Pharmacy and Pharmaceutical Sciences Commons^™

Strategies To Improve Control Of Blood A1c In Diabetics, Jennifer Aronson, Leanne Bellino, Elizabeth Eisenhardt, Diane Bryant, Haley Pelletier, Internal Medicine Team, Adult Outpatient Clinic

MaineHealth Maine Medical Center

A1c monitoring is an important aspect of controlling the health of a diabetic patient. An adult internal medicine clinic noted that the percentage of their diabetic patients who had an A1c higher than 9 or no reading within the past year exceeded the national average. As a result, operational excellence methods were implemented with the overall goal to reduce their percentage to 18% or less.

A root cause analysis identified several deficiencies to includelack of essential equipment, variations in

staff education and the absence of daily reminders.

Post KPI implementations, an overall decrease in the percentage of patients with poorly …

Delirium Reduction Strategies For The Critically Ill, June Chaves, Sam Canonico, Will Cheney, Tammy Corey, Gil Fraser, Alex Kowalewski, Jen Low, Cardiac Intensive Care Unit, Haley Pelletier, Cathy Palleschi, Stephen Tyzik, Suneela Nayak, Ruth Hanselman

MaineHealth Maine Medical Center

Delirium, an acute and fluctuating disturbance of consciousness and cognition, is a common manifestation of acute brain dysfunction in critically ill patients. Patients with delirium have longer hospital stays and a lower 6-month survival rate than do patients without delirium. Preliminary research suggests that delirium may be associated with cognitive impairment that persists months to years after discharge.

In a large acute care hospital, the cardiac intensive care staff became interested in mitigating their unit’s high delirium rate of ventilated patients. At baseline, many members of the healthcare team did not believe that delirium could be prevented and the predominant …

Communication Of Medication Side Effects In An Acute Care Hospital, Deb Bachand, Rachel Caiola, R6 Neurology Med-Surg Unit, Haley Pelletier, Brendan Lilley, Suneela Nayak, Ruth Hanselman, Stephen Tyzik

MaineHealth Maine Medical Center

COMMUNICATION OF MEDICATION SIDE EFFECTS IN AN ACUTE CARE HOSPITAL

Effective patient education of prescribed medication side effects improves patient safety and reduces overall risk. On an acute care hospital unit, nursing staff felt previous attempts at this education had been ineffective as demonstrated by their HCAHPs scores for communication about medications.

A root cause analysis demonstrated some flaws and several countermeasures were instituted. The goal of this KPI project was to attain a higher than national average for the specific HCAHPs score.

Post KPI inception, the unit’s HCAHPs data showed steady improvement. Within one month, the goal of an …

Selective Inhibitors Of Human Mpges-1 From Structure-Based Computational Screening, Ziyuan Zhou, Yaxia Yuan, Shuo Zhou, Kai Ding, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Human mPGES-1 is recognized as a promising target for next generation of anti-inflammatory drugs. Although various mPGES-1 inhibitors have been reported in literature, few have entered clinical trials and none has been proven clinically useful so far. It is highly desired for developing the next generation of therapeutics for inflammation-related diseases to design and discover novel inhibitors of mPGES-1 with new scaffolds. Here, we report the identification of a series of new, potent and selective inhibitors of human mPGES-1 with diverse scaffolds through combined computational and experimental studies. The computationally modeled binding structures of these new inhibitors with mPGES-1 provide …

Polymer Nanoassemblies With Hydrophobic Pendant Groups In The Core Induce False Positive Sirna Transfection In Luciferase Reporter Assays, Steven Rheiner, Derek Alexander Reichel, Piotr G. Rychahou, Tadahide Izumi, Hsin-Sheng Yang, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(L-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P′), PEG-PLL-PAL (3P′), and PEG-PEI-DOC (2PD). In vitro transfection and western blot assays of luciferase …

Effectiveness Of Switching Smoking-Cessation Medications Following Relapse, Bryan W. Heckman, K. Michael Cummings, Karin A. Kasza, Ron Borland, Jessica L. Burris, Geoffrey T. Fong, Ann Mcneill, Matthew J. Carpenter

Psychology Faculty Publications

Introduction—Nicotine dependence is a chronic disorder often characterized by multiple failed quit attempts (QAs). Yet, little is known about the sequence of methods used across multiple QAs or how this may impact future ability to abstain from smoking. This prospective cohort study examines the effectiveness of switching smoking-cessation medications (SCMs) across multiple QAs.

Methods—Adult smokers (aged ≥ 18 years) participating in International Tobacco Control surveys in the United Kingdom, U.S., Canada, and Australia (N=795) who: (1) completed two consecutive surveys between 2006 and 2011; (2) initiated a QA at least 1 month before each survey; and (3) provided …

Blocking An N-Terminal Acetylation-Dependent Protein Interaction Inhibits An E3 Ligase, Daniel C. Scott, Jared T. Hammill, Jaeki Min, David Y. Rhee, Michele Connelly, Vladislav O. Sviderskiy, Deepak Bhasin, Yizhe Chen, Su-Sien Ong, Sergio C. Chai, Asli N. Goktug, Guochang Huang, Julie K. Monda, Jonathan Low, Ho Shin Kim, Joao A. Paulo, Joe R. Cannon, Anang A. Shelat, Taosheng Chen, Ian R. Kelsall, Arno F. Alpi, Vishwajeeth Pagala, Xusheng Wang, Junmin Peng, Bhuvanesh Singh, J. Wade Harper, Brenda A. Schulman, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

N-terminal acetylation is an abundant modification influencing protein functions. Because ∼80% of mammalian cytosolic proteins are N-terminally acetylated, this modification is potentially an untapped target for chemical control of their functions. Structural studies have revealed that, like lysine acetylation, N-terminal acetylation converts a positively charged amine into a hydrophobic handle that mediates protein interactions; hence, this modification may be a druggable target. We report the development of chemical probes targeting the N-terminal acetylation–dependent interaction between an E2 conjugating enzyme (UBE2M or UBC12) and DCN1 (DCUN1D1), a subunit of a multiprotein E3 ligase for the ubiquitin-like protein NEDD8. The inhibitors are …

A Direct In Vivo Comparison Of The Melanocortin Monovalent Agonist Ac-His-Dphe-Arg-Trp-Nh2 Versus The Bivalent Agonist Ac-His-Dphe-Arg-Trp-Pedg20-His-Dphe-Arg-Trp-Nh2: A Bivalent Advantage, Cody J Lensing, Danielle N Adank, Stacey L Wilber, Katie T Freeman, Sathya M Schnell, Robert Charles Speth, Adam T Zarth, Carrie Haskell-Luevano

Faculty Articles

Bivalent ligands targeting putative melanocortin receptor dimers have been developed and characterized in vitro, however studies of their functional in vivo effects have been limited. The current report compares the effects of homobivalent ligand CJL-1-87, Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH₂, to monovalent ligand CJL-1-14, Ac-His-DPhe-Arg-Trp-NH₂ on energy homeostasis in mice after central intracerebroventricular (ICV) administration into the lateral ventricle of the brain. Bivalent ligand CJL-1-87 had noteworthy advantages as an anti-obesity probe over CJL-1-14 in a fasting-refeeding in vivo paradigm. Treatment with CJL-1-87 significantly decreased food intake compared to CJL-1-14 or saline (50% less intake 2 to 8 hours after …

A Consensus Definitive Classification Of Scavenger Receptors And Their Roles In Health And Disease, Mercy R Prabhudas, Cynthia L Baldwin, Paul L Bollyky, Dawn M E Bowdish, Kurt Drickamer, Maria Febbraio, Joachim Herz, Lester Kobzik, Monty Krieger, John Loike, Benita Mcvicker, Terry K Means, Soren K Moestrup, Steven R Post, Tatsuya Sawamura, Samuel Silverstein, Robert Charles Speth, Janice C Telfer, Geoffrey M Thiele, Xiang-Yang Wang, Samuel D Wright, Joseph El Khoury

Faculty Articles

Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and …

Application Of Fluoroquinolone Resistance Score In Management Of Complicated Urinary Tract Infections, Ansal Shah, Julie Ann Justo, P Brandon Bookstaver, Joseph Kohn, Helmut Albrecht, Majdi N. Al-Hasan

Faculty Publications

The fluoroquinolone resistance score (FQRS) predicts the probability of fluoroquinolone resistance with good discrimination. The score has been derived from patients with bloodstream infections caused by Gram-negative bacteria and is based on fluoroquinolone use within the past 6 months, among other clinical and health care exposure criteria. This study aims to examine the utility of the FQRS in patients with complicated urinary tract infections (cUTI) and determine whether extension of prior fluoroquinolone use to 12 months improves model discrimination. Adults with cUTI at Palmetto Health in central South Carolina, USA, from 1 April 2015 through 31 July 2015 were prospectively …

Outcomes After Diagnosis Of Mild Cognitive Impairment In A Large Autopsy Series, Erin L. Abner, Richard J. Kryscio, Frederick A. Schmitt, David W. Fardo, Daniela C. Moga, Eseosa T. Ighodaro, Gregory A. Jicha, Lei Yu, Hiroko H. Dodge, Chengjie Xiong, Randall L. Woltjer, Julie A. Schneider, Nigel J. Cairns, David A. Bennett, Peter T. Nelson

Epidemiology and Environmental Health Faculty Publications

OBJECTIVE: To determine clinical and neuropathological outcomes following a clinical diagnosis of mild cognitive impairment (MCI).

METHODS: Data were drawn from a large autopsy series (N = 1,337) of individuals followed longitudinally from normal or MCI status to death, derived from 4 Alzheimer Disease (AD) Centers in the United States.

RESULTS: Mean follow‐up was 7.9 years. Of the 874 individuals ever diagnosed with MCI, final clinical diagnoses were varied: 39.2% died with an MCI diagnosis, 46.8% with a dementia diagnosis, and 13.9% with a diagnosis of intact cognition. The latter group had pathological features resembling those with a final clinical …

Buprenorphine Physician Supply: Relationship With State-Level Prescription Opioid Mortality, Hannah K. Knudsen, Jennifer R. Havens, Michelle R. Lofwall, Jamie L. Studts, Sharon L. Walsh

Behavioral Science Faculty Publications

Background: Buprenorphine is an effective treatment for opioid use disorder but the supply of buprenorphine physicians is currently inadequate to address the nation’s prescription opioid crisis. Perception of need due to rising opioid overdose rates is one possible reason for physicians to adopt buprenorphine. This study examined associations between rates of growth in buprenorphine physicians and prescription opioid overdose mortality rates in US states.

Methods: The total buprenorphine physician supply and number of physicians approved to treat 100 patients (per 100,000 population) were measured from June 2013 to January 2016. States were divided into two groups: those with rates of …

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P. Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N. Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A. Valeriote, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS² runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …

Mccrearamycins A-D, Geldanamycin-Derived Cyclopentenone Macrolactams From An Eastern Kentucky Abandoned Coal Mine Microbe, Xiachang Wang, Yinan Zhang, Larissa V. Ponomareva, Qingchao Qiu, Ryan M. Woodcock, Sherif I. Elshahawi, Xiabin Chen, Ziyuan Zhou, Bruce E. Hatcher, James C. Hower, Chang-Guo Zhan, Sean Parkin, Madan K. Kharel, S. Randal Voss, Khaled A. Shaaban, Jon S. Thorson

Center for Pharmaceutical Research and Innovation Faculty Publications

Four cyclopentenone‐containing ansamycin polyketides (mccrearamycins A–D), and six new geldanamycins (Gdms B–G, including new linear and mycothiol conjugates), were characterized as metabolites of Streptomyces sp. AD‐23‐14 isolated from the Rock Creek underground coal mine acid drainage site. Biomimetic chemical conversion studies using both simple synthetic models and Gdm D confirmed that the mccrearamycin cyclopentenone derives from benzilic acid rearrangement of 19‐hydroxy Gdm, and thereby provides a new synthetic derivatization strategy and implicates a potential unique biocatalyst in mccrearamycin cyclopentenone formation. In addition to standard Hsp90α binding and cell line cytotoxicity assays, this study also highlights the first assessment of Hsp90α …

Adverse Events And Treatment Discontinuations Of Antimuscarinics For The Treatment Of Overactive Bladder In Older Adults: A Systematic Review And Meta-Analysis, Scott Martin Vouri, Clark D. Kebodeaux, Paul M. Stranges, Besu F. Teshome

Pharmacy Practice and Science Faculty Publications

Introduction

Antimuscarinics should be used with caution in older adults with overactive bladder (OAB) due to anticholinergic adverse events (AEs). Systematic reviews and meta-analyses (SRMAs) have analyzed safety-related outcomes but have not specified risk in the elderly, the population at highest risk for AEs. The aim of this review is to explore and evaluate AEs and treatment discontinuations in adults 65 or older taking antimuscarinics for OAB.

Methods

Keywords were searched in MEDLINE, EMBASE, SCOPUS, and Cochrane Central Register for Controlled Trials. Randomized controlled trials (RCTs) along with sub-analyses and pooled analyses that compared antimuscarinics to placebo or another antimuscarinic …

Efficacy And Tolerability Of Adjunctive Brivaracetam In Patients With Prior Antiepileptic Drug Exposure: A Post-Hoc Study., Ali A. Asadi-Pooya, Michael R. Sperling, Steve Chung, Pavel Klein, Anyzeila Diaz, Sami Elmoufti, Jimmy Schiemann, John Whitesides

Department of Neurology Faculty Papers

Brivaracetam (BRV), a selective, high-affinity ligand for synaptic vesicle protein 2A, is a new antiepileptic drug (AED) for adjunctive treatment of focal (partial-onset) seizures in adults with epilepsy. This post-hoc analysis was conducted to explore the efficacy of adjunctive BRV in patients with prior levetiracetam (LEV) exposure and whether changes in efficacy were related to the similar mechanism of action of these two drugs. Data were pooled from three Phase III studies (NCT00490035; NCT00464269; NCT01261325) of adults with focal seizures taking 1-2 AEDs who received placebo or BRV 50-200mg/day without titration over a 12-week treatment period. Patients taking concomitant LEV …

Inhibition Of Cdk8 Mediator Kinase Suppresses Estrogen Dependent Transcription And The Growth Of Estrogen Receptor Positive Breast Cancer, Martina S. Mcdermott, Alexander A. Chumanevich, Chang-Uk Lim, Jiaxin Liang, Mengqian Chen, Serena Altilia, David Oliver, James M. Rae, Michael Shtutman, Hippokratis Kiaris, Balázs Győrffy, Igor Roninson, Eugenia Broude

Faculty Publications

Hormone therapy targeting estrogen receptor (ER) is the principal treatment for ER-positive breast cancers. However, many cancers develop resistance to hormone therapy while retaining ER expression. Identifying new druggable mediators of ER function can help to increase the efficacy of ER-targeting drugs. Cyclin-dependent kinase 8 (CDK8) is a Mediator complex-associated transcriptional regulator with oncogenic activities. Expression of CDK8, its paralog CDK19 and their binding partner Cyclin C are negative prognostic markers in breast cancer. Meta-analysis of transcriptome databases revealed an inverse correlation between CDK8 and ERα expression, suggesting that CDK8 could be functionally associated with ER. We have found that …

Mechanisms Of Modulation Of Brain Microvascular Endothelial Cells Function By Thrombin., Eugen Brailoiu, Megan M. Shipsky, Guang Yan, Mary E. Abood, G. Cristina Brailoiu

College of Pharmacy Faculty Papers

Brain microvascular endothelial cells are a critical component of the blood-brain barrier. They form a tight monolayer which is essential for maintaining the brain homeostasis. Blood-derived proteases such as thrombin may enter the brain during pathological conditions like trauma, stroke, and inflammation and further disrupts the permeability of the blood-brain barrier, via incompletely characterized mechanisms. We examined the underlying mechanisms evoked by thrombin in rat brain microvascular endothelial cells (RBMVEC). Our results indicate that thrombin, acting on protease-activated receptor 1 (PAR1) increases cytosolic Ca

A Quantitative Lc-Ms/Ms Method For Simultaneous Determination Of Cocaine And Its Metabolites In Whole Blood, Xiabin Chen, Xirong Zheng, Kai Ding, Ziyuan Zhou, Chang-Guo Zhan, Fang Zheng

Molecular Modeling and Biopharmaceutical Center Faculty Publications

As new metabolic pathways of cocaine were recently identified, a high performance liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed to simultaneously determine cocaine and nine cocaine-related metabolites in whole blood samples. One-step solid phase extraction was used to extract all of the ten compounds and corresponding internal standards from blood samples. All compounds and internal standards extracted were separated on an Atlantis T3 (100 Å, 3 μm, 2.1 mm × 150 mm I.D) column and detected in positive ion and high sensitivity mode with multiple reaction monitoring. This method was validated for its sensitivity, linearity, specificity, accuracy, precision, …

Nephrotoxicity During Vancomycin Therapy In Combination With Piperacillin-Tazobactam Or Cefepime, Wilbur Cliff Rutter, Jessica N. Cox, Craig A. Martin, Donna R. Burgess, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Recent reports have demonstrated that vancomycin (VAN) may lead to an increase in the incidence of acute kidney injury (AKI) when it is combined with antipseudomonal beta-lactams. This study compared the incidence of AKI associated with VAN plus piperacillin-tazobactam (TZP) or cefepime (FEP). This was a retrospective, matched cohort study that was conducted at an academic medical center between September 2010 and September 2014 and that included adult patients without severe chronic or structural kidney disease, dialysis, pregnancy, cystic fibrosis, or a hospital transfer receiving TZP-VAN or FEP-VAN for at least 48 h. The primary outcome was the difference in …

Obesity: Current And Potential Pharmacotherapeutics And Targets, Vidya Narayanaswami, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Publications

Obesity is a global epidemic that contributes to a number of health complications including cardiovascular disease, type 2 diabetes, cancer and neuropsychiatric disorders. Pharmacotherapeutic strategies to treat obesity are urgently needed. Research over the past two decades has increased substantially our knowledge of central and peripheral mechanisms underlying homeostatic energy balance. Homeostatic mechanisms involve multiple components including neuronal circuits, some originating in hypothalamus and brain stem, as well as peripherally-derived satiety, hunger and adiposity signals that modulate neural activity and regulate eating behavior. Dysregulation of one or more of these homeostatic components results in obesity. Coincident with obesity, reward mechanisms …

Moderating Effects Of Immunosuppressive Medications And Risk Factors For Post-Operative Joint Infection Following Total Joint Arthroplasty In Patients With Rheumatoid Arthritis Or Osteoarthritis, Elizabeth G. Salt, Amanda T. Wiggins, Mary Kay Rayens, Brent J. Morris, David M. Mannino, Andrew Hoellein, Ryan P. Donegan, Leslie J. Crofford

Nursing Faculty Publications

Objective—Inconclusive findings about infection risks, importantly the use of immunosuppressive medications, in patients who have undergone large-joint total joint arthroplasty challenge efforts to provide evidenced-based perioperative total joint arthroplasty recommendations to improve surgical outcomes. Thus, the aim of this study was to describe risk factors for developing a postoperative infection in patients undergoing TJA of a large joint [total hip arthroplasty, total knee arthroplasty, or total shoulder arthroplasty] by identifying clinical and demographic factors, including the use of high risk medications (i.e., prednisone and immunosuppressive medications) and diagnoses (i.e., rheumatoid arthritis [RA], osteoarthritis [OA], gout, obesity, diabetes mellitus), that …

Caphosol For Prevention Of Oral Mucositis In Pediatric Myeloablative Haematopoietic Cell Transplantation., Nathaniel Treister, Michael Nieder, Christina Baggott, Ellen Olson, Lu Chen, Ha Dang, Mark Krailo, Amanda August, Lillian Sung

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The primary objective was to determine whether topically administered Caphosol, rinsed orally four times daily at the initiation of conditioning, reduces the duration of severe oral mucositis (OM) compared with placebo among children and adolescents undergoing haematopoietic cell transplantation (HCT).

METHODS: This was a Children's Oncology Group multicentre randomised double-blinded placebo-controlled clinical trial. Patients between the ages of 4 and 21 years who were scheduled to undergo myeloablative HCT for any indication were randomised to Caphosol or placebo saline rinses four times daily from initiation of conditioning through day +20. Subjects were assessed daily for OM using the World …

The Application Of Half-Life In Clinical Decision Making: Comparison Of The Pharmacokinetics Of Extended-Release Topiramate (Usl255) And Immediate-Release Topiramate, Barry E. Gidal, Annie M. Clark, Bob Anders, Frank Gilliam

Neuroscience Faculty Publications

Objective: For extended-release drugs with multi-compartment kinetics, such as topiramate, effective half-life (t_1/2eff) may be a more clinically relevant parameter than elimination half-life (t_1/2z). Using topiramate as a real-life example, the objective was to compare these half-life values for immediate- and extended-release topiramate (TPM-IR and USL255, respectively) to understand how drug pharmacokinetics may impact drug dosing recommendations.

Methods: The t_1/2z and t_1/2eff for USL255 and TPM-IR were compared using data from a phase I study (N = 36) of 200 mg USL255 administered once daily (QD) or TPM-IR twice daily (BID); effect of sampling duration …

Bis(N-Amidinohydrazones) And N-(Amidino)-N'-Aryl-Bishydrazones: New Classes Of Antibacterial/Antifungal Agents, Sanjib K. Shrestha, Liliia M. Kril, Keith D. Green, Stefan Kwiatkowski, Vitaliy M. Sviripa, Justin Robert Nickell, Linda Phyliss Dwoskin, David S. Watt, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicr obial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N'-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step, resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of …

Developmental Toxicity Of Nicotine: A Transdisciplinary Synthesis And Implications For Emerging Tobacco Products, Lucinda J. Enland, Kjersti Aagaard, Michele Bloch, Kevin Conway, Kelly Cosgrove, Rachel Grana, Thomas J. Gould, Dorothy Hatsukami, Frances Jensen, Denise Kandel, Bruce Lanphear, Frances Leslie, James R. Pauly, Jenae Neiderhiser, Mark Rubinstein, Theodore A. Slotkin, Eliot Spindel, Laura Stroud, Lauren Wakschlag

Pharmaceutical Sciences Faculty Publications

While the health risks associated with adult cigarette smoking have been well described, effects of nicotine exposure during periods of developmental vulnerability are often overlooked. Using MEDLINE and PubMed literature searches, books, reports and expert opinion, a transdisciplinary group of scientists reviewed human and animal research on the health effects of exposure to nicotine during pregnancy and adolescence. A synthesis of this research supports that nicotine contributes critically to adverse effects of gestational tobacco exposure, including reduced pulmonary function, auditory processing defects, impaired infant cardiorespiratory function, and may contribute to cognitive and behavioral deficits in later life. Nicotine exposure during …

Utilization Of Free Medication Samples In The United States In A Nationally Representative Sample: 2009-2013, Joshua D. Brown, Pratik A. Doshi, Jeffery C. Talbert

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Background—Manufacturers provide free sample medications as a means to increase use of branded medications. Sample use varies year-to-year as branded product patents expire and new products come to market.

Objective—This study sought to describe the use of sample medications during 2009–2013 and assess individual characteristics associated with sample use.

Methods—Data from the 2009–2013 U.S. Medical Expenditure Panel Survey (MEPS) were used. MEPS asks participants whether they received each medication they are taking as a sample. The top 10 medications and medication classes used each year by volume were identified as well as the proportion of people who …

From Dose To Response: In Vivo Nanoparticle Processing And Potential Toxicity, Uschi M. Graham, Gary Jacobs, Robert A. Yokel, Burtron H. Davis, Alan K. Dozier, M. Eileen Birch, Michael T. Tseng, Günter Oberdörster, Alison Elder, Lisa Delouise

Pharmaceutical Sciences Faculty Publications

Adverse human health impacts due to occupational and environmental exposures to manufactured nanoparticles are of concern and pose a potential threat to the continued industrial use and integration of nanomaterials into commercial products. This chapter addresses the inter-relationship between dose and response and will elucidate on how the dynamic chemical and physical transformation and breakdown of the nanoparticles at the cellular and subcellular levels can lead to the in vivo formation of new reaction products. The dose-response relationship is complicated by the continuous physicochemical transformations in the nanoparticles induced by the dynamics of the biological system, where dose, bio-processing, and …

Effects Of Target-Controlled Infusion Of High-Dose Naloxone On Pain And Hyperalgesia In A Human Thermal Injury Model: A Study Protocol, Anders D. Springborg, Elisabeth K. Jensen, Bradley K. Taylor, Mads U. Werner

Physiology Faculty Publications

Mu-opioid-receptor antagonists have been extensively studied in experimental research as pharmacological tools uncovering mechanisms of pain modulation by the endogenous opioid system. In rodents, administration of high doses of mu-opioid-receptor antagonists after the resolution of an inflammatory injury has demonstrated reinstatement of nociceptive hypersensitivity indicating unmasking of latent sensitization. In a recent human study, pain hypersensitivity assessed as secondary hyperalgesia area (SHA), was reinstated 7 days after a mild thermal injury, in 4 out of 12 subjects after a naloxone infusion.

The aims of the present study are first, to replicate our previous findings in a larger-sized study; second, to …

Plant Expression Of Cocaine Hydrolase-Fc Fusion Protein For Treatment Of Cocaine Abuse, Guojun Wang, Ting Zhang, Haifeng Huang, Shurong Hou, Xiabin Chen, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.

RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to …