Characterization And Engineering Of Interrupted Adenylation Domains, Taylor A. Lundy

Theses and Dissertations--Pharmacy

Nature has historically served as a prolific source of biologically active molecules produced by plants, fungi, and bacteria termed natural products (NPs). These NPs often serve as therapeutic leads due to their structural diversity and unique mechanisms of action. However, many need modifications to make them more effective or safer for human use. This can be a daunting and complicated task to do via traditional organic chemistry because of their complexity, copious stereocenters, and a multitude of reactive functional groups. For this reason, enzymatic modification of these NP during their biosynthesis is an appealing option. One major class of NPs …

Opioid Use In Vulnerable Populations, Gyeon Oh

Theses and Dissertations--Epidemiology and Biostatistics

Opioid-related negative health outcomes, such as substance use disorder, misuse, and overdose deaths, have risen as long-term opioid use has increased. The benefit of using long-term opioids for pain is yet to be established. The Centers for Disease Control and Prevention provides guidelines for opioid prescribing in chronic pain, but detailed recommendations on opioid prescribing for vulnerable populations are missing due to lack of evidence-based studies. The purpose of this dissertation is to describe patterns and predictors of opioid use and assess outcomes related to prescribing opioid medications in vulnerable populations, specifically older adults with various levels of cognitive function, …

Gynecologic Large Cell Neuroendocrine Carcinoma: A Review, Grant Burkeen, Aman Chauhan, Rohitashva Agrawal, Riva Raiker, Jill M. Kolesar, Lowell B. Anthony, B. Mark Evers, Susanne Arnold

Internal Medicine Faculty Publications

Large cell neuroendocrine carcinomas (LCNEC) are rare, aggressive high-grade neuroendocrine neoplasms within the neuroendocrine cell lineage spectrum. This manuscript provides a detailed review of published literature on LCNEC of gynecological origin. We performed a PubMed search for material available on gynecologic LCNEC. We analyzed 104 unique cases of gynecologic LCNECs, of which 45 were cervical primary, 45 were ovarian, 13 were uterine, and 1 was vaginal. A total of 45 cases of cervical LCNEC were identified with a median age of 36 years. Median overall survival was 16 months. We identified 45 ovarian LCNEC cases in the published literature with …

The Effects Of Scheduling Acetaminophen And Methocarbamol Administration On Postoperative Opioid Use And Related Side Effects Among Cardiac Surgery Patients, Whitney Jamison

DNP Projects

The Effects of Scheduled Acetaminophen and Methocarbamol Administration on Postoperative Opioid Use and Related Side Effects Among Cardiac Surgery Patients

ABSTRACT

Purpose

Opioid therapy is commonly prescribed to combat surgical pain in hospitals across the United States and is associated with many negative side effects including dependence and nausea. The purpose of this study was to retrospectively examine the effects of scheduling acetaminophen and methocarbamol administration postoperatively throughout the cardiac surgery patients’ hospital stay. Through retrospective chart reviews, the aims of postoperative opioid use, postoperative opioid use according to hospital length of stay, antiemetic use, and opioid prescription at discharge …

Intervention For Cognitive Reserve Enhancement In Delaying The Onset Of Alzheimer's Symptomatic Expression (Increase), A Randomized Controlled Trial: Rationale, Study Design, And Protocol, Daniela C. Moga, Brooke F. Beech, Erin L. Abner, Frederick A. Schmitt, Riham H. El Khouli, Ashley I. Martinez, Lynne Eckmann, Mark Huffmyer, Rosmy George, Gregory A. Jicha

Pharmacy Practice and Science Faculty Publications

BACKGROUND: The course of Alzheimer's disease (AD) includes a 10-20-year preclinical period with progressive accumulation of amyloid β (Aβ) plaques and neurofibrillary tangles in the absence of symptomatic cognitive or functional decline. The duration of this preclinical stage in part depends on the rate of pathologic progression, which is offset by compensatory mechanisms, referred to as cognitive reserve (CR). Comorbid medical conditions, psychosocial stressors, and inappropriate medication use may lower CR, hastening the onset of symptomatic AD. Here, we describe a randomized controlled trial (RCT) designed to test the efficacy of a medication therapy management (MTM) intervention to reduce inappropriate …

