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Molecular Virology Of Kshv In The Lymphocyte Compartment—Insights From Patient Samples And De Novo Infection Models, Farizeh Aalam, Jennifer Totonchy Dec 2020

Molecular Virology Of Kshv In The Lymphocyte Compartment—Insights From Patient Samples And De Novo Infection Models, Farizeh Aalam, Jennifer Totonchy

Pharmacy Faculty Articles and Research

The incidence of Kaposi’s sarcoma-associated herpesvirus (KSHV)-associated Kaposi Sarcoma has declined precipitously in the present era of effective HIV treatment. However, KSHV-associated lymphoproliferative disorders although rare, have not seen a similar decline. Lymphoma is now a leading cause of death in people living with HIV (PLWH), indicating that the immune reconstitution provided by antiretroviral therapy is not sufficient to fully correct the lymphomagenic immune dysregulation perpetrated by HIV infection. As such, novel insights into the mechanisms of KSHV-mediated pathogenesis in the immune compartment are urgently needed in order to develop novel therapeutics aimed at prevention and treatment of KSHV-associated lymphoproliferations. …


Structural Characterization And In Vitro Lipid Binding Studies Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa, Bushra Siraj, Shamshad Zarina, Aftab Ahmed Dec 2020

Structural Characterization And In Vitro Lipid Binding Studies Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa, Bushra Siraj, Shamshad Zarina, Aftab Ahmed

Pharmacy Faculty Articles and Research

Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and the antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds. Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the Mediterranean …


An Update Of The Virion Proteome Of Kaposi Sarcoma-Associated Herpesvirus, Ramina Nabiee, Basir Syed, Jesus Ramirez Castano, Rukhsana Lalani, Jennifer Totonchy Dec 2020

An Update Of The Virion Proteome Of Kaposi Sarcoma-Associated Herpesvirus, Ramina Nabiee, Basir Syed, Jesus Ramirez Castano, Rukhsana Lalani, Jennifer Totonchy

Pharmacy Faculty Articles and Research

The virion proteins of Kaposi sarcoma-associated herpesvirus (KSHV) were initially characterized in 2005 in two separate studies that combined the detection of 24 viral proteins and a few cellular components via LC-MS/MS or MALDI-TOF. Despite considerable advances in the sensitivity and specificity of mass spectrometry instrumentation in recent years, leading to significantly higher yields in detections, the KSHV virion proteome has not been revisited. In this study, we have re-examined the protein composition of purified KSHV virions via ultra-high resolution Qq time-of-flight mass spectrometry (UHR-QqTOF). Our results confirm the detection of all previously reported virion proteins, in addition to 17 …


Regiospecific Synthesis Of Calcium‐Independent Daptomycin Antibiotics Using A Chemoenzymatic Method, Nagaraju Mupparapu, Yu-Hsin Cindy Lin, Tae Ho Kim, Sherif I. Elshahawi Nov 2020

Regiospecific Synthesis Of Calcium‐Independent Daptomycin Antibiotics Using A Chemoenzymatic Method, Nagaraju Mupparapu, Yu-Hsin Cindy Lin, Tae Ho Kim, Sherif I. Elshahawi

Pharmacy Faculty Articles and Research

Daptomycin (DAP) is a calcium (Ca2+)‐dependent FDA‐approved antibiotic drug for the treatment of Gram‐positive infections. It possesses a complex pharmacophore hampering derivatization and/or synthesis of analogs. In order to mimic the Ca2+‐binding effect we uses a chemoenzymatic approach to modify the tryptophan (Trp) residue of DAP and synthesize kinetically characterized and structurally elucidated regiospecific Trp‐modified DAP analogs. We demonstrated that the modified DAPs are several‐folds active than the parent molecule against antibiotic‐susceptible and antibiotic‐resistant Gram‐positive bacteria. Strikingly and in contrast to the parent molecule, the DAP derivatives do not rely on calcium or any additional elements for activity.


Seroprevalence Of Novel Coronavirus Sars-Cov-2 At A Community Hospital Emergency Department And Outpatient Laboratory In Northern Orange County, California, Jason Yamaki, Harry Peled, Sajen Mathews, David Park, Mina Firoozi, Kim Smith, Lee Nguyen Nov 2020

Seroprevalence Of Novel Coronavirus Sars-Cov-2 At A Community Hospital Emergency Department And Outpatient Laboratory In Northern Orange County, California, Jason Yamaki, Harry Peled, Sajen Mathews, David Park, Mina Firoozi, Kim Smith, Lee Nguyen

Pharmacy Faculty Articles and Research

Introduction

The severe acute respiratory syndrome related coronavirus 2 (SARS-CoV-2) has infected more than 20 million people worldwide, and the spread is most prevalent in the USA, where California had accounted over 240,000 cases in the initial 5 months of the pandemic. To estimate the number of infected persons in our community, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection.

Methods

This cross-sectional study evaluated the presence of immunoglobulin G, antibody for SARS-CoV-2 during the time period of July 15, 2020, to July 27, 2020. Testing was done on serum samples from patients who had visited affiliated …


The Inclusion Of Health Data Standards In The Implementation Of Pharmacogenomics Systems: A Scoping Review, Don Roosan, Angela Hwang, Anandi V. Law, Jay Chok, Moom Roosan Oct 2020

The Inclusion Of Health Data Standards In The Implementation Of Pharmacogenomics Systems: A Scoping Review, Don Roosan, Angela Hwang, Anandi V. Law, Jay Chok, Moom Roosan

Pharmacy Faculty Articles and Research

Background: Despite potential benefits, the practice of incorporating pharmacogenomics (PGx) results in clinical decisions has yet to diffusewidely. In this study,we conducted a review of recent discussions on data standards and interoperability with a focus on sharing PGx test results among health systems. Materials & methods:We conducted a literature search for PGx clinical decision support systems between 1 January 2012 and 31 January 2020. Thirty-two out of 727 articles were included for the final review. Results: Nine of the 32 articles mentioned data standards and only four of the 32 articles provided solutions for the lack of …


Analysis Of Kshv B Lymphocyte Lineage Tropism In Human Tonsil Reveals Efficient Infection Of Cd138+ Plasma Cells, Farizeh Aalam, Ramina Nabiee, Jesus Ramirez Castano, Jennifer Totonchy Oct 2020

Analysis Of Kshv B Lymphocyte Lineage Tropism In Human Tonsil Reveals Efficient Infection Of Cd138+ Plasma Cells, Farizeh Aalam, Ramina Nabiee, Jesus Ramirez Castano, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Despite 25 years of research, the basic virology of Kaposi Sarcoma Herpesviruses (KSHV) in B lymphocytes remains poorly understood. This study seeks to fill critical gaps in our understanding by characterizing the B lymphocyte lineage-specific tropism of KSHV. Here, we use lymphocytes derived from 40 human tonsil specimens to determine the B lymphocyte lineages targeted by KSHV early during de novo infection in our ex vivo model system. We characterize the immunological diversity of our tonsil specimens and determine that overall susceptibility of tonsil lymphocytes to KSHV infection varies substantially between donors. We demonstrate that a variety of B lymphocyte …


What’S The Big Deal About Statins?, Albert Bach, Jelena Lewis, Susie Yoo Oct 2020

What’S The Big Deal About Statins?, Albert Bach, Jelena Lewis, Susie Yoo

Pharmacy Faculty Articles and Research

"Statins are a group of cholesterol-lowering medications that have been shown evidence to be beneficial for tens of millions of Americans. Some examples of statin medications you may have heard of include: atorvastatin (Lipitor), rosuvastatin (Crestor), simvastatin (Zocor), pravastatin (Pravachol) and lovastatin (Mevacor). Statins are one of the most commonly prescribed medications in the United States. One in four adults over the age of 45 years old are currently taking a statin for its many benefits. See below for more information about its use."


