Medicine and Health Sciences Commons^™

Development And Ex Vivo Characterization Of Enteric Coated Chitosan Beads For Crohn’S Disease Management, Craig Mendonca

University Scholar Projects

Drug delivery is the process of transporting a drug to its site of action. It includes controlled delivery, where the drug is released at the tissue in a regulated manner. Additionally, it includes targeted delivery, where the drug is aimed at a specific tissue or region to avoid unwanted side effects (that would occur if the drug were distributed throughout the body). A cellulose acetate phthalate coated chitosan bead was developed as a formulation for controlled and targeted release of dexamethasone to the ilium and colon. This formulation was determined to be effective in delaying dexamethasone release until the formulation …

December 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

September/October/November 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Improving The Palatability Of Colonoscopy Preparations, Phuong Anh Hoang Nguyen, Darnell Leon Cuylear, Heather Elizabeth Canavan

Shared Knowledge Conference

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. The most reliable screening method of CRC is a colonoscopy which requires a 4-Liter polymer with electrolytes preparation. Two in five patients are non-compliant to their colonoscopy schedules, with many patients who abstain reporting refusal due to significant discomfort associated with this preparation. Furthermore, there are distinct gender differences in the tolerance of colonoscopy preparations in male and female populations. We hypothesize the differences in clinic are a result of toxic effects of the drug associated with poor mixing by individual patients. PEG, the drug, …

Azithromycin For Early Pseudomonas Infection In Cystic Fibrosis. The Optimize Randomized Trial., Nicole Mayer-Hamblett, George Retsch-Bogart, Margaret Kloster, Frank Accurso, Margaret Rosenfeld, Gary Albers, Philip Black, Perry Brown, Annemarie Cairns, Stephanie D. Davis, Gavin R. Graff, Gwendolyn S. Kerby, David Orenstein, Rachael Buckingham, Bonnie W. Ramsey, Optimize Study Group

Manuscripts, Articles, Book Chapters and Other Papers

RATIONALE: New isolation of Pseudomonas aeruginosa (Pa) is generally treated with inhaled antipseudomonal antibiotics such as tobramycin inhalation solution (TIS). A therapeutic approach that complements traditional antimicrobial therapy by reducing the risk of pulmonary exacerbation and inflammation may ultimately prolong the time to Pa recurrence.

OBJECTIVES: To test the hypothesis that the addition of azithromycin to TIS in children with cystic fibrosis and early Pa decreases the risk of pulmonary exacerbation and prolongs the time to Pa recurrence.

METHODS: The OPTIMIZE (Optimizing Treatment for Early Pseudomonas aeruginosa Infection in Cystic Fibrosis) trial was a multicenter, double-blind, randomized, placebo-controlled, 18-month trial …

Duet: A Phase 2 Study Evaluating The Efficacy And Safety Of Sparsentan In Patients With Fsgs., Howard Trachtman, Peter Nelson, Sharon Adler, Kirk N. Campbell, Abanti Chaudhuri, Vimal Kumar Derebail, Giovanni Gambaro, Loreto Gesualdo, Debbie S. Gipson, Jonathan Hogan, Kenneth Lieberman, Brad Marder, Kevin Edward Meyers, Esmat Mustafa, Jai Radhakrishnan, Tarak Srivastava, Miganush Stepanians, Vladimír Tesar, Olga Zhdanova, Radko Komers, Duet Study Group

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: We evaluated and compared the effects of sparsentan, a dual endothelin type A (ETA) and angiotensin II type 1 receptor antagonist, with those of the angiotensin II type 1 receptor antagonist irbesartan in patients with primary FSGS.

METHODS: In this phase 2, randomized, double-blind, active-control Efficacy and Safety of Sparsentan (RE-021), a Dual Endothelin Receptor and Angiotensin Receptor Blocker, in Patients with Focal Segmental Glomerulosclerosis (FSGS): A Randomized, Double-blind, Active-Control, Dose-Escalation Study (DUET), patients aged 8-75 years with biopsy-proven FSGS, eGFR>30 ml/min per 1.73 m2, and urinary protein-to-creatinine ratio (UP/C) ≥1.0 g/g received sparsentan (200, 400, or 800 …

Glimepiride Administered In Chow Reversibly Impairs Glucose Tolerance In Mice, Dana M. Niedowicz, Sabire Özcan, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

