Pharmacy and Pharmaceutical Sciences Commons^™

Eecp Improves Markers Of Functional Capacity Regardless Of Underlying Ranolazine Therapy, Sanaz Ziad, Jamil Malik, Obinna Isiguzo, Lang Xu, Leqi Chen, Annette Cox, Sachin Shah

School of Pharmacy Faculty Articles

OBJECTIVE: Enhanced external counterpulsation (EECP) and ranolazine are approved treatments for patients with chronic stable angina by the United States Food and Drug Administration (FDA). Whether EECP offers clinical benefits regardless of underlying ranolazine therapy needs further investigation.

METHODS: This was a retrospective evaluation of patients referred to a specialized EECP center. Patients having data on 6-Minute Walk Distance (6MWD) or Duke Activity Status Index (DASI) were categorized into two groups (EECP with ranolazine or EECP only). The primary endpoints were change in 6MWD and DASI before and after a full course of EECP within each of the two groups. …

Modulation Of K V 7 Channel Deactivation By Pi(4,5)P 2, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The activity of K_V7 channels critically contributes to the regulation of cellular electrical excitability in many cell types. In the central nervous system, the heteromeric K_V7.2/K_V7.3 channel is thought to be the chief molecular entity giving rise to M-currents. These K⁺-currents as so called because they are inhibited by the activation of Gq protein-coupled muscarinic receptors. In general, activation of Gq protein-coupled receptors (GqPCRs) decreases the concentration of the phosphoinositide PI(4,5)P₂ which is required for K_V7 channel activity. It has been recently reported that the deactivation rate of K …

Multicellular Spheroids Of A549 And A549-Irfp As An In Vitro Model Of Lung Cancer, Xinyu Pei

University of the Pacific Theses and Dissertations

Lung cancer is the second most common cancer in both men and women around the world, and 85% of it is non-small cell lung cancer (NSCLC). It is estimated that in 2020, there will be 228,820 cases of lung cancer and 135,720 deaths from lung (American Cancer Society, 2020). The prognosis of lung cancer is poor (

Traditionally, the most commonly used in vitro method for screening therapeutic drugs is monolayer cell cultures, which are reproducible, convenient and of low cost. However, monolayer cell culture models are unable to reproduce many properties of in vivo solid tumors such as the …

Effects Of Chronic Energy Drink Consumption On Cardiometabolic Endpoints, May Chen

University of the Pacific Theses and Dissertations

Background: Since its introduction in the early 2000s, energy drinks have become increasingly popular among an extensive range of consumers, including adolescents and young adults. Currently, the United States Food and Drug Administration (FDA) does not regulate the formulation of energy drinks, which may vary widely in the amounts of caffeine and sugar, as well as various types of supplements. Recent reports of severe and fatal adverse effects related to energy drinks have led to growing concerns on the safety of energy drink consumption.

Objective: This study aimed to investigate the effects of chronic daily consumption of energy drinks on …

Regulation Of Intracellular Aryl Hydrocarbon Receptor Protein Levels, Jinyun Chen

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor (AHR) is a ligand-activated signaling molecule which controls tumor growth and metastasis, T cell differentiation, and liver development. Expression levels of this receptor protein are sensitive to the cellular p23 protein levels in immortalized cancer cell lines. As little as 30% reduction of the p23 cellular content can suppress the AHR function. Here we reported that down-regulation of the p23 protein content in normal, untransformed human bronchial/tracheal epithelial cells to 48% of its content also suppresses the AHR protein levels to 54% of its content. This p23-mediated suppression of AHR is responsible for the repression of …

Midazole-Based Ph-Sensitive Convertible Liposomes For Anticancer Drug Delivery, Ruiqi Huang

University of the Pacific Theses and Dissertations

Solid tumors possess biological features that are different from those in healthy tissues, which provides opportunities of anticancer treatment by nanomedicines. Due to the presence of the fenestrated tumor vasculatures, nanomedicines can selectively accumulate in tumor tissues by the enhanced permeability and retention (EPR) effect. The acidic pH in tumor interstitium (pH 6.0-7.0) also provides a promising mechanism to trigger the nanomedicines to promote the cellular uptake of cargo drugs. The previously reported stealth liposomes coated with PEG are known to accumulate in tumors owing to their prolonged circulation time. The PEG coating on liposomes can hinder serum protein adsorption …

Role Of Polymer Physicochemical Properties On In Vitro Mucoadhesion, Qing Zhang

University of the Pacific Theses and Dissertations

Polymers with mucoadhesive properties are universally used in the development of mucoadhesive drug delivery system. Their physicochemical properties as well as the mechanisms related to their adhesive actions draw great attention for the modification of mucoadhesive properties.

In this study, relationships between physicochemical properties of hydroxypropyl methylcellulose (HPMC) compacts and mucoadhesive performance were investigated. Different commercial grades of HPMC (K3, E3, E5, E50, K4M, E4M and K15M) were prepared into compacts, and their surface hydrophilicity and hydration behavior were characterized. The in vitro mucoadhesive performance was determined by the tension strength between the compacts and different regions of mucous membrane …

Development Of Lipid-Based Nano Formulations Of Miriplatin Against Lung Cancer, Zizhao Xu

University of the Pacific Theses and Dissertations

Cancer is the second leading cause of death and is responsible for approximately 9.6 million deaths worldwide in 2018. Among all oncological diseases, lung cancer claims the highest mortality (male: 23.5%; female: 22%) and the second most new cases (male: 13%; female: 12%) in the US. Approximately 40% of newly diagnosed lung cancer patients are in the advanced stage IV, for which platinum-based chemotherapy is the first-line treatment, either by itself or in combination with surgery or radiotherapy.

Cisplatin, the first-generation platinum-based anticancer chemotherapeutic agent, has the highest potency against lung cancer but carries many severe adverse effects. Cisplatin also …

Elephant And Anchors ‒ Photoelectron Photoion Coincidence Spectroscopy Of Small Oxygenated Molecules, Apeter Weidner

University of the Pacific Theses and Dissertations

The dissociative photoionization reactions of two small, oxygenated organics, namely 1,3-dioxolane and methyl vinyl ketone, were studied by photoelectron photoion coincidence (PEPICO) spectroscopy. Experiments involving 1,3-dioxolane were carried out in the photon energy range of 9.5‒13.5 eV. The statistical thermodynamics model shows that a total of six dissociation channels are involved in the formation of three fragment ions, namely C3H5O2+ (m/z 73), C2H5O+ (m/z 45) and C2H4O+ (m/z 44), with two channels contributing to the formation of each. By comparing the results of ab initio quantum chemical calculations to the experimentally derived appearance energies of the fragment ions, the most …

Studies On The Size And Non-Planarity Of Aromatic Stacking Moiety On Conformation Selectivity And Thermal Stabilization Of G-Quadruplexes, Mandeep Singh

University of the Pacific Theses and Dissertations

Targeting DNA has the advantage over proteins for cancer remediation because of the fewer copies of the ligands required for the desired therapeutic effect. Traditionally, covalent DNA binders like alkylating agents have been used to induce genetic instability through the formation of DNA lesions and strand breaks, leading to cellular apoptosis. The primary drawback of this treatment is the non-specific binding that affects both cancerous and non-cancerous cells. G-quadruplexes are the DNA secondary structures that are present in abundance near the promoter regions of the oncogenes and are involved in the regulation of their activities. A ligand-mediated stabilization of G-quadruplexes …

Impact Of High Volume Energy Drink Consumption On Electrocardiographic And Blood Pressure Parameters: A Randomized Trial, Sachin A. Shah, Andy H. Szeto, Raechel Farewell, Allen Shek, Dorothy Fan, Kathy N. Quach, Mouchumi Bhattacharyya, Jasmine Elmiari, Winny Chan, Kate O'Dell, Nancy Nguyen, Tracey J. Mcgaughey, Javed M. Nasir, Sanjay Kaul

School of Pharmacy Faculty Articles

Background Energy drinks have been linked to an increase in emergency room visits and deaths. We aim to determine the impact of energy drinks on electrocardiographic and hemodynamic parameters in young healthy volunteers. Methods and Results A randomized, double-masked, placebo-controlled, crossover study was conducted in healthy volunteers. Participants consumed 32 oz of either energy drink A, energy drink B, or placebo within 60 minutes on 3 study days with a 6-day washout period in between. The primary end point of QT c interval and secondary end points of QT interval, PR interval, QRS duration, heart rate, and brachial and central …

A Rational Approach For Creating Peptides Mimicking Antibody Binding, Sameer Sachdeva, Hyun Joo, Jerry Tsai, Bhaskara Jasti, Xiaoling Li

School of Pharmacy Faculty Articles

This study reports a novel method to design peptides that mimic antibody binding. Using the Knob-Socket model for protein-protein interaction, the interaction surface between Cetuximab and EGFR was mapped. EGFR binding peptides were designed based on geometry and the probability of the mapped knob-sockets pairs. Designed peptides were synthesized and then characterized for binding specificity, affinity, cytotoxicity of drug-peptide conjugate and inhibition of phosphorylation. In cell culture studies, designed peptides specifically bind and internalize to EGFR overexpressing cells with three to four-fold higher uptake compared to control cells that do not overexpress EGFR. The designed peptide, Pep11, bound to EGFR …

The Role Of Sex Hormones On Monocarboxylate Transporter Expression In Tissues Related To Drug Disposition, Jieyun Cao

University of the Pacific Theses and Dissertations

Proton- and sodium-dependent monocarboxylate transporters (MCTs (SLC16A) and SMCTs (SLC5A)) transport monocarboxylates such as ketone bodies, lactate and pyruvate, as well as drugs such as gamma-hydroxybutyric acid. CD147 acts as an ancillary protein for MCT1 and MCT4, and is involved in membrane trafficking. Previously, it has been shown that MCT expression changes under different sex hormone conditions in skeletal muscle and Sertoli cells. However, it is unknown if MCTs, SMCTs or CD147 demonstrate sex differences in tissues where they play an important role in drug disposition. Monocarboxylate transporter substrates GHB and valproic acid have demonstrated sex differences in pharmacokinetic profiles. …

I3: Isomerization Of Isomer Ions, Krisztián Gabor Torma

University of the Pacific Theses and Dissertations

Photoelectron Photoion Coincidence (PEPICO) spectroscopy is a robust tool for elucidating complex unimolecular dissociation mechanisms and for determining thermochemical and kinetic data of gas-phase ion dissociations with high accuracy. In this work, the dissociative photoionization of two sets of isomeric systems were analyzed with PEPICO: 1) C7H7+ ions of toluene (Tol) and 1,3,5-cycloheptatriene (CHT), and 2) two butyl alcohol isomers, 1-butanol and isobutanol. Threshold dissociative photoionization data on these four molecules of interest were collected on the imaging PEPICO apparatus at the VUV beamline of the Swiss Light Source. Data analysis was aided by ab initio calculations and Rice-Ramsperger-Kassel-Marcus (RRKM) …

Intrapulmonary Inoculation Of Multicellular Tumor Spheroids To Construct An Orthotopic Lung Cancer Xenograft Model That Mimics Four Clinical Stages Of Non-Small Cell Lung Cancer, Yingbo Huang

University of the Pacific Theses and Dissertations

Lung cancer leads in mortality among all types of cancer in the US and Non-small cell lung cancer (NSCLC) is the major type of lung cancer. Immuno-compromised mice bearing xenografts of human lung cancer cells represent the most common animal models for studying lung cancer biology and for evaluating potential anticancer agents. However, orthotopic lung cancer models based on intrapulmonary injection of suspended cancer cells feature premature leakage of the cancer cells to both sides of the lung within five days, which generates a quick artifact of metastasis and thus belies the development and progression of lung cancer as seen …

Developmental Expression Of Monocarboxylate Transporter 1 And 4 In Rat Liver, Michael Ng, Justin Louie, Jieyun Cao, Melanie A. Felmlee

