Pharmacy and Pharmaceutical Sciences Commons^™

Age Adjusted Comorbidity Risk Index Does Not Predict Outcomes In An Autologous Hematopoietic Stem Cell Transplant Population, Dylan Barth, Michael Singleton, Gregory Monohan, Brian Mcclune, Val Adams

Pharmacy Practice and Science Faculty Publications

The hematopoietic comorbidity risk index (HCT-CI) is a pre-transplant risk assessment tool used to prognosticate morbidity and mortality of patients undergoing allogeneic hematopoietic stem cell transplantation. Recently, the HCT-CI was updated to include an age component (HCT-CI-age). Although other studies have validated this tool in allogeneic stem cell transplant recipients, it has never been studied in an autologous transplant patient population. We retrospectively reviewed 181 patients who underwent their first autologous hematopoietic stem cell transplant. We aimed (1) to assess whether an HCT-CI score of 3 or greater is associated with greater mean transplant hospital days, greater total hospital days, …

Variants Associated With Bedaquiline (Bdq) Resistance Identified In Rv0678 And Efflux Pump Genes In Mycobacterium Tuberculosis Isolates From Bdq Naïve Tb Patients In Pakistan, Dania Khalid Saeed, Sadia Shakoor, Safina Abdul Razzak, Zahra Hasan, Saba Faraz Sabzwari, Zahida Azizullah, Akber Kanji, Asghar Nasir, Samreen Shafiq, Najia Karim Ghanchi, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: Mutations in the Rv0678, pepQ and atpE genes of Mycobacterium tuberculosis (MTB) have been reported to be associated with reduced antimycobacterial susceptibility to bedaquiline (BDQ). Resistance conferring mutations in treatment naïve MTB strains is likely to have implications for BDQ based new drug regimen that aim to shorten treatment duration. We therefore investigated the genetic basis of resistance to BDQ in MTB clinical isolates from BDQ naïve TB patients from Pakistan. In addition, mutations in genes associated with efflux pumps were investigated as an alternate mechanism of resistance.
Methods: Based on convenience sampling, we studied 48 MTB clinical isolates …

The Beneficial Effects Of Ferula Asafoetida Oleo-Gum Resin In Gastrointestinal Disorders, Mohaddese Mahboubi

Bulletin of Faculty of Pharmacy Cairo University

Ferula asafoetida is a plant from Umbelliferae Family, which its gum is traditionally used to treat the gastrointestinal disorders (parasite, bloating, digestion, cancer). According to its traditional applications, the subject of this review was to evaluate the efficacy of F. asafoetida in management of different gastrointestinal disorders in modern medicine. For this purpose, the scientific resources (PubMed, Web of Science, Scopus, Google Scholar, SpringerLink, SciFinder, ACS Publications, and Wiley), traditional books, and thesis were investigated by the word of Ferula asafoetida, Hing, and gastrointestinal tract and the results were evaluated. There was one clinical trial on the efficacy of F. …

Integration Of Liquid Biopsy And Pharmacogenomics For Precision Therapy Of Egfr Mutant And Resistant Lung Cancers, Jill M. Kolesar, Spencer Peh, Levin Thomas, Gayathri Baburaj, Nayonika Mukherjee, Raveena Kantamneni, Shirley Lewis, Ananth Pai, Karthik S. Udupa, Naveena Kumar An, Vivek M. Rangnekar, Mahadev Rao

Pharmacy Practice and Science Faculty Publications

The advent of molecular profiling has revolutionized the treatment of lung cancer by comprehensively delineating the genomic landscape of the epidermal growth factor receptor (EGFR) gene. Drug resistance caused by EGFR mutations and genetic polymorphisms of drug metabolizing enzymes and transporters impedes effective treatment of EGFR mutant and resistant lung cancer. This review appraises current literature, opportunities, and challenges associated with liquid biopsy and pharmacogenomic (PGx) testing as precision therapy tools in the management of EGFR mutant and resistant lung cancers. Liquid biopsy could play a potential role in selection of precise tyrosine kinase inhibitor (TKI) therapies during different phases …

Editorial: Anticancer Potential Of Artemisia Annua, Jill M. Kolesar, Peter H. Seeberger

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Risk Of Opioid Overdose Associated With Concomitant Use Of Oxycodone And Selective Serotonin Reuptake Inhibitors, Ismaeel Yunusa, Joshua J. Gagne, Kazuki Yoshida, Katsiaryna Bykov

Faculty Publications

Importance Some selective serotonin reuptake inhibitors (SSRIs) inhibit the enzymes responsible for the metabolism of oxycodone, a potent prescription opioid. The clinical consequences of this interaction on the risk of opioid overdose have not been elucidated.

Objective To compare opioid overdose rates in patients initiating oxycodone while taking SSRIs that are potent inhibitors of the cytochrome-P450 2D6 enzyme (CYP2D6) vs SSRIs that are not.

Design, Setting, and Participants This cohort study included adults who initiated oxycodone while receiving SSRI therapy between 2000 and 2020 whose data were included in 3 US health insurance databases.

Exposures Use of SSRIs that strongly …

Patients With Obesity And A History Of Metformin Treatment Have Lower Influenza Mortality: A Retrospective Cohort Study, Tammy H. Cummings, Joseph Magagnoli Ph.D., Ms, James W. Hardin, S. Scott Sutton

Faculty Publications

Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of …

Sex Differences In Kappa Opioid Receptor Agonist Mediated Attenuation Of Chemotherapy-Induced Neuropathic Pain In Mice, Kelly F. Paton, Dan Luo, Anne C. La Flamme, Thomas E. Prisinzano, Bronwyn M. Kivell

Pharmaceutical Sciences Faculty Publications

Chemotherapy-induced neuropathic pain is a common side effect for cancer patients which has limited effective treatment options. Kappa opioid receptor (KOR) agonists are a promising alternative to currently available opioid drugs due to their low abuse potential. In the current study, we have investigated the effects of Salvinorin A (SalA) analogues, 16-Ethynyl SalA, 16-Bromo SalA and ethyoxymethyl ether (EOM) SalB, and in a preclinical model of paclitaxel-induced neuropathic pain in male and female C57BL/6J mice. Using an acute dose-response procedure, we showed that compared to morphine, 16-Ethynyl SalA was more potent at reducing mechanical allodynia; and SalA, 16-Ethynyl SalA, and …

Blood-Brain Barrier Disruption Mediated By Ffa1 Receptor-Evidence Using Miniscope, Kristen L Lindenau, Jeffrey L Barr, Christopher R Higgins, Kevin T Sporici, Eugen Brailoiu, G Cristina Brailoiu

College of Pharmacy Faculty Papers

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), obtained from diet and dietary supplements, have been tested in clinical trials for the prevention or treatment of several diseases. n-3 PUFAs exert their effects by activation of free fatty acid (FFA) receptors. FFA1 receptor, expressed in the pancreas and brain, is activated by medium- to long-chain fatty acids. Despite some beneficial effects on cognition, the effects of n-3 PUFAs on the blood-brain barrier (BBB) are not clearly understood. We examined the effects of FFA1 activation on BBB permeability in vitro, using rat brain microvascular endothelial cells (RBMVEC), and in vivo, by assessing Evans …

Late-Stage Chemoenzymatic Installation Of Hydroxy-Bearing Allyl Moiety On The Indole Ring Of Tryptophan-Containing Peptides, Nagaraju Mupparapu, Lauren Brewster, Katrina F. Ostrom, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

The late-stage functionalization of indole- and tryptophan-containing compounds with reactive moieties facilitates downstream diversification and leads to changes in their biological properties. Here, the synthesis of two hydroxy-bearing allyl pyrophosphates is described. A chemoenzymatic method is demonstrated which uses a promiscuous indole prenyltransferase enzyme to install a dual reactive hydroxy-bearing allyl moiety directly on the indole ring of tryptophan-containing peptides. This is the first report of late-stage indole modifications with this reactive group.

