Vaccines In Current Culture: The Hpv Vaccine Controversy, Alyssa Johnston

Senior Honors Theses

The use of vaccinations has drastically decreased mortality and morbidity rates related to infectious disease and has become an intrinsic part of modern health care. However, the fear of risks related to vaccines has been partially responsible for the decisions of many parents to delay or avoid vaccinating their children. The human papilloma virus (HPV) vaccine specifically is one of the most controversial vaccines in current culture due to reports of new onset or exacerbation of autoimmune diseases, infertility, and even death following its administration. This review synthesizes information regarding the relevance and safety of the HPV vaccine, as well …

First-In-Human Studies Of Mw01-6-189wh, A Brain-Penetrant, Antineuroinflammatory Small-Molecule Drug Candidate: Phase 1 Safety, Tolerability, Pharmacokinetic, And Pharmacodynamic Studies In Healthy Adult Volunteers, Linda J. Van Eldik, Lumy Sawaki, Karen Bowen, Daniel T. Laskowitz, Robert J. Noveck, Byron Hauser, Lynn Jordan, Tracy G. Spears, Huali Wu, Kevin Watt, Shruti Raja, Saktimayee M. Roy, D. Martin Watterson, Jeffrey T. Guptill

Sanders-Brown Center on Aging Faculty Publications

MW01-6-189WH (MW189) is a novel central nervous system-penetrant small-molecule drug candidate that selectively attenuates stressor-induced proinflammatory cytokine overproduction and is efficacious in intracerebral hemorrhage and traumatic brain injury animal models. We report first-in-human, randomized, double-blind, placebo-controlled phase 1 studies to evaluate the safety, tolerability, and pharmacokinetics (PK) of single and multiple ascending intravenous doses of MW189 in healthy adult volunteers. MW189 was safe and well tolerated in single and multiple doses up to 0.25 mg/kg, with no clinically significant concerns. The most common drug-related treatment-emergent adverse event was infusion-site reactions, likely related to drug solution acidity. No clinically concerning changes …

Coronavirus Disease 2019 (Covid-19), Matthew Dunbar

Pharmacy Student Scholarship

No abstract provided.

Characterizing The Public Sector Contribution To Drug Discovery And Development: The Role Of Government As A First Investor, Ekaterina Galkina Cleary, Matthew Jackson, Andrew Acevedo, Fred D. Ledley

CISI Publication

This research is focused on examining the role of the public sector as an early investor in biopharmaceutical discovery and development. In the United States, the National Institutes of Health (NIH) is the primary source of funding for basic biomedical research designed to elucidate fundamental mechanisms of biology, health, and disease. This research is expected to establish the scientific foundation for the discovery and development of new biopharmaceutical products. This interim report reviews the linear model of innovation underlying these expectations, and evidence for the effectiveness of this pathway. We also describe new data demonstrating that every new drug approved …

Immunogenicity In Clinical Practice And Drug Development: When Is It Significant?, Valentina Shakhnovich, Bernd Meibohm, Amy Rosenberg, Andrzej M. Kierzek, Rachel Hasenkamp, Ryan S. Funk, Craig J. Thalhauser, Piet H. Van Der Graaf, Yow Ming C. Wang, Lora Hamuro

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.

Tobacco/Hiv-1-Induced Myeloid Cell-Derived Extracellular Vesicles In Hiv-1 Pathogenesis, Sanjana Haque

Theses and Dissertations (ETD)

Introduction. Smoking, which is highly prevalent in people living with HIV/AIDS, has been shown to exacerbate HIV-1 replication, in part via cytochrome P450 (CYP)-induced oxidative stress. CYP enzymes metabolize cigarette smoke condensate (CSC), causing oxidative stress and cytotoxicity. Our previous studies have demonstrated that CSC and specific CSC constituents, benzo(a)pyrene and nicotine, potentially induce CYPs, resulting in higher oxidative stress and subsequent exacerbation of HIV-1 replication in monocytes and macrophages. However, the exact mechanism behind tobacco-induced, oxidative stress-mediated enhancement of HIV-1 replication is still poorly understood. Extracellular vesicles (EVs) have recently gained attention for their unique nature as intercellular messengers …

Determining The Advantageous Acute Migraine Treatment: Rimegepant And Lasmiditan Review Of Literature, Tiffany A. Johnson

Honors Undergraduate Theses

This research aims to evaluate two new pharmaceuticals on the market. Rimegepant and Lasmiditan target the trigeminovascular system and respectively, are characterized in the gepant and ditan classes of pharmaceuticals. Based on a review of studies, Rimegepant was determined to be the advantageous acute treatment. This is not conclusive due to inequivalent comparison in sample size and amount of research completed. It is encouraged for additional research to be imposed before a conclusive determination of the advantageous acute treatment can be distinguished.

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 …

Novel Small Molecule Antifungals For Invasive Fungal Infections, Emily Dennis

Theses and Dissertations--Pharmacy

Human fungal pathogens cause a range of diseases from benign skin conditions (i.e., ringworm) to thrush, mucosal membrane infections, and life-threatening systemic infections including bloodstream infections (i.e., aspergillosis and candidiasis) and Cryptococcal meningitis. These systemic infections occur most often in immunocompromised individuals and have high mortality rates. Current antifungal agents used in the clinic belong to three main classes: the polyenes (e.g., amphotericin B (AmB)), the echinocandins (e.g., caspofungin (CFG)), and the azoles (e.g., fluconazole (FLC)). In addition, the antimetabolite pyrimidine analogue flucytosine is used in combination with AmB. The …

Enhancing Chemosensitivity Of Lung Cancers By Manipulating The Tumor Microenvironment: Local Lung Delivery And Nanocarrier-Based Therapies, Hanming Zhang

Theses and Dissertations

Cancer is the second leading cause of death in United States causing an estimated six hundred thousand death in 2019. Among different types of cancer, lung cancer is the leading cause of cancer related death in both male and female. While targeted therapy and immunotherapy have shown promising clinical outcomes, currently there remain a significant proportion of patients who do not benefit from these strategies or who cannot tolerate them, making Pt based doublet chemotherapy still an indispensable component in almost all stages of treatment. However, partially due to the poor tumor distribution of small molecule drug, the development of …

The Effects Of Scheduling Acetaminophen And Methocarbamol Administration On Postoperative Opioid Use And Related Side Effects Among Cardiac Surgery Patients, Whitney Jamison

DNP Projects

The Effects of Scheduled Acetaminophen and Methocarbamol Administration on Postoperative Opioid Use and Related Side Effects Among Cardiac Surgery Patients

ABSTRACT

Purpose

Opioid therapy is commonly prescribed to combat surgical pain in hospitals across the United States and is associated with many negative side effects including dependence and nausea. The purpose of this study was to retrospectively examine the effects of scheduling acetaminophen and methocarbamol administration postoperatively throughout the cardiac surgery patients’ hospital stay. Through retrospective chart reviews, the aims of postoperative opioid use, postoperative opioid use according to hospital length of stay, antiemetic use, and opioid prescription at discharge …

Population Pharmacokinetics Of Intravenous Colistin In Pediatrics (Poppicop Study), Noppadol Wacharachaisurapol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Colistin use in pediatrics is surging in line with the increase of multidrug-resistant Gram-negative bacteria (MDR-GNB). However, the appropriate dose is uncertain owing to the lack of pharmacokinetics data. In this study, we aimed to characterize the pharmacokinetic parameters of colistin in pediatric patients, identify the factors influencing the pharmacokinetic parameters, and propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Serial blood samples were obtained from patients after receiving the standard colistin recommended dose of 5 mg of colistin base activity (CBA)/kg/day. Plasma colistin concentrations were measured. Data were pooled from this study …

Development Of Dexamethsone Sodium Phosphate Loaded Nanoparticles For Treating Corneal Allograft Rejection, Vineet R. Kulkarni

Theses and Dissertations

Corneas are the most commonly transplanted tissue worldwide, with approximately 80,000 transplantations performed in the United States in 2018 alone. Corneal transplantation is used to restore the vision due to opaque corneas in various diseases such as fungal keratitis, keratoconus, Fuchs’s dystrophy, corneal ulceration, traumatic injury, abrasions or scarring, inflammation, and infection. Corneal transplant surgery could involve replacing the entire cornea (penetrating keratoplasty) or selective replacement of the corneal layers (e.g. Descemet’s membrane endothelial keratoplasty and deep anterior lamellar keratoplasty). Immunologic graft rejection is one of the main causes of graft failure in these corneal transplantations. The 2-year rejection rate …

3-D Homology Modeling Of Organic Anion Transporters (Oats): Defining The Biochemical Basis For Oat-Substrate Interactions, Christopher Jay

Theses and Dissertations

A goal in the drug development process, as indicated by the FDA, is to evaluate a drug’s ADME profile, as potential drug interactions could exist, leading to adverse drug reactions or loss of efficacy. Transport proteins, specifically organic anion transporters (OATs) are involved in the absorption, distribution, and elimination of small, negatively charged compounds. Although there is an exhaustive list of structurally diverse organic anions which interact with OATs, interactions at a molecular level are still shrouded in mystery particularly due to the lack of a solved crystal structure. Therefore, in silico homology models (hOAT1, 2, 3) were generated using …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

Vaccine Hesitancy: Experimentalism As Regulatory Opportunity, Ana Santos Rutschman, Timothy L. Wiemken

All Faculty Scholarship

This symposium on patient innovation has prompted us to explore problems related to departures from official vaccination schedules. At a time in which vaccine confidence has been plummeting across the world, we argue that a more granular understanding—and ultimately a more finely tuned regulatory framework—is needed to reflect the current behavioral heterogeneity among indicated patients who choose to forego or delay administration of recommended vaccines. In particular, we focus on a phenomenon we term “vaccine staggering:” a departure from vaccination schedules in the form of delays in receiving one or more vaccines, which is motivated by the desire to boost …

Effect Of 3d Printed Tablet Shape On Drug Release Profile, Christina Gedeon

Theses

There is a growing interest in utilizing additive manufacturing (AM) as a manufacturing tool to develop oral tablets for personalized medicine. This ultimate goal in mind, this study explores the feasibility of extrusion-based fused deposition modeling (FDM) to 3D print oral tablets with tunable design to control drug release profile. Tablets are printed using poly(vinyl alcohol) (PVA) loaded with model drugs: acetaminophen and caffeine. Hot melt extrusion (HME) is used to fabricate PVA filaments loaded with acetaminophen and caffeine. These filaments are used to fabricate a range of tablets with varying designs to prepare immediate and delayed release tablets. Thermal …

Chemical Components Of Ocimum Basilicum L. And Ocimum Tenuiflorum L. Stem Essential Oils And Evaluation Of Their Antioxidant Activities Using Dpph Method, Ni Putu Ermi Hikmawanti, Hariyanti, Nurkamalia, Sahera Nurhidayah

Pharmaceutical Sciences and Research

Ocimum basilicum L. and Ocimum tenuiflorum L. are two types of plants from Ocimum (Lamiaceae). One of their chemical compounds is essential oil. Essential oil might have an antioxidant activities. The part of the plants which are often wasted and never used are stem. This study aimed to analyze the chemical components of O. basilicum L. and O. tenuiflorum L. stem essential oils and evaluate their antioxidant activities. Essential oils were obtained by steam-water distillation. Analysis of chemical component of essential oil was performed using Gas Chromatography-Mass Spectroscopy (GC-MS). Antioxidant activities were evaluated with DPPH method and then the IC50 …

Identification And Evaluation Of Antibacterial Compounds From The Vibrio Sp. Associated With The Ascidian Pycnoclavella Diminuta, Abdurraafi’ Maududi Dermawan, Elin Julianti, Masteria Yunovilsa Putra

Pharmaceutical Sciences and Research

This study aims to obtain secondary metabolites that have antibacterial activity from bacteria endophytic of ascidian Pycnoclavella diminuta collected from the coast of Bitung, North Sulawesi, Indonesia. The research was started with screening antibacterial activity of six bacteria isolated from P. diminuta. The active bacteria were selected for identification using standard biological molecular method and further fermentation to produce secondary metabolites. The isolation of secondary metabolites was conducted by various chromatography method and then selected fraction was based on the antibacterial activity from bioautography results. The result showed that the active isolate by coding M2.Tnk.Bt 5.10-3.2 was identified as Vibrio …

Cytotoxic Activity Of Stem Of Pycnarrhena Cauliflora Through Apoptosis Induction On Human Breast Cancer Cell Line T47d, Masriani, Rudiyansyah, Rini Muharini, Eny Enawaty

Pharmaceutical Sciences and Research

Cytotoxic activities of extracts of Pycnarrhena cauliflora leaves, stems and roots on some human cancer cells have been known. However, the cytotoxicity of stem of Pycnarrhena cauliflora on human breast cancer cell line T47D through an apoptosis induction has not been proven yet. This study was an effort in understanding the cytotoxic activity of stem of Pycnarrhena cauliflora through apoptosis induction. The crude ethanol extract was partitioned between n-hexane and dichloromethane at pH 3, 7 and 9, which was subsequently tested for their cytotoxic activity against human breast cancer cell line T47D by using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT). Flow cytometric …

Model Hewan Coba Pada Penelitian Diabetes, Fauzul Husna, Franciscus D. Suyatna, Wawaimuli Arozal, Erni H. Purwaningsih

Pharmaceutical Sciences and Research

The animal model has been widely used and contributed vastly to the scientific research over the years. While it can be used as an alternate subject in a study, the selection of the animal is crucial to assess and investigate the influence of the environment and genes on the pathogenesis of a disease. Many factors contribute to the choosing of the animal. They can be ranged from the similarities with the modelled object, easily looked after with less expensive cost, good reproductive performance, ability to produce blood and tissue samples, well-known genetic composition, and the status of the disease can …

Synthesis And Characterization Of Long Acting Darunavir Prodrugs, Mary Banoub

Theses & Dissertations

Patient adherence is critical for ART success to ensure adequate viral suppression, therefore, long-acting antiretrovirals are soon replacing current daily regimens. In recent years, two drugs were successfully transformed into long-acting injectables; CAB LA and RPV LA. These long-acting nanoformulations made it possible to abandon the daily pill burden, instead approximately a bimonthly injection of both drugs is enough to suppress and maintain viral load suppression. Our laboratory has been instrumental in transforming FDA-approved and experimental-HIV medications into long-acting slow effective release drugs, also known as LASER ART. LASER ART consists of slow drug metabolism and high permeability and retention …

Engineering Hyaluronic Acid For Biomedical Applications, Deep S. Bhattacharya

Theses & Dissertations

This work presents research using the naturally available non- sulfated carbohydrate glycosaminoglycan hyaluronic acid (HA) for the synthesis of different chemical derivatives of HA for evaluation of binding kinetics with CD44 and P- selectin proteins for applications in fluorescence image-guided surgery. Chemical derivatives of HA such as deacetylated HA (deHA), sulfated HA (sHA), and deacetylated and sulfated HA (s-deHA) were synthesized by modulating sulfating and deacetylating reagents to alter binding specificities to CD44. Modified HA derivatives and CD44 biophysical interactions were assessed by fluorescence polarization. In silico techniques were also used to determine binding using molecular docking and MM-PBSA approaches. …

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

The Development Of Hyaluronan-Based Contract Agents For The Intraoperative Detection Of Pancreatic Tumors, Bowen Qi

Theses & Dissertations

Pancreatic ductal adenocarcinoma is highly lethal and surgical resection is the only potential curative treatment for the disease. Tumor-specific intraoperative fluorescence imaging could improve staging and surgical resection, thereby improving prognosis. In the first study, hyaluronic acid derived NPs with physico-chemically entrapped indocyanine green, termed NanoICG, were utilized for intraoperative near infrared fluorescence detection of pancreatic cancer. NanoICG accumulated significantly in an orthotopic pancreatic ductal adenocarcinoma model with safety profile both in vitro and in vivo. To maximize tumor signal, while minimizing signal in healthy pancreas and RES capture of macromolecules, in the next study, we describe the rational …

The Development Of Novel Apurinic/Aprymidinic Endonuclease/Redox-Factor 1 Inhibitors For The Treatment Of Human Melanoma, Bella Sharifi

Pharmaceutical Sciences (MS) Theses

Apurinic/apyrimidinic DNA repair endonuclease-1 (APE1), first recognized as an important DNA excision repair enzyme, is also known as Redox Factor-1 (Ref-1) involved in the activation of many nuclear transcription factors in both redox-dependent and independent manner. It has been well-documented that the overexpression of APE/Ref-1 contributes to the development of chemo-resistance and is associated with tumor progression in many human malignancies [1].

Our previous study in melanoma demonstrated that the development of novel inhibitors targeting the redox regulation domain of APE/Ref-1 is a promising strategy for melanoma treatment. To date, limited successes have been reported in developing novel …

Amphiphilic Cell-Penetrating Hybrid Cyclic-Linear Peptides As A Drug Delivery System, Saghar Mozaffari

Pharmaceutical Sciences (PhD) Dissertations

A number of cyclic peptides containing a positively charged ring composed of arginine residues attached to hydrophobic tail made of tryptophan residues through a lysine linker namely [R₅K]W₅, [R₆K]W₅, [R₅K]W₆, [R₇K]W₅, [R₅K]W₇, [R₆K]W₆, and [R₇K]W₇ were synthesized and evaluated as molecular transporters. The peptides were evaluated for their ability to deliver, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI), and fluorescent labeled anti-HIV drugs (F′-FTC and F′-d4T). The results indicated that the presence of positively …

After-Action Report: Tabletop Exercise On Opioid Crisis Response And Resilience, Alexander Siedschlag, Tiangeng Lu

Publications

AGENCY BRIEFINGS The opioid overdose epidemic has been characterized as the worst public health crisis in Pennsylvania, and the nation. Not only practitioners but also institutions of higher education with high research capacity, such as Penn State, are applying existing and developing new instruments to address opioid the crisis. Identifying best practices of preventing, protecting from, mitigating against, responding to, and recovering from opioid overdose outbreak is necessary for public health and safety and important for the overall homeland security enterprise, in consistency with the objectives of the Quadrennial Homeland Security Reviews (QHSR), the National Preparedness Goal (NPG), and the …

Ramucirumab: A New Agent For Advanced Or Metastatic Gastric Junction Adenocarcinoma, Adam Smith, Rebecca Worden, Jessica Hoffert, Brendon Rasor, Hannah Stewart, David Koh

Pharmacy and Wellness Review

Ramucirumab (Cyramza®), approved April 21, 2014, is a vascular endothelial growth factor receptor 2 (VEGFR2) antagonist with a U.S. Food and Drug Administration (FDA) indication for the treatment of advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. Gastric cancer is a prevalent cancer in the United States with a poor prognosis. The phase 3 trial, REGARD, shows that ramucirumab, when used within four months after the last dose of first-line chemotherapy or six months after the last dose of adjuvant chemotherapy, increases overall survival. Also, ramucirumab has been included in combination therapy, such as in the RAINBOW trial, which demonstrated its effectiveness …