Sulfonylureas are a class of antidiabetes medications prescribed to millions of individuals worldwide. Rodents have been used extensively to study sulfonylureas in the laboratory. Here, we report the results of studies treating mice with a sulfonylurea (glimepiride) in order to understand how the drug affects glucose homeostasis and tolerance. We tested the effect of glimepiride on fasting blood glucose, glucose tolerance, and insulin secretion, using glimepiride sourced from a local pharmacy. We also examined the effect on glucagon, gluconeogenesis, and insulin sensitivity. Unexpectedly, glimepiride exposure in mice was associated with fasting hyperglycemia, glucose intolerance, and decreased insulin. There was no …

Improving The Management Of Nationwide Drug And Iv Bag Shortages, Stephen Tyzik, Mark Parker, Suneela Nayak, Ruth Hanselman, Amy Sparks

Operational Transformation

IMPROVING THE MANAGEMENT OF NATIONWIDE DRUG AND IV SHORTAGE

In September of 2017, Hurricane Maria struck the island of Puerto Rico where over 50 pharmaceutical factories had previously operated. The impact of this was felt not only in the drastic reduction of products that are produced on the island, but it also exacerbated the supply chain issues for key drugs nationwide.

The pharmacy department and supply chain in an academic tertiary care medical center did not have a consistent and reliable process for communication, planning and real-time updates. This resulted in a tremendous amount of wasted staff time at their …

Oxcarbazepine Overdose In A Polysubstance Related Suicide, Melissa Beals, Robert J. Krumsick, C. Clinton Frazee Iii, Lindsey J. Haldiman, Uttam Garg

Posters

Introduction
Oxcarbazepine is a derivative of carbamazepine that is used primarily in the treatment of epilepsy, and experimentally as a mood-stabilizer in adjunctive therapy for the treatment of bipolar disorder. Oxcarbazepine is converted through oxidation to its pharmacologically active metabolite 10-OH-Carbazepine, which is thought to be responsible for most of the anticonvulsant action of the drug. Adverse effects of oxcarbazepine are generally dose-dependent and may include fatigue, somnolence, dizziness, diplopia, nystagmus, and ataxia. Additive sedative effects have been noted when oxcarbazepine is used in combination with other CNS depressionproducing medications. Furthermore, oxcarbazepine and 10-OH-Carbazepine are powerful CYP2C19 inhibitors, potentially increasing …

Brain Endothelial Erythrophagocytosis And Hemoglobin Transmigration Across Brain Endothelium: Implications For Pathogenesis Of Cerebral Microbleeds, Rudy Chang, Juan Castillo, Alexander C. Zambon, Tatiana B. Krasieva, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Peripheral endothelial cells are capable of erythrophagocytosis, but data on brain endothelial erythrophagocytosis are limited. We studied the relationship between brain endothelial erythrophagocytosis and cerebral microhemorrhage, the pathological substrate of MRI-demonstrable cerebral microbleeds. To demonstrate the erythrophagocytic capability of the brain endothelium, we studied the interactions between brain endothelial cells and red blood cells exposed to oxidative stress in vitro, and developed a new in vitro cerebral microbleeds model to study the subsequent passage of hemoglobin across the brain endothelial monolayer. Using multiple approaches, our results show marked brain endothelial erythrophagocytosis of red blood cells exposed to oxidative stress compared …

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …

Leveraging Pharma To Lower Premiums: Medical Loss Ratio Regulation In The Pharmaceutical Industry, Cami R. Schiel

BYU Law Review

Many recognize escalating drug prices as a significant dilemma related to America’s rising healthcare costs. Yet few can agree on what to do about them. Unaffordable drug prices are a result of many complex forces. One theory to address this problem is to reduce all government intervention and let normal market forces act as they usually do to bring the goods’ prices down to consumer-friendly ranges. However, the prescription drug market is not, and perhaps never can be, a normal market. Reasons for this include (1) a lack of price transparency, (2) information and control asymmetries between patients and physicians, …

Recombinant Human Proteoglycan-4 Reduces Phagocytosis Of Urate Crystals And Downstream Nuclear Factor Kappa B And Inflammasome Activation And Production Of Cytokines And Chemokines In Human And Murine Macrophages, Marwa Qadri, Gregory D. Jay, Ling X. Zhang, Wendy Wong, Anthony M. Reginato, Changqi Sun, Tannin A. Schmidt

