Medical Pharmacology Commons^™

Variation In Systemic Corticosteroid Prescribing During Asthma-Related Hospitalizations Across Children's Hospitals, Sian Best, Kathryn Kyler, Matt Hall, Jessica L. Bettenhausen, Shelby Chesbro, Nicholas Clark, Adrienne Deporre, Jonathan Ermer, Leah Jones, Jessica Markham, Maria Newmaster, Laura Plencner, Henry T. Puls, Smit Shah, Bridgette Jones, Megan Collins, Elisha Mccoy

Research Days

This abstract describes the variability and trends in inpatient systemic corticosteroid prescribing practices for acute asthma exacerbations in children's hospitals, and aims to determine associations between the prescribed steroid and hospitalization outcomes.

Transcriptomic Signature, Bioactivity And Safety Of A Non-Hepatotoxic Analgesic Generating Am404 In The Midbrain Pag Region, Hernan A. Bazan, Surjyadipta Bhattacharjee, Madigan M. Reid, Bokkyoo Jun, Connor Polk, Madeleine Strain, Linsey A. St Pierre, Neehar Desai, Patrick W. Daly, Jessica A. Cucinello-Ragland, Scott Edwards, Javier Recio, Julio Alvarez-Builla, James J. Cai, Nicolas G. Bazan

School of Medicine Faculty Publications

Safe and effective pain management is a critical healthcare and societal need. The potential for acute liver injury from paracetamol (ApAP) overdose; nephrotoxicity and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use; and opioids’ addiction are unresolved challenges. We developed SRP-001, a non-opioid and non-hepatotoxic small molecule that, unlike ApAP, does not produce the hepatotoxic metabolite N-acetyl-p-benzoquinone-imine (NAPQI) and preserves hepatic tight junction integrity at high doses. CD-1 mice exposed to SRP-001 showed no mortality, unlike a 70% mortality observed with increasing equimolar doses of ApAP within 72 h. SRP-001 and ApAP have comparable antinociceptive effects, including the complete …

Fake Xanax: Designer Emerging Benzodiazepine Epidemic Linked To Morbidity And Mortality A Narrative Review, Alan D. Kaye, Joseph P. Tassin, William C. Upshaw, Camille M. Robichaux, Mark V. Frolov, Mark M. Dupaquier, Julia E. Fox, Jeffrey Sterritt, Jibin Mathew, Sahar Shekoohi, Adam M. Kaye, Amber N. Edinoff

School of Dentistry Faculty Publications

Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. …

Examining The Effects Of Menstrual Cycle Phase And Hormonal Contraceptive Use On Women's Sleep, Charles Ethan Coombs

Psychological Science Undergraduate Honors Theses

Women overrepresent men for sub-optimal sleep, a consequence of hormone fluctuation in the menstrual cycle affecting sleep regulatory pathways. While research has examined the prevalence of sub-optimal sleep through cycle phases, little research has examined how hormonal contraceptives (HC’s) could similarly affect women’s sleep, while also neglecting to utilize subjective sleep measures. In this study, we examine subjective sleep quality among naturally cycling (NC) women, women using different HC types, and between active and inactive phase pill users by subjecting 463 women to a subjective sleep battery. We hypothesized that HC users would report more sub-optimal sleep than NC women. …

Epiregulin As A Novel Target For Antibody-Drug Conjugate Development For The Treatment Of Colorectal Cancer, Joan Jacob

Dissertations and Theses (Open Access)

Antibody-drug conjugates (ADCs) are a fast-growing class of molecularly targeted therapies with 13 currently approved and over a 100 in clinical trials. ADCs consist of a monoclonal antibody (mAb) conjugated to a potent cytotoxic payload to selectively target tumor antigens highly expressed on the cell surface. ADC development has been limited in colorectal cancer (CRC) by the lack of novel and effective therapeutic targets. Epiregulin (EREG), is an epidermal growth factor receptor (EGFR) ligand that is highly expressed in CRCs of different subtypes and mutational statuses with low expression in normal tissues. Here, we have characterized the role of EREG …

Selective Serotonin Reuptake Inhibitors And Pharmacological Resetting Of The Mind, Ion G. Motofei, David L. Rowland

Journal of Mind and Medical Sciences

Mental activity is capable of processing analytical data (mathematics, physics, socio-political science, philosophy, etc.) similar to computer software. At the same time, mental activity largely depends on the brain, which works like a hard component of a computer. While the computer stores data on a physical medium, mental activity and data are supported by physiological mechanisms that are constantly operating (both in wakefulness and sleep). For this reason, the lack of brain oxygenation even for short periods of time (5-10 minutes) causes the loss of all data, including the disappearance of the individual's existence as a mental entity. This means …

Testosterone Supplementation In Patients With Burn Hypermetabolism, Alexandra Dewitt, Anastasiya Ivanko, Jonathan E. Schoen, Aimee Keating, Herb A. Phelan Iii, Jeffrey E. Carter

School of Medicine Faculty Publications

56th Annual Meeting of the American Burn Association, 2024; April 9 - April 12, 2024; Chicago, IL

Evaluating Serum Copper And Kidney Function In A Cohort Of Bariatric Surgery Patients, Katherine Mckeon, Mchael Cook, John Baker, Kyle Lapenna, Hua He, Amanda Anderson, Felicia Rabito

School of Medicine Faculty Publications

Association for Clinical and Translational Science 2024; April 3 - April 5, 2024; Las Vegas, NV

Balancing The Mind: The Role Of Selective Serotonin Reuptake Inhibitors In Managing Anxiety, Olivia Mace

Best Integrated Writing

Olivia’s senior capstone review article focuses on the role of the selective serotonin reuptake inhibitor (SSRI) escitalopram in the management of anxiety. SSRIs have been successfully used to treat depression for decades, with fluoxetine (Prozac) being introduced to the US market in 1987. Recently it has been found that the SSRI escitalopram has efficacy in treating anxiety as well as depression. Olivia’s review is detailed and timely. Unmanaged anxiety and depression are common among students and this review will be of interest to students, parents and the university population in general.

If1 Promotes Cellular Proliferation And Inhibits Oxidative Phosphorylation In Mouse Embryonic Fibroblasts Under Normoxia And Hypoxia, Lothar Lauterboeck, Sung Wook Kang, Donnell White, Rong Bao, Parnia Mobasheran, Qinglin Yang

School of Graduate Studies Faculty Publications

ATP synthase inhibitory factor subunit 1 (IF1) is an inhibitory subunit of mitochondrial ATP synthase, playing a crucial role in regulating mitochondrial respiration and energetics. It is well-established that IF1 interacts with the F1 sector of ATP synthase to inhibit the reversal rotation and, thus, ATP hydrolysis. Recent evidence supports that IF1 also inhibits forward rotation or the ATP synthesis activity. Adding to the complexity, IF1 may also facilitate mitophagy and cristae formation. The implications of these complex actions of IF1 for cellular function remain obscure. In the present study, we found that IF1 expression was markedly upregulated in hypoxic …

Catatonia As A Result Of A Traumatic Brain Injury, Jessica Berthelot, Jacob Cambre, Madeline Erwin, Jennifer Phan

School of Medicine Faculty Publications

Catatonia is a neuropsychiatric syndrome typically marked by disturbances in motor activity, speech, and behavior. It has historically been associated with psychiatric illness, but acute medical illness, neurocognitive disorders, and neurodevelopmental disorders can cause catatonia as well. Catatonia is likely underrecognized and underdiagnosed in the general medical hospital, despite high risks of morbidity and mortality and the availability of rapidly effective treatment. Here, we present a case of catatonia secondary to traumatic brain injury that responded to lorazepam after a delayed diagnosis. A young male patient who was incarcerated and assaulted was sent to the emergency department multiple times for …

Targeting Cyp51 In The Treatment Of Acanthamoeba Keratitis, Ashkan Hassani, Vineet Sadarangani, Brad Haubrich

Annual Research Symposium

Acanthamoeba castellanii causes a rare but serious ocular infection called Acanthamoeba keratitis. Risk factors for infection include contact with contaminated water and poor hygiene of contact lenses. The first-line treatment is comprised of a months-long schedule of antibiotics. However, in cases where pharmacological interventions fail to address the infection, surgery may be necessary, with the continued risk of potential vision loss. Consequently, new treatments are needed, whether new pharmacological agents or new combination therapies with current agents. As an aerobic parasite, Acanthamoeba synthesizes ergosterol as a cell membrane insert, and ergosterol biosynthesis inhibitors (EBIs), common in antifungal pharmaceuticals, could potentially …

Alginate Dressings- Revisiting The Past, Oshine Jha, Oshine Jha

Annual Research Symposium

Wound healing in simple terms is the healing of skin which involves various mechanisms. It is not dressings themselves that heal wounds, but the careful selection of appropriate dressings that provide the optimal wound-healing environment for the individual wound. Wound dressings are prepared from biopolymers, synthetic polymers and biomaterials.

Medication Errors Among Als Providers In The Prehospital Setting, Cody Vaughn Gibson, Victor Jimenez Jr

Annual Research Symposium

EMS providers administer a variety of medications to patients in the prehospital environment, and while there are numerous published studies on medication errors pertaining to the hospital environment, there are comparatively fewer studies which focus on the prehospital environment. Therefore, the purpose of this survey is to investigate the type and frequency of medication errors occurring in the prehospital environment.

Early Renal Denervation Attenuates Cardiac Dysfunction In Heart Failure With Preserved Ejection Fraction, Jake E. Doiron, Zhen Li, Xiaoman Yu, Kyle B. Lapenna, Heather Quiriarte, Timothy D. Allerton, Kashyap Koul, Andrew Malek, Sanjiv J. Shah, Thomas E. Sharp, Traci T. Goodchild, Daniel R. Kapusta, David J. Lefer

School of Graduate Studies Faculty Publications

BACKGROUND: The renal sympathetic nervous system modulates systemic blood pressure, cardiac performance, and renal function. Pathological increases in renal sympathetic nerve activity contribute to the pathogenesis of heart failure with preserved ejection fraction (HFpEF). We investigated the effects of renal sympathetic denervation performed at early or late stages of HFpEF progression. METHODS AND RESULTS: Male ZSF1 obese rats were subjected to radiofrequency renal denervation (RF-RDN) or sham procedure at either 8 weeks or 20 weeks of age and assessed for cardiovascular function, exercise capacity, and cardiorenal fibrosis. Renal norepinephrine and renal nerve tyrosine hydroxylase staining were performed to quantify denervation …

Exploring The Developmental Effects Of Antidepressants In Caenorhabditis Elegans, Alexandra Van Stone

Annual Research Symposium

It is so important to explore the potential side effects of antidepressants especially if these side effects could lead to a future detriment to an individual’s financial and social well-being. A better understanding of these side effects in regards to human developmental issues is imperative considering issues related to mental health and depression affect a large percentage of the population. In this study, we tested if Caenorhabditis (C.) elegans could be a potential model organism to predict possible side effects associated with select antidepressants. Their developmental problems potentially encountered upon drug treatment may be encountered in humans.

Effects Of Metformin On Glucose Metabolism And Mitochondrial Function In Patients With Obstructive Sleep Apnea: A Pilot Randomized Trial, Elizabeth R.M. Zunica, Elizabeth C. Heintz, Wagner S. Dantas, R. Caitlin Hebert, Ma Kayla Tanksley, Robbie A. Beyl, Edward C. Mader, John P. Kirwan, Christopher L. Axelrod, Prachi Singh

School of Medicine Faculty Publications

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = …

A Review Of Current And Pipeline Drugs For Treatment Of Melanoma, Nicole Natarelli, Sarah J. Aleman, Isabella M. Mark, Jasmine T. Tran, Sean Kwak, Elizabeth Botto, Shaliz Aflatooni, Michael J. Diaz, Shari R. Lipner

School of Medicine Faculty Publications

Malignant melanoma is the most aggressive form of skin cancer. Standard treatment options include surgery, radiation therapy, systemic chemotherapy, targeted therapy, and immunotherapy. Combining these modalities often yields better responses. Surgery is suitable for localized cases, sometimes involving lymph node dissection and biopsy, to assess the spread of the disease. Radiation therapy may be sometimes used as a standalone treatment or following surgical excision. Systemic chemotherapy, while having low response rates, is utilized as part of combination treatments or when other methods fail. The development of resistance to systemic chemotherapies and associated side effects have prompted further research and clinical …

Potential Causal Association Between Gut Microbiome And Posttraumatic Stress Disorder, Qiang He, Wenjing Wang, Dingkang Xu, Yang Xiong, Chuanyuan Tao, Chao You, Lu Ma, Junpeng Ma, Caroline M. Nievergelt, Adam X. Maihofer, Torsten Klengel, Elizabeth G. Atkinson, Chia Yen Chen, Karmel W. Choi, Jonathan R.I. Coleman, Shareefa Dalvie, Laramie E. Duncan, Mark W. Logue, Allison C. Provost, Andrew Ratanatharathorn, Murray B. Stein, Katy Torres, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Søren B. Andersen, Ole A. Andreassen, Paul A. Arbisi, Ariane Rung, Et Al

School of Public Health Faculty Publications

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the …

Ogilvie's Syndrome: Acute Colonic Pseudoobstruction. A Review For Residents., Tyler Bayliss, Caleb Clark, Errington C. Thompson

Marshall Journal of Medicine

Ogilvie's syndrome (acute colonic pseudoobstruction) was first described in 1948. Acute colonic pseudoobstruction can occur in a variety of clinical settings, including postsurgical, obstetrics, pelvic surgery, critical care and sepsis. Clinicians need to recognize the syndrome early. Colonic distention without evidence of obstruction can be seen on plain films of the abdomen or CT scan. Successful therapies, including bowel rest, neostigmine and colonoscopic decompression, have been used. Avoiding respiratory compromise from abdominal distention and colonic perforation of the primary goals of treatment. Surgical intervention should be reserved for patients who are refractory to medical treatment or develops signs and symptoms …

Cd133-Dependent Activation Of Phosphoinositide 3-Kinase /Akt/Mammalian Target Of Rapamycin Signaling In Melanoma Progression And Drug Resistance, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Youssef Al Hmada, Sofie Yasmin Hassan, Hosam Shalaby, Simeon Santourlidis, Sarah Lilly Hassan, Youssef Haikel, Mossad Megahed, Robert T. Brodell, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent …

Sex-Specific Negative Affect-Like Behaviour And Parabrachial Nucleus Activation Induced By Bnst Stimulation In Adult Mice With Adolescent Alcohol History, Lucas Albrechet-Souza, Chelsea R. Kasten, Natalia B. Bertagna, Tiffany A. Wills

School of Medicine Faculty Publications

Adolescent alcohol use is a strong predictor for the subsequent development of alcohol use disorders later in life. Additionally, adolescence is a critical period for the onset of affective disorders, which can contribute to problematic drinking behaviours and relapse, particularly in females. Previous studies from our laboratory have shown that exposure to adolescent intermittent ethanol (AIE) vapour alters glutamatergic transmission in the bed nucleus of the stria terminalis (BNST) and, when combined with adult stress, elicits sex-specific changes in glutamatergic plasticity and negative affect-like behaviours in mice. Building on these findings, the current work investigated whether BNST stimulation could substitute …

Mechanisms Of Melanoma Progression And Treatment Resistance: Role Of Cancer Stem-Like Cells, Youssef Al Hmada, Robert T. Brodell, Naji Kharouf, Thomas W. Flanagan, Abdulhadi A. Alamodi, Sofie Yasmin Hassan, Hosam Shalaby, Sarah Lilly Hassan, Youssef Haikel, Mosaad Megahed, Simeon Santourlidis, Mohamed Hassan

School of Medicine Faculty Publications

Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% …

Interplay Between Acetylation And Ubiquitination Of Imitation Switch Chromatin Remodeler Isw1 Confers Multidrug Resistance In Cryptococcus Neoformans, Yang Meng, Yue Ni, Zhuoran Li, Tianhang Jiang, Tianshu Sun, Yanjian Li, Xindi Gao, Hailong Li, Chenhao Suo, Chao Li, Sheng Yang, Tian Lan, Guojian Liao, Tongbao Liu, Ping Wang, Chen Ding

School of Medicine Faculty Publications

Cryptococcus neoformans poses a threat to human health, but anticryptococcal therapy is hampered by the emergence of drug resistance, whose underlying mechanisms remain poorly understood. Herein, we discovered that Isw1, an imitation switch chromatin remodeling ATPase, functions as a master modulator of genes responsible for in vivo and in vitro multidrug resistance in C. neoformans. Cells with the disrupted ISW1 gene exhibited profound resistance to multiple antifungal drugs. Mass spectrometry analysis revealed that Isw1 is both acetylated and ubiquitinated, suggesting that an interplay between these two modification events exists to govern Isw1 function. Mutagenesis studies of acetylation and ubiquitination sites …

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Stable, Neuron-Specific Gene Expression In The Mouse Brain, Osama Ahmed, Kingsley M. Ekumi, Francesco V. Nardi, Gulimiheranmu Maisumu, Khaled Moussawi, Eric D. Lazartigues, Bo Liang, Abraam M. Yakoub

School of Medicine Faculty Publications

Gene delivery to, and expression in, the mouse brain is important for understanding gene functions in brain development and disease, or testing gene therapies. Here, we describe an approach to express a transgene in the mouse brain in a cell-type-specific manner. We use stereotaxic injection of a transgene-expressing adeno-associated virus into the mouse brain via the intracerebroventricular route. We demonstrate stable and sustained expression of the transgene in neurons of adult mouse brain, using a reporter gene driven by a neuron-specific promoter. This approach represents a rapid, simple, and cost-effective method for global gene expression in the mouse brain, in …

The Effects Of Physical Activity On Experimental Models Of Vascular Dementia; A Systematic Review And Meta-Analysis, Ifechukwude J. Biose, Wesley H. Chastain, Rebecca J. Solch-Ottaiano, Viktoriya S. Grayson, Hanyun Wang, Somdeb Banerjee, Gregory J. Bix

School of Medicine Faculty Publications

Background; Physical activity is associated with improved brain health and cognition in humans. However, the validity, range, and quality of evidence for the beneficial outcomes linked to exercise in experimental models of vascular dementia (VaD) have not been evaluated. We performed a systematic review and meta-analysis of studies that assessed the effect of exercise intervention on models of VaD to provide an unbiased and comprehensive determination of the cognitive function and brain morphology benefits of exercise. Summary; A systematic search in three databases as well as study design characteristics and experimental data extraction were completed in December 2021. We investigated …

Hypothyroid: New Insights On An Old Disease, Sara Ward

Graduate Research Projects

No abstract provided.

High-Cost Drug Formulary Stewardship: Health System Evaluation Of Intravenous Immunoglobulin (Ivig) Utilization, Christine J. Hurteau Pharmd, Christopher Flores Pharmd, Pcscp, Rebecca Pulk Pharmd, Ms, Bsp

Posters

• Intravenous immunoglobulin (IVIG) therapy is essential for treating various immune mediated conditions
• Dosing and duration of IVIG varies based on indication, and there is lack of consensus for some indications on ideal dosing strategy
• IVIG is a high cost medication that is being used at higher rates in a five hospital health system compared to similarly sized institutions
• Given the high utilization rates, evaluation of IVIG prescribing patterns and clinical appropriateness was

Ultrasound-Guided Erector Spinae Plane Block: An Objective Structured Clinical Examination For First-Year Anesthesia Providers, Andrew Edwards, Jonathan Mardis

Doctoral Projects

The use of ultrasound-guided regional anesthesia (UGRA) in anesthetic practice is an invaluable tool for anesthesia providers to implement into their daily practice. One of these regional techniques is the erector spinae plane block (ESPB) which has anesthetic implications in numerous surgical procedures including cervical spine, thoracolumbar spine, thoracic wall, and chest wall procedures. Because of the novelty of this regional anesthetic technique, it is important to educate first-year anesthesia providers about the implications, skillset, and complications of the ESPB.

To bridge the gap between didactic knowledge and clinical practice in first-year anesthesia providers, an objective structured clinical examination (OSCE) …