoosh

Pharmacy Faculty Articles and Research

BACKGROUND: Numerous methods have been devised to combat human immunodeficiency virus (HIV) replication and disease progression. Composed of an integrase strand transfer inhibitor, a pharmacoenhancer, and two reverse transcriptase inhibitors, Stribild is a relatively new combination HIV drug formulated for once-a-day dosing.

METHODS: Relevant information, original research articles and reviews, were gathered primarily through the use of the PubMed database. The search was conducted without date restrictions in order to collect both historical and recent information concerning HIV, individual drugs, and combinations for a thorough overview.

RESULTS: Stribild, when taken with food, provides therapeutic drug concentrations as …

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 …

The Effect Of Δ9-Tetrahydrocannabinol, Cannabidiol, Menthol And Propofol On 5-Hydroxytryptamine Yype 3 Receptors--A Computational Approach, Andreas C. Schilbach, Tatiana Prytkova, Keun-Hang Susan Yang

Mathematics, Physics, and Computer Science Faculty Articles and Research

This study investigates the function of 5-HT type 3 (5- HT3) receptors using a computational approach.

A Pharmacist’S Role In The Prevention And Management Of Perioperative Atrial Fibrillation And Flutter, Amanda Harmon, Bethany Smith, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE has been developed to educate pharmacists about recently published guidelines for perioperative atrial fibrillation and flutter management and prevention, and discuss the role a pharmacist can have in the care of these patients.

Comparing The 2013 Acc/Aha & 2014 Nla Dyslipidemia Guidelines And Their Impact On Clinical Decision Making, Alexander Forbes, Kevin Grimes, Jocelyn York, Laura Tsu

Pharmacy Faculty Articles and Research

This home-study CPE activity has been developed to educate pharmacists on the similarities and differences between the 2014 NLA Recommendations for Dyslipidemia Management and the 2013 ACC/AHA Guidelines for Treatment of Blood Cholesterol.

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 …

Effect Of Formulation Variables On Preparation Of Celecoxib Loaded Polylactide-Co-Glycolide Nanoparticles, Dustin L. Cooper, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Polymer based nanoparticle formulations have been shown to increase drug bioavailability and/or reduce drug adverse effects. Nonsteroidal anti-inflammatory drugs (e.g. celecoxib) reduce prostaglandin synthesis and cause side effects such as gastrointestinal and renal complications. The aim of this study was to formulate celecoxib entrapped poly lactide-co-glycolide based nanoparticles through a solvent evaporation process using didodecyldimethylammonium bromide or poly vinyl alcohol as stabilizer. Nanoparticles were characterized for zeta potential, particle size, entrapment efficiency, and morphology. Effects of stabilizer concentration (0.1, 0.25, 0.5, and 1% w/v), drug amount (5, 10, 15, and 20 mg), and emulsifier (lecithin) on nanoparticle characterization were examined …

Nucleoside Reverse Transcriptase Inhibitors Possess Intrinsic Anti-Inflammatory Activity, Benjamin J. Fowler, Bradley D. Gelfand, Younghee Kim, Nagaraj Kerur, Valeria Tarallo, Yoshio Hirano, Shoba Amarnath, Daniel H. Fowler, Marta Radwan, Mark T. Young, Keir Pittman, Paul Kubes, Hitesh Agarwal, Keykavous Parang, David R. Hinton, Ana Bastos-Carvalho, Shengjian Li, Testuhiro Yasuma, Takeshi Mizutani, Reo Yasuma, Charles Wright, Jayakrishna Ambati

Pharmacy Faculty Articles and Research

Nucleoside reverse transcriptase inhibitors (NRTIs) are mainstay therapeutics for HIV that block retrovirus replication. Alu (an endogenous retroelement that also requires reverse transcriptase for its life cycle)–derived RNAs activate P2X7 and the NLRP3 inflammasome to cause cell death of the retinal pigment epithelium in geographic atrophy, a type of age-related macular degeneration. We found that NRTIs inhibit P2X7-mediated NLRP3 inflammasome activation independent of reverse transcriptase inhibition. Multiple approved and clinically relevant NRTIs prevented caspase-1 activation, the effector of the NLRP3 inflammasome, induced by Alu RNA. NRTIs were efficacious in mouse models of geographic atrophy, choroidal neovascularization, graft-versus-host disease, and sterile …

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 …

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 …

Transgender Patients: Communication Pearls For Pharmacists, Emmanuelle Schwartzmann, Thomas Kleyn

Pharmacy Faculty Articles and Research

Understanding the unique communication needs of transgender patients is critical in order to minimize health disparities and patient barriers to care. As this population gains more social and political acceptance, pharmacists must be equipped to provide medical acceptance through knowledge of how to appropriately communicate with these patients through active listening, empathy, and sensitivity, while maintaining a high standard of respect and privacy.

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 …

Structural Similarity Between Β3-Peptides Synthesized From Β3-Homo-Amino Acids Or L-Aspartic Acid Monomers, Sahar Ahmed, Tara Sprules, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Formation of stable secondary structures by oligomers that mimic natural peptides is a key asset for enhanced biological response. Here we show that oligomeric β³‐hexapeptides synthesized from l‐aspartic acid monomers (β³‐peptides 1, 5a, and 6) or homologated β³‐amino acids (β³‐peptide 2), fold into similar stable 14‐helical secondary structures in solution, except that the former form right‐handed 14‐helix and the later form left‐handed 14‐helix. β³‐Peptides from l‐Asp monomers contain an additional amide bond in the side chains that provides opportunities for more hydrogen bonding. However, based on the …