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Full-Text Articles in Medicine and Health Sciences

Tigecycline In The Treatment Of Complicated Intra-Abdominal And Complicated Skin And Skin Structure Infections, M. L. Townsend, M. W. Pound, R. H. Drew Sep 2019

Tigecycline In The Treatment Of Complicated Intra-Abdominal And Complicated Skin And Skin Structure Infections, M. L. Townsend, M. W. Pound, R. H. Drew

Melanie Pound

Tigecycline, a glycylcycline related to the tetracycline class of antibiotics, represents a new option for the treatment of complicated intra-abdominal and complicated skin and skin structure infections. It displays favorable activity in vitro against the most common causative Gram-positive, Gram-negative and anaerobic pathogens. In addition, tigecycline demonstrates activity against drug-resistant pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and organisms (such as Escherichia coli and Klebsiella pneumoniae) producing extended-spectrum beta-lactamases. Tigecycline lacks activity in vitro against Pseudomonas and Proteus spp. In randomized clinical trials, tigecycline administered intravenously twice daily has demonstrated efficacy similar to comparators for a variety …


Complex Acylation Of Angiotensin Ii By N-Hydroxysulfosuccinimide Linked Biotin Reagents, Q. Liu, A. Lam, A. Kathuria Sep 2019

Complex Acylation Of Angiotensin Ii By N-Hydroxysulfosuccinimide Linked Biotin Reagents, Q. Liu, A. Lam, A. Kathuria

Qinfeng Liu

N-Hydroxysulfosuccinimide-linked biotins (sulfoNHS-biotins) are water soluble biotin tags commonly used to conjugate a biotin moiety to proteins by rapid N-acylation of primary amines. Unexpected O-acylation by sulfoNHSbiotin on tyrosine of Angiotensin II (Ag-II) and an acylation on third site unable to characterize were identified by LC-MS in addition to the expected N-acylation on the N-terminal of Ag-II. The N-acylation only undergoes incomplete hydrolysis in 0.1% formic acid not at pH 7.2 and 8.0, while two unexpected acylation hydrolyze at both conditions, but their hydrolysis in 0.1% formic acid was much more rapid. Dithiothreitol treatment selectively catalyzed hydrolysis of both of …


Effects Of Three Dry Powder Inhalers On Deposition Of Aerosolized Medicine In The Human Oral-Pharyngeal-Laryngeal Regions, Mohammed Ali Sep 2019

Effects Of Three Dry Powder Inhalers On Deposition Of Aerosolized Medicine In The Human Oral-Pharyngeal-Laryngeal Regions, Mohammed Ali

Mohammed Ali

The dry powder inhaler (DPI) is a popular, effective and convenient drug delivery device for inhalation therapy to treat asthma. However, a large quantity (approximately 54%) of inhaled aerosols deposit in the oropharyngeal region. Deposition in this region is undesirable because it provides minimum therapeutic benefits and has adverse localized or systemic side effects. This study reports a method of examining electrostatic charge effects on deposition of three DPI aerosols (Spiriva Handihaler, Advair Diskus, and Pulmicort Turbohaler) in a cadaver-based cast of the human oral-pharyngeal-laryngeal (OPL) regions. Experimental aerosols were generated from the three commercially available …


Report Of The Aacp Criminal Background Check Advisory Panel, H. Anderson, M. A. Kirkpatrick, M. Mckenzie, W. M. Moore, K. Williams, W. Wuller, E. Anagnostiadis, L. Ross Aug 2019

Report Of The Aacp Criminal Background Check Advisory Panel, H. Anderson, M. A. Kirkpatrick, M. Mckenzie, W. M. Moore, K. Williams, W. Wuller, E. Anagnostiadis, L. Ross

W. Mark Moore

No abstract provided.