School of Pharmacy Faculty Articles

PURPOSE: Monocarboxylate transporters (MCT) are proton-coupled integral membrane proteins that control the influx and efflux of endogenous monocarboxylates such as lactate, acetate and pyruvate. They also transport and mediate the clearance of drugs such as valproate and gamma-hydroxybutyrate. CD147 functions as ancillary protein that chaperones MCT1 and MCT4 to the cell membrane. There is limited data on the maturation of MCT and CD147 expression in tissues related to drug distribution and clearance. The objective of the present study was to quantify hepatic MCT1, MCT4, and CD147 mRNA, whole cell and membrane protein expression from birth to sexual maturity.

METHODS: Liver …

Hiv Viral Rebound Due To A Possible Drug-Drug Interaction Between Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide And Calcium-Containing Products: Report Of 2 Cases, S. Lena Kang-Birken, Dena El-Sayed, John Prichard

School of Pharmacy Faculty Articles

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is a potent fixed-dose, once-daily regimen for HIV-1 treatment and has rare emergence of drug resistance. We report a potential drug-drug interaction in 2 female patients both receiving treatment for HIV and cerebral toxoplasmosis: one case between E/C/F/TAF with calcium carbonate and a second case involving leucovorin as calcium salt. Both cases resulted in rise in HIV RNA levels and emergence of M184 V mutation and resistance to elvitegravir and raltegravir. To the best of our knowledge, these 2 cases are the first reports of rapid emergence of mutation from coadministration of E/C/F/TAF and calcium.

Responsible, Safe, And Effective Use Of Biologics In The Management Of Low Back Pain: American Society Of Interventional Pain Physicians (Asipp) Guidelines, Annu Navani, Laxmaiah Manchikanti, Sheri L. Albers, Richard E. Latchaw, Jaya Sanapati, Alan David Kaye, Sairam Atluri, Sheldon Jordan, Ashim Gupta, David Cedeno, Alejandro Vallejo, Bert Fellows, Nebojsa Nick Knezevic, Miguel Pappolla, Sudhir Diwan, Andrea M. Trescot, Amol Soin, Adam M. Kaye, Steve M. Aydin, Aaron K. Calodney, Kenneth D. Candido, Sanjay Bakshi, Ramsin M. Benyamin, Ricardo Vallejo, Art Watanabe, Douglas Beall, Todd P. Stitik, Patrick M. Foye, Erik M. Helander, Joshua A. Hirsch

School of Pharmacy Faculty Articles

BACKGROUND: Regenerative medicine is a medical subspecialty that seeks to recruit and enhance the body's own inherent healing armamentarium in the treatment of patient pathology. This therapy's intention is to assist in the repair, and to potentially replace or restore damaged tissue through the use of autologous or allogenic biologics. This field is rising like a Phoenix from the ashes of underperforming conventional therapy midst the hopes and high expectations of patients and medical personnel alike. But, because this is a relatively new area of medicine that has yet to substantiate its outcomes, care must be taken in its public …

Mechanisms Underlying Neuroprotection By The Nsaid Mefenamic Acid In An Experimental Model Of Stroke, Parto S. Khansari, Robert F. Halliwell

School of Pharmacy Faculty Articles

Stroke is a devastating neurological event with limited treatment opportunities. Recent advances in understanding the underlying pathogenesis of cerebral ischemia support the involvement of multiple biochemical pathways in the development of the ischemic damage. Fenamates are classical non-steroidal anti-inflammatory drugs but they are also highly subunit-selective modulators of GABAA receptors, activators of IKS potassium channels and antagonists of non-selective cation channels and the NLRP3 inflammosome. In the present study we investigated the effect of mefenamic acid (MFA) in a rodent model of ischemic stroke and then addressed the underlying pharmacological mechanisms in vitro for its actions in vivo. The efficacy …

Developing A Rational Peptide Ligand Design Method Using Cd13 As A Prototype Target Receptor, Md Zahir Uddin

