Chemicals and Drugs Commons^™

Structure-Function Investigation Of Proteins Involved In Cellulose Biosynthesis By Escherichia Coli, Thomas Brenner

Theses and Dissertations (Comprehensive)

Bacteria thrive within multicellular communities called biofilms consisting of a self-produced matrix. Biofilm matrices improve bacterial adherence to surfaces while creating a barrier from host immune responses, disinfectants, antibiotics and other environmental factors. Persistent colonization by the widely distributed pathogens, Escherichia coli and Salmonella spp., has been linked to production of biofilms composed of the exopolysaccharide cellulose. Cellulose-containing biofilms are also important to Acetobacter, Sarcina, Rhizobium and Agrobacterium species to form symbiotic and pathogenic interactions. In Enterobacteriaceae, two operons (bcsABZC and bcsEFG) are proposed to encode for proteins that form a cellulose biosynthetic complex that spans the …

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 …

Infusion Of Essentail Oils In Agarose Gels To Create Antimicrobial Surfaces, Simran Guron

Honors College Theses

The current use of antibiotics is very excessive in multiple settings, from treating patients to being present in cleaning products. This overuse of antibiotics is resulting in multiple consequences, ranging from having a negative impact on human health to breeding antibiotic-resistant strains of microorganisms. Antimicrobial surfaces are useful today to aid in sterilization, especially in the medical setting. This would help prevent the spread of infection of microorganisms in these settings. In our research, agarose acts as the antimicrobial surface and essential oils would act as the solution incorporated into the surface that has the antimicrobial properties. Agarose is a …

Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker

All Master's Theses

The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition …

Identification Of “Kratom” (Mitragyna Speciosa) Alkaloids In Commercially Available Products, Julia Grzymkowski, Michelle R. Peace, Justin Poklis

UROP Posters

“Kratom” is the common name for the botanical mitragyna speciosa. It is a tree native to Southeast Asia in which leaves contain the psychoactive alkaloids mitragynine and 7-hydroxymitragynine. Kratom is often ingested as teas, chewed, or smoked. It acts as a stimulant in small doses and as an opioid in large doses. Overdoses can result in vomiting, seizures, and death. Recently the Drug Enforcement Agency (DEA) placed Kratom on Schedule 1, but, due to public outcry, it was almost immediately removed.

Eleven kratom based products were obtained from various tobacco shops, “headshops” and via the internet including: Choice brand …

Borneol, A Novel Agent That Improves Central Nervous System Drug Delivery By Enhancing Blood–Brain Barrier Permeability, Qun-Lin Zhang, Bingmei M. Fu, Zhang-Jin Zhang

Publications and Research

The clinical application of central nervous system (CNS) drugs is limited by their poor bioavailability due to the blood–brain barrier (BBB). Borneol is a naturally occurring compound in a class of ‘orificeopening’ agents often used for resuscitative purposes in traditional Chinese medicine. A growing body of evidence confirms that the ‘orifice-opening’ effect of borneol is principally derived from opening the BBB. Borneol is therefore believed to be an effective adjuvant that can improve drug delivery to the brain. The purpose of this paper is to provide a comprehensive review of information accumulated over the past two decades on borneol’s chemical …

Synergism Of Quercetin And Sodium Butyrate For Controlling Growth Of Glioblastoma, Matthew Alan Taylor

Theses and Dissertations

Glioblastoma multiforme (GBM), or simply glioblastoma, is the most common and aggressive primary brain tumor, with a prevalence of approximately 20,000 new cases per year in the United States and a 3-year survival rate of just 2%. Quercetin (QCT) is a dietary flavonoid that can be found in common foods such as red kidney beans, cilantro, and onions. Despite little evidence showing any benefits through dietary intake of QCT, various studies show its promising anti-cancer results in vitro. In glioblastoma, QCT is able to cause significant amounts of apoptosis through a variety of mechanisms. These include activation of caspase-9 and …

Investigation Of Anticoagulation Properties Of Sulfated Glycosaminoglycan Mimetics, Elsamani I. Abdelfadiel

Theses and Dissertations

Abstract

INVESTEGATION OF ANTICOAGULATION PROPERTIES OF SULFATED

GLYCOSAMINOGLYCAN MIMETICS

By Elsamani Ismail Abdelfadiel, MS

A thesis submitted in partial fulfillment of the requirements for the degree of Master of

Science at Virginia Commonwealth University

Virginia Commonwealth University, 2017.

Supervisor: Umesh R Desai

Professor, Department of Medicinal Chemistry

The existence of thrombosis in numerous pathophysiological situations formed a vast necessity for anticoagulation therapy. Thrombin and factor Xa are the only two factors of the entire coagulation cascade that have been major targets for regulation of clotting via the direct and indirect mechanism of inhibition. Our recent discovery of sulfated non-saccharide glycosaminoglycan …

Chemical Probes For Protein Α-N-Terminal Methylation, Brianna D. Mackie

Theses and Dissertations

While protein α-N-terminal methylation has been known for nearly four decades since it was first uncovered on bacteria ribosomal proteins L33, the function of this modification is still not entirely understood. Recent discoveries have demonstrated α-N-terminal methylation is essential to stabilize the interactions between regulator of chromosome condensation 1 (RCC1) and chromatin during mitosis, to localize and enhance the interaction of centromere proteins (CENPs) with chromatin, and to facilitate the recruitment of DNA damage-binding protein 2 (DDB2) to DNA damage foci. Identification of N-terminal methyltransferase 1 (NTMT1) unveiled the eukaryotic methylation writer for protein α-N-termini. In addition, NTMT2 that shares …

Rapid Detection Of In Vitro Antituberculous Drug Resistance Among Smear-Positive Respiratory Samples Using Microcolony Detection-Based Direct Drug Susceptibility Testing Method, Irim Iftikhar, Seema Irfan, Joveria Farooqi, Zahida Azizullah, Rumina Hasan

Department of Pathology and Laboratory Medicine

Background: With the rise in multidrug-resistant tuberculosis, there is a search for newer techniques that will rapidly detect drug-resistant Mycobacterium tuberculosis. Although molecular techniques can detect resistance, culture is still considered gold standard, especially in resource-limited settings where quick, cheap, and easy techniques are needed. The aim of the study was to evaluate microcolony method thin layer agar (TLA) for quick detection of resistance against the first- and second-line antituberculous drugs in clinical isolates. This was a cross-sectional study performed at Aga Khan University Hospital.
Material and Methods: A total of 87 Z-N stain smear-positive pulmonary samples were received and …

The Role Of Inflammation In Atherosclerosis, Fatma Saaoud

Theses and Dissertations

Atherosclerosis is both a chronic inflammatory disease and lipid deposition disorder characterized by accumulation of lipids, fibrous tissue, and inflammatory cells in the arterial wall. Thus, investigating the role of inflammation and the immune system in the progression of atherosclerosis may help in the development of novel therapeutics for atherosclerotic disease. Current atherosclerosis therapy is aimed at lipid targets and focused primarily on reducing plasma cholesterol levels. Clinical and experimental data support the critical role of inflammation in atherosclerosis and suggest that reducing inflammation even without affecting lipid levels may reduce the event rate of cardiovascular disease. Yet, no pure …

Muscarinic Acetylcholine Receptor M1’S Impact On Fear Extinction Learning, Joshua R. Mcelroy

Theses and Dissertations

Post-Traumatic Stress Disorder (PTSD) is a mental health disorder that can occur following a traumatic event like combat, assault, or disaster. Individuals with PTSD are unable to extinguish fear memories which can become chronic and disabling. However, it remains unclear why some individuals exposed to a traumatic event develop PTSD while others are resilient. Acetylcholine plays a critical role in fear learning, but its role in fear extinction is less well understood. In this investigation, we used a rat model of fear extinction to determine if individual differences in extinction learning are correlated with markers of cholinergic signaling. Cholinergic markers …

A Rational Design Of A Selective Inhibitor For Kv1.1 Channels Prevalent In Demyelinated Nerves That Improves Their Impaired Axonal Conduction, Ahmed Al-Sabi, Declan Daly, Patrick Hoefer, Gemma K. Kinsella, Charles Metais, Mark Pickering, Caroline Herron, Seshu Kumar Kaza, Kieran Nolan, J. Oliver Dolly

Articles

K+ channels containing Kv1.1 α subunits, which become prevalent at internodes in demyelinated axons, may underlie their dysfunctional conduction akin to muscle weakness in multiple sclerosis. Small inhibitors were sought with selectivity for the culpable hyper-polarizing K+ currents. Modeling of interactions with the extracellular pore in a Kv1.1-deduced structure identified diaryldi(2-pyrrolyl)methane as a suitable scaffold with optimized alkyl ammonium side chains. The resultant synthesized candidate [2,2′-((5,5′(di-p-topyldiaryldi(2-pyrrolyl)methane)bis(2,2′carbonyl)bis(azanediyl)) diethaneamine·2HCl] (8) selectively blocked Kv1.1 channels (IC50 ≈ 15 μM) recombinantly expressed in mammalian cells, induced a positive shift in the voltage dependency of K+ current activation, and slowed its kinetics. It …

Mucosal Fluid Glycoprotein Dmbt1 Suppresses Twitching Motility And Virulence Of The Opportunistic Pathogen Pseudomonas Aeruginosa, Jianfang Li, Matteo E. O. Metruccio, David J. Evans, Suzanne M. J. Fleiszig

Faculty Publications & Research of the TUC College of Pharmacy

It is generally thought that mucosal fluids protect underlying epithelial surfaces against opportunistic infection via their antimicrobial activity. However, our published data show that human tear fluid can protect against the major opportunistic pathogen Pseudomonas aeruginosa independently of bacteriostatic activity. Here, we explored the mechanisms for tear protection, focusing on impacts of tear fluid on bacterial virulence factor expression. Results showed that tear fluid suppressed twitching motility, a type of surface-associated movement conferred by pili. Previously, we showed that twitching is critical for P. aeruginosa traversal of corneal epithelia, exit from epithelial cells after internalization, and corneal virulence. Inhibition …

Similar Adverse Events From Two Disparate Agents Implicate Lipid Inflammatory Mediators For A Role In Anxiety States, Gordon Mccarter, Lauren B. Blanchard

Faculty Publications & Research of the TUC College of Pharmacy

We recently reported a case in which a 54-year-old male experienced maintenance insomnia, generalized anxiety and panic symptoms associated with consumption of a fish oil supplement enriched in eicosapentaenoic acid (EPA). We report here that the same patient has experienced identical but more severe symptoms in response to the use of the leukotriene receptor antagonist montelukast, in accordance with other cases reported to the Food and Drug Administration. Since omega-3 fatty acids like EPA are precursors for the biosynthesis of eicosanoids including leukotrienes, a common factor to these psychiatric adverse events may be perturbations in this highly complex system of …