Treating Nonalcoholic Fatty Liver Disease In Patients With Type 2 Diabetes Mellitus: A Review Of Efficacy And Safety, E. P. Mills, K. P. Brown, K. Trotta, P. W. Vang, J. D. Smith Aug 2019

Treating Nonalcoholic Fatty Liver Disease In Patients With Type 2 Diabetes Mellitus: A Review Of Efficacy And Safety, E. P. Mills, K. P. Brown, K. Trotta, P. W. Vang, J. D. Smith

Beth Mills

Objective:

To review current literature for the efficacy and safety of treatment for nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

Data sources:

A PubMed literature search from January 1990 to June 2017 was conducted using the search terms nonalcoholic fatty liver disease, diabetes mellitus, type 2, therapy, treatment, treat, therapeutics, nonalcoholic fatty liver, nonalcoholic hepatosteatosis, NASH, NAFLD, metformin, and statin. Bibliographies of chosen articles were reviewed.

Study selection and data extraction:

Relevant articles on metformin, thiazolidinediones (TZD), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and statins for the treatment of NAFLD which included patients with …


Advocate Aurora Apc Grand Rounds Dm Pharm Update 7 2019 Chojnacki.Pptx, Carl Chojnacki Jul 2019

Advocate Aurora Apc Grand Rounds Dm Pharm Update 7 2019 Chojnacki.Pptx, Carl Chojnacki

Carl Chojnacki, MBA, MSN, APNP, ANP-BC, AWLS

This is a discussion regarding new recommendations for use of GLP 1 RA and SGLT2i agents for patients with diabetes mellitus type 2. Information includes benefits for cardiac and renal outcomes with these agents.


A Review Of Osteoporosis Management In Younger, Premenopausal Women, A. N. Mclendon, C. B. Woodis Jul 2019

A Review Of Osteoporosis Management In Younger, Premenopausal Women, A. N. Mclendon, C. B. Woodis

Amber McLendon

The purpose of this review is to describe the available evidence for osteoporosis treatments in young and premenopausal women. A review of articles evaluating the treatment or prevention of osteoporosis in young (age less than 50 years) or premenopausal women was conducted. Several trials evaluating the treatment of anorexia nervosa and use of hormone therapy in those women, the use of bisphosphonates in women undergoing chemotherapy for breast cancer and the use of bisphosphonates, teriparatide and vitamin D in women with glucocorticoid-induced osteoporosis are described. Limited data were found to support the treatment of osteoporosis in women with idiopathic osteoporosis …


Nonmodal Clinical Decision Support And Antimicrobial Restriction Effects On Rates Of Fluoroquinolone Use In Uncomplicated Infections, L R. Gunn, R Tunney, K E. Kelly Jul 2019

Nonmodal Clinical Decision Support And Antimicrobial Restriction Effects On Rates Of Fluoroquinolone Use In Uncomplicated Infections, L R. Gunn, R Tunney, K E. Kelly

Kim Kelly

No abstract provided.


Predictors Of Neonatal Abstinence Syndrome In Buprenorphine Exposed Newborn: Can Cord Blood Buprenorphine Metabolite Levels Help?, Darshan Shah, Stacy Brown, Nick Hagemeier, Shimin Zheng, Amy Kyle, Jason Pryor, Nilesh Dankhara, Piyuesh Singh Jun 2019

Predictors Of Neonatal Abstinence Syndrome In Buprenorphine Exposed Newborn: Can Cord Blood Buprenorphine Metabolite Levels Help?, Darshan Shah, Stacy Brown, Nick Hagemeier, Shimin Zheng, Amy Kyle, Jason Pryor, Nilesh Dankhara, Piyuesh Singh

Stacy D. Brown

Background

Buprenorphine is a semi-synthetic opioid used for the treatment of opioid dependence. Opioid use, including buprenorphine, has been increasing in recent years, in the general population and in pregnant women. Consequently, there has been a rise in frequency of neonatal abstinence syndrome (NAS), associated with buprenorphine use during pregnancy. The purpose of this study was to investigate correlations between buprenorphine and buprenorphine-metabolite concentrations in cord blood and onset of NAS in buprenorphine exposed newborns.

Methods

Nineteen (19) newborns who met inclusion criteria were followed after birth until discharge in a double-blind non-intervention study, after maternal consent. Cord blood and …


A Pilot Process To Identify And Switch High-Risk Warfarin Patients To Direct Oral Anticoagulants, S. Lee, J. B. Groce, J. Kim Jun 2019

A Pilot Process To Identify And Switch High-Risk Warfarin Patients To Direct Oral Anticoagulants, S. Lee, J. B. Groce, J. Kim

James Groce

No abstract provided.