Pharmacy Faculty Articles and Research

Microbial biofilms are organized communities of cells that are associated with a wide spectrum of resistant and chronic infections that lead to the treatment failure. Accordingly, there is an urgent demand to create novel effective therapeutic drugs that can inhibit biofilm formation with new mechanisms of action to surmount the current escalating resistance. In this study, in silico hybrid model was utilized to develop three novel short linear peptides (4, 5, and 6) with potential biofilm inhibiting activities (scores > 1.0). The peptides were composed of cationic and hydrophobic residues. They were synthesized using solid-phase strategy. Synthesized peptides were purified and …

August 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Macromolecule Loading On Plga Particles Through Surface Adsorption, Yiwei Wang

Electronic Theses and Dissertations

The advent of biotherapeutics have impacted the ways in which diseases are treated. In many instances development of recombinant proteins and oligonucleotides into therapeutics are slowed by poor stability of the candidate drugs. Progress has been made in using polymeric particles as carriers of macromolecule drugs. Historically the method is to encapsulate biological drugs into spherical polymeric matrices. Owing to its biocompatible and biodegradable nature, poly (d,l-lactic-co-glycolic acid) (PLGA) has been used extensively in formulating biological drugs into nano- and micro-sized particles. The development of PLGA biologic formulations, however, has been hampered by matrix acidification; the hydrolysis of the polymer …

A V-To-F Substitution In Sk2 Channels Causes Ca2+ Hypersensitivity And Improves Locomotion In A C. Elegans Als Model, Young-Woo Nam, Sabia N. Baskoylu, Dimitris Gazgalis, Razan Orfali, Meng Cui, Anne C. Hart, Miao Zhang

Pharmacy Faculty Articles and Research

Small-conductance Ca2+-activated K+ (SK) channels mediate medium afterhyperpolarization in the neurons and play a key role in the regulation of neuronal excitability. SK channels are potential drug targets for ataxia and Amyotrophic Lateral Sclerosis (ALS). SK channels are activated exclusively by the Ca2+-bound calmodulin. Previously, we identified an intrinsically disordered fragment that is essential for the mechanical coupling between Ca2+/calmodulin binding and channel opening. Here, we report that substitution of a valine to phenylalanine (V407F) in the intrinsically disordered fragment caused a ~6 fold increase in the Ca2+ sensitivity of SK2-a channels. This substitution resulted in a novel interaction between …

July 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Design, Synthesis, And Evaluation Of Homochiral Peptides Containing Arginine And Histidine As Molecular Transporters, Naglaa Salem El-Sayed, Taryn Miyake, Amir Nasrolahi Shirazi, Shang Eun Park, Jimmy Clark, Stephani Buchholz, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0–15% cytotoxicity at 5–100 μM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0–12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the …

Efficient Intracellular Delivery Of Cell-Impermeable Cargo Molecules By Peptides Containing Tryptophan And Histidine, Amir Nasrolahi Shirazi, Saghar Mozaffari, Rinzhin Tshering Sherpa, Rakesh Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously evaluated and reported numerous classes of linear and cyclic peptides containing hydrophobic and hydrophilic segments for intracellular delivery of multiple molecular cargos. Herein, a combination of histidine and tryptophan amino acids were designed and evaluated for their efficiency in intracellular delivery of cell-impermeable phosphopeptides and the anti-HIV drug, emtricitabine. Two new decapeptides, with linear and cyclic natures, both containing alternate tryptophan and histidine residues, were synthesized using Fmoc/tBu solid-phase chemistry. The peptides were characterized and purified by using matrix-assisted laser desorption/ionization (MALDI) spectroscopy and high-performance liquid chromatography (HPLC), respectively. These peptides did not show significant toxicity up …

June 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Microgel Core/Shell Architectures As Targeted Agents For Fibrinolysis, Purva Kodlekere, L. Andrew Lyon

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

We demonstrate the utility of microgel core/shell structures conjugated to fibrin-specific peptides as fibrinolytic agents. Poly(N-isopropylmethacrylamide) (pNIPMAm) based microgels conjugated to the peptide GPRPFPAC (GPRP) were observed to bring about fibrin clot erosion, merely through exploitation of the dynamic nature of the clots. These results suggest the potential utility of peptide–microgel hybrids in clot disruption and clotting modulation.

Preparation Of Supramolecular Amphiphilic Cyclodextrin Bilayer Vesicles For Pharmaceutical Applications, Kate E. Frischkorn

Master's Theses

Recent pharmaceutical developments have investigated using supramolecular nanoparticles in order to increase the bioavailability and solubility of drugs delivered in various methods. Modification of the carbohydrate cyclodextrin increases the ability to encapsulate hydrophobic pharmaceutical molecules by forming a carrier with a hydrophobic core and hydrophilic exterior. Guest molecules are commonly added to these inclusion complexes in order to add stability and further increase targeting abilities of the carriers. One such guest molecule is adamantine combined with a poly(ethylene glycol) chain. Vesicles are formed by hydrating a thin film of amphiphilic cyclodextrin and guest molecules in buffer solution that mimics physiological …

Part 1: Synthesis Of 3,7 Dimethyl-7-Methoxyoctane-2-Ol (Osyrol) From Citronellol Utilizing The Wacker Process Part 2: Developing A Methodology For C(Sp3)-H Arylation On The Β Position Of A Carboxylic Acid Using A Removable Directing Group, Stephen Lo

Master's Theses

The synthesis of 3,7-dimethyl-7-methoxyoctane-2-ol (Osyrol), an important sandalwood odorant, from 3,7-dimethylocta-1,6-diene (dihydromyrcene) was recently accomplished by two groups, both utilizing a two-step epoxide formation and ring opening approach. Here, the synthesis of Osyrol from 3,7-Dimethyloct-6-en-1-ol (citronellol) is accomplished in a novel six-step approach. The key steps in this synthesis is the Wacker Oxidation of a terminal double bond followed by sodium borohydride (NaBH₄) reduction. Though most of the steps in this reaction scheme resulted in limited success, the key steps occurred with high yields.

In the second chapter, the effects of 2-aminophenyl-1H-pyrazole (2-APP) as a removable directing group …

May 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy

Dexmedetomidine (Precedex) Induced Fever, Patrick Dealmeida Do, Michael Matrale Do

Rowan-Virtua Research Day

Precedex is an intravenous, α-2 receptor agonist broadly used for analgesia, maintenance of sedation, and alcohol withdrawal treatment in the intensive care unit (ICU).

The most commonly reported adverse effects associated with precedex are hypotension and bradycardia1.

Fever has been reported with a 5-7% incidence rate. Our case shows a very impressive pyrexia in a 49 year old patient most likely associated to Precedex. When compared to the previously three reported cases his fever reached the largest value (T= 107ºF).

As its use becomes more and more common in the ICU, clinicians should be aware of this adverse effect especially …

Total Synthesis Of 6,7-Dimethyl-N-Methyl Aziridinomitosene, Thaaer N. Muhammed

Boise State University Theses and Dissertations

Mitomycin C (MC) is a naturally occurring antitumor agent isolated from a soil bacterium. MC is effective against solid hypoxic tumors that respond poorly to radiotherapy, such as colorectal, gastric, and lung tumors. Also, it has a role in the treatment of bladder, head and neck, and non-small cell lung cancers in combination with other chemotherapeutic.

MC and other members of the mitomycin family of antitumor agents fight cancer by forming DNA interstrand crosslinks (ICLs), which leads to apoptosis. In order to form ICLs, MC requires a reductive activation step that produces reactive oxygen species. This activation step is proposed …

Characterization Of The Hepatotoxicity Of Rifampicin And Isoniazid, Christopher T. Brewer

Theses and Dissertations (ETD)

In a mouse model, rifampicin and isoniazid combination treatment results in cholestatic liver injury that is associated with an increase of protoporphyrin ix (PPIX), the penultimate heme precursor. Excess PPIX is believed to bind to bile acids, precipitate in bile canaliculi, and form bile plugs leading to cholestasis fol owed by liver injury. Both ferrochelatase (FECH/Fech) and aminolevulinic acid synthase 1 (ALAS1/Alas1) are crucial enzymes in regulating heme biosynthesis. Isoniazid has recently been reported to up-regulate Alas1 but down-regulate Fech protein levels in mice; however the mechanism of isoniazid mediated heme synthesis …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

April 2018, Randy Curry, Cindy Brooks

RURAL ROCKS

Rural Rocks, the Rural Health Network newsletter by the SWOSU College of Pharmacy