Pharmacy and Pharmaceutical Sciences Commons^™

Reactive Oxygen Species And Mitochondrial Sensitivity To Oxidative Stress Determine Induction Of Cancer Cell Death By P21, Ionica Masgras, Samantha Carrera, Petra J. De Verdier, Paul Brennan, Aneela Majid, Wan Makhtar, Eugene Tulchinsky, George D. Jones, Igor Roninson, Salvador Macip

Faculty Publications

p21(Waf1/Cip1/Sdi1) is a cyclin-dependent kinase inhibitor that mediates cell cycle arrest. Prolonged p21 up-regulation induces a senescent phenotype in normal and cancer cells, accompanied by an increase in intracellular reactive oxygen species (ROS). However, it has been shown recently that p21 expression can also lead to cell death in certain models. The mechanisms involved in this process are not fully understood. Here, we describe an induction of apoptosis by p21 in sarcoma cell lines that is p53-independent and can be ameliorated with antioxidants. Similar levels of p21 and ROS caused senescence in the absence of significant death in other cancer …

The American Psychiatric Association’S Guideline For Major Depressive Disorder: A Commentary, Lisa Cosgrove, Allen F. Shaughnessy, Emily E. Wheeler, Kirsten E. Austad, Irving Kirsch, Harold J. Bursztajn

Counseling, School Psychology & Sport Faculty Publication Series

The American Psychiatric Association (APA) published a new guideline for Major Depressive Disorder (MDD) which will undoubtedly be used by many practitioners to guide clinical decision-making. In fact, it is non-psychiatrist clinicians who prescribe the majority of antidepressants (AD). We review the APA’s most recent guideline on MDD and report on our observations.

A Comparison Of Dsm-Iv And Dsm-5 Panel Members’ Financial Associations With Industry: A Pernicious Problem Persists, Lisa Cosgrove, Sheldon Krimsky

Counseling, School Psychology & Sport Faculty Publication Series

All medical subspecialties have been subject to increased scrutiny about the ways by which their financial associations with industry, such as pharmaceutical companies, may influence, or give the appearance of influencing, recommendations in review articles and clinical practice guidelines. Psychiatry has been at the epicenter of these concerns, in part because of high-profile cases involving ghostwriting and failure to report industry-related income, and studies highlighting conflicts of interest in promoting psychotropic drugs. The revised 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 …

Species And Tissue-Specificity Of Prokinetic, Laxative And Spasmodic Effects Of Fumaria Parviflora, Najeeb-Ur-Rehman, Malik Hassan Mehmood, Adnan J. Al-Rehaily, Ramzi A. A. Mothana, Anwar H. Gilani

Department of Biological & Biomedical Sciences

Background: Fumaria parviflora Linn. (Fumariaceae), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of Fumaria parviflora in gut motility disorders. Methods: The in-vivo prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37 degrees C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system. Results: …

Comparative Tuberculosis (Tb) Prevention Effectiveness In Children Of Bacillus Calmette-Guérin (Bcg) Vaccines From Different Sources, Kazakhstan, Michael Favorov, Mohammad Ali, Aigul Tursunbayeva, Indira Aitmagambetova, Paul Kilgore, Shakhimurat Ismailov, Terence Chorba

Department of Pharmacy Practice

Background: Except during a 1-year period when BCG vaccine was not routinely administered, annual coverage of infants with Bacillus Calmette-Guérin (BCG) in Kazakhstan since 2002 has exceeded 95%. BCG preparations from different sources (Japan, Serbia, and Russia) or none were used exclusively in comparable 7-month time-frames, September through March, in 4 successive years beginning in 2002. Our objective was to assess relative effectiveness of BCG immunization.

Methods/Findings: We compared outcomes of birth cohorts from the 4 time-frames retrospectively. Three cohorts received vaccine from one of three manufacturers exclusively, and one cohort was not vaccinated. Cohorts were followed for 3 years …

Phosphatidylserine Colocalizes With Epichromatin In Interphase Nuclei And Mitotic Chromosomes, Igor Prudovsky, Calvin P.H. Vary, Yolanda Markaki, Ada L. Olins, Donald E. Olins

Pharmaceutical Sciences Faculty Publications

Cycling eukaryotic cells rapidly re-establish the nuclear envelope and internal architecture following mitosis. Studies with a specific anti-nucleosome antibody recently demonstrated that the surface (“epichromatin”) of interphase and mitotic chromatin possesses a unique and conserved conformation, suggesting a role in postmitotic nuclear reformation. Here we present evidence showing that the anionic glycerophospholipid phosphatidylserine is specifically located in epichromatin throughout the cell cycle and is associated with nucleosome core histones. This suggests that chromatin bound phosphatidylserine may function as a nucleation site for the binding of ER and re-establishment of the nuclear envelope.

Inhibition Of Adhesion And Invasion Of Pseudomonas Aeruginosa To Lung Epithelial Cells: A Model Of Cystic Fibrosis Infection, Ayman Noreddin, Ghada Sawy, Walid Elkhatib, Ehab Noreddin, Atef Shibl

Pharmacy Faculty Books and Book Chapters

"Over their life time, CF patients experience multiple infections by various pneumoniacausing bacteria [6]. With more patients surviving to adulthood, chronic infections with Pseudomonas aeruginosa are coming to the forefront as a leading cause of death [7]. Problems presented by infected CF lung are multi-dimensional; the electrolyte balance and pH of the fluids are abnormal. The mucus is thick and of an alternative composition compared to normal lung and may contribute to colonization with Pseudomonas aeruginosa [2, 3, 5]. As such, research is multi-pronged and includes gene therapy to correct the defective protein, amelioration of inflammatory response and thinning of …

Compounding Vs Standardized Commercial Parenteral Nutrition Product: Pros And Cons, Jane M. Gervasio

Scholarship and Professional Work – COPHS

Standardized commercial parenteral nutrition (PN) formulations have advantages and disadvantages as compared with PN formulations compounded using an automated compounding device. These advantages and disadvantages are discussed along with the supporting available research.

A Novel Experimental Scheme To Fully Separate Permethylated Glycans And Allow Online Rp-Lc-Ms With Simplified Esi-Ms Analysis, Jesse Hines, Shujuan Tao, Ron Orlando, Stacy D. Brown

ETSU Faculty Works

Abstract available for download.

Spring 2012, Southwestern Oklahoma State University

The Sig

The Sig Newsletter from the Southwestern Oklahoma State University College of Pharmacy - Spring 2012

Pharmacy Newsletter : March 2012, Pharmacy Department

Department of Pharmacy Archives

Content:

• ‘Warfarin’ – High Alert Medication Policy Update
• Rational use of Antibiotics 2011 – a Snapshot
• Pharmacist Interventions – Curbing Potential Prescribing Errors
• Reporting Adverse Drug Reactions - An Important Tool for Patient Safety!
• Drug Safety Updates

Implementing A Substances Of Abuse Outreach Program In The Rochester City School District., R L. Jarbe, N M. Piette, Chirag Dave, Amy L. Parkhill, Melinda E. Lull, Jennifer Mathews

Pharmacy Faculty/Staff Publications

Objective: This program aims to provide substances of abuse education to local high school students.

Methods: An outreach program, modeled after the National Institute on Drug Abuse instructional materials, was developed by student pharmacists and faculty for delivery to the Rochester City School District. Strict regulations prevented admittance into any classrooms until the program was presented to all health teachers at a district-wide meeting. Approval was given to begin working in the classrooms in April 2011. The program was first adopted in two health education classes at Edison Tech (May 2011). Information was presented to students using lecture, small group …

Environmental Toxins Linked To Neurodegeneration And Autism Activate The Brain’S Immune System, J. L. Hill, C. Teijelo, H. M. To, A. Meyer, E. S. Micca, N. Vaughn, Melinda E. Lull

Pharmacy Faculty/Staff Publications

Microglia are the primary immune cells of the central nervous system and become activated in response to noxious stimuli, leading to a cycle of inflammation and cell death that has been implicated in the development of Parkinson’s disease and autism. This study examines the effects of environmental toxins, at levels commonly found in humans, on microglial cell survival and activation. The toxins used in this study include polybrominated diphenyl ether (PBDE) flame retardants, the food additive propionic acid (PPA), and the organochlorine pesticide dieldrin. These chemicals have been linked to neuronal damage, although their effects on microglial cells have not …

Use Of Parthenolide Derivatives As Antileukemic And Cytotoxic Agents, Peter A. Crooks, Craig T. Jordan, Xiaochen Wei

Pharmaceutical Sciences Faculty Patents

To view this abstract, please download this patent.

Anti-Malarial Activity Of Geldanamycin Derivatives In Mice Infected With Plasmodium Yoelii, Rubul Mout, Zhi-Dong Xu, Angela Kh Wolf, Vincent J. Davisson, Gotam K. Jarori

Borch Department of Medicinal Chemistry and Molecular Pharmacology Faculty Publications

Background

Geldanamycin (GA), a benzoquinone ansamycin antibiotic has been shown in vitro to possess anti-plasmodial activity. Pharmacological activity of this drug is attributed to its ability to inhibit PfHSP90. The parasite growth arrest has been shown to be due to drug-induced blockage of the transition from ring to trophozoite stage. To further evaluate the consequences of this pharmacodyamic feature, the anti-malarial activity of GA analogs with enhanced drug properties in a Plasmodium-infected animal model have been evaluated for their capacity to induce clearance of the parasite. In the process, a hypothesis was subsequently tested regarding the susceptibility of the …

Aluminum In Food – The Nature And Contribution Of Food Additives, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

No abstract provided.

Sex Hormones And Vascular Function, M. Bowling, S. Oparil, F. Hage, R. H. Hilgers, D. Xing

Pharmaceutical Sciences

No abstract provided.

Nurse Practitioner And Pharmacist Interactions: Implications For Effectiveness Of Interdisciplinary Health Care Teams, Mary P. Bennett, M. Laurie Branstetter, Cherie Howk, Melinda Joyce

Nursing Faculty Publications

The Institute of Medicine report, “The Future of Nursing: Leading Change, Advancing Health,” makes specific recommendations for removing barriers to advanced practice nursing scope of practice. The report also makes important recommendations concerning interdisciplinary teamwork. This article examines the challenges on the professional working relationship between nurse practitioners and pharmacists and provides some insight into the difficulties faced as health care practitioners attempt to work toward the goal of collaborative efforts to advance the care of our patients.

Library Impact Statement For Bps 540 Advanced Drug Delivery Systems, Robin B. Devin

Library Impact Statements

Library Impact Statement for BPS 540 Advanced Drug Delivery Systems new course proposal. No new library resource are needed to support this course. Responding library faculty member: Robin Devin. Requesting faculty member: Wei Lu.

The Value Proposition Of Molecular Medicine., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Individualized patient management is rapidly evolving, driven by the emergence of insights in discovery, development, regulatory, and comparative effectiveness sciences.^1-4 The pace of discovery is accelerating, enabled by platforms, including “omics”, stem cell biology, network medicine, and medical and biological informatics that provide unanticipated insights into pathophysiology.^{2, 4-6} The integration of these paradigms has established a model for identifying the mechanistic underpinnings of disease, offering novel opportunities to individualize diagnostics that shape how modern therapies are deployed, including markers of disease prognosis, clinical predictors of therapeutic responses, and molecular determinants that optimize clinical management.^7-10 Importantly, deconvolution of …

Impact Of A Dietary Supplement Containing 1,3-Dimethylamylamine On Blood Pressure And Bloodborne Markers Of Health: A 10-Week Intervention Study, Paul Whitehead, Brian Schilling, Tyler Farney, Richard Bloomer

Kinesiology and Nutrition Sciences Faculty Research

No abstract provided.

Preparation Of Different Polyamide Nanofiltration Membranes By Interfacial Polymerization And The Effect Of Post-Polymerization Treatment On Separation Performance, Yu Qin

Theses

Interfacial polymerization (IP) is a powerful technique for fabrication of thin film composite (TFC) membranes. In this study, polyamide nanofiltration (NF) composite membranes ware prepared by interfacial polymerization of polyethylenimine (PEI) or m-phenylene diamine (MPD) with isophthaloyl dichloride (IPD) on the surface of a porous polyethersulfone (PES) support. Concentrations of monomer reactants for this reaction were decided by equivalent weight ratio. A standard IP procedure was applied to successfully coat PES flat films. After preparation, three different post-polymerization treatments were employed and one optimal treatment was proven after membrane testing.

The TFC flat film membranes were characterized by nanofiltration of …

Enantioselective Synthesis Of (+) And (–)-2-[1-(2,6-Dichlorophenoxy)-Ethyl]-1,3-Diazacyclopent-2-Ene, Peter A. Crooks, Ashish Pramod Vartak

Pharmaceutical Sciences Faculty Patents

Methods for the enantioselective synthesis of (+) and (−) lofexidine or 2-[1-(2,6)-dichlorophenoxy)-ethyl]-1,3-diazacyclopent-2-ene involve converting (+) or (−) 1-methyl-1-[2,6-dichlorophenoxy]ethanamide to an (+) or (−) imino-ether intermediate by electrophilic attack of the amide oxygen by a trimethoxonium ion and, without isolation, converting the (+) or (−) imino-ether intermediate to (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene by adding ethylene diamine; and optionally converting the (+) or (−) 2-[1-(2,6-dichlorophenoxy)-ethyl]1,3-diazacyclopent-2-ene into a pharmaceutically acceptable acid addition salt thereof.

Ginkgo Extract Egb761 Confers Neuroprotection By Reduction Of Glutamate Release In Ischemic Brain, Alexander Mdzinarishvili, Rachita K. Sumbria, Dorothee Lang, Jochen Klein

Pharmacy Faculty Articles and Research

Purpose - Ginkgo extract EGb761 has shown anti-edema and anti-ischemic effects in various experimental models. In the present study, we demonstrate neuroprotective effects of EGb761 in experimental stroke while monitoring brain metabolism by microdialysis. Methods - We have used oxygen-glucose deprivation in brain slices in vitro and middle cerebral artery occlusion (MCAO) in vivo to induce ischemia in mouse brain. We used microdialysis in mouse striatum to monitor extracellular concentrations of glucose and glutamate. Results - In vitro, EGb761 reduced ischemia-induced cell swelling in hippocampal slices by 60%. In vivo, administration of EGb761 (300 mg/kg) reduced cell degeneration and edema …

Synthetic Peptides Derived From The Sequence Of A Lasso Peptide Microcin J25 Show Antibacterial Activity, Rania Soudy, Liru Wang, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Microcin J25 (MccJ25) is a plasmid-encoded, ribosomally synthesized antibacterial peptide with a unique lasso structure. The lasso structure, produced with the aid of two processing enzymes, provides exceptional stability to MccJ25. We report the synthesis of six peptides (1–6), derived from the MccJ25 sequence, that are designed to form folded conformation by disulfide bond formation and electrostatic or hydrophobic interactions. Two peptides (1 and 6) display good activity against Salmonella newport, and are the first synthetic derivatives of MccJ25 that are bactericidal. Peptide 1 displays potent activity against several Salmonella strains including two …

Identification Of Membrane-Bound Variant Of Metalloendopeptidase Neurolysin (Ec 3.4.24.16) As The Non-Angiotensin Type 1 (Non-At1), Non-At2 Angiotensin Binding Site, Naomi J. Wangler, Kira L. Santos, Ines Schadock, Fred K. Hagen, Emanuel Escher, Michael Bader, Robert C. Speth, Vardan T. Karamyan

HPD Articles

Recently, we discovered a novel non-angiotensin type 1 (non-AT1), non-AT2 angiotensin binding site in rodent and human brain membranes, which is distinctly different from angiotensin receptors and key proteases processing angiotensins. It is hypothesized to be a new member of the renin-angiotensin system. This study was designed to isolate and identify this novel angiotensin binding site. An angiotensin analog, photoaffinity probe 125I-SBpa-Ang II, was used to specifically label the non-AT1, non-AT2 angiotensin binding site in mouse forebrain membranes, followed by a two-step purification procedure based on the molecular size and isoelectric point of the photoradiolabeled binding protein. Purified samples were …

Enhanced Interleukin-1 Activity Contributes To Exercise Intolerance In Patients With Systolic Heart Failure, Benjamin W. Van Tassell, Ross A. Arena, Stefano Toldo, Eleonora Mezzaroma, Tania Azam, Ignacio M. Seropian, Keyur Shah, Justin Canada, Norbert F. Voelkel, Charles A. Dinarello, Antonio Abbate

Pharmacotherapy and Outcomes Science Publications

Background

Heart failure (HF) is a complex clinical syndrome characterized by impaired cardiac function and poor exercise tolerance. Enhanced inflammation is associated with worsening outcomes in HF patients and may play a direct role in disease progression. Interleukin-1β (IL-1β) is a pro-inflammatory cytokine that becomes chronically elevated in HF and exerts putative negative inotropic effects.

Methods and Results

We developed a model of IL-1β-induced left ventricular (LV) dysfunction in healthy mice that exhibited a 32% reduction in LV fractional shortening (P

Conclusions

These findings suggest that IL-1β activity contributes to poor exercise tolerance in patients with systolic HF and identifies …

Atorvastatin With Or Without An Antibody To Pcsk9 In Primary Hypercholesterolemia, Eli M. Roth, James M. Mckenny, Corinne Hanotin, Gaelle Asset, Evan A. Stein

Pharmacotherapy and Outcomes Science Publications

Background

Serum proprotein convertase subtilisin/kexin 9 (PCSK9) binds to low-density lipoprotein (LDL) receptors, increasing the degradation of LDL receptors and reducing the rate at which LDL cholesterol is removed from the circulation. REGN727/SAR236553 (designated here as SAR236553), a fully human PCSK9 monoclonal antibody, increases the recycling of LDL receptors and reduces LDL cholesterol levels.

Methods

We performed a phase 2, multicenter, double-blind, placebo-controlled trial involving 92 patients who had LDL cholesterol levels of 100 mg per deciliter (2.6 mmol per liter) or higher after treatment with 10 mg of atorvastatin for at least 7 weeks. Patients were randomly assigned to …

Botanical Medicine: The Need For Better Quality Research, Antoine Al-Achi

Pharmaceutical Sciences

No abstract provided.

On The Specificity Of Heparin/Heparan Sulfate Binding To Proteins. Anion-Binding Sites On Antithrombin And Thrombin Are Fundamentally Different, Philip D. Mosier, Chandravel Krishnasamy, Glen E. Kellogg, Umesh R. Desai

Medicinal Chemistry Publications

Background

The antithrombin–heparin/heparan sulfate (H/HS) and thrombin–H/HS interactions are recognized as prototypic specific and non-specific glycosaminoglycan (GAG)–protein interactions, respectively. The fundamental structural basis for the origin of specificity, or lack thereof, in these interactions remains unclear. The availability of multiple co-crystal structures facilitates a structural analysis that challenges the long-held belief that the GAG binding sites in antithrombin and thrombin are essentially similar with high solvent exposure and shallow surface characteristics.

Methodology

Analyses of solvent accessibility and exposed surface areas, gyrational mobility, symmetry, cavity shape/size, conserved water molecules and crystallographic parameters were performed for 12 X-ray structures, which include 12 …