Medicine and Health Sciences Commons^™

Protein Phosphatase 2a Regulates Xanthine Oxidase-Derived Ros Production In Macrophages And Influx Of Inflammatory Monocytes In A Murine Gout Model, Sandy Elsayed, Khaled A. Elsaid

Pharmacy Faculty Articles and Research

Background: Gout is a common arthritis, due to deposition of monosodium urate (MSU) crystals which results in IL-1β secretion by tissue-resident macrophages. Xanthine oxidase (XO) catalyzes uric acid (UA) production and in the process, reactive oxygen species (ROS) are generated which contributes to NLRP3 inflammasome activation. Protein phosphatase 2A (PP2A) may be involved in regulating inflammatory pathways in macrophages. The objective of this study was to investigate whether PP2A regulates gout inflammation, mediated by XO activity modulation. We studied UA and ROS generations in MSU stimulated murine bone marrow derived macrophages (BMDMs) in response to fingolimod phosphate, a PP2A activator, …

Is There A Role For Allogeneic Hematopoietic Stem Cell Transplantation For Refractory Follicular Lymphoma?, Yang Yang, Xia Bi, Mia Gergis, Usama Gergis

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

No abstract provided.

Dynamics Of Prion Proliferation Under Combined Treatment Of Pharmacological Chaperones And Interferons, Yair Antonio Castillo

Annual Symposium on Biomathematics and Ecology Education and Research

No abstract provided.

Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …

Synthesis Of Trifluoromethyl Ketones By (Diethylamino) Sulfur Trifluoride (Dast)-Mediated Nucleophilic Trifluoromethylation Of Benzoic Acids, Michael A. Vescio

Honors College Theses

Within the past few decades, the presence of fluorine containing

organic molecules has increased significantly. Many of the

current industrial production methods are not cost-effective,

practical, or inherently safe. This work describes a new methodology

for the synthesis of trifluoromethyl ketones. Our new method involves

the use of benzoic acid and trifluoromethyl trimethylsilane (TMSCF₃) as starting

materials along with diethylamino sulfur trifluoride (DAST) as a reagent

to obtain moderate to good yields of expected products in a short

reaction times.

Electromechanical Effects On Micro And Nano Particles Generated From Drug Delivery Devices And Their Implications In Flow And Deposition Efficiency, Mohammed Ali, Mark Miller

Technology Faculty Publications and Presentations

This experimental investigation was undertaken to quantify the electrostatic charge and aerodynamic size distribution of the medicinal drug particles inhaled through an in-vitro mouth-throat (MT) in order to compare the amount of drugs can be delivered to the human lung while mimicking a patient is either sitting or lying. The MT model is a cadaver-based replica cast of human oral-pharyngeal-laryngeal region. Tested drug aerosols were generated by a commercially available metered dose inhaler (MDI). The MT model was placed inside a humidity (95%) and temperature (37^oC) controlled chamber. Its mouth-inlet was positioned horizontally and vertically to simulate sitting …

Differential Expression And Activities Of Cytochrome P450 3a In The Rat Brain Microsomes And Mitochondria, Nouf Alshammari, Devaraj Venkatapura Chandrashekar, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

Midazolam (MDZ), a benzodiazepine derivative, is metabolized to 1′- and 4-hydroxylated metabolites (1′-OH-MDZ and 4-OH-MDZ, respectively) by cytochrome P450 3A (CYP3A). The purpose of this study was to investigate the CYP3A-mediated hydroxylation of MDZ in the rat brain mitochondria (MT). Brain microsomes (MC) and MT fractions were prepared from rats (n = 8) using differential and density gradient centrifugations, and the purity of the fractions was evaluated using VDAC1 and calreticulin as markers of MT and MC, respectively. The formation rates of 1′-OH-MDZ and 4-OH-MDZ in the rat brain MC and MT samples were determined using an LC–MS/MS method …

Metabolic Pathways Enriched According To Erg Status Are Associated With Biochemical Recurrence In Hispanic/Latino Patients With Prostate Cancer, Natalia L. Acosta-Vega, Rodolfo Varela, Jorge Andrés Mesa, Jone Garai, Melody C. Baddoo, Alberto Gómez-Gutiérrez, Silvia J. Serrano-Gómez, Marcela Nuñez Lemus, Martha Lucía Serrano, Jovanny Zabaleta, Alba L. Combita, María Carolina Sanabria-Salas

School of Medicine Faculty Publications

Background: The role of ERG-status molecular subtyping in prognosis of prostate cancer (PCa) is still under debate. In this study, we identified differentially expressed genes (DEGs) according to ERG-status to explore their enriched pathways and implications in prognosis in Hispanic/Latino PCa patients. Methods: RNA from 78 Hispanic PCa tissues from radical prostatectomies (RP) were used for RNA-sequencing. ERGhigh/ERGlow tumor groups were determined based on the 1.5-fold change median expression in non-tumor samples. DEGs with a False Discovery Rate (FDR) < 0.01 and a fold change >2 were identified between ERGhigh and ERGlow tumors and submitted to enrichment analysis in MetaCore. Survival and association analyses were performed …

The Effect Of Fatty Acid Synthase (Fasn) Depletion In Pulmonary Metastatic Formation In Breast Cancer Murine Models, Zilin Xianyu

The Journal of Purdue Undergraduate Research

No abstract provided.

Gutka Consumption And Dietary Partialities Explaining Anemia In Women Of A Coastal Slum Of Karachi, Pakistan: A Mixed-Method Study, Ameer Muhammad, Sarah Saleem, Daniyaal Ahmad, Eleze Tariq, Yasir Shafiq

Community Health Sciences

Background: Limited literature is available on the dietary pattern and its consequences on health of women living in coastal slums of Karachi, Pakistan.
Material and methods: The study employed a mixed-method approach where concurrent quantitative and qualitative assessments were carried out. An analytical cross-sectional survey was conducted to collect information on demographic, household, obstetrics characteristics, and dietary pattern of married women of reproductive age (MWRA). Blood samples were collected to identify the hemoglobin level to determine anemia. For the qualitative component, focus group discussions were carried out with women and in-depth interviews with shopkeepers to understand the availability of food …

Naloxone Administration And Relationship To Opioid Overdose Outcomes, Devon Kane, Allison Mendonca, Leah Wald

Non-Thesis Student Work

This study aimed to look at naloxone administration in opioid overdose patients age 18-35 and its effect on patient outcomes in healthcare settings. From 1999 to 2018, deaths due to opioid overdoses experienced a six-fold increase in the United States. Naloxone is now being used in over 1% of all emergency medical service (EMS) encounters nationwide and EMS use is associated with subsequent overdose due to not receiving the community resources from the local emergency department (ED). Databases used were Umaine One Search, Nursing Reference Center Plus, and Cinahl Full Text Search. Search terms and phrases included, “naloxone availability,” “narcan,” …

Identification And Characterization Of Epicuticular Proteins Of Nematodes Sharing Motifs With Cuticular Proteins Of Arthropods, Bruno Betschart, Marco Bisoffi, Ferial Alaeddine

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Specific collagens and insoluble proteins called cuticlins are major constituents of the nematode cuticles. The epicuticle, which forms the outermost electron-dense layer of the cuticle, is composed of another category of insoluble proteins called epicuticlins. It is distinct from the insoluble cuticlins localized in the cortical layer and the fibrous ribbon underneath lateral alae. Our objective was to identify and characterize genes and their encoded proteins forming the epicuticle. The combination between previously obtained laboratory results and recently made available data through the whole-genome shotgun contigs (WGS) and the transcriptome Shotgun Assembly (TSA) sequencing projects of Ascaris suum allowed us …

Frontiers In The Self-Assembly Of Charged Macromolecules, Khatcher O. Margossian

Doctoral Dissertations

The self-assembly of charged macromolecules forms the basis of all life on earth. From the synthesis and replication of nucleic acids, to the association of DNA to chromatin, to the targeting of RNA to various cellular compartments, to the astonishingly consistent folding of proteins, all life depends on the physics of the organization and dynamics of charged polymers. In this dissertation, I address several of the newest challenges in the assembly of these types of materials. First, I describe the exciting new physics of the complexation between polyzwitterions and polyelectrolytes. These materials open new questions and possibilities within the context …

