Medicinal and Pharmaceutical Chemistry Commons^™

Beyond Single Nucleotide Polymorphisms: Cyp3a5∗3 ∗6 ∗7 Composite And Abcb1 Haplotype Associations To Tacrolimus Pharmacokinetics In Black And White Renal Transplant Recipients, Daniel A. Brazeau, Kristopher Attwood, Calvin J. Meaney, Gregory E. Wilding, Joseph D. Consiglio, Shirley S. Chang, Aijaz Gundroo, Rocco C. Venuto, Louise Cooper, Kathleen M. Tornatore

Pharmaceutical Science and Research

Interpatient variability in tacrolimus pharmacokinetics is attributed to metabolism by cytochrome P-450 3A5 (CYP3A5) isoenzymes and membrane transport by P-glycoprotein. Interpatient pharmacokinetic variability has been associated with genotypic variants for both CYP3A5 or ABCB1. Tacrolimus pharmacokinetics was investigated in 65 stable Black and Caucasian post-renal transplant patients by assessing the effects of multiple alleles in both CYP3A5 and ABCB1. A metabolic composite based upon the CYP3A5 polymorphisms: ^∗3(rs776746), ^∗6(10264272), and ^∗7(41303343), each independently responsible for loss of protein expression was used to classify patients as extensive, intermediate and poor metabolizers. In addition, the …

Prospects For Rnai Therapy Of Covid-19, Hasan Uludağ, Kylie Parent, Hamidreza Montazeri Aliabadi, Azita Haddadi

Pharmacy Faculty Articles and Research

COVID-19 caused by the SARS-CoV-2 virus is a fast emerging disease with deadly consequences. The pulmonary system and lungs in particular are most prone to damage caused by the SARS-CoV-2 infection, which leaves a destructive footprint in the lung tissue, making it incapable of conducting its respiratory functions and resulting in severe acute respiratory disease and loss of life. There were no drug treatments or vaccines approved for SARS-CoV-2 at the onset of pandemic, necessitating an urgent need to develop effective therapeutics. To this end, the innate RNA interference (RNAi) mechanism can be employed to develop front line therapies against …

Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

The second messenger molecule 3′5′-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has led to interest in defining how specific PDE isoforms maintain these signaling microdomains. The possible altered expression of PDEs, and thus abnormal …

Oral Anticoagulants For Nonvalvular Atrial Fibrillation In Frail Elderly Patients: Insights From The Aristophanes Study, G. Y. H. Lip, A. V. Keshishian, A. L. Kang, A. D. Dhamane, X. Luo, X. Li, N. Balachander, L. Rosenblatt, J. Mardekian, X. Pan, M. Di Fusco, A. B. Garcia Reeves, Huseyin Yuce, S. Deitelzweig

Publications and Research

Background

Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population.

Objectives

This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin.

Methods

This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013‐30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare …

Synthesizing Modified Polymeric Nanoparticles For Biofilm Inhibition, Antibiotic Encapsulation, And Specific Targeting Against Pseudomonas Aeruginosa, Logan Schnorbus

Theses and Dissertations

Widespread usage of antibiotics is a growing concern due to antibiotic resistance development in bacteria. This is due to common use of antibiotics in agricultural, livestock, and clinical usage. Antibiotic resistance is developing at a rate in which it is outpacing new drugs on the market. New strategies in drug development are necessary to combat the increasing resistance. We designed several motifs of sugar-modified nanoparticles to inhibit the biofilm formation of Pseudomonas aeruginosa.

P. aeruginosa is an opportunistic pathogenic bacterium that is responsible for common life-threatening infection in hospitals. This gram-negative opportunistic pathogenic bacterium infects hosts with compromised immune systems …

An In Silico Study Of Small Molecule Anti-Cancer Agents Targeting Dna G-Quadruplexes, Holli-Joi Sullivan

Theses and Dissertations

Free ligand binding molecular dynamic simulations are a powerful tool used to probe the ligand binding process, mechanism and pathway and the insight gained can help expedite the early stages of drug discovery. Using these methods, we model the binding of two small molecule anti-cancer agents BRACO19 and CX-5461 to a variety of DNA G-quadruplexes (G4s) and a DNA Duplex. The first study focuses on the binding of BRACO19 to three different topological folds (parallel, anti-parallel and hybrid) of the human telomeric G4s. Our detailed analysis identified the most stable binding modes were end stacking and groove binding for the …

Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli

Pharmacy Faculty Articles and Research

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Nih Funding For Research Underlying New Cancer Therapies, Ekaterina Galkina Cleary, Fred D. Ledley

Natural & Applied Sciences Faculty Publications

Contemporary discovery and development of cancer drugs are based on the model that investments in basic biomedical science will provide insights that can be translated into new cures. In the USA, basic research is primarily funded by the National Institutes of Health (NIH),1 which allocates half of its research budget to basic science,2 with smaller amounts contributed by philanthropy, academics, or industry.1 Basic science is formally defined as the “systematic study directed toward fuller knowledge or understanding of the fundamental aspects of phenomena and observable facts without specific application towards processes or products in mind”.3 However, science is often useinspired,4 …

Recombinant Human Proteoglycan-4 Mediates Interleukin-6 Response In Both Human And Mouse Endothelial Cells Induced Into A Sepsis Phenotype, Holly A. Richendrfer, Mitchell M. Levy, Khaled A. Elsaid, Tannin A. Schmidt, Ling Zhang, Ralph Cabezas, Gregory D. Jay

Pharmacy Faculty Articles and Research

Objectives:

Sepsis is a leading cause of death in the United States. Putative targets to prevent systemic inflammatory response syndrome include antagonism of toll-like receptors 2 and 4 and CD44 receptors in vascular endothelial cells. Proteoglycan-4 is a mucinous glycoprotein that interacts with CD44 and toll-like receptor 4 resulting in a blockade of the NOD-like receptor pyrin domain-containing-3 pathway. We hypothesized that endothelial cells induced into a sepsis phenotype would have less interleukin-6 expression after recombinant human proteoglycan 4 treatment in vitro.

Design:

Enzyme-linked immunosorbent assay and reverse transcriptase-quantitative polymerase chain reaction to measure interleukin-6 protein and gene expression.

Setting: …

Comparative Antiviral Activity Of Remdesivir And Anti-Hiv Nucleoside Analogs Against Human Coronavirus 229e (Hcov-229e), Keykavous Parang, Naglaa Salem El-Sayed, Assad J. Kazeminy, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Remdesivir is a nucleotide prodrug that is currently undergoing extensive clinical trials for the treatment of COVID-19. The prodrug is metabolized to its active triphosphate form and interferes with the action of RNA-dependent RNA polymerase of SARS-COV-2. Herein, we report the antiviral activity of remdesivir against human coronavirus 229E (HCoV-229E) compared to known anti-HIV agents. These agents included tenofovir (TFV), 4′-ethynyl-2-fluoro-2′-deoxyadenosine (EFdA), alovudine (FLT), lamivudine (3TC), and emtricitabine (FTC), known as nucleoside reverse-transcriptase inhibitors (NRTIs), and a number of 5′-O-fatty acylated anti-HIV nucleoside conjugates. The anti-HIV nucleosides interfere with HIV RNA-dependent DNA polymerase and/or act as chain terminators. …

Proteoglycan-4 Regulates Fibroblast To Myofibroblast Transition And Expression Of Fibrotic Genes In The Synovium, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Holly Richendrfer, Tannin A. Schmidt, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Synovial tissue fibrosis is common in advanced OA with features including the presence of stress fiber-positive myofibroblasts and deposition of cross-linked collagen type-I. Proteoglycan-4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and is a major component of synovial fluid. PRG4 is a ligand of the CD44 receptor. Our objective was to examine the role of PRG4-CD44 interaction in regulating synovial tissue fibrosis in vitro and in vivo.

Methods: OA synoviocytes were treated with TGF-β ± PRG4 for 24h and α-SMA content was determined using immunofluorescence. Rhodamine-labeled rhPRG4 was incubated with OA synoviocytes ± anti-CD44 or …

Ocular, Neural, And Cellular Biodistribution Of Multifunctional Antioxidants, Damian Daszynski

Theses & Dissertations

Aging is a complex biological process which stems from a growing imbalance between the regenerative capacity of an organism and endogenous as well as exogenous damaging factors. This imbalance leads to the slow deterioration of individual cells, organs, and eventually the entire organism. The free radical theory of aging combines the evolutionary and mechanistic aspects of aging, postulating that the innate process is caused by deleterious, irreversible, and inevitable changes in biological systems caused by oxidative damage that accumulates over the lifespan. Evidence of this phenomenon is supported by the pathogenesis of age-related diseases, such as age-related macular degeneration and …

Synthesis Of Fluorinated Pyrazoles Via Intra- And Intermolecular Cyclization Reactions, Matthew Saucier

Honors Theses

Pyrazole-based pharmaceuticals treat a wide array of diseases and conditions including obesity, diabetes, cancer, microbial and viral infections, pain and inflammation, and many neurological disorders. Syntheses for this biologically significant substrate have been well developed, but current methods to afford fluorinated pyrazoles are limited by variability and selectivity. By 2013, over 25% of all drugs available on the market contained the element fluorine due to its unique characteristics leading to improved target protein binding, bioavailability, and metabolic stability. In order to harness these pharmaceutical benefits of fluorine and overcome its difficulty in handling and stability, we set out to develop …

Synthesis Of Aromatic Fluorinated Ketones For Evaluation At The Gaba Receptor, Madeline Griffin

Honors Theses

GABA is a neurotransmitter that inhibits the excitation of neurons. Targeting this specific receptor has the potential to inhibit the central nervous system and possibly treat addiction, anxiety, or mood disorders. Previous research has shown that fluorinated ketones can have valuable applications in the medicinal chemistry of addiction. Some fluorinated ketones have shown activity at the GABA receptor. The main goal of this project was to synthesize aromatic fluorinated ketones for biological evaluation at the GABA_B receptor. Another goal was to compare both the monofluorinated and difluorinated analogues synthesized in order to quantify differences in activity from fluorination state. …

Studies Of Salvinorin-Based Antagonists To Elucidate Pertinent Interactions For Kappa Opioid Receptor Antagonism, Madeline Keane

Honors Theses

Opioid abuse, leading to addiction and related deaths, has created a chronic epidemic in the United States for the past 30 years. This crisis has sprung from reliance on the prescription of opioid analgesics as the primary method for the management of pain in the 1990s. At that time, these drugs, specifically Purdue Pharma’s OxyContin, were marketed as non-addictive. Due to this systemic minimization of the addictive properties of opioid analgesics, as prescription rates increased, opioid-related mortality rates climbed. This epidemic continues to be pervasive, as opioid-related overdose resulted in 47,600 deaths in 2017. In addition to the opioid epidemic, …

In-Vitro Assessment Of Cb1/Cb2 Receptor Binding And Function, Joey M. Davis

Honors Theses

Cannabinoid receptors CB1 and CB2 are G protein-coupled receptors that have a variety of physiological effects on the human body. Many natural product agonists and antagonists are presumed to interact with the cannabinoid receptors and are therefore heavily studied in drug discovery. Assays are used to study the binding of compounds to these receptors. However, a limited number of these assays are efficient in determining the functional activity of ligands associated with CB1 and CB2. Of those, many use radioactivity which is both expensive and potentially dangerous to the researcher. In this study, we first validated the assays already found …

Delivery For Hydrophobic Drugs For Treating Pancreatic Cancer, Saud Almawash

Theses & Dissertations

Purpose The aim of this study was to determine whether coadministration of hedgehog (Hh) pathway inhibitor cyclopamine (CYP) and microtubule stabilizer docetaxel (DTX) as polymer-drug conjugates, methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylenecarbonategraft- dodecanol-graft-cyclopamine) (P-CYP) and methoxy poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-docetaxel) (P-DTX) could synergistically inhibit orthotopic pancreatic tumor growth in NSG mice.

Methods P-DTX and P-CYP were synthesized from mPEGb- PCC through carbodiimide coupling reaction and characterized by 1H–NMR. The micelles were prepared by film hydration and particle size was measured by dynamic light scattering (DLS). Cytotoxicity, apoptosis and cell cycle analysis of P-DTX and P-CYP were evaluated in MIA PaCa-2 cells. In vivo efficacy …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

Phenylpyrazalopyrimidines As Tyrosine Kinase Inhibitors: Synthesis, Antiproliferative Activity, And Molecular Simulations, Bhupender S. Chhikara, Sajda Ashraf, Saghar Mozaffari, Nicole St. Jeans, Dindyal Mandal, Rakesh Kumar Tiwari, Zaheer Ul-Haq, Keykavous Parang

Pharmacy Faculty Articles and Research

N1-(α,β-Alkene)-substituted phenylpyrazolopyrimidine derivatives with acetyl and functionalized phenyl groups at α- and β-positions, respectively, were synthesized by the reaction of 3-phenylpyrazolopyrimidine (PhPP) with bromoacetone, followed by a chalcone reaction with differently substituted aromatic aldehydes. The Src kinase enzyme assay revealed modest inhibitory activity (half maximal inhibitory concentration, IC₅₀ = 21.7–192.1 µM) by a number of PhPP derivatives. Antiproliferative activity of the compounds was evaluated on human leukemia (CCRF-CEM), human ovarian adenocarcinoma (SK-OV-3), breast carcinoma (MDA-MB-231), and colon adenocarcinoma (HT-29) cells in vitro. 4-Chlorophenyl carbo-enyl substituted 3-phenylpyrazolopyrimidine (10) inhibited the cell proliferation of HT-29 and SK-OV-3 by 90% …

Imatinib-Induced Interstitial Pneumonitis – A Literature Review And Case Report, Olga Hilda Orasan, Andreea Maria Stefan, Iulia Minciuna, Adela Sitar-Taut, George Ciulei, Simina Tarmure, Ioana Para, Flaviu Muresan, Ovidiu Fabian, Sorina Cezara Coste, Vasile Negrean, Angela Cozma, Laura Urian

Journal of Mind and Medical Sciences

Imatinib is generally well tolerated, with mild common side effects such as nausea and vomiting, diarrhea, muscle cramps, fatigue, skin rash and edema; however, pulmonary complications are uncommon. A 73-year-old woman undergoing one month treatment with Imatinib for chronic myeloid neoplasm associated with eosinophilia was admitted for sudden alteration of her performance status, dyspnea at rest and productive cough. On clinical examination, the patient was hypoxic (oxygen saturation on room air was 87%), and auscultation of her lungs revealed diffuse bilateral fine crackles. Computed tomography showed bilateral pulmonary interstitial syndrome. Imatinib was discontinued and the patient received systemic corticosteroid therapy …

Coronavirus Disease 2019 (Covid-19), Matthew Dunbar

Pharmacy Student Scholarship

No abstract provided.

Cd44 Receptor Mediates Urate Crystal Phagocytosis By Macrophages And Regulates Inflammation In A Murine Peritoneal Model Of Acute Gout, Emira Bousoik, Marwa Qadri, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Gout is a chronic arthritis caused by the deposition of poorly soluble monosodium urate monohydrate (MSU) crystals in peripheral joints. Resident macrophages initiate inflammation in response to MSU mediated by NF-κB nuclear translocation and NLRP3 inflammasome activation. We investigated the role of CD44, a transmembrane receptor, in mediating MSU phagocytosis by macrophages. We used an antibody that sheds the extracellular domain (ECD) of CD44 to study the role of the receptor and its associated protein phosphatase 2A (PP2A) in macrophage activation. We also studied the significance of CD44 in mediating MSU inflammation in-vivo. Cd44^−/− BMDMs showed reduced MSU …

Diabetes Debunked: What You Need To Know, Maggie Hutson

Honors Program: Senior Projects (Public)

The goal of this Honors creative project is to encourage health literacy in populations who are curious about Type 2 Diabetes or have Type 2 Diabetes. From personal experience, I have seen noncompliance in diabetics and wondered why since it is a serious, progressive disease. After researching, I found that some diabetics do not understand the scope of their disease, especially since many of the dangerous complications that arise from Type 2 Diabetes do not present until later in the disease when it is too late. For my senior project, I decided to write an educational paper as a supplement …

Functional Blockade Of E-Selectin In Tumor-Associated Vessels Enhances Anti-Tumor Effect Of Doxorubicin In Breast Cancer, Yoshihiro Morita, Macall Leslie, Hiroyasu Kameyama, Ganesh L R Lokesh, Norihisa Ichimura, Rachel Davis, Natalie Hills, Nafis Hasan, Roy Zhang, Yuji Kondo, David G Gorenstein, David E Volk, Inna Chervoneva, Hallgeir Rui, Takemi Tanaka

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Chemotherapy is a mainstay of treatment for solid tumors. However, little is known about how therapy-induced immune cell infiltration may affect therapy response. We found substantial CD45+ immune cell density adjacent to E-selectin expressing inflamed vessels in doxorubicin (DOX)-treated residual human breast tumors. While CD45 level was significantly elevated in DOX-treated wildtype mice, it remained unchanged in DOX-treated tumors from E-selectin null mice. Similarly, intravenous administration of anti-E-selectin aptamer (ESTA) resulted in a significant reduction in CD45+ immune cell density in DOX-treated residual tumors, which coincided with a delay in tumor growth and lung metastasis in MMTV-pyMT mice. Additionally, both …

Pcsk9 Inhibitors In Secondary Prevention – An Opportunity For Personalized Therapy, Chase Board, Michael S. Kelly, Michael D. Shapiro, Dave L. Dixon

Pharmacy Faculty Articles and Research

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is the primary cause of ASCVD and reducing LDL-C levels with statin therapy significantly reduces ASCVD risk; however, significant residual risk remains. Two monoclonal antibodies (mAbs), alirocumab and evolocumab, that target proprotein convertase subtilisin/kexin-type 9 (PCSK9), reduce LDL-C levels by up to 60% when used in combination with statins and significantly reduce the risk of recurrent ASCVD events in both stable secondary prevention and acute coronary syndrome populations. Pre-specified analyses of recent randomized controlled trials have shed light on how best to prioritize these therapies …

Genomic Context And Tp53 Allele Frequency Define Clinical Outcomes In Tp53-Mutated Myelodysplastic Syndromes, Guillermo Montalban-Bravo, Rashmi Kanagal-Shamanna, Christopher B. Benton, Caleb A. Class, Kelly S. Chien, Koji Sasaki ,, Kiran Naqvi, Yesid Alvarado, Tapan M. Kadia, Farhad Ravandi, Naval Daver, Koichi Takahashi, Elias Jabbour, Gautham Borthakur, Naveen Pemmaraju, Marina Konopleva, Kelly A. Soltysiak, Sherry R. Pierce, Carlos E. Bueso-Ramos, Keyur P. Patel, Hagop Kantarjian, Guillermo Garcia-Manero

Scholarship and Professional Work – COPHS

TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate …

Antiproliferative And Apoptotic Effects Of Proteins From Black Seeds (Nigella Sativa) On Human Breast Mcf-7 Cancer Cell Line, Yamna Khursid, Basir Syed, Shabana U. Simjee, Obaid Beg, Aftab Ahmed

Pharmacy Faculty Articles and Research

Background

Nigella sativa (NS), a member of family Ranunculaceae is commonly known as black seed or kalonji. It has been well studied for its therapeutic role in various diseases, particularly cancer. Literature is full of bioactive compounds from NS seed. However, fewer studies have been reported on the pharmacological activity of proteins. The current study was designed to evaluate the anticancer property of NS seed proteins on the MCF-7 cell line.

Methods

NS seed extract was prepared in phosphate-buffered saline (PBS), and proteins were precipitated using 80% ammonium sulfate. The crude seed proteins were partially purified using gel filtration …

Measuring The Effects Of Lobinaline-N-Bioxide (419) On Alcohol Consumption, Nicotine Locomotor Sensitization, And Conditioned Place Preference In Mice And Rats, Cocanut M. Suhail

Theses and Dissertations--Medical Sciences

Objective: Novel drug 419 was examined to see the effect it has in vivo mice and rats on alcohol consumption, nicotine locomotor sensitization, and conditioned place preference (CPP) models regarding behavioral tests on dopamine transporter activity.

Methods: Mice and rats were used to see how they react to the drug 419 and control vehicle, in each of the models. The animals were assessed to pre- and post- drug administration of novel drug 419. We examined each model to see the association between how drug 419 will help with treating drug abuse.

Results: We found that in alcohol consumption model the …

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …