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David Xu, Liwei Li, Donghui Zhou, Degang Liu, Andy Hudmon, Samy O Meroueh
Target-specific scoring methods are more commonly used to identify small-molecule inhibitors among compounds docked to a target of interest. Top candidates that emerge from these methods have rarely been tested for activity and specificity across a family of proteins. In this study we docked a chemical library into CaMKIIδ, a member of the Ca(2+) /calmodulin (CaM)-dependent protein kinase (CaMK) family, and re-scored the resulting protein-compound structures using Support Vector Machine SPecific (SVMSP), a target-specific method that we developed previously...
March 29, 2017: ChemMedChem
Aarti R Chawla, Derrick E Johnson, Agnes S Zybura, Benjamin P Leeds, Ross M Nelson, Andy Hudmon
Glutamate clearance by astrocytes is an essential part of normal excitatory neurotransmission. Failure to adapt or maintain low levels of glutamate in the central nervous system is associated with multiple acute and chronic neurodegenerative diseases. The primary excitatory amino acid transporters in human astrocytes are EAAT1 and EAAT2 (GLAST and GLT-1, respectively, in rodents). While the inhibition of calcium/calmodulin-dependent kinase (CaMKII), a ubiquitously expressed serine/threonine protein kinase, results in diminished glutamate uptake in cultured primary rodent astrocytes (Ashpole et al...
February 2017: Journal of Neurochemistry
Ramy Habashy Malty, Andy Hudmon, Jill C Fehrenbacher, Michael R Vasko
BACKGROUND: Acute exposure to prostaglandin E2 (PGE2) activates EP receptors in sensory neurons which triggers the cAMP-dependent protein kinase A (PKA) signaling cascade resulting in enhanced excitability of the neurons. With long-term exposure to PGE2, however, the activation of PKA does not appear to mediate persistent PGE2-induced sensitization. Consequently, we examined whether homologous desensitization of PGE2-mediated PKA activation occurs after long-term exposure of isolated sensory neurons to the eicosanoid...
2016: Journal of Neuroinflammation
Zifan Pei, Yucheng Xiao, Jingwei Meng, Andy Hudmon, Theodore R Cummins
Cardiac voltage-gated sodium channels (Nav1.5) play an essential role in regulating cardiac electric activity by initiating and propagating action potentials in the heart. Altered Nav1.5 function is associated with multiple cardiac diseases including long-QT3 and Brugada syndrome. Here, we show that Nav1.5 is subject to palmitoylation, a reversible post-translational lipid modification. Palmitoylation increases channel availability and late sodium current activity, leading to enhanced cardiac excitability and prolonged action potential duration...
June 23, 2016: Nature Communications
Mitra Assemi, Karen Suchanek Hudmon, Kevin M Sowinski, Robin L Corelli
Objective. To characterize the educational background and academic rank of faculty members in US schools of pharmacy, estimate the extent to which they are employed by institutions where they received previous training, and determine whether differences in degree origin and rank exist between faculty members in established (≤1995) vs newer programs. Methods. A cross-sectional study was conducted using the American Association of Colleges of Pharmacy (AACP) faculty database and demographic information from the public domain...
May 25, 2016: American Journal of Pharmaceutical Education
Jose L Barboza, Radha Patel, Pooja Patel, Karen Suchanek Hudmon
INTRODUCTION: Cigarette smoking can damage every organ in the body and is the leading known preventable cause of death globally. It is estimated that 70% of patients want to quit, and about 50% report a quit attempt in the past year, yet only 4-7% are successful. These low quit rates represent the importance of appropriate treatment for smoking cessation through behavioral and pharmacotherapeutic means. AREAS COVERED: Pharmacotherapy approximately doubles patients' chances of quitting, and the first-line approved pharmacotherapetuic options include nicotine gum, lozenge, patch, nasal spray, and inhaler, sustained-release bupropion, and varenicline...
August 2016: Expert Opinion on Pharmacotherapy
Chaoming Zhou, Swarna S Ramaswamy, Derrick E Johnson, Dario A Vitturi, Franciso J Schopfer, Bruce A Freeman, Andy Hudmon, Edwin S Levitan
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) oxidation controls excitability and viability. While hydrogen peroxide (H2O2) affects Ca(2+)-activated CaMKII in vitro, Angiotensin II (Ang II)-induced CaMKIIδ signaling in cardiomyocytes is Ca(2+) independent and requires NADPH oxidase-derived superoxide, but not its dismutation product H2O2. To better define the biological regulation of CaMKII activation and signaling by Ang II, we evaluated the potential for peroxynitrite (ONOO(-)) to mediate CaMKII activation and downstream Kv4...
April 15, 2016: Scientific Reports
Robin L Corelli, Michael A Muchnik, Ryan J Beechinor, Gary Fong, Eleanor M Vogt, Jennifer M Cocohoba, Candy Tsourounis, Karen Suchanek Hudmon
OBJECTIVE: To improve the quality of admissions interviews for a doctor of pharmacy program, using a multiple mini-interview (MMI) in place of the standard interview. METHODS: Stakeholders completed an anonymous web-based survey. This study characterized perceptions of the MMI format across 3 major stakeholders (candidates, interviewers, admissions committee members) and included comparative cost estimates.Costs were estimated using human and facility resources from the 2012 cycle (standard format) and the 2013 cycle (MMI format)...
November 25, 2015: American Journal of Pharmaceutical Education
Rajshekhar Y Gaji, Derrick E Johnson, Moritz Treeck, Mu Wang, Andy Hudmon, Gustavo Arrizabalaga
Members of the family of calcium dependent protein kinases (CDPK's) are abundant in certain pathogenic parasites and absent in mammalian cells making them strong drug target candidates. In the obligate intracellular parasite Toxoplasma gondii TgCDPK3 is important for calcium dependent egress from the host cell. Nonetheless, the specific substrate through which TgCDPK3 exerts its function during egress remains unknown. To close this knowledge gap we applied the proximity-based protein interaction trap BioID and identified 13 proteins that are either near neighbors or direct interactors of TgCDPK3...
2015: PLoS Pathogens
Hongwei Yu, Bin Pan, Andy Weyer, Hsiang-En Wu, Jingwei Meng, Gregory Fischer, Daniel Vilceanu, Alan R Light, Cheryl Stucky, Frank L Rice, Andy Hudmon, Quinn Hogan
UNLABELLED: The sensation of touch is initiated when fast conducting low-threshold mechanoreceptors (Aβ-LTMRs) generate impulses at their terminals in the skin. Plasticity in this system is evident in the process of adaption, in which a period of diminished sensitivity follows prior stimulation. CaMKII is an ideal candidate for mediating activity-dependent plasticity in touch because it shifts into an enhanced activation state after neuronal depolarizations and can thereby reflect past firing history...
October 21, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Katherine Rider, Hatice Kaya, Vinayak Jha, Karen Suchanek Hudmon
OBJECTIVES: Accreditation guidelines in the USA suggest that experiential sites for pharmacy students should demonstrate 'a strong commitment to health promotion and illness prevention'; however, most community pharmacies sell tobacco products. This study aimed to determine the proportion of students rotating through advanced pharmacy practice experience (APPE) sites where tobacco is sold and experiential education directors' perception regarding the sales of tobacco in APPE sites. METHODS: A brief survey was distributed by mail to experiential education directors at US pharmacy schools...
April 2016: International Journal of Pharmacy Practice
Alicia A Bergman, Heather A Jaynes, Jasmine D Gonzalvo, Karen Suchanek Hudmon, Richard M Frankel, Amanda L Kobylinski, Alan J Zillich
Expanded clinical pharmacist professional roles in the team-based patient-centered medical home (PCMH) primary care environment require cooperative and collaborative relationships among pharmacists and primary care physicians (PCPs), but many PCPs have not previously worked in such a direct fashion with pharmacists. Additional roles, including formulary control, add further elements of complexity to the clinical pharmacist-PCP relationship that are not well described. Our objective was to characterize the nature of clinical pharmacist-PCP interprofessional collaboration across seven federally funded hospitals and associated primary care clinics, following pharmacist placement in primary care clinics and incorporation of expanded pharmacist roles...
2016: Health Communication
Joaquin Barnoya, Linda Jin, Karen Suchanek Hudmon, Mario Schootman
OBJECTIVES: To compare availability of nicotine replacement therapy (NRT), tobacco products, and electronic cigarettes (e-cigarettes) in pharmacies in St. Louis, MO. DESIGN: Cross-sectional study, on-site store audits of 322 pharmacies. SETTING: St. Louis, MO. PARTICIPANTS: 242 eligible community pharmacies located in the study area. INTERVENTION: Pharmacies were visited by trained research assistants who conducted a 5- to 10-minute store audit using a paper-based data collection tool...
July 2015: Journal of the American Pharmacists Association: JAPhA
Wan-Hung Lee, Zhili Xu, Nicole M Ashpole, Andy Hudmon, Pushkar M Kulkarni, Ganesh A Thakur, Yvonne Y Lai, Andrea G Hohmann
Aberrant increases in NMDA receptor (NMDAR) signaling contributes to central nervous system sensitization and chronic pain by activating neuronal nitric oxide synthase (nNOS) and generating nitric oxide (NO). Because the scaffolding protein postsynaptic density 95kDA (PSD95) tethers nNOS to NMDARs, the PSD95-nNOS complex represents a therapeutic target. Small molecule inhibitors IC87201 (EC5O: 23.94 μM) and ZL006 (EC50: 12.88 μM) directly inhibited binding of purified PSD95 and nNOS proteins in AlphaScreen without altering binding of PSD95 to ErbB4...
October 2015: Neuropharmacology
M L Y Bangaru, J Meng, D J Kaiser, H Yu, G Fischer, Q H Hogan, A Hudmon
Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) decodes neuronal activity by translating cytoplasmic Ca(2+) signals into kinase activity that regulates neuronal functions including excitability, gene expression, and synaptic transmission. Four genes lead to developmental and differential expression of CaMKII isoforms (α, β, γ, δ). We determined mRNA levels of these isoforms in the dorsal root ganglia (DRG) of adult rats with and without nerve injury in order to determine if differential expression of CaMKII isoforms may contribute to functional differences that follow injury...
August 6, 2015: Neuroscience
Kelly C Lee, Karen Suchanek Hudmon, Joseph D Ma, Grace M Kuo
AIM: This national dissemination study evaluated pharmacy students' self-reported overall ability, self-efficacy and attitudes toward applying pharmacogenomics and perceptions of Pharmacogenomics Education Program, a shared pharmacogenomics curriculum. PATIENTS & METHODS: Following a series of train-the-trainer programs for pharmacy faculty, pre- (n = 2674) and post-training surveys (n = 2542) were administered to Doctor of Pharmacy students (n = 43 pharmacy schools)...
2015: Pharmacogenomics
Nikolai Otmakhov, Elena V Gorbacheva, Shaurav Regmi, Ryohei Yasuda, Andy Hudmon, John Lisman
Over-activation of excitatory NMDA receptors and the resulting Ca2+ overload is the main cause of neuronal toxicity during stroke. CaMKII becomes misregulated during such events. Biochemical studies show either a dramatic loss of CaMKII activity or its persistent autonomous activation after stroke, with both of these processes being implicated in cell toxicity. To complement the biochemical data, we monitored CaMKII activation in living hippocampal neurons in slice cultures using high spatial/temporal resolution two-photon imaging of the CaMKIIα FRET sensor, Camui...
2015: PloS One
Anne Bouchut, Aarti R Chawla, Victoria Jeffers, Andy Hudmon, William J Sullivan
Lysine acetylation is a reversible post-translational modification (PTM) that has been detected on thousands of proteins in nearly all cellular compartments. The role of this widespread PTM has yet to be fully elucidated, but can impact protein localization, interactions, activity, and stability. Here we present the first proteome-wide survey of lysine acetylation in cortical astrocytes, a subtype of glia that is a component of the blood-brain barrier and a key regulator of neuronal function and plasticity...
2015: PloS One
Carl W Tong, Xin Wu, Yang Liu, Paola C Rosas, Sakthivel Sadayappan, Andy Hudmon, Mariappan Muthuchamy, Patricia A Powers, Héctor H Valdivia, Richard L Moss
BACKGROUND: Mammalian hearts exhibit positive inotropic responses to β-adrenergic stimulation as a consequence of protein kinase A-mediated phosphorylation or as a result of increased beat frequency (the Bowditch effect). Several membrane and myofibrillar proteins are phosphorylated under these conditions, but the relative contributions of these to increased contractility are not known. Phosphorylation of cardiac myosin-binding protein-C (cMyBP-C) by protein kinase A accelerates the kinetics of force development in permeabilized heart muscle, but its role in vivo is unknown...
May 2015: Circulation. Heart Failure
Margie E Snyder, Karen S Pater, Caitlin K Frail, Karen Suchanek Hudmon, Brad N Doebbeling, Randall B Smith
BACKGROUND: Medication therapy management (MTM) services position pharmacists to prevent, detect, and resolve medication-related problems (MRPs.) However, selecting patients for MTM who are most at risk for MRPs is a challenge. Using self-administered scales that are practical for use in clinical practice are one approach. OBJECTIVE: The objective of this study was to estimate the psychometric properties of a brief self-administered scale as a screening tool for MRPs...
March 2015: Research in Social & Administrative Pharmacy: RSAP
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