University of the Pacific Theses and Dissertations

Structure based computational peptide design methods have gained significant interest in recent years with the availability of structural insights of protein-protein interactions obtained from the crystal structures. Most of these approaches design new peptide ligands by connecting the crucial amino acid residues from the protein interface and are generally not based on any predicted receptor-ligand interaction. In this work, a peptide design method based on the Knob-Socket model was used to identify the specific ligand residues packing into the receptor interface. This method enables rational peptide ligand design by predicting amino acid residues that will fit best at the binding …

Fliposomes With A Ph-Sensitive Conformational Switch For Anticancer Drug Delivery Against Triple Negative Breast Cancer, Yifan Lu

University of the Pacific Theses and Dissertations

Cancer is the second leading cause of death in the US and worldwide, accounting for 16% of deaths worldwide in 2015. Of more than 100 types of cancers affecting humans, breast cancer is the most common cancer among women and is the second leading cause of death in women. Triple negative breast cancer (TNBC) is a subtype of breast carcinomas defined by the lack of the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2 /neu). The prognosis and survival of TNBC patients remains the poor due to the lack of effective targeted therapy. …

Synthesis And Conformational Studies Of Various Amides, Marcos Beltran-Sanchez

University of the Pacific Theses and Dissertations

In the past, aminocyclohexanol rings have been successfully utilized as pH-triggered molecular switches in various trans-2-aminocyclohexanol derivatives. By changing the groups on the amine nitrogen, these models provided a wide pH range in which a switch can occur. The pH-induced switch of conformation was monitored by 1H-NMR spectroscopy. The models were also incorporated into the bilayer membrane of liposome structures and tested for their ability to disrupt their membrane upon their conformational flip induced by a decrease in pH.

In this work, the amide bond has been studied as a molecular switch and various amide derivatives have been tested for …

The Role Of Aryl Hydrocarbon Receptor (Ahr) In Drug-Drug Interaction And The Expression Of Ahr In Pichia Pastoris, Yujuan Zheng

University of the Pacific Theses and Dissertations

The aryl hydrocarbon receptor is a ligand-activated transcription factor that is involved in many important functions in the body. To study the role and function of AHR, an abundant amount of in vitro expressed and purified protein is needed. A baculovirus insect expression system is commonly employed to express AHR, however, there are several drawbacks with this method, such as mutation potential and high cost. A better in overexpression system is needed and we hypothesize that Pichia pastoris, a yeast expression system, could stably express AHR and ARNT (aryl hydrocarbon receptor nuclear translocator) in sufficient amount with reasonable cost. Codon …

The Potency Of Ag10 In Stabilizing Transthyretin Is Driven By Interactions Mimicking The Disease-Suppressing T119m Variant, Dengpan Liang

University of the Pacific Theses and Dissertations

Transthyretin (TTR) amyloid cardiomyopathy (ATTR-CM) is a fatal disease with no available disease-modifying therapies. While destabilizing TTR mutations increase the risk of developing ATTR-CM, the naturally occurring Thr119Met (T119M) variant stabilizes TTR and prevent disease. The two Serine 117 and Serine 117’ (S117/S117’) side chain hydroxyl groups of monomers A and B in T119M variant TTR form direct hydrogen bonds with each other. AG10 is an orally available, small molecule TTR stabilizer in Phase 3 clinical development for ATTR-CM. Structural features that infer high potency of AG10 for stabilizing TTR remains incompletely characterized.

In order to investigate the contribution of …

Development And Characterization Of Ldv Peptide Targeted Nanocarriers For Paclitaxel Delivery: A Comparative Study Of Micelles, Liposomes And Solid Lipid Nanoparticles, Poonam Dattani

University of the Pacific Theses and Dissertations

Nanocarriers have been established as delivery vehicles to target cancer tumors. However, premature drug leakage is one of the major reasons for inefficient drug delivery of nanocarriers to the tumor. Drug diffusion out of the nanocarriers or destabilization of drug loaded nanocarriers by physiological interactions with blood cells, serum proteins, and cell membranes upon systemic administration contribute to premature drug release. In this study, targeted micelles, liposomes and solid lipid nanoparticles (SLNs) of similar composition were prepared and characterized to compare physicochemical characteristics, in vitro stability, in vitro release rates in release media and in vivo performance. Peptide Amphiphiles (PAs) …

