Pharmacy and Pharmaceutical Sciences Commons^™

Pyridoxal 5′-Phosphate Is A Slow Tight Binding Inhibitor Of E. Coli Pyridoxal Kinase, Mohini S. Ghatge, Roberto Contestabile, Martino L. Di Salvo, Jigar V. Desai, Amit Gandhi, Christina M. Camara, Rita Florio, Isabel N. Gonzalez, Alessia Parroni, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Pyridoxal 5′-phosphate (PLP) is a cofactor for dozens of B6 requiring enzymes. PLP reacts with apo-B6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4′-aldehyde moiety forms covalent adducts with other compounds and non-B6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell …

Design, Synthesis, And In Vitro And In Vivo Biological Studies Of A 3′-Deoxythymidine Conjugate That Potentially Kills Cancer Cells Selectively, Qiong Wei, Dejun Zhang, Anna Yao, Liyi Mai, Zhiwei Zhang, Qibing Zhou

Medicinal Chemistry Publications

Thymidine kinases (TKs) have been considered one of the potential targets for anticancer therapeutic because of their elevated expressions in cancer cells. However, nucleobase analogs targeting TKs have shown poor selective cytotoxicity in cancer cells despite effective antiviral activity. 3′-Deoxythymidine phenylquinoxaline conjugate (dT-QX) was designed as a novel nucleobase analog to target TKs in cancer cells and block cell replication via conjugated DNA intercalating quinoxaline moiety. In vitro cell screening showed that dT-QX selectively kills a variety of cancer cells including liver carcinoma, breast adenocarcinoma and brain glioma cells; whereas it had a low cytotoxicity in normal cells such as …

Insulin-Stimulated Phosphorylation Of Protein Phosphatase 1 Regulatory Subunit 12b Revealed By Hplc-Esi-Ms/Ms, Kimberly Pham, Paul Langlais, Xiangmin Zhang, Alex Chao, Morgan Zingsheim, Zhengping Yi

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Protein phosphatase 1 (PP1) is one of the major phosphatases responsible for protein dephosphorylation in eukaryotes. Protein phosphatase 1 regulatory subunit 12B (PPP1R12B), one of the regulatory subunits of PP1, can bind to PP1cδ, one of the catalytic subunits of PP1, and modulate the specificity and activity of PP1cδ against its substrates. Phosphorylation of PPP1R12B on threonine 646 by Rho kinase inhibits the activity of the PP1c-PPP1R12B complex. However, it is not currently known whether PPP1R12B phosphorylation at threonine 646 and other sites is regulated by insulin. We set out to identify phosphorylation sites in PPP1R12B and to …

Empiric Guideline-Recommended Weight-Based Vancomycin Dosing And Mortality In Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Retrospective Cohort Study, Ronald G. Hall Ii, Christopher A. Giuliano, Krystal K. Haase, Kathleen A. Hazlewood, Chistopher R. Frei, Nicolas A. Forcade, Sara D. Brouse, Todd Bell, Roger J. Bedimo, Carlos A. Alvarez

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

No studies have evaluated the effect of guideline-recommended weight-based dosing on in-hospital mortality of patients with methicillin-resistant Staphylococcus aureus bacteremia.

Methods

This was a multicenter, retrospective, cohort study of patients with methicillin-resistant Staphylococcus aureus bacteremia receiving at least 48 hours of empiric vancomycin therapy between 01/07/2002 and 30/06/2008. We compared in-hospital mortality for patients treated empirically with weight-based, guideline-recommended vancomycin doses (at least 15 mg/kg/dose) to those treated with less than 15 mg/kg/dose. We used a general linear mixed multivariable model analysis with variables identified a priori through a conceptual framework based on the literature.

Results

A total …

Increased Prevalence Of Methicillin-Resistant Staphylococcus Aureus Nasal Colonization In Household Contacts Of Children With Community Acquired Disease, Yaseen Rafee, Nahed Abdel-Haq, Basim Asmar, Tanaz Salimnia, Celine Pharm, Michael J. Rybak Pharm, Muhammad Amjad

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

To measure Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization prevalence in household contacts of children with current community associated (CA)-MRSA infections (study group) in comparison with a group of household contacts of children without suspected Staphylococcus aureus infection (a control group).

Methods

This is a cross sectional study. Cultures of the anterior nares were taken. Relatedness of isolated strains was tested using pulse field gel electrophoresis (PFGE).

