Medical Pharmacology Commons^™

Delineating The Upc2a Regulon In Candida Glabrata, Yu Li

Theses and Dissertations (ETD)

Candida glabrata is the second most common cause of invasive candidiasis. Intrinsic resistance has greatly limited the utility of the triazole antifungal, fluconazole, in the treatment of invasive fungal infection. The transcription factor Upc2 regulates the expression of sterol biosynthesis genes in yeast. Disrupting UPC2A in C. glabrata greatly increases its susceptibility to fluconazole (FLU) in both FLU-susceptible and -resistant clinical isolates. Therefore, the Upc2A and its target genes represent a potential pathway for overcoming FLU resistance in C. glabrata. We aimed to delineate the Upc2A regulon to determine its target genes involved in FLU resistance. Transcriptome sequencing (RNA-seq) analysis …

Opioid And Naloxone Training In A Rural School District, Allyson C. Waldron

UNLV Theses, Dissertations, Professional Papers, and Capstones

The opioid epidemic is a national health emergency in the United States, with over 128 people dying each day due to an opioid overdose. It is estimated that 4.3 million people over the age of 12 use opioids without a medical need, and 1.3 million youth ages 12-17 use opioids inappropriately. Drug overdose deaths have become the leading cause of accidental death in the United States, prompting the U.S. Surgeon General and the World Health Organization to advise that more Americans have access to naloxone and understand how to use this life-saving drug correctly. Naloxone is an opioid antagonist, used …

The Effects Of Progesterone Induced Blocking Factor And 17-Hydroxyprogesterone Caproate On The Pathophysiology Of Preeclampsia, Kyleigh M. Comley

Honors Theses

Preeclampsia (PE) is responsible for about 20% of the 13 million preterm births each year worldwide, including 100,000 cases annually in the United States. Despite being a leading cause of maternal and perinatal morbidity, the mechanisms of pathogenesis are still largely unknown. PE is progesterone deficient state characterized by hypertension, chronic immune activation, endothelial dysfunction and severe forms can lead to seizures. Treatment of seizures includes the administration of magnesium sulfate (MgSO4) though not all PE patients are responsive, and it does not decrease PE-associated hypertension. To resolve these conditions, PE patients are delivered early thereby making PE the leading …

Magnitude Based Inference, Sharlo Bayless, Trevor J. Bihl

Medical Student Research Symposium Abstracts and Posters

Though its use is widespread in research, null hypothesis significance testing is not without flaws. Out of a desire to provide a more practical approach to solving statistical problems in certain fields, Magnitude Based Inference (MBI) was created. MBI is a statistical method that was developed by Will G Hopkins and Alan M Batterham, two researchers in Sports and Exercise Science, in 2009.The main issues that they wanted to address with null hypothesis significance testing (NHST),were: 1) the need for a large sample size,2) the confusing language, and 3) the arbitrary selection of a p value of 0.05 in testing …

Triamcinolone With Vitamin D Synergistic Efficacy In Psoriasis, Steven Repas, Jeffrey B. Travers

Medical Student Research Symposium Abstracts and Posters

Psoriasis is one of the most common skin conditions in the United States affecting more than 8 million people. High amounts of vitamin D has been shown to be effective in treatment of psoriasis. It also has a well-documented safety profile at the doses and duration that will be used during this study. Triamcinolone and other topical corticosteroids are considered a first line treatment for mild to moderate psoriasis with a well-documented safety profile. Individually both of these medications have shown effectiveness in the management and treatment of mild to moderate psoriasis. This study is designed to test whether a …

Uvb-Induced Microvesicle Particle Release In Human Skin In Vivo Is Diminished Following Oral Vitamin C And E Antioxidant Administration, Benjamin Schmeusser, Cameron Mcglone, Jeffrey B. Travers

Medical Student Research Symposium Abstracts and Posters

An important question in photobiology asks how Ultraviolet B (UVB, 290 – 320 nm) radiation, which mostly absorbs in the outer epidermis of skin, can generate a systemic response such as immunosuppression. Previous in vitro and ex vivo studies demonstrate UVB-dependent release of bioactive molecule-containing microvesicle particles (MVPs) from keratinocytes. Furthermore, MVP release is diminished upon antioxidant administration. The purpose of this study is to examine UVB-induced MVP release and antioxidant response in vivo. In this IRB-approved study, 8 male participants with Fitzpatrick type I or II skin were treated with 1000 J/m2 UVB irradiation to a 5 by 5 …

The Crosstalk Between Insulin Resistance, Systemic Inflammation, Redox Imbalance And The Thyroid In Subjects With Obesity, Nicoleta Răcătăianu, Nicoleta Valentina Leach, Sorana D. Bolboacă, Maria Loredana Soran, Mirela Flonta, Ana Valea, Andrada-Luciana Lazăr, Cristina Ghervan

Journal of Mind and Medical Sciences

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels …

Response To Correspondence On "Reproducibility Of Crispr-Cas9 Methods For Generation Of Conditional Mouse Alleles: A Multi-Center Evaluation", Channabasavaiah B. Gurumurthy, Aidan R. O'Brien, Rolen M. Quadros, John Adams, Pilar Alcaide, Shinya Ayabe, Johnathan Ballard, Surinder K. Batra, Marie-Claude Beauchamp, Kathleen A. Becker, Guillaume Bernas, David Brough, Francisco Carrillo-Salinas, Wesley Chan, Hanying Chen, Ruby Dawson, Victoria Demambro, Jinke D'Hont, Katharine Dibb, James D. Eudy, Lin Gan, Jing Gao, Amy Gonzales, Anyonya Guntur, Huiping Guo, Donald W. Harms, Anne Harrington, Kathryn E. Hentges, Neil Humphreys, Shiho Imai, Hideshi Ishii, Mizuho Iwama, Eric Jonasch, Michelle Karolak, Bernard Keavney, Nay-Chi Khin, Masamitsu Konno, Yuko Kotani, Yayoi Kunihiro, Imayavaramban Lakshmanan, Catherine Larochelle, Catherine B. Lawrence, Lin Li, Volkhard Lindner, Xian-De Liu, Gloria Lopez-Castejon, Andrew Loudon, Jenna Lowe, Loydie Jerome-Majeweska, Taiji Matsusaka, Hiromi Miura, Yoshiki Miyasaka, Benjamin Morpurgo, Katherine Motyl, Yo-Ichi Nabeshima, Koji Nakade, Toshiaki Nakashiba, Kenichi Nakashima, Yuichi Obata, Sanae Ogiwara, Mariette Ouellet, Leif Oxburgh, Sandra Piltz, Ilka Pinz, Moorthy P. Ponnusamy, David Ray, Ronald J. Redder, Clifford J. Rosen, Nikki Ross, Mark T. Ruhe, Larisa Ryzhova, Ane M. Salvador, Sabrina Shameen Alam, Radislav Sedlacek, Karan Sharma, Chad Smith, Katrien Staes, Lora Starrs, Fumihiro Sugiyama, Satoru Takahashi, Tomohiro Tanaka, Andrew Trafford, Yoshihiro Uno, Leen Vanhoutte, Frederique Vanrockeghem, Brandon J. Willis, Christian S. Wright, Yuko Yamauchi, Xin Yi, Kazuto Yoshimi, Xuesong Zhang, Yu Zhang, Masato Ohtsuka, Satyabrata Das, Daniel J. Garry, Tino Hochepied, Paul Thomas, Jan Parker-Thornburg, Antony D. Adamson, Atsushi Yoshiki, Jean-Francois Schmouth, Andrei Golovko, William R. Thompson, K C Kent Lloyd, Joshua A. Wood, Mitra Cowan, Tomoji Mashimo, Seiya Mizuno, Hao Zhu, Petr Kasparek, Lucy Liaw, Joseph M. Miano, Gaetan Burgio

Journal Articles: Pharmacology & Experimental Neuroscience

No abstract provided.

Novel Insights Into The Anti-Diabetic Mechanism(S) Of Withania Coagulans And Its Active Constituent, Coagulansin-A, Mariyam Khalid Naeem

Dissertations

Type 2 diabetes mellitus has become a serious medical challenge of the 21st century with a dramatic surge in diabetes cases since the last decade. It accounts for 90-95% of all cases of diabetes mellitus. The interplay between insulin resistance and beta cells dysfunction plays a crucial role in the pathophysiology of diabetes mellitus. Type 2 diabetes mellitus is characterized by peripheral insulin resistance in skeletal muscles that leads to a constellation of metabolic disorders, and exhaustion of pancreatic beta cells to maintain euglycemia. The inability of pancreatic beta cells to compensate insulin demand in an insulin-resistant state, result in …

Anti‑Estrogenic And Anti‑Aromatase Activities Of Citrus Peels Major Compounds In Breast Cancer, Maha Salama, Dina Mahmoud Elkersh, Shahira M. Ezzat, Yasmeen Attiaa, Engy A. Mahrous, Mohey Elmazar

Pharmacy

Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC50s and were therefore selected for further assays. In silico molecular modeling …

Point-Of-Care Lung Ultrasound For Covid-19: Findings And Prognostic Implications From 105 Consecutive Patients, Kosuke Yasukawa, Taro Minami, David R Boulware, Ayako Shimada, Ernest A Fischer

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Background: The prognostic value of point-of-care lung ultrasound has not been evaluated in a large cohort of patients with COVID-19 admitted to general medicine ward in the United States. The aim of this study was to describe lung ultrasound findings and their prognostic value in patients with COVID-19 admitted to internal medicine ward.

Method: This prospective observational study consecutively enrolled 105 hospitalized participants with COVID-19 at 2 tertiary care centers. Ultrasound was performed in 12 lung zones within 24 hours of admission. Findings were assessed relative to 4 outcomes: intensive care unit (ICU) need, need for intensive respiratory support, length …

Methamphetamine Associated Cardiomyopathy In Pregnancy: The Distinctions And The Implications, Ashan Hatharasinghe, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction

Methamphetamine associated cardiomyopathy (MAC) and peripartum cardiomyopathy (PPCM) are both rare obstetric conditions. Literature regarding methamphetamine associated cardiomyopathy in the obstetric population is limited, and it can be difficult to make the distinction between the two given the similarities in clinical presentation. However similar, there are significant distinctions in the pathophysiology of these two that can help clinicians with the management process.

Clinical Findings and Outcomes

This case involves a 35-year-old Hispanic G6P5005 at 37 weeks gestation presenting with acute respiratory failure secondary to acute decompensated heart failure with reduced ejection fraction and superimposed preeclampsia leading to urgent cesarean …

Correspondence Between Perceived Pubertal Development And Hormone Levels In 9-10 Year-Olds From The Adolescent Brain Cognitive Development Study., Megan M Herting, Kristina A Uban, Marybel Robledo Gonzalez, Fiona C Baker, Eric C Kan, Wesley K Thompson, Douglas A Granger, Matthew D Albaugh, Andrey P Anokhin, Kara S Bagot, Marie T Banich, Deanna M Barch, Arielle Baskin-Sommers, Florence J Breslin, B J Casey, Bader Chaarani, Linda Chang, Duncan B Clark, Christine C Cloak, R Todd Constable, Linda B Cottler, Rada K Dagher, Mirella Dapretto, Anthony S Dick, Nico Dosenbach, Gayathri J Dowling, Julie A Dumas, Sarah Edwards, Thomas Ernst, Damien A Fair, Sarah W Feldstein-Ewing, Edward G Freedman, Bernard F Fuemmeler, Hugh Garavan, Dylan G Gee, Jay N Giedd, Paul E A Glaser, Aimee Goldstone, Kevin M Gray, Samuel W Hawes, Andrew C Heath, Mary M Heitzeg, John K Hewitt, Charles J Heyser, Elizabeth A Hoffman, Rebekah S Huber, Marilyn A. Huestis, Luke W Hyde, M Alejandra Infante, Masha Y Ivanova, Joanna Jacobus, Terry L Jernigan, Nicole R Karcher, Angela R Laird, Kimberly H Leblanc, Krista Lisdahl, Monica Luciana, Beatriz Luna, Hermine H Maes, Andrew T Marshall, Michael J Mason, Erin C Mcglade, Amanda S Morris, Bonnie J Nagel, Gretchen N Neigh, Clare E Palmer, Martin P Paulus, Alexandra S Potter, Leon I Puttler, Nishadi Rajapakse, Kristina Rapuano, Gloria Reeves, Perry F Renshaw, Claudiu Schirda, Kenneth J Sher, Chandni Sheth, Paul D Shilling, Lindsay M Squeglia, Matthew T Sutherland, Susan F Tapert, Rachel L Tomko, Deborah Yurgelun-Todd, Natasha E Wade, Susan R B Weiss, Robert A Zucker, Elizabeth R Sowell

Institute of Emerging Health Professions Faculty Papers

Aim: To examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.

Methods: Cross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study—a multi-site sample of 9–10 year-olds (n = 11,875)—and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal …

The Role Of Mirnas, Mirna Clusters, And Isomirs In Development Of Cancer Stem Cell Populations In Colorectal Cancer., Victoria A Stark, Caroline O B Facey, Vignesh Viswanathan, Bruce M Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

MicroRNAs (miRNAs or miRs) have a critical role in regulating stem cells (SCs) duringdevelopment and altered expression can cause developmental defects and/or disease. Indeed,aberrant miRNA expression leads to wide-spread transcriptional dysregulation which has beenlinked to many cancers. Mounting evidence also indicates a role for miRNAs in the developmentof the cancer SC (CSC) phenotype. Our goal herein is to provide a review of: (i) current researchon miRNAs and their targets in colorectal cancer (CRC), and (ii) miRNAs that are differentiallyexpressed in colon CSCs. MicroRNAs can work in clusters or alone when targeting different SC genesto influence CSC phenotype. Accordingly, we discuss …

Macrophage-Derived Thrombospondin 1 Promotes Obesity-Associated Non-Alcoholic Fatty Liver Disease, Taesik Gwag, Raja Gopal Reddy Mooli, Dong Li, Sangderk Lee, Eun Young Lee, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Background

Thrombospondin 1 (TSP1) is a multifunctional matricellular protein. We previously showed that TSP1 has an important role in obesity-associated metabolic complications, including inflammation, insulin resistance, cardiovascular, and renal disease. However, its contribution to obesity-associated non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD or NASH) remains largely unknown; thus, we aimed to determine its role.

Methods

High-fat diet or AMLN (amylin liver NASH) diet-induced obese and insulin-resistant NAFLD/NASH mouse models were utilised, in addition to tissue-specific Tsp1-knockout mice, to determine the contribution of different cellular sources of obesity-induced TSP1 to NAFLD/NASH development.

Results

Liver TSP1 levels were increased in experimental obese …

Targeting Parp-1 With Metronomic Therapy Modulates Mdsc Suppressive Function And Enhances Anti-Pd-1 Immunotherapy In Colon Cancer, Mohamed A. Ghonim, Salome V. Ibba, Abdelmetalab F. Tarhuni, Youssef Errami, Hanh H. Luu, Matthew J. Dean, Ali H. El-Bahrawy, Dorota Wyczechowska, Ilyes A. Benslimane, Luis Del Valle, Amir A. Al-Khami, Augusto C. Ochoa, A Hamid Boulares

School of Graduate Studies Faculty Publications

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored. METHODS: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression. Mice treated with azoxymethane/four dextran-sulfate-sodium cycles or mice bred into PARP-1 or treated with olaparib were used to examine the role of PARP-1 in colitis-induced or spontaneous colon …

The Association Of Circulating Amylin With Β-Amyloid In Familial Alzheimer's Disease, Han Gia Ly, Nirmal Verma, Savita Sharma, Deepak Kotiya, Sanda Despa, Erin L. Abner, Peter T. Nelson, Gregory A. Jicha, Donna M. Wilcock, Larry B. Goldstein, Rita Guerreiro, José Brás, Angela J. Hanson, Suzanne Craft, Andrew J. Murray, Geert Jan Biessels, Claire Troakes, Henrik Zetterberg, John Hardy, Tammaryn Lashley, Alzheimer’S Disease Exome Sequencing Group, Florin Despa

Pharmacology and Nutritional Sciences Faculty Publications

Introduction

This study assessed the hypothesis that circulating human amylin (amyloid‐forming) cross‐seeds with amyloid beta (Aβ) in early Alzheimer's disease (AD).

Methods

Evidence of amylin‐AD pathology interaction was tested in brains of 31 familial AD mutation carriers and 20 cognitively unaffected individuals, in cerebrospinal fluid (CSF) (98 diseased and 117 control samples) and in genetic databases. For functional testing, we genetically manipulated amylin secretion in APP/PS1 and non‐APP/PS1 rats.

Results

Amylin‐Aβ cross‐seeding was identified in AD brains. High CSF amylin levels were associated with decreased CSF Aβ42 concentrations. AD risk and amylin gene are not correlated. Suppressed amylin secretion protected …

High-Density Lipoproteins And Serum Amyloid A (Saa), Nancy R. Webb

Pharmacology and Nutritional Sciences Faculty Publications

PURPOSE OF REVIEW: Serum amyloid A (SAA) is a highly sensitive acute phase reactant that has been linked to a number of chronic inflammatory diseases. During a systemic inflammatory response, liver-derived SAA is primarily found on high-density lipoprotein (HDL). The purpose of this review is to discuss recent literature addressing the pathophysiological functions of SAA and the significance of its association with HDL.

RECENT FINDINGS: Studies in gene-targeted mice establish that SAA contributes to atherosclerosis and some metastatic cancers. Accumulating evidence indicates that the lipidation state of SAA profoundly affects its bioactivities, with lipid-poor, but not HDL-associated, SAA capable of …

Heme Oxygenase-1 Affects Cytochrome P450 Function Through The Formation Of Heteromeric Complexes: Interactions Between Cyp1a2 And Heme Oxygenase-1, J. Patrick Connick, James R. Reed, George F. Cawley, Wayne L. Backes

School of Medicine Faculty Publications

Heme oxygenase 1 (HO-1) and the cytochromes P450 (P450s) are endoplasmic reticulum–bound enzymes that rely on the same protein, NADPH-cytochrome P450 reductase (POR), to provide the electrons necessary for substrate metabolism. Although the HO-1 and P450 systems are interconnected owing to their common electron donor, they generally have been studied separately. As the expressions of both HO-1 and P450s are affected by xenobiotic exposure, changes in HO-1 expression can potentially affect P450 function and, conversely, changes in P450 expression can influence HO-1. The goal of this study was to examine interactions between the P450 and HO-1 systems. Using bioluminescence resonance …

Drug Delivery Systems: Exploring Rheological Properties And Therapeutic Effect Of 5-Fu Chitosan Gel For Topical Wound Healing, Samuel Tetteh-Quarshie

Theses, Dissertations and Capstones

Diabetic skin wound is a common complication of diabetes that occurs in about 15% of diabetic patients and often requires prolonged hospitalization for its management and treatment. Natural polymers are used for wound dressing due to their biological adhesiveness, non-toxicity, and biodegradable nature. 5-Fluorouracil (FU) has been shown to alter adipokine expression which is implicated in cutaneous wound repair. Thus, our overall objective was to investigate the utility of chitosan (CS) gel for topical delivery of 5-FU to treat diabetic wounds. We prepared chitosan gel (2% w/w) in serial dilutions of 5-FU (25μg/mL, 2.5μg/mL, 0.25μg/mL, and 0.025μg/mL) and evaluated their …

Cd4+ Effector T Cells Accelerate Alzheimer's Disease In Mice, Jatin Machhi, Pravin Yeapuri, Yaman Lu, Emma Foster, Rupesh Chikhale, Jonathan Herskovitz, Krista L. Namminga, Katherine E. Olson, Mai Mohamed Abdelmoaty, Ju Gao, Rolen M. Quadros, Tomomi Kiyota, Liang Jingjing, Bhavesh D. Kevadiya, Xinglong Wang, Yutong Liu, Larisa Y. Poluektova, Channabasavaiah B. Gurumurthy, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by pathological deposition of misfolded self-protein amyloid beta (Aβ) which in kind facilitates tau aggregation and neurodegeneration. Neuroinflammation is accepted as a key disease driver caused by innate microglia activation. Recently, adaptive immune alterations have been uncovered that begin early and persist throughout the disease. How these occur and whether they can be harnessed to halt disease progress is unclear. We propose that self-antigens would induct autoreactive effector T cells (Teffs) that drive pro-inflammatory and neurodestructive immunity leading to cognitive impairments. Here, we investigated the role of effector immunity and …