Chemicals and Drugs Commons^™

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 …

Contraceptive Hormone Influences On The Role Of Primary Reinforcement And Reinforcer-Enhancement In Nicotine Self-Administration, Kathleen Robin Mcnealy

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Hormonal contraceptives contain a synthetic estrogen (e.g., ethinyl estradiol/EE) and/or a synthetic progestin (e.g., levonorgestrel/LEVO) and can exacerbate nicotine intake. However, whether altered intake reflects changes in nicotine reinforcement or enhancement by nicotine of co-occurring reinforcers is unknown. This reinforcer-enhancement effect is evidenced in rats when nicotine self-administration is increased by the presence of a visual stimulus (VS) reinforcer. This dissertation examined the effects of EE and LEVO on nicotine reinforcement and reinforcer-enhancement in ovary-intact female Sprague-Dawley rats. Rats were implanted with a jugular catheter and assigned to receive daily injections of EE (Vehicle, 0.125 [Low], or 0.18 [High] μg/day; …

Applications Of Archaeal Antioxidant Coenzyme M As An Agricultural Biostimulant, Jeremy Hunter Brown

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

As the demand to meet global food security goals continue to increase, the need to increase efficiency and productivity of agricultural output also rises. This calls for innovative and cost-effective methods for improving plant growth and yield. Here we explore how antioxidants, molecules that inhibit oxidation and are necessary for redox based signaling and redox homeostasis, can be utilized as chemical biostimulants. Specifically, we investigated Coenzyme M, an antioxidant from archaea that holds potential economic advantages over other antioxidants. Chapter 1 provides a comprehensive review of antioxidants and how exogenously application of them affects plant growth and biology, highlighting the …

March 2025, Swosu Rural Health Center

RURAL ROCKS

This is the March 2025 issue of Rural Rocks from the SWOSU College of Pharmacy.

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), …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Terlipressin-Induced Hyponatremic Seizures In A Patient With Congenital Hepatic Fibrosis, Luca Gauci, Jorge Gafa, Suzanne Cauchi, Jurgen Gerada

HCA Healthcare Journal of Medicine

Introduction

Acute variceal bleeding from portal hypertension is one of the most serious complications with a mortality rate of 15% to 25%. Terlipressin is a vasopressor that controls variceal bleeding by lowering the portal pressure and reducing blood flow to the varices.

Case Presentation

We report a case of a patient with acute variceal bleeding, treated endoscopically and with terlipressin, who developed severe hyponatremia and seizures requiring admission to intensive care. Clinical and biochemical improvements were noticeable upon the cessation of terlipressin, with an eventual discharge from the hospital.

Conclusion

Prompt management of acute variceal bleeding with both endoscopic and …

Role Of Urolithin A In Cancer Therapy, Aanya S. Chauhan, Vinita Karumuru, Mahi P. Yallapu, Anupam Dhasmana

Research Symposium

Background: Cancer is a big health problem around the world, causing many deaths even though there have been improvements in treatments. Some of the main challenges in treating cancer include side effects, resistance to treatments, cancer spreading to other parts of the body (metastasis), and the disease coming back (recurrence). Scientists are looking for safer and better ways to treat cancer. One promising option is using natural substances that come from plants, which are less toxic and have a lot of potential for fighting diseases. One of these substances is Urolithin A (UA), a compound made in the body when …

Alcohol And Cannabis Use For Pain Management: Translational Findings Of Relative Risks, Benefits, And Interactions, Sumin Lee, Scott Edwards

School of Medicine Faculty Publications

Chronic pain affects over 20% of the global population and contributes to the vast burden of psychiatric illness. While effective treatments for chronic pain remain limited, both alcohol and cannabis have been used for centuries to manage pain and closely associated negative affective symptoms. However, persistent misuse of alcohol and/or cannabis in such a negative reinforcement fashion is hypothesized to increase the risk of severity of substance use disorders (SUDs). The current review describes neurobiological evidence for the analgesic efficacy of alcohol and primary cannabis constituents and how use or co-use of these substances may influence SUD risk.

Refractory Dermatitis Evolving Into Lupus Spectrum Disease In The Setting Of Dupilumab Use, Jonathan M. Joseph, Jacob Kilgore, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous lupus erythematosus (CLE) encompasses a broad range of clinical and histopathologic variants that can overlap with other dermatologic entities, complicating accurate diagnosis. We report the case of a 42-year-old male patient who initially presented with a diffuse pruritic eruption presumed to be atopic dermatitis, for which dupilumab was initiated. Within the following weeks, the patient developed a fever of unknown origin and diarrhea, raising concern for an atypical drug-related reaction or an unmasked autoimmune process. Subsequent biopsies demonstrated evolving histopathologic features, including superficial and deep perivascular dermatitis suggestive of drug eruption. In addition, a dermal mucin deposition with mixed …

Bilateral Carotid Body Paragangliomas With Succinate Dehydrogenase Complex Subunit D Gene Mutation, Abdul R. Khan, Kelvin Li, Neel D. Gupta, Jagan D. Gupta, Mohammed M. Ansari, Triet M. Do, Enrique Palacios

School of Medicine Faculty Publications

No abstract provided.

Exploring The Potential Of Oncolytic Viruses As A Novel Therapeutic Approach For Breast Cancer Treatment, Renad Alsayyad, Claudia M. Tellez Freitas

Annual Research Symposium

No abstract provided.

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …

Effect Of Steroids On The Progression Of Alzheimer's Dementia: A Retrospective Chart Review., Julijana Zoran Conic, Alexandra Chetty, Lily Chen, Audrey Marsh, Sean Barry, Rodney Pattabhi, Thomas Reske, Erwin Aguilar, Lobna Ali

School of Medicine Faculty Publications

Objectives: Alzheimer's disease (AD) is a prevalent age‐related neurodegenerative disease that affects millions of individuals in the United States. Neuroinflammation is a driver of the neurodegenerative changes that characterize AD, prompting interest in how inflammation can be modulated for treatment and prevention. Methods: ICD‐10 codes were quarried from electronic medical records to identify patients diagnosed with AD from 2012 to 2020. The patients were then divided into those who used systemic steroids and those who did not before the progression of their disease. Data on medication prescribed was used to measure the disease's progression. Clinical findings and laboratory results were …

The Unfolding Story Of Protein Misfolding Causing Alzheimer Disease In Recipients Of Human Pituitary Growth Hormone, Evan G. Graber, Sayed M. Hadi Hosseini, Darrell M. Wilson, Alan D. Rogol

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are …

Aspartame: Is It Truly Safe For Human Consumption?, Zachary Bernstein, Kamran Awan

Annual Research Symposium

Poster Presentation

Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment In Adults With Early Syphilis: Secondary Analysis Of A Randomized Clinical Trial., Jodie A. Dionne, Chunming Zhu, Jorge Mejia-Galvis, Kimberly Workowski, Teresa A. Batteiger, Julia C. Dombrowski, Kenneth H. Mayer, Candice J. Mcneil, Arlene C. Seña, Stephanie Taylor, Harold C. Wiesenfeld, Matthew M. Hamill, Charlotte Perlowski, Edward W. Hook Iii

School of Medicine Faculty Publications

Key Points: Question: What proportion of patients with early syphilis have symptoms of the Jarisch-Herxheimer reaction (JHR) after treatment with benzathine penicillin G, and what are the associated characteristics? Findings: This prespecified secondary analysis of a multisite US randomized clinical trial found that, among 249 adults with early syphilis, JHR symptoms occurred after benzathine penicillin G treatment in 59 participants (23.7%). Onset of JHR was within 12 hours of treatment for 86.0% of participants, and JHR was associated with successful treatment response, secondary syphilis, and absence of HIV. Meaning: This study suggests that patients treated with benzathine penicillin G for …

Cucumis Melo. L- An Oral Wellness Oasis For The Prevention And Remineralisation Of White Spot Lesions, Gokilla Priya Murugan, Prema Anbarasu, Saravanakumar S, Balaji R

Annual Research Symposium

No abstract provided.

Investigating The Impact Of Tirzepatide Treatment On Alcohol And Cigarette Consumption, Yvannia Gray, Benjamin Latey, Hayden Mcaffee, Karissa Mccown, Seth Maki, Victoria Nguyen, Andrew Payne

Annual Research Symposium

No abstract provided.

A Galleria Mellonella Study: Protective Effects Of Sulforaphane On Immune Function In Binge Alcohol Exposure, Robert Kento Darby, Braydon Black, Vincent Tran, Dallen James, Scott Quimby

Annual Research Symposium

Alcohol is associated with increased mortality and morbidity. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, hazardous alcohol exposure like binge alcohol intoxication (≥ 0.08% BAC) is a major risk factor. We’ve previously investigated the efficacy of Sulforaphane (SFN) prophylaxis in protecting human and murine alveolar macrophage function against opportunistic infections when exposed to binge alcohol conditions in vitro. However, an in vivo model investigating SFN and hazardous alcohol exposure in the context of infection is not well understood. The aim of this study is to 1) establish a G. mellonella larvae model by determining the LD50 …