Results

The prevalence of MRSA colonization in the study group was significantly higher than in the control group (18/77 (23%) vs 3/77 (3.9%); p ≤ 0.001). The prevalence of SA colonization was …

Effect Of Spermidine On Misfolding And Interactions Of Alpha-Synuclein., Alexey V. Krasnoslobodtsev, Jie Peng, Josephat M. Asiago, Jagadish Hindupur, Jean-Christophe Rochet, Yuri L. Lyubchenko

Journal Articles: Pharmaceutical Sciences

Alpha-synuclein (α-Syn) is a 140 aa presynaptic protein which belongs to a group of natively unfolded proteins that are unstructured in aqueous solutions. The aggregation rate of α-Syn is accelerated in the presence of physiological levels of cellular polyamines. Here we applied single molecule AFM force spectroscopy to characterize the effect of spermidine on the very first stages of α-Syn aggregation--misfolding and assembly into dimers. Two α-Syn variants, the wild-type (WT) protein and A30P, were studied. The two protein molecules were covalently immobilized at the C-terminus, one at the AFM tip and the other on the substrate, and intermolecular interactions …

College Of Pharmacy 2012, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

A Gga Plus U Approach To Effective Electronic Correlations In Thiolate-Ligated Iron-Oxo (Iv) Porphyrin, Justin Elenewski, John C. Hackett

Medicinal Chemistry Publications

High-valent oxo-metal complexes exhibit correlated electronic behavior on dense, low-lying electronic state manifolds, presenting challenging systems for electronic structure methods. Among these species, the iron-oxo (IV) porphyrin denoted Compound I occupies a privileged position, serving a broad spectrum of catalytic roles. The most reactive members of this family bear a thiolate axial ligand, exhibiting high activity toward molecular oxygen activation and substrate oxidation. The default approach to such systems has entailed the use of hybrid density functionals or multi-configurational/multireference methods to treat electronic correlation. An alternative approach is presented based on the GGA+U approximation to density functional theory, in …

The Use Of Peppermint Oil To Reduce The Nausea Of The Palliative Care And Hospice Patient, Mary Seale

Nursing Theses and Capstone Projects

A descriptive study was initiated to investigate the use of peppermint oil to reduce the nausea of the palliative care and hospice patient. Two local palliative care and hospice programs were used as sites for the study. Patients eighteen and older complaining of nausea were invited to participate in the study. The study was conducted for one and a half months. A total of eight patients consented to participate in the study with a mean age of seventy one years. The Bieri Scale, a visual-numeric analog, was used as the measurement instrument for the patients to evaluate their nausea. Results …

Single Mutation To A Sex Pheromone Receptor Provides Adaptive Specificity Between Closely Related Moth Species, Gregory Patrick Leary, Jean E. Allen, Peggy L. Bunger, Jena B. Luginbill, Charles E. Linn Jr., Irene E. Macallister, Michael Kavanaugh, Kevin W. Wanner

Biomedical and Pharmaceutical Sciences Faculty Publications

Sex pheromone communication, acting as a prezygotic barrier to mating, is believed to have contributed to the speciation of moths and butterflies in the order Lepidoptera. Five decades after the discovery of the first moth sex pheromone, little is known about the molecular mechanisms that underlie the evolution of pheromone communication between closely related species. Although Asian and European corn borers (ACB and ECB) can be interbred in the laboratory, they are behaviorally isolated from mating naturally by their responses to subtly different sex pheromone isomers, (E)-12- and (Z)-12-tetradecenyl acetate and (E)-11- and (Z)-11-tetradecenyl acetate (ACB: E12, Z12; ECB; E11, …

Anthocyanins And Flavonoids Of Vaccinium L., Zushang Su

Faculty Publications

Vaccinium L., comprising approximately 450 species primarily in the Northern Hemisphere, is a genus of shrubs or lianas in the family Ericaceae. The berries of many species are harvested for household consumption and commercial sale. The genus produces a wide range of compounds such as anthocyanins, flavonoids, chromones, coumarins, lignans, benzoic acids, iridoids, sterols, and triterpenoids, but is best known for the production of anthocyanins and flavonoids. Extracts and isolates of anthocyanins and flavonoids from Vaccinium fruits or leaves showed antioxidative, anti-inflammatory, antitumor, antiviral, vasoprotective, and antifungal activities. To data, more than 116 anthocyanins and flavonoids compounds have been isolated …

Phytochemical Constituents And Pharmacological Activities Of Eryngium L.(Apiaceae), Ping Wang, Zushang Su, Wei Yuan, Guangrui Deng, Shiyou Li

Faculty Publications

Eryngium L. is the largest and arguably the most taxonomically complex genus of the family Apiaceae. The genus has approximately 250 species throughout the world, with the center of diversity in South America. Some Eryngium species are cultivated as ornamental, vegetable, or medicinal crops for folk uses. With increasing chemical and biological investigations, Eryngium has shown its potential as pharmaceutical crops. This review focuses on phytochemistry and pharmacological activities of 127 compounds isolated and identified from 23 species of Eryngium, particularly nonessential oil compounds such as terpenoids, triterpenoid saponins, flavonoids, coumarins, polyacetylenes, and steroids. Eryngium extracts or isolates have shown …

Use Of Cilostazol For Secondary Stroke Prevention: An Old Dog With New Tricks?, Alex J. Ansara, Dane L. Shiltz, Jennifer B. Slavens

Scholarship and Professional Work – COPHS

OBJECTIVE: To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke.

DATA SOURCES: PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed.

STUDY SELECTION AND DATA EXTRACTION: Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included.

DATA SYNTHESIS: Antiplatelet therapy plays a vital role in the multifaceted approach …

Hemopericardium And Cardiac Tamponade Associated With Dabigatran Use, Eliza A. Dy, Dane L. Shiltz

Scholarship and Professional Work – COPHS

OBJECTIVE: To describe 2 cases of hemopericardium following treatment with dabigatran.

CASE SUMMARIES: A 70-year-old male with a history of dabigatran use presented with cough, fatigue, and bloody stools. The patient had a large hyperdense pericardial effusion caused by accumulation of bloody fluid, leading to hypotension and shock. Approximately 1000 mL of hemorrhagic fluid was drained from the pericardial space. A 77-year-old female was admitted for treatment of pneumonia and atrial fibrillation. Dabigatran was initiated and, after 6 doses, the patient developed abdominal pain, respiratory distress, and shock. She was diagnosed with pericardial effusion leading to cardiac tamponade. Pericardiocentesis and …

Winter 2011 - 2012, Southwestern Oklahoma State University

The Sig

The Sig Newsletter from the Southwestern Oklahoma State University College of Pharmacy - Winter 2011 - 2012

The College Of Pharmacy, South Dakota State University

Jackrabbits Script and Scope (Formerly called College of Pharmacy and Allied Health Professions Magazine)

[Page] 2 A rural residency Liebe Drug is teaming with the College to create a rural residency program.
[Page] 4 A small-town summer Program putting P2 students in six communities this summer.
[Page] 6 Good things in small packages Rural pharmacies face serious challenges.
[Page] 8 Changing landscape Visiting dean foresees new roles for pharmacist, the industry.
[Page] 10 Jim Roeman After forty-seven years, the cornerstone of Rock Rapids, Iowa, plans to turn a corner.
[Page] 11 Brian Kaatz The 1974 grad and former dean is named Alumnus of the Year by the College.
[Page] 12 Alex VanOverschelde P2 student …

Crystal Structures Of Human Pyridoxal Kinase In Complex With The Neurotoxins, Ginkgotoxin And Theophylline: Insights Into Pyridoxal Kinase Inhibition, Amit Gandhi, Jigar V. Desai, Mohini S. Ghatge, Martino L. Di Salvo, Stefano Di Biase, Richmond Danso-Danquah, Faik N. Musayev, Roberto Contestabile, Verne Schirch, Martin A. Safo

Medicinal Chemistry Publications

Several drugs and natural compounds are known to be highly neurotoxic, triggering epileptic convulsions or seizures, and causing headaches, agitations, as well as other neuronal symptoms. The neurotoxic effects of some of these compounds, including theophylline and ginkgotoxin, have been traced to their inhibitory activity against human pyridoxal kinase (hPL kinase), resulting in deficiency of the active cofactor form of vitamin B6, pyridoxal 5′-phosphate (PLP). Pyridoxal (PL), an inactive form of vitamin B6 is converted to PLP by PL kinase. PLP is the B6 vitamer required as a cofactor for over 160 enzymatic activities essential in primary and secondary metabolism. …

Retrospective Comparison Of The Incidence Of Acute Kidney Injury In Patients Treated With Intravenous Polymyxin B Or Intravenous Colistimethate Sodium, Rebecca A. Sumner Pharmd, Jarrod W. Kile Rph, Bcps

Department of Pharmacy

No abstract provided.

Retrospective Evaluation Of Admissions For Chemotherapy-Inducednausea, Vomiting, And Dehydration, Katelin Van Leer Pharmad, Janine Barnaby Rph, Bcop

Department of Pharmacy

No abstract provided.

System-Wide Implementation Of The Use Of An Extended-Infusion Piperacillin/Tazobactam Dosing Strategy: Feasibility Of Utilization From A Children's Hospital Perspective, Kristen R. Nichols, Chad A. Knoderer, Elaine G. Cox

Scholarship and Professional Work – COPHS

Background

Use of extended infusions of piperacillin/tazobactam (PT) in adult patients has been described, but data in children are limited.

Objective

The goal of this study was to determine the feasibility of using an extended-infusion PT dosing strategy as the standard of care in a children's hospital.

Methods

This was a prospective observational study of patients aged >30 days who received PT after admission to a freestanding, tertiary care children's hospital. After institution of an extended-infusion PT dosing protocol as the standard dosing option, patients receiving PT were prospectively assessed for presence of and reasons for changes in dosing regimen. …

Nonsteroidal Anti-Inflammatory Drugs Are An Important Cause Of Acute Kidney Injury In Children, Jason M. Misurac, Chad A. Knoderer, Jeffrey D. Leiser, Corina Nilescu, Amy C. Wilson, Sharon P. Andreoli

Scholarship and Professional Work – COPHS

Objective

To characterize nonsteroidal anti-inflammatory drug (NSAID)-associated acute kidney injury (AKI) in children.

Study design

We conducted a retrospective chart review of children diagnosed with AKI through the use of International Classification of Diseases, Ninth Revision diagnosis code 584.5 or 584.9 from January 1999 to June 2010. Medical records were reviewed to confirm the diagnosis of AKI and to quantify NSAID administration. Pediatric RIFLE criteria were used to codify AKI. Patients were not classified as having NSAID-associated AKI if they had a diagnosis explaining AKI or comorbid clinical conditions predisposing to AKI development.

Results

Patients (N = 1015) were identified …

Tissue-Specific Alterations Of Prl-1 And Prl-2 Expression In Cancer, Carmen M. Dumaual, George E. Sandusky, Han Weng Soo, Sean R. Werner, Pamela L. Crowell, Stephen K. Randall

Scholarship and Professional Work – COPHS

The PRL-1 and PRL-2 phosphatases have been implicated as oncogenic, however the involvement of these molecules in human neoplasms is not well understood. To increase understanding of the role PRL-1 and PRL-2 play in the neoplastic process, in situ hybridization was used to examine PRL-1 and PRL-2 mRNA expression in 285 normal, benign, and malignant human tissues of diverse origin. Immunohistochemical analysis was performed on a subset of these. PRL-1 and PRL-2 mRNA expression was also assessed in a small set of samples from a variety of diseases other than cancer. Where possible, associations with clinicopathological characteristics were evaluated. Alterations …

Delayed-Onset Malignant Hyperthermia In Association With Rocuronium Use, Ashton E. Beggs, Jennifer Quinn Mccann, Jan M. Powers

Scholarship and Professional Work – COPHS

Purpose Two cases of malignant hyperthermia suspected to be related to the use of a nondepolarizing neuromuscular blocker are reported.

Summary A pharmacogenetic disorder that may occur in as many as 1 in 3000 anesthesia procedures, malignant hyperthermia has been linked to the use of certain anesthetic gases and depolarizing neuromuscular blocking agents (e.g., succinylcholine). Although nondepolarizing neuromuscular blockers were cited as contributing to the development of malignant hyperthermia in a small number of published reports, the agents are generally considered safe for use in at-risk patients. Here investigators report two cases in which the nondepolarizing agent rocuronium is thought …

Rocuronium And Malignant Hyperthermia, Jennifer Quinn Mccann, Ashton E. Beggs

Scholarship and Professional Work – COPHS

Authors response to a comment on: Beggs A, McCann J, Powers J. “Delayed-onset malignant hyperthermia in association with rocuronium use ” Am J Health-Syst Pharm 2012; 69:1128-34.

Do Antibiotics Improve Outcomes For Patients Hospitalized With Copd Exacerbations?, Sagi Mathew, Deborah S. Zeitlin, Katherine Rickett

Scholarship and Professional Work – COPHS

EVIDENCE-BASED ANSWER

YES. Antibiotic use reduced mortality and treatment failure in patients hospitalized with acute exacerbations of chronic obstructive pulmonary disease (COPD) (strength of recommendation [SOR]: A, systematic reviews of randomized controlled trials [RCTs]).

Giving antibiotics early to hospitalized patients decreased the need for later ventilation and readmission within 30 days for exacerbation of COPD (SOR: B, a retrospective cohort study).

Bone Health Management In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Vishnuprabha Dhanapal, David J. Reeves

Scholarship and Professional Work – COPHS

Purpose. Patients receiving androgen deprivation therapy undergo a rapid decline in bone mineral density during the first 6 to 12 months of initiating therapy. The World Health Organization has developed and implemented the Fracture Risk Assessment Tool (FRAX) to predict the ten year risk of a major fracture & hip fracture. Additionally, the National Comprehensive Cancer Network and the National Osteoporosis Foundation have developed osteoporosis guidelines. This study aims to characterize the fracture risk (based on the FRAX tool) and the current management of bone health based on national guidelines compliance.

Methods. A retrospective chart review of patients receiving a …

Successful Desensitization To Docetaxel After Severe Hypersensitivity Reactions In Two Patients, David J. Reeves, Michael J. Callahan, Gregory P. Sutton

Scholarship and Professional Work – COPHS

Purpose Two cases of successful desensitization to docetaxel after severe hypersensitivity reactions are reported.

Summary Two patients with gynecological malignancies (uterine leiomyosarcoma and ovarian adenocarcinoma) experienced severe hypersensitivity reactions with docetaxel, including flushing, numbness, sharp radiating pain, severe nausea and vomiting, apnea, and unresponsiveness. Both patients received ondansetron before docetaxel. One patient received dexamethasone, diphenhydramine, and famotidine premedication before docetaxel, as she had previously reacted to paclitaxel. Docetaxel infusions were stopped, and the reactions were treated with diphenhydramine and dexamethasone (one patient also received famotidine). After resolution of symptoms, the docetaxel was not reinitiated due to the nature of the …

Leukopenia Associated With Long-Term Colchicine Adminsitration, Ashton E. Beggs, David J. Reeves, Nancy S. Noel

Scholarship and Professional Work – COPHS

Purpose A case of leukopenia in a patient receiving colchicine for calcium pyrophosphate dihydrate deposition disease, or pseudogout, is reported.

Summary An 85-year-old man experienced leukopenia likely due to colchicine. His medical history included chronic lymphocytic leukemia (CLL), pseudogout, osteoarthritis, and hypertension. In February 2011, his white blood cell (WBC) count was 2700 cells/μL, and his absolute neutrophil count (ANC) was 2200 cells/μL. Colchicine 0.6 mg orally daily was initiated in March for the prophylaxis of pseudogout. His WBC count decreased, and his colchicine dosage was reduced to 0.6 mg every other day. Despite this decreased dosage, his WBC count …

Analytical Strategies For Drug Residues In Various Matrices In A Regulatory Laboratory., Geraldine Dowling

Dissertations

Abstract

Today, in modern farming practices veterinary drugs are given to food-producing animals. The generic term “veterinary drugs” covers a broad variety of classes of chemical compounds and the list of drugs is enormous and it is a significant analytical challenge in regulatory control to provide monitoring programmes. The major concerns in veterinary drug usage are the presence of harmful residues that may be introduced into the human food chain. The aim of this research is the development of analytical methods capable of screening and confirming increased numbers of these residues in target matrices by Gas Chromatography Tandem Mass Spectrometry …

Benefits Versus Costs Of Statin Drugs, Sara Shilcrat

The Science Journal of the Lander College of Arts and Sciences

Statins have been prescribed to the masses as primary and secondary prevention for coronary disease caused by hypercholesterolemia after their initial discovery in the late 1980s. Their actions in reducing low-density lipoproteins and increasing high-density lipoproteins are well documented; however, many negative effects have been reported related to muscle pathology and kidney function. The goal of this study is to investigate whether the benefits of this class of drugs outweigh the costs. Intense review of the literature was conducted using scholarly articles with original research findings that were located via electronic databases such as Medline, Science Direct, Proquest Medical Library, …