Medical Pharmacology Commons^™

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …

Therapeutic Efficacy Of Antioxidants In Ameliorating Obesity Phenotype And Associated Comorbidities, Steven Tun, Caleb James Spainhower, Cameron Lee Cottrill, Hari Vishal Lakhani, Sneha S. Pillai, Anum Dilip, Hibba Chaudhry, Joseph I. Shapiro, Komal Sodhi

Pharmacology, Physiology and Toxicology

Obesity has been a worldwide epidemic for decades. Despite the abundant increase in knowledge regarding the etiology and pathogenesis of obesity, the prevalence continues to rise with estimates predicting considerably higher numbers by the year 2030. Obesity is characterized by an abnormal lipid accumulation, however, the physiological consequences of obesity are far more concerning. The development of the obesity phenotype constitutes dramatic alterations in adipocytes, along with several other cellular mechanisms which causes substantial increase in systemic oxidative stress mediated by reactive oxygen species (ROS). These alterations promote a chronic state of inflammation in the body caused by the redox …

Fatal Case Of Newborn Lassa Fever Virus Infection Mimicking Late Onset Neonatal Sepsis: A Case Report From Northern Nigeria, Taofik Oluwaseun Ogunkunle, Surajudeen Oyeleke Bello, Chinwe Immaculata Anderson, Rashida Musa, Rasaq Olaosebikan, Abdulazeez Imam

Department of Pharmacology and Experimental Therapeutics Faculty Papers

BACKGROUND: Lassa fever is a zoonotic viral infection endemic to the West Africa countries. It is highly fatal during pregnancy and as such reports of neonatal onset Lassa fever infections are rare in scientific literature. We report a fatal case of Lassa fever in a 26-day-old neonate mimicking the diagnosis of late-onset neonatal sepsis.

CASE PRESENTATION: The patient is a 26-day-old neonate who was admitted with a day history of fever, poor feeding, pre-auricular lymphadenopathy and sudden parental death. He was initially evaluated for late onset neonatal sepsis. He later developed abnormal bleeding and multiple convulsions while on admission, prompting …

Crnas And Sugammadex Use: A Qualitative Analysis, Natalia Izquierdo Bsn, Rn, Emily Mancewicz Bsn, Rn

Grace Peterson Nursing Research Colloquium

Background: The availability of Sugammadex has increased options for Certified Registered Nurse Anesthetists’ (CRNAs) and their choice of neuromuscular reversal agents, however administration is impacted by a variety of provider and institutional factors.

Objectives: The purpose of this study was to examine and describe the personal and institutional factors impacting the use of Sugammadex in Illinois by CRNAs.

Method: A qualitative study design using an open-ended survey yielded 209 responses. The three main themes that emerged were 1) Why CRNAs choose to use or avoid Sugammadex 2) How CRNAs dose Sugammadex and 3) Practice variations existing within the clinical setting. …

Cytokine Storm In Covid-19: An Overview, Mechanism, Treatment Strategies, And Stem Cell Therapy Perspective, Nuriza Ulul Azmi, Meidi Utami Puteri, Donny Lukmanto

Pharmaceutical Sciences and Research

Coronavirus disease 2019 (COVID-19) is the disease caused by the highly transmittable novel coronavirus (SARS-CoV-2) infections. The disease was found at the end of December 2019, in Wuhan, China, and quickly spread worldwide with a higher mortality rate compared to the previous coronavirus disease. Cytokine plays an important role in the inflammatory response against coronavirus infection. However, in severely ill patients with COVID-19, an excessive amount of cytokine serum level (cytokine storm) has been associated with the aggravation of coronavirus disease leading to acute respiratory distress syndrome (ARDS). Thus, the management of the cytokine storm could be the key to …

The Inhibitory Effects Of An Antimicrobial Gel On The Staphylococcus Species, Mara Trinkle

Undergraduate Honors Theses

The prevalence of antibiotic resistant bacteria has made the choices for topical treatments for patients who experience burns wounds extremely limited. The Staphylococcus genus is naturally occurring in and on the human body but can become harmful once it enters the bloodstream. A novel antimicrobial gel has been shown by our laboratory to inhibit both the planktonic growth and biofilm formation of Staphylococcus aureus in previous studies. The antimicrobial gel is made of seven natural compounds including antioxidants (vitamin C and E). We wanted to examine the effects of the antimicrobial gel on numerous other Staphylococcal species because it is …

Mechanisms Of Chromate-Induced Suppression Of Rad51: A One Environmental Health Approach., Rachel M. Speer

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death. Lung cancer is commonly associated with smoking, however, 1 in 5 women and 1 in 12 men who develop lung cancer are never-smokers. Environmental exposures, therefore, account for a significant portion of lung cancer cases. Hexavalent chromium [Cr(VI)] is a global environmental contaminant and known human lung carcinogen. Cr(VI) and other carcinogenic metals induce chromosome instability, an early event in lung cancer. Structural chromosome instability arises in part due to failed DNA repair. Particulate Cr(VI), the most potent form of Cr(VI), induces DNA double strand breaks and inhibits the high-fidelity DNA …

Soluble Epoxide Hydrolase Inhibition: A Novel Therapeutic Strategy In Alcoholic Liver Disease., Jeffrey Barr Warner

Electronic Theses and Dissertations

Emerging evidence suggests that soluble epoxide hydrolase (sEH) inhibition is a valuable therapeutic strategy for the treatment of numerous diseases. sEH rapidly degrades cytochrome P450-produced epoxygenated lipids (epoxy-fatty acids, epFAs), which generally exert beneficial effects on several cellular processes. sEH hydrolysis of epoxy-fatty acids produces dihydroxy-fatty acids which are typically less biologically active than their parent epoxide. sEH inhibition has shown efficacy in treating numerous pathologies associated with non-alcoholic liver disease, yet no efforts to date have tested the efficacy of sEH inhibition in alcoholic liver disease (ALD). Herein, we measured the levels of sEH expression and epFAs in human …

N-Acetyltranserase 2 (Nat2) Genotype Polymorphism In Cryopreserved Human Hepatocytes And Chinese Hamster Ovary (Cho) Cells., Mariam Refaat Zaky Habil

Electronic Theses and Dissertations

Arylamine N-acetyltransferases, NAT1 and NAT2, catalyze the detoxification and/or activation of drugs and aromatic amine carcinogens. Single nucleotide polymorphisms or SNPs result in different human NAT2 genotypes thus dividing the population into rapid, intermediate, and slow acetylators. We hypothesize allelic variants of NAT2 genotype will decrease levels of N-acetylation, cytotoxicity, oxidative stress, DNA adduct formation, and mutagenesis compared to the reference allele NAT2*4. Cryopreserved human hepatocytes expressing different NAT2 genotypes and NER-deficient Chinese hamster ovary (CHO) cells transfected with human CYP1A2 and human NAT2*4, NAT2*5B or NAT2*7B have been used to investigate N-acetylation of different xenobiotics. In …

Engineered Extracellular Vesicles Loaded With Mir-124 Attenuate Cocaine-Mediated Activation Of Microglia, Ernest T. Chivero, Ke Liao, Fang Niu, Ashutosh Tripathi, Changhai Tian, Shilpa Buch, Guoku Hu

Journal Articles: Pharmacology & Experimental Neuroscience

MicroRNA-124 (miR-124), a brain-enriched microRNA, is known to regulate microglial quiescence. Psychostimulants such as cocaine have been shown to activate microglia by downregulating miR-124, leading, in turn, to neuroinflammation. We thus rationalized that restoring the levels of miR-124 could function as a potential therapeutic approach for cocaine-mediated neuroinflammation. Delivering miRNA based drugs in the brain that are effective and less invasive, however, remains a major challenge in the field. Herein we engineered extracellular vesicles (EVs) and loaded them with miR-124 for delivery in the brain. Approach involved co-transfection of mouse dendritic cells with Dicer siRNA and RVG-Lamp2b plasmid to deplete …

Endocrine Significance Of Sars-Cov-2'S Reliance On Ace2, Eric Lazartigues, Mirza Muhammad Fahd Qadir, Franck Mauvais-Jarvis

School of Medicine Faculty Publications

The current COVID-19 pandemic is the most disruptive event in the past 50 years, with a global impact on health care and world economies. It is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a coronavirus that uses angiotensin-converting enzyme 2 (ACE2) as an entry point to the cells. ACE2 is a transmembrane carboxypeptidase and member of the renin-angiotensin system. This mini-review summarizes the main findings regarding ACE2 expression and function in endocrine tissues. We discuss rapidly evolving knowledge on the potential role of ACE2 and SARS coronaviruses in endocrinology and the development of diabetes mellitus, hypogonadism, and pituitary and …

Β-Amyloid And Tau Drive Early Alzheimer's Disease Decline While Glucose Hypometabolism Drives Late Decline, Tyler C. Hammond, Xin Xing, Chris Wang, David Ma, Kwangsik Nho, Paul K. Crane, Fanny Elahi, David A. Ziegler, Gongbo Liang, Qiang Cheng, Lucille M. Yanckello, Nathan Jacobs, Ai-Ling Lin

Sanders-Brown Center on Aging Faculty Publications

Clinical trials focusing on therapeutic candidates that modify β-amyloid (Aβ) have repeatedly failed to treat Alzheimer’s disease (AD), suggesting that Aβ may not be the optimal target for treating AD. The evaluation of Aβ, tau, and neurodegenerative (A/T/N) biomarkers has been proposed for classifying AD. However, it remains unclear whether disturbances in each arm of the A/T/N framework contribute equally throughout the progression of AD. Here, using the random forest machine learning method to analyze participants in the Alzheimer’s Disease Neuroimaging Initiative dataset, we show that A/T/N biomarkers show varying importance in predicting AD development, with elevated biomarkers of Aβ …

Efficacy Of A Novel Mitochondrial-Derived Peptide In A Porcine Model Of Myocardial Ischemia/Reperfusion Injury, Thomas E. Sharp, Zhenwei Gong, Amy Scarborough, Eric S. Goetzman, Murtuza J. Ali, Pablo Spaletra, David J. Lefer, Radhika H. Muzumdar, Traci T. Goodchild

School of Medicine Faculty Publications

With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac …

Evolving Role For Pharmacotherapy In Nafld/Nash, Suzanna L. Attia, Samir Softic, Marialena Mouzaki

Pediatrics Faculty Publications

Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent, dynamic disease that occurs across the age spectrum and can lead to cirrhosis and hepatocellular carcinoma. There are currently no US Food and Drug Administration (FDA) approved treatments for NAFLD; however, this is a field of active research. This review summarizes emerging pharmacotherapies for the treatment of adult and pediatric NAFLD. Investigated pharmacotherapies predominantly target bile acid signaling, insulin resistance, and lipid handling within the liver. Three drugs have gone on to phase III trials for which results are available. Of those, obeticholic acid is the single agent that demonstrates promise …

A Follow-Up Phone Call To Post-Operative Patients Using The Five A’S, Brittney Ochs

Doctor of Nursing Practice Final Manuscripts

Abstract

Background: The 2016 National Survey on Drug Use and Health reported that 53 percent of people that misused pain relievers in the past year received them from a friend or relative. The NIDA describes that from 2002 to 2008 that drug abuse in service members went from 2% to 11%. Often patients are initially prescribed and introduced to opioid medication for acute pain. One such circumstance is in the perioperative period that could provide an opportunity to promote opioid-sparing techniques to reduce the exposure to opioids.

Purpose of Project: To assess discharge medication characteristics and reinforce discharge medication instructions …

Fall Prevention Assessment In The Intermediate Care Patient Population, Dawn Rose

Doctor of Nursing Practice Final Manuscripts

Fall Prevention Assessment in the Intermediate Care Patient Population

Falls cause greater than 600,000 deaths per year and are the most common injury in people over 65 years of age. Fall prevention in the acute care setting has been identified as key goal in the most recent JCAHO review process. Falls on an intermediary care unit lead to an increased rate of morbidity, delayed discharge, and excess cost expenditure.

Even with appropriate evidence-based tools in place, Hospital A’s intermediate care unit, recorded an increased rate of falls; the highest rate in its health care system. An investigation identified factors contributing …

Twice-Daily Doravirine Overcomes The Interaction Effect From Once-Weekly Rifapentine And Isoniazid In Healthy Volunteers., Edwin Lam, Joseph Schaefer, Richard Zheng, Tingting Zhan, Walter K. Kraft

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Doravirine (DOR) is a non‐nucleoside reverse transcriptase inhibitor indicated for the treatment of human immunodeficiency virus‐1 (HIV‐1). Its use in combination with rifapentine (RPT), an anti‐tuberculosis antibiotic, may reduce the exposure of DOR compromising viral suppression in those living with HIV‐1 co‐infected with tuberculosis. We conducted a prospective, phase I, open label, two‐period, fixed sequence, drug interaction study to evaluate the effect of once‐weekly RPT and isoniazid (INH) on the pharmacokinetics of DOR in healthy volunteers. DOR 100 mg was administered alone twice‐daily for 4 days in period 1. In period 2, once‐weekly RPT+INH was co‐administered with multiple doses of …

A Review Of Human Immunodeficiency Virus, Sophie Silver

Senior Honors Theses

Human immunodeficiency virus, also referred to as HIV, is a devastating virus which has infected millions. Characterized as a retrovirus, HIV has an RNA genome, which is reverse transcribed into DNA upon entry into the host cell. HIV primarily affects CD4⁺ T cells and is diagnosed by the significant reduction of CD4⁺ T cells. While no cure has been discovered yet, antiretroviral therapy (ART) has been demonstrated as an effective treatment option. In the progression of HIV, additional HIV-associated diseases may arise, including HIV-associated psoriasis and sensory neuropathy. In addition to the use of ART, clinicians often prescribe …

Myeloid-Specific Deficiency Of Pregnane X Receptor Decreases Atherosclerosis In Ldl Receptor-Deficient Mice, Yipeng Sui, Zhaojie Meng, Se-Hyung Park, Wei-Wei Lu, Christopher Livelo, Qi Chen, Tong Zhou, Changcheng Zhou

Pharmacology and Nutritional Sciences Faculty Publications

Abstract The pregnane X receptor (PXR) is a nuclear receptor that can be activated by numerous drugs and xenobiotic chemicals. PXR thereby functions as a xenobiotic sensor to coordinately regulate host responses to xenobiotics by transcriptionally regulating many genes involved in xenobiotic metabolism. We have previously reported that PXR has pro-atherogenic effects in animal models, but how PXR contributes to atherosclerosis development in different tissues or cell types remains elusive. In this study, we generated an LDL receptor-deficient mouse model with myeloid-specific PXR deficiency (PXR^ΔMyeLDLR^−/−) to elucidate the role of macrophage PXR signaling in atherogenesis. The …

Photoactivatable Cre Recombinase 3.0 For In Vivo Mouse Applications, Kumi Morikawa, Kazuhiro Furuhashi, Carmen De Sena-Tomas, Alvaro L. Garcia-Garcia, Ramsey Bekdash, Alison D. Klein, Nicholas Gallerani, Hannah E. Yamamoto, Seon Hye E. Park, Grant S. Collins, Fuun Kawano, Moritoshi Sato, Chyuan Sheng Lin, Kimara L. Targoff, Edmund Au, Michael C. Salling, Masayuki Yazawa

School of Medicine Faculty Publications

Optogenetic genome engineering tools enable spatiotemporal control of gene expression and provide new insight into biological function. Here, we report the new version of genetically encoded photoactivatable (PA) Cre recombinase, PA-Cre 3.0. To improve PA-Cre technology, we compare light-dimerization tools and optimize for mammalian expression using a CAG promoter, Magnets, and 2A self-cleaving peptide. To prevent background recombination caused by the high sequence similarity in the dimerization domains, we modify the codons for mouse gene targeting and viral production. Overall, these modifications significantly reduce dark leak activity and improve blue-light induction developing our new version, PA-Cre 3.0. As a resource, …