Medicine and Health Sciences Commons^™

Clostridium Difficile Infection Risk With Important Antibiotic Classes: An Analysis Of The Fda Adverse Event Reporting System, Chengwen Teng Pharm.D., Ph.D., Kelly R. Reveles, Obiageri O. Obodozie-Ofoegbu, Christopher R. Frei

Faculty Publications

Introduction: Antibiotic use is an important risk factor for Clostridium difficile infection (CDI). Prior meta-analyses have identified antibiotics and antibiotic classes that pose the greatest risk for CDI; however, CDI epidemiology is constantly changing and contemporary analyses are needed.

Objectives: The objective of this study was to evaluate the association between CDI and important antibiotic classes in recent years using the FDA Adverse Event Report System (FAERS).

Methods: FAERS reports from January 1, 2015 to December 31, 2017 were analyzed. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CDI cases. We computed the Reporting Odds Ratios (RORs) …

Development Of Approaches Of Tumor Trapping Enhanced Bb2r-Targeted Radiopharmaceuticals For Prostate Cancer, Wenting Zhang

Theses & Dissertations

The Gastrin-Releasing Peptide Receptor (BB2r) has been intensively investigated as a cancer target over the years. Numerous diagnostic and therapeutic BB2r-targeted agents have been developed for various solid tumors, including prostate cancers, due to the high expression level of BB2r on neoplastic relative to normal tissues. The development of those targeted agents have mainly utilized the modified c-terminal of bombesin(BBN), a peptide that has nanomolar binding affinity to human BB2r. However, a major issue that hinders the clinical translational potential of low-molecular weight, receptor-targted agents, is their short residence time at tumor tissues due to the intrinsically high diffusion and …

Synthesis And Characterization Of A Long-Acting Emtricitabine Prodrug Nanoformulation, Ibrahim M. Ibrahim

Theses & Dissertations

The introduction of highly active antiretroviral therapy led to a paradigm shift in the management of HIV/AIDS changing a disease considered “a death sentence” to “a manageable chronic disease”. Nevertheless, challenges exist for successful treatment of HIV, including patient adherence to the complex daily regimens and the inability of current formulations to target viral sanctuaries. Introduction of nanoformulated antiretroviral therapy (ART) is a promising alternative to tackle these challenges. Our laboratory has been focusing on developing long-acting (LA) nanoformulated antiretrovirals and has succeeded in developing LA integrase inhibitors. However, challenges for this approach extend to a range of short-acting hydrophilic …

Development Of Macromolecular Prodrug Conjugates For The Treatment Of Inflammatory Diseases, Gang Zhao

Theses & Dissertations

Inflammation is the complex biological response to the stimuli triggered by various factors like pathogens, damaged cells, or irritants. Constant uncontrolled acute inflammation may become chronic conditions, leading to significant tissue damage, contributing to a series of chronic inflammatory diseases. Our lab has been working on the different types of inflammatory diseases and has developed multiple macromolecular prodrug conjugates for the better therapeutic efficacy and reduced toxicity. The general approach we have taken is to incorporate small molecules containing monomers into water-soluble and biocompatible polymers, such as N-(2-Hydroxypropyl) methacrylamide (HPMA) copolymers. The superior and the sustained efficacy of those macromolecular …

Human Immunodeficiency Virus Theranostics, Christopher J. Woldstad

Theses & Dissertations

RATIONALE: Long-acting slow effective release antiretroviral therapy (LASER ART) was developed to improve patient regimen adherence, prevent new infections, and facilitate drug delivery to human immunodeficiency virus cell and tissue reservoirs. However, maintenance of sustained plasma drug levels, for weeks or months, after a single high-level dosing, could improve regimen adherence but, at the same time, affect systemic toxicities. Of these, the most troubling are those that affect the central nervous system (CNS) In an effort to facilitate LASER ART development, “multimodal imaging theranostic nanoprobes” were created. These allow combined bioimaging, drug pharmacokinetics and tissue biodistribution tests in animal …

Ethnic And Demographic Differences In Colectomy Rates And Timing For Ulcerative Colitis: 2007-2014, Daniel Bodek, Alana Persaud, Brian Blair, Ahlawat Sushil

Rowan-Virtua Research Day

Ulcerative Colitis (UC) is a chronic inflammatory disease of the bowel, with one third of patients requiring a colectomy for fulminant disease and tissue dysplasia. In 2007, infliximab was approved for induction and maintenance of remission in UC, with some evidence to suggest a potential reduction in colectomies. The aim of this study is to examine relative colectomy rates for UC among different ethnicities from 2007 to 2014 in order to evaluate for development of new trends or disparities.

Discrepancies in colectomy rates and timing are seen in our models which mirror closely findings in a prior study from 1999-2003 …

Integration Of Native American Medicinal Plants Into The Heber W. Youngken Jr. Garden, Emily Lyn Murray

Senior Honors Projects

Healthcare among Native American tribes was focused on all aspects of a patient’s life, such as physical, spiritual, and environmental elements. Healthy outcomes were obtained by maintaining a balance among all of these components. This “bio-psycho-socio-spiritual” approach to healthcare was thought to not only play a role in the health of a certain individual, but the health of the tribe as a whole. An illness was not only precipitated by a physical source, but by an imbalance of these components. Medicinal plants served as an integral role in direct physical healing, as well as an important element for the execution …

A New Prenylated Isoflavonoid From Limonium Leptophyllum, Asset Dizamatova, Kamila Zhumanova, Galiya E. Zhusupova, Aizhan I. Zhussupova, Radhakrishnan Srivedavyasasri, Mohamed A. Ibrahim, Samir A. Ross

Faculty and Student Publications

© 2019, Mary Ann Liebert, Inc., publishers 2019. Purpose: Cannabidiol (CBD), active component of plant Cannabis sativa, has anti-inflammatory properties that could potentially help treat diabetic retinopathy-induced pain and inflammation. However, CBD is a lipophilic molecule making its topical delivery to back of the eye challenging. This study aims at improving ocular penetration of CBD by means of analog derivatization. Methods: Analogs were designed using various ligands, such as amino acids (AAs) and dicarboxylic acids (DCAs) and their combinations. Select analogs were screened in vitro with respect to their stability in ocular tissue homogenates. Based on in vitro stability, analogs …

Δ9-Tetrahydrocannabinol Leads To Endoplasmic Reticulum Stress And Mitochondrial Dysfunction In Human Bewo Trophoblasts., Tina Lojpur, Zachary Easton, Sergio Raez-Villanueva, Steven Laviolette, Alison C Holloway, Daniel B Hardy

Physiology and Pharmacology Publications

While studies have demonstrated that the main psychoactive component of cannabis, Δ9-tetrahydrocannabinol (Δ9-THC) alone induces placental insufficiency and fetal growth restriction, the underlying mechanisms remain elusive. Given that both (i) endoplasmic reticulum (ER) stress in pregnancy and (ii) gestational exposure to Δ9-THC leads to placental deficiency, we hypothesized that Δ9-THC may directly induce placental ER stress, influencing trophoblast gene expression and mitochondrial function. BeWo human trophoblast cells treated with Δ9-THC (3-30 μM) led to a dose-dependent increase in all ER stress markers and CHOP; these effects could be blocked with CB1R/CB2R antagonists. Moreover, expression of ER stress-sensitive genes ERRγ, VEGFA, …

Effects Of Renal Ischemia-Reperfusion Injury On Cytochrome P450 Activity, Milleah Sawtelle

