Pharmacology Commons^™

Variability In Methotrexate Metabolites In A Cohort Of Jia Patients, Nuria Lara Castillo, Mara Becker, Marc Sudman, Susan Thompson, Laura Ramsey

Research Days

Background: Methotrexate (MTX) is the cornerstone disease-modifying anti-rheumatic drug for the treatment of Juvenile Idiopathic Arthritis (JIA). While most patients receiving MTX have a favorable outcome, approximately 30% do not respond, and several experience toxic events, suggesting interindividual difference. Furthermore, evaluation of MTX response takes several months, with the risk of missing the early “window of opportunity” for treatment. Predicting MTX response prior to administration would greatly benefit these patients and their treating physicians by saving valuable time during the early stages of the disease onset. MTX is a folate antagonist and, similar to folate, it undergoes polyglutamation inside the …

Fc Gamma Receptors Facilitate Antigenic Modulation Of Lilrb4 And Function As Predictive Biomarkers In Acute Monocytic Leukemia, Joshua Morse

Dissertations and Theses (Open Access)

Acute monocytic leukemia (monocytic AML) is a subtype of AML marked by a proliferation of abnormal monoblasts. This subtype represents approximately 10% of AML cases. The prognosis of monocytic AML is poor, with a 5-year survival of ~30%. Most patients are diagnosed at an age when they are unlikely to survive first-line non-targeted cytotoxic chemotherapy as a bridge to hematopoietic stem cell transplant (HSCT). Even patients who achieve remission commonly relapse. This population of patients would greatly benefit from precision-targeted therapies but currently there are none approved for monocytic AML.

Leukocyte immunoglobulin-like receptor B4 (LILRB4) is an immune checkpoint expressed …

Investigating Prefrontal Cortex Neuronal Signatures Of Opioid-Induced Risk-Taking Behavior, Cana Quave

Dissertations and Theses (Open Access)

Opioid use disorder occurs alongside impaired risk-related decision-making, but the underlying neural correlates are unclear. We developed an approach-avoidance conflict task using a modified conditioned place preference procedure to study neural signals of risky opioid seeking in the prefrontal cortex, a region implicated in executive decision-making. Following morphine conditioned place preference, rats underwent a conflict test in which fear-inducing cat odor was introduced in the previously drug-paired side of the apparatus. While the saline-exposed control group avoided cat odor, the morphine group included two subsets of rats that either maintained a preference for the paired side despite the presence of …

Investigating The Role Of The Hypocretin/Orexin System In A Novel Model Of Polysubstance Dependence, Tyler Zarin

Electronic Theses and Dissertations

Substance use disorders (SUD) in the United States are steadily increasing. Potent and dangerous substances such as methamphetamine (MA) and fentanyl (FEN) are often co-used as a polysubstance (POLY), either intentionally or unknowingly as FEN is a common adulterant. SUD is characterized by physiological and psychological dependence involving the negative reinforcement of anhedonia and withdrawal which drive hypermotivated drug-taking behaviors. Current theory suggests that recruitment of hypocretin/orexin (HCRT) neuropeptide in reward and stress associated brain regions contributes to drug dependence. Despite strong evidence for HCRT’s role in mono-drug dependence, a relevant model for POLY dependence has yet to be developed, …

Assessing The Behavioral Impact Of Pyridostigmine Bromide In Rats, Noah A. Martin

Honors Theses

Pyridostigmine bromide (PB) is an organophosphate (OP) nerve agent prophylactic used to protect warfighters against chemical warfare agents. OPs inhibit the neural enzyme acetylcholinesterase (AChE) in the brain. This leads to the buildup of acetylcholine, causing respiratory failure, seizures, and death. PB functions by inhibiting ~30% of peripheral AChE temporarily, protecting the enzymes so that the body is able to restore sufficient cholinergic function post-exposure. PB does not cross the blood-brain barrier, though it may still indirectly affect toxicity in the brain due to repeated AChE inhibition throughout treatment, or by inhibition of non-target ChE’s in the blood. The aim …

