Medical Pharmacology Commons^™

Identification Of The Metabolic Enzyme Involved Morusin Metabolism And Characterization Of Its Metabolites By Ultraperformance Liquid Chromatogaphy Quadrupole Time-Of-Flight Mass Spectrometry (Uplc/Q-Tof-Ms/Ms), Xianbao Shi, Brianna Mackie, Gang Zhang, Shuman Yang, Yonggui Song, Dan Su, Yali Liu, Lina Shan

Pharmacology and Toxicology Publications

Morusin, the important active component of a traditional Chinese medicine, Morus alba L., has been shown to exhibit many vital pharmacological activities. In this study, six recombinant CYP450 supersomes and liver microsomes were used to perform metabolic studies. Chemical inhibition studies and screening assays with recombinant human cytochrome P450s were also used to characterize the CYP450 isoforms involved in morusin metabolism. The morusin metabolites identified varied greatly among different species. Eight metabolites of morusin were detected in the liver microsomes from pigs (PLMs), rats (RLMs), and monkeys (MLMs) by LC-MS/MS and six metabolites were detected in the liver microsomes from …

Micrornas Are Involved In The Development Of Morphine-Induced Analgesic Tolerance And Regulate Functionally Relevant Changes In Serpini1., Jenica D. Tapocik, Kristin Ceniccola, Cheryl L. Mayo, Melanie L. Schwandt, Matthew Solomon, Bi-Dar Wang, Truong V. Luu, Jacqueline Olender, Thomas Harrigan, Thomas M. Maynard, Greg I. Elmer, Norman H. Lee

Pharmacology and Physiology Faculty Publications

Long-term opioid treatment results in reduced therapeutic efficacy and in turn leads to an increase in the dose required to produce equivalent pain relief and alleviate break-through or insurmountable pain. Altered gene expression is a likely means for inducing long-term neuroadaptations responsible for tolerance. Studies conducted by our laboratory (Tapocik et al., 2009) revealed a network of gene expression changes occurring in canonical pathways involved in neuroplasticity, and uncovered miRNA processing as a potential mechanism. In particular, the mRNA coding the protein responsible for processing miRNAs, Dicer1, was positively correlated with the development of analgesic tolerance. The …

The Mixed Lineage Kinase-3 Inhibitor Urmc-099 Improves Therapeutic Outcomes For Long-Acting Antiretroviral Therapy., Gang Zhang, Dongwei Guo, Prasanta Dash, Mariluz Araínga, Jayme Wiederin, Nicole A. Haverland, Jaclyn Knibbe-Hollinger, Andrea Martinez-Skinner, Pawel Ciborowski, Val S. Goodfellow, Tadeusz A. Wysocki, Beata J. Wysocki, Larisa Y. Poluektova, Xin-Ming Liu, Joellyn Mcmillan, Santhi Gorantla, Harris A. Gelbard, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

During studies to extend the half-life of crystalline nanoformulated antiretroviral therapy (nanoART) the mixed lineage kinase-3 inhibitor URMC-099, developed as an adjunctive neuroprotective agent was shown to facilitate antiviral responses. Long-acting ritonavir-boosted atazanavir (nanoATV/r) nanoformulations co-administered with URMC-099 reduced viral load and the numbers of HIV-1 infected CD4+ T-cells in lymphoid tissues more than either drug alone in infected humanized NOD/SCID/IL2Rγc-/- mice. The drug effects were associated with sustained ART depots. Proteomics analyses demonstrated that the antiretroviral responses were linked to affected phagolysosomal storage pathways leading to sequestration of nanoATV/r in Rab-associated recycling and late endosomes; sites associated with viral …

Health Professions Division 2016-2017 Catalog, Nova Southeastern University

Health Professions Divisions Course Catalogs and Course Descriptions

No abstract provided.

Novel Cellular Targets Of Aspirin In Chemoprevention Studies On P53, G6pd And C-Myc, Guoqiang Ai

Electronic Theses and Dissertations

Background

Aspirin has generated a significant interest in recent years as a potential chemopreventive agent supported by strong evidence from epidemiological data; however, the mechanisms are not well understood. The objective of this dissertation is to identify novel cyclooxygenase (COX)-independent pathways by which aspirin exerts its anticancer effects in epithelial cancer cell lines. We investigated the effect of aspirin on p53, glucose 6-phosphate dehydrogenase (G6PD), and c-Myc, all of which are known to play a major role in cancer development. p53 is a tumor suppressor protein, often mutated in cancers causing its inactivation. Expression of G6PD is elevated in many …

Bioinnovation Enterprise: An Engine Driving Breakthrough Therapies., Scott A. Waldman, Andre Terzic

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Biological advances have radically expanded our insights into the underpinnings of health and disease. New knowledge has formed the substrate for translation-expedited in turn by the biotechnology and pharmaceutical industry into novel therapeutic solutions impacting the management of patients and populations. Indeed, this Bioinnovation Enterprise has become the dominant growth sector in drug development and the engine driving the translation of breakthrough therapies worldwide. This annual Therapeutic Innovations issue highlights recent exceptional advances by the Bioinnovation Enterprise in translating molecular insights in pathobiology into transformative therapies.

