Pharmacy and Pharmaceutical Sciences Commons^™

Local Renin-Angiotensin System Activation And Myofibroblast Formation In Graft Versus Host Disease–Associated Conjunctival Fibrosis, Kiumars Shamloo, Judy Weng, Christopher Ross, Jenni Lee, Saleh Alfuraih, Jennifer Totonchy, Ajay Sharma

Pharmacy Faculty Articles and Research

Purpose: The present study was designed to investigate the role of myofibroblast transdifferentiation and the conjunctival renin–angiotensin system (RAS) in the pathogenesis of graft-versus-host disease (GVHD)–associated conjunctival fibrosis.

Methods: A mouse model of major histocompatibility-matched allogeneic transplantation was used to induce GVHD, with male B10.D2 mice as donors and female BALB/c mice as recipients. Male BALB/c to female BALB/c syngeneic transplantation was used as control. Y chromosome staining in the spleen cells obtained from female recipient mice was used to confirm engraftment. The phenol red thread test and fluorescein staining were used to quantify tears and corneal keratopathy. …

Lessons Learned From The Hiv/Aids Pandemic And Access To Medicines For Covid-19 Treatment, Thalia Le

Independent Study Project (ISP) Collection

There is an imminent need to address the healthcare disparities in accessing all COVID-19 medicinal products in developing countries. While logistical issues like inadequate production facilities such as the lack of vaccines administration capacity, storage issues, gap between supply and demand as well as vaccine hesitancy can certainly play a part in impeding COVID19 medicines distribution, patent monopolies and intellectual property protection laws further exacerbated the problem, especially when vaccines were at its early stages of authorization. Historical and contemporary case studies of efforts to challenge patents on HIV AVRs treatment provide a useful lens through which we may glean …

September / October 2021, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Sharksrx Newsletter Fall 2021, Nova Southeastern University

NSU Sharks Rx

No abstract provided.

A Comparison Of Calcium Aggregation And Ultracentrifugation Methods For The Preparation Of Rat Brain Microsomes For Drug Metabolism Studies, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

Preparation of brain microsomes by the calcium chloride aggregation method has been suggested as an alternative to the ultracentrifugation method. However, the effects of the calcium chloride concentration on the quality of the microsomal fractions are not known. Brain microsomes were prepared from the adult rat brains using the high-speed ultracentrifugation and low-speed calcium chloride (10–100 mM) aggregation methods (n = 5–6 per group). The microsomal protein yield (spectrometry), the cytochrome P450 reductase (CPR) activity (spectrometry), and the monooxygenase activities (UPLC-MS/MS) of CYP2D and CYP2E1 were determined in the obtained fractions. Increasing the concentrations of calcium chloride progressively increased …

Global, Regional, And National Burden Of Stroke And Its Risk Factors, 1990–2019: A Systematic Analysis For The Global Burden Of Disease Study 2019, Valery L. Feigin, Benjamin A. Stark, Catherine Owens Johnson, Gregory A. Roth, Gdiom Gebreheat Abady, Ismaeel Yunusa Ph. D., Et Al.

Faculty Publications

Background

Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels.

Methods

We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and …

Global, Regional, And National Sex-Specific Burden And Control Of The Hiv Epidemic, 1990-2019, For 204 Countries And Territories: The Global Burden Of Diseases Study 2019, Deepa Jahagirdar, Magdalene K. Walters, Amanda Novotney, Edmond D. Brewer, Tahvi D. Frank, Ismaeel Yunusa Ph.D., Et. Al.

Faculty Publications

Background The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic.

Methods To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal …

Age-Dependent Increase In Tyrosine Level Depletes Tyrosyl-Trna Synthetase And Causes Neuronal Oxidative Dna Damage In Alzheimer’S Disease, Megha Jhanji

Theses and Dissertations

Alzheimer’s disease (AD) is the most common form of dementia, and it currently affects more than 50 million people worldwide. Much of the population develop late-onset AD after 65 and constitute more than 95% of the cases. Currently, there is no definitive cure or way to slow down the progression of this disease that addresses the neurodegeneration and loss of cognitive functions. Although the underlying cause of AD is still unknown, the “amyloid cascade hypothesis” attributed it to the aggregation of amyloid beta (AU+03B2) peptides and has been the focus for targeting most disease-modifying drugs in clinical trials. However, emerging …

The Development Of Novel Cdk8 And Cdk19 Inhibitors And Degraders As Potential Anti-Cancer Agents, Li Zhang

Theses and Dissertations

CDK8 and its homolog CDK19 are essential for transcription regulation and their dysregulation has been identified in numerous diseases, especially in cancers. CDK8 and CDK19 have been implicated in cancer development through their kinase activity and kinase independent functions. Despite the existing CDK8/19 inhibitors, there is still a need to develop novel CDK8/19 inhibitors with improved potency and PK profile. It is also necessary to develop CDK8/19 degraders that are able to eliminate the kinase-independent functions. Although two CDK8-degrading PROteolysis Activating Chimeras (PROTACs) have been reported, they have limited CDK8 degradation efficacy and no effect on CDK19. PROTACs with improved …