Ispe-Endorsed Guidance In Using Electronic Health Records For Comparative Effectiveness Research In Covid-19 Opportunities And Trade-Offs, Grammati Sarri, Dimitri Bennett, Thomas P. A. Debray, Anouk Deruaz-Luyet, Montse Soriano Gabarró, Joan A. Largent, Xiaojuan Li, Wei Liu, Jennifer L. Lund, Daniela Claudia Moga, Mugdha Gokhale, Christopher T. Rentsch, Xuerong Wen, Chen Yanover, Yizhou Ye, Huifeng Yun, Andrew R. Zullo, Kueiyu Joshua Lin

Pharmacy Practice and Science Faculty Publications

As the scientific research community along with healthcare professionals and decision makers around the world fight tirelessly against the coronavirus disease 2019 (COVID-19) pandemic, the need for comparative effectiveness research (CER) on preventive and therapeutic interventions for COVID-19 is immense. Randomized controlled trials markedly under-represent the frail and complex patients seen in routine care, and they do not typically have data on long-term treatment effects. The increasing availability of electronic health records (EHRs) for clinical research offers the opportunity to generate timely real-world evidence reflective of routine care for optimal management of COVID-19. However, there are many potential threats to …

Similarly Efficacious Anti-Malarial Drugs Sj733 And Pyronaridine Differ In Their Ability To Remove Circulating Parasites In Mice, Arya Sheelanair, Aleksandra S. Romanczuk, Rosemary A. Aogo, Rohit Nemai Haldar, Lianne I. M. Lansink, Deborah Cromer, Yandira G. Salinas, R. Kiplin Guy, James S. Mccarthy, Miles P. Davenport, Ashraful Haque, David S. Khoury

Pharmaceutical Sciences Faculty Publications

BACKGROUND: Artemisinin-based combination therapy (ACT) has been a mainstay for malaria prevention and treatment. However, emergence of drug resistance has incentivised development of new drugs. Defining the kinetics with which circulating parasitized red blood cells (pRBC) are lost after drug treatment, referred to as the "parasite clearance curve", has been critical for assessing drug efficacy; yet underlying mechanisms remain partly unresolved. The clearance curve may be shaped both by the rate at which drugs kill parasites, and the rate at which drug-affected parasites are removed from circulation.

METHODS: In this context, two anti-malarials, SJ733, and an ACT partner drug, pyronaridine …

Which Pharmacists Are Performing Antimicrobial Stewardship: A National Survey And A Call For Collaborative Efforts, Brandon Dionne, Jamie L. Wagner, Daniel B. Chastain, Meagen Rosenthal

Faculty and Student Publications

Abstract Objectives: To determine how pharmacists with formal antimicrobial stewardship program (ASP) responsibilities prioritize their time and pharmacists without formal antimicrobial stewardship program responsibilities contribute to ASP activities. Design: A nationwide survey. Respondents: Members of the American College of Clinical Pharmacy who subscribe to the following practice and research network e-mail listservs: infectious diseases, adult medicine, cardiology, critical care, hematology-oncology, immunology and transplantation, and pediatrics. Methods: A survey was distributed via listservs. Respondents were asked about their personal and institutional demographics and ASP activities. Results: In total, 245 pharmacists responded: 135 pharmacists with formal antimicrobial stewardship program responsibilities; 110 pharmacists …

A Prospective Cohort Study Of The Clinical Predictors Of Bacteremia In Under-Five Children With Acute Undifferentiated Fever Attending A Secondary Health Facility In Northwestern Nigeria, Taofik Oluwaseun Ogunkunle, Timothy Olanrewaju Adedoyin, Samuel Kolade Ernest, Fatimah Hassan-Hanga, Abdulazeez Imam, Rasaq Olaosebikan, Stephen K Obaro

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: Children with acute febrile illness with no localizing signs often receive antibiotics empirically in most resource-poor settings. However, little is known about the burden of bacteremia in this category of patients, and an appraisal is thus warranted. This will guide clinical practice and promote rational antibiotics use.

Methods: We prospectively followed up 140 under-five children who presented with acute undifferentiated fever at the emergency/outpatient pediatric unit of a secondary healthcare facility. Baseline clinical and laboratory information was obtained and documented in a structured questionnaire. We compared baseline characteristics between participants with bacteremia and those without bacteremia. We further fitted …

“Hiccups” With Covid-19 Management, Yong W. Lee, Jacob Psomiadis, Sarah Akbani, Marvin Lopez-Medal, Aisha Miller

Advances in Clinical Medical Research and Healthcare Delivery

Hiccups, medically referred as singultus, is a condition that results from involuntary contraction of the diaphragm and intercostal muscles. Singultus is usually a self-limiting condition which typically lasts less than 48 hours but in rare cases, can persist greater than 48 hours. This is a case of a 48 year-old male who was prescribed dexamethasone for COVID-19 but developed intractable singultus for two weeks. Patient was unable to tolerate diet due to intractable singultus leading to vomiting. He underwent various non-pharmacological maneuvers and pharmacotherapy without resolution. Dexamethasone- induced hiccups have been reported as an under recognized side effect of dexamethasone. …

The Use Of Advanced Spectral Imaging To Reveal Nanoparticle Identity In Biological Samples, Qamar A. Alshammari, Rajasekharreddy Pala, Ayan K. Barui, Saud O. Alshammari, Andromeda M. Nauli, Nir Katzir, Ashraf M. Mohieldin, Surya M. Nauli

Pharmacy Faculty Articles and Research

Nanoparticles (NPs) have been used in drug delivery therapies, medical diagnostic strategies, and as current Covid-19 vaccine carriers. Many microscope-based imaging systems have been introduced to facilitate detection and visualization of NPs. Unfortunately, none can differentiate the core and the shell of NPs. Spectral imaging has been used to distinguish a drug molecule and its metabolite. We have recently integrated this technology to a resolution of 9 nm by using artificial intelligence-driven analyses. Such a resolution allowed us to collect many robust datapoints for each pixel of an image. Our analyses could recognize 45 spectral points within a pixel to …

Cilia Proteins Are Biomarkers Of Altered Flow In The Vasculature, Ankan Gupta, Karthikeyan Thirugnanam, Madhan Thamilarasan, Ashraf M. Mohieldin, Hadeel T. Zedan, Shubhangi Prabhudesai, Meghan R. Griffin, Andrew D. Spearman, Amy Pan, Sean P. Palecek, Huseyin C. Yalcin, Surya M. Nauli, Kevin R. Rarick, Rahima Zennadi, Ramani Ramchandran

Pharmacy Faculty Articles and Research

Cilia, microtubule-based organelles that project from the apical luminal surface of endothelial cells (ECs), are widely regarded as low-flow sensors. Previous reports suggest that upon high shear stress, cilia on the EC surface are lost, and more recent evidence suggests that deciliation—the physical removal of cilia from the cell surface—is a predominant mechanism for cilia loss in mammalian cells. Thus, we hypothesized that EC deciliation facilitated by changes in shear stress would manifest in increased abundance of cilia-related proteins in circulation. To test this hypothesis, we performed shear stress experiments that mimicked flow conditions from low to high shear stress …

A Semi-Physiological Three-Compartment Model Describes Brain Uptake Clearance And Efflux Of Sucrose And Mannitol After Iv Injection In Awake Mice, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Md Sanaullah Sajib, Yeseul Ahn, Ehsan Nozohouri, Dhavalkumar Patel, Constantinos Mikelis, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Purpose

To evaluate a three-compartmental semi-physiological model for analysis of uptake clearance and efflux from brain tissue of the hydrophilic markers sucrose and mannitol, compared to non-compartmental techniques presuming unidirectional uptake.

Methods

Stable isotope-labeled [¹³C]sucrose and [¹³C]mannitol (10 mg/kg each) were injected as IV bolus into the tail vein of awake young adult mice. Blood and brain samples were taken after different time intervals up to 8 h. Plasma and brain concentrations were quantified by UPLC-MS/MS. Brain uptake clearance (K_in) was analyzed using either the single-time point analysis, the multiple time point graphical method, …

Bladder Tumor In A Young Leukemic Patient Cured By Chemotherapy: A Case Report, Mohamed Tebaa, Mamoutou Dit Mody, Sylla Mahamadou, Mohamed Amine Lakmichi

Health Sciences

Adult bladder tumor is estimated to be the 10th most common tumor worldwide. However, its incidence is much less common in children. It is a disease of the elderly that peaks in the sixth decade of life. Nevertheless, bladder tumors could also affect children, adolescents, and young adults with a prevalence of

Unraveling The Anti-Inflammatory And Cardioprotective Mechanism Of Prenylated Stilbenoids From Peanut Hairy Root Cultures In Vitro And In Vivo, Md Rokib Hasan

Student Theses and Dissertations

Stilbenoids are a non-flavonoid class of polyphenols that are important for their potential medicinal applications. Resveratrol, ione of the most well-studied compounds of this group, has various medicinal properties including anti-inflammatory, antioxidant, anti-cancer and many other properties. Prenylated stilbenoids which include arachidin-1 and arachidin-3 are produced as a defense response to biotic and abiotic stresses in peanut (Arachis hypogaea). Prenylation has been shown to enhance the biological activities of polyphenolic compounds and thus arachidins may have higher anti-inflammatory activity than resveratrol in addition to many other potential health applications. However, the molecular mechanism of the arachidins as an anti-inflammatory and …

Prostacyclin Promotes Degenerative Pathology In A Model Of Alzheimer’S Disease, Tasha R. Womack, Craig T. Vollert, Odochi Ohia-Nwoko, Monika Schmitt, Saghi Montazari, Tina L. Beckett, David Mayerich, M. Paul Murphy, Jason L. Eriksen

Molecular and Cellular Biochemistry Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that is the most common form of dementia in aged populations. A substantial amount of data demonstrates that chronic neuroinflammation can accelerate neurodegenerative pathologies. In AD, chronic neuroinflammation results in the upregulation of cyclooxygenase and increased production of prostaglandin H2, a precursor for many vasoactive prostanoids. While it is well-established that many prostaglandins can modulate the progression of neurodegenerative disorders, the role of prostacyclin (PGI2) in the brain is poorly understood. We have conducted studies to assess the effect of elevated prostacyclin biosynthesis in a mouse model of AD. Upregulated prostacyclin expression …

Uplc-Pda-Ms/Ms Profiling And Healing Activity Of Polyphenol-Rich Fraction Of Alhagi Maurorum Against Oral Ulcer In Rats, Noha Swilam, Hala El Zahar, Esther Menze, Heba Handousa, Mohamed El Shazly, Nada Mostafa

Pharmacy

Camelthorn, Alhagi maurorum Boiss, family Fabaceae has long been used in African folk medicine owing to its richness in pharmacologically active metabolites. The crude extract (CEAM), ethylacetatefraction(EFAM)andn-butanol(BFAM)fractionofA.maurorumaerialpartswereinvestigated for their total polyphenols and oral antiulcer activity using in-vitro and in-vivo models. The major phenolic compound was isolated from the polyphenol-rich EFAM fraction and identified by conventional and spectroscopic methods of analysis as isorhamnetin-3-O-rutinoside. Furthermore, standardization of EAFM using UPLC-PDA-UV quantified isorhamnetin-3-O-rutinoside as 262.91 0.57 g/mg of the fraction. Analysis of EFAM using UPLC-PDA-MS/MS revealed tentative identification of 25 polyphenolic compounds. EFAM exhibited the most potent free radical scavenging activity against DPPH, …

Antidiabetic Activity And In Silico Molecular Docking Of Polyphenols From Ammannia Baccifera L. Subsp. Aegyptiaca (Willd.) Koehne Waste: Structure Elucidation Of Undescribed Acylated Flavonol Diglucoside, Noha Swilam, Mahmoud Nawwar, Rasha Radwan, Eman Mostafa

Pharmacy

Chemical investigation of the aerial parts of Ammania aegyptiaca ethanol extract (AEEE) showed high concentrations of polyphenol and flavonoid content, with notable antioxidant activity. Undescribed acylated diglucoside flavonol myricetin 3-O-β-4C1-(600-O-galloyl glucopyranoside) 7-Oβ-4C1-glucopyranoside (MGGG) was isolated from the aerial parts of AEEE, along with four known polyphenols that had not been characterized previously from AEEE. The inhibitory effects of MGGG, AEEE, and all compounds against α-amylase, pancreatic lipase and β-glucosidase were assessed. In addition, molecular docking was used to determine the inhibition of digestive enzymes, and this confirmed that the MGGG interacted strongly with the active site residues of these enzymes, …

Studying Patterns And Predictors Of Hiv Viral Suppression Using A Big Data Approach: A Research Protocol, Jiajia Zhang Ph.D., Bankole Olatosi Ph.D., Xueying Yang Ph.D., Zhenglong Li, Jianjun Hu, Xiaoming Li

Faculty Publications

Background: Given the importance of viral suppression in ending the HIV epidemic in the US and elsewhere, an optimal predictive model of viral status can help clinicians identify those at risk of poor viral control and inform clinical improvements in HIV treatment and care. With an increasing availability of electronic health record (EHR) data and social environmental information, there is a unique opportunity to improve our understanding of the dynamic pattern of viral suppression. Using a statewide cohort of people living with HIV (PLWH) in South Carolina (SC), the overall goal of the proposed research is to examine the dynamic …

Essential Methods Of Pharmacoeconomics Php 589, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Application Of Medication Outcomes Evaluation Php 649, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Essential Methods Of Pharmacoecoepidemiology Php 559, Joanna Burkhardt

Library Impact Statements

No abstract provided.

Conditional Drug Approval As A Path To Market For Oncology Drugs In Canada: Challenges And Recommendations For Assessing Eligibility And Regulatory Responsiveness, Melanie Mcphail, Emma Weiss, Tania M. Bubela

Office of the Provost

International drug regulators use conditional drug approval mechanisms to facilitate faster patient access to drugs based on a lower evidentiary standard typically required of drug approvals. Faster and earlier access is justified by limiting eligibility to drugs intended for serious and life-threatening diseases and by requiring post-market evidence collection to confirm clinical benefit. One such mechanism in Canada, the Notice of Compliance with Conditions (NOC/c) policy, was introduced in 1998. Today, most of the drugs approved under the NOC/c policy are for oncology indications. We analyze oncology drugs approvals under the NOC/c policy to inform discussions of two tradeoffs applied …

Introduction To Medication Outcomes Php 509, Joanna Burkhardt

Library Impact Statements

No abstract provided.

The Natural Isoflavone Biochanin-A Synergizes 5-Fluorouracil Anticancer Activity In Vitro And In Vivo In Ehrlich Solid-Phase Carcinoma Model, Mohamed Mahmoud, Maha R.A. Abdollah, Mohamed E. Elsesy, Dalal A. Abou El Ella, Suher K. Zada, Mai Fathy Tolba

Pharmacy

Isoflavones are considered one of the most extensively studied plant-derived phytoestrogenic compounds. Of these, Biochanin A (Bio-A), a natural isoflavone abundant in cabbage, alfalfa, and red clover, has drawn a lot of attention. As reported in multiple studies, Bio-A possesses a promising anticancer activity against estrogen receptor–positive (ER+)  breast cancer. The current study investigated the working hypothesis that Bio-A could synergistically enhance the potency of 5-fluorouracil (5-FU) in ER+ breast cancer. The hypothesis was tested both in vitro on hormone receptor–positive (MCF-7) and triple-negative breast cancer cells (MDA-MB231). Additionally, in vivo studies were performed in the Ehrlich solid-phase carcinoma mouse …