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …

Protein Kinase A And Epac Mediate Chronic Pain After Injury: Prolonged Inhibition By Endogenous Y1 Receptors In Dorsal Horn, Weisi Fu

Theses and Dissertations--Physiology

Inflammation or nerve injury sensitizes several populations of nociceptive neurons in the dorsal horn of the spinal cord, including those that express the neuropeptide Y (NPY) Y1 receptor (Y1R). Our overall hypothesis is that after tissue or nerve injury, these Y1R-expressing neurons enter a state of latent sensitization (LS) that contributes to vulnerability to the development of chronic pain; furthermore, LS is under the tonic inhibitory control of endogenous Y1R signaling. First, we evaluated the intracellular signaling pathways that become activated in Y1R-expressing neurons and participate in LS. To do this, we established behavioral models of inflammatory or neuropathic pain, …

Temporal Trends Of Corporate Sponsorship In Medical Research, Elijah Bodey

Honors Projects

Data will be collected from medical journals to assessed changes in the nature and prevalence of corporate sponsorship. The journals that will be reviewed are the Journal of the American Medical Association (JAMA), the New England Journal of Medicine (NEJM), the British Medical Journal (BMJ), and the Lancet. These journals were chosen because of their high impact on medical research representing both American and British Medical editorials. It has been shown that corporate sponsorship has been associated with bias results (Kjaergard et al 2002). Changes in the nature of corporate sponsorship would be linked to changes in economic climate and …

Constellation: A Tool For Rapid, Automated Phenotype Assignment Of A Highly Polymorphic Pharmacogene,, Greyson P. Twist, Andrea Gaedigk, Neil A. Miller, Emily G. Farrow, Laurel K. Willig, Darrell L. Dinwiddie, Josh E. Petrikin, Sarah E. Soden, Suzanne Herd, Margaret Gibson, Julie A. Cakici, Amanda K. Riffel, J Steven Leeder, Deendayal Dinakarpandian, Stephen F. Kingsmore

Manuscripts, Articles, Book Chapters and Other Papers

An important component of precision medicine-the use of whole-genome sequencing (WGS) to guide lifelong healthcare-is electronic decision support to inform drug choice and dosing. To achieve this, automated identification of genetic variation in genes involved in drug absorption, distribution, metabolism, excretion and response (ADMER) is required. CYP2D6 is a major enzyme for drug bioactivation and elimination. CYP2D6 activity is predominantly governed by genetic variation; however, it is technically arduous to haplotype. Not only is the nucleotide sequence of CYP2D6 highly polymorphic, but the locus also features diverse structural variations, including gene deletion, duplication, multiplication events and rearrangements with the nonfunctional, …

Effects Of Traumatic Brain Injury On Oxycodone Reinstatement And Physical Dependence, Neil B. Varshneya

Theses and Dissertations

Epidemiological data indicate that patients who experience a traumatic brain injury (TBI) have an elevated risk of developing a substance use disorder (SUD), but the underlying neurobiological connections remain unclear. To further understand the relationship between TBI and SUD, we investigated the effects of TBI on the abuse-related effects of oxycodone in preclinical models. Our evaluation utilized a lateral fluid percussion injury of moderate severity in adult male Sprague-Dawley rats. In the first aim, we tested the hypothesis that moderate TBI increases the risk for relapse to an opioid use disorder as measured by reinstatement of lever-pressing behavior following extinction …

Molecular Determinants And Interaction Data Of Cyclic Peptide Inhibitor With The Extracellular Domain Of Trkb Receptor, Nitin Chitranshi, Vivek Gupta, Yogita Dheer, Veer Gupta, Roshana Vander Wall, Stuart Graham

Research outputs 2014 to 2021

TrkB is a high affinity receptor for the brain derived neurotrophic factor (BDNF) and its phosphorylation stimulates activation of several intracellular signalling pathways linked to cellular growth, differentiation and maintenance. Identification of various activators and inhibitors of the TrkB receptor and greater understanding their binding mechanisms is critical to elucidate the biochemical and pharmacological pathways and analyse various protein crystallization studies. The data presented here is related to the research article entitled "Brain Derived neurotrophic factor is involved in the regulation of glycogen synthase kinase 3β (GSK3β) signalling" [1]. Cyclotraxin B (CTXB) is a disulphide bridge linked cyclic peptide molecule …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Cellular Responses And Tissue Depots For Nanoformulated Antiretroviral Therapy., Andrea L. Martinez-Skinner, Mariluz Araínga, Pavan Puligujja, Diana L. Palandri, Hannah M. Baldridge, Benson J. Edagwa, Joellyn Mcmillan, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

Long-acting nanoformulated antiretroviral therapy (nanoART) induces a range of innate immune migratory, phagocytic and secretory cell functions that perpetuate drug depots. While recycling endosomes serve as the macrophage subcellular depots, little is known of the dynamics of nanoART-cell interactions. To this end, we assessed temporal leukocyte responses, drug uptake and distribution following both intraperitoneal and intramuscular injection of nanoformulated atazanavir (nanoATV). Local inflammatory responses heralded drug distribution to peritoneal cell populations, regional lymph nodes, spleen and liver. This proceeded for three days in male Balb/c mice. NanoATV-induced changes in myeloid populations were assessed by fluorescence-activated cell sorting (FACS) with CD45, …

Selective Vip Receptor Agonists Facilitate Immune Transformation For Dopaminergic Neuroprotection In Mptp-Intoxicated Mice., Katherine E. Olson, Lisa M. Kosloski-Bilek, Kristi M. Anderson, Breha J. Diggs, Barbara E. Clark, John M. Gledhill, Scott J. Shandler, R. Lee Mosley, Howard Gendelman

Journal Articles: Pharmacology & Experimental Neuroscience

UNLABELLED: Vasoactive intestinal peptide (VIP) mediates a broad range of biological responses by activating two related receptors, VIP receptor 1 and 2 (VIPR1 and VIPR2). Although the use of native VIP facilitates neuroprotection, clinical application of the hormone is limited due to VIP's rapid metabolism and inability to distinguish between VIPR1 and VIPR2 receptors. In addition, activation of both receptors by therapeutics may increase adverse secondary toxicities. Therefore, we developed metabolically stable and receptor-selective agonists for VIPR1 and VIPR2 to improve pharmacokinetic and pharmacodynamic therapeutic end points. Selective agonists were investigated for their abilities to protect mice against MPTP-induced neurodegeneration …

The Incidence Of Early Stage Postoperative Nausea And Vomiting Following The Use Of Nitrous Oxide And Prophylactic Antiemetic Therapy: Implications For Clinical Practice, James Sullivan

Doctoral Projects

Nitrous oxide (N₂O) is a volatile agent currently used during the induction and maintenance of general anesthesia. Since it’s discovery in 1786 by Dr. Priestly, it is the oldest volatile agent to find continued use in current practice (Kossick, 2014). In conjunction with its extensive history is the debate regarding its emetic properties. Numerous studies have investigated the effect of nitrous oxide to produce postoperative nausea and vomiting (PONV) with varying and often conflicting results. Generally speaking, nitrous oxide is theoretically an emetic and is believed to be associated with PONV (Tramer, Moore, & McQuay, 1996). This has …

The Effectiveness Of A Preoperative Multimodal Antiemetic Regimen On Reducing Early Postoperative Nausea And Vomiting In Total Joint Arthroplasty Patients, Jerry Mosley

Doctoral Projects

Postoperative nausea and vomiting (PONV) occurs frequently in all types of surgeries including after total joint orthopedic procedures. The resulting PONV can lead to many unwanted occurrences including immobilization, distress, and many serious adverse health complications. These unwanted occurrences may then lead to increased cost to the patient and healthcare facility. Administration of a preoperative multimodal regimen known to reduce PONV has the potential to reduce such unwanted anesthetic side effects influencing a reduction in overall healthcare cost. The purpose of this study is to determine the effectiveness of the preoperative kit which includes the administration of metoclopramide, famotidine, ondansetron, …

Chronic Ethanol Exposure Enhances The Aggressiveness Of Breast Cancer: The Role Of P38Γ, Mei Xu, Siying Wang, Zhenhua Ren, Jacqueline A. Frank, Xiuwei H. Yang, Zhuo Zhang, Zun-Ji Ke, Xianglin Shi, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Both epidemiological and experimental studies suggest that ethanol may enhance aggressiveness of breast cancer. We have previously demonstrated that short term exposure to ethanol (12–48 hours) increased migration/invasion in breast cancer cells overexpressing ErbB2, but not in breast cancer cells with low expression of ErbB2, such as MCF7, BT20 and T47D breast cancer cells. In this study, we showed that chronic ethanol exposure transformed breast cancer cells that were not responsive to short term ethanol treatment to a more aggressive phenotype. Chronic ethanol exposure (10 days - 2 months) at 100 (22 mM) or 200 mg/dl (44 mM) caused the …

Endoplasmic Reticulum Stress And Ethanol Neurotoxicity, Fanmuyi Yang, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Ethanol abuse affects virtually all organ systems and the central nervous system (CNS) is particularly vulnerable to excessive ethanol exposure. Ethanol exposure causes profound damages to both the adult and developing brain. Prenatal ethanol exposure induces fetal alcohol spectrum disorders (FASD) which is associated with mental retardation and other behavioral deficits. A number of potential mechanisms have been proposed for ethanol-induced brain damage; these include the promotion of neuroinflammation, interference with signaling by neurotrophic factors, induction of oxidative stress, modulation of retinoid acid signaling, and thiamine deficiency. The endoplasmic reticulum (ER) regulates posttranslational protein processing and transport. The accumulation of …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …