Other Pharmacy and Pharmaceutical Sciences Commons^™

The Influence Of Age, Gender, And Thiol Repletion In An In Vivo Model Of Lewy Body Disorders, Daniel Mason

Electronic Theses and Dissertations

Lewy body disorders are a family of neurological brain disorders associated with olfactory, motor, and cognitive deficits and are collectively defined as α-synucleinopathies, as they are characterized by hallmark “Lewy bodies” composed of aggregated, fibrillar α-synuclein. It is not certain but often posited that fibrillar α-synuclein seeds the progressive, self-propagating spread of Lewy pathology through neuroanatomical circuitry. Furthermore, the site of disease induction is still debated. In Aim I, we developed a novel protocol for generating reproducible and robust α-synucleinopathy in the limbic temporal lobe following infusions of preformed α-synuclein iv fibrils into the mouse olfactory bulb, which is frequently …

Efficacy And Renal Outcomes Of Sglt2 Inhibitors In Patients With Type 2 Diabetes And Chronic Kidney Disease, Michael S. Kelly, Jelena Lewis, Ashley M. Huntsberry, Lauren Dea, Ivan Portillo

Pharmacy Faculty Articles and Research

Objective: To review glucose-lowering efficacy and changes in renal function associated with sodium-glucose co-transporter 2 (SGLT2) inhibitors among patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM).

Data sources: A literature search of MEDLINE and Cochrane databases was performed from 2000 to August 2018 using search terms: SGLT2 inhibitors, sodium glucose co-transporter 2, canagliflozin, empagliflozin, dapagliflozin, ertugliflozin, and chronic kidney disease. References of identified articles were also reviewed.

Study selection and data extraction: English-language studies investigating glucose-lowering endpoints and/or changes in renal function with one of four U.S. approved SGLT2 inhibitors were included. A …

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial …

Non-Genomic Effects Of Glucocorticoids: An Updated View, Reynod A. Panettieri, Dedmer Schaafsma, Yassine Amrani, Cynthia Koziol-White, Rennolds S. Ostrom, Omar Tliba

Pharmacy Faculty Articles and Research

Glucocorticoid (GC) anti-inflammatory effects generally require a prolonged onset of action and involve genomic processes. Because of the rapidity of some of the GC effects, however, the concept that non-genomic actions may contribute to GC mechanisms of action has arisen. While the mechanisms have not been completely elucidated, the non-genomic effects may play a role in the management of inflammatory diseases. For instance, we recently reported that GCs ‘rapidly’ enhanced the effects of bronchodilators, agents used in the treatment of allergic asthma. In this review article, we discuss (i) the non-genomic effects of GCs on pathways relevant to the pathogenesis …

The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh

Purdue Journal of Service-Learning and International Engagement

Christian Egly is a fourth-year (P4) pharmacy student in the Purdue University College of Pharmacy. During his years at Purdue, he worked in labs performing bench research in clinical pharmacology and biochemistry. He plans to work in the pharmaceutical industry after graduation. During his fourth year, he completed rotations in business development at Kashiv Pharma, LLC, and was hired there for an internship in 2017. In the article, Christian describes his personal experiences at Kashiv Pharma, LLC, and how industry can positively affect patient communities.

Peer Health Educators On Campus: Teaching Safe Medication Practices, Baylee Q. Bryan, Olga O. Vlashyn, Stephanie A. Deremiah, Murphy K. O'Toole, Katherine M. Joseph, Jane E. Krause

Purdue Journal of Service-Learning and International Engagement

Baylee Q. Bryan, Olga O. Vlashyn, Stephanie A. Deremiah, and Murphy K. O’Toole are advanced professional students in the Doctor of Pharmacy program at Purdue University, graduating in May 2019. Katherine M. Joseph is a senior in the School of Nursing, graduating in December 2018. Jane E. Krause (Clinical Associate Professor of Pharmacy Practice, Purdue College of Pharmacy) served as a faculty mentor for this project. In this article, the authors describe their service-learning project intended to increase awareness on campus regarding prescription drug abuse and misuse.

Leveraging Technology: Enhancing Study Time Through Competition, Ming Yang, Lindsey Eble, Patricia Darbishire

Purdue Journal of Service-Learning and International Engagement

Ming (Max) Yang and Lindsey Eble are students in their final year of the Doctor of Pharmacy program in the Purdue University College of Pharmacy. Max is originally from Chesterfield, Missouri, and Lindsey is from Newburgh, Indiana. After graduation in May 2018, Max will complete residency training at Aurora St. Luke’s Medical Center in Milwaukee, Wisconsin. Lindsey will complete residency training at Barnes-Jewish Hospital in St. Louis, Missouri. Both plan to work in a hospital or clinic setting providing patient care within an interdisciplinary healthcare team. They both worked under the guidance of Dr. Patricia Darbishire to develop a website …

Kinetics Of Dextromethorphan-O-Demethylase Activity And Distribution Of Cyp2d In Four Commonly-Used Subcellular Fractions Of Rat Brain, Barent N. Dubois, Farideh Amirrad, Reza Mehvar

Pharmacy Faculty Articles and Research

The purpose of this study was to compare the enzymatic kinetics and distribution of cytochrome P450 2D (CYP2D) among different rat brain subcellular fractions.

Rat brains were used to prepare total membrane, crude mitochondrial, purified mitochondrial, and microsomal fractions, in addition to total homogenate. Michaelis–Menten kinetics of the brain CYP2D activity was estimated based on the conversion of dextromethorphan (DXM) to dextrorphan using UPLC-MS/MS. Protein levels of CYP2D and subcellular markers were determined by Western blot.

Microsomal CYP2D exhibited high affinity and low capacity, compared with the mitochondrial CYP2D that had a much lower (∼50-fold) affinity but a higher (∼six-fold) …

Diffusion Through The Ex Vivo Vitreal Body – Bovine, Porcine, And Ovine Models Are Poor Surrogates For The Human Vitreous, Sara Shafaie, Victoria Hutter, Marc B. Brown, Michael T. Cook, David Y.S. Chau

Pharmacology and Animal Models in Research Collection

The human vitreous humour is a complex gel structure whose composition and physical properties can vary considerably from person to person and also change with age. To date, the viscoelastic properties of the human vitreous gel has not been thoroughly investigated and despite many years of intensive research, an ideal vitreous substitute remains a challenge. Understanding the physical structure and properties of the vitreous is of fundamental and therapeutic interest, providing a clear insight into diffusion and transport of administered ophthalmic drug molecules into the vitreous. A number of mammalian surrogates, mainly bovine, porcine and ovine vitreous humours have been …

Synthesis And Antiproliferative Activities Of Doxorubicin Thiol Conjugates And Doxorubicin-Ss-Cyclic Peptide, Shaban Darwish, Neda Sadeghiani, Shirley Fong, Saghar Mozaffari, Parinaz Hamidi, Thimanthi Withana, Sun Yang, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Myocardial toxicity and drug resistance caused by drug efflux are major limitations of doxorubicin (Dox)-based chemotherapy. Dox structure modification could be used to develop conjugates with an improved biological profile, such as antiproliferative activity and higher cellular retention. Thus, Dox thiol conjugates, Dox thiol (Dox-SH), thiol-reactive Dox-SS-pyridine (SS = disulfide), and a Dox-SS-cell-penetrating cyclic peptide, Dox-SS-[C(WR)4K], were synthesized. Dox was reacted with Traut's reagent to generate Dox-SH. The thiol group was activated by the reaction with dithiodipyridine to afford the corresponding Dox-SS-Pyridine (Dox-SS-Pyr). A cyclic cell-penetrating peptide containing a cysteine residue [C(WR)4K] was prepared using Fmoc solid-phase strategy. Dox-SS-Py was …

Design, Synthesis, And Evaluation Of Amphiphilic Cyclic And Linear Peptides Composed Of Hydrophobic And Positively-Charged Amino Acids As Antibacterial Agents, Neda Riahifard, Saghar Mozaffari, Taibah Aldakhil, Francisco Nunez, Qamar Alshammari, Saud Alshammari, Jason Yamaki, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Antimicrobial peptides (AMPs) contain amphipathic structures and are derived from natural resources. AMPs have been found to be effective in treating the infections caused by antibiotic-resistant bacteria (ARB), and thus, are potential lead compounds against ARB. AMPs’ physicochemical properties, such as cationic nature, amphiphilicity, and their size, will provide the opportunity to interact with membrane bilayers leading to damage and death of microorganisms. Herein, AMP analogs of [R₄W₄] were designed and synthesized by changing the hydrophobicity and cationic nature of the lead compound with other amino acids to provide insights into a structure-activity relationship against selected …

Modulation Of Hypoxia-Induced Chemoresistance To Polymeric Micellar Cisplatin: The Effect Of Ligand Modification Of Micellar Carrier Versus Inhibition Of The Mediators Of Drug Resistance, Hoda Soleymani Abyaneh, Amir Hassan Soleimani, Mohammad Reza Vakili, Rania Soudy, Kamaljit Kaur, Francesco Cuda, Ali Tavassoli, Afsaneh Lavasanifar

Pharmacy Faculty Articles and Research

Hypoxia can induce chemoresistance, which is a significant clinical obstacle in cancer therapy. Here, we assessed development of hypoxia-induced chemoresistance (HICR) against free versus polymeric cisplatin micelles in a triple negative breast cancer cell line, MDA-MB-231. We then explored two strategies for the modulation of HICR against cisplatin micelles: a) the development of actively targeted micelles; and b) combination therapy with modulators of HICR in MDA-MB-231 cells. Actively targeted cisplatin micelles were prepared through surface modification of acetal-poly(ethylene oxide)-poly(-carboxyl-"-caprolactone) (acetal-PEO-PCCL) micelles with epidermal growth factor receptor (EGFR)-targeting peptide, GE11 (YHWYGYTPQNVI). Our results showed that hypoxia induced resistance against free and …

Use Of Virtual Games For Interactive Learning In A Pharmacy Curriculum, Jerika Lam, Mary Gutierrez, Jeff A. Goad, Larisa Odessky, Jason Bock

Pharmacy Faculty Articles and Research

Background and purpose: To evaluate student pharmacists’ attitudes and satisfaction toward playing educational virtual games in the classroom.

Educational activity and setting: The study setting was playing virtual games in the classroom setting. First year student pharmacists participated in two Mimycx quests in the Healthcare Communication and the Psychiatry/Neurology courses. Students were randomly assigned into teams and worked together to complete the assigned quest games. Completion of the pre- and post-quest questionnaires via Qualtrics was voluntary.

Findings: A total of 79 student pharmacists played the Mimycx quests. Only 66 students completed both pre- and post-quest questionnaires. Students …

In Vitro And Ex-Vivo Evaluation Of Topical Formulations Designed To Minimize Transdermal Absorption Of Vitamin K1, Ramina Nabiee, Barent Dubois, Laura Green, Ajay Sharma, Siu Fun Wong, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using …

Hptlc Assay Of Nicotine And Cotinine In Biological Samples, Ana Maria Vlasceanu, Daniela Luiza Baconi, Anne Marie Ciobanu, Vlad D. Constantin, Liana Ples, Cristian Balalau, Miriana Stan

Journal of Mind and Medical Sciences

This study presents the development of a simple high-performance thin layer chromatography (HPTLC) method for the determination of nicotine and its metabolite cotinine in human plasma and urine.

The following mobile phases: methanol: ammonia (100:1.5, v:v), chloroform: acetone: ammonia (48.75: 48.75: 2.5, v:v:v), methanol: chloroform: ammonia (48.75: 48.75: 0.5, v:v:v) and glass plates precoated with silicagel 60 F254 (20x20) as a stationary phase were used. Densitometric scanning was performed at 263 nm. Two different extraction procedures have been applied: liquid-liquid extraction using dichloromethane at alkaline pH and solid-phase extraction using C18 cartridges.

Preliminary tests in order to establish the system …

New Oral Anticoagulants And Their Reversal Agents, Crista L. Laslo, Anca Pantea Stoian, Bogdan Socea, Dan N. Paduraru, Oana Bodean, Laura I. Socea, Tiberiu P. Neagu, Ana Maria Alexandra Stanescu, Dragos Marcu, Camelia C. Diaconu

Journal of Mind and Medical Sciences

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients' quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile …

Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen

Pharmacy Faculty Articles and Research

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the …

Integration Of A Pharmacist In A Pediatric Medical Home For Children With Medical Complexity, Alannah K. Yoder, Richard K. Ogden Jr., Ingrid A. Larson, Emily J. Goodwin

Pharmacy Posters

Background/Objectives

Children with medical complexity require unique care, specialized attention, and a dedicated team to meet the needs of the patient & caregivers. Drug-therapy related problems in complex, chronic conditions influence financial, institutional, and patient outcomes. The addition of a pharmacist allows for collaboration and delivery of comprehensive medication management in order to provide value-added medication services to optimize complex therapeutic regimens and patient outcomes through evidence-based practice, medication adherence, medication use coordination, and medication safety processes.

Description

Our program provides a pediatric medical home for hundreds of children with medical complexity. Families are cared for by a comprehensive …

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 …