Other Chemicals and Drugs Commons^™

Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang

Dissertations, Theses, and Capstone Projects

Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community and industry. …

Small Molecule Inhibitors Of Inflammatory Caspases-1, -4, And -5, Christopher D. Ahlers

DePaul Discoveries

Inflammatory caspases-1, -4, and -5 play critical roles in mediating the innate immune response to pathogen- and damage-associated molecular patterns. Caspase-1 produces the cytokine interleukin-1β (IL-1β), while caspases-4 and -5 activate the NOD-like receptor protein 3 inflammasome via the non-canonical pathway. Overactivation of these enzymes is associated with an increased risk for inflammatory diseases such as lupus, psoriasis, and rheumatoid arthritis. Small molecule inhibitors (SMIs) have been developed to attenuate the production of IL-1β, but unfavorable bioavailability and toxicity have provided an insurmountable barrier in clinical trials. This work is concerned with delivering an overview of current progress in the …

Uplc-Ms/Ms Analysis Of The Michaelis-Menten Kinetics Of Cyp3a-Mediated Midazolam 1′- And 4-Hydroxylation In Rat Brain Microsomes, Devaraj Venkatapura Chandrashekar, Barent Dubois, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ) is a short-acting benzodiazepine with rapid onset of action, which is metabolized by CYP3A isoenzymes to two hydroxylated metabolites, 1′-hydroxymidazolam and 4-hydroxymidazolam. The drug is also commonly used as a marker of CYP3A activity in the liver microsomes. However, the kinetics of CYP3A-mediated hydroxylation of MDZ in the brain, which contains much lower CYP content than the liver, have not been reported. In this study, UPLC-MS/MS and metabolic incubation methods were developed and validated for simultaneous measurement of low concentrations of both hydroxylated metabolites of MDZ in brain microsomes. Different concentrations of MDZ (1–500 µM) were incubated with …

Insights Into The Mechanisms Of Brain Endothelial Erythrophagocytosis, Jiahong Sun, Prema Vyas, Samar Mann, Annlia Paganini-Hill, Ane C. F. Nunes, Wei Ling Lau, David H. Cribbs, Mark J. Fisher, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

The endothelial cells which form the inner cellular lining of the vasculature can act as non-professional phagocytes to ingest and remove emboli and aged/injured red blood cells (RBCs) from circulation. We previously demonstrated an erythrophagocytic phenotype of the brain endothelium for oxidatively stressed RBCs with subsequent migration of iron-rich RBCs and RBC degradation products across the brain endothelium in vivo and in vitro, in the absence of brain endothelium disruption. However, the mechanisms contributing to brain endothelial erythrophagocytosis are not well defined, and herein we elucidate the cellular mechanisms underlying brain endothelial erythrophagocytosis. Murine brain microvascular endothelial cells (bEnd.3 …

In-Line Monitoring Of Sitagliptin Dissolution Profile From Tablets Utilizing An Eco-Friendly Potentiometric Sensor, Shereen Mowaka, Manar M. Elhassan, Amr M. Mahmoud, Maha A. Hegazy

Pharmacy

Sitagliptin, an oral antidiabetic drug, is an effective medication for lowering blood glucose level either as monotherapy or in combination with other antidiabetic drugs. This work aims for the fabrication of a potentiometric sensor for sitagliptin detection. The sensor was designed by doping the polyvinyl chloride polymeric ion-selective membrane with calix[4]arene as an ionophore which highly improved the linearity range (1 × 10−6—1 × 10−2 M), sensitivity, selectivity and limit of detection (6.3 × 10−7 M) compared to ionophore-free membrane. The method was then validated according to the International Council for Harmonization (ICH) guidelines. The sensor was successfully employed to …

Exploration Of Patient Variables And Characteristics Best Suited For Medical Marijuana Treatment For Anxiety And Depressive Disorders, Corey Gazoo

Dissertations

Individuals with posttraumatic stress, anxiety and depressive disorders are currently being prescribed medical marijuana as a treatment in many states across the United States. However, marijuana is still considered a schedule one narcotic by the Drug Enforcement Administration and federal government, which provides several barriers and challenges to conduct research such as approval from the U.S. Food and Drug Administration and following guidelines from the National Institute on Drug Abuse issued by the DEA. Additionally, individuals prescribed medical marijuana for mental health disorders are not always thoroughly instructed on the type of medical marijuana, the dosage, and how frequently to …

Complexation Of Glycoalkaloid Α- Tomatine With Sterols And Its Potential Application As An Anti-Cancer Drug, Bishal Nepal

Dissertations

Glycoalkaloids (GAs) are secondary metabolites found mostly in higher plant species and some marine invertebrates. They are known to form complexes with 3β-hydroxy sterols such as cholesterol causing membrane disruption. So far the visual evidence showcasing the complexes formed between glycoalkaloids and sterols has been mainly restricted to some earlier studies using Brewster angle microscopy. This study aimed to develop a method for topographic and morphological analysis of sterol-glycoalkaloid complexes. Langmuir-Blodgett (LB) transfer of monolayers comprising of glycoalkaloid tomatine, sterols, and lipids in varying molar ratios onto mica followed by AFM examination was performed. The AFM method used required minimal …

Ganglioside Alters Phospholipase Trafficking, Inhibits Nf-Κb Assembly, And Protects Tight Junction Integrity, John J. Miklavcic, Qun Li, Jordan Skolnick, Alan B. R. Thomson, Vera C. Mazurak, Michael Tom Clandinin

Food Science Faculty Articles and Research

Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health.

Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. …

Radiologic Contrast-Induced Transmetallation In Mineral Rich Fruits: X-Ray Imaging To Understand Heat Cycling During Climate Change And Map Metal Redistribution In Biological Media For Biomedical Applications, Lin Mousa, Hayley Sanchez, Subhendra Sarkar, Zoya Vinokur

Publications and Research

Heat cycling due to climate change can affect hydrated protein or carbohydrate functions, the latter is not well studied. The project started with involving the study of heat-stressed carbohydrate behavior when bulk water was partly stripped from carbohydrates in model microwaved fruits and vegetables, like apples and sweet potatoes (that are mineral-rich) and was set in mineral exchange competition with toxic metals like Gadolinium and chelating complexes like iodinated EDTA. These are common radiologic contrast medias that strongly absorb x-rays and are currently implicated in man-made environmental toxins. Our goal was to map diffusion of injected heavy atoms as well …

A Comparative Study On Cannabidiol In Melanoma Migration And Invasion: Charlotte's Web Vs. Purified Cbd, 2020–2021, Ruby Thamert

Theses

Over the last decade, much attention has been focused on compounds from Cannabis sativa in treating a variety of diseases including cancer. This study examines the abilities of two different cannabidiol oils to decrease the migration and invasion of melanoma cells in vitro. Skin cancers are the most common cancers in the world. While malignant melanoma is the least common type of skin cancer, it is the deadliest. Patients diagnosed with stage IV disease have only a 15-20% five-year survival rate even with aggressive multimodal treatment, demonstrating the need for additional therapeutic options. Because melanoma is often fatal when …

The Effect Of Diazepam On Early Neural Stem Cells Proliferative Activity And Hippocampal-Dependent Memory After Traumatic Brain Injury, Van Khanh Doan

University Honors Theses

Traumatic brain injury (TBI) induces an upregulation of neurogenesis in the brain specifically in the hippocampus, an area pertaining to learning and memory formation. Although this upregulated response is intuitively thought to be restorative, previous studies show that the nascent neurons generated after TBI exhibit abnormalities, such as aberrant morphologies and early migrations, which could suggest to be maladaptive. The GABA-A agonist diazepam has been shown to inhibit this upregulation in neurogenesis and normalizes dendrites after TBI. To determine whether this modulation of neurogenesis is ultimately beneficial or detrimental to cognitive recovery, diazepam was administered to C57BI/6J wild-type mice following …

Formulation Of Coffee Extract As Polymeric Nanoparticles And Studying Their Potential Biological Activities, Nouran Sharaf

Theses and Dissertations

Coffee extract was prepared and optimized (by solvent extraction) and subsequently entrapped into PLGA nanoparticles using single emulsion-solvent evaporation method (using Design Expert software). Dynamic Light Scattering, Scanning Electron Microscope, Fourier Transform-Infrared Spectroscopy and Folin Ciocalteau assay were used to characterize the NPs and to aid in selecting the optimum formulation conditions. The optimized NPs were in-vitro evaluated for their antimicrobial (by agar-well diffusion method), antioxidant (by DPPH assay) and anticancer (by MTT assay) activities. Finally, the release rate study was conducted for the NP sample showing the highly promising results.

The succeeded NP sample, in terms of the most …

Differential Effect Of Proinflammatory Cytokines On Corneal And Conjunctival Epithelial Cell Mucins And Glycocalyx, Kiumars Shamloo, Priya Mistry, Ashley Barbarino, Christopher Ross, Vishal Jhanji

Pharmacy Faculty Articles and Research

Purpose: Ocular surface mucins and glycocalyx are critical for providing ocular hydration as well lubrication and repelling pathogens or allergens. Elevated levels of tear proinflammatory cytokines in dry eye may have detrimental effect on mucins and glycocalyx. The present study tested the effect of proinflammatory cytokines IL-6, TNF-α, and IFN-γ on membrane-tethered mucins expression, glycocalyx, and viability of ocular surface epithelial cells.

Methods: Stratified cultures of human corneal and conjunctival epithelial cells were exposed to different concentrations of IL-6, TNF-α, and IFN-γ for 24 hours. The mucins gene and protein expressions were quantified by real-time polymerase chain reaction …

The Comorbidity Of Drug And Alcohol Consumption In Relation To Mental Health Disorders, Sydney Dawson

Intuition: The BYU Undergraduate Journal of Psychology

The constantly increasing use of drugs and alcohol in young adults has created great controversy in the medical community on the long-term effects of these substances. The average brain development of adolescence and young adults is not complete until the age of 25, though drug and alcohol intake occur across the United States at younger ages each year. Impulsive behavior and underdeveloped neural pathways create a strong pull for addiction formulations and the development of severe mental-health problems. This paper reviews the positive and negative effects of illicit drugs and alcohol intake and their comorbidity with mental health disorders. There …

Making The Case For Psychedelics: Comparing Alternative Treatment Options For Depression, Nicole Amavisca

Undergraduate Honors Theses

Given the number of people who are treated for depression each year and the knowledge that treatments work differently for everyone, there is a pressing need to provide a variety of treatment options. Although psychedelic research had been halted for a few decades due to recreational abuse, there has been revived interest due to its therapeutic potential in the treatment of mood disorders and addiction. As an example, the hallucinogen ketamine has recently been approved as a treatment for depression, which has opened the door for broadening the discussion on psychedelic research. Although the research is limited, psilocybin mimics ketamine …

Posterior Reversible Encephalopathy Syndrome After Dinutuximab, Kayeleigh Higgerson Do, Chandni Dargan Md

Research Days

Background: Posterior reversible encephalopathy syndrome (PRES) is a reversible disorder associated with edema of subcortical white matter and cortical gray matter that usually involves the occipital and parietal lobes. Endothelial injury secondary to abrupt blood pressure changes breaks down the blood brain barrier leading to brain edema. Per the ANBL0032 Fall 2015 Study Progress Report, Dinutuximab was the probable cause of PRES in two patients. There have been published reports of PRES with other anti-GD2 antibody therapies but very few reports of Dinutuximab as the causative agent.

Objectives/Goal: To report a case of PRES after Dinutuximab

Methods/Design: Case Report

Results: …

Reeling In New Antibiotics: Synthesis And Antimicrobial Susceptibility Testing Of Zinc-Binding Clavanins From Styela Clava (Sea Squirt), Eduardo Badillo-Colberg

Honors Scholar Theses

Clavanins have been a quite rarely studied antimicrobial peptide (AMP) family. Though the data in the few studies published on the matter and in theoretical experimental data presented by the Wang lab in their peptide library creation [14], in that the members of this family could potentially be quite effective novel antimicrobial candidates. Among those that have been targets of studies, Clavanin A has been at the forefront of this endeavor of finding effective novel antimicrobial peptides[14]. In these aforementioned studies, Clavanin A has been shown to be quite effective against many different bacterial strains, which begs the question as …

Characterization Of Di-Aryl Urea Compounds Against Acute And Chronic Toxoplasma Gondii, Austin Sanford

Theses & Dissertations

Toxoplasma gondii is an obligate intracellular parasite that has infected nearly 60 million individuals in the United States alone. Acute infection causes ill effects to the fetus in utero when mothers are primarily infected, and to immunocompromised individuals. Chronic infection consists of quiescent tissue cysts located primarily in brain tissue and is capable of reverting back to the acute stage causing severe toxoplasma encephalitis in immunocompromised individuals. Current treatments for acute infection are lacking while there are no approved treatments for the clearance of chronic infection. The aim of this research was to evaluate a family of di-aryl urea compounds …

Fucoxanthin: A Review Of Potential Benefits Relative To Human Health, Michael R. White

Masters Theses, 2020-current

Fucoxanthin is a carotenoid sourced and extracted mainly from dark orange and brown seaweeds found in the pacific ocean, such as the wakame algae. The allenic bonds and unique oxygen groups give fucoxanthin its unique structure and are thought to be part of the reason fucoxanthin has unique physiological functions. Fucoxanthin has potentially numerous effects on the physiology of human health, ranging from skin health to metabolic health, which have been demonstrated in animal model research. The goal of this review is to examine current literature to discuss fucoxanthin’s potential application as a nutraceutical, treatment for obesity, type 2 diabetes, …

Interfacial Dynamics And Ionic Transport Of Radiologic Contrast Media In Carbohydrate Matrix: Utility And Limits Of X-Ray Imaging, Lin Mousa, Hayley Sanchez, Subhendra Sarkar, Zoya Vinokur

Publications and Research

Hello, our names are Lin Mousa and Hayley Sanchez, this semester we participated in a research project dedicated to analyzing the interactions of contrast media with the molecular components of fruits to compare how they would react with the human brain. This project involved the injection of fruits with varying contrasts and the imaging of the diffusion and interactions of the contrast within the fruits with X-rays. With setup technical parameters on the x-ray equipment images were taken with identical setups at an hourly rate for several days. The final results of this experiment indicated that contrasts such as Gadolinium …