Medicine and Health Sciences Commons^™

Ryanodine Receptor Adaptation, Michael Fill, A. Zahradníková, Carlos A. Villalba-Galea, I. Zahradník, A. L. Escobar, S. Györke

School of Pharmacy Faculty Articles

In the heart, depolarization during the action potential activates voltage-dependent Ca²⁺ channels that mediate a small, localized Ca²⁺ influx (I_Ca). This small Ca²⁺ signal activates specialized Ca²⁺ release channels, the ryanodine receptors (RyRs), in the sarcoplasmic reticulum (SR). This process is called Ca²⁺-induced Ca²⁺ release (CICR). Intuitively, the CICR process should be self-regenerating because the Ca²⁺ released from the SR should feedback and activate further SR Ca²⁺ release. However, the CICR process is precisely controlled in the heart and, consequently, some sort of negative control mechanism(s) must exist to …

Hybridization Of Dna By Sequential Immobilization Of Oligonucleotides At The Air-Water Interface, Murali Sastry, Vidya Ramakrishnan, Mrunalini Pattarkine, Anand Gole, K. N. Ganesh

Faculty Works

The hybridization of DNA by sequential electrostatic and hydrogen-bonding immobilization of single-stranded complementary oligonucleotides at the air-water interface with cationic Langmuir monolayers is demonstrated. The complexation of the single-stranded DNA molecules with octadecylamine (ODA) Langmuir monolayers was followed in time by monitoring the pressure-area isotherms. A large (and slow) expansion of the ODA monolayer was observed during each stage of complexation in the following sequence: primary single-stranded DNA followed by complementary single-stranded DNA followed by the intercalator, ethidium bromide. Langmuir-Blodgett (LB) films of the ODA-DNA complex were formed on different substrates and characterized using quartz-crystal microgravimetry (QCM), Fourier transform infrared …

Research News: 2000, No. 4, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Oxandrolone In Trauma Patients, Jane M. Gervasio, Roland N. Dickerson, Jessica Swearingen, Mary E.D. Yates, Ceaminia Yuen, Timothy C. Fabian, Martin A. Croce, Rex O. Brown

Scholarship and Professional Work – COPHS

Study Objective

To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma.

Design

Prospective, randomized, double-blind, placebo-controlled study. Setting. Level 1 trauma center in a university teaching hospital.

Patients

Sixty-two patients requiring enteral nutrition, 60 of whom completed the study.

Intervention

Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days.

Measurements and Main Results

Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients …

7. Richard S. Stein, Otto Vogl, Judith Balise Stein

Emeritus Faculty Author Gallery

No abstract provided.

The Toxicology Of Aluminum In The Brain: A Review, Robert A. Yokel

Pharmaceutical Sciences Faculty Publications

Aluminum is environmentally ubiquitous, providing human exposure. Usual human exposure is primarily dietary. The potential for significant Al absorption from the nasal cavity and direct distribution into the brain should be further investigated. Decreased renal function increases human risk of Al-induced accumulation and toxicity. Brain Al entry from blood may involve transferrin-receptor mediated endocytosis and a more rapid process transporting small molecular weight Al species. There appears to be Al efflux from the brain, probably as Al citrate. There is prolonged retention of a fraction of Al that enters the brain, suggesting the potential for accumulation with repeated exposure. Al …

7. Richard S. Stein, Otto Vogl, Judith Balise Stein

Otto Vogl

No abstract provided.

Nutraceuticals, Jane Gervasio

Jane M. Gervasio

No abstract provided.

Ouabain Interaction With Cardiac Na+/K+-Atpase Initiates Signal Cascades Independent Of Changes In Intracellular Na+ And Ca2+, Jiang Liu, Jiang Tian, Michael Haas, Joseph I. Shapiro, Amir Askari, Zijian Xie

Pharmaceutical Science and Research

We have shown previously that partial inhibition of the cardiac myocyte Na⁺/K⁺-ATPase activates signal pathways that regulate myocyte growth and growth-related genes and that increases in intracellular Ca²⁺ concentration ([Ca²⁺]i) and reactive oxygen species (ROS) are two essential second messengers within these pathways. The aim of this work was to explore the relation between [Ca²⁺]i and ROS. When myocytes were in a Ca²⁺-free medium, ouabain caused no change in [Ca²⁺]i, but it increased ROS as it did when the cells were in …

Allelic Modifications Of The Cg2 And Cg1 Genes Do Not Alter The Chloroquine Response Of Drug-Resistant Plasmodium Falciparum, David A. Fidock, Takashi Nomura, Roland A. Cooper, Xin-Zhuan Su, Angela K. Talley, Thomas E. Wellems

Roland A. Cooper

Research News: 2000, No. 3, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Pathogen-Inducible Regulatory Element, Joseph Chappell, Catherine A. G. Cornett, Shauhui Yui

Pharmaceutical Sciences Faculty Patents

Qualitative transcriptional regulatory sequences functional in plants, plant tissue and in plant cells for inducible gene expression and quantitative transcriptional regulatory sequences for increasing the transcriptional expression of downstream genetic information in plants, plant tissue and plant cells are disclosed. Also disclosed are methods and recombinant DNA molecules for improving the disease resistance of transgenic plants, especially wherein an inducible promoter controls the expression of a protein capable of evoking the hypersensitive response in a plant.

Sequential Group Trial To Determine Gastrointestinal Site Of Absorption And Systemic Exposure Of Azathioprine, Jane M. Gervasio, Rex O. Brown, John Lima, M. G. Tabbaa, Thomas Abell, Robert Werkman, Lynda J. Haberer, Lawrence J. Hak

Scholarship and Professional Work – COPHS

Azathioprine (AZA) is used in the treatment of patients with refractory inflammatory bowel disease; however, its use is limited because of systemic toxicity associated with long-term use. Ileocecal delivery of AZA might be advantageous if local intestinal therapeutic effects could be provided with decreased systemic side effects. Decreased cecal systemic absorption would allow higher dosages of AZA to be administered. A two-phase study was performed to compare the systemic exposure of AZA and 6-mercaptopurine (6-MP) following administration of AZA into the stomach, jejunum, and cecum and to compare the systemic exposure to AZA and 6-MP following administration of three different …

2000 Apothecary, Southwestern Oklahoma State University

Apothecary

The 2000 Apothecary staff wishes to congratulate the graduating seniors! With the knowledge and skills gained while attending Southwestern's School of Pharmacy, you will certainly succeed in advancing the profession of pharmacy. Best wishes for a successful career.

Use Of Lobeline Compounds In The Treatment Of Central Nervous System Diseases And Pathologies, Peter A. Crooks, Linda P. Dwoskin

Pharmaceutical Sciences Faculty Patents

Lobeline and nicotine evoke [³H]overflow from rat striatal slices preloaded with [³H]dopamine ([³H]DA). The lobeline-evoked overflow is calcium-independent and not antagonized by mecamylamine, suggesting a mechanism of action other than the stimulation of nicotinic receptors. Whereas nicotine stimulates nicotinic receptors, lobeline inhibits [³H]DA uptake into synaptic vesicles and striatal synaptosomes. The results suggest that different mechanisms are responsible for the increase in striatal DA release evoked by lobeline and nicotine. [³H]-Dihydrotetrabenazine [³H]DTBZ), used routinely to probe a high-affinity binding site-on the vesicular monoamine transporter (VMAT2) binds to vesicle …

Formulations For Sustained-Release Of Topical Anesthetics And Methods Of Making And Using Same, Michael Joseph Jay, G. Thomas Kluemper, Sang Hun Kim

Pharmaceutical Sciences Faculty Patents

The present invention provides, inter alia, formulations useful to ameliorate symptoms associated with mucosal abrasions, specifically those due to dental orthodontic brackets; oral surgery; periodontal surgery or other procedures. For instance, there is a formulation comprising: 65 to 75% microcrystalline wax; 5 to 15% non-ionic polymer; 15 to 25% topical anesthetic; and 1 to 5% surfactant, wherein the ratio of non-ionic polymer to microcrystalline wax is no greater than 0.2. Preferably, for solid topical anesthetics, the particle size is less than the apertures of a 100-mesh screen. However, the topical anesthetic may also be a liquid. Formulations wherein the mixture …

Chemical Isoprenoid Synthases And Uses Thereof, Joseph Chappell, Kyoungwhan Back

Pharmaceutical Sciences Faculty Patents

Disclosed is a chimeric isoprenoid synthase polypeptide including a first domain from a first isoprenoid synthase joined to a second domain from a second, heterologous isoprenoid synthase, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced in the absence of the second domain of the second, heterologous isoprenoid synthase. Also disclosed is a chimeric isoprenoid synthase polypeptide including an asymmetrically positioned homologous domain, whereby the chimeric isoprenoid synthase is capable of catalyzing the production of isoprenoid reaction products that are not produced when the domain is positioned at its naturally-occurring …

Angiotensin Ii Promotes Atherosclerotic Lesions And Aneurysms In Apolipoprotein E-Deficient Mice, Alan Daugherty, Michael W. Manning, Lisa A. Cassis

Gill Heart & Vascular Institute Faculty Publications

Increased plasma concentrations of angiotension II (Ang II) have been implicated in atherogenesis. To examine this relationship directly, we infused Ang II or vehicle for 1 month via osmotic minipumps into mature apoE^–/– mice. These doses of Ang II did not alter arterial blood pressure, body weight, serum cholesterol concentrations, or distribution of lipoprotein cholesterol. However, Ang II infusions promoted an increased severity of aortic atherosclerotic lesions. These Ang II–induced lesions were predominantly lipid-laden macrophages and lymphocytes; moreover, Ang II promoted a marked increase in the number of macrophages present in the adventitial tissue underlying lesions. Unexpectedly, pronounced abdominal …

Enteral Nutrition, Jane Gervasio

Jane M. Gervasio

No abstract provided.

Technical Aspects, Jane Gervasio

Jane M. Gervasio

No abstract provided.

Host-Derived Signals For Inducing Isoprenoid Gene Expression And Uses Thereof, Joseph Chappell, Marcos Lusso

Pharmaceutical Sciences Faculty Patents

Disclosed is a method for preparing a composition that is capable of activating the expression of a gene involved in the synthesis of an isoprenoid, the method involving: (a) contacting a plant cell with an elicitor under conditions that allow an elicitor-induced release of a compound that activates the synthesis of an isoprenoid; and (b) recovering a composition including the compound, wherein the compound is diffusible and has a molecular weight less than or equal to 10,000 daltons. Also disclosed is a substantially pure elicitor-induced composition, the composition being capable of activating a gene involved in the synthesis of a …

Spring 2000, Southwestern Oklahoma State University

The Sig

The Sig Newsletter from the Southwestern Oklahoma State University College of Pharmacy - Spring 2000

Novel Function Of Phosphoinositide 3-Kinase In T Cell Ca2+ Signaling, Ao-Lin Hsu, Tsui-Ting Ching, Goutam Sen, Da-Sheng Wan, Subbarao Bondada, Kalwant S. Authi, Ching-Shih Chen

Pharmaceutical Sciences Faculty Publications

This study presents evidence that phosphoinositide (PI) 3-kinase is involved in T cell Ca²⁺ signaling via a phosphatidylinositol 3,4,5-trisphosphate PI(3,4,5)P₃-sensitive Ca²⁺entry pathway. First, exogenous PI(3,4,5)P₃ at concentrations close to its physiological levels induces Ca²⁺ influx in T cells, whereas PI(3,4)P₂, PI(4,5)P₂, and PI(3)P have no effect on [Ca²⁺]_i. This Ca²⁺ entry mechanism is cell type-specific as B cells and a number of cell lines examined do not respond to PI(3,4,5)P₃ stimulation. Second, inhibition of PI 3-kinase by wortmannin and by overexpression of the …

Sequential Single Doses Of Cisapride, Erythromycin, And Metoclopramide In Critically Ill Patients Intolerant To Enteral Nutrition: A Randomized, Placebo-Controlled, Crossover Study, Robert Maclaren, David A. Kuhl, Jane M. Gervasio, Rex O. Brown, Roland N. Dickerson, Teresa N. Livingston, Kyle Swift, Stacey Headley, Kenneth A. Kudsk, John J. Lima

Scholarship and Professional Work – COPHS

Objective: To evaluate the comparative efficacy of enteral cisapride, metoclopramide, erythromycin, and placebo for promoting gastric emptying in critically ill patients with intolerance to gastric enteral nutrition (EN).

Design: A randomized, crossover study.

Setting: Adult medical intensive care unit at a university-affiliated private hospital and trauma intensive care unit at a university teaching hospital.

Patients: Ten adult, critically ill, mechanically ventilated patients not tolerating a fiber-containing EN product defined as a single aspirated gastric residual volume >150 mL or two aspirated gastric residual volumes >120 mL during a 12-hr period.

Interventions: Patients received 10 mg …

Effect Of Ceftazidime On Systemic Cytokine Concentrations In Rats, Khalid M. Alkharfy, John A. Kellum, Reginald F. Frye, Gary R. Matzke

Pharmacotherapy and Outcomes Science Publications

The effect of a single dose of ceftazidime on circulating concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in a rat model of sepsis was studied. IL-6 concentrations were significantly elevated (100 to 200 times the baseline) 6 h after ceftazidime administration in both septic and nonseptic (control) rats. TNF-α concentrations increased significantly in nonseptic (∼40 times the baseline) rats but not septic (∼2 to 3 times the baseline) rats. Ceftazidime administration was not associated with an increase in endotoxin concentrations. These findings suggest that ceftazidime modulation of proinflammatory cytokine concentrations may be independent of its antimicrobial properties.

Effect Of Formulation Variables On The Percutaneous Permeation Of Ketoprofen From Gel Formulations, Ayman F. El-Kattan, C. Scott Asbill, Nanhye Kim, Bozena B. Michniak

Pharmaceutical Sciences

No abstract provided.

Cell Cycle-Dependent Binding Of Yeast Heat Shock Factor To Nucleosomes, Christina Bourgeois Venturi, Alexander M. Erkine, David S. Gross

Scholarship and Professional Work – COPHS

In the nucleus, transcription factors must contend with the presence of chromatin in order to gain access to their cognate regulatory sequences. As most nuclear DNA is assembled into nucleosomes, activators must either invade a stable, preassembled nucleosome or preempt the formation of nucleosomes on newly replicated DNA, which is transiently free of histones. We have investigated the mechanism by which heat shock factor (HSF) binds to target nucleosomal heat shock elements (HSEs), using as our model a dinucleosomal heat shock promoter (hsp82-ΔHSE1). We find that activated HSF cannot bind a stable, sequence-positioned nucleosome in G₁-arrested …

The Skn7 Response Regulator Of Saccharomyces Cerevisiae Interacts With Hsf1 In Vivo And Is Required For The Induction Of Heat Shock Genes By Oxidative Stress, Desmond C. Raitt, Anthony L. Johnson, Alexander M. Erkine, Kozo Makino, Brian Morgan, David S. Gross, Leland H. Johnston

Scholarship and Professional Work – COPHS

The Skn7 response regulator has previously been shown to play a role in the induction of stress-responsive genes in yeast, e.g., in the induction of the thioredoxin gene in response to hydrogen peroxide. The yeast Heat Shock Factor, Hsf1, is central to the induction of another set of stress-inducible genes, namely the heat shock genes. These two regulatory trans-activators, Hsf1 and Skn7, share certain structural homologies, particularly in their DNA-binding domains and the presence of adjacent regions of coiled-coil structure, which are known to mediate protein–protein interactions. Here, we provide evidence that Hsf1 and Skn7 interact in vitro and …

Determinants Of Ceftazidime Clearance By Continuous Venovenous Hemofiltration And Continuous Venovenous Hemodialysis, Gary R. Matzke, Reginald F. Frye, Melanie S. Joy, Paul M. Palevsky

Pharmacotherapy and Outcomes Science Publications

Although several dosage adjustment regimens have been proposed, there is little quantitative information to guide the initiation of ceftazidime therapy in patients who are receiving continuous renal replacement therapy. To determine the clearance of ceftazidime by continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD), we performed controlled clearance studies with stable hemodialysis patients with three hemofilters: a 0.6-m2 acrylonitrile copolymer (AN69; Hospal) filter, a 2.1-m2 polymethylmethacrylate filter (PMMA; Toray) filter and a 0.65-m2 polysulfone (PS; Fresenius) filter. Subjects received 1,000 mg of ceftazidime intravenously prior to the start of a clearance study. The concentration of ceftazidime in multiple plasma …

Isolation Of Current Components And Partial Reaction Cycles In The Glial Glutamate Transporter Eaat2, Thomas S. Otis, Michael Kavanaugh

Biomedical and Pharmaceutical Sciences Faculty Publications

The kinetic properties of the excitatory amino acid transporter EAAT2 were studied using rapid applications of l-glutamate to outside-out patches excised from transfected human embryonic kidney 293 cells. In the presence of the highly permeant anion SCN⁻, pulses of glutamate rapidly activated transient anion channel currents mediated by the transporter. In the presence of the impermeant anion gluconate, glutamate pulses activated smaller currents predicted to result from stoichiometric flux of cotransported ions. Both anion and stoichiometric currents displayed similar kinetics, suggesting that anion channel gating and stoichiometric charge movements are linked to early transitions in the transport cycle. …