Medicine and Health Sciences Commons^™

Pharmacologically Distinct Nicotinic Acetylcholine Receptors Drive Efferent-Mediated Excitation In Calyx-Bearing Vestibular Afferents, J. Chris Holt, Kevin Kewin, Paivi M. Jordan, Peter Cameron, Marcin Klapczynski, J. Michael Mcintosh, Peter A. Crooks, Linda P. Dwoskin, Anna Lysakowski

Pharmaceutical Sciences Faculty Publications

Electrical stimulation of vestibular efferent neurons rapidly excites the resting discharge of calyx/dimorphic (CD) afferents. In turtle, this excitation arises when acetylcholine (ACh), released from efferent terminals, directly depolarizes calyceal endings by activating nicotinic ACh receptors (nAChRs). Although molecular biological data from the peripheral vestibular system implicate most of the known nAChR subunits, specific information about those contributing to efferent-mediated excitation of CD afferents is lacking. We sought to identify the nAChR subunits that underlie the rapid excitation of CD afferents and whether they differ from α9α10 nAChRs on type II hair cells that drive efferent-mediated inhibition in adjacent bouton …

Mdr1 Sirna Loaded Hyaluronic Acid-Based Cd44 Targeted Nanoparticle Systems Circumvent Paclitaxel Resistance In Ovarian Cancer, Xiaoqian Yang, Arun K. Iyer, Amit Singh, Edwin Choy, Francis J. Hornicek, Mansoor M. Amiji, Zhenfeng Duan

Pharmaceutical Sciences Faculty Publications

Development of multidrug resistance (MDR) is an almost universal phenomenon in patients with ovarian cancer, and this severely limits the ultimate success of chemotherapy in the clinic. Overexpression of the MDR1 gene and corresponding P-glycoprotein (Pgp) is one of the best known MDR mechanisms. MDR1 siRNA based strategies were proposed to circumvent MDR, however, systemic, safe, and effective targeted delivery is still a major challenge. Cluster of differentiation 44 (CD44) targeted hyaluronic acid (HA) based nanoparticle has been shown to successfully deliver chemotherapy agents or siRNAs into tumor cells. The goal of this study is to evaluate the ability of …

No Evidence Of A Drug-Drug Interaction Between Letermovir (Mk-8228) And Mycophenolate Mofetil, Wl Marshall, C. Badshah, F. Liu, Walter K. Kraft, Md, F. Colon-Gonzalez, A. Van Schanke, Cr. Cho, E. Hulskotte, Jr Butterton, Ee Marcantonio

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Introduction:

Letermovir (MK-8228) is a potent, oncedaily inhibitor of the cytomegalovirus (CMV) terminase complex that is being developed for the prophylaxis of CMV infection in transplant patients. This study evaluated the pharmacokinetic interactions, safety, and tolerability of letermovir when coadministered in healthy subjects with mycophenolate mofetil (MMF), which is the morpholinoethyl ester prodrug of mycophenolic acid (MPA).

Methods:

This was an open-label trial in 14 healthy female subjects that explored the pharmacokinetic parameters of a single 1 g oral dose of MMF administered alone on Day 1 and coadministered on Day 12 with 480 mg oral once-daily letermovir given on …

Cerium Oxide Nanoparticle Aggregates Affect Stress Response And Function In Caenorhabditis Elegans, Steven Rogers, Kevin M. Rice, Nandini Manne, Tolou Shokuhfar, Kun He, Vellaisamy Selvaraj, Eric Blough

Pharmaceutical Science and Research

Objective: The continual increase in production and disposal of nanomaterials raises concerns regarding the safety of nanoparticles on the environmental and human health. Recent studies suggest that cerium oxide (CeO2) nanoparticles may possess both harmful and beneficial effects on biological processes. The primary objective of this study is to evaluate how exposure to different concentrations (0.17–17.21 µg/mL) of aggregated CeO2 nanoparticles affects indices of whole animal stress and survivability in Caenorhabditis elegans.

Methods: Caenorhabditis elegans were exposed to different concentrations of CeO2 nanoparticles and evaluated.

Results: Our findings demonstrate that chronic exposure of CeO2 nanoparticle aggregates is …

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang, Lin Xue, Shurong Hou

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

2014 Brings New Drugs, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

A Coming Disruption In Pharmacy?, Frank Romanelli, Timothy S. Tracy

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Effects Of Three Dry Powder Inhalers On Deposition Of Aerosolized Medicine In The Human Oral-Pharyngeal-Laryngeal Regions, Mohammed Ali

Technology Faculty Publications and Presentations

The dry powder inhaler (DPI) is a popular, effective and convenient drug delivery device for inhalation therapy to treat asthma. However, a large quantity (approximately 54%) of inhaled aerosols deposit in the oropharyngeal region. Deposition in this region is undesirable because it provides minimum therapeutic benefits and has adverse localized or systemic side effects. This study reports a method of examining electrostatic charge effects on deposition of three DPI aerosols (Spiriva^™ Handihaler, Advair Diskus^™, and Pulmicort^™ Turbohaler) in a cadaver-based cast of the human oral-pharyngeal-laryngeal (OPL) regions. Experimental aerosols were generated from the three commercially available …

Factors Affecting The Pharmacokinetics And Pharmacodynamics Of Pegylated Liposomal Irinotecan (Ihl-305) In Patients With Advanced Solid Tumors, Huali Wu, Jeffrey R. Infante, Vicki L. Keedy, Suzanne F. Jones, Emily Chan, Johanna C. Bendell, Wooin Lee, Whitney P. Kirschbrown, Beth A. Zamboni, Satoshi Ikeda, Hiroshi Kodaira, Mace L. Rothenberg, Howard A. Burris, William C. Zamboni

Pharmaceutical Sciences Faculty Publications

IHL-305 is a PEGylated liposomal formulation of irinotecan (CPT-11). The objective of this study was to evaluate the factors associated with interpatient variability in the pharmacokinetics and pharmacodynamics of IHL-305 in patients with advanced solid tumors. IHL-305 was administered intravenously once every 4 weeks as part of a Phase I study. Pharmacokinetic studies of the liposomal sum total CPT-11, released CPT-11, SN-38, SN-38G, 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin, and 7-ethyl-10-[4-amino-1-piperidino]-carbonyloxycamptothecin in plasma were performed. Noncompartmental and compartmental pharmacokinetic analyses were conducted using pharmacokinetic data for sum total CPT-11. The pharmacokinetic variability of IHL-305 is associated with linear and nonlinear clearance. Patients whose age …

Insulin/Insulin-Like Growth Factors In Cancer: New Roles For The Aryl Hydrocarbon Receptor, Tumor Resistance Mechanisms, And New Blocking Strategies, Travis B. Salisbury

Pharmaceutical Science and Research

The insulin-like growth factor 1 receptor (IGF1R) and the insulin receptor (IR) are receptor tyrosine kinases that are expressed in cancer cells.The results of different studies indicate that tumor proliferation and survival is dependent on the IGF1R and IR, and that their inhibition leads to reductions in proliferation and increases in cell death. Molecular targeting therapies that have been used in solid tumors include anti-IGF1R antibodies, anti-IGF1/IGF2 antibodies, and small molecule inhibitors that suppress IGF1R and IR kinase activity. New advances in the molecular basis of anti-IGF1R blocking antibodies reveal they are biased agonists and promote the binding of IGF1 …

Knowledge Gap In Adolescent Heart Transplant Recipients, Pamela Finn, Brian Birnbaum, Audrey R. Kennedy, Jennifer A. Marshall, Mark Gelatt

Posters

Background:

 Studies have reported a knowledge gap Studies have reported a knowledge gap among adolescent and young adult heart heart transplant patients upon transitioning to adult cardiology practices.

 This population is vulnerable to life-threatening complications as they progress to adult care.

Framework/Methods:

We assess the current knowledge deficit of our adolescent and young adult patients and their caregivers in order to inform pediatric providers of their unique needs as they prepare to transition.

Heart transplant patients >10 yrs and their caregivers completed a written questionnaire prior to a clinic visit. 17 questions were asked including the need for …

Pneumonia: Not Getting Vaccinated May Take Your Breath Away, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Impact Of A High-Fat Meal On Assessment Of Clopidogrel-Induced Platelet Inhibition In Healthy Subjects., Paul P. Dobesh, Jamela F. Urban, Scott W. Shurmur, Julie H. Oestreich

Journal Articles: Pharmacy Practice

BACKGROUND: Ideal conditions for platelet reactivity testing are critical for optimal selection of a P2Y12 inhibitor. Data are inconsistent regarding the impact of high-fat meals on test assessment.

METHODS: Participants included 12 healthy subjects not taking antiplatelet drugs after a 12-hour fast. After baseline assessment, subjects were given a 600 mg dose of clopidogrel. Four hours later, maximum platelet inhibition was tested in the fasting state by light transmission aggregometry (LTA), VerifyNow P2Y12, vasodilator-stimulated phosphoprotein (VASP), and whole blood aggregometry (WBA). Subjects were then provided a high-fat meal, and platelet function was evaluated two hours later. Change in measured platelet …

Local Uterine Ang-(1–7) Infusion Augments The Expression Of Cannabinoid Receptors And Differentially Alters Endocannabinoid Metabolizing Enzymes In The Decidualized Uterus Of Pseudopregnant Rats, K. B. Brosnihan, V. M. Pulgar, P. E. Gallagher, L. A. Neves, L. M. Yamaleyeva

Pharmaceutical Sciences

Background

Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1–7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation. We determined the effects of intra-uterine angiotensin-(1–7) [Ang-(1–7)] (24 microg/kg/h) or vehicle given into the left uterine horn on the ECs in the decidualized uterus.

Methods

Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment and decidualization was induced by a bolus of oil …

Local Uterine Ang-(1-7) Infusion Augments The Expression Of Cannabinoid Receptors And Differentially Alters Endocannabinoid Metabolizing Enzymes In The Decidualized Uterus Of Pseudopregnant Rats, K. B. Brosnihan, V. M. Pulgar, P. E. Gallagher, L. A. Neves, L. M. Yamaleyeva

Pharmaceutical Sciences

No abstract provided.

Bridged Filaments Of Histone-Like Nucleoid Structuring Protein Pause Rna Polymerase And Aid Termination In Bacteria., Matthew V. Kotlajich, Daniel R. Hron, Beth A. Boudreau, Zhiqiang Sun, Yuri L. Lyubchenko, Robert Landick

Journal Articles: Pharmaceutical Sciences

Bacterial H-NS forms nucleoprotein filaments that spread on DNA and bridge distant DNA sites. H-NS filaments co-localize with sites of Rho-dependent termination in Escherichia coli, but their direct effects on transcriptional pausing and termination are untested. In this study, we report that bridged H-NS filaments strongly increase pausing by E. coli RNA polymerase at a subset of pause sites with high potential for backtracking. Bridged but not linear H-NS filaments promoted Rho-dependent termination by increasing pause dwell times and the kinetic window for Rho action. By observing single H-NS filaments and elongating RNA polymerase molecules using atomic force microscopy, we …

Cd163 Interacts With Tweak To Regulate Tissue Regeneration After Ischaemic Injury, Hirokuni Akahori, Vinit Karmali, Rohini Polavarapu, Adrienne L. King

Faculty Articles

biological sciences, medical research

Is Kava Safe To Be Used By The Public?, Antoine Al-Achi

Pharmaceutical Sciences

No abstract provided.

Does Epigallocatechin-3-Gallate-Insulin Complex Protect Human Insulin From Proteolytic Enzyme Action?, Antoine Al-Achi, Deepthi Kota

Pharmaceutical Sciences

No abstract provided.

Physical Characteristics Of Sixteen Non-Prescription Medications: Specific Gravity, Ph, Surface Tension, And Rheological Characteristics, Antoine Al-Achi, A. Kathuria, M. Zahid Khan

Pharmaceutical Sciences

No abstract provided.

Evaluating The Effects Of An Interdisciplinary Practice Model With Pharmacist Collaboration On Hiv Patient Co-Morbidities, Rebecca Cope, Leonard Berkowitz, Rebecca Arcebido, Jun-Yen Yeh, Nathan Trustman, Agnes Cha

Touro College of Pharmacy (New York) Publications and Research

Treatment of HIV now occurs largely within the primary care setting, and the principal focus of most visits has become the management of chronic disease states. The clinical pharmacist’s potential role in improving chronic disease outcomes for HIV patients is unknown. A retrospective cohort study was performed for HIV-positive patients also diagnosed with diabetes, hypertension, or hyperlipidemia. Characteristics and outcomes in 96 patients treated by an interdisciplinary team which included a clinical pharmacist (i.e., the intervention group) were compared to those in 50 patients treated by an individual healthcare provider (i.e., the control group). Primary outcomes were changes from baseline …

Customized Order-Entry Sets Can Prevent Antiretroviral Prescribing Errors: A Novel Opportunity For Antimicrobial Stewardship, Yi Guo, Philip Chung, Caryn Weiss, Keith Veltri, Grace Y. Minamoto

Touro College of Pharmacy (New York) Publications and Research

Background: Patients with human immunodeficiency virus (HIV) infection on antiretroviral (ARV) therapy are at increased risk for medication errors during transitions of care between the outpatient and inpatient settings. This can lead to treatment failure or toxicity. Previous studies have emphasized the prevalence of medication errors in such patients, but few have reported initiatives to prevent errors from occurring.

Methods: The study was conducted in a 1,400-bed health care center with a state-designated Acquired Immunodeficiency Syndrome (AIDS) Center in the Bronx, New York. The antimicrobial stewardship team and HIV specialists developed customized order-entry sets (COES) to guide ARV …

Majority Of Hiv/Hcv Patients Need To Switch Antiretroviral Therapy To Accommodate Direct Acting Antivirals, Rebecca Cope, Aaron Pickering, Thomas Glowa, Samantha Faulds, Peter Veldkamp, Ramakrishna Prasad

Touro College of Pharmacy (New York) Publications and Research

The impact of drug–drug interactions (DDIs) between interferon-free direct acting antiviral (DAA) regimens and antiretrovirals (ART) among HIV/HCV co-infected individuals in clinical practice settings is unknown. A singlecenter, retrospective chart review of co-infected patients was conducted from June 2014 to February 2015. Significant interactions between simeprevir (SMV), ledipasvir (LDV), and paritaprevir/ritonavir/ombitasvir plus dasabuvir (3D regimen) with ART were identified based on available literature. SMV had the largest number of DDIs and was further investigated to determine the feasibility of ART switch to allow for DAA use. Of 127 subjects, 23% had advanced liver disease; 86% of those with known HCV …

Treatment Outcomes For Infections Caused By “Spice” (S–Serratia, P–Pseudomonas Aeruginosa, I–Indole Positive Proteus, C–Citrobacter, E– Enterobacter) Organisms: Carbapenem Versus Non-Carbapenem Regimens, Stanley Moy, Roopali Sharma

Touro College of Pharmacy (New York) Publications and Research

Background. Techniques to identify AmpC β-lactamases in SPICE organisms are not yet optimized for the clinical laboratory and are not routinely done. Clinicians are often left with an uncertainty on the choice of antibiotic when a SPICE organism is isolated. The purpose of this study is to evaluate the outcomes of carbapenem versus non-carbapenem regimens in treating bacteremia or urinary tract infection (UTI) from a SPICE organism in a “real-world” setting.

Methods. This was a single-center, retrospective, case-cohort study consisting of adult patients who had clinical infection with a SPICE organism isolated from blood or urine cultures. Patients …

Defining The Role Of Dexmedetomidine In The Prevention Of Delirium In The Intensive Care Unit (Icu), S. Nelson, A. J. Muzyk, M. Bucklin, S. Brundey, J. P. Gagliardi

Pharmacy Practice

No abstract provided.

Manifestations Of Anxiety? Explaining Tachycardia And Hypertension In A Patient With Pots, B. B. Kincaid, A. J. Muzyk, R. J. Kanter, X. A. Preud'homme

Pharmacy Practice

No abstract provided.

Inhibition Of Lapatinib-Induced Kinome Reprogramming In Erbb2-Positive Breast Cancer By Targeting Bet Family Bromodomains, T. J. Stuhlmiller, S. M. Miller, J. S. Zawistowski, K. Nakamura, A. S. Beltran, J. S. Duncan, S. P. Angus, K. A. L. Collins, D. A. Granger, R. A. Reuther, L. M. Graves, S. M. Gomez, P-F Kuan, J. S. Parker, X. Chen, N. Sciaky, L. A. Carey, H. S. Earp, J. Jin, G. L. Johnson

Pharmaceutical Sciences

No abstract provided.

Anticancer Activity Of A Thymidine Quinoxaline Conjugate Is Modulated By Cytosolic Thymidine Pathways, Qiong Wei, Haijuan Liu, Honghao Zhou, Dejun Zhang, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Background

High levels of thymidine kinase 1 (TK1) and thymidine phosphorylase (TYMP) are key molecular targets by thymidine therapeutics in cancer treatment. The dual roles of TYMP as a tumor growth factor and a key activation enzyme of anticancer metabolites resulted in a mixed outcome in cancer patients. In this study, we investigated the roles of TK1 and TYMP on a thymidine quinoxaline conjugate to evaluate an alternative to circumvent the contradictive role of TYMP.

Methods

TK1 and TYMP levels in multiple liver cell lines were assessed along with the cytotoxicity of the thymidine conjugate. Cellular accumulation of the thymidine …

6-Hydroxyflavone And Derivatives Exhibit Potent Anti-Inflammatory Activity Among Mono-, Di- And Polyhydroxylated Flavones In Kidney Mesangial Cells, Xing Wang, Zhiwei Wang, Preetpal Singh Sidhu, Umesh R. Desai, Qibing Zhou

Medicinal Chemistry Publications

Inflammatory responses by kidney mesangial cells play a critical role in the glomerulonephritis. The anti-inflammatory potential of nineteen mono-, di- and polyhydroxylated flavones including fisetin, quercetin, morin, tricetin, gossypetin, apigenin and myricetin were investigated on rat mesangial cells with lipopolysaccharide (LPS) as the inflammatory stimuli. 6-Hydroxyflavone and 4′,6-dihydroxyflavone exhibited high activity with IC50 in the range of 2.0 μM, a much better inhibition potential in comparison to the well-studied polyhydroxylated flavones. Interestingly, the anti-inflammatory activity was not due to direct quenching of NO radicals. Investigation on derivatives with methylation, acetylation or sulfation of 6-hydroxyl group revealed that 6-methoxyflavone was the …

Evaluation Of Methyl-Binding Domain Based Enrichment Approaches Revisited, Karolina A. Aberg, Linying Xie, Robin F. Chan, Min Zhao, Ashutosh K. Pandey, Gaurav Kumar, Shaunna L. Clark, Edwin Jcg Van Den Oord

Biomarker Research and Personalized Medicine Publications

Methyl-binding domain (MBD) enrichment followed by deep sequencing (MBD-seq), is a robust and cost efficient approach for methylome-wide association studies (MWAS). MBD-seq has been demonstrated to be capable of identifying differentially methylated regions, detecting previously reported robust associations and producing findings that replicate with other technologies such as targeted pyrosequencing of bisulfite converted DNA. There are several kits commercially available that can be used for MBD enrichment. Our previous work has involved MethylMiner (Life Technologies, Foster City, CA, USA) that we chose after careful investigation of its properties. However, in a recent evaluation of five commercially available MBD-enrichment kits the …