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Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara 2019 Southern Methodist University

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of these ...


Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel 2019 Iowa State University

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel

Jonathan Mochel

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at ...


Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel 2019 Iowa State University

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel

Joe Smith

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at ...


Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel 2019 Iowa State University

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel

Lionel Sebbag

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at ...


Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel 2019 Iowa State University

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel

Rachel A. Allbaugh

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at ...


Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel 2019 Iowa State University

Tear Fluid Pharmacokinetics Following Oral Prednisone Administration In Dogs With And Without Conjunctivitis, Lionel Sebbag, Yuqi Yan, Joe S. Smith, Rachel A. Allbaugh, Larry W. Wulf, Jonathan P. Mochel

Veterinary Clinical Sciences Publications

Purpose: To describe the pharmacokinetics (PK) of prednisone and prednisolone in tear fluid of dogs receiving oral prednisone at anti-inflammatory to immunosuppressive doses and to assess the impact of induced conjunctivitis on lacrimal drug levels.

Methods: Six healthy Beagle dogs were administered 4 courses of prednisone at 0.5, 1.0, 2.0, and 4.0 mg/kg given orally once a day for 5 days. At steady state, topical histamine was applied to induce mild (1 mg/mL) or severe (375 mg/mL) conjunctivitis in 1 eye of each dog and tear samples were collected from both eyes at ...


Effects Of Chronic Ethanol Exposure On Stress Coping Style And Genetic States Of Zebrafish (Danio Rerio), Alexander Goodman 2019 University of Nebraska at Omaha

Effects Of Chronic Ethanol Exposure On Stress Coping Style And Genetic States Of Zebrafish (Danio Rerio), Alexander Goodman

Student Research and Creative Activity Fair

Neurotransmitter systems are important in regulating the stress response. If a behavioral response is disproportional to a stressor it is characterized as anxiety-like behavior. Many anxiolytic compounds, such as ethanol, increase stressor engagement, but how these compounds interact with an organism on a neurogenetic level is less understood. In this study, I assessed the impact of chronic ethanol treatment on behavior and gene expression of GABAAreceptors subunits on two strains of zebrafish. Each strain was selectively bred to display the proactive or reactive stress coping style where proactive individuals will actively engage a stressor more than reactive individuals ...


5-Ht2a Deletion Protects Against Clozapine-Induced Hyperglycemia, Radhika Sudhir Joshi, Shishu Pal Singh, Mitradas M. Panicker 2019 University of Massachusetts Medical School

5-Ht2a Deletion Protects Against Clozapine-Induced Hyperglycemia, Radhika Sudhir Joshi, Shishu Pal Singh, Mitradas M. Panicker

Open Access Articles

Clozapine is an antipsychotic known for its superior efficacy in treating drug-resistant Schizophrenia. However, Clozapine induces various side effects such as hyperglycemia, agranulocytosis, weight gain etc. The mechanisms of these Clozapine-induced side effects have remained largely elusive though an important role is ascribed to 5-HT2A (Serotonin receptor subtype-2A). In this pilot study, we report for the first time that the 5-HT2A 'global' knockout mice (Htr2a(-/-)) are resistant to the Clozapine-induced hyperglycemia. Importantly though, the Htr2a(-/-) mice exhibit near normal basal glucose metabolism in the glucose tolerance tests. Collectively, the Htr2a(-/-) mice provide an important tool to study the Clozapine-induced hyperglycemia.


Residual Next-Day Effects Of Alprazolam On Psychomotor Performance And Simulated Driving In Healthy Normal Volunteers, Marion A. Coe 2019 University of Kentucky

Residual Next-Day Effects Of Alprazolam On Psychomotor Performance And Simulated Driving In Healthy Normal Volunteers, Marion A. Coe

Theses and Dissertations--Pharmacology and Nutritional Sciences

The prevalence of drugged driving has increased in the United States, and some prescription medications (e.g., zolpidem) cause impairment after the predicted duration of therapeutic action has elapsed. The aim of this study is to determine if bedtime administration of alprazolam similarly impacts driving performance the following day.

