Pharmacology Commons^™

Efficacy And Tolerability Of Atomoxetine Use For Patients With Autism Spectrum Disorders And Attention-Deficit/Hyperactivity Disorder (Adhd) Symptoms: A Systematic Review And Meta-Analysis, Angie El-Said

Honors Undergraduate Theses

Introduction: Patients with autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) show more symptoms of ADHD. Since there are more adverse events caused by psychostimulants compared to non-psychostimulants, the use of a non-psychostimulant such as atomoxetine might prove more beneficial for younger patients and/or those with comorbid ADHD. Objective: The aim of this thesis is to determine the efficacy and tolerability of atomoxetine in ASD patients presenting with ADHD, by examining (a) differences in ADHD symptoms for participants receiving atomoxetine versus those receiving placebos, and (b) risk differences in adverse events between these participants. Methods: An electronic search of both …

Development Of Mithramycin Analogues With Improved Efficacy And Reduced Toxicity For Treatment Of Ets-Dependent Tumors In Ewing Sarcoma And Prostate Cancer, Joseph Michael Eckenrode

Theses and Dissertations--Pharmacy

Introduction: Genetic rearrangements in Ewing sarcoma, prostate, and leukemia cells result in activation of oncogenic ETS transcription factor fusions. Mithramycin (MTM) has been identified as an inhibitor of EWS-FLI1 transcription factor, a gene fusion product responsible for oncogenesis in Ewing sarcoma. Despite preclinical success, a phase I/II clinical trial testing MTM therapy in refractory Ewing sarcoma was terminated. Liver and blood toxicities resulted in dose de-escalation and sub-therapeutic exposures. However, the promise of selectively targeting oncogenic ETS transcription factors like EWS-FLI1 prompted us to undertake the discovery of more selective, less toxic analogues of MTM. MTM is a potent inhibitor …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction, Ahmed Hamish Neamah Al-Darraji

Theses and Dissertations--Pharmacology and Nutritional Sciences

Introduction: Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Induced by cardiomyocyte death, MI initiates a prolonged and uncontrolled inflammatory response which impairs the healing process. Immune cells, such as macrophages, play a central role in organizing the early post-MI inflammatory response and the subsequent repair phase. Two activation states of macrophages have been identified with distinct and complementary functions (inflammatory vs. reparatory). This bimodal pattern of macrophage activation is an attractive therapeutic target to favorably resolve post-MI inflammation and enhance recovery. It has been demonstrated that azithromycin (AZM), a commonly used antibiotic with immunomodulatory effects, …

Exploring The Role Of Insulin Receptor Signaling In Hippocampal Learning And Memory, Neuronal Calcium Dysregulation, And Glucose Metabolism, Hilaree N. Frazier

Theses and Dissertations--Pharmacology and Nutritional Sciences

In the late 90’s, emerging evidence revealed that the brain is insulin-sensitive, highlighted by broad expression of brain-specific insulin receptors and reports of circulating brain insulin. Contemporary literature robustly supports the role of insulin signaling in normal brain function and suggests that insulin-related processes diminish with aging, evidenced by decreased signaling markers, reduced insulin receptor density, and lower levels of insulin transport across the blood-brain barrier. In the context of pathological cognitive decline, clinical trials using intranasal insulin delivery have reported positive outcomes on memory and learning in patients with mild cognitive decline or early-stage Alzheimer’s disease. However, while the …

Role Of Mcp-1 And Ccr2 In Ethanol-Induced Damage In The Developing Brain, Kai Zhang

Theses and Dissertations--Pharmacology and Nutritional Sciences

Fetal alcohol spectrum disorders (FASD) are caused by alcohol exposure during pregnancy and is the leading cause of mental retardation. Alcohol exposure during development results in the loss of neurons in the developing brain. The underlying molecular mechanisms are unclear and there currently is no cure for FASD. Ethanol-induced neuronal death is accompanied by neuroinflammation. Chemokine monocyte chemoattractant protein 1 (MCP-1) and its receptor C-C chemokine receptor type 2 (CCR2) are critical mediators of neuroinflammation and microglial activation. Using a third trimester equivalent mouse model of ethanol exposure, we found that treatment of Bindarit (MCP-1 synthesis inhibitor) and RS504393 (CCR2 …

The Effect Of Glucose, Adenosine-5’-Triphosphate, And Adenosine On Glucose Transporter 9 Expression In Mdck Cells, Jamras Kanchanapiboon, Thitima Pengsuparp

The Thai Journal of Pharmaceutical Sciences

This study aimed to investigate the effect of glucose, adenosine triphosphate (ATP) and adenosine and their concentration dependence on GLUT9 expression in hyperglycemic conditions. These compounds have been reported to be associated with hyperglycemia i.

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports (ETD)

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Effects Of A Heroin Conjugate Vaccine On The Antinociceptive And Abuse-Related Effects Of Heroin In Rats And Monkeys, Kathryn L. Schwienteck

Theses and Dissertations

The increase in heroin use is one factor contributing to the current opioid epidemic in the United States. There are three Food and Drug Administration (FDA) approved medications for the treatment of opioid use disorder (OUD), and these include agonist (i.e. methadone and buprenorphine) and antagonist (i.e. naltrexone) therapies. Although these medications are effective for some patients, regulatory constraints for agonist therapies limit access and patient compliance for naltrexone is poor. The development of new therapies, such as immunopharmacotherapies, for the treatment of OUD is a priority for the National Institute of Drug Abuse. A heroin immunopharmacotherapy, or vaccine, produces …

The Analgesic-Like Properties Of Alcohol In Animal Models Of Chronic Pain, Bradley Neddenriep

Theses and Dissertations

Chronic pain and excessive alcohol consumption are individually problems in our society today. Alcohol Use Disorder (AUD) affects 15.1 million adult Americans each year. Chronic pain affects over 100 million people annually in the United States. However, there is growing evidence suggesting that these two conditions can often be interrelated with chronic pain increasing consumption of alcohol, and excessive alcohol consumption increasing pain that leaves a feedback cycle trapping millions of patients in an ever worsening spiral. Large population-based studies show an association between pain and alcohol abuse, suggesting a link between increased alcohol use and reduced pain. While rodent …

Diuretic And Natriuretic Activity Of Faah Inhibition In The Renal Medulla: A Proposed Role Of Palmitoylethanolamide And Its Regulation By Renal Medullary Interstitial Cells, Sara Dempsey

Theses and Dissertations

Hypertension is a critical public health issue worldwide, and in the United States, it is the leading cause of heart disease, stroke, and kidney failure, contributing to more than 1,100 deaths per day. It is proposed that the renal medulla combats increased blood pressure by releasing a neutral lipid from the lipid droplets of medullary interstitial cells, termed medullipin, which induces diuresis- natriuresis and vasodepression. The renal medulla is enriched with fatty acid lipid ethanolamides including the endocannabinoid anandamide (AEA), palmitoylethanolamide (PEA), and oleoylethanolamide (OEA), along with their primary hydrolyzing enzyme fatty acid amide hydrolase (FAAH). Our lab is investigating …

Mitragynine Reduced Morphine-Induced Conditioned Place Preference And Withdrawal In Rodents, Rittinarong Meepong, Thongchai Sooksawate

The Thai Journal of Pharmaceutical Sciences

Introduction: Kratom (Mitragyna speciosa Korth) has been long used in folklore medicine in Southeast Asian countries for its analgesic effects and the treatment of opioid withdrawal. Mitragynine is a major alkaloid found in the leaves of kratom plant th.

Structure-Activity Relationship Studies Of Synthetic Cathinones And Related Agents, Rachel A. Davies

Theses and Dissertations

Synthetic cathinones and related agents represent an international drug abuse problem, and at the same time an important class of clinically useful compounds. Structure-activity relationship studies are needed to elucidate molecular features underlying the pharmacology of these agents. Illicit methcathinone (i.e., MCAT), the prototype of the synthetic cathinone class, exists as a racemic mixture. Though the differences in potency and target selectivity between the positional and optical isomers of synthetic cathinones and related agents have been demonstrated to have important implications for abuse and therapeutic potential, the two MCAT isomers have never been directly compared at their molecular targets: the …

Molecular Targets Of Psychedelics And Their Role In Behavioral Models Of Hallucinogenic Action, Hiba Z. Vohra

