Pharmacy and Pharmaceutical Sciences Commons^™

Biological Nanomotors With A Revolution, Linear, Or Rotation Motion Mechanism, Peixuan Guo, Hiroyuki Noji, Christopher M. Yengo, Zhengyi Zhao, Ian Grainge

Nanobiotechnology Center Faculty Publications

The ubiquitous biological nanomotors were classified into two categories in the past: linear and rotation motors. In 2013, a third type of biomotor, revolution without rotation (http://rnanano.osu.edu/movie.html), was discovered and found to be widespread among bacteria, eukaryotic viruses, and double-stranded DNA (dsDNA) bacteriophages. This review focuses on recent findings about various aspects of motors, including chirality, stoichiometry, channel size, entropy, conformational change, and energy usage rate, in a variety of well-studied motors, including F_oF₁ ATPase, helicases, viral dsDNA-packaging motors, bacterial chromosome translocases, myosin, kinesin, and dynein. In particular, dsDNA translocases are used to illustrate how …

Micro- And Nanoparticulate Cancer Vaccines: A Vision For The Future, Lipika Chablani

Pharmacy Faculty/Staff Publications

In lieu of an abstract, here is the article's first paragraph:

Formulation scientists are constantly challenged with unique opportunities to deliver chemotherapeutic drug molecules to cancer patients. With the growing rate of cancer diagnoses, new therapies are being introduced to pave their way to the market. Along with drug delivery, these formulation approaches are being screened for formulation, design, and development of cancer vaccines. Can a vaccine be formulated to obtain a protective or therapeutic immune response against cancer?

Retigabine Holds Kv7 Channels Open And Stabilizes The Resting Potential, Aaron Corbin-Leftwich, Sayeed M. Mossadeq, Junghoon Ha, Iwona Ruchala, Audrey Han Ngoc Le, Carlos A. Villalba-Galea

School of Pharmacy Faculty Articles

The anticonvulsant Retigabine is a KV7 channel agonist used to treat hyperexcitability disorders in humans. Retigabine shifts the voltage dependence for activation of the heteromeric KV7.2/KV7.3 channel to more negative potentials, thus facilitating activation. Although the molecular mechanism underlying Retigabine's action remains unknown, previous studies have identified the pore region of KV7 channels as the drug's target. This suggested that the Retigabine-induced shift in voltage dependence likely derives from the stabilization of the pore domain in an open (conducting) conformation. Testing this idea, we show that the heteromeric KV7.2/KV7.3 channel has at least two open states, which we named O1 …

Unexpected Reaction Pathway For Butyrylcholinesterase-Catalyzed Inactivation Of "Hunger Hormone" Ghrelin, Jianzhuang Yao, Yaxia Yuan, Fang Zheng, Chang-Guo Zhan

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Extensive computational modeling and simulations have been carried out, in the present study, to uncover the fundamental reaction pathway for butyrylcholinesterase (BChE)-catalyzed hydrolysis of ghrelin, demonstrating that the acylation process of BChE-catalyzed hydrolysis of ghrelin follows an unprecedented single-step reaction pathway and the single-step acylation process is rate-determining. The free energy barrier (18.8 kcal/mol) calculated for the rate-determining step is reasonably close to the experimentally-derived free energy barrier (~19.4 kcal/mol), suggesting that the obtained mechanistic insights are reasonable. The single-step reaction pathway for the acylation is remarkably different from the well-known two-step acylation reaction pathway for numerous ester hydrolysis reactions …

Incidence And Risk Factors Of Thromboembolism With Multiple Myeloma In The Presence Of Death As A Competing Risk: An Empirical Comparison Of Statistical Methodologies, Joshua D. Brown, Val R. Adams

Pharmacy Practice and Science Faculty Publications

Multiple myeloma (MM) has an inherent high risk of thromboembolic events associated with patient as well as disease- and treatment-related factors. Previous studies have assessed the association of MM-related thromboembolism using “traditional” Kaplan–Meier (KM) and/or Cox proportional hazard (PH) regression. In the presence of high incidence of death, as would be the case in cancer patients with advanced age, these statistical models will produce bias estimates. Instead, a competing risk framework should be used. This study assessed the baseline patient demographic and clinical characteristics associated with MM-related thromboembolism and compared the cumulative incidence and the measures of association obtained using …

Optimizing Guideline-Recommended Antibiotic Doses For Pediatric Infective Endocarditis, Chad A. Knoderer, Kristen R. Nichols, Emily N. Israel, Christopher A. Thomas