Sex Differences And Neuroimmune Effects Of Microglial Response In The Mesolimbic Reward Pathway In Nicotine Substance Use Disorder, Erin Leigh Anderson

Theses and Dissertations

Smoking remains the leading cause of morbidity and mortality in the United States, with less than 5% of smokers attempting to quit succeeding. This is due to the unpleasant withdrawal symptomology, which includes affective symptoms, such as irritability, weight gain, anxiety, and severe craving among others, as well as the cognitive effects, such as difficulty concentrating. This low smoking cessation success rate is also thought to be due to the long-lasting sensitization of nicotinic acetylcholine receptors (nAChRs) leading to long-term neuroadaptations in the brain’s reward system and alterations in synaptic plasticity that occur following chronic nicotine exposure and withdrawal. Glial …

Variations In Er Stress And Unfolded Protein Response Predict Disease Susceptibility, Youwen Zhang

Theses and Dissertations

Numerous studies linked endoplasmic reticulum (ER) stress and unfolded protein response (UPR) to physiological responses to stress and various human pathologies, including metabolic disorders. Although variability in stress responses among individuals has been widely recognized, how such variations in the UPR affect susceptibility to diseases remains unknown. Using outbred deer mice as a model, we explored the consequences of the differential propensity to UPR at the transcriptomic, cellular, and organismic level.

Initially, we analyzed the correlation between several UPR-related genes in primary fibroblasts, at the whole transcriptome level, after ER stress induction. The analysis of correlated transcripts revealed that their …

Decreasing Unintentional Pregnancies For Tennesseans, Paula M. Todd

Electronic Theses and Dissertations

In 2018, 49% of all pregnancies in the United States were unintended, with women with a lower- income status being five times more likely to experience an unplanned pregnancy. Tennessee has a high rate of unintended pregnancies, particularly among the uninsured, low-income, and rural teen populations; some 22% of these unintended pregnancies end in abortion. Oral or transdermal contraceptives that are affordable and accessible for women of childbearing age can reduce unintentional pregnancies. The addressed gap in clinical practice was that contraceptives are not currently available over the counter in Tennessee pharmacies without a prescription, which necessitates a costly medical …

Coronary Heart Disease (Chd) In Elderly Patients: Which Drug To Choose, Ticagrelor And Clopidogrel? A Systematic Review And Meta-Analysis Of Randomized Controlled Trials, Mohammed Ahmed Akkaif, Abubakar Sha'aban, Nur Aizati Athirah Daud, Ismaeel Yunusa Ph.D., Mei Li Ng, Muhamad Ali Sk Abdul Kader, Dzul Azri Mohamed Noor, Baharudin Ibrahim

Faculty Publications

Background: A new generation P2Y12 receptor inhibitor (ticagrelor) is recommended in current therapeutic guidelines to treat patients with coronary heart disease (CHD). However, it is unknown if ticagrelor is more effective than clopidogrel in elderly patients. Therefore, a systematic review was done to assess the effectiveness and safety of ticagrelor and clopidogrel in older patients with CHD to determine the appropriate antiplatelet treatment plan. Methodology: We performed a systematic review of randomized controlled trials (RCTs) to compare the effectiveness and safety of ticagrelor vs. clopidogrel in elderly patients with CHD. We selected eligible RCTs based on specified study criteria following …

Clinical Implications Of Combinatorial Pharmacogenomic Tests Based On Cytochrome P450 Variant Selection, Michael R. Sayer, Ashley Duche, Trang Jenny Tran Nguyen, Michelle Le, Kunj Patel, Jacqueline Vu, Danny Pham, Brianne Vernick, Richard Beuttler, Don Roosan, Moom R. Roosan

Pharmacy Faculty Articles and Research

Despite the potential to improve patient outcomes, the application of pharmacogenomics (PGx) is yet to be routine. A growing number of PGx implementers are leaning toward using combinatorial PGx (CPGx) tests (i.e., multigene tests) that are reusable over patients’ lifetimes. However, selecting a single best available CPGx test is challenging owing to many patient- and population-specific factors, including variant frequency differences across ethnic groups. The primary objective of this study was to evaluate the detection rate of currently available CPGx tests based on the cytochrome P450 (CYP) gene variants they target. The detection rate was defined as the percentage of …

Behavioral Effects Of Novel Treatments For Pain And Alcohol Use Disorder, Christa Marie Donegan

Theses and Dissertations

Opioid use disorder (OUD) and alcohol use disorder (AUD) are pressing public health problems in the United States that require new pharmacotherapies to be explored. Current FDA-approved treatment options for these two disorders are only moderately effective. Thus, there is a demand for the identification of new targets for drug development. Previous research initiatives have shown that when morphine is co-administered with the novel imidazodiazepine, MP-III-024, synergistic effects in models of analgesia and antinociception are produced. Our research efforts were concerned with understanding if morphine in combination with MP-III-024 produced synergistic effects in measures of undesirable pharmacological responses: opioid side …

Effectiveness And Safety Of Apixaban Versus Warfarin Among Older Patients With Venous Thromboembolism With Different Demographics And Socioeconomic Status, Alexander T. Cohen, Janvi Sah, Amol Dhamane, Theodore Lee, Lisa Rosenblatt, Patrick Hlavacek, Birol Emir, Allison V. Keshishian, Huseyin Yuce, Xuemei Luo

Publications and Research

Introduction

Impact of demographics and socioeconomic status (SES) on anticoagulant treatment outcomes among patients with venous thromboembolism (VTE) is not well understood. This study evaluated risks of recurrent VTE, major bleeding (MB), and clinically relevant non-major bleeding (CRNMB) among older patients with VTE initiating apixaban or warfarin stratified by demographics and SES.

Methods

Adult patients (≥ 65 years) who initiated apixaban or warfarin after a VTE event were selected from the US CMS Medicare database (September 2014–December 2017). Stabilized inverse probability treatment weighting (IPTW) was used to balance patient characteristics between treatment cohorts. Patients were stratified by age, gender, race, …

Activation Of Gene Expression By Detergent-Like Protein Domains, Bradley K. Broyles, Andrew T. Gutierrez, Theodore P. Maris, Daniel A. Coil, Thomas M. Wagner, Xiao Wang, Daisuke Kihara, Caleb Class, Alexandre M. Erkine

Scholarship and Professional Work – COPHS

The mechanisms by which transcriptional activation domains (tADs) initiate eukaryotic gene expression have been an enigma for decades because most tADs lack specificity in sequence, structure, and interactions with targets. Machine learning analysis of data sets of tAD sequences generated in vivo elucidated several functionality rules: the functional tAD sequences should (i) be devoid of or depleted with basic amino acid residues, (ii) be enriched with aromatic and acidic residues, (iii) be with aromatic residues localized mostly near the terminus of the sequence, and acidic residues localized more internally within a span of 20–30 amino acids, (iv) be with both …

Metal-Free Domino Amination-Knoevenagel Condensation Approach To Access New Coumarins As Potent Nanomolar Inhibitors Of Vegfr-2 And Egfr, Essam M. Eliwa, Marcel Frese, Ahmed H. Halawa, Maha M. Soltan, Larissa V. Ponomareva, Jon S. Thorson, Khaled A. Shaaban, Mohamed Shaaban, Ahmed M. El-Agrody, Norbert Sewald

Center for Pharmaceutical Research and Innovation Faculty Publications

A metal-free, atom-economy and simple work-up domino amination-Knoevenagel condensation approach to construct new coumarin analogous (4a-f and 8a-e) was described. Further, new formyl (5a,d-f) and nitro (9a,d-f) coumarin derivatives were synthesized via C-N coupling reaction of various cyclic secondary amines and 4-chloro-3-(formyl-/nitro)coumarins (1a,c), respectively. The confirmed compounds were screened for their in vitro anti-proliferative activity against KB-3-1, A549 and PC3 human cancer cell lines using resazurin cellular-based assay. Among them, coumarin derivatives 4e and 8e displayed the best anti-cervical cancer potency (KB-3-1) with IC₅₀ values of 15.5 ± 3.54 …

Prenatal Diagnosis Of Maternal Serum From Mothers Carrying Β-Thalassemic Fetus, Yumna Fazal, Muhammad Zohaib, Basir Syed, Saqib H. Ansari, Zehra Hashim, Aftab Ahmed, Shamshad Zarina

Pharmacy Faculty Articles and Research

Background

Current study focused on discovering protein biomarkers from the maternal serum of β-thalassemic trait mothers carrying the normal fetus and β-thalassemic major fetus.

Method

Serum samples from β-thalassemic trait mothers carrying major (N=5) and normal fetuses (N=5) were studied. IVS1-5 thalassemia mutation was common among β-thalassemic trait mothers who were carrying homozygous β-thalassemic fetus (IVS1-5/ IVS1-5 mutation) or normal fetus (no mutation). We employed two-dimensional gel electrophoresis and mass spectrometric analysis to explore differentially expressed maternal serum proteins from thalassemia carrier couples having the same β-thalassemia mutation. Western blotting was performed for one of the identified proteins to validate …

Computationally Assisted Lead Optimization Of Novel Potent And Selective Mao-B Inhibitors, Vedanjali Goineni, Manal A. Neal, Narayan D. Chaurasiya, Khaled M. Elokely, Christopher R. Mccurdy, John M. Rimoldi, Stephen J. Cutler Ph.D., Babu L. Tekwani, Francisco León Ph.D.

Faculty Publications

A series of dietary flavonoid acacetin 7-O-methyl ether derivatives were computationally designed aiming to improve the selectivity and potency profiles against monoamine oxidase (MAO) B. The designed compounds were evaluated for their potential to inhibit human MAO-A and -B. Compounds 1c, 2c, 3c, and 4c were the most potent with a Ki of 37 to 68 nM against MAO-B. Compounds 1c–4c displayed more than a thousand-fold selectivity index towards MAO-B compared with MAO-A. Moreover, compounds 1c and 2c showed reversible inhibition of MAO-B. These results provide a basis for further studies on the potential application of these modified flavonoids for …