5-Ht Receptors: Pharmacology And Functional Selectivity, Benjamin R. Cummins, Gerald B. Billac, David E. Nichols, Charles D. Nichols

School of Medicine Faculty Publications

Serotonin 5-HT receptors were one of the first serotonin receptors to be pharmacologically characterized. In mammals, they are expressed throughout the body in nearly every cell and tissue type, with the highest density in cortical layer V of the brain. They are involved in several aspects of normal physiological processes and behaviors and have been implicated in the etiology of neuropsychiatric diseases such as schizophrenia. Atypical antipsychotics have targeted blockade of 5-HT receptors as part of their therapeutic mechanism. More recently, 5-HT receptors have come to prominence for their role as the primary target for psychedelic drugs, which activate this …

Psilocybin Impairs The Extinction Of Contextual Fear In Adult Female, But Not Male, Rats, Lillianna P. Puppel, Aleece K. Al-Olimat, Kylie M. King, Marisa J. Savini, Claire E. Miller, Colin R. Del Valle, Heather R. Sparkman, Brooke E. Bramlage, Phillip R. Zoladz

ONU Student Research Colloquium

Fear-related disorders are often treated with exposure therapy, a technique based on the concept of extinction. However, this type of therapy is ineffective for many individuals, so finding a pharmacological adjunct that augments the extinction of fear could lead to better treatment outcomes. In recent preclinical work, investigators have shown that psychedelics can accelerate the extinction of fear, potentially through their impact on neurotrophic signaling. We previously found that psilocybin exerted sex-dependent effects on the extinction of conditioned fear to an isolated cue (i.e., a tone). Specifically, psilocybin enhanced the extinction of cue fear in male rats but impaired it …

The Pharmaceutical Applications Of Poisonous Compounds Found In Datura Stramonium, Ruby M. Raffaldt

Senior Theses

Datura stramonium is a plant that is known for its toxicity. However, a facet of this plant’s noxious chemicals, namely its tropane alkaloids, can be used medicinally. The aim of this paper was to compile knowledge on the botanical, chemical, and medicinal properties of Datura stramonium L with a focus on atropine, scopolamine, and anisodamine; three tropane alkaloid compounds with the ability to be both a poison and a medicine. Information was compiled using pre-existing studies, articles, and literature reviews on D. stramonium. For each of the three alkaloids, their biosynthetic pathways, targets, administration, distribution, metabolism, and excretion were discussed. …

Enhancing Topical Drug Delivery Of Apremilast Through Niosomal Gel Formulation: Ex Vivo Skin Permeation And In Vivo Evaluation For Psoriasis, Megha Shyam Matlapudi, Anka Rao Areti, Yukti Jaiswal, Veeresh Bantal, Raghavender Medishetti

The Thai Journal of Pharmaceutical Sciences

Background: Psoriasis is a dynamic and chronic disease characterized by inflammatory changes and an increased rate of keratinocyte proliferation leading to the formation of erythematous scleroderma plaques with a silvery sheen. The existing therapies come with shortcomings in terms of effectiveness and leave behind a trail of side effects. Hence, there is a need of alternative therapeutic measures. Objectives: This study aimed to assess the therapeutic potential of Apremilast Niosomal Gel (APR Nio Gel) in treating psoriasis, comparing its effectiveness with conventional gel (APR Gel) and oral suspension (APR Oral) formulations. Materials and Methods: Apremilast niosomes were prepared by thin …

Bacillus Coagulans 198 And L-Glutamine In Combination Attenuated Intestinal Mucositis In A 5-Fu-Induced Balb/C Mouse Model Via Modulation Of Gut Microbial Community Structure And Diversity, Wei-Jen Chen, Siou-Ru Shen, Wei-Hsuan Hsu, Bao-Hong Lee, Yu-Shan Wei, Hui-Fang Chu, Ming-Chung Tseng, Tang-Long Shen

