Chemicals and Drugs Commons^™

Therapeutic Application Of Carbon Monoxide In Acute Limb Compartment Syndrome, Aurelia Bihari

Electronic Thesis and Dissertation Repository

Acute limb compartment syndrome (CS), a devastating complication of musculoskeletal trauma, develops in response to elevation of the pressure within a closed osseofascial compartment, producing muscle- and limb-threatening ischemia. Full decompression of all involved compartments by fasciotomy is the current gold-standard therapy, but it must be performed within a surgical window of 6-8 hours, before tissue damage becomes permanent.

Carbon monoxide (CO), a byproduct of heme metabolism, has been shown protective in ischemia. While inhalation of CO leads to elevation of carboxyhemoglobin (COHb), recent development of transitional metal carbonyls, CO-releasing molecules (CO-RMs), particularly the water-soluble CORM-3, delivers CO in a …

Neurofeedback Or Neuroplacebo?, Robert T. Thibault, Michael Lifshitz, Amir Raz

Psychology Faculty Articles and Research

This scientific commentary refers to ‘Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia’, by Schabus et al.. (doi:10.1093/brain/awx011).

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 …

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 …

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 …

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 …

“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 …

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 …

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 …

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 …