Lipid-Coated Magnesium Phosphate Nanoparticles For Intrapulmonary Protein Delivery In Mice, Mallika Vadlamudi

University of the Pacific Theses and Dissertations

Proteins are a diverse category of biomolecules with great therapeutic potential. Intracellular delivery of proteins can augment the deficient activities of dysfunctional or poorly expressed innate proteins and therefore represents a promising strategy to treat the associated diseases. One major barrier to intracellular protein delivery is the translocation of the protein across the cellular membrane. Endocytosis provides an important pathway for protein nanocarriers to enter cells across the plasma membrane. However, the cargo protein must then promptly escape from the endosomes to avoid degradation in the lysosome and to exert its cellular function.

Previously, we reported a cationic lipid-coated magnesium …

The Effect Of Energy Drinks On Cardiovascular Variables: A Randomized Controlled Trial, Cynthia Lee

University of the Pacific Theses and Dissertations

Many studies have investigated the effects of energy drinks on cardiovascular parameters. These studies were typically conducted with high volume (32 ounces) energy drinks and have demonstrated association with QT prolongation and blood pressure elevation after consumption. Currently, there is inconclusive evidence with lower volume energy drinks. This study intends to evaluate the effects of the largest commercially available energy drink can (24 ounces) in the United States on cardiovascular parameters compared with placebo arm. A randomized, double-blinded, placebo-controlled, crossover trial was conducted over 2 separate days with a minimum of 6-day wash out period. Healthy volunteers between the age …

Development Of A New Class Of Ligand-Targeted Chemotherapeutics With Enhanced Safety And Efficacy Profile, Arindom Pal

University of the Pacific Theses and Dissertations

The hydrophobicity of many chemotherapeutic agents usually results in their nonselective passive distribution into healthy cells and organs causing collateral toxicity. Ligand-targeted drugs (LTDs) are a promising class of targeted anticancer agents. The hydrophilicity of the targeting ligands in LTDs limits its nonselective passive tissue distribution and toxicity to healthy cells. In addition, the small size of LTDs allows for better tumor penetration, especially in the case of solid tumors. However, the short circulation half-life of LTDs, due to their hydrophilicity and small size, remains a significant challenge for achieving their full therapeutic potential. Therefore, extending the circulation half-life of …

Investigating The Effect Of Rutaecarpine On The Benzo[A]Pyrene-Induced Dna Damage In Vitro, You Li

University of the Pacific Theses and Dissertations

Benzo[a]pyrene (BaP), is one of the most potent mutagens and carcinogens known. It requires metabolic activation through cytochrome P450 (CYP)1A1 to yield the ultimate carcinogenic metabolite, benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE). BPDE can bind to DNA and form predominantly covalent (+) trans adducts at the N2 position of guanine causing DNA damage. Rutaecarpine (RTC) is an herbal medicine that has been used to treat several diseases such as headache, hypertension, gastrointestinal disorders, amenorrhea, and anti-inflammation. It has also been reported as a potent inducer of CYP enzymes, including CYP1A1, and CYP1A2. The mechanisms underlying up-regulation of CYP1A1 by RTC is dependent on aryl …

A Cost Control Model For Inpatient Medications Among Adults With Mental And Behavioral Health Disorders, Huanan Li

University of the Pacific Theses and Dissertations

Pharmaceutical expenditures are an important part of the entire hospital operating budget, and inpatient pharmaceuticals denote one of the highest costs in hospital care. Predictions for medication budgets based on the types of patients have been largely undertaken in medical hospitals and not psychiatric facilities. According to several previous studies, gender, age, diagnosis, comorbidity and length of stay (LOS) affect the general inpatient treatment expenditures. However, whether or not the impact of these factors differs in psychiatric hospitals remains to be investigated. To that end, the current study examines medication costs for mental and behavioral health disorder as well as …