Journal of Food and Drug Analysis

5-Fluorouracil (5-FU) disrupts intestinal cells and causes dysbiosis in the gut microbiota. This study explores the potential of Bacillus coagulans-198 (BC198) to mitigate gut microbiota imbalance and mucositis caused by 5-fluorouracil. L-glutamine is used to alleviate mucositis, and this study found that BC198 exhibits protective effects on the gut, including maintaining a healthy microbiota and reducing intestinal inflammation, regardless of whether L-glutamine is used in combination. Therefore, it can help reduce the deterioration of the gut environment caused by 5-fluorouracil. BC198 can be provided to cancer patients to prevent severe side effects, thereby improving their treatment outcomes and nutritional …

Protective Role Of Hsian-Tsao Ethanol Extract Against Body Fat, Serum Lipid Profiles, And Hepatic Lipid Profiles In High-Fat Diet-Fed Rats, Ching-Chang Cho, Gow-Chin Yen, Hsin-Yi Lee, Chun-Tse Tsai, Wei-Tang Chang, Chin-Lin Hsu

Journal of Food and Drug Analysis

This study investigated the preventive effects of a 40% ethanol extract of Hsian-tsao (40EEHT) on obesity in high-fat diet (HFD)-induced obese rats. Male Wistar rats were administered 0, 100, 200, or 500 mg/kg of 40EEHT, resulting in reduced body weight, total body fat, and hepatic tissue weight after 8 weeks. 40EEHT also decreased adipocyte size, improved lipid profiles, alleviated oxidative stress, and enhanced hepatic antioxidant enzyme activities. Additionally, it regulated fatty acid metabolism by reducing lipogenesis and increasing lipolysis and β-oxidation, suggesting its potential as an anti-obesity dietary supplement.

Xanthohumol As A Potential Therapeutic Strategy For Acute Myeloid Leukemia: Targeting The Flt3/Srpk1 Signaling Axis, Duan-Na Zhang, Wen-Ya Yang, Xiao-Xue Hu, Xiao-Min-Ting Song, Chuan-Jie Guo, Fu Peng, Yu-Zhi Li, Zhi-Xing Cao

Journal of Food and Drug Analysis

Xanthohumol (XN) is an isoprene chalcone found in hops (Humulus lupulus L.), a food ingredient with a wide range of pharmacological activities. The aim of this study was to reveal the therapeutic effect of XN on acute myeloid leukemia (AML) and the potential underlying molecular mechanism. Through network pharmacology analysis, molecular docking, and HTRF determination, XN was shown to inhibit the kinase activities of FLT3 and SRPK1 by targeting their ATP-binding domains, with IC₅₀ values of 1.51 ± 0.44 μM and 0.37 ± 0.15 μM, respectively. By inhibiting AML cell proliferation, promoting apoptosis, regulating autophagy, and inhibiting …

Within-Trial Cost-Effectiveness Of Novel Macrophage-Regulating Treatment On Wound Healing In Patients With Diabetic Foot Ulcers, Hsuan-Yu Su, Chen-Yi Yang, Yi-Hsin Chang, Shyi-Gen Chen, Jui-Ching Chen, Hui-Ju Ho, Huang-Tz Ou, Shihchen Kuo

Journal of Food and Drug Analysis

An M1/M2 macrophage-regulating treatment, ON101 cream, has shown its superior healing efficacy for diabetic foot ulcers (DFUs) versus standard absorbent dressing, according to a phase Ⅲ trial. Given its high cost, corroborating the economic value of ON101 treatment can facilitate clinical and policy decision-makings. This study sought to evaluate the cost-effectiveness of ON101 versus an absorbent dressing for patients with DFUs from Taiwan's healthcare sector perspective. This economic evaluation utilized effectiveness and cost data (in 2022 USD) from a randomized controlled trial of ON101, published literature, and Taiwan’s National Health Insurance program. Incremental cost-effectiveness ratio (ICER) against willingness-to-pay (WTP) threshold …

Method Development For The Determination Of Phosphine Residues In Foods, Shu-Wei Lin, Yu-Ting Liu, Ya-Chun Chou, Yu-Ching Hung, Shu-Han Chang, Ya-Min Kao, Su-Hsiang Tseng, Der-Yuan Wang

Journal of Food and Drug Analysis

Phosphine (PH₃) is a fumigant used for pest control of stored products and foods. In Taiwan, PH₃ has the maximum residue level (MRL) in 14 foods, including dried fruits, vegetables, spices, nuts, crops, roots, and tuber vegetables. In this study, gas chromatography/mass spectrometry coupled with a headspace sampler (HS-GC/MS) was used to determine the PH₃ content in foods. The stability of the PH₃ standard was evaluated either directly using the gas standard or indirectly using zinc phosphide (Zn₃P₂) with an acid. The optimal conditions for the headspace agitator were determined to …

A Deep Dive Into The Orchard Of Health: Exploring The Anti-Cancer And Anti-Aging Potential Of Apple Polyphenols, Li-Ching Chen, Han-Sheng Chang, Yuan-Soon Ho

Journal of Food and Drug Analysis

Apples, a ubiquitous and beloved fruit, harbor a treasure trove of bioactive compounds, with apple polyphenols (APs) taking center stage. This review delves into the latest scientific advancements illuminating the anti-cancer and anti-aging properties of APs. We dissect the intricate mechanisms by which APs combat cancer initiation, progression, and metastasis, highlighting their prowess in inducing apoptosis, inhibiting angiogenesis, and modulating cell signaling pathways. Furthermore, we explore the multifaceted ways APs combat aging, including their potent antioxidant and anti-inflammatory actions, DNA protective effects, and ability to modulate cellular processes like autophagy and metabolism. This comprehensive review underscores the therapeutic promise of …

Editorial: Old Drugs: Confronting Recent Advancements And Challenges, Anna Wiktorowska-Owczarek, Diego Iacono, Magdalena Jasińska-Stroschein

Department of Neurology Faculty Papers

No abstract provided.

Adiporon, Adiponectin Receptor Agonist, Exhibits Antiproliferative And Apoptotic Effects In Ht29 And Hct116 Colon Cancer Cells, Arwa Fairaq, Ashraf N. Abdalla, Alanood S. Algarni, Yosra Alhindi

Saudi Toxicology Journal

AdipoRon is the first synthetic analog of endogenous adiponectin, which is an adipose tissue derived hormone. As it is characterized with pharmacological properties like adiponectin through binding and activating AdipoR1 and AdipoR2 receptors this makes it a target for therapeutic treatments for a multitude of disorders. In this study AdipoRon effect on HT29 and HCT116 colon cancer cells were investigated. Cytotoxic activity of AdipoRon was observed, with a significant inhibition rate in HT29 and HCT116 cells. Moreover, there was a significant decrease in the number of HCT116 colonies by clonogenicity test. In addition, cell migration assay showed significant decrease in …

Awareness Of Aspirin’S Dual Role As An Anti-Cancer Agent And Anti- Thrombotic Agent And Its Association With Medication Adherence To Low-Dose Aspirin: A Cross-Sectional Study, Hadhyah N. Alabdali, Sarah S. Al- Harbi, Layan Z. Sharalahi, Yosra Z. Alhindi

Saudi Toxicology Journal

Background: Aspirin is known to be an effective antithrombotic agent. Multiple studies have been studying its effect on cancer as colorectal cancer. Aim: This study aimed to measure the Awareness of Aspirin's Dual Function as an Anti-Cancer Agent and Anti-Thrombotic among Residents of the Makkah region in the Kingdom of Saudi Arabia. Methods: A cross-sectional study was conducted involving 490 participants from the Makkah region. Data collection was achieved through a self-reported online questionnaire and distributed via social media platforms from period of November 2024 until January 2025. Results: Over 340 of the participants in this research have bachelor's degrees. …

Could Psilocin Rescue Chronic, Stress-Accelerated, Transcriptional Aging In Brain?, Danny R. Craig, Eric M. Blalock

Journal of Pharmacology & Nutritional Sciences

Brain aging (BA) processes are complex, often affect multiple systems, and frequently lead to cognitive decline and increased susceptibility to insults. BA appears to be a primary risk for the development of many prominent neurodegenerative pathologies. The US Census Bureau predicts that the aging population (65+) will represent a greater proportion of the US population than children (under 18) by 2034, dramatically increasing the burden on health-care infrastructure.¹⁷ Several mechanisms of stress driven, aging-related neurologic dysfunction have been advanced in the past 50 years and include: Stress hormone exposure and glucocorticoid cascade;^{7, 16} calcium ion dyshomeostasis;⁸ allostatic …

Putting The Substance In Substantial Evidence: An Evidence-Based Approach To Flexible Drug Regulation, Emanuel Krebs, Tania M. Bubela, Melanie Mcphail, Christopher Mccabe, Dean A. Regier

Office of the Provost

For new drugs or indications, substantial evidence of clinical effectiveness is required for market authorization. In most jurisdictions, substantial evidence is not explicitly defined. Health regulators exercise discretion and are increasingly tolerant of earlier or less mature evidence. To align with flexible evidentiary standards, we argue for the adoption of a principle and, context-based approach to the evidence threshold. Our approach aims to balance the potential benefits and harms of accelerated authorization, low therapeutic value, and safety, based on a value of information (VoI) framework. In our VoI framework, substantial evidence exists when the expected net health value of further …

Overexpression And Biophysical And Functional Characterization Of A Recombinant Fgf21, Phuc Phan, Jason Hoang, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast growth factor 21 (FGF21) is an endocrine FGF that plays a vital role in regulating essential metabolic pathways. FGF21 increases glucose uptake by cells, promotes fatty acid oxidation, reduces blood glucose levels, and alleviates metabolic diseases. However, detailed studies on its stability and biophysical characteristics have not been reported. Herein, we present the overexpression, biophysical characterization, and metabolic activity of a soluble recombinant FGF21 (rFGF21). The far-UV circular dichroism spectra of rFGF21 show a negative trough at 215 nm, indicating that the protein’s backbone predominantly adopts a β sheet conformation. rFGF21 shows intrinsic tyrosine fluorescence at 305 nm. Thermal …

Pharmacodynamics Of Aspirin Through Gestation: Predictors Of Aspirin Response And Association With Pregnancy Outcome, A Prospective Cohort Study, Rupsa C. Boelig, Emily Foecke Munden, Tingting Zhan, Steven E. Mckenzie, Walter K. Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Low-dose aspirin is recommended for prevention of hypertensive disorders of pregnancy (HDP) and preterm birth (PTB) in high-risk pregnancies. There is limited data on factors impacting aspirin response in pregnancy. We aimed to evaluate predictors of aspirin response and association with pregnancy outcome with a prospective study of high-risk pregnancies taking 81 mg aspirin daily. Aspirin response was evaluated with Platelet Function Assay-100 (PFA-100) epinephrine closure time at baseline (< 16 weeks' gestation), follow-up 1 (2-4 weeks after aspirin initiation), and follow-up 2 (28-32 weeks gestation). Multivariable regression was used to identify factors associated with PFA-100 at each visit, and results presented with beta coefficient (B) and confidence interval. The median difference (MD) in PFA-100 in those with and without HDP or PTB was compared. Results included 108 who completed follow-up 1 and 96 who completed both visits with > 75% adherence. PFA-100 was increased from baseline at follow-ups 1 and 2 (MD 37 (27-49); MD 26 (15.5-38.5) respectively). At follow-up 1, obesity (B = -30 (-53 to -7) seconds), …

Antiseizure Medications And Their Differing Effects On Cardiovascular Risk, Aleena Abbasi, Bassil Abbasi, Scott Mintzer, Carla Lopinto-Khoury

Department of Neurology Faculty Papers

This review discusses the differing effects of enzyme-inducing and non-inducing antiseizure medications on cardiovascular risk and their implications for the management strategies of epilepsy patients. Traditional risk markers, including low density lipoprotein, high density lipoprotein and triglycerides, can be altered by both enzyme induction and inhibition. Other markers of vascular risk, including c-reactive protein, non-high-density lipoprotein and homocysteine, are affected by antiseizure medications, although adults and children may have different responses. The overall atherosclerotic risk picture is more complex due to indirect effects such as neuroendocrine function and the metabolic syndrome. Large scale data shows an evolving understanding of cardiovascular …

Pulmonopoly: A Game-Based Approach To Teach And Reinforce Basic Concepts Of Pulmonary Medicine To Medical Students, Michael Dong, James Uricheck, Urvashi Vaid

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

INTRODUCTION: Pulmonopoly is an innovative active-learning medical board game addressses core pulmonary concepts in an engaging, competitive style. The strength of Pulmonopoly lies in its ability to combine ease of setup and play with comprehensive content coverage that comprises a significant proportion of national board examinations, offering a gamification experience that can be readily applied in different settings and modified for learner levels.

METHODS: We created an instructional game, Pulmonopoly, based on pulmonary content delivered to preclinical medical students and required for national board examinations. We invited first-year medical students to participate in 60-minute small-group sessions. Content addressed pulmonary subject …

Retrospective Analysis Of Angiotensin Receptor Blockers And Knee Cartilage Volume In Osteoarthritis: Evidence From The Osteoarthritis Initiative, Parv Kale, Vijay Kale

Annual Research Symposium

No abstract provided.

Pharmacogenomics Implications Of Tamoxifen In Breast Cancer Treatment: Clinical Relevance And Future Directions, Khalda E. M. Elhaj, Mahmoud M. E. Mudawi, Hamad A. Albagir A. Ali, Kamal A.A. Mohammed

Saudi Toxicology Journal

Tamoxifen is a cornerstone therapy for estrogen receptor-positive (ER+) breast cancer, improving survival and reducing recurrence. Its efficacy and toxicity, however, vary due to genetic polymorphisms influencing metabolism and transport. Key genes, such as CYP2D6, CYP3A4, and ATP-binding cassette transporters (ABCB1, ABCC2), are crucial in forming and distributing active metabolites like endoxifen. This review explores tamoxifen pharmacogenetics through an analysis of literature from PubMed, Scopus, Google Scholar, and PharmaGKB. Genetic variations like CYP2D6*10 in Asians and CYP2D6*17/29 in Africans impact therapeutic outcomes. Barriers to personalized tamoxifen therapy include inconsistent guidelines, limited access to genetic testing, and underrepresentation of ethnic groups …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Improving The Safety Of N,N-Dimethylacetamide As A Potential Treatment For Preterm Birth Using A Vaginal Nanoformulation, Asad Mir

Theses and Dissertations

With no available treatment for preterm birth, the field of reproductive medicine has been repurposing small molecule candidates into vaginal nanoformulations as potential treatments for the condition. The commercial solvent N,N-Dimethylacetamide (DMA) has previously been shown to delay and prevent inflammation-induced preterm birth in a mouse model. A vaginal nanoformulation of DMA loaded into a self-nanoemulsifying drug delivery system (SNEEDS) was studied to see if it can also be efficacious. A side by-side histological comparison was done in the more pertinent tissues of the reproductive tract between the traditional formulation of DMA given intraperitoneally (IP) and the vaginal nanoformulation of …

Gene Ontology Enrichment Reveals Pufa-Responsive Functional Themes In The Nucleus Accumbens Of Female Dba/2j Mice, Eman Mahjoub, Jennifer Wolstenholme Ph.D.

IRBEH/Spit for Science Publications and Presentations

No abstract provided.

Validating A Genetic Knockout Of Ninein In A Mouse Model, Jessikah M. Buys, E R. Gnatowski, L Vermuri, A Safeer, L Holmes, M. F. Miles

IRBEH/Spit for Science Publications and Presentations

Ninein (Nin) is a microtubule associated protein that has been previously characterized by the Miles Lab for regulating the anxiety-reducing (anxiolytic) effects of alcohol, which is thought to contribute to development of Alcohol Use Disorder (AUD). Previous studies in the lab have investigated the role of Nin deletion on anxiety and ethanol-related behaviors in a conditional knockout model. The following set of studies seek to validate this genetic model. The model was validated using three main methods: immunofluorescence, qRT-PCR, and gel electrophoresis. In PCR studies, Ninein was significantly reduced in cre-expressing animals compared to controls. Gel Electrophoresis confirmed this reduction …