Other Chemicals and Drugs Commons^™

Novel 3,6-Disubstituted Pyridazine Derivatives Targeting Jnk1 Pathway: Scaffold Hopping And Hybridization-Based Design, Synthesis, Molecular Modeling, In Vitro And In Vivo Anticancer Evaluation., Mai M. Shaalan, Essam Eldin A. Osman, Yasmeen M. Attia, Olfat A. Hammam, Riham F. George, Bassem H. Naguib

Pharmacy

A series of novel 3,6-disubstituted pyridazine derivatives was designed, synthesized, and biologically evaluated as preclinical anticancer candidates. Compound 9e exhibited the highest growth inhibition against most of the NCI-60 cancer cell lines. The in vivo anticancer activity of 9e was subsequently investigated at two dose levels using the Ehrlich ascites carcinoma solid tumor animal model where a reduction in the mean tumor volume allied with necrosis induction was reported, without any signs of toxicity in the treated groups. Interestingly, compound 9e was capable of downregulating c-jun N-terminal kinase-1 (JNK1) gene expression and curbing the protein levels of its phosphorylated form, …

Successful Rapid Benzodiazepine Detoxification In An Acute Care Hospital: A Case Report, Taku Harada, Kazuki Tatebayashi, Mori Nakai

Journal of Community Hospital Internal Medicine Perspectives

Introduction: Benzodiazepine (BZD) dependence and withdrawal are significant public health concerns, affecting 15–30% of regular users within 4-6 weeks of administration. Rapid BZD tapering protocols in acute care settings can mitigate withdrawal symptoms and facilitate rehabilitation, yet are challenging due to variability in patient responses. Case Presentation: We report a case of a 67-year-old male with a history of high-dose BZD use for panic disorder and depression and recent mild ischemic stroke, presenting with worsening left lower limb paralysis. The patient's complex medication regimen included multiple BZDs and other psychotropic drugs. Given the risks associated with high-dose BZD use, particularly …

Amiodarone-Induced Lung Toxicity: An Underrecognized And Fatal Presentation, Andrew Takla, Fahad Eid, Hina Ukrani, Moghniuddin Mohamed, Elizabeth Lee

Advances in Clinical Medical Research and Healthcare Delivery

Amiodarone, a widely utilized antiarrhythmic drug, poses a significant risk of amiodarone-induced lung toxicity (ALT) in up to 10% of patients and can be fatal. This report presents the diagnostic challenges associated with ALT, given its non-specific clinical and radiological presentation. Clinicians should maintain a high index of suspicion for potential ALT, especially in patients with progressive respiratory failure despite optimization of other potential causes such as CHF. The mainstay of treatment is discontinuing amiodarone and initiating steroids. However, outcomes can remain unpredictable, emphasizing the need for heightened awareness and regular monitoring of patients on amiodarone therapy.

Combined Use Of Donepezil And Memantine Increases The Probability Of Five-Year Survival Of Alzheimer’S Disease Patients, Ehsan Yaghmaei, Hongxia Lu, Louis Ehwerhemuepha, Jianwei Zheng, Sidy Danioko, Ahmad Rezaie, Seyed Ahmad Sajjadi, Cyril Rakovski

Mathematics, Physics, and Computer Science Faculty Articles and Research

Background

Alzheimer’s disease (AD) is the most common neurodegenerative disease. Studying the effects of drug treatments on multiple health outcomes related to AD could be beneficial in demonstrating which drugs reduce the disease burden and increase survival.

Methods

We conducted a comprehensive causal inference study implementing doubly robust estimators and using one of the largest high-quality medical databases, the Oracle Electronic Health Records (EHR) Real-World Data. Our work was focused on the estimation of the effects of the two common Alzheimer’s disease drugs, Donepezil and Memantine, and their combined use on the five-year survival since initial diagnosis of AD patients. …

Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication, Lay Paw

Honors Projects

Viruses, including herpesviruses, contribute up to 15% of all human cancers. Murine gammaherpesvirus-68 (MHV-68), a pathogen commonly found in mice, is studied due to its shared homology with several human herpesviruses. Studies done in the Delgado lab via metabolomics analysis show MHV-68 infected cells increase host cell metabolism. Clinically relevant metabolic inhibitor drugs, ɑ-Difluoromethylornithine (DFMO) and Orlistat, respectively block polyamine and lipid production demonstrated a reduction in MHV-68 viral production. Repurposing clinically relevant drugs through the exploration of a different target shows great promise in reducing oncogenic viral titer.

Understanding The Relationship Between How The Availability Of Vaping Devices And Student Use Are Related: A Quantitative Study, Felicia L. Owen

ATU Theses and Dissertations 2021 - Present

The number of teens in Arkansas who are vaping continues to increase despite state and national laws and regulations. The availability of vaping devices to teens continues to occur; but limited research is available that explores if the availability is accessible through peers, families, or community members, or is self-sought. It is crucial to gain a better understanding of why vaping continues to increase among high school students in Arkansas. The purpose of this study is to understand the relationship between how the availability of vaping devices and student use are related. The analysis of exposure and student use varies …

Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5⁺ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …

Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith

Theses & Dissertations

Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …

The Effects Of Psychedelic Microdosing On Mental Health: A Systematic Review, David F. Lo, Hasan Zia, Adarsh Thakur, Praneetha Rajkumar, Don D. Shamilov

Rowan-Virtua Research Day

This poster explores the effects of psychedelic microdosing on mental health conditions. Roughly 5.5 million individuals in the U.S. utilize psychedelics to treat their mental health issues. The primary substances used for microdosing currently include LSD and psilocybin, but mescaline, DMT, and amphetamines are used less commonly. This systematic review included 16 unique articles. The types of articles included: observational, placebo, self-reported, motivational, literature review, and comparative studies. The studies indicated lower levels of anxiety, depression, and stress among those that microdose. However, drawbacks such as difficulty sleeping and headaches were reported. Various studies have been published on the effects …

Vitamin Level Differences Across The Asd Spectrum, Rohan Mehra, Wendy F. Aita, Andrea Iannuzzelli

Rowan-Virtua Research Day

Background: In the United States, 2.7% of children are diagnosed with Autism Spectrum Disorder (ASD). Environmental factors such as vitamin levels, including D, B9, and B12, may have a significant impact on the risk of development. Children conceived in winter months, with low sunlight and Vitamin D levels, have a higher risk of developing ASD. Vitamin B12 deficiency is generally linked with an increased risk of neurodevelopmental disorders. Additionally, vitamin B9 deficiency of a mother during gestation is linked to a higher risk of her child developing ASD.

Purpose: To assess potential differences in vitamin levels between patients of differing …

Sdrnas Participate In The Maintenance And Onset Of Prostate Cancer, Neil Chaudhary

Poster Presentations

What is an sdRNA? Noncoding RNA (ncRNA) is a class of RNA that includes microRNA (miRNA) and small nucleolar RNA (snoRNA). Fragments excised from ncRNAs are known as noncodingderived RNA (ndRNA). A certain class of ndRNAs that are derived from snoRNAs have been denoted as Small Nucleolar Derived RNAs (sdRNAs). Our lab has previously hypothesized and demonstrated that sdRNAs display regulatory functions on target genes, similar to the functions of miRNAs. sdRNAs are almost identical to microRNAs and differ mainly in their source of origin.

Our lab has shown that sdRNA-93 is frequently misexpressed in breast cancer cell lines and …

Investigating The Antibacterial Properties Of Capsaicin In Synergy With Antibiotics Against A. Baumannii, Jack Guffey

Undergraduate Theses

As the ever-increasing issue of antibiotic resistance looms, naturally derived compounds have been increasingly investigated as possible synergists with antibiotics. One of these compounds, capsaicin, is a potent vanilloid that is the dominant cause of Capsicum peppers’ spiciness. Capsaicin’s intrinsic ability to inhibit a wide array of bacterial growth has been well documented. The focal organism of this study, Acinetobacter baumannii, has become an increasingly common hospital acquired infection due to its persistence on fomites. Capsaicin, however, is able to inhibit this growth at higher concentrations as well as reduce the necessary minimum inhibitory concentration while decreasing biofilm formation …

Photon Irradation And Cisplatin Enrich Cancer Stem Cells In Ovarian Cancer, Ashley Antonissen

Electronic Theses, Projects, and Dissertations

High Grade Serous Ovarian Cancer (HGSOC) has a 5-year survival rate of less than 50%. Ovarian cancer is one of the deadliest gynecological diseases and the 7th most common female cancer worldwide. Ovarian cancer patients generally have a poor prognosis despite the relatively successful treatments. When conventional cancer treatments, such as cisplatin chemotherapy and photon irradiation, are administered, residual cancer stem-like cells (CSCs) can survive, leading to CSC enrichment. CSCs are a small population of cancer cells that exhibit stem-like characteristics: quiescence (slowing of the cell cycle), differentiation, proliferation, and self-renewal to regenerate new CSCs. We hypothesized that providing cancer …

Beyond Mitragynine: Composition Survey And Stability Assessment Of Kratom Tea Ordered Via Food Delivery Platforms In Bangkok, Thailand, Yuta Tokuda, Apinya Tubtimrattana, Nat Tansrisawad, Kornvalee Meesilpavikkai, Parath Thirati

Chulalongkorn Medical Journal

Background: Kratom is a native tree to Southeast Asia. Kratom leaves have long been used medicinally and recreationally due to their stimulative and opioid-like effects attributed to high endogenous levels of mitragynine and related alkaloids. Kratom is widely consumed as tea and is now publicly sold, including on food delivery platforms, after recent decriminalization despite selling of kratom products being still considered illegal by other acts.

Objectives: To assess the formulas of kratom teas sold on Thai food delivery platform together with their consistency and the stability of refrigerated teas.

Methods: Kratom alkaloids, mitragynine and 7-hydroxymitragynine, and additive contents of …

Killing Cancer: Manipulating Hydrophobic Vanadium Complexes To Improve Anti-Cancer Activity, Levi Ausherman, Debbie C. Crans, Peter A. Lay, Maggi Braasch-Turi

SACAD: Scholarly Activities

Hydrophobic vanadium complexes have recently shown improved anti-cancer activities compared to cisplatin. The hydrophobicity and anti-proliferative activity of [VO(Hshed)(dtb)] ([Hshed= N-(salicylideneaminato)-N’-(2-hydroxyethyl)-1,2-ethanediamine and dtb= 3,5-di(tert-butyl)catechol)]) have inspired the development of a library of hydrophobic vanadium complexes. Increasing the steric bulk of the catechol ligand has been shown to have a direct impact on hydrophobicity and anti-proliferative activities. Currently at Fort Hays State University, the Braasch-Turi group is synthesizing VO(HSHED)(dtb) to build up material to support the chemical analysis and biological assay performed by our collaborators at Colorado State University and the University of Sydney, Australia, respectively. In the future, we plan …

Cold Medicine Abuse And Increased Odds Of Recreational Drug Use, Luis Barco

Posters - 2024

Over the counter (OTC) medications are frequently used to address the symptoms associated with common illnesses that affect the public. (SOURCE) Of these OTC medications, cold and cough medications are some of the most widely used. However, cold medications pose a risk in exhibiting different effects depending on which active ingredient is the most prevalent. Dextromethorphan (DXM), one of the most common ingredients in cough medicine, can lead to the development of symptoms that mirror psychosis associated with phencyclidine abuse (1). Though less common, abuse of codeine can also result in the formation of gastric ulcers, internal bleeding, and inflammation …

From Cough To Crip: The Development Of Codeine From A Purely Medical Substance Into A Popular Recreational Drug, Rhett C. Vaughn

Senior Theses

The research that was conducted aimed to elicit the influence that pop culture has on recreational drug consumption. Specifically, the usage of the drug codeine has become very popular in social media among many influencers. The research focuses on the prevalence of this drug across several media platforms, alongside the growing rate of consumption globally. Research was conducted primarily through combining various databases at various organizations and this study aims to compile the data into one coherent paper regarding codeine in pop culture. While, it cannot be solely attributed to one specific outlet or influence, this study found that alongside …

Accurate Characterization Of Binding Kinetics And Allosteric Mechanisms For The Hsp90 Chaperone Inhibitors Using Ai-Augmented Integrative Biophysical Studies, Chao Xu, Xianglei Zhang, Lianghao Zhao, Gennady M. Verkhivker, Fang Bai

Mathematics, Physics, and Computer Science Faculty Articles and Research

The binding kinetics of drugs to their targets are gradually being recognized as a crucial indicator of the efficacy of drugs in vivo, leading to the development of various computational methods for predicting the binding kinetics in recent years. However, compared with the prediction of binding affinity, the underlying structure and dynamic determinants of binding kinetics are more complicated. Efficient and accurate methods for predicting binding kinetics are still lacking. In this study, quantitative structure–kinetics relationship (QSKR) models were developed using 132 inhibitors targeting the ATP binding domain of heat shock protein 90α (HSP90α) to predict the dissociation rate …

Changes In Real-World Dispensing Of Adhd Stimulants In Youth From 2019 To 2021 In California, Anika Patel, Rishikesh Chavan, Cyril Rakovski, Richard C. Beuttler, Sun Yang

Mathematics, Physics, and Computer Science Faculty Articles and Research

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common pediatric neurobehavioral disorders in the U.S. Stimulants, classified as controlled substances, are commonly used for ADHD management. We conducted an analysis of real-world stimulants dispensing data to evaluate the pandemic’s impact on young patients (≤ 26 years) in California.

Methods: Annual prevalence of patients on stimulants per capita across various California counties from 2019 and 2021 were analyzed and further compared across different years, sexes, and age groups. New patients initiating simulants therapy were also examined. A case study was conducted to determine the impact of socioeconomic status on patient …

Psilocybin With Acceptance And Commitment Therapy (Act) For The Treatment Of Social Anxiety Disorder (Sad), Aspen E. Allred

University Honors Theses

Social Anxiety Disorder (SAD) is a debilitating mental health condition characterized by an overwhelming fear and anxiety of social rejection that can lead to chronic patterns of social behavioral avoidance. Despite the existence of traditional efficacious treatments, a significant number of individuals either do not respond to treatment or experience a recurrence of symptoms over extended periods, spanning 10-12 years. Acceptance and Commitment Therapy (ACT), a form of acceptance-based behavioral therapy considered part of the "third wave" of cognitive behavioral therapies, has shown promising results in early studies, comparable to those of Cognitive Behavioral Therapy (CBT) that is considered the …