A Dual Inhibitor Of The Proteasome Catalytic Subunits Lmp2 And Y Attenuates Disease Progression In Mouse Models Of Alzheimer's Disease, In Jun Yeo, Min Jae Lee, Ahruem Baek, Zachary Miller, Deepak Bhattarai, Yu Mi Baek, Hyun Jung Jeong, Yun Kyung Kim, Dong-Eun Kim, Jin Tae Hong, Kyung Bo Kim

Pharmaceutical Sciences Faculty Publications

The immunoproteasome (iP) is a variant of the constitutive proteasome (cP) that is abundantly expressed in immune cells which can also be induced in somatic cells by cytokines such as TNF-α or IFN-γ. Accumulating evidence support that the iP is closely linked to multiple facets of inflammatory response, eventually leading to the development of several iP inhibitors as potential therapeutic agents for autoimmune diseases. Recent studies also found that the iP is upregulated in reactive glial cells surrounding amyloid β (Aβ) deposits in brains of Alzheimer's disease (AD) patients, but the role it plays in the pathogenesis of AD remains …

Simulated Biological Fluid Exposure Changes Nanoceria’S Surface Properties But Not Its Biological Response, Robert A. Yokel, Matthew L. Hancock, Benjamin Cherian, Alexandra J. Brooks, Marsha L. Ensor, Hemendra J. Vekaria, Patrick G. Sullivan, Eric A. Grulke

Pharmaceutical Sciences Faculty Publications

Nanoscale cerium dioxide (nanoceria) has industrial applications, capitalizing on its catalytic, abrasive, and energy storage properties. It auto-catalytically cycles between Ce³⁺ and Ce⁴⁺, giving it pro-and anti-oxidative properties. The latter mediates beneficial effects in models of diseases that have oxidative stress/inflammation components. Engineered nanoparticles become coated after body fluid exposure, creating a corona, which can greatly influence their fate and effects. Very little has been reported about nanoceria surface changes and biological effects after pulmonary or gastrointestinal fluid exposure. The study objective was to address the hypothesis that simulated biological fluid (SBF) exposure changes nanoceria’s surface properties …

Co-Prescription Network Reveals Social Dynamics Of Opioid Doctor Shopping, Brea L. Perry, Kai Cheng Yang, Patrick Kaminski, Meltem Odabas, Jaehyuk Park, Michelle M. Martel, Carrie B. Oser, Patricia R. Freeman, Yong-Yeol Ahn, Jeffery C. Talbert

Psychology Faculty Publications

This paper examines network prominence in a co-prescription network as an indicator of opioid doctor shopping (i.e., fraudulent solicitation of opioids from multiple prescribers). Using longitudinal data from a large commercially insured population, we construct a network where a tie between patients is weighted by the number of shared opioid prescribers. Given prior research suggesting that doctor shopping may be a social process, we hypothesize that active doctor shoppers will occupy central structural positions in this network. We show that network prominence, operationalized using PageRank, is associated with more opioid prescriptions, higher predicted risk for dangerous morphine dosage, opioid overdose, …

Phenylethynyl-Substituted Benzenes And Heterocycles For The Treatment Of Cancer, David S. Watt, Chunming Liu, Vitaliy M. Sviripa, Wen Zhang, Markos Leggas

Molecular and Cellular Biochemistry Faculty Patents

Halogenated phenylethynyl-substituted heterocycles that possess either an N-alkylamino or N,N-dialkylamino group attached to the heterocycle or halogenated phenylethynyl-substituted benzenes that a nitrogen-containing heterocycle attached to the benzene inhibit the proliferation cancer cells and are useful antineoplastic agents.

Image Anaysis For Predicting Body Weight In Humans, Jeffrey S. Barrett, Chee Ng

Pharmaceutical Sciences Faculty Patents

Systems and methods for determining body weight predictions and human conditions are disclosed. A body weight may be predicted by capturing at least one image of a human, and determining, from the image, a body weight prediction of the human by processing the at least one image with a data processor. The body weight prediction may further be based on an age-based weight factor. A model such as a neural network model may be used to predict body weight.

Multiple Sclerosis Outcomes After Cancer Immunotherapy, Catherine R. Garcia, Rani Jayswal, Val R. Adams, Lowell B. Anthony, John L. Villano

Markey Cancer Center Faculty Publications

INTRODUCTION: Neurological immune-related adverse events are a rare but potentially deadly complication after immune checkpoint inhibitor (ICI) treatment. As multiple sclerosis (MS) is an immune-mediated disease, it is unknown how ICI treatment may affect outcomes.

METHODS: We analyzed the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database for pembrolizumab, atezolizumab, nivolumab, ipilimumab, avelumab, and durvalumab 2 years prior their FDA approval until December 31, 2017, to include all cases with confirmed diagnosis/relapse of MS. We also included cases reported in the literature and a patient from our institution.

RESULTS: We identified 14 cases of MS …

Imatinib Mesylate Effects On Zebrafish Reproductive Success: Gonadal Development, Gamete Quality, Fertility, Embryo-Larvae Viability And Development, And Related Genes, Nader Ahmadi, Seyed-Mohammadreza Samaee, Robert A. Yokel, Aliasghar Tehrani

Pharmaceutical Sciences Faculty Publications

Imatinib (IM) is a tyrosine kinase (TK) inhibitor (TKI) used to treat chronic myeloid leukemia. Clinical case reports and a few laboratory mammal studies provide inconclusive evidence about its deleterious effects on reproduction. The aim of the current study was to evaluate the potential of zebrafish to characterize IM-induced effects on reproduction and clarify IM effects on reproductive success. To this end, we exposed adult zebrafish to four concentrations of IM for 30 days followed by a 30-day depuration period. IM exposure caused a concentration-dependent, irreversible, suppression of folliculogenesis, reversible decrease in sperm density and motility, decreased fecundity and fertility, …

Altered Gating Of KV1.4 In The Nucleus Accumbens Suppresses Motivation For Reward, Bernadette O'Donovan, Adewale Adeluyi, Erin L Anderson, Robert D. Cole, Jill R. Turner, Pavel I. Ortinski

Neuroscience Faculty Publications

Deficient motivation contributes to numerous psychiatric disorders, including withdrawal from drug use, depression, schizophrenia, and others. Nucleus accumbens (NAc) has been implicated in motivated behavior, but it remains unclear whether motivational drive is linked to discrete neurobiological mechanisms within the NAc. To examine this, we profiled cohorts of Sprague-Dawley rats in a test of motivation to consume sucrose. We found that substantial variability in willingness to exert effort for reward was not associated with operant responding under low-effort conditions or stress levels. Instead, effort-based motivation was mirrored by a divergent NAc shell transcriptome with differential regulation at potassium and dopamine …

N-Glycosylation-Defective Splice Variants Of Neuropilin-1 Promote Metastasis By Activating Endosomal Signals, Xiuping Huang, Qing Ye, Min Chen, Aimin Li, Wenting Mi, Yuxin Fang, Yekaterina Y. Zaytseva, Kathleen L. O'Connor, Craig W. Vander Kooi, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Neuropilin-1 (NRP1) is an essential transmembrane receptor with a variety of cellular functions. Here, we identify two human NRP1 splice variants resulting from the skipping of exon 4 and 5, respectively, in colorectal cancer (CRC). Both NRP1 variants exhibit increased endocytosis/recycling activity and decreased levels of degradation, leading to accumulation on endosomes. This increased endocytic trafficking of the two NRP1 variants, upon HGF stimulation, is due to loss of N-glycosylation at the Asn150 or Asn261 site, respectively. Moreover, these NRP1 variants enhance interactions with the Met and β1-integrin receptors, resulting in Met/β1-integrin co-internalization and co-accumulation on endosomes. This provides persistent …

Rna-Based Compositions And Adjuvants For Prophylactic And Therapeutic Treatment, Peixuan Guo, Hui Li, Emil F. Khisamutdinov, Daniel L. Jasinski

Pharmaceutical Sciences Faculty Patents

The present invention is directed towards an artificial RNA nano structure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an …

Innovative Solutions For State Medicaid Programs To Leverage Their Data, Build Their Analytic Capacity, And Create Evidence-Based Policy, Lauren Adams, Susan Kennedy, Lindsay Allen, Andrew Barnes, Tom Bias, Dushka Crane, Paul Lanier, Rachel Mauk, Shamis Mohamoud, Nathan Pauly, Jeffery C. Talbert, Cynthia Woodcock, Kara Zivin, Julie Donohue

Pharmacy Practice and Science Faculty Publications

As states have embraced additional flexibility to change coverage of and payment for Medicaid services, they have also faced heightened expectations for delivering high-value care. Efforts to meet these new expectations have increased the need for rigorous, evidence-based policy, but states may face challenges finding the resources, capacity, and expertise to meet this need. By describing state-university partnerships in more than 20 states, this commentary describes innovative solutions for states that want to leverage their own data, build their analytic capacity, and create evidence-based policy. From an integrated web-based system to improve long-term care to evaluating the impact of permanent …

Quantitative Systems Pharmacology Model Of Chimeric Antigen Receptor T-Cell Therapy, Deni Hardiansyah, Chee Meng Ng

Pharmaceutical Sciences Faculty Publications

Chimeric antigen receptor T‐cell (CART) therapy is a new and promising cancer therapy. However, severe toxicity due to cytokine release syndrome (CRS) in CART‐treated patients highlighted the possible danger of this new therapy. Disease burden and CART doses are the potential factors associated with CRS but the detail relationships between these factors and the severity of the CRS remain largely unknown. In this study, the quantitative systems pharmacology (QSP) approach is used to quantify the complex relationships among CART doses, disease burden, and pro inflammatory cytokines in human subjects and to gain relevant insights into the determinant of clinical toxicity/efficacy …

Association Of Naloxone Coprescription Laws With Naloxone Prescription Dispensing In The United States, Minji Sohn, Jeffery C. Talbert, Zhengyan Huang, Michelle R. Lofwall, Patricia R. Freeman

Institute for Pharmaceutical Outcomes and Policy Faculty Publications

Importance: To mitigate the opioid overdose crisis, states have implemented a variety of legal interventions aimed at increasing access to the opioid antagonist naloxone. Recently, Virginia and Vermont mandated the coprescription of naloxone for potentially at-risk patients.

Objective: To assess the association between naloxone coprescription legal mandates and naloxone dispensing in retail pharmacies.

Design, Setting, and Participants: This was a population-based, state-level cohort study. The sample included all prescriptions dispensed for naloxone in the retail pharmacy setting contained in IQVIA's national prescription audit, which represents 90% of all retail pharmacies in the United States. The unit of observation was state-month …

Diagnosis, Treatment And Follow Up Of Acute Pulmonary Embolism: Consensus Practice From The Pert Consortium, Belinda Rivera-Lebron, Michael Mcdaniel, Kamran Ahrar, Abdulah Alrifai, David M. Dudzinski, Christina Fanola, Danielle Blais, David Janicke, Roman Melamed, Kerry Mohrien, Elizabeth Rozycki, Charles B. Ross, Andrew J. Klein, Parth Rali, Nicholas R. Teman, Leoara Yarboro, Eugene Ichinose, Aditya M. Sharma, Jason A. Bartos, Mahir Elder, Brent Keeling, Harold Palevsky, Soophia Naydenov, Parijat Sen, Nancy Amoroso, Josanna M. Rodriguez-Lopez, George A. Davis, Rachel Rosovsky, Kenneth Rosenfield, Christopher Kabrhel, James Horowitz, Jay S. Giri, Victor Tapson, Richard Channick, Pert Consortium

Pharmacy Practice and Science Faculty Publications

Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute …

Compositions And Methods Of Modulating 15-Pgdh Activity, Sanford Markowitz, James K. Willson V, Bruce Posner, Joseph Ready, Youngyou Zhang, Hsin-Hsiung Tai, Monika Antezak, Stanton Gerson, Kibeom Bae, Sung Yeun Yang, Amar Desai

Pharmaceutical Sciences Faculty Patents

Compounds and methods of modulating 15-PGDH activity, modulating tissue prostaglandin levels, treating disease, diseases disorders, or conditions in which it is desired to modulate 15-PGDH activity and/or prostaglandin levels include 15-PGDH inhibitors and 15-PGDH activators described herein.

A High-Throughput Screen Indicates Gemcitabine And Jak Inhibitors May Be Useful For Treating Pediatric Aml, Christina D. Drenberg, Anang Shelat, Jinjun Dang, Anitria Cotton, Shelley J. Orwick, Mengyu Li, Jae Yoon Jeon, Qiang Fu, Daelynn R. Buelow, Marissa Pioso, Shuiying Hu, Hiroto Inaba, Raul C. Ribeiro, Jeffrey E. Rubnitz, Tanja A. Gruber, R. Kiplin Guy, Sharyn D. Baker

Pharmaceutical Sciences Faculty Publications

Improvement in survival has been achieved for children and adolescents with AML but is largely attributed to enhanced supportive care as opposed to the development of better treatment regimens. High risk subtypes continue to have poor outcomes with event free survival rates < 40% despite the use of high intensity chemotherapy in combination with hematopoietic stem cell transplant. Here we combine high-throughput screening, intracellular accumulation assays, and in vivo efficacy studies to identify therapeutic strategies for pediatric AML. We report therapeutics not currently used to treat AML, gemcitabine and cabazitaxel, have broad anti-leukemic activity across subtypes and are more effective relative to the AML standard of care, cytarabine, both in vitro and in vivo. JAK inhibitors are selective for acute megakaryoblastic leukemia and significantly prolong survival in multiple preclinical models. Our approach provides advances in the development of treatment strategies for pediatric AML.

Deregulation Of A Network Of Mrna And Mirna Genes Reveals That Ck2 And Mek Inhibitors May Synergize To Induce Apoptosis Kras-Active Nsclc, Madeline Krentz Gober, Robert M. Flight, Joshua W. Lambert, Hunter N. B. Moseley, Arnold Stromberg, Esther P. Black

Pharmaceutical Sciences Faculty Publications

KRAS-activation mutations occur in 25% to 40% of lung adenocarcinomas and are a known mechanism of epidermal growth factor receptor inhibitor (EGFRI) resistance. There are currently no targeted therapies approved specifically for the treatment of KRAS-active non–small cell lung cancers (NSCLC). Attempts to target mutant KRAS have failed in clinical studies leaving no targeted therapy option for these patients. To circumvent targeting KRAS directly, we hypothesized that targeting proteins connected to KRAS function rather than targeting KRAS directly could induce cell death in KRAS-active NSCLC cells. To identify potential targets, we leveraged 2 gene expression data sets derived from NSCLC …

Macrolide Derivatives Reduce Proinflammatory Macrophage Activation And Macrophage‐Mediated Neurotoxicity, Bei Zhang, Timothy J. Kopper, Xiaodong Liu, Zheng Cui, Steven G. Van Lanen, John C. Gensel

Physiology Faculty Publications

Introduction: Azithromycin (AZM) and other macrolide antibiotics are applied as immunomodulatory treatments for CNS disorders. The immunomodulatory and antibiotic properties of AZM are purportedly independent.

Aims: To improve the efficacy and reduce antibiotic resistance risk of AZM‐based therapies, we evaluated the immunomodulatory and neuroprotective properties of novel AZM derivatives. We semisynthetically prepared derivatives by altering sugar moieties established as important for inhibiting bacterial protein synthesis. Bone marrow‐derived macrophages (BMDMs) were stimulated in vitro with proinflammatory, M1, stimuli (LPS + INF‐gamma) with and without derivative costimulation. Pro‐ and anti‐inflammatory cytokine production, IL‐12 and IL‐10, respectively, was quantified using ELISA. Neuron culture …

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Patents

Compounds and compositions are disclosed, which are useful as inhibitors of acetyltransferase Eis, a mediator of kanamycin resistance in Mycobacterium tuberculosis.

Surface-Controlled Dissolution Rates: A Case Study Of Nanoceria In Carboxylic Acid Solutions, Eric A. Grulke, Matthew J. Beck, Robert A. Yokel, Jason M. Unrine, Uschi M. Graham, Matthew L. Hancock

Chemical and Materials Engineering Faculty Publications

Nanoparticle dissolution in local milieu can affect their ecotoxicity and therapeutic applications. For example, carboxylic acid release from plant roots can solubilize nanoceria in the rhizosphere, affecting cerium uptake in plants. Nanoparticle dispersions were dialyzed against ten carboxylic acid solutions for up to 30 weeks; the membrane passed cerium-ligand complexes but not nanoceria. Dispersion and solution samples were analyzed for cerium by inductively coupled plasma mass spectrometry (ICP-MS). Particle size and shape distributions were measured by transmission electron microscopy (TEM). Nanoceria dissolved in all carboxylic acid solutions, leading to cascades of progressively smaller nanoparticles and producing soluble products. The dissolution …

Unusual Substrate And Halide Versatility Of Phenolic Halogenase Pltm, Shogo Mori, Allan H. Pang, Nishad Thamban Chandrika, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov

Pharmaceutical Sciences Faculty Publications

Controlled halogenation of chemically versatile substrates is difficult to achieve. Here we describe a unique flavin-dependent halogenase, PltM, which is capable of utilizing a wide range of halides for installation on a diverse array of phenolic compounds, including FDA-approved drugs and natural products, such as terbutaline, fenoterol, resveratrol, and catechin. Crystal structures of PltM in complex with phloroglucinol and FAD in different states yield insight into substrate recognition and the FAD recycling mechanism of this halogenase.

H727 Cells Are Inherently Resistant To The Proteasome Inhibitor Carfilzomib, Yet Require Proteasome Activity For Cell Survival And Growth, Min Jae Lee, Zachary Miller, Ji Eun Park, Deepak Bhattarai, Wooin Lee, Kyung Bo Kim

Pharmaceutical Sciences Faculty Publications

The second-in-class proteasome inhibitor (PI) carfilzomib (Kyprolis, Cfz) has contributed to a substantial advancement in multiple myeloma treatment by improving patient survival and quality of life. A considerable portion of patients however display intrinsic resistance to Cfz. Our mechanistic understanding of intrinsic Cfz resistance is limited due to a lack of suitable cell-based models. We report that H727 human bronchial carcinoid cells are inherently resistant to Cfz, yet susceptible to other PIs and inhibitors targeting upstream components of the ubiquitin-proteasome system (UPS). These results indicate that H727 cells remain dependent on the UPS for cell survival and growth despite harboring …

Mutational Effects Of Human Dopamine Transporter At Tyrosine88, Lysine92, And Histidine547 On Basal And Hiv-1 Tat-Inhibited Dopamine Transport, Wei-Lun Sun, Pamela M. Quizon, Yaxia Yuan, Matthew J. Strauss, Richard Mccain Jr., Chang-Guo Zhan, Jun Zhu

Molecular Modeling and Biopharmaceutical Center Faculty Publications

Dysregulation of dopaminergic system induced by HIV-1 Tat protein-mediated direct inhibition of the dopamine transporter (DAT) has been implicated as a mediating factor of HIV-1 associated neurocognitive disorders. We have reported that single point mutations on human DAT (hDAT) at tyrosine88 (Y88F), lysine92 (K92M), and histidine547 (H547A) differentially regulate basal dopamine uptake but diminish Tat-induced inhibition of dopamine uptake by changing dopamine transport process. This study evaluated the effects of double (Y88F/H547A) and triple (Y88F/K92M/H547A) mutations on basal dopamine uptake, Tat-induced inhibition of DAT function, and dynamic transport process. Compared to wild-type hDAT, the V_max values of [^{3 …}

Spore Forming Actinobacterial Diversity Of Cholistan Desert Pakistan: Polyphasic Taxonomy, Antimicrobial Potential And Chemical Profiling, Adeela Fatima, Usman Aftab, Khaled A. Shaaban, Jon S. Thorson, Imran Sajid

Center for Pharmaceutical Research and Innovation Faculty Publications

Background: Actinobacteria are famous for the production of unique secondary metabolites that help in controlling the continuously emerging drug resistance all over the globe. This study aimed at the investigation of an extreme environment the Cholistan desert, located in southern Punjab, Pakistan, for actinobacterial diversity and their activity against methicillin resistant Staphylococcus aureus (MRSA). The Cholistan desert is a sub-tropical and arid ecosystem with harsh environment, limited rainfall and low humidity. The 20 soil and sand samples were collected from different locations in the desert and the actinobacterial strains were selectively isolated. The isolated strains were identified using a polyphasic …

Eis Inhibitors, Sylvie Garneau-Tsodikova, Oleg V. Tsodikov, James E. Posey

Pharmaceutical Sciences Faculty Patents

Provided herein are novel small-molecules that have use in the inhibition of Eis, which mediates kanamycin resistance in Mycobacterium tuberculosis. The presently-disclosed subject matter further includes a pharmaceutical composition including a small molecule inhibitor, as described herein, and a suitable pharmaceutical carrier. Methods of treating tuberculosis comprising administering to an individual an effective amount of the disclosed small molecule inhibitors to mediate kanamycin A resistance and treat tuberculosis are also provided.