Volunteers were 14 healthy adults (6 males) who completed a double-blind, double-dummy within-subjects design study examining the effects of alprazolam (0.5, 1, & 2mg), zolpidem (10mg), and placebo administered at bedtime on driving performance the following day. The positive control condition was alprazolam (1mg) administered on the test morning. Driving simulator ...


Examination Of The Role Of Neuroimmune Signaling In Drug Addiction, Catherine Levy 2019 University of Colorado, Boulder

Examination Of The Role Of Neuroimmune Signaling In Drug Addiction, Catherine Levy

Undergraduate Honors Theses

Cocaine and oxycodone addictions are chronic, relapsing disorders characterized by maladaptive patterns of drug seeking that create significant impairment for the user. While the homeostatic functions of neuroimmune cells such as microglia and astrocytes have been well characterized, little work has examined the structural and functional alterations of these neuroglial cells following repeated drug intake. The first experiment of this study used male and female Sprague-Dawley rats to examine sex differences in microglial cells following repeated cocaine intake. The second experiment used a rodent model of oxycodone self-administration to test the ability of ibudilast, a non-selective anti-inflammatory drug, to reduce ...


A Revisit To The Pretargeting Concept - A Target Conversion, Guozheng Liu 2018 University of Massachusetts Medical School

A Revisit To The Pretargeting Concept - A Target Conversion, Guozheng Liu

Radiology Publications and Presentations

Pretargeting is often used as a tumor targeting strategy that provides much higher tumor to non-tumor ratios than direct-targeting using radiolabeled antibody. Due to the multiple injections, pretargeting is investigated less than direct targeting, but the high T/NT ratios have rendered it more useful for therapy. While the progress in using this strategy for tumor therapy has been regularly reviewed in the literature, this review focuses on the nature and quantitative understanding of the pretargeting concept. By doing so, it is the goal of this review to accelerate pretargeting development and translation to the clinic and to prepare the ...


Epidermal Growth Factor-Like Ligands Regulate Dimer Selection., Jamie S. Rush 2018 University of Louisville

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 ...


Expression Of Hepatic Cytochrome P450 Drug Metabolizing Enzymes In Diabetes And Diabetic Nephropathy, Cheng Jay Fang 2018 The University of Western Ontario

Expression Of Hepatic Cytochrome P450 Drug Metabolizing Enzymes In Diabetes And Diabetic Nephropathy, Cheng Jay Fang

Electronic Thesis and Dissertation Repository

The prevalence of diabetes worldwide is rapidly increasing. Polypharmacy, along with a high risk of adverse drug reactions, is common in diabetic patients. Cytochrome P450 (CYP) 3A and 2C drug metabolizing enzymes are reduced in chronic kidney disease (CKD), altering drug pharmacokinetics and contributing to adverse drug reactions. A large fraction of commonly prescribed drugs are metabolized by CYP3A and CYP2C. Approximately 40% of all CKD cases are attributed to diabetic nephropathy (DN) and early DN presents as mild kidney disease. This study aims to evaluate the impact of diabetes and DN on levels and activity of hepatic CYP3A and ...


Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle 2018 Worcester Polytechnic Institute

Targeted Delivery Of Bioactive Molecules For Vascular Intervention And Tissue Engineering, Hannah A. Strobel, Elisabet I. Qendro, Eben Alsberg, Marsha W. Rolle

Open Access Articles

Cardiovascular diseases are the leading cause of death in the United States. Treatment often requires surgical interventions to re-open occluded vessels, bypass severe occlusions, or stabilize aneurysms. Despite the short-term success of such interventions, many ultimately fail due to thrombosis or restenosis (following stent placement), or incomplete healing (such as after aneurysm coil placement). Bioactive molecules capable of modulating host tissue responses and preventing these complications have been identified, but systemic delivery is often harmful or ineffective. This review discusses the use of localized bioactive molecule delivery methods to enhance the long-term success of vascular interventions, such as drug-eluting stents ...


The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen 2018 The University of Western Ontario

The Use Of Current Steering During Subthalamic Deep Brain Stimulation To Alleviate Upper Limb Symptoms Of Parkinson's Disease, Shabna Iftikar Mohideen

Electronic Thesis and Dissertation Repository

Subthalamic (STN) deep brain stimulation (DBS) is an established treatment to alleviate the appendicular motor symptoms of Parkinson's Disease (PD). Current steering during DBS allows the unequal fractionation of current between two electrodes on the lead, resulting in a non-spherical electrical field. It is hypothesized that the way the electrical field is shaped will affect a patient’s upper limb symptom alleviation. Seven PD patients who underwent bilateral STN-DBS were tested over four weeks post-operation. 16 current fractionation settings were tested each week at an amplitude that increased weekly. Optimal setting was defined as the setting that provided the ...


Profile Interview With Norman E. Fenn, Shannon L. Castek 2018 Purdue University

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.


The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh 2018 Purdue University

The Pharmaceutical Industry: A Pharmacy Student's Guide, Christian Egly, Yaman Kaakeh

Purdue Journal of Service-Learning and International Engagement

Christian Egly is a fourth-year (P4) pharmacy student in the Purdue University College of Pharmacy. During his years at Purdue, he worked in labs performing bench research in clinical pharmacology and biochemistry. He plans to work in the pharmaceutical industry after graduation. During his fourth year, he completed rotations in business development at Kashiv Pharma, LLC, and was hired there for an internship in 2017. In the article, Christian describes his personal experiences at Kashiv Pharma, LLC, and how industry can positively affect patient communities.


Enriched Physical Environment Attenuates Spatial And Social Memory Impairments Of Aged Socially Isolated Mice, Linmei Wang, Min Cao, Tinglin Pu, Huang Huang, Charles Marshall, Ming Xiao 2018 Nanjing Medical University, China

Enriched Physical Environment Attenuates Spatial And Social Memory Impairments Of Aged Socially Isolated Mice, Linmei Wang, Min Cao, Tinglin Pu, Huang Huang, Charles Marshall, Ming Xiao

Rehabilitation Sciences Faculty Publications

Background: Social isolation in the elderly is one of the principal health risks in an aging society. Physical environmental enrichment is shown to improve sensory, cognitive, and motor functions, but it is unknown whether environmental enrichment can protect against brain impairments caused by social isolation.

Methods: Eighteen-month-old mice were housed, either grouped or isolated, in a standard or enriched environment for 2 months, respectively. Behavioral tests were performed to evaluate cognitive functional and social interaction ability. Synaptic protein levels, myelination, neuroinflammation, brain derived neurotrophic factor, and NOD-like receptor protein 3 inflammasome signaling pathways were examined in the medial prefrontal cortex ...


Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim 2018 Old Dominion University

Macrophages But Not Astrocytes Harbor Hiv Dna In The Brains Of Hiv-1-Infected Aviremic Individuals On Suppressive Antiretroviral Therapy, Allen Ko, Guobin Kang, Julian B. Hattler, Hadiza I. Galadima, Junfeng Zhang, Qingsheng Li, Woong-Ki Kim

Community & Environmental Health Faculty Publications

The question of whether the human brain is an anatomical site of persistent HIV-1 infection during suppressive antiretroviral therapy (ART) is critical, but remains unanswered. The presence of virus in the brains of HIV patients whose viral load is effectively suppressed would demonstrate not only the potential for CNS to act as an anatomical HIV reservoir, but also the urgent need to understand the factors contributing to persistent HIV behind the blood-brain barrier. Here, we investigated for the first time the presence of cells harboring HIV DNA and RNA in the brains from subjects with undetectable plasma viral load and ...


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