Biomedical Applications Of Protein Films And Polymeric Nanomaterials, Sanjana Gopalakrishnan

Doctoral Dissertations

Biomaterials are widely applied for the diagnosis and treatment of numerous diseases. In addition to fulfilling specific biological functions, biomaterials must also be non-toxic, biocompatible, and sterilizable to be regarded as safe-for-use. Polymers are excellent candidates for fabricating functional biomaterials due to their wide availability and varied properties and may be natural or synthetic. Polymer precursors are fabricated into coatings, foams, scaffolds, gels, composites, and nanomaterials for several biomedical applications. This dissertation focuses on two types of polymeric biomaterials – protein-based materials and synthetic polymeric nanoparticles. Proteins are biopolymers that naturally occur with a variety of structural and functional properties. …

Innovative Therapeutic Approach To Chemical Burns Produced By Vesicants; An Experimental Study, Cristina Anca Secara, Otilia Liudmila Cinteza, Diana Popescu, Claudia Valentina Popa, Camelia Andreea Hirjeu, Oana Cristina Voinea, Luiza Georgia Serbanescu, Andreea Marilena Pauna, Mihail Tudosie

Journal of Mind and Medical Sciences

Vesicants are compounds that cause severe toxic effects on various tissues. Such chemical action causes tissue necrosis, with clinical expression of skin lesions with a burning character and characteristic blisters. Clinical toxic effects of cutaneous vesicles are correlated with the absorbed dose and exposure time. The goals of the study are to evaluate in vitro the skin toxicity produced by the vesicant chemical compound 2-chloroethyl-ethyl sulfide (CEES), to develop a complex antidote formula, and to optimize the therapeutic efficacy by inclusion in controlled release systems. The experimental protocol aims at the in vitro evaluation of the cytotoxicity of the vesicant …

Maternal Prenatal Cortisol Trajectories Predict Accelerated Growth In Infancy, Jennifer Hahn-Holbrook, Elysia Poggi Davis, Curt A. Sandman, Laura M. Glynn

Psychology Faculty Articles and Research

Higher maternal cortisol in pregnancy has been linked to childhood obesity. Much of the previous research has been limited in that cortisol in pregnancy is only measured at one time-point, precluding the ability to examine critical timing effects of prenatal maternal cortisol. To fill this gap, this longitudinal study measured maternal plasma cortisol at 15, 19, 25, and 31 weeks of pregnancy, and assessed infant body mass index percentile (BMIP)1 at birth, 3, 6, 12, and 24 months in 189 mother-infant pairs. Three distinct patterns of maternal cortisol in pregnancy (typical, steep, and flat trajectories) were identified using general growth …

A Machine Learning Model Of Response To Hypomethylating Agents In Myelodysplastic Syndromes, Nathan Radakovich, David A. Sallman, Rena Buckstein, Andrew Brunner, Amy Dezern, Sudipto Mukerjee, Rami Komrokji, Najla Al-Ali, Jacob Shreve, Yazan Rouphail, Anne Parmentier, Alexandre Mamedov, Mohammed Siddiqui, Yihong Guan, Teodora Kuzmanovic, Metis Hasipek, Babal Jha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Aziz Nazha

Department of Medical Oncology Faculty Papers

Hypomethylating agents (HMA) prolong survival and improve cytopenias in individuals with higher-risk myelodysplastic syndrome (MDS). Only 30-40% of patients, however, respond to HMAs, and responses may not occur for more than 6 months after HMA initiation. We developed a model to more rapidly assess HMA response by analyzing early changes in patients’ blood counts. Three institutions’ data were used to develop a model that assessed patients’ response to therapy 90 days after the initiation using serial blood counts. The model was developed with a training cohort of 424 patients from2 institutions and validated on an independent cohort of 90 patients. …

Seasonal Affective Disorder Treatment: Light Therapy Versus Ssri Therapy, Gabriella M. Hinde, Hannah Dyer, Ash Werner, Michaela Cisowski

Non-Thesis Student Work

To determine the effect of pharmacological and nonpharmacological treatments for seasonal depression in college students, we asked the following evidence-based PICO question: In college students (ages 18-25) with seasonal affective disorder (SAD), how does SSRI (Selective Serotonin Reuptake Inhibitor) therapy compared to light therapy affect seasonal depression syndrome? Seasonal affective disorder is synonymously used with the terminology seasonal depression due to the clinical manifestations that encompass depression, such as low energy, feelings of sadness, emptiness, or hopelessness. SAD begins in the fall months and peaks in the winter months due to a decrease in Vitamin D and ultraviolet (UV) ray …

September / October 2022, Randy Curry, Cindy Brooks

RURAL ROCKS

PLS presents the 7^th Annual Substance Use Disorder Seminar with Dr. Jake Nichols.

Fighting Heroin Abuse With Heroin: How Legalizing Prescription Heroin Has Changed The Way New Generations Use Drugs, Claire Ridley

Independent Study Project (ISP) Collection

In the 1980s, Switzerland was embroiled in two simultaneous crises: widespread heroin use and spreading HIV/AIDS. Zurich became the capital of heroin consumption, with groups gathering in public parks and sharing needles to inject heroin. In response to these crises, several Swiss cities started conducting randomized control trials where they offered prescription heroin to help people addicted to heroin consume the drug safely and eventually recover from their addiction. As these trials reported positive results of maintaining better health outcomes for those undergoing treatment, the Swiss people supported federally legalizing heroin-assisted treatment and expanding access to harm reduction services in …

Detailing The Effects Of Cbd On Parp And Survivin Expression In Ewing Sarcoma, Tyler Carter

Theses

Ewing sarcoma (ES) is an aggressive pediatric bone cancer with low five-year survival rates, particularly with recurrent disease because ES often becomes resistant to chemotherapy in these recurrences. Cannabidiol (CBD) has been identified as a potentially promising therapeutic for patients with ES. In other cancer types, CBD has demonstrated effects on two major proteins that contribute to chemotherapy resistance. The first, Poly (ADP-ribose) Polymerase I (PARP1), is a DNA damage repair enzyme that is overexpressed in recurrent ES. Though chemotherapy induces DNA damage in these cancer cells, the high levels of PARP1 facilitate repair of the DNA, allowing the mutated …

Developing An Alcohol And Other Drug Serious Game For Adolescents: Considerations For Improving Student Engagement, Joanna Nicholas, Brennen Mills, Sara Hansen, Stephen J. Bright, Heather Boyd, Luke Brook, Jess Watson, Luke Hopper

Research outputs 2022 to 2026

Objectives: To explore perceptions of alcohol and other drug (AOD) education and digital game design preferences among Australian adolescents with the goal of identifying key factors to promote engagement in an AOD serious game for Australian secondary school students. Methods: Semi-structured focus groups were conducted with 36 adolescents aged between 13 and 18 years. Qualitative data was analysed using thematic analysis. Results: Participants described heightened engagement with AOD education that incorporated relatable and relevant real-life stories and interactive discussions. They also expressed a desire for learning to focus on practical strategies to reduce AOD harm and overcome social pressure to …

State Trends Of Cannabis Liberalization As A Causal Driver Of Increasing Testicular Cancer Rates Across The Usa, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Background:

The cause of the worldwide doubling-tripling of testicular cancer rates (TCRs) in recent decades is unknown. Previous cohort studies associated cannabis use with TCR including dose–response relationships but the contribution of cannabis to TCRs at the population level is unknown. This relationship was tested by analyzing annual trends across US states and formally assessed causality. Four US datasets were linked at state level: age-adjusted TCRs from Centers for Disease Control Surveillance Epidemiology and End Results database; drug use data from annual National Survey of Drug Use and Health including 74.1 % response rate; ethnicity and median household income data …

Pharmacists’ Response To The Opioid Crisis: A California Naloxone Survey, Jerika T. Lam, Moom Roosan, Mary A. Gutierrez, Enrique Seoane-Vazquez

Pharmacy Faculty Articles and Research

This study aimed to assess pharmacists’ response to the current opioid crisis in California, particularly regarding the prevalence of naloxone furnishing (or dispensing without a prescription) and prescriptions for medication-assisted treatment (MAT) drugs for opioid use disorder (OUD) to patients and consumers.

The Effects Of Cannabidiol On Aqueous Humor Outflow And Trabecular Meshwork Cell Signaling, Alyssa S. Aebersold, Zhao-Hui Song

Faculty Scholarship

Intraocular pressure (IOP) is regulated primarily through aqueous humor production by ciliary body and drainage through uveoscleral and trabecular meshwork (TM) tissues. The goal of this study was to measure the effect of non-psychotropic cannabidiol (CBD) on aqueous humor outflow through TM and assess the effect of CBD on the TM cell signaling pathways that are important for regulating outflow. Perfused porcine eye anterior segment explants were used to investigate the effects of CBD on aqueous humor outflow. Cultured porcine TM cells were used to study the effects of CBD on TM cell contractility, myosin light chain (MLC) and myosin …

Interpretable Machine Learning Models For Molecular Design Of Tyrosine Kinase Inhibitors Using Variational Autoencoders And Perturbation-Based Approach Of Chemical Space Exploration, Keerthi Krishnan, Ryan Kassab, Steve Agajanian, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

In the current study, we introduce an integrative machine learning strategy for the autonomous molecular design of protein kinase inhibitors using variational autoencoders and a novel cluster-based perturbation approach for exploration of the chemical latent space. The proposed strategy combines autoencoder-based embedding of small molecules with a cluster-based perturbation approach for efficient navigation of the latent space and a feature-based kinase inhibition likelihood classifier that guides optimization of the molecular properties and targeted molecular design. In the proposed generative approach, molecules sharing similar structures tend to cluster in the latent space, and interpolating between two molecules in the latent space …

Controlling Myosin’S Function Via Interactions Between The Substrate And The Active Site, Mike K. Woodward

Doctoral Dissertations

Molecular motors, such as myosin, have evolved to transduce chemical energy from ATP into mechanical work to drive essential cellular processes, from muscle contraction to vesicular transport. Dysfunction in these motors is a root cause of many pathologies necessitating the application of intrinsic control over molecular motor function. We hypothesized that altering the myosin’s energy substrate via minor positional changes to the triphosphate portion of the molecule will allow us to control the protein and affect its in vitro function. We utilized positional isomers of a synthetic non-nucleoside triphosphate, azobenzene triphosphate, and assessed whether myosin’s force- and motion-generating capacity could …

Novel Designer Benzodiazepines: Comprehensive Review Of Evolving Clinical And Adverse Effects., Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan David Kaye

School of Pharmacy Faculty Articles

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4

Novel Designer Benzodiazepines: Comprehensive Review Of Evolving Clinical And Adverse Effects, Amber N. Edinoff, Catherine A. Nix, Amira S. Odisho, Caroline P. Babin, Alyssa G. Derouen, Salim C. Lutfallah, Elyse M. Cornett, Kevin S. Murnane, Adam M. Kaye, Alan D. Kaye

School of Medicine Faculty Publications

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. …

Targeted Next-Generation Sequencing Of Congenital Hypothyroidism-Causative Genes Reveals Unexpected Thyroglobulin Gene Variants In Patients With Iodide Transport Defect, Carlos Eduardo Bernal Barquero, Romina Celeste Geysels, Virginie Jacques, Gerardo Hérnan Carro, Mariano Martín, Victoria Peyret, María Celeste Abregú, Patricia Papendieck, Ana María Masini-Repiso, Frédérique Savagner, Ana Elena Chiesa, Cintia E. Citterio, Juan Pablo Nicola

Pharmacy Faculty Articles and Research

Congenital iodide transport defect is an uncommon autosomal recessive disorder caused by loss-of-function variants in the sodium iodide symporter (NIS)-coding SLC5A5 gene and leading to dyshormonogenic congenital hypothyroidism. Here, we conducted a targeted next-generation sequencing assessment of congenital hypothyroidism-causative genes in a cohort of nine unrelated pediatric patients suspected of having a congenital iodide transport defect based on the absence of 99mTc-pertechnetate accumulation in a eutopic thyroid gland. Although, unexpectedly, we could not detect pathogenic SLC5A5 gene variants, we identified two novel compound heterozygous TG gene variants (p.Q29* and c.177-2A>C), three novel heterozygous TG gene variants (p.F1542Vfs*20, p.Y2563C, and …