Scholarship and Professional Work – COPHS

The American Heart Association recently published an updated scientific statement on the management of infective endocarditis in childhood. The recommendations included for vancomycin, aminoglycoside, and β-lactam dosing and monitoring are based primarily on expert opinion and do not consider available evidence for dose optimization based on pharmacokinetic and pharmacodynamic principles in pediatric patients. This is concerning because even when clinically necessary, some practitioners may be hesitant to deviate from guideline-recommended doses. In this perspective, we highlight potential areas for improvement in the statement-recommended doses and summarize evidence supporting antibiotic dosing optimization. The addition of a pediatric clinical pharmacist with expertise …

Methemoglobinemia In Acetaminophen Overdose And Glucose-6-Phosphate Dehydrogenase Deficiency, Maelen Ignacio, Pharmd, Colin Craft, Md, Fern M. Martin, Md, Cara Mcdaniel, Pharmd, Bcps

College of Pharmacy Posters

Background:

• Methemoglobin (MetHb) is formed when the iron moiety of hemoglobin (Hgb) is oxidized from ferrous (Fe²⁺) to ferric (Fe³⁺) state à impaired O₂ delivery to tissues
• Acetaminophen Metabolism:

~90% is metabolized in liver via sulfation and glucuronidation

remainder is metabolized via CYP450 to a toxic oxidizing agent, N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified via glutathione¹

• Acute Acetaminophen Overdose:

saturates sulfation and glucuronidation pathways

depletes glutathione stores

leads to excess NAPQI à oxidative stress à methemoglobinemia¹

• MetHb Reduction Pathway:

cytochrome b5 reductase removes 95% to 99% of endogenous MetHb

nicotinamide adenine dinucleotide phosphate …

February 2016, Randy Curry, Cindy Brooks

RURAL ROCKS

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

Flow-Through Filter To Remove Aluminum From Medical Solutions, Robert A. Yokel, Wesley R. Harris, Christopher D. Spilling, Robert Joseph Kuhn, Vasiliy Paul Abramov, Jason Matthew Lone

Pharmaceutical Sciences Faculty Patents

A flow through filter assembly includes a trivalent and tetravalent metal ion capturing agent and a flow controller providing a predetermined flow rate which allows capture of the trivalent and tetravalent metal ions by the capturing agent.

Treatment Modalities And Antimicrobial Stewardship Initiatives In The Management Of Intra-Abdominal Infections, Charles Hoffmann, Matthew Zak, Lisa M. Avery, Jack Brown

Pharmacy Faculty/Staff Publications

Antimicrobial stewardship programs (ASPs) focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs) commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.

Development And Validation Of A Sensitive Uplc-Ms/Ms Method For The Quantitation Of [13c]Sucrose In Rat Plasma, Blood, And Brain: Its Application To The Measurement Of Blood-Brain Barrier Permeability, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

Accurate and reproducible measurement of blood-brain barrier (BBB) integrity is critical in the assessment of the pathophysiology of the central nervous system disorders and in monitoring therapeutic effects. The widely-used low molecular weight marker [14C]sucrose is non-specific in the absence of chromatographic separation. The purpose of this study was to develop and validate a sensitive and reproducible LC-MS/MS method for the analysis of stable isotopemodified [13C12]sucrose in brain, plasma, and blood to determine BBB permeability to sucrose. After addition of internal standard (IS, [13C6]sucrose), the marker and IS were recovered from diluted rat blood, plasma, and brain homogenate by protein …

Selective Binding Of Airapl Tandem Uims To Lys48-Linked Tri-Ubiquitin Chains, Simin Rahighi, Ilauna Braunstein, Nicola Ternette, Benedikt Kessler, Masato Kawasaki, Ryuichi Kato, Tsutomu Matsui, Ariel Stanhill, Soichi Wakatsuki

Pharmacy Faculty Articles and Research

Lys48-linked ubiquitin chains act as the main targeting signals for protein degradation by the proteasome. Here we report selective binding of AIRAPL, a protein that associates with the proteasome upon exposure to arsenite, to Lys48-linked tri-ubiquitin chains. AIRAPL comprises two ubiquitin-interacting motifs in tandem (tUIMs) that are linked through a flexible inter-UIM region. In the complex crystal structure UIM1 binds the proximal ubiquitin, whereas UIM2 (the double-sided UIM) binds non-symmetrically to the middle and distal ubiquitin moieties on either side of the helix. Specificity of AIRAPL for Lys48-linked ubiquitin chains is determined by UIM2, and the flexible inter-UIM linker increases …

Fda Has A Banner Quarter To Finish Out 2016, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.

Targeting An Essential Gtpase Obg For The Development Of Broad-Spectrum Antibiotics, Josephine A. Bonventre, Ryszard A. Zielke, Konstantin V. Korotkov, Aleksandra E. Sikora

Molecular and Cellular Biochemistry Faculty Publications

A promising new drug target for the development of novel broad-spectrum antibiotics is the highly conserved small GTPase Obg (YhbZ, CgtA), a protein essential for the survival of all bacteria including Neisseria gonorrhoeae (GC). GC is the agent of gonorrhea, a prevalent sexually transmitted disease resulting in serious consequences on reproductive and neonatal health. A preventive anti-gonorrhea vaccine does not exist, and options for effective antibiotic treatments are increasingly limited. To address the dire need for alternative antimicrobial strategies, we have designed and optimized a 384-well GTPase assay to identify inhibitors of Obg using as a model Obg protein from …

Effectiveness Of Pharmacist-Led Amiodarone Monitoring Services On Improving Adherence To Amiodarone Monitoring Recommendations: A Systematic Review, Dave L. Dixon, Steven P. Dunn, Michael S. Kelly, Timothy R. Mcllarky, Roy E. Brown

Pharmacy Faculty Articles and Research

Amiodarone remains the mostly frequently used antiarrhythmic in clinical practice and is most often used to maintain normal sinus rhythm in patients with atrial fibrillation who have failed a rate control strategy. Amiodarone has superior efficacy over other antiarrhythmics, a lower risk of torsade de pointes, and a better cardiovascular safety profile in patients with structural heart disease. However, amiodarone is associated with notable noncardiac toxicities affecting the thyroid, lungs, eyes, liver, and central nervous system. Since 2000, clinicians have been advised to follow amiodarone monitoring guidelines provided by the Heart Rhythm Society. Adherence to these recommendations in clinical practice, …

Venous Thromboembolism Prophylaxis Compliance Before And After Electronic Health Record Implementation, Lindsay Saum, David Reeves

Scholarship and Professional Work – COPHS

Background: Adherence to American College of Chest Physicians (CHEST) and National Comprehensive Cancer Network (NCCN) guidelines for venous thromboembolism (VTE) prophylaxis helps avoid thromboembolic complications during hospitalization. Electronic health records (EHR) have the potential to make an impact on guideline adherence, but data are lacking.

Objectives: To determine compliance with VTE prophylaxis guidelines in internal medicine and oncology populations and to determine whether EHR implementation had any effect on the rate and appropriateness of prophylaxis practices.

Methods: A retrospective chart review was conducted on medical and oncology patients admitted to the hospital for a 2-month period pre-EHR and post-EHR implementation. …

Loop Dynamics Of Thymidine Diphosphate-Rhamnose 3'-O-Methyltransferase (Cals11), An Enzyme In Calicheamicin Biosynthesis, Lu Han, Shanteri Singh, Jon S. Thorson, George N. Phillips Jr.

Center for Pharmaceutical Research and Innovation Faculty Publications

Structure analysis and ensemble refinement of the apo-structure of thymidine diphosphate (TDP)-rhamnose 3'-O-methyltransferase reveal a gate for substrate entry and product release. TDP-rhamnose 3'-O-methyltransferase (CalS11) catalyses a 3'-O-methylation of TDP-rhamnose, an intermediate in the biosynthesis of enediyne antitumor antibiotic calicheamicin. CalS11 operates at the sugar nucleotide stage prior to glycosylation step. Here, we present the crystal structure of the apo form of CalS11 at 1.89 Å resolution. We propose that the L2 loop functions as a gate facilitating and/or providing specificity for substrate entry or promoting product release. Ensemble refinement analysis slightly improves the …

Nitrogen And Phosphorus Availability From Various Composted Wastes For Use In Irish Agriculture And Horticulture, Alan Lee

Doctoral

Current environmental EU legislation promotes recycling and recovery from organic waste products. Compost has been identified as an alternative to inorganic fertilisers and animal slurries as a nutrient source for crop plants. This study aimed to investigate nitrogen (N) and phosphorus (P) availability from various composted waste through detailed characterisations, complemented by short term lab incubations and long term plant growth experiments. Twenty-five composts were selected and classified by their groups. The composts were characterised by multiple different analytical techniques. Two incubation studies were conducted. One investigating N and P mineralisation potential of the composts and the second on the …

Utilization And Costs Of Compounded Medications For Commercially Insured Patients, 2012 – 2013, Timothy Mcpherson, Patrick Fontane Phd, Express Scripts Holding Company

SIUE Faculty Research, Scholarship, and Creative Activity

Background: Although compounding has a long-standing tradition in clinical practice, insurers and pharmacy benefit managers have instituted policies to decrease claims for compounded medications, citing questions about their safety, efficacy, high costs, and lack of Food and Drug Administration (FDA) approval. There are no reliable published data on the extent of compounding by community pharmacists nor the fraction of patients who use compounded medications. Prior research suggests that compounded medications represent a relatively small proportion of prescription medications, but these surveys were limited by small sample sizes, subjective data collection methods, and low response rates.

Objective: To determine the number …

Your Heart And Diabetes, Rodney Richmond

Faculty Research ​and Publications

No abstract provided.