Theses and Dissertations

Psychedelics are a subset of hallucinogenic drugs that exert their characteristic effects through agonist activity at the serotonin receptor 2A (5-HT_2A). In this study, I aimed to characterize the modulatory role of the metabotropic glutamate subtype 2 receptor (mGluR2) in the 5-HT_2A-specific rodent model of hallucinogenic action, head-twitch response (HTR). Secondly, I aimed to explore if 5-HT_2A agonist-induced deficits in prepulse inhibition (PPI) of the startle response, an additional model of hallucinogenic action, could be produced in mice. Though 5-HT_2A agonist-induced PPI deficits, which represent interruptions in normal sensorimotor gating, have been described in …

Functionalized Carbon Nanotubes In Hydrophobic Drug Delivery, Kun Chen

Dissertations

The direct incorporation of carboxylated carbon nanotubes (f-CNTs) into hydrophobic drug particles during their formation via anti-solvent precipitation is presented. The approach is tested using two drugs namely antifungal agent Griseofulvin (GF) and antibiotic Sulfamethoxazole (SMZ) that have very different aqueous solubility. It is observed that the f-CNTs dispersed in the water serve as nucleating sites for crystallization and are readily incorporated into the drug particles without altering crystal structure or other properties. The results show that the hydrophilic f-CNTs dramatically enhance dissolution rate for both drugs. The increased degree of functionalization leads to higher hydrophilicity and therefore faster dissolution …

Network Pharmacology-Guided Development Of A Novel Integrative Regimen To Prevent Acute Graft-Vs.-Host Disease, Ming Lyu, Zhengcan Zhou, Xiaoming Wang, Hong Lv, Mei Wang, Guixiang Pan, Yuefei Wang, Guanwei Fan, Xiumei Gao, Benjamin Feng, Yan Zhu

Peer Reviewed Articles

Lapses in the graft-vs.-host disease (GVHD) prophylaxis and side effects of current standard care following allogeneic hematopoietic stem cell transplantation (allo-HSCT) call for novel regimens. Traditional approaches targeting T cells showed limited success in preventing acute GVHD (aGVHD). System medicine showed promising results treating complex diseases such as sepsis and multi-organ dysfunction syndrome (MODS). Adapting established network pharmacology analysis methods, we aimed to develop novel integrative regimens to prevent aGVHD. Our network pharmacology analysis predicted that Xuebijing injection (XBJ) targets a series of key node proteins in aGVHD network. It also unveiled that Salviae miltiorrhizae (Danshen), an herb in Xuebijing …

Targeting Ph Domain Proteins For Cancer Therapy, Zhi Tan

Dissertations and Theses (Open Access)

Targeted therapy has been one of the most promising treatment options for cancer during the past decade. Discoveries of potent and selective small molecule inhibitors are critical to new and promising targeted therapy. Pleckstrin Homology (PH) domain proteins are one of the biggest protein families in the human proteome. However, no drugs have been achieved to the late development stages, let alone getting to the market. Thus, a deeper understanding of this protein family is required and there is an urgent need to develop novel small molecule compounds targeting these proteins.

Studies of PH domains began around two decades ago …

Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush

Electronic Theses and Dissertations

There are thirteen known endogenous EGF-like ligands. We previously reported that Betacellulin (BTC) increases ligand-mediated corneal wound healing more than Epidermal Growth Factor (EGF) [Peterson et al. (2014) IOVS 55(5):2870-80], although the molecular reason for this is unknown. Despite being better at promoting wound healing via enhanced cell migration, BTC has reduced receptor affinity and weaker induction of EGFR phosphorylation. These data indicate that BTC’s response is not due to enhanced affinity or EGFR-kinase activity. Receptor phosphorylation and proximity ligation assays indicate that BTC treatment significantly increases ErbB3 phosphorylation and EGFR:ErbB3 heterodimers. BTC traffics EGFR at a faster rate than …

Profile Interview With Norman E. Fenn, Shannon L. Castek

Purdue Journal of Service-Learning and International Engagement

Shannon L. Castek is a fourth-generation Boilermaker and fourth-professional-year student in the Purdue University College of Pharmacy. Throughout her time in pharmacy school, Shannon has enjoyed supplementing her curricular work with service-learning activities, participating in health screenings and immunization events with the Purdue chapter of the American Pharmacists Association–Academy of Student Pharmacists. She plans to pursue a pharmacy residency following graduation to achieve her dream of becoming an ambulatory care pharmacist. In this article, Shannon highlights the service-learning endeavors of Dr. Norman Fenn in the College of Pharmacy.