Lc–Ms/Ms-Based In Vitro And In Vivo Investigation Of Blood–Brain Barrier Integrity By Simultaneous Quantitation Of Mannitol And Sucrose, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Yeseul Ahn, Dhavalkumar Patel, Abraham Al-Ahmad, Reza Mehvar, Ulrich Bickel Oct 2020

Lc–Ms/Ms-Based In Vitro And In Vivo Investigation Of Blood–Brain Barrier Integrity By Simultaneous Quantitation Of Mannitol And Sucrose, Behnam Noorani, Ekram Ahmed Chowdhury, Faleh Alqahtani, Yeseul Ahn, Dhavalkumar Patel, Abraham Al-Ahmad, Reza Mehvar, Ulrich Bickel

Pharmacy Faculty Articles and Research

Background

Understanding the pathophysiology of the blood brain–barrier (BBB) plays a critical role in diagnosis and treatment of disease conditions. Applying a sensitive and specific LC–MS/MS technique for the measurement of BBB integrity with high precision, we have recently introduced non-radioactive [13C12]sucrose as a superior marker substance. Comparison of permeability markers with different molecular weight, but otherwise similar physicochemical properties, can provide insights into the uptake mechanism at the BBB. Mannitol is a small hydrophilic, uncharged molecule that is half the size of sucrose. Previously only radioactive [3H]mannitol or [14C]mannitol has been …


Overcoming Barriers For Sirna Therapeutics: From Bench To Bedside, Muhammad Imran Sajid, Muhammad Moazzam, Shun Kato, Kayley Yeseom Cho, Rakesh Kumar Tiwari Oct 2020

Overcoming Barriers For Sirna Therapeutics: From Bench To Bedside, Muhammad Imran Sajid, Muhammad Moazzam, Shun Kato, Kayley Yeseom Cho, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The RNA interference (RNAi) pathway possesses immense potential in silencing any gene in human cells. Small interfering RNA (siRNA) can efficiently trigger RNAi silencing of specific genes. FDA Approval of siRNA therapeutics in recent years garnered a new hope in siRNA therapeutics. However, their therapeutic use is limited by several challenges. siRNAs, being negatively charged, are membrane-impermeable and highly unstable in the systemic circulation. In this review, we have comprehensively discussed the extracellular barriers, including enzymatic degradation of siRNAs by serum endonucleases and RNAases, rapid renal clearance, membrane impermeability, and activation of the immune system. Besides, we have thoroughly described …


Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo Sep 2020

Effects Of Germline And Somatic Events In Candidate Brca-Like Genes On Breast-Tumor Signatures, Weston R. Bodily, Brian H. Shirts, Tom Walsh, Suleyman Gulsuner, Mary-Claire King, Alyssa Parker, Moom Roosan, Stephen R. Piccolo

Pharmacy Faculty Articles and Research

Mutations in BRCA1 and BRCA2 cause deficiencies in homologous recombination repair (HR), resulting in repair of DNA double-strand breaks by the alternative non-homologous end-joining pathway, which is more error prone. HR deficiency of breast tumors is important because it is associated with better responses to platinum salt therapies and PARP inhibitors. Among other consequences of HR deficiency are characteristic somatic-mutation signatures and gene-expression patterns. The term “BRCA-like” (or “BRCAness”) describes tumors that harbor an HR defect but have no detectable germline mutation in BRCA1 or BRCA2. A better understanding of the genes and molecular events associated with tumors being …


Cytokine-Targeted Therapeutics For Kshv-Associated Disease, Nedaa Alomari, Jennifer Totonchy Sep 2020

Cytokine-Targeted Therapeutics For Kshv-Associated Disease, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Kaposi’s sarcoma-associated herpesvirus (KSHV) also known as human herpesvirus 8 (HHV-8), is linked to several human malignancies including Kaposi sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman’s disease (MCD) and recently KSHV inflammatory cytokine syndrome (KICS). As with other diseases that have a significant inflammatory component, current therapy for KSHV-associated disease is associated with significant off-target effects. However, recent advances in our understanding of the pathogenesis of KSHV have produced new insight into the use of cytokines as potential therapeutic targets. Better understanding of the role of cytokines during KSHV infection and tumorigenesis may lead to new preventive or therapeutic …


Artificial Intelligence–Powered Smartphone App To Facilitate Medication Adherence: Protocol For A Human Factors Design Study, Don Roosan, Jay Chok, Mazharul Karim, Anandi V. Law, Andrius Baskys, Angela Hwang, Moom Roosan Sep 2020

Artificial Intelligence–Powered Smartphone App To Facilitate Medication Adherence: Protocol For A Human Factors Design Study, Don Roosan, Jay Chok, Mazharul Karim, Anandi V. Law, Andrius Baskys, Angela Hwang, Moom Roosan

Pharmacy Faculty Articles and Research

Background: Medication Guides consisting of crucial interactions and side effects are extensive and complex. Due to the exhaustive information, patients do not retain the necessary medication information, which can result in hospitalizations and medication nonadherence. A gap exists in understanding patients’ cognition of managing complex medication information. However, advancements in technology and artificial intelligence (AI) allow us to understand patient cognitive processes to design an app to better provide important medication information to patients.

Objective: Our objective is to improve the design of an innovative AI- and human factor–based interface that supports patients’ medication information comprehension that could potentially …


Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria Sep 2020

Acute And Chronic Dosing Of A High-Affinity Rat/Mouse Chimeric Transferrin Receptor Antibody In Mice, Demi M. Castellanos, Jiahong Sun, Joshua Yang, Weijun Ou, Alexander C. Zambon, William M. Pardridge, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Non-invasive brain delivery of neurotherapeutics is challenging due to the blood-brain barrier. The revived interest in transferrin receptor antibodies (TfRMAbs) as brain drug-delivery vectors has revealed the effect of dosing regimen, valency, and affinity on brain uptake, TfR expression, and Fc-effector function side effects. These studies have primarily used monovalent TfRMAbs with a human constant region following acute intravenous dosing in mice. The effects of a high-affinity bivalent TfRMAb with a murine constant region, without a fusion partner, following extravascular dosing in mice are, however, not well characterized. Here we elucidate the plasma pharmacokinetics and safety of a high-affinity bivalent …


Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang Sep 2020

Click-Free Synthesis Of A Multivalent Tricyclic Peptide As A Molecular Transporter, Sumit Kumar, Dindyal Mandal, Shaima Ahmed El-Mowafi, Saghar Mozaffari, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The cellular delivery of cell-impermeable and water-insoluble molecules remains an ongoing challenge to overcome. Previously, we reported amphipathic cyclic peptides c[WR]4 and c[WR]5 consisting of alternate arginine and tryptophan residues as nuclear-targeting molecular transporters. These peptides contain an optimal balance of positive charge and hydrophobicity, which is required for interactions with the phospholipid bilayer to facilitate their application as a drug delivery system. To further optimize them, we synthesized and evaluated a multivalent tricyclic peptide as an efficient molecular transporter. The monomeric cyclic peptide building blocks were synthesized using Fmoc/tBu solid-phase chemistry and cyclization in the …


Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma Sep 2020

Effect Of High Glucose On Ocular Surface Epithelial Cell Barrier And Tight Junction Proteins, Saleh M. Alfuraih, Ashley Barbarino, Christopher Ross, Kiumars Shamloo, Vishal Jhanji, Miao Zhang, Ajay Sharma

Pharmacy Faculty Articles and Research

PURPOSE. Patients with diabetes mellitus are reported to have ocular surface defects, impaired ocular surface barrier function, and a higher incidence of corneal and conjunctival infections. Tight junctions are critical for ocular surface barrier function. The present study was designed to investigate the effect of high glucose exposure on human corneal and conjunctival epithelial cell barrier function and tight junction proteins.

METHODS. Human corneal and conjunctival epithelial cells were exposed to 15 mM and 30 mM glucose for 24 and 72 hours. The barrier function was measured using transepithelial electrical resistance (TEER). The cell migration was quantified using scratch assay. …


Hydrophobic Interactions Between The Ha Helix And S4‐S5 Linker Modulate Apparent Ca2+ Sensitivity Of Sk2 Channels, Young-Woo Nam, Meng Cui, Razan Orfali, Adam Viegas, Misa Nguyen, Eman H. M. Mohammed, Khalid Zoghebi, Simin Rahighi, Keykavous Parang, Miao Zhang Aug 2020

Hydrophobic Interactions Between The Ha Helix And S4‐S5 Linker Modulate Apparent Ca2+ Sensitivity Of Sk2 Channels, Young-Woo Nam, Meng Cui, Razan Orfali, Adam Viegas, Misa Nguyen, Eman H. M. Mohammed, Khalid Zoghebi, Simin Rahighi, Keykavous Parang, Miao Zhang

Pharmacy Faculty Articles and Research

Aim

Small‐conductance Ca2+‐activated potassium (SK) channels are activated exclusively by increases in intracellular Ca2+, that binds to calmodulin constitutively associated with the channel. Wild‐type SK2 channels are activated by Ca2+ with an EC50 value of ~0.3 μM. Here, we investigate hydrophobic interactions between the HA helix and the S4‐S5 linker as a major determinant of channel apparent Ca2+ sensitivity.

Methods

site‐directed mutagenesis, electrophysiological recordings and molecular dynamic (MD) simulations were utilized.

Results

Mutations that decrease hydrophobicity at the HA‐S4‐S5 interface lead to Ca2+ hyposensitivity of SK2 channels. Mutations that increase hydrophobicity result in …


Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review Of Annovera With A Pharmacist Perspective, Jennifer J. Virro, Kathleen Besinque, Christiane E. Carney, Danielle Gross, Brian Bernick, Sebastian Mirkin Aug 2020

Long-Lasting, Patient-Controlled, Procedure-Free Contraception: A Review Of Annovera With A Pharmacist Perspective, Jennifer J. Virro, Kathleen Besinque, Christiane E. Carney, Danielle Gross, Brian Bernick, Sebastian Mirkin

Pharmacy Faculty Articles and Research

Annovera (segesterone acetate and ethinyl estradiol vaginal system) is a US Food and Drug Administration FDA-approved long-lasting, reversible contraceptive that is fully administered by the user and does not require a procedure for insertion or removal. The vaginal system is in the shape of a ring and contains low doses of a novel progestin, egesterone acetate, and ethinyl estradiol. It is made of silicone and is fully pliable and flexible. The vaginal system is reusable for 13 cycles, using a 21 days in/7 days out regimen, providing women with the ability to control their fertility. Particularly now during the COVID-19 …


Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan Aug 2020

Pharmacogenomics Cascade Testing (Phact): A Novel Approach For Preemptive Pharmacogenomics Testing To Optimize Medication Therapy, Don Roosan, Angela Hwang, Moom Roosan

Pharmacy Faculty Articles and Research

The implementation of pharmacogenomics (PGx) has come a long way since the dawn of utilizing pharmacogenomic data in clinical patient care. However, the potential benefits of sharing PGx results have yet to be explored. In this paper, we explore the willingness of patients to share PGx results, as well as the inclusion of family medication history in identifying potential family members for pharmacogenomics cascade testing (PhaCT). The genetic similarities in families allow for identifying potential gene variants prior to official preemptive testing. Once a candidate patient is determined, PhaCT can be initiated. PhaCT recognizes that further cascade testing throughout a …


Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari Aug 2020

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)5C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl3 with [(WR)5C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …


Understanding Covid-19: From Origin To Potential Therapeutics, Muhammad Moazzam, Muhammad Imran Sajid, Hamza Shahid, Jahanzaib Butt, Irfan Bashir, Muhammad Jamshaid, Amir Nasrolahi Shirazi, Rakesh Kumar Tiwari Aug 2020

Understanding Covid-19: From Origin To Potential Therapeutics, Muhammad Moazzam, Muhammad Imran Sajid, Hamza Shahid, Jahanzaib Butt, Irfan Bashir, Muhammad Jamshaid, Amir Nasrolahi Shirazi, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Currently, a global pandemic era of public health concerns is going on with the Coronavirus Disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of COVID-19 was reported from Wuhan’s Huanan seafood market in China late December 2019. Bats, pangolins, and snakes have been nominated as salient carriers of the virus. Thanks to its high pathogenicity, it can cause severe respiratory infections. Fever, dry cough, sore throat, pneumonia, septic shock, and ground-glass opacities are the foremost clinical manifestations of COVID-19. Immunocompromised patients are at high risk for COVID-19 infection and may lead to …


Cyclic Peptide [R4w4] In Improving The Ability Of First-Line Antibiotics To Inhibit Mycobacterium Tuberculosis Inside In Vitro Human Granulomas, Joshua Hernandez, David Ashley, Ruoqiong Cao, Rachel Abrahem, Timothy Nguyen, Kimberly To, Aram Yegiazaryan, Ajayi Akinwale David, Rakesh Kumar Tiwari, Vishwanath Venketaraman Aug 2020

Cyclic Peptide [R4w4] In Improving The Ability Of First-Line Antibiotics To Inhibit Mycobacterium Tuberculosis Inside In Vitro Human Granulomas, Joshua Hernandez, David Ashley, Ruoqiong Cao, Rachel Abrahem, Timothy Nguyen, Kimberly To, Aram Yegiazaryan, Ajayi Akinwale David, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Tuberculosis (TB) is currently one of the leading causes of global mortality. Medical non-compliance due to the length of the treatment and antibiotic side effects has led to the emergence of multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (M. tb) that are difficult to treat. A current therapeutic strategy attempting to circumvent this issue aims to enhance drug delivery to reduce the duration of the antibiotic regimen or dosage of first-line antibiotics. One such agent that may help is cyclic peptide [R4W4], as it has been shown to have antibacterial properties (in combination with tetracycline) …


Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi Jul 2020

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …


Uplc-Ms/Ms Analysis Of Cyp1a-Mediated Ethoxyresorufin-O-Deethylation Activity In The Rat Kidney Microsomes, Devaraj Venkatapura Chandrashekar, Reza Mehvar Jul 2020

Uplc-Ms/Ms Analysis Of Cyp1a-Mediated Ethoxyresorufin-O-Deethylation Activity In The Rat Kidney Microsomes, Devaraj Venkatapura Chandrashekar, Reza Mehvar

Pharmacy Faculty Articles and Research

Ethoxyresorufin (ER)-O-deethylation (EROD) activity has been widely used to assess cytochrome P450 1A (CYP1A) activity. The kinetics of CYP1A activity have been well characterized in the liver microsomes. However, studies in kidney microsomes are limited due to the much lower EROD activity in this organ. Here, we developed and validated a sensitive UPLC-MS/MS assay for the characterization of the EROD activity in the rat kidney microsomes. In a 50 µL reaction mixture, rat kidney microsomes (0.25 mg/mL) were incubated with ER (0.1–5 µM) and NADPH (1 mM) for 10 min. Acidic solvents, such as trichloroacetic acid or formic …


A Prospective Study To Validate The Functional Assessment Of Cancer Therapy (Fact) For Epidermal Growth Factor Receptor Inhibitor (Egfri)-Induced Dermatologic Toxicities Fact-Egfri 18 Questionnaire: Swog S1013, Siu Fun Wong, Joseph M. Unger, James L. Wade Iii, Lynne I. Wagner, Mario E. Lacouture, Keisha C. Humphries, Anna Moseley, Kathryn Arnold, Mario R. Velasco Jr., Justin D. Floyd, Benjamin T. Esparaz, Afsaneh Barzi, Heinz-Josef Lenz, Marianna Koczywas, Shaker Dakhil, Gary V. Burton, Michael J. Fisch, N. Lynn Henry, Dawn L. Hershman, Carol M. Moinpour Jul 2020

A Prospective Study To Validate The Functional Assessment Of Cancer Therapy (Fact) For Epidermal Growth Factor Receptor Inhibitor (Egfri)-Induced Dermatologic Toxicities Fact-Egfri 18 Questionnaire: Swog S1013, Siu Fun Wong, Joseph M. Unger, James L. Wade Iii, Lynne I. Wagner, Mario E. Lacouture, Keisha C. Humphries, Anna Moseley, Kathryn Arnold, Mario R. Velasco Jr., Justin D. Floyd, Benjamin T. Esparaz, Afsaneh Barzi, Heinz-Josef Lenz, Marianna Koczywas, Shaker Dakhil, Gary V. Burton, Michael J. Fisch, N. Lynn Henry, Dawn L. Hershman, Carol M. Moinpour

Pharmacy Faculty Articles and Research

Background

Papulopustular rash is a common class effect of epidermal growth factor receptor inhibitors (EGFRI) that can affect patients’ health-related quality of life and cause disruptions to treatment. SWOG S1013 (NCT01416688) is a multi-center study designed to validate the Functional Assessment of Cancer Therapy EGFRI 18 (FACT-EGFRI 18) using 7-items from the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 to assess EGFRI-induced skin-related toxicities and their impact on functional status.

Methods

Patients with a diagnosis of colorectal or lung cancer to receive EGFRI therapies for at least 6 weeks were enrolled. Patient self-assessments using …


Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom Jul 2020

Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

The second messenger molecule 3′5′-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has led to interest in defining how specific PDE isoforms maintain these signaling microdomains. The possible altered expression of PDEs, and thus abnormal …


Use Of National Consumer Survey Data To Explore Perceptions Of Complementary And Alternative Medicine, Alina Cernasev, Basma Gomaa, Keri Hager, Jon C. Schommer, Lawrence B. Brown Jun 2020

Use Of National Consumer Survey Data To Explore Perceptions Of Complementary And Alternative Medicine, Alina Cernasev, Basma Gomaa, Keri Hager, Jon C. Schommer, Lawrence B. Brown

Pharmacy Faculty Articles and Research

Background: Although Complementary and Alternative Medicine (CAM) has been the standard of therapy in Asia for centuries, it started receiving more attention in the U.S. in the last three decades.

Objectives: The primary study objective was to explore individuals' perspectives of CAM. A secondary objective was to describe individuals' perceptions of pharmacists’ roles in facilitating their use of these services and products.

Methods: Data were obtained from the 2015 and 2016 National Consumer Surveys on the Medication Experience and Pharmacist Roles. Data were collected from adults residing in the United States via on-line, self-administered surveys coordinated by …


Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli Jun 2020

Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli

Pharmacy Faculty Articles and Research

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system …


Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria Jun 2020

Targeting The Transferrin Receptor To Develop Erythropoietin For Alzheimer’S Disease, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

"Alzheimer’s disease (AD) is the sixth leading cause of death in the United States with approximately 5.8 million Americans currently living with AD. Due to the lack of a disease modifying treatment for AD and the aging baby boomer generation, this number is projected to grow to 13.8 million by 2050 (Gaugler et al., 2019). Amyloid-beta (Aβ) plaque accumulation, one of the major pathological hallmarks of AD, can begin > 20 years before clinical symptoms of AD. By the time AD is clinically diagnosed, neuronal loss and neuropathological lesions (Aβ plaques and tau tangles) have already occurred in many brain regions …


Medication Safety During Transitions Of Care:The Importance Of Checklists In Preventing Patient Harm, Laressa Bethishou, Olivia Lounsbury, Donna Prosser Jun 2020

Medication Safety During Transitions Of Care:The Importance Of Checklists In Preventing Patient Harm, Laressa Bethishou, Olivia Lounsbury, Donna Prosser

Pharmacy Faculty Articles and Research

There is a need to optimize patient safety as patients navigate through the healthcare system. With each transition of care, patients are vulnerable to changes that may cause adverse effects, including changes in their healthcare team, health status, and medications. The Centers for Medicare & Medicaid Services (CMS) defines a transition of care as “the movement of a patient from one setting of care to another.” While the concept itself may seem simple, this definition fails to capture the many potential handoff complications which classify these transitions as high risk for patients. With 67% of patients facing unintended medication discrepancies …