Metabolism Of Primaquine In Normal Human Volunteers: Investigation Of Phase I And Phase Ii Metabolites From Plasma And Urine Using Ultra-High Performance Liquid Chromatography-Quadrupole Time-Of-Flight Mass Spectrometry, B. Avula, B. L. Tekwani, N. D. Chaurasiya, P. S. Fasinu, N. D. Nanayakkara, H. B. Herath, Y. H. Wang, J. Y. Bae, S. I. Khan, M. A. Elsohly, J. D. Mcchesney Apr 2019

Metabolism Of Primaquine In Normal Human Volunteers: Investigation Of Phase I And Phase Ii Metabolites From Plasma And Urine Using Ultra-High Performance Liquid Chromatography-Quadrupole Time-Of-Flight Mass Spectrometry, B. Avula, B. L. Tekwani, N. D. Chaurasiya, P. S. Fasinu, N. D. Nanayakkara, H. B. Herath, Y. H. Wang, J. Y. Bae, S. I. Khan, M. A. Elsohly, J. D. Mcchesney

Pius Fasinu

No abstract provided.


Formation Primaquine-5, 6-Orthoquinone, The Putative Active And Toxic Metabolite Of Primaquine Via Direct Oxidation In Human Erythrocytes, P. S. Fasinu, N. D. Nanayakkara, Y. H. Wang, N. D. Chaurasiya, H. B. Herath, J. D. Mcchesney, B. Avula, I. Khan, B. L. Tekwani, L. A. Walker Apr 2019

Formation Primaquine-5, 6-Orthoquinone, The Putative Active And Toxic Metabolite Of Primaquine Via Direct Oxidation In Human Erythrocytes, P. S. Fasinu, N. D. Nanayakkara, Y. H. Wang, N. D. Chaurasiya, H. B. Herath, J. D. Mcchesney, B. Avula, I. Khan, B. L. Tekwani, L. A. Walker

Pius Fasinu

No abstract provided.


Sex Hormones And Vascular Function, M. Bowling, S. Oparil, F. Hage, R. H. Hilgers, D. Xing Apr 2019

Sex Hormones And Vascular Function, M. Bowling, S. Oparil, F. Hage, R. H. Hilgers, D. Xing

Rob Hilgers

No abstract provided.


Decreased Edhf-Mediated Relaxation Is A Major Mechanism In Endothelial Dysfunction In Resistance Arteries In Aged Mice On Prolonged High- Fat Sucrose Diet, S. M. Dunn, R. H. Hilgers, K. C. Das Apr 2019

Decreased Edhf-Mediated Relaxation Is A Major Mechanism In Endothelial Dysfunction In Resistance Arteries In Aged Mice On Prolonged High- Fat Sucrose Diet, S. M. Dunn, R. H. Hilgers, K. C. Das

Rob Hilgers

No abstract provided.


Evaluation Of An Empiric Vancomycin Dosing Nomogram In Achieving Goal Steady-State Trough Concentrations In Obese Adults Weighing At Least 100 Kilograms, S. W. Johnson, R. D. Bowers, A. A. Cooper, C. L. Wente, D. Wilson Mar 2019

Evaluation Of An Empiric Vancomycin Dosing Nomogram In Achieving Goal Steady-State Trough Concentrations In Obese Adults Weighing At Least 100 Kilograms, S. W. Johnson, R. D. Bowers, A. A. Cooper, C. L. Wente, D. Wilson

April Cooper

No abstract provided.


Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey Mar 2019

Non-Human Primates In Medical Research And Drug Development: A Critical Review, Jarrod Bailey

Jarrod Bailey, PhD

There is much current debate surrounding the use of non-human primates (NHPs) in medical research and drug development. This review, stimulated by calls for evidence from UK-based inquiries into NHP research, takes a critical view in order to provide some important balance against papers supporting NHP research and calling for it to be expanded. We show that there is a paucity of evidence to demonstrate the positive contribution or successful translation of NHP research to human medicine, that there is a great deal of often overlooked data showing NHP research to be irrelevant, unnecessary, even hazardous to human health and …


Using An "Escape Room" Toolbox Approach To Enhance Pharmacology Education, Melinda Hermanns, Belinda Deal, Ann M. C, Shawn Hillhouse, J. Brian Opella, Casey Faigle, Robert H. Campbell Iv Mar 2019

Using An "Escape Room" Toolbox Approach To Enhance Pharmacology Education, Melinda Hermanns, Belinda Deal, Ann M. C, Shawn Hillhouse, J. Brian Opella, Casey Faigle, Robert H. Campbell Iv

Barbara Haas

Background: Faculty are encouraged to use a variety of teaching/learning strategies to engage nursing students. While simulation and games are now common, there were no reports in the nursing literature using an “escape room” concept. Escape rooms use an entertainment approach as teams engage in critical thinking to solve puzzles and find clues to escape a room. In the classroom setting, this concept is modified to solve a mystery by finding various objects through a series of puzzles to locate clues. Some of these games involve finding numerical clues to open locks on a box, such as a toolbox. The …


Associations Between Dietary Intake Of Fruits And Vegetables In Relation To Urinary Estrogen Dna Adduct Ratio, K. W. Reding, M. Zahid, E. Cavalieri, E. G. Rogan, B. S. Raccor, C. Atkinson, M. Yong, K. M. Newton, J. W. Lampe Mar 2019

Associations Between Dietary Intake Of Fruits And Vegetables In Relation To Urinary Estrogen Dna Adduct Ratio, K. W. Reding, M. Zahid, E. Cavalieri, E. G. Rogan, B. S. Raccor, C. Atkinson, M. Yong, K. M. Newton, J. W. Lampe

Brianne S. Raccor

No abstract provided.


Comparison Of Pharmaceutical Calculations Learning Outcomes Achieved Within A Traditional Lecture Or Flipped Classroom Andragogy, H. Glenn Anderson Jr., Lisa Frazier, Stephanie L. Anderson, Robert B. Stanton, Chris Gillette, Kim Broedel-Zaugg, Kevin W. Yingling Mar 2019

Comparison Of Pharmaceutical Calculations Learning Outcomes Achieved Within A Traditional Lecture Or Flipped Classroom Andragogy, H. Glenn Anderson Jr., Lisa Frazier, Stephanie L. Anderson, Robert B. Stanton, Chris Gillette, Kim Broedel-Zaugg, Kevin W. Yingling

Kim Broedel-Zaugg

Objective. To compare learning outcomes achieved from a pharmaceutical calculations course taught in a traditional lecture (lecture model) and a flipped classroom (flipped model).

Methods. Students were randomly assigned to the lecture model and the flipped model. Course instructors, content, assessments, and instructional time for both models were equivalent. Overall group performance and pass rates on a standardized assessment (Pcalc OSCE) were compared at six weeks and at six months post-course completion.

Results. Student mean exam scores in the flipped model were higher than those in the lecture model at six weeks and six months later. Significantly more students passed …


Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews Mar 2019

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Tyler Johnson

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …


Nadolol In Pregnancy: A Medical Student’S Reflection On Her Pregnancy, Rebecca King-Mallory, Shawndra Barker, Kaitlin Mcgrogan, Adam M. Franks Mar 2019

Nadolol In Pregnancy: A Medical Student’S Reflection On Her Pregnancy, Rebecca King-Mallory, Shawndra Barker, Kaitlin Mcgrogan, Adam M. Franks

Adam M. Franks, MD

Hypertension is a common concern during pregnancy. Beta-blockers are one potential treatment, but third trimester exposure has correlated with an increased risk of perinatal events. Nadolol, a nonselective beta blocker, has properties that differ from those of its selective counterparts, including longer half-life, decreased protein binding, and renal excretion in the unchanged form. There is very limited data on the use of nadolol during pregnancy, and its safety has not been completely evaluated. This case study documents the perinatal outcomes of nadolol use throughout a medical student’s pregnancy and explores the experience in obtaining and undergoing medical care.


The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A Beniddir, Maique W Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S Butler, Robert J Capon, Young H Choi, David Coppage, Phillip Crews, Michael T Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M Egan, Mary J Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G I Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli Feb 2019

The Value Of Universally Available Raw Nmr Data For Transparency, Reproducibility, And Integrity In Natural Product Research., James B Mcalpine, Shao-Nong Chen, Andrei Kutateladze, John B Macmillan, Giovanni Appendino, Andersson Barison, Mehdi A Beniddir, Maique W Biavatti, Stefan Bluml, Asmaa Boufridi, Mark S Butler, Robert J Capon, Young H Choi, David Coppage, Phillip Crews, Michael T Crimmins, Marie Csete, Pradeep Dewapriya, Joseph M Egan, Mary J Garson, Grégory Genta-Jouve, William H Gerwick, Harald Gross, Mary Kay Harper, Precilia Hermanto, James M Hook, Luke Hunter, Damien Jeannerat, Nai-Yun Ji, Tyler A. Johnson, David G I Kingston, Hiroyuki Koshino, Hsiau-Wei Lee, Guy Lewin, Jie Li, Roger G Linington, Miaomiao Liu, Kerry L Mcphail, Tadeusz F Molinski, Bradley S Moore, Joo-Won Nam, Ram P Neupane, Matthias Niemitz, Jean-Marc Nuzillard, Nicholas H Oberlies, Fernanda M M Ocampos, Guohui Pan, Ronald J Quinn, D Sai Reddy, Jean-Hugues Renault, José Rivera-Chávez, Wolfgang Robien, Carla M Saunders, Thomas J Schmidt, Christoph Seger, Ben Shen, Christoph Steinbeck, Hermann Stuppner, Sonja Sturm, Orazio Taglialatela-Scafati, Dean J Tantillo, Robert Verpoorte, Bin-Gui Wang, Craig M Williams, Philip G Williams, Julien Wist, Jian-Min Yue, Chen Zhang, Zhengren Xu, Charlotte Simmler, David C Lankin, Jonathan Bisson, Guido F Pauli

Tyler Johnson

With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data …


The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A Valeriote, Phillip Crews Feb 2019

The Potential Of Achiral Sponge-Derived And Synthetic Bromoindoles As Selective Cytotoxins Against Panc-1 Tumor Cells., Nicholas Lorig-Roach, Frances Hamkins-Indik, Tyler A. Johnson, Karen Tenney, Frederick A Valeriote, Phillip Crews

Tyler Johnson

Our quest to isolate and characterize natural products with in vitro solid tumor selectivity is driven by access to repositories of Indo-Pacific sponge extracts. In this project an extract of a species of Haplosclerida sponge obtained from the US NCI Natural Products Repository displayed, by in vitro disk diffusion assay (DDA) and IC


Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela Feb 2019

Mass Stranding Of Marine Birds Caused By A Surfactant-Producing Red Tide., David A. Jessup, Melissa A. Miller, John P. Ryan, Hannah M Nevins, Heather A. Kerkering, Abdou Mekebri, David B. Crane, Tyler A. Johnson, Raphael M. Kudela

Tyler Johnson

In November-December 2007 a widespread seabird mortality event occurred in Monterey Bay, California, USA, coincident with a massive red tide caused by the dinoflagellate Akashiwo sanguinea. Affected birds had a slimy yellow-green material on their feathers, which were saturated with water, and they were severely hypothermic. We determined that foam containing surfactant-like proteins, derived from organic matter of the red tide, coated their feathers and neutralized natural water repellency and insulation. No evidence of exposure to petroleum or other oils or biotoxins were found. This is the first documented case of its kind, but previous similar events may have gone …


Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester Feb 2019

Rapid Enzyme-Linked Immunosorbent Assay For Detection Of The Algal Toxin Domoic Acid, R Wayne Litaker, Thomas N. Stewart, Bich-Thuy L. Eberhart, John C. Wekell, Vera L. Trainer, Raphael M. Kudela, Peter E. Miller, Alice Roberts, Cassandra Hertz, Tyler A. Johnson, Greg Frankfurter, G. Jason Smith, Astrid Schnetzer, Joe Schumacker, Jonnette L. Bastian, Anthony Odell, Patrick Gentien, Dominique Le Gal, D Ransom Hardison, Patricia A. Tester

