Other Chemicals and Drugs Commons^™

Docking Studies Of Isoform-Selectivity Of Phosphatidylinositol 3-Kinase (Pi3k) Inhibitors, Kaitlin Goettsch

UNO Student Research and Creative Activity Fair

Phosphatidylinositol 3-kinases (PI3Ks) and their related pathways are reputed targets for drug-based anticancer therapies. Mutations in PI3K genes, expression, and pathways are frequent among multiple cancer types. Four isoforms of PI3Ks exist: α, β, γ, & δ and studies have identified several ligands for each isoform which are capable of serving as inhibitory therapeutic compounds. However, the biochemical efficacy of these molecules varies and the isoform selectivity is not well understood. In this study, we applied in silico docking methods and free energy calculation methods to estimate the binding of reported PI3K ligands against 5 PI3K structures: PI3Kα (PBD ID: …

Metastatic Biomarkers In Synovial Sarcoma, Rosalia De Necochea-Campion, Lee M. Zuckerman, Hamid R. Mirshahidi, Shahrzad Khosrowpour, Chien-Shing Chen, Saied Mirshahidi

Library Articles and Research

Synovial sarcoma (SS) is an aggressive soft tissue sarcoma (STS) that typically occurs in the extremities near a joint. Metastatic disease is common and usually occurs in the lungs and lymph nodes. Surgical management is the mainstay of treatment with chemotherapy and radiation typically used as adjuvant treatment. Although chemotherapy has a positive impact on survival, the prognosis is poor if metastatic disease occurs. The biology of sarcoma invasion and metastasis remain poorly understood. Chromosomal translocation with fusion of the SYT and SSX genes has been described and is currently used as a diagnostic marker, although the full impact of …

Ethical Imperatives Of Timely Access To Orphan Drugs: Is Possible To Reconcile Economic Incentives And Patients’ Health Needs?, Rosa Rodriguez-Monguio, T. Spargo, Enrique Seoane-Vazquez

Pharmacy Faculty Articles and Research

Background

More than 6,800 rare diseases and conditions have been identified in the US, which affect 25–30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs.

Methods

Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of …

Exploration Of Bioactive Compounds Of Ginger As A Folk Remedy For Migraines, Nathan Vorbes Aleger

Honors Undergraduate Theses

Ginger (Zingiber Officinale) has been used in Asia for centuries to treat various ailments. Ginger has been reported to alleviate migraine pain via four bioactive compounds that can reduce nitric oxide synthase (NOS) resulting in the inhibition of nitric oxide (NO). The inhibition of nitric oxide results in the vasoconstriction of the intracranial blood vessels alleviating migraine pain. It is hypothesized that ginger has structural similarities to vasoconstrictor drugs causing similar receptor interactions. A review of the bioactive compounds in ginger and popular vasoconstrictor drugs was done to determine structural similarities. The results of this study show that …

“Whatever It Takes To Beat Parkinson’S”: A Controversial Approach For Symptom Relief, Sondra M. Deskins

WRIT: Journal of First-Year Writing

It is known that there is no cure for Parkinson's disease. So, physicians who treat Parkinson's patients must decide what is the best treatment option for the patients symptoms to improve their quality of life. Currently, there are pharmaceutical options for treatment, but they include adverse side effects. What if there were a way to treat patients for the side effects as well as improve the patient's symptoms? The recent commotion around the legalization of marijuana, both recreational and medicinal, has caused interest among patients and physicians. One must decide if the benefits of using marijuana as a form of …

Steroids: A Growing Dilemma In Athletics, Seara Ontiveros

Nebraska College Preparatory Academy: Senior Capstone Projects

A comprehensive and straight forward description of what exactly steroids are and what they do to the body is described by Gary Wadler, a health major at the New York University School of Medicine, he comments: “When the receptor sites in their bodies, which don’t have much testosterone in them, suddenly are presented with a lot of testosterone, they get activated…The unbalance of hormones increases the red blood cell formations... They’ll get more muscular, more defined. They’ll lose some fat, and increase their lean body mass, [they’ll] get stronger”. Although anabolic steroids and other hormones are consumed by many athletes …

Synthesis Of Oxadeazoles With Electron Withdrawing Groups And The Analysis Of Product Yield With Bond Length, Elizabeth Ann Hall Peters

Undergraduate Honors Thesis Projects

2,5-disubstituted 1,3,4-oxadiazoles are a class of organic compound that are widely used and successful in pharmaceutical chemistry because they demonstrate strong biological activity. They are part of a larger class of compound called heterocycles, which make up most pharmaceutical drugs today. When synthesizing the compounds, higher yield means higher reactivity of the compound, and this is important for pharmaceuticals that need to have a strong biological activity. Per past studies, electron withdrawing groups on the compound allow higher, product yields. Along with electron withdrawing group addition, the bond length from electron withdrawing group and its corresponding carbon is analyzed to …

The Autocrine Role Of Proteoglycan-4 (Prg4) In Modulating Osteoarthritic Synoviocyte Proliferation And Expression Of Matrix Degrading Enzymes, Ali Alquraini, Maha Jamal, Ling Zhang, Tannin Schmidt, Gregory D. Jay, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Lubricin/proteoglycan 4 (PRG4) is a mucinous glycoprotein secreted by synovial fibroblasts and superficial zone chondrocytes. Recently, we showed that recombinant human PRG4 (rhPRG4) is a putative ligand for CD44 receptor. rhPRG4-CD44 interaction inhibits cytokine-induced rheumatoid arthritis synoviocyte proliferation. The objective of this study is to decipher the autocrine function of PRG4 in regulating osteoarthritic synoviocyte proliferation and expression of catabolic and pro-inflammatory mediators under basal and interleukin-1 beta (IL-1β)- stimulated conditions.

Methods: Cytosolic and nuclear levels of nuclear factor kappa B (NFκB) p50 and p65 subunits in Prg4+/+ and Prg4-/- synoviocytes were studied using western blot. Nuclear …

Discovery Of Pyrimidine-Based Heterocycles As Single Agents With Combination Chemotherapy Potential And As Inhibitors Of Purine Nucleotide Biosynthesis For The Treatment Of Cancer, Rishabh Mohan

Electronic Theses and Dissertations

This dissertation describes the design, synthesis and biological evaluation of monocyclic and bicyclic pyrimidine-base heterocycles as single agents with combination chemotherapy potential having both antiangiogenic effects and cytotoxic effects. This dissertation also describes selective tumor targeting with 5-substituted pyrrolo[2,3-d]pyrimidines analogs with heteroatom bridge substitution as GARFTase inhibitors.

The work in this dissertation is centered on identifying structural features that are necessary for inhibition of tubulin polymerization as well as for inhibition of one or more of the receptor tyrosine kinases (RTKs)- vascular endothelial growth factor receptor-2 (VEGFR2), platelet derived growth factor receptor-β (PDGFRβ) and epidermal growth factor receptor …

A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin

All Master's Theses

Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of …

Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain., Avery E. Villa-Gonzalez

Dissertations and Theses

Adolescence is a developmentally critical transition from childhood to adulthood including both maturation of the body and the brain. Neuroplastic changes result in dynamic organization of the brain during adolescence, leaving them vulnerable to development of mental illness and drug-seeking behavior. According to the United Nations Office on Drugs and Crime, the psychostimulant cocaine is the second most popular illicit drug in the world. Cocaine, amongst having many detrimental effects, has shown to also decrease hippocampal neurogenesis, resulting in decreased neuroplasticity and cognitive dysfunction. Previous students in our laboratory have shown that treatment of adult male rats with the essential …

Antibiotic Overuse: The History, Consequences, And Possible Solutions, Brooke A. Bost

Senior Honors Theses

Antibiotic overuse has become alarmingly accepted in the developed world. This overuse is leading to drug resistance in microbes, resulting in bacterial infections that are impossible to treat. Steps must be taken to reverse the damage that has already been done and prevent further resistance from developing. This thesis will examine the context and societal situations that led to this acceptance of antibiotic overuse and misuse seen in both health care professionals and the public, the biochemical and genetic pathways that allow a microbe to develop drug resistance, the various methods that have been suggested by experts to prevent and …

The Effects Of Tranexamic Acid On Mortality Rate In Trauma Patients Compared To Trauma Patients With No Tranexamic Acid Treatment, Bradley Earl Tolar

Doctoral Projects

Traumatic injury is the leading cause of death for many age groups. Traumatic accidents caused over 130,000 deaths in the United States in 2014. This DNP project studied the effects of Tranexamic acid on mortality rate in trauma patients. After the completion of a needs assessment at a local level II trauma center, a literature review was performed. The literature showed a decrease in mortality rate when patients were administered Tranexamic acid within 3 hours of injury with statistically significant statistics. Also, the data from the literature showed no correlation between vascular occlusive events and Tranexamic acid use in trauma …

Partial Amino Acid Sequence Of Lipid Transfer Protein From Fennel (Foeniculum Vulgare) Seeds, Hasan Al-Shiyab, Caroline Aziz

Student Scholar Symposium Abstracts and Posters

Fennel (Foeniculum vulgare) is a biennial Egyptian medicinal plant with an aromatic odor that belongs to the family Apiaceae (Umbelliferae). Fennel seeds are commonly used in traditional medicine, as they are known to have anti-inflammatory, anti-fungal and anti-cancerous activities. The major constituents of the fennel plant are sugars, minerals, essential fatty acids, proteins and fibers. Although, there are numerous studies on the medicinal properties of essential oils of the fennel seeds, but there is limited data reported on the proteins and peptides. The aims of this project are to fully characterize the primary structure of proteins and to determine their …

Flavored Electronic Cigarette Use And Smoking Among Youth., Hongying Dai, Jianqiang Hao

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVE: Flavored electronic cigarettes (e-cigarettes) are not prohibited in the United States, and e-cigarette flavors proliferate on the market. This study sought to examine flavored e-cigarette use and its association with smoking among youth.

METHODS: Estimates of flavored e-cigarette use from the 2014 National Youth Tobacco Survey were investigated. A logistic regression model was used to assess whether flavored e-cigarette use was associated with (1) intention to initiate cigarette use among never-smoking youth (n = 16 471), (2) intention to quit tobacco use among current-smoking youth (n = 1338), and (3) perception of tobacco's danger among all respondents …

Network Inference Driven Drug Discovery, Gergely Zahoránszky-Kőhalmi, Tudor I. Oprea, Cristian G. Bologa, Subramani Mani, Oleg Ursu

Biomedical Sciences ETDs

The application of rational drug design principles in the era of network-pharmacology requires the investigation of drug-target and target-target interactions in order to design new drugs. The presented research was aimed at developing novel computational methods that enable the efficient analysis of complex biomedical data and to promote the hypothesis generation in the context of translational research. The three chapters of the Dissertation relate to various segments of drug discovery and development process.

The first chapter introduces the integrated predictive drug discovery platform „SmartGraph”. The novel collaborative-filtering based algorithm „Target Based Recommender (TBR)” was developed in the framework of this …

Use Of A Modified Greenscreen Tool To Conduct A Screening-Level Comparative Hazard Assessment Of Conventional Silver And Two Forms Of Nanosilver., Jennifer Sass, Lauren Heine, Nina Hwang

Environmental and Occupational Health Faculty Publications

BACKGROUND: Increased concern for potential health and environmental impacts of chemicals, including nanomaterials, in consumer products is driving demand for greater transparency regarding potential risks. Chemical hazard assessment is a powerful tool to inform product design, development and procurement and has been integrated into alternative assessment frameworks. The extent to which assessment methods originally designed for conventionally-sized materials can be used for nanomaterials, which have size-dependent physical and chemical properties, have not been well established. We contracted with a certified GreenScreen profiler to conduct three GreenScreen hazard assessments, for conventional silver and two forms of nanosilver. The contractor summarized publicly …

A Murine Model Of Inflammation-Induced Cerebral Microbleeds, Rachita K. Sumbria, Mher Mahoney Grigoryan, Vitaly Vasilevko, Tatiana B. Krasieva, Miriam Scadeng, Alexandra K. Dvornikova, Annlia Paganini-Hill, Ronald Kim, David H. Cribbs, Mark J. Fisher

Pharmacy Faculty Articles and Research

Background: Cerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to …

Multipurpose Tenofovir Disoproxil Fumarate Electrospun Fibers For The Prevention Of Hiv-1 And Hsv-2 Infections., Kevin Tyo

Electronic Theses and Dissertations

Sexually transmitted infections affect hundreds of millions of worldwide. Both human immunodeficiency virus (HIV-1 and -2) and herpes simplex virus-2 (HSV-2) remain incurable, urging the development of new prevention strategies. While current prophylactic technologies are dependent on strict user adherence to achieve efficacy, there is a dearth of delivery vehicles that provide discreet and convenient administration, combined with prolonged-delivery of active agents. To address these needs, we created electrospun fibers (EFs) comprised of FDA-approved polymers, poly(lactic-co-glycolic acid) (PLGA) and poly(DL-lactide-co-ε-caprolactone) (PLCL), to provide sustained-release and in vitro protection against HIV-1 and HSV-2. PLGA and PLCL EFs, incorporating the antiretroviral, tenofovir …

Addiction: Physiology In Performance, Opioid Pharmacology In Character Development For The Theater, Lacey M. Smith

Honors Thesis

Actors inquire into the physical, mental, and emotional impulses of their respective characters in the effort to develop a cohesive persona for the stage. The goal of this research is to determine whether a more thorough, scientific understanding of the physiopyschological phenomena a character experiences, specifically opioid withdrawal, will aid in the depiction of symptoms on stage. The project began with a research period and culminated in physical dissemination through theater performance. Both video, audio, and text media were utilized to establish a thorough comprehension of the physiological mechanisms in opioid addiction. Further profiling of the characteristics and symptomatic episodes …

Novel Reversal Agents For Non-Vitamin K Oral Anticoagulants, Kimberly Hoilman, Melanie Reyer

Physician Assistant Capstones, 2016 to 2019

Background Non-vitamin K oral anticoagulants have become an appealing alternative treatment for the prevention of stroke in non-valvular atrial fibrillation and in treatment of venous thromboembolism. The major limitation to the use of these drugs is the lack of reversal agents. The purpose of this review is to investigate the development and efficacy of novel agents for reversal of NOACs. Methods Two separate literature searches were conducted in the PubMed database using the terms “prothrombin complex concentrate” and “idarucizumab”, respectively. Only in vivo clinical trials involving human subjects within the last five years were included for possible analysis. Studies with …

Studies On The Prevalence And Control Of Parasitic Helminths In "Natural" Laying Hens, Brittany R. Weir

Animal Science Undergraduate Honors Theses

One societal trend that has been gaining much traction and popularity since the 21^st century began is “organic” and/or “natural” food products. In 1999, the global market accounted for $15.2 billion dollars worth of organic food and drink, compared to the market in 2014 where we consumed $80 billion dollars worth (Willer et. al, 2016). With “natural” production of food animals however, “natural” parasite transmission may be a consequence. To that end, this experiment examines the prevalence of helminths in 110 “natural” laying hens from three regional farms and the efficacies of fenbendazole, piperazine, and levamisole on what should …

Comparing The Quantitation Of Opiates From Possible Drug Overdose Cases Using Results Of Blood Analysis And Liver Analysis, Lee Ann Garozzo

Forensic Science Theses

Currently the quantitation of opiates at the Erie County Medical Examiner’s Office Toxicology Laboratory is conducted through whole blood analysis. The objective of this thesis project was to determine if the analysis of opiates could be conducted through liver analysis, and if the analysis of opiates would provide a more accurate quantitation compared to the blood analysis. The quantitation of opiates was conducted from the livers of sixty-four possible overdose cases that were brought into the Erie County Medical Examiner’s Office between 2013 and 2015. Results showed that the opiate drugs could successfully be quantitated using the liver analysis. Generally …

Anti-Cancer Diets: Revolution Or Ruse?, Lauren Hogan

First Year Inquiry: Student Scholarship & Creative Works

This paper discusses how the foods we consume can play a role in the diagnosis of cancer.

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, …

Identification Of Potential Drug Targets In Cancer Signaling Pathways Using Stochastic Logical Models, Peican Zhu, Hamidreza Montazeri Aliabadi, Hasan Uludag, Jie Han

Pharmacy Faculty Articles and Research

The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no …

Inhibition Of Human Α7 Nicotinic Acetylcholine Receptors By Cyclic Monoterpene Carveol, Yusra Lozon, Ahmed Sultan, Stuart J. Lansdell, Tatiana Prytkova, Bassem Sadek, Keun-Hang Susan Yang, Frank Christopher Howarth, Neil S. Millar, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Cyclic monoterpenes are a group of phytochemicals with antinociceptive, local anesthetic, and anti-inflammatory actions. Effects of cyclic monoterpenes including vanilin, pulegone, eugenole, carvone, carvacrol, carveol, thymol, thymoquinone, menthone, and limonene were investigated on the functional properties of the cloned α₇ subunit of the human nicotinic acetylcholine receptor expressed in Xenopus oocytes. Monoterpenes inhibited the α₇ nicotinic acetylcholine receptor in the order carveol>thymoquinone>carvacrol>menthone>thymol>limonene>eugenole>pulegone≥carvone≥vanilin. Among the monoterpenes, carveol showed the highest potency on acetylcholine-induced responses, with IC₅₀ of 8.3 µM. Carveol-induced inhibition was independent of the membrane potential and could not be …

Artificial Sweeteners And Weight Gain: Fighting Or Feeding The Obesity Epidemic?, Shanna Frisch

The Science Journal of the Lander College of Arts and Sciences

Our world has developed an obsession with weight control and, as a result, has begun replacing high calorie foods with low-fat and non-caloric substitutes. Artificial sweeteners are a widely used solution to this growing problem. Though the intention when using artificial sweeteners is to lose weight, studies have shown that the opposite sometimes occurs. Researchers attempt to explain this surprising phenomenon with multiple hypotheses. Lack of appetite suppression and reward response may cause individuals to search for more food and to consume more calories. Artificial sweeteners can also have negative affects on biological mechanisms such as resting metabolic rate, as …

Synthesis And Biochemical Evaluation Of 3-Phenoxy-1,4-Diarylazetidin-2-Ones As Tubulin-Targeting Antitumor Agents, Thomas F. Greene, Shu Wang, Lisa M. Greene, Seema M. Nathwani, Jade K. Pollock, Azizah M. Malebari, Thomas Mccabe, Brendan Twamley, Niamh O'Boyle, Daniela M. Zisterer, Mary J. Meegan

Articles

Structure-activity relationships for a series of 3-phenoxy-1,4-diarylazetidin-2-ones were investigated leading to the discovery of a number of potent antiproliferative compounds, including trans-4-(3-hydroxy-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (78b) and trans-4-(3-amino-4-methoxyphenyl)-3-phenoxy-1-(3,4,5-trimethoxyphenyl)azetidin-2-one (90b). X-ray crystallography studies indicate the potential importance of the torsional angle between the 1-phenyl ‘A’ ring and 4-phenyl ‘B’ ring for potent antiproliferative activity, and that a trans configuration between the 3-phenoxy and 4-phenyl rings is generally optimal. These compounds displayed IC₅₀ values of 38 nM and 19 nM respectively in MCF-7 breast cancer cells, inhibited the polymerization of isolated tubulin in vitro, disrupted the microtubular …

Piperlongumine (Piplartine) And Analogues: Antiproliferative Microtubule-Destabilising Agents, Mary J. Meegan, Seema M. Nathwani, Brendan Twamley, Daniela M. Zisterer, Niamh O'Boyle

Articles

Piperlongumine (piplartine, 1) is a small molecule alkaloid that is receiving intense interest due to its antiproliferative and anticancer activities. We investigated the effects of 1 on tubulin and microtubules. Using both an isolated tubulin assay, and a combination of sedimentation and Western blotting, we demonstrated that 1 is a tubulin-destabilising agent. This result was confirmed by immunofluorescence and confocal microscopy, which showed that microtubules in MCF-7 breast cancer cells were depolymerised when treated with 1. We synthesised a number of analogues of 1 to explore structure-activity relationships. Compound 13 had the best cytotoxic profile of this series, …