Medicine and Health Sciences Commons^™

Materials For Pharmaceutical Dosage Forms: Molecular Pharmaceutics And Controlled Release Drug Delivery Aspects, Heidi M. Mansour, Minji Sohn, Abeer Al-Ghananeem, Patrick P. Deluca

Pharmaceutical Sciences Faculty Publications

Controlled release delivery is available for many routes of administration and offers many advantages (as microparticles and nanoparticles) over immediate release delivery. These advantages include reduced dosing frequency, better therapeutic control, fewer side effects, and, consequently, these dosage forms are well accepted by patients. Advances in polymer material science, particle engineering design, manufacture, and nanotechnology have led the way to the introduction of several marketed controlled release products and several more are in pre-clinical and clinical development.

Identification Of Thioaptamer Ligand Against E-Selectin: Potential Application For Inflamed Vasculature Targeting., Aman P Mann, Anoma Somasunderam, René Nieves-Alicea, Xin Li, Austin Hu, Anil K Sood, Mauro Ferrari, David G Gorenstein, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Active targeting of a drug carrier to a specific target site is crucial to provide a safe and efficient delivery of therapeutics and imaging contrast agents. E-selectin expression is induced on the endothelial cell surface of vessels in response to inflammatory stimuli but is absent in the normal vessels. Thus, E-selectin is an attractive molecular target, and high affinity ligands for E-selectin could be powerful tools for the delivery of therapeutics and/or imaging agents to inflamed vessels. In this study, we identified a thiophosphate modified aptamer (thioaptamer, TA) against E-selectin (ESTA-1) by employing a two-step selection strategy: a recombinant protein-based …

Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …

Development And Applications Of The Hint Forcefield In Prediction Of Antibiotic Efflux And Virtual Screening For Antivirals, Aurijit Sarkar

Theses and Dissertations

This work was aimed at developing novel tools that utilize HINT, an empirical forcefield capable of quantitating both hydrophobic and hydrophilic (hydropathic) interactions, for implementation in theoretical biology and drug discovery/design. The role of hydrophobicity in determination of macromolecular structure and formation of complexes in biological molecules is undeniable and has been the subject of research across several decades. Hydrophobicity is introduced, with a review of its history and contemporary theories. This is followed by a description of various methods that quantify this all-pervading phenomenon and their use in protein folding and contemporary drug design projects – including a detailed …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Synthesis Of A Water Soluble Resveratrol Derivative As A Potential Anti-Cancer Drug., Augustine Essel

Electronic Theses and Dissertations

Research on development of water soluble anti-cancer drugs is one of the great challenges of modern medicinal chemistry. Resveratrol (Res) is one of the many phytoalexins producing stilbenoids present in several medicinal plants, grape skin, peanuts, and red wine. It has been found to exhibit anti-cancer, anti-inflammatory, and anti-oxidant properties. Water solubility and bioavailability are some of the setbacks of this interesting compound. In view of this, effort has been made to synthesize amino acid derivative of resveratrol to improve its bioavailability and solubility in water. Methyl 4-{-[(1E)-2-(3, 5-dihydroxyphenyl)-ethenyl] - phenoxy} butyrate (7), a novel ester intermediate, has been synthesized …

Comparison Of Estrogens And Estrogen Metabolites In Human Breast Tissue And Urine, Emanuela Taioli, Annie Im, Xia Xu, Timothy D. Veenstra, Gretchen Ahrendt, Seymour Garte

Pharmaceutical Sciences Faculty Publications

BACKGROUND: An important aspect of the link between estrogen and breast cancer is whether urinary estrogen levels are representative of the intra-tissue levels of bioavailable estrogens.

METHODS: This study compares 15 estrogen and estrogen metabolite levels in breast tissue and urine of 9 women with primary breast cancer using a quantitative liquid chromatography-mass spectrometry method.

RESULTS: The average levels of estrogens (estrone, 17 beta-estradiol) were significantly higher in breast tissue than in urine. Both the 2 and the 16-hydroxylation pathways were less represented in breast tissue than urine; no components of the 4-hydroxypathway were detected in breast tissue, while 4-hydroxyestrone …

A Bayesian Approach To Dose-Response Assessment And Drug-Drug Interaction Analysis: Application To In Vitro Studies, Violeta G. Hennessey

Dissertations & Theses (Open Access)

The considerable search for synergistic agents in cancer research is motivated by the therapeutic benefits achieved by combining anti-cancer agents. Synergistic agents make it possible to reduce dosage while maintaining or enhancing a desired effect. Other favorable outcomes of synergistic agents include reduction in toxicity and minimizing or delaying drug resistance. Dose-response assessment and drug-drug interaction analysis play an important part in the drug discovery process, however analysis are often poorly done. This dissertation is an effort to notably improve dose-response assessment and drug-drug interaction analysis.

The most commonly used method in published analysis is the Median-Effect Principle/Combination Index method …

A New Approach To Measuring Estrogen Exposure And Metabolism In Epidemiologic Studies, R. G. Ziegler, J. M. Faupel-Badger, L. Y. Sue, B. J. Fuhrman, R. T. Falk, J. Boyd-Morin, M. K. Henderson, R. N. Hoover, Timothy D. Veenstra, L. K. Keefer, X. Xu

Pharmaceutical Sciences Faculty Publications

Endogenous estrogen plays an integral role in the etiology of breast and endometrial cancer, and conceivably ovarian cancer. However, the underlying mechanisms and the importance of patterns of estrogen metabolism and specific estrogen metabolites have not been adequately explored. Long-standing hypotheses, derived from laboratory experiments, have not been tested in epidemiologic research because of the lack of robust, rapid, accurate measurement techniques appropriate for large-scale studies. We have developed a stable isotope dilution liquid chromatography-tandem mass spectrometry (LC-MS(2)) method that can measure concurrently all 15 estrogens and estrogen metabolites (EM) in urine and serum with high sensitivity (level of detection=2.5-3.0fmol …

Investigation And Optimization Of A Solvent / Anti-Solvent Crystallization Process For The Production Of Inhalation Particles, Swati Agrawal

Theses and Dissertations

Dry powder inhalers (DPIs) are commonly used to deliver drugs to the lungs. The drug particles used in these DPIs should possess a number of key properties. These include an aerodynamic particle size < 5μm and particle crystallinity for long term formulation stability. The conventionally used micronization technique to produce inhalation particles offers limited opportunities to control and optimize the particle characteristics. It is also known to induce crystalline disorder in the particles leading to formulation instability. Hence, this research project investigates and optimizes a solvent/anti-solvent crystallization process capable of directly yielding inhalation particles using albuterol sulfate (AS) as a model drug. Further, the feasibility of the process to produce combination particles of AS and ipratropium bromide monohydrate (IB) in predictable proportions and in a size suitable for inhalation is also investigated. The solvent / anti-solvent systems employed were water / ethyl acetate (EA) and water / isopropanol (IPA). Investigation and optimization of the crystallization variables with the water / EA system revealed that particle crystallinity was significantly influenced by an interaction between the drug solution / anti-solvent ratio (Ra ratio), stirring speed and crystal maturation time. Inducing a temperature difference between the drug solution and anti-solvent (Tdrug solution > Tanti-solvent) resulted in smaller particles being formed at a positive temperature difference of 65°C. IPA was shown to be the optimum anti-solvent for producing AS particles (IPA-AS) in a size range suitable for inhalation. In vitro aerosol performance of these IPA-AS particles was found to be superior compared to the conventionally used micronized particles when aerosolized from the Novolizer®. The solvent / anti-solvent systems investigated and optimized …

Research News: 2010, No. 1, University Of Mississippi. School Of Pharmacy

Research News: Grants and Publications (2000-2014)

Grants, publications, technology transfer, special announcements

Insights Into The Catalytic Mechanism Of Retro-Aldol Cleavage Of Β-Hydroxy Amino Acids By Escherichia Coli L-Threonine Aldolase, Remsh Soumya Govinda

Theses and Dissertations

With over 140 vitamin B6 (Pyridoxal 5’-phosphate, PLP) dependent enzymes, serving vital roles in various transamination, decarboxylation, retro-aldol cleavage and synthesis pathways these enzymes constitute the most versatile catalytic systems in nature. Enzymes of this group have an inherent reaction as well as substrate specificity. A single co-factor namely, PLP is used by specific enzymes of this group to serve distinct roles during the catalytic reaction. An ordered evolutionary adaptation in these enzymes has led to specialization achieved by each enzyme for catalyzing specific reactions. L-Threonine aldolase (L-TA) is one such PLP- dependent enzyme that catalyzes the retro-aldol cleavage of …

The Effect Of Anticholinergic Burden On Functional Outcomes In Patients With Moderate To Severe Alzheimer’S Disease, Sheetal Dharia

Theses and Dissertations

Background: Alzheimer’s disease (AD) is the most common form of dementia and is characterized by a progressive loss of memory, judgment, and thinking in older adults. The current treatment is cholinesterase inhibitors, which increase acetylcholine at the synapse. Medications with anticholinergic (AC) activity are given for a variety reasons including for the treatment of comorbid conditions or side effects of cholinesterase inhibitors (ChEIs). These drugs inhibit acetylcholine in the brain. Studies have shown the detrimental outcomes of using AC medications with ChEIs in older adults. Moreover, older patients take more medications and have an increased risk of developing AC toxicity …

Bioactive Peptide-Based Probes, Clair D. Hicks, Peter A. Crooks

Pharmaceutical Sciences Faculty Patents

A method for preparing a site-specific peptide probe, wherein the peptide is specific to a receptor, includes modifying a marker to include a tether molecule and covalently binding the tether molecule to the peptide. The present invention also provides a labeled probe, comprising a peptide specific for a receptor and a marker. The marker is modified to include a tether molecule capable of covalently binding to the peptide. The peptide is typically derived from a bacteriophage or is a synthetic analog or derivative of the peptide. The receptor will typically be found on a surface of a bacterial cell. The …

Antispasmodic, Bronchodilator And Blood Pressure Lowering Properties Of Hypericum Oblongifolium - Possible Mechanism Of Action, Arif-Ullah Khan, Munasib Khan, Fazal Subhan, Anwar Gilani

Department of Biological & Biomedical Sciences

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration-dependent (0.1-1.0 mg/mL) relaxation of spontaneous and high K(+) (80 mM)-induced contractions in isolated rabbit jejunum preparations, suggesting a Ca(++) antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca(++) concentration-response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 mu M) and high K(+)-induced contractions in guinea pig tracheal preparations. It caused a dose-dependent (3-100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition …

Self-Assessed Proficiency And Application Of Various Skills Learned During Postgraduate Pharmacy Teaching Skills Development Programs, Anna Ratka, Paul O. Gubbins, Carol A. Motycka, Jane M. Gervasio, Mark S. Johnson, Ron W. Maddox

Scholarship and Professional Work – COPHS

The purpose of this study was to identify teaching skills commonly taught during the postgraduate pharmacy teaching skills development programs, to describe trainees' perceived teaching proficiency, and the extent to which the learned teaching skills are applied in trainees' current positions. An online survey was developed for pharmacists who completed postgraduate teaching skills development programs. The survey included demographic and program queries as well as questions on 23 teaching skills. Participants self-assessed their proficiency in and application of their learned teaching skills. The online survey resulted in 122 qualified responses. After training, the perceived proficiency in nearly all 23 teaching …

The College Of Pharmacy, South Dakota State University

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

[Page] 2 Avera Health and Science Center Time for construction to yield to classroom work
[Page] 4 Dean’s Club Spotlight Donors Manthei, Casey, Markl, Stai help complete the Avera Center
[Page] 6 Community involvement P3 students engage in health outreach in Sioux Falls
[Page] 7 Patel’s Studies Zambian student says she has found another home in friendly South Dakota
[Page] 8 Spring Convocation Kelly Gellerman - lessons from a cancer survivor
[Page] 9 White Coat Ceremony P1 students cautioned to keep white coats clean [Page] 10 2010 Graduates
[Page] 12 Awards Students receive honors at hooding ceremony
[Page] 13 Distinguished …

New Intravenous Antibiotics: A Focused Pharmacotherapy Update, Kathryn A. Connor

Pharmacy Faculty/Staff Publications

Infections due to multidrug-resistant pathogens are increasing throughout the world, in particular due to the emergence of resistant Staphylococcus aureus, vancomycin-resistant enterococcus (VRE) penicillin-resistant Streptococcus pneumonia, multidrug-resistant (MDR) Pseudomonas and Acinetobacter spp, extended-spectrum β-lactamase- (ESBL) producing enteric organisms, etc. These serious pathogens are a major cause of severe hospital and community-acquired infections and are associated with high morbidity and mortality. Several new parenteral antibiotics have been approved in the past several years to help treat these infections, including telavancin, doripenem, tigecycline and daptomycin. This article reviews the pharmacology and limitations of these new antibiotics in treating infections in …

Who Is Exposed To Smoke At Home? A Population-Based Cross-Sectional Survey In Central Vietnam, Motoi Suzuki, Vu Dinh Thiem, Lay-Myint Yoshida, Dang Duc Anh, Paul E. Kilgore, Koya Ariyoshi

Department of Pharmacy Practice

No abstract provided.

High Activity Mutants Of Butyrylcholinesterase For Cocaine Hydrolysis, Chang-Guo Zhan, Fang Zheng, Wenchao Yang

Pharmaceutical Sciences Faculty Patents

Butyrylcholinesterase (BChE) polypeptide variants of the presently-disclosed subject matter have enhanced catalytic efficiency for (−)-cocaine, as compared to wild-type BChE. Pharmaceutical compositions of the presently-disclosed subject matter include a BChE polypeptide variant having an enhanced catalytic efficiency for (−)-cocaine. A method of the presently-disclosed subject matter for treating a cocaine-induced condition includes administering to an individual an effective amount of a BChE polypeptide variant, as disclosed herein, to lower blood cocaine concentration.

Hart County, Kentucky - Prescriptions (Sc 2279), Manuscripts & Folklife Archives

MSS Finding Aids

Finding aid and scans (Click on "Additional Files" below) for Manuscripts Small Collection 2279. Prescriptions written primarily by physicians practicing in Hart County, Kentucky and surrounding counties. Some are written on the physician's own form while others are written on the form of a local druggist or drugstore.

Troglitazone Stimulates Beta-Arrestin-Dependent Cardiomyocyte Contractility Via The Angiotensin Ii Type 1a Receptor., Douglas G G. Tilley, Anny D. Nguyen, Howard A. Rockman

College of Pharmacy Faculty Papers

Peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists are commonly used to treat cardiovascular diseases, and are reported to have several effects on cardiovascular function that may be due to PPAR gamma-independent signaling events. Select angiotensin receptor blockers (ARBs) interact with and modulate PPAR gamma activity, thus we hypothesized that a PPAR gamma agonist may exert physiologic effects via the angiotensin II type 1(A) receptor (AT1(A)R). In AT1(A)R-overexpressing HEK 293 cells, both angiotensin II (Ang II) and the PPAR gamma agonist troglitazone (Trog) enhanced AT1(A)R internalization and recruitment of endogenous beta-arrestin 1/2 (beta arr1/2) to the AT1(A)R. A fluorescence assay to …

Distribution Of A Novel Binding Site For Angiotensins Ii And Iii In Mouse Tissues, Felicia M. Rabey, Vardan T. Karamyan, Robert C. Speth

HPD Articles

A novel binding site for angiotensins II and III that is unmasked by parachloromercuribenzoate has been reported in rat, mouse and human brains. Initial studies of this binding site indicate that it is not expressed in the adrenal, liver or kidney of the rat and mouse. To determine if this binding site occurs in other mouse tissues, 8 tissues were assayed for expression of this binding site by radioligand binding assay and compared with the expression of this binding site in the forebrain. Particulate fractions of homogenates of testis, epididymis, seminal vesicles, heart, spleen, pancreas, lung, skeletal muscle, and forebrain …

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, …

Can Daytime Use Of Bed Nets Not Treated With Insecticide Reduce The Risk Of Dengue Hemorrhagic Fever Among Children In Vietnam?, Ataru Tsuzuki, Vu Dinh Thiem, Motoi Suzuki, Hideki Yanai, Toru Matsubayashi, Lay-Myint Yoshida, Le Huu Tho, Truong Tan Minh, Dang Duc Anh, Paul E. Kilgore, Masahiro Takagi, Koya Ariyoshi

Department of Pharmacy Practice

The purpose of this study was to investigate the prevalence of bed net use and elucidate the effect of daytime bed net use on preventing dengue hemorrhagic fever (DHF) among children in Vietnam. We conducted a population-based cross-sectional survey and a matched case–control study in Khanh Hoa Province where not only some pre-schoolchildren but also some school children, who take a nap during lunch break prior to returning to school, used bed nets during the day. Among 36,901 children 2–10 years of age, most used untreated bed nets during the night (98.3%) compared with 8.4% during the day. The results …

Commencement Program 2010, Loma Linda University

Commencement Programs

CONTENTS

1 | Message from the President

3 | 2010 Events of Commencement

4 | The Academic Procession

6 | Significance of Academic Regalia

8 | The Good Samaritan

9 | University History Highlights

11 | Loma Linda University Song - "Healing Love"

12 | The Speakers

22 | The University Honorees

36 | The School Honorees

59 | The Programs

• School of Medicine, 60
• School of Pharmacy, 77
• School of Dentistry, 83
• School of Science and Technology and School of Religion, 99
• School of Nursing, 112
• School of Allied Health Professions - Physical Therapy, 121
• School of Allied Health …

Sizing Up Pharmacotherapy For Obesity., Michael A. Valentino, Andre Terzic, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Obesity has increased over the last 20 years, from a condition affecting only a small portion of populations in developed countries, into a global pandemic. The impact of obesity can be appreciated in the context of the populations at risk, and it is estimated that >1 billion adults worldwide are overweight (BMI >25 kg/m2), 300 million of whom are clinically obese (BMI >30 kg/m2). In the United States, 65% of adults are overweight, and 32.2% of them are obese, a prevalence that has doubled over 20 years. In industrialized countries, obesity rates have tripled, coinciding with adoption of a Western …

Preliminary Biochemical Characterization Of The Novel, Non-At1, Non-At2 Angiotensin Binding Site From The Rat Brain, Vardan T. Karamyan, Jason Arsenault, Emanuel Escher, Robert C. Speth

HPD Articles

A novel binding site for angiotensins II and III was recently discovered in brain membranes in the presence of the sulfhydryl reactive angiotensinase inhibitor parachloromercuribenzoate. This binding site is distinctly different from the other known receptors for angiotensins: AT₁, AT₂, AT₄, and mas oncogene protein (Ang 1-7 receptor). Preliminary biochemical characterization studies have been done on this protein by crosslinking it with (125)I-labeled photoaffinity probes and solubilizing the radiolabeled binding site. Polyacrylamide gel electrophoresis studies and isoelectric focusing indicate that this membrane bound binding site is a protein with a molecular weight of 70-85 kDa and an isoelectric point of …

Minimum Agitation Speed For Solid Suspension And Mixing Time In A Torispherical -Bottomed Pharmaceutical Stirred Tank Under Different Baffling Conditions, Dilanji Bhagya Wijayasekara

Theses

The minimum agitation speed, NS, required to just suspend solid particles dispersed in water was experimentally determined in this work for a glass-lined type of mixing tank provided with a torispherical bottom and agitated with a retreat-blade impeller under different baffling configurations. Ns for the same tank but equipped with a different agitation system, namely an axial impeller, was also experimentally determined for the purpose of comparing of performances of the two systems. The effect of impeller off- bottom clearance and the vessel's liquid level on the minimum agitation speed were also experimentally studied. Njs, was experimentally determined …

Intravenous Ibuprofen: The First Injectable Product For The Treatment Of Pain And Fever, P Brandon Bookstaver, April D. Miller, Celeste N. Rudisill, Leann B. Norris

Faculty Publications

This paper reviews the current data on the use of the first approved intravenous ibuprofen product for the management of post-operative pain and fever in the United States. The management of acute and post-operative pain and fever with nonsteroidal anti-inflammatory agents (NSAIDs) is well documented. A search in Medline and International Pharmaceutical Abstracts of articles until the end of November 2009 and references of all citations were conducted. Available manufacturer data on file were also analyzed for this report. Several randomized controlled studies have demonstrated the opioid-sparing and analgesic effects of 400 and 800 mg doses of intravenous ibuprofen in …