Tyler Johnson

Domoic acid (DA) is a potent toxin produced by bloom-forming phytoplankton in the genus Pseudo-nitzschia, which is responsible for causing amnesic shellfish poisoning (ASP) in humans. ASP symptoms include vomiting, diarrhea, and in more severe cases confusion, loss of memory, disorientation, and even coma or death. This paper describes the development and validation of a rapid, sensitive, enzyme linked immunosorbent assay test kit for detecting DA using a monoclonal antibody. The assay gives equivalent results to those obtained using standard high performance liquid chromatography, fluorenylmethoxycarbonyl high performance liquid chromatography, or liquid chromatography—mass spectrometry methods. It has a linear range …


Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews Feb 2019

Myxobacteria Versus Sponge-Derived Alkaloids: The Bengamide Family Identified As Potent Immune Modulating Agents By Scrutiny Of Lc-Ms/Elsd Libraries., Tyler A. Johnson, Johann Sohn, Yvette M Vaske, Kimberly N White, Tanya L Cohen, Helene C Vervoort, Karen Tenney, Frederick A Valeriote, Leonard F Bjeldanes, Phillip Crews

Tyler Johnson

A nuclear factor-κB (NF-κB) luciferase assay has been employed to identify the bengamides, previously known for their anti-tumor activity, as a new class of immune modulators. A unique element of this study was that the bengamide analogs were isolated from two disparate sources, Myxococcus virescens (bacterium) and Jaspis coriacea (sponge). Comparative LC-MS/ELSD and NMR analysis facilitated the isolation of M. viriscens derived samples of bengamide E (8) and two congeners, bengamide E' (13) and F' (14) each isolated as an insperable mixture of diastereomers. Additional compounds drawn from the UC, Santa Cruz repository allowed expansion of the structure activity relationship …


The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou Feb 2019

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B Jekabsons, Tyler A. Johnson, Koneni V Sashidhara, Phillip Crews, Dale G Nagle, Yu-Dong Zhou

Tyler Johnson

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …


Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn Feb 2019

Lipophilic Stinging Nettle Extracts Possess Potent Anti-Inflammatory Activity, Are Not Cytotoxic And May Be Superior To Traditional Tinctures For Treating Inflammatory Disorders., Tyler A. Johnson, Johann Sohn, Wayne D Inman, Leonard F Bjeldanes, Keith Rayburn

Tyler Johnson

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate …


Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A Valeriote, Phillip Crews Feb 2019

Another Look At Pyrroloiminoquinone Alkaloids-Perspectives On Their Therapeutic Potential From Known Structures And Semisynthetic Analogues., Sheng Lin, Erin P Mccauley, Nicholas Lorig-Roach, Karen Tenney, Cassandra N Naphen, Ai-Mei Yang, Tyler A. Johnson, Thalia Hernadez, Ramandeep Rattan, Frederick A Valeriote, Phillip Crews

Tyler Johnson

This study began with the goal of identifying constituents from Zyzzya fuliginosa extracts that showed selectivity in our primary cytotoxicity screen against the PANC-1 tumor cell line. During the course of this project, which focused on six Z. fuliginosa samples collected from various regions of the Indo-Pacific, known compounds were obtained consisting of nine makaluvamine and three damirone analogues. Four new acetylated derivatives were also prepared. High-accuracy electrospray ionization mass spectrometry (HAESI-MS) m/z ions produced through MS2 runs were obtained and interpreted to provide a rapid way for dereplicating isomers containing a pyrrolo[4,3,2-de]quinoline core. In vitro human pancreas/duct epithelioid …


Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L Mooberry Feb 2019

Chemically Diverse Microtubule Stabilizing Agents Initiate Distinct Mitotic Defects And Dysregulated Expression Of Key Mitotic Kinases., Cristina C Rohena, Jiangnan Peng, Tyler A. Johnson, Phillip Crews, Susan L Mooberry

Tyler Johnson

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent …