Pharmacy and Pharmaceutical Sciences Commons^™

Mri Of Neuronal Recovery After Low-Dose Methamphetamine Treatment Of Traumatic Brain Injury In Rats, Guang Liang Ding, Michael Chopp, David J. Poulsen, Lian Li, Changsheng Qu, Qingjiang Li, Siamak P. Nejad-Davarani, John S. Budaj, Hongtao Wu, Asim Mahmood, Quan Jiang

Biomedical and Pharmaceutical Sciences Faculty Publications

We assessed the effects of low dose methamphetamine treatment of traumatic brain injury (TBI) in rats by employing MRI, immunohistology, and neurological functional tests. Young male Wistar rats were subjected to TBI using the controlled cortical impact model. The treated rats (n = 10) received an intravenous (iv) bolus dose of 0.42 mg/kg of methamphetamine at eight hours after the TBI followed by continuous iv infusion for 24 hrs. The control rats (n = 10) received the same volume of saline using the same protocol. MRI scans, including T2-weighted imaging (T2WI) and diffusion tensor imaging (DTI), were performed one day …

Low Soluble Drug Encapsulation Based On Architecture Of Layer-By-Layer Assembly For Longer Circulation Time And Targeted Therapy, Pravin Pattekari

Doctoral Dissertations

A combined effect of sonication and layer-by-layer assembly (LbL) enhances the solubility of many poorly soluble inorganic and organic materials by forming stable particles with ca. 200 nm size and up to 90 wt% of loading. The entire method is reproducible, easy-to-handle, and flexible for varying surface properties according to the application of the materials. The method develops good colloidal stability of materials in buffers and maintains architecture for future improvement. A top-down approach, with a combined effect of sonication and LbL assembly, ruptures the material and allows adsorption of oppositely charged polyelectrolytes simultaneously. Thus, the approach is applicable for …

Biodistribution And Biopersistence Of Ceria Engineered Nanomaterials: Size Dependence, Robert A. Yokel, Michael T. Tseng, Mo Dan, Jason M. Unrine, Uschi M. Graham, Peng Wu, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

The aims were to determine the biodistribution, translocation, and persistence of nanoceria in the brain and selected peripheral organs. Nanoceria is being studied as an anti-oxidant therapeutic. Five, 15, 30, or 55 nm ceria was iv infused into rats which were terminated 1, 20, or 720 h later. Cerium was determined in blood, brain, liver, and spleen. Liver and spleen contained a large percentage of the dose, from which there was no significant clearance over 720 h, associated with adverse changes. Very little nanoceria entered brain parenchyma. The results suggest brain delivery of nanoceria will be a challenge.

FROM THE …

High-Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis And Method Of Generating The Same, Chang-Guo Zhan, Hoon Cho, Hsin-Hsiung Tai

Pharmaceutical Sciences Faculty Patents

A novel computational method and generation of mutant butyrylcholinesterase for cocaine hydrolysis is provided. The method includes molecular modeling a possible BChE mutant and conducting molecular dynamics simulations and hybrid quantum mechanical/molecular mechanical calculations thereby providing a screening method of possible BChE mutants by predicting which mutant will lead to a more stable transition state for a rate determining step. Site-directed mutagenesis, protein expression, and protein activity is conducted for mutants determined computationally as being good candidates for possible BChE mutants, i.e., ones predicted to have higher catalytic efficiency as compared with wild-type BChE. In addition, mutants A199S/A328W/Y332G, A199S/F227A/A328W/Y332G, A199S/S287G/A328W/Y332G, …

Embedded Assessment And Evidence-Based Curriculum Mapping: The Promise Of Learning Analytics, Jane M. Souza

Pharmacy Faculty/Staff Publications

At Wegmans School of Pharmacy, we have adopted an embedded assessment approach to curriculum mapping and data collection on student learning outcomes achievement. In essence, we capture the data from the course level exams that our faculty members craft to measure student learning.

Resolution Of Clinical And Laboratory Abnormalities After Diagnosis Of Ventilator-Associated Pneumonia In Trauma Patients, Joseph M. Swanson, Kathryn A. Connor, Louis J. Magnotti, Martin A. Croce, Jessica Johnson, G. Christopher Wood, Timothy C. Fabian

Pharmacy Faculty/Staff Publications

Background: Guidelines advise that patients with ventilator-associated pneumonia (VAP) should respond clinically by Day 3 of antibiotics. White blood cell (WBC) count, maximum temperature (Tmax), and PaO2:FIO2 ratio are all said to respond significantly by Day 6. Resolution of abnormalities has not been evaluated in trauma patients.

Methods: Retrospective review of trauma patients with VAP. The WBC count, Tmax, and PaO2:FIO2 were evaluated for 16 days after diagnosis. Patients were grouped into uncomplicated VAP, complicated VAP (those with inadequate empirical therapy [IEAT], VAP relapse/superinfection, or acute respiratory distress syndrome), and concurrent infection +VAP (those also infected at another site).

Results: …

A Novel Anti-Inflammatory And Pro-Resolving Role For Resolvin D1 In Acute Cigarette Smoke-Induced Lung Inflammation, Hsi-Min Hsiao, Ramil E. Sapinoro, Thomas H. Thatcher, Amanda Croasdell, Elizabeth P. Levy, Robert A. Fulton, Keith C. Olsen, Stephen J. Pollock, Charles N. Serhan, Richard P. Phipps, Patricia J. Sime

Pharmacy Faculty/Staff Publications

Introduction: Cigarette smoke is a profound pro-inflammatory stimulus that contributes to acute lung injuries and to chronic lung disease including COPD (emphysema and chronic bronchitis). Until recently, it was assumed that resolution of inflammation was a passive process that occurred once the inflammatory stimulus was removed. It is now recognized that resolution of inflammation is a bioactive process, mediated by specialized lipid mediators, and that normal homeostasis is maintained by a balance between pro-inflammatory and pro-resolving pathways. These novel small lipid mediators, including the resolvins, protectins and maresins, are bioactive products mainly derived from dietary omega-3 and omega-6 polyunsaturated fatty …

Pharmacy Law Brief: Contemporary Legal Issues For Leadership In Non-Profits - Iv, Joseph L. Fink Iii

Pharmacy Practice and Science Faculty Publications

No abstract provided.

Physicochemical Characterization And Aerosol Dispersion Performance Of Organic Solution Advanced Spray-Dried Cyclosporine A Multifunctional Particles For Dry Powder Inhalation Aerosol Delivery, Xiao Wu, Weifen Zhang, Don Hayes Jr., Heidi M. Mansour

Pharmaceutical Sciences Faculty Publications

In this systematic and comprehensive study, inhalation powders of the polypeptide immunosuppressant drug - cyclosporine A - for lung delivery as dry powder inhalers (DPIs) were successfully designed, developed, and optimized. Several spray drying pump rates were rationally chosen. Comprehensive physicochemical characterization and imaging was carried out using scanning electron microscopy, hot-stage microscopy, differential scanning calorimetry, powder X-ray diffraction, Karl Fischer titration, laser size diffraction, and gravimetric vapor sorption. Aerosol dispersion performance was conducted using a next generation impactor with a Food and Drug Administration-approved DPI device. These DPIs displayed excellent aerosol dispersion performance with high values in emitted dose, …

Warum Gesunde Menchen Immer Häufiger Fur Psychisch Krank Erklärt Werden, Lisa Cosgrove

Counseling, School Psychology & Sport Faculty Publication Series

zuerst einmal nicht schaden": Das ist der wohl wichtigste Grundsatz der Medizin. Aber diese Mission droht durch den Einfluss großer Pharmafirmen unterhöhlt zu werden. Der Vorwurf einer Verstrickung von Ärzten und Arzneimittelherstellern ist schon in fast allen medizinischen Fachrichtungen aufgekommen. Vor allem aber die Psychiatrie steckt in einer Glaubwürdigkeitskrise. Das zeigt sich in der aktuellen Debatte um die neue Auflage des "Diagnostischen und Statistischen Manual Psychischer Störungen" (DSM).

Dieses von der US-Psychiater-Vereinigung APA herausgegebene Handbuch definiert, was eine psychische Erkrankung ist. Die Bedeutung dieser Wertung geht weit über die USA hinaus - das Handbuch nimmt oft Definitionen der Weltgesundheitsorganisation vorweg. …

Impact Of Sugar Substitutes On Glucose Control In Diabetic Patients, Mckenzie C. Ferguson, Erin Marie Timpe Behnen, Amy Carlson

Pharmacy Faculty Research, Scholarship, and Creative Activity

Objective: To evaluate the impact of nonnutritive sugar substitutes on glycemic control in patients with diabetes.

Data Sources: A comprehensive review of the literature was conducted in PubMed (1966-March 2012) and Scopus. A combination of MeSH terms and keywords were used, including acesulfame, aspartame, diabetes, neotame, rebiana, saccharin, stevia, and sucralose.

Study Selection and Data Extraction: Clinical studies evaluating the impact of nonnutritive sweeteners on measures of diabetic control, including, but not limited to, blood glucose levels, postprandial blood glucose, and hemoglobin A_1c were selected for review. Searches were limited to only nonnutritive sweeteners available in the US.

Data …

Kinetic And Thermodynamic Studies Of Thrombin Inhibitors, Aziz May Abdel

Theses and Dissertations

Sulfated low molecular weight lignins (LMWLs), CDSO3 and FDSO3, designed recently as macromolecular mimetics of heparin, were found to exhibit potent anticoagulant activity. Small molecules based on the same scaffold, SBD and SBT, showed promising thrombin inhibition. We were able to address the mechanism of the inhibition using Michaelis-Menten kinetics. All the molecules were found to be allosterically impairing thrombin activity using either noncompetitive or uncompetitive mechanism. Absence of competition with hirugen, an exosite 1 ligand, and competition with polymeric heparin points to exosite 2 as the site of interaction for these inhibitors. Yet mixed competition results with other exosite …

Impact Of The Tohoku Earthquake And Tsunami On Pneumonia Hospitalisations And Mortality Among Adults In Northern Miyagi, Japan: A Multicentre Observational Study, Hisayoshi Daito, Motoi Suzuki, Jun Shiihara, Paul E. Kilgore, Hitoshi Ohtomo, Konosuke Morimoto, Masayuki Ishida, Taro Kamigaki, Hitoshi Oshitani, Masahiro Hashizume, Wataru Endo, Koichi Hagiwara, Koya Ariyoshi, Shoji Okinaga

Department of Pharmacy Practice

Background On 11 March 2011, the Tohoku earthquake and tsunami struck off the coast of northeastern Japan. Within 3 weeks, an increased number of pneumonia admissions and deaths occurred in local hospitals.

Methods A multicentre survey was conducted at three hospitals in Kesennuma City (population 74000), northern Miyagi Prefecture. All adults aged ≥18 years hospitalised between March 2010 and June 2011 with community-acquired pneumonia were identified using hospital databases and medical records. Segmented regression analyses were used to quantify changes in the incidence of pneumonia.

Results A total of 550 pneumonia hospitalisations were identified, including 325 during the pre-disaster period …

Positive Allosteric Modulators Of Alpha4beta2 Neuronal Nicotinic Receptors: Synthesis And In Vitro Studies, Atul Jain

Theses and Dissertations

des-Formylflustrabromine (dFBr), isolated from the marine organism Flustra foliacea, is the first selective, positive allosteric modulator (PAM) of α4β2 nicotinic acetylcholine receptors that potentiates the action of the neurotransmitter acetylcholine (ACh). Most agonists for this receptor population are not selective and can activate other nACh receptors. A selective PAM, which activates α4β2 nACh receptors only in the presence of ACh, might find application in the treatment of of various neurological diseases such as Alzheimer’s disease or autism. dFBr was examined and found to produce a biphasic dose-response curve over a wide concentration range (i.e., potentiation at low concentration, but inhibition …

Block Copolymer Cross-Linked Nanoassemblies Improve Particle Stability And Biocompatibility Of Superparamagnetic Iron Oxide Nanoparticles, Mo Dan, Daniel F. Scott, Peter A. Hardy, Robert J. Wydra, J. Zach Hilt, Robert A. Yokel, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

PURPOSE: To develop cross-linked nanoassemblies (CNAs) as carriers for superparamagnetic iron oxide nanoparticles (IONPs).

METHODS: Ferric and ferrous ions were co-precipitated inside core-shell type nanoparticles prepared by cross-linking poly(ethylene glycol)-poly(aspartate) block copolymers to prepare CNAs entrapping Fe(3)O(4) IONPs (CNA-IONPs). Particle stability and biocompatibility of CNA-IONPs were characterized in comparison to citrate-coated Fe(3)O(4) IONPs (Citrate-IONPs).

RESULTS: CNA-IONPs, approximately 30 nm in diameter, showed no precipitation in water, PBS, or a cell culture medium after 3 or 30 h, at 22, 37, and 43°C, and 1, 2.5, and 5 mg/mL, whereas Citrate-IONPs agglomerated rapidly (> 400 nm) in all …

Industry’S Colonization Of Psychiatry: Ethical And Practical Implications Of Financial Conflicts Of Interest In The Dsm-5, Lisa Cosgrove, Emily E. Wheeler

Counseling, School Psychology & Sport Faculty Publication Series

The revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM), scheduled for publication in May 2013 by the American Psychiatric Association (APA), has created a firestorm of controversy because of questions about undue industry influence. Specifically, concerns have been raised about financial conflicts of interest between DSM-5 panel members and the pharmaceutical industry. The authors argue that current approaches to the management of these relationships, particularly transparency of them, are insufficient solutions to the problem of industry’s capture of organized psychiatry. The conceptual framework of institutional corruption is used to understand psychiatry’s dependence on the pharmaceutical industry and …

Impacts Of Black Box Warning, National Coverage Determination, And Risk Evaluation And Mitigation Strategies On The Inpatient On-Label And Off-Label Use Of Erythropoiesis-Stimulating Agents, Arpamas Seetasith

Theses and Dissertations

Background: FDA black box warning, Risk Evaluation and Mitigation Strategies (REMS), and CMS national coverage determination (NCD) aim to reduce inappropriate use of erythropoiesis-stimulating agents (ESAs) that are widely used in anemic patients. Previous studies have not linked specific safety interventions to changes in ESA utilization patterns in the inpatient settings nor assessed such interventions on off-label use of the drugs. Ineffectiveness of the intervention and lag time between such interventions and the observed change in clinical practice could lead to serious clinical outcomes. In addition, such interventions may unintentionally reduce on-label and some off-label use of ESAs considered “appropriate” …

Design, Syntheses, And Biological Evaluation Of 14-N-Substituted Naltrexone Derivatives As Opioid Receptor Ligands, Orgil Elbegdorj

Theses and Dissertations

Opium, the dried resin obtained from the unripe seedpods of the poppy flower, has been used for medicinal and euphoric purposes since ancient times. Morphine, the main active ingredient of opium, and other clinically useful opioid analgesics all mediate their effects through activating the mu opioid receptor. Studies involving the mu opioid receptor knockout mice showed that the interaction with the mu opioid receptor is also responsible for many notorious side effects associated with these drugs including dependence and addiction. Therefore, selective antagonists for the mu opioid receptor are needed to study its function in drug abuse and addiction. Previously, …

Nuclear Envelope Composition Determines The Ability Of Neutrophil-Type Cells To Passage Through Micron-Scale Constrictions, Amy C. Rowat, Diana E. Jaalouk E. Jaalouk, Monika Zwerger, W. Lloyd Ung, Irwin A. Eydelnant, Donald E. Olins, Ada L. Olins, Harald Herrmann, David A. Weitz, Jan Lammerding

Pharmaceutical Sciences Faculty Publications

Neutrophils are characterized by their distinct nuclear shape, which is thought to facilitate the transit of these cells through pore spaces less than one-fifth of their diameter. We used human promyelocytic leukemia (HL-60) cells as a model system to investigate the effect of nuclear shape in whole cell deformability. We probed neutrophil-differentiated HL-60 cells lacking expression of lamin B receptor, which fail to develop lobulated nuclei during granulopoiesis and present an in vitro model for Pelger-Huët anomaly; despite the circular morphology of their nuclei, the cells passed through micron-scale constrictions on similar timescales as scrambled controls. We then investigated the …

Gambogic Acid Is A Tissue-Specific Proteasome Inhibitor In Vitro And In Vivo, Xiaofen Li, Shouting Liu, Hongbiao Huang, Ningning Liu, Chong Zhao, Siyan Liao, Changshan Yang, Yurong Liu, Canguo Zhao, Shujue Li, Xiaoyu Lu, Chunjiao Liu, Lixia Guan, Kai Zhao, Xiaoqing Shi, Wenbin Song, Ping Zhou, Xiaoxian Dong, Haiping Guo, Guanmei Wen, Change Zhang, Lili Jiang, Ningfang Ma, Bing Li, Shunqing Wang, Huo Tan, Xuejun Wang, Q. Ping Dou, Jinbao Lin

Oncology Faculty Publications

Gambogic acid (GA) is a natural compound derived from Chinese herbs that has been approved by the Chinese Food and Drug Administration for clinical trials in cancer patients; however, its molecular targets have not been thoroughly studied. Here, we report that GA inhibits tumor proteasome activity, with potency comparable to bortezomib but much less toxicity. First, GA acts as a prodrug and only gains proteasome-inhibitory function after being metabolized by intracellular CYP2E1. Second, GA-induced proteasome inhibition is a prerequisite for its cytotoxicity and anticancer effect without off-targets. Finally, because expression of the CYP2E1 gene is very high in tumor tissues …