Chemicals and Drugs Commons^™

Improving The Palatability Of Colonoscopy Preparations, Phuong Anh Hoang Nguyen, Darnell Leon Cuylear, Heather Elizabeth Canavan

Shared Knowledge Conference

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The most reliable screening method of CRC is a colonoscopy which requires a 4-Liter polymer with electrolytes preparation. Two in five patients are non-compliant to their colonoscopy schedules, with many patients who abstain reporting refusal due to significant discomfort associated with this preparation. Furthermore, there are distinct gender differences in the tolerance of colonoscopy preparations in male and female populations. We hypothesize the differences in clinic are a result of toxic effects of the drug associated with poor mixing by individual patients. PEG, the drug, …

Computational Investigation Of The Interactions Between Bioactive Compounds And Biological Assemblies, Tye D. Martin

Shared Knowledge Conference

Design of small molecules is an ongoing focus for developing agents against pathogenic viruses and bacteria that are threats to worldwide health. Viruses such as Zika feature assemblies of repeat peptide subunits or capsid proteins which are potential targets for antiviral compounds. Other protein assemblies are implicated in pathology of Alzheimer’s Disease (AD) and additional neurodegenerative diseases characterized by large assemblies of misfolded proteins such as amyloid-beta (Aβ) and tau. Recent studies on a class of conjugated polyelectrolytes (CPEs) with phenylene ethynylene moieties and charged functional groups have shown potential both as bioactive antimicrobials and theragnostic sensing agents for tracking …

Improving The Palatability Of Colonoscopy Preparations, Phuong Anh Hoang Nguyen, Sarah Mounho, Darnell Cuylear, Heather Canavan

Shared Knowledge Conference

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The most reliable screening method of CRC is a colonoscopy which requires a 4-Liter polymer with electrolytes preparation. Two in five patients are non-compliant to their colonoscopy schedules, with many patients who abstain reporting refusal due to significant discomfort associated with this preparation. Furthermore, there are distinct gender differences in the tolerance of colonoscopy preparations in male and female populations. We hypothesize the differences in clinic are a result of toxic effects of the drug associated with poor mixing by individual patients. PEG, the drug, …

L-Serine Reduces Reactive Oxygen Species Yield In Cisplatin Treated Zebrafish Utricles, Satya A. Moolani, Elvin Irihamye, Jerry D. Monroe, Michael E. Smith

Posters-at-the-Capitol

Cisplatin is a chemotherapy compound effective against a variety of cancers. However, it can act as an ototoxin and cause hearing loss by promoting reactive oxygen species (ROS) production in auditory tissues. The antioxidant amino acid, L-serine has been hypothesized to lower levels of cisplatin-mediated ROS. In this project, we investigated whether L-serine can reduce cisplatin-mediated ROS production in auditory tissue and potentially act as an otoprotectant during cisplatin chemotherapy. We used a zebrafish utricular tissue culture system and fluorescent ROS indicator dye to spectrophotometrically measure if L-serine could decrease reactive oxygen species levels in cisplatin-treated tissues. We found that …

Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions.

Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis–Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot.

Microsomal CYP2D exhibited high affinity and low capacity, compared with the mitochondrial CYP2D that had a much lower (∼50-fold) affinity but a higher (∼six-fold) …

A Xenopus Oocyte Model System To Study Action Potentials, Aaron Corbin-Leftwich, Hannah E Small, Helen H Robinson, Carlos A. Villalba-Galea, Linda M Boland

School of Pharmacy Faculty Articles

Action potentials (APs) are the functional units of fast electrical signaling in excitable cells. The upstroke and downstroke of an AP is generated by the competing and asynchronous action of Na+- and K+-selective voltage-gated conductances. Although a mixture of voltage-gated channels has been long recognized to contribute to the generation and temporal characteristics of the AP, understanding how each of these proteins function and are regulated during electrical signaling remains the subject of intense research. AP properties vary among different cellular types because of the expression diversity, subcellular location, and modulation of ion channels. These complexities, in addition to the …

Ethical Implications Of Treatment For Gender Dysphoria In Youth, Kelsey Hayes

Journal of Health Ethics

This manuscript explores ethical implications on treatment for youth with diagnosed gender dysphoria. The ethical considerations outlined and analyzed in this essay involve illuminating an understanding of whether the administration of pubertal suppression with GnRH agonists, and cross-sex hormones to children with gender dysphoria is morally justified as treatment to manage their psychological distress, or if safer more understood alternatives exist. This essay emphasizes that as health care professionals we must ensure youth with gender dysphoria receive adequate medical treatment and care however, this essay concludes through extensive literature review, that the use of inconclusive and under researched methods to …

Duet: A Phase 2 Study Evaluating The Efficacy And Safety Of Sparsentan In Patients With Fsgs., Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N. Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S. Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers, Duet Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

Nrh:Quinone Oxidoreductase 2 (Nqo2) And Glutaminase (Gls) Both Play A Role In Large Extracellular Vesicles (Lev) Formation In Preclinical Lncap-C4-2b Prostate Cancer Model Of Progressive Metastasis, Thambi Dorai, Ankeeta Shah, Faith Summers, Rajamma Mathew, Jing Huang, Tze-Chen Hsieh, Joseph M. Wu

NYMC Faculty Publications

In the course of studies aimed at the role of oxidative stress in the development of metastatic potential in the LNCaP-C4-2B prostate cancer progression model system, we found a relative decrease in the level of expression of the cytoplasmic nicotinamide riboside: quinone oxidoreductase (NQO2) and an increase in the oxidative stress in C4-2B cells compared to that in LNCaP or its derivatives C4 and C4-2. It was also found that C4-2B cells specifically shed large extracellular vesicles (LEVs) suggesting that these LEVs and their cargo could participate in the establishment of the osseous metastases. The level of expression of caveolin-1 …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Design, Synthesis, And Evaluation Of Amphiphilic Cyclic And Linear Peptides Composed Of Hydrophobic And Positively-Charged Amino Acids As Antibacterial Agents, Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R₄W₄] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected …

Using Drosophila Behavioral Assays To Characterize Terebrid Venompeptide Bioactivity, Anders Eriksson, Prachi Anand, Juliette Gorson, Corina Grijuc, Elina Hadelia, James C. Stewart, Mandë Holford, Adam Claridge-Chang

Publications and Research

The number of newly discovered peptides from the transcriptomes and proteomes of animal venom arsenals is rapidly increasing, resulting in an abundance of uncharacterized peptides. There is a pressing need for a systematic, cost effective, and scalable approach to identify physiological effects of venom peptides. To address this discovery-to-function gap, we developed a sequence driven:activity-based hybrid approach for screening venom peptides that is amenable to large-venom peptide libraries with minimal amounts of peptide. Using this approach, we characterized the physiological and behavioral phenotypes of two peptides from the venom of predatory terebrid marine snails, teretoxins Tv1 from Terebra variegata and …

The Smarxt Media Literacy Program: Improving Evidence-Based Prescribing Among Medical Students, Bethany D. Corbin, Jason B. Colditz, Galen E. Switzer, Jaime E. Sidani, Patricia M. Klatt, Ted Schaffer, Brian A. Primack

Journal of Media Literacy Education

Many prescriptions written are not evidence-based, resulting in unnecessary morbidity and mortality. Media literacy may help medical trainees optimize evidence-based decision-making. In this study, we aimed to assess feasibility, acceptability, and initial efficacy of a media literacy prescribing program. We recruited 30 medical students, who completed animated video modules about pharmaceutical marketing and prescribing. We used a process evaluation and open-ended items to assess feasibility and acceptability, and knowledge tests before and after the intervention to assess efficacy. The program was feasible to implement and well-accepted. Knowledge and attitude targets around evidence-based prescribing and drug marketing improved after the intervention.

In Vitro And Ex-Vivo Evaluation Of Topical Formulations Designed To Minimize Transdermal Absorption Of Vitamin K1, Ramina Nabiee, Barent Dubois, Laura Green, Ajay Sharma, Siu Fun Wong, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using …

Determination Of Pyrrolizidine Alkaloids In Dietary Sources Using A Spectrophotometric Method, Oana C. Șeremet, Octavian T. Olaru, Mihaela Ilie, Claudia M. Guțu, Mihai G. Nițulescu, Camelia Diaconu, Catalina Motofei, Denisa Margină, Simona Negreș, Cristina E. Zbârcea, Emil Ștefănescu

Journal of Mind and Medical Sciences

Pyrrolizidine alkaloids (PAs) are a class of toxic compounds found in the composition of more than 6000 plants. People can be exposed to PAs by consuming phytotherapeutic products, food from crops contaminated with seeds of some species with high content of PAs, and/ or contaminated animal products like bee products. For this reason we developed and validated a method for quantitative determination of PAs, from the most frequently contaminated food sources, honey and flour. Colorimetric Ehrlich reagent method was used with standard addition (1mg/kg senecionine). The extraction solvent was methanol 50% acidified with citric acid to pH 2-3, as this …

The Switch From Patented Medicine To The Generic One: An Option Or A Necessity?, Păduraru Dan Nicolae, Ion Daniel, Nica Adriana Elena, Coman Florentina, Coțofană Marius, Badiu Dumitru Cristinel, Grigorean Valentin Titus, Bolocan Alexandra, Andronic Octavian

Journal of Mind and Medical Sciences

This paper assesses the influence of a number of factors taken into account when a brand name drug is replaced by a generic one. It also evaluates responses of health professionals – physicians and pharmacist—and patients regarding the issue of switching. We compared and contrasted their responses in order to identify new points of cooperation for the intended benefit of the patient. Thus, the sample drew from all three groups, consisting of 50 doctors, 50 pharmacists, and 50 patients. We collected information regarding the age, residence, income level, and education level for the patients, and age and experience for the …

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the …

Moderate Exercise Enhances Endothelial Progenitor Cell Exosomes Release And Function, Chunlian Ma, Jinju Wang, Hua Liu, Yanyu Chen, Xiaotang Ma, Shuzhen Chen, Yanfang Chen, Ji Chen Bihl, Yi Yang

Pharmacology and Toxicology Faculty Publications

Purpose: Exercise has cardiovascular benefits which might be related to endothelial progenitor cells (EPC). Meanwhile, there is evidence suggesting that EPC-derived exosomes (EPC-EX) promote vascular repair and angiogenesis through their carried microRNA (miR)-126. In this study, we investigated whether exercise could increase the levels of circulating EPC-EX and their miR-126 cargo, and by which promote the protective function of EPC-EX on endothelial cells (EC). Methods: Plasma EPC-EX from sedentary, low, or moderate exercise mice, respectively, denoted as EPC-EXS, EPC-EXL, and EPC-EXM, were isolated using microbead-based sorting techniques and characterized by nanoparticle tracking analysis, Western blot, and quantitative real-time polymerase chain …