Senior Honors Projects

Approximately 2 million people worldwide and more than 670,000 Americans are affected by end-stage renal diseases (ESRD). The current standard of care for ESRD is kidney transplantation. However, the surgical procedure of kidney transplantation inherently involves ischemia, which interrupts blood flow and reduces oxygen, during kidney graft preservation. The ischemic period is followed by reperfusion (the restoration of blood flow to the transplanted graft), resulting in varying degrees of ischemia and reperfusion (I/R) injury. I/R injury is a leading cause of both organ dysfunction and graft failure. Furthermore, kidney I/R injury has been shown to cause remote organ damage, especially …

Identification Of Molecules By Spectral Imaging, Qamar Alshammari

Pharmaceutical Sciences (MS) Theses

Spectral imaging is a powerful technique which uses the wavelength to identify/quantify the exact location and amount of the molecules. It facilitates the identification of materials and studying their properties through analyzing the way they interact with light. The study of light interaction with elements is called spectroscopy; spectroscopy examines how light behaves in the target and recognizes materials based on their spectral signatures. Spectral signatures can be compared to fingerprints which can be used to identify a person; spectral signatures can be used to identify materials. Therefore, we hypothesize that identifying the exact location and quantity of molecules present …

A Screening Tool To Identify Qualified Pharmacy Residency Candidates., Daniel Hu, Danny Veenhouwer, Julie Mccoy, Dominick A Caselnova

Articles, Abstracts, and Reports

No abstract provided.

Comparative Effectiveness Of Drugs Used To Constrict The Patent Ductus Arteriosus: A Secondary Analysis Of The Pda-Tolerate Trial (Nct01958320)., Melissa Liebowitz, Joseph Kaempf, Omer Erdeve, Ali Bulbul, Stellan Håkansson, Johanna Lindqvist, Aijaz Farooqi, Anup Katheria, Jason Sauberan, Jaideep Singh, Kelly Nelson, Andrea Wickremasinghe, Lawrence Dong, Denise C Hassinger, Susan W Aucott, Madoka Hayashi, Anne Marie Heuchan, William A Carey, Matthew Derrick, Ilene Sue Wolf, Amy Kimball, Meera Sankar, Tina Leone, Jorge Perez, Arturo Serize, Ronald I Clyman

Articles, Abstracts, and Reports

OBJECTIVE: To evaluate the effectiveness of drugs used to constrict patent ductus arteriosus (PDA) in newborns < 28 weeks.

METHODS: We performed a secondary analysis of the multi-center PDA-TOLERATE trial (NCT01958320). Infants with moderate-to-large PDAs were randomized 1:1 at 8.1 ± 2.1 days to either Drug treatment (n = 104) or Conservative management (n = 98). Drug treatments were assigned by center rather than within center (acetaminophen: 5 centers, 27 infants; ibuprofen: 7 centers, 38 infants; indomethacin: 7 centers, 39 infants).

RESULTS: Indomethacin produced the greatest constriction (compared with spontaneous constriction during Conservative management): RR (95% CI) = 3.21 (2.05-5.01)), followed by ibuprofen …

Pharmacotherapy For Impulsivity-Hyperactivity Behaviors In Autism Spectrum Disorder, Jenna Katnis

Physician Assistant Scholarly Project Papers

The incidence of Autism Spectrum Disorder (ASD) in 8-year old children is 1 in 59. This increased from approximately 1 in 150 reported in 2000-2002 (Baio et al., 2014). Autism includes deficits in social emotional reciprocity, non-verbal communication for social interactions, developing and maintaining relationships and in some cases, hyperactivity response to sensory input. Hyperactivity is a shared behavior with ASD and Attention Deficit Hyperactivity Disorder (ADHD). Medications such as Methylphenidate (MPH) and α 2-a adrenergic receptor agonists are used to modify hyperactivity behavior in ADHD and thus have been used as management in ASD. A review of literature was …

The Characterization Of A New Metabolite From A Trichodesmium Bloom, Kelly M. Mcmanus

Senior Honors Projects

Our laboratory has been investigating blooms of Trichodesmium, a genus of ecologically important, nitrogen-fixing cyanobacteria, collected from Padre Island in the Gulf of Mexico. Trichodesmium species are an underexplored biological source of cyanobacteria – a taxa that has been shown to produce chemically diverse secondary metabolites. With our focus on the isolation and structure characterization of new bioactive marine natural products, our research group has discovered over 25 new-to-science compounds over the past three years from these blooms. UV and mass spectrometry-guided isolation of Trichodesmium chromatography fractions were utilized to isolate a new metabolite. Isolation of this metabolite was …

Comparison Of Quetiapine Abuse And Misuse Reports To The Fda Adverse Event Reporting System With Other Second-Generation Antipsychotics, Kirk E. Evoy, Chengwen Teng Pharm.D., Ph.D., Victor G. Encarnacion, Brian Frescas, John Hakim, Stephen Saklad, Christopher R. Frei

Faculty Publications

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Methods:

Development Of A Lectin-Fc Fusion Protein With Antiviral And Anti-Cancer Activity., Matthew William Dent

Electronic Theses and Dissertations

This thesis describes the development of a novel lectin-Fc fusion protein and its antiviral and anti-cancer activity. The molecule, Avaren-Fc (AvFc), is a fusion of a variant of the actinomycete lectin actinohivin (Avaren) and the Fc region of human IgG1, and is selective for the terminal α1,2-mannose residues found at the ends of high-mannose-type glycans that can be found on the surface of certain heavily glycosylated viruses and cancer cells. Here, AvFc was found to be able to neutralize simian immunodeficiency virus as well as Hepatitis C virus with nanomolar IC₅₀ values. Furthermore, AvFc recognizes a number of cell …

An Exploratory Study Of Suboxone (Buprenorphine/ Naloxone) Film Splitting: Cutting Methods, Content Uniformity, And Stability, Kristin L. Reindel, Michael J. Deangelis, Alexander S. Ferrara, Kelly Conn, Elizabeth Phillips, Anthony Corigliano, Fang Zhao

Doctoral External Publications

Suboxone films are U.S. Food and Drug Administration approved to treat opioid dependence. While the package insert states that films should not be cut, physicians often prescribe film fractions for treatment and tapering. There is no data to support this practice, and this study was initiated to evaluate cutting methods, content uniformity, and stability of split films. Suboxone 8-mg buprenorphine/2-mg naloxone films were split using four methods: 1) ruler/razor cut, 2) scissor cut, 3) fold/rip, and 4) fold/scissor cut. United States Pharmacopeia Chapter <905> was used to evaluate the weight variation and content uniformity of split films. The stability of split …

Macrolide Derivatives Reduce Proinflammatory Macrophage Activation And Macrophage‐Mediated Neurotoxicity, Bei Zhang, Timothy J. Kopper, Xiaodong Liu, Zheng Cui, Steven G. Van Lanen, John C. Gensel

Physiology Faculty Publications

Introduction: Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.

Aims: To improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture …

Cellular Localization Of Rad51d Mutant Proteins And The Application Of Art To Increase Scientific Literacy In America, Claire L. Chabot

Senior Theses

Ovarian cancers are the leading cause of death from cancer of the female reproductive system. Approximately 50% of ovarian cancers have defects in the homologous recombination (HR) DNA repair pathway that is required for the repair of DNA double-stranded breaks. The status of HR genes, such as BRCA1, BRCA2, and the RAD51 family, contributes to ovarian cancer development as well as treatment decisions regarding chemotherapy, radiation, and immunotherapy. The overarching goal of this project is to identify new insights into HR that can integrate with Precision Medicine Initiatives and align with the goals of the Cancer Moonshot 2020 Program. I …

Injectable Systems For Long-Lasting Insulin Therapy, Kumar Kulldeep Niloy

Theses and Dissertations (ETD)

Diabetes mellitus is one of the major global health problems and the prevalence rate is ever increasing reaching to 48% increase by the year of 2040 causing significant economic burdens. Insulin therapy has been the mainstay of diabetes treatment since its discovery in 1922. However, insulin is an unstable peptide with a half-life of only 4-6 min which poses significant challenge in prolonging duration of action of insulin. Nevertheless, the advances in recombinant DNA technology and protein engineering have enabled the development of several long-acting insulin analogue products which show duration of action up to 42 h. However, these insulin …

Exploring The Relationship Of Digital Information Sources And Medication Adherence, Cody Arbuckle, Daniel Tomaszewski, Lawrence Brown, Jon C. Schommer, Donald Morisky, Chelsea Parlett-Pelleriti, Erik J. Linstead

Pharmacy Faculty Articles and Research

We present a retrospective analysis of data collected in the United States from the 2015 National Consumer Survey on the Medication Experience and Pharmacists’ Role in order to model the relationship between health information sources and medication adherence and perception. Our results indicate that while the digital age has presented prescription users with many non-traditional alternatives for health information, the use of digital content has a significant negative correlation with pharmaceutical adherence and attitudes toward medication. These findings along with previous research suggest that in order to fully realize the potential benefits of the digital age in regards to patient …

Experimental Pharmacological Research Regarding Some New Quinazolin-4-Ones Derivatives, Cornel Chiriță, Emil Ștefănescu, Cristina E. Zbârcea, Simona Negreș, Mihaela Bratu, Diana C. Nuță, Carmen Limban, Ileana C. Chiriță, Cristina D. Marineci

Journal of Mind and Medical Sciences

A series of new compounds with quinazolin-4-one structure, synthesized by the Pharmaceutical Chemistry Department of the Faculty of Pharmacy of the University of Medicine and Pharmacy “Carol Davila” Bucharest, was studied. Five of them were selected, conventionally named S1, S2, S3, S4, S5, and investigated in terms of their potential influence on the central nervous system (CNS). For this purpose, the antidepressant effect was determined using the forced swimming test; the anxiolytic/ anxiogenic effect was determined using the suspended plus-shaped maze (Ugo Basile); the effect on the motor activity was determined using the Ugo Basile activity cage; and the potential …

Sensory Primary Cilium Is A Responsive Camp Microdomain In Renal Epithelia, Rinzhin T. Sherpa, Ashraf M. Mohieldin, Rajasekharreddy Pala, Dagmar Wachten, Rennolds S. Ostrom, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are hair-like cellular extensions that sense microenvironmental signals surrounding cells. The role of adenylyl cyclases in ciliary function has been of interest because the product of adenylyl cyclase activity, cAMP, is relevant to cilia-related diseases. In the present study, we show that vasopressin receptor type-2 (V2R) is localized to cilia in kidney epithelial cells. Pharmacologic inhibition of V2R with tolvaptan increases ciliary length and mechanosensory function. Genetic knockdown of V2R, however, does not have any effect on ciliary length, although the effect of tolvaptan on ciliary length is dampened. Our study reveals that tolvaptan may have a cilia-specific …

A Background Of The Opioid Epidemic And Its Relationship To The Medicaid Expansion, Er Yearn Jang

Senior Honors Theses

Despite the recent increase in public awareness of the opioid epidemic, the background of this epidemic is still disappointingly unknown to the public. The opioid epidemic is a national crisis which impacts, not only individuals’ wellbeing but the economy of the United States. The federal government sought to mitigate it through the enactment of the Patient Protection and Affordable Care Act. The Medicaid expansion, which was built into this law, sparked controversy; controversy which has yet to be solved to this day. Going forward, the knowledge we gather from examining the connection between this epidemic and the Medicaid expansion will …

Responding To Opioid Use Disorder: Identifying The Therapeutic Commitment Of Maine Nurse Practitioners, Jordan S. Porter

DNP Projects

Background: Buprenorphine, an underutilized pharmacotherapy, can play a key role in closing the substantial opioid use disorder (OUD) treatment gap in the United States. Although 2016 US legislation authorized trained nurse practitioners (NPs) to obtain the Drug Enforcement Agency waiver to prescribe buprenorphine for OUD, many NPs do not have the waiver, and a large proportion of waivered NPs do not prescribe to capacity. Purpose: To identify the therapeutic commitment of Maine NPs to OUD as well as understand why Maine NPs do not adopt and utilize buprenorphine for the treatment of OUD. Review of Evidence: Commitment …

Status Of Teaching Certificate Programs Offered By Us Colleges And Schools Of Pharmacy, Mohammed Islam, Rose Bagheri, Lydia Lung, Sung Y. Park, Rahmat Talukder

Pharmacy Faculty Publications and Presentations

Purpose: Teaching certificate programs have been developed by US colleges and schools of pharmacy to provide organized instruction for pharmacy residents seeking competence in classroom teaching or clinical precepting. The objective of this study is to appraise current status of teaching certificate programs offered by US colleges and schools of pharmacy. Method: A survey instrument was developed and sent to pharmacy practice department chairs/vice chairs at 132 US colleges/schools of Pharmacy. In addition, data collection was conducted by visiting websites of 132 colleges and schools of pharmacy. Descriptive statistics and content analysis methods were used for data analysis. Results: Out …

Targeting Primary Cilia Immune Receptor Proteins For The Treatment Of Polycystic Kidney Disease Mechanisms, Nedaa Alomari

Pharmaceutical Sciences (MS) Theses

Background: Primary cilia are cellular organelles project from the cell surface of mammalian cell and play important roles in vertebrate development, organogenesis, health, and others genetic diseases. Primary cilium functions as a mechano-sensor and chemo-sensor. Defect in primary cilia causes the progression of polycystic kidney disease (PKD) which further leads to the inflammatory responses. We, therefore, investigated the role of Toll-like receptors 4 and 9 (TLR) in primary cilia towards PKD.

Purpose: The main purpose of the proposed study is to identify and target the immune reactive proteins i.e. TLRs in the primary cilia. By targeting those primary cilia immune …

Amphiphilic Peptides For Efficient Sirna Delivery, Saghar Mozaffari, Emira Bousoik, Farideh Amirrad, Robert Lamboy, Melissa Coyle, Ryley Hall, Abdulaziz Alasmari, Parvin Mahdipoor, Keykavous Parang, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

A number of amphiphilic cyclic peptides—[FR]4, [WR]5, and [WK]5—containing hydrophobic and positively-charged amino acids were synthesized by Fmoc/tBu solid-phase peptide methods and evaluated for their efficiency in intracellular delivery of siRNA to triple-negative breast cancer cell lines, MDA-MB-231 and MDA-MB-468, in the presence and absence of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Among the peptides, [WR]5, which contains alternate tryptophan (W) and arginine (R) residues, was found to be the most efficient in the delivery of siRNA by improving the delivery by more than 3-fold when compared to other synthesized cyclic peptides that were not efficient. The data also showed that co-formulation of [WR]5 …

Application Of Beers Criteria And A Brown Bag Event To Increase Prescribing Safety In Older Adults, Kristen Garza

Evidence-Based Practice Project Reports

With older adults making up about 14.5% of the U.S. population, polypharmacy may be an unintended consequence of adhering to clinical practice guidelines (Kim & Luck Parish, 2017). Effective polypharmacy interventions are needed in the primary care setting to increase prescribing safety and lower the risk of adverse drug events among older adults. The application of the Beers criteria, in conjunction with a brown bag medication reconciliation event, was initiated as focused interventions for a private primary practice without electronic health records. Outcomes included medication reduction, identification of possible inappropriate medication, decrease of medication dosages, and identification of duplicate medication. …