DOCSLIB.ORG

Brevenal, a Marine Natural Product, Is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Brevenal, a Marine Natural Product, Is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells marine drugs Article Brevenal, a Marine Natural Product, is Anti-Inflammatory and an Immunomodulator of Macrophage and Lung Epithelial Cells Devon M. Keeler, Meghan K. Grandal and Jennifer R. McCall * UNCW Center for Marine Science, 5600 Marvin K Moss Lane, Wilmington, NC 28409, USA; [email protected] (D.M.K.); [email protected] (M.K.G.) * Correspondence: [email protected]; Tel.: +1-910-962-2081; Fax: +1-910-962-2410 Received: 12 February 2019; Accepted: 17 March 2019; Published: 20 March 2019 Abstract: Chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD), cystic fibrosis, and asthma, are some of the leading causes of illness and fatalities worldwide. The search for novel treatments led to the exploration of marine natural products as drug candidates to combat the debilitating effects of mucus accumulation and chronic inflammation. Previous research showed that an alga-derived compound, brevenal, could attenuate the effects of inflammatory agents, but the mechanisms by which it exerted its effects remained unclear. We investigated the effects of brevenal on lipopolysaccharide (LPS) induced cytokine/chemokine production from murine macrophages and human lung epithelial cells. It was found that brevenal reduces proinflammatory mediator secretion while preserving anti-inflammatory secretion from these cells. Furthermore, we found that brevenal does not alter cell surface Toll-like receptor 4 (TLR4) expression, thereby maintaining the cells’ ability to respond to bacterial infection. However, brevenal does alter macrophage activation states, as demonstrated by reduced expression of both M1 and M2 phenotype markers, indicating this putative anti-inflammatory drug shifts innate immune cells to a less active state. Such a mechanism of action would be ideal for reducing inflammation in the lung, especially with patients suffering from chronic respiratory diseases, where inflammation can be lethal. Keywords: brevenal; marine natural product; immunomodulator; anti-inflammatory; cystic fibrosis; COPD; asthma; cytokine; chemokine; macrophage activation; macrophage phenotype; mucociliary clearance 1. Introduction Chronic respiratory diseases are some of the leading causes of illness and death globally [1]. Chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), and asthma can all be fatal diseases that affect lung function by increasing inflammation and decreasing mucus clearance. Inflammation is a natural biological response, and at a local site of damage or infection, it is an important mechanism for the immune system to clear harmful stimuli. However, excessive inflammation, like that which occurs during sepsis, can damage delicate organ structures, such as those found in the respiratory system. Prolonged inflammation and corresponding damage of critical organ systems can be lethal [2,3]). Millions of people suffer globally from chronic respiratory diseases, including estimates of 65 million with COPD, 300 million with asthma, and 70,000 with CF [1,4–9]. Approximately 3 million people die each year from COPD [1,4,5]. Regrettably, it is estimated that 250,000 deaths are attributed to asthma each year, many of which could have been prevented with sufficient medical intervention [9]. Life expectancy of a patient with CF was only 5 years in the 1960s, and while the quality and length of Mar. Drugs 2019, 17, 184; doi:10.3390/md17030184 www.mdpi.com/journal/marinedrugs Mar. Drugs 2019, 17, 184 2 of 14 life have improved dramatically since then, CF remains a debilitating and ultimately fatal disease [6–8]. Mar. Drugs 2019, 17, x 2 of 14 As these diseases continue to have such an aggressive impact on human mortality, it is critical to progressdisease [6 research–8]. As these into the diseases causes, continue prevention, to have and such new an treatments aggressive of impact these diseases.on human mortality, it is criticalSearching to progress for novelresearch treatments into the causes, for these prevention, diseases and requires new treatments exploring of newthese drug diseases. candidates with bioactivitySearching for that novel can combat treatments inflammation for these diseases and mucus requires accumulation. exploring new The drug marine candidates environment with providesbioactivity a diversethat can source combat of naturalinflammation products and with mucus potential accumulation. to treat humanThe ailments.marine environment The marine dinoflagellateprovides a diverseKarenia source brevis isof onenatural such products source of with bioactive potential compounds. to treat human This unicellular ailments. alga The produces marine adinoflagellate number of bioactive Karenia compoundsbrevis is one with such therapeutic source of potential, bioactive including compounds. the neurotoxicThis unicellular brevetoxins alga (PbTxs),produces hemibrevetoxin a number of bioactive B, brevisin, compounds brevisamide, with therapeutic tamulamides potential, A and including B, and brevenal the neurotoxic [10–16 ]. Brevenalbrevetoxins (Figure (PbTxs),1) was hemibrevetoxin the first natural B, nontoxic brevisin, ligand brevisamide, described tamulamides that displaces A and PbTxs B, and from brevenal binding to[10 voltage-sensitive–16]. Brevenal (Figure sodium 1) was channels the first [16 natural]. In cell nontoxic models, ligand brevenal described has beenthat displaces found to PbTxs antagonize from PbTx-inducedbinding to voltage elevations-sensitive in intracellular sodium channels calcium [16 levels]. In [ 17cell] and models, reduce brevenal cell death has in been the presence found to of highlyantagonize toxic PbTx concentrations-induced elevations of PbTxs in [18 intrace]. In vivollularmodels calcium have levels shown [17] and that reduce brevenal cell can death attenuate in the PbTx-inducedpresence of highly bronchoconstriction toxic concentrations and of increase PbTxs tracheal[18]. In vivo mucosal models velocity have shown in sheep that [19 brevenal]. The ability can ofattenuate brevenal PbTx to increase-induced tracheal bronchoconstriction mucosal velocity and and increase mucocilliary tracheal clearance mucosal has velocity led to in the sheep patenting [19]. ofThe brevenal ability of as brevenal a treatment to increase for COPD, tracheal cystic mucosal fibrosis, velocity and asthma,and mucocilliary as well asclearance attempts has by led Silurian to the Pharmaceuticalspatenting of brevenal to begin as Phasea treatment I clinical for testingCOPD, for cystic the treatmentfibrosis, and of cysticasthma fibrosis., as well as attempts by Silurian Pharmaceuticals to begin Phase I clinical testing for the treatment of cystic fibrosis. FigureFigure 1.1. ChemicalChemical structures of relevant Karenia brevis natural products products.. DuringDuring thethe inin vivovivoinvestigation of of the the antagonistic antagonistic effects effects of ofbrevenal brevenal against against brevetoxins, brevetoxins, it itwas was discovered discovered that that brevenal brevenal alone alone cou couldld also also attenuate attenuate the theeffects effects of other of other inflammatory inflammatory agents. agents.For Forexample, example, brevenal brevenal has hasbeen been shown shown to attenuate to attenuate neutrophil neutrophil elastase elastase-induced-induced bronchoconstriction bronchoconstriction and anddecrease decrease neutrophil neutrophil recruitment recruitment into into the the lung lung[20 [20–22–22]. ].These These results results indicate indicate anti anti-inflammatory-inflammatory effectseffects not not typically typically seenseen withwith traditionaltraditional lunglung clearingclearing pharmaceuticals [20 [20––2323]].. Brevenal Brevenal has has also also beenbeen found found to to attenuateattenuate PbTx-inducedPbTx-induced activity and sodium influx influx in, in, but but not not activation activation of, of, mast mast cells, cells, aa keykey immuneimmune cellcell thatthat coordinatescoordinates allergicallergic responsesresponses [ 24]].. While brevenal brevenal shows shows promise promise as as a a potentialpotential therapeutic therapeutic forfor lunglung disease,disease, the the mechanism by which brevenal brevenal can can attenuate attenuate inflammation inflammation remainsremains unclear. unclear. SecondarySecondary to to airway airway restriction, restriction, chronic chronic respiratory respiratory diseases diseases are oftenare often compounded compounded by the by effects the ofeffects inflammation. of inflammation. An excessiveAn excessive inflammatory inflammatory response response can cause can seriouscause serious damage damage to lung to tissues, lung decreasingtissues, decreasing quality of quality life and increasingof life and debilitating increasing symptomsdebilitating associated symptoms with associated COPD, asthma, with COPD, and CF. Asasthma, such, andideal CF. drug As such, candidates ideal drug for chroniccandidates respiratory for chronic disease respirato willry have disease a dual will effect:have a Combatdual effect: the rootCombat cause the of diseaseroot cause (e.g., bronchoconstrictionof disease (e.g., bronchoconstriction or mucus accumulation) or mucus and simultaneously accumulation) reduce and damagingsimultaneously inflammation. reduce damaging The purpose inflammation. of our studyThe was purpose to examine of our the study effects was of to brevenal examine on the pro- effects and of brevenal on pro- and anti-inflammatory cytokine production from lung epithelial cells and immune cells, as an additive mechanism to its influence on airway restriction. Macrophages were used for
Load more

Recommended publications
  • Development of a Quantitative PCR Assay for the Detection And
    bioRxiv preprint doi: https://doi.org/10.1101/544247; this version posted February 8, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. Development of a quantitative PCR assay for the detection and enumeration of a potentially ciguatoxin-producing dinoflagellate, Gambierdiscus lapillus (Gonyaulacales, Dinophyceae). Key words:Ciguatera fish poisoning, Gambierdiscus lapillus, Quantitative PCR assay, Great Barrier Reef Kretzschmar, A.L.1,2, Verma, A.1, Kohli, G.S.1,3, Murray, S.A.1 1Climate Change Cluster (C3), University of Technology Sydney, Ultimo, 2007 NSW, Australia 2ithree institute (i3), University of Technology Sydney, Ultimo, 2007 NSW, Australia, [email protected] 3Alfred Wegener-Institut Helmholtz-Zentrum fr Polar- und Meeresforschung, Am Handelshafen 12, 27570, Bremerhaven, Germany Abstract Ciguatera fish poisoning is an illness contracted through the ingestion of seafood containing ciguatoxins. It is prevalent in tropical regions worldwide, including in Australia. Ciguatoxins are produced by some species of Gambierdiscus. Therefore, screening of Gambierdiscus species identification through quantitative PCR (qPCR), along with the determination of species toxicity, can be useful in monitoring potential ciguatera risk in these regions. In Australia, the identity, distribution and abundance of ciguatoxin producing Gambierdiscus spp. is largely unknown. In this study we developed a rapid qPCR assay to quantify the presence and abundance of Gambierdiscus lapillus, a likely ciguatoxic species. We assessed the specificity and efficiency of the qPCR assay. The assay was tested on 25 environmental samples from the Heron Island reef in the southern Great Barrier Reef, a ciguatera endemic region, in triplicate to determine the presence and patchiness of these species across samples from Chnoospora sp., Padina sp.
    [Show full text]
  • Treatment Protocol Copyright © 2018 Kostoff Et Al
    Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al PREVENTION AND REVERSAL OF ALZHEIMER'S DISEASE: TREATMENT PROTOCOL by Ronald N. Kostoffa, Alan L. Porterb, Henry. A. Buchtelc (a) Research Affiliate, School of Public Policy, Georgia Institute of Technology, USA (b) Professor Emeritus, School of Public Policy, Georgia Institute of Technology, USA (c) Associate Professor, Department of Psychiatry, University of Michigan, USA KEYWORDS Alzheimer's Disease; Dementia; Text Mining; Literature-Based Discovery; Information Technology; Treatments Prevention and reversal of Alzheimer's disease: treatment protocol Copyright © 2018 Kostoff et al CITATION TO MONOGRAPH Kostoff RN, Porter AL, Buchtel HA. Prevention and reversal of Alzheimer's disease: treatment protocol. Georgia Institute of Technology. 2018. PDF. https://smartech.gatech.edu/handle/1853/59311 COPYRIGHT AND CREATIVE COMMONS LICENSE COPYRIGHT Copyright © 2018 by Ronald N. Kostoff, Alan L. Porter, Henry A. Buchtel Printed in the United States of America; First Printing, 2018 CREATIVE COMMONS LICENSE This work can be copied and redistributed in any medium or format provided that credit is given to the original author. For more details on the CC BY license, see: http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License<http://creativecommons.org/licenses/by/4.0/>. DISCLAIMERS The views in this monograph are solely those of the authors, and do not represent the views of the Georgia Institute of Technology or the University of Michigan. This monograph is not intended as a substitute for the medical advice of physicians. The reader should regularly consult a physician in matters relating to his/her health and particularly with respect to any symptoms that may require diagnosis or medical attention.
    [Show full text]
  • 1 Gambierol 1 2 3 4 Makoto Sasaki, Eva Cagide, and 5 M
    34570 FM i-xviii.qxd 2/9/07 9:16 AM Page i PHYCOTOXINS Chemistry and Biochemistry 34570 FM i-xviii.qxd 2/9/07 9:16 AM Page iii PHYCOTOXINS Chemistry and Biochemistry Luis M. Botana Editor 34570 FM i-xviii.qxd 2/9/07 9:16 AM Page iv 1 2 3 Dr. Luis M. Botana is professor of Pharmacology, University of Santiago de Compostela, Spain. His group is a 4 world leader in the development of new methods to monitor the presence of phycotoxins, having developed 5 methods to date for saxitoxins, yessotoxin, pectenotoxin, ciguatoxins, brevetoxins, okadaic acid and dinophy- 6 sistoxins. Dr. Botana is the editor of Seafood and Freshwater Toxins: Pharmacology, Physiology and Detection, 7 to date the only comprehensive reference book entirely devoted to marine toxins. 8 ©2007 Blackwell Publishing 9 All rights reserved 10 1 Blackwell Publishing Professional 2 2121 State Avenue, Ames, Iowa 50014, USA 3 4 Orders: 1-800-862-6657 5 Office: 1-515-292-0140 6 Fax: 1-515-292-3348 7 Web site: www.blackwellprofessional.com 8 Blackwell Publishing Ltd 9 9600 Garsington Road, Oxford OX4 2DQ, UK 20 Tel.: +44 (0)1865 776868 1 2 Blackwell Publishing Asia 3 550 Swanston Street, Carlton, Victoria 3053, Australia 4 Tel.: +61 (0)3 8359 1011 5 6 Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, 7 is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Cen- 8 ter, 222 Rosewood Drive, Danvers, MA 01923.
    [Show full text]
  • A A–803467, 98 Absorption, Distribution, Metabolism, Elimination
    Index A Anxiety disorders, 55 A–803467, 98 APD. See Action potential duration Absorption, distribution, metabolism, Arrhythmias, 45, 46 elimination and toxicity Aryl sulfonamido indanes, 126–128, 130 (ADMET), 193 ATP-sensitive potassium channels (KATP Absorption, distribution, metabolism, channels), 61 excretion, and toxicity Atrial effective refractory period (AERP), 122, (ADMET), 68 124–126, 128, 129, 132, 138 Acetylcholine binding protein (AChBP), Autoimmune diseases, 254 61, 62, 64 AZD7009, 101 Acetylcholine receptor (AChR), 57, 64 Azimilide, 139 Action potential duration (APD), 120, 122, 123, 128, 132 B Action potentials, 243, 256, 259 Basis set, 69–70 ADME/T, 299, 304 b-Barrel membrane proteins AERP. See Atrial effective refractory period genome-wide annotation, 13 Agitoxin (AgTX), 60 machine-learning techniques Agonists, 59–61, 64 residue pair preference, 11 Alinidine, 40–42 TMBs, 10 ALS. See Amyotrophic lateral sclerosis pipeline, genomic sequences, 14 Alzheimer, 55, 61 statistical method, 9–10 AMBER, 61, 65 Bending hinge, 64 2-Amino–2-imidazolidinone, 123, 125 Benzanilide, 256–257 Ammi visnaga, 254 Benzimidazolone, 256–257 b-Amyloid peptide (Ab), 62–63, 65 Benzocaine, 140 Amyotrophic lateral sclerosis (ALS), 90, 94, Benzodiazepines, 245 101 Benzopyrane, 127–128 Anionic channel blockers Benzopyrans, 61, 246–251, 261 mechanism of action of, 329–330 Benzothiadiazine 1,1-dioxide, 252–254 Antagonists, 59, 60 Benzothiadiazines, 253 Antiarrhythmic, 65–66, 68, 99, 101 Benzothiazepine, 70 Antiarrhythmic agents Benzothiazine derivatives, 251–252 class I, 245 Benzotriazole, 256–257 class II, 245 Bestrophins, 321, 322, 330, 331 class III, 245 Big potassium channels (BK channels), Antidepressant, 65–67 256, 257 Antiepileptic, 46 Bupivacaine, 56, 58, 59, 64, 69, 140 S.P.
    [Show full text]
  • Marine Natural Products and Their Potential Application in the Future
    AJSTD Vol. 22 Issue 4 pp. 297-311 (2005) MARINE NATURAL PRODUCTS AND THEIR POTENTIAL APPLICATION IN THE FUTURE Chau Van Minh*, Phan Van Kiem, and Nguyen Hai Dang Institute of Natural Products Chemistry, Vietnamese Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay, Hanoi, Vietnam Received 04 November 2005 1. INTRODUCTION Oceans are the diverse resource, which cover more than 70% of the earth’s surface. No doubt, with 34 of 36 phyla of life represented, oceans are the greatest biodiversity in the world [1]. They are the extraordinary natural source of microorganism, algae, sponge, coelenterate, bryozoan, mollusk, and echinoderm… Especially, on coral reef, where shelter more than 1000 species per m2. Surprisingly, there is only a small number of researches in this field. Therefore increasing research on marine natural source may provide good results for exploiting and developing valuable natural products which benefit for human. Marine environment is a rich source of biological and chemical diversity. The diversity has been unique source of chemical compounds of potential for pharmaceuticals, cosmetics, dietary supplements, and agrochemicals. Ecological pressure, including competitions for food and space, the fouling of predator and surface, has led to the evolution of secondary metabolites with various biological activities. Many organisms are soft bodies and/or unmoved, hardly survive with the threat from around environment. Hence they have evolved the ability to synthesize toxic compounds or obtain them from microorganism to defense against predator or to paralyze their prey. The questions such as, why do fish not eat particular algae? Why do two sponges grow and expand until they reach but not grow over each other? may be explained by these reasons.
    [Show full text]
  • Influence of Lipid-Soluble Gating Modifier Toxins on Sodium Influx in Neocortical Neurons
    0022-3565/08/3262-604–613$20.00 THE JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS Vol. 326, No. 2 Copyright © 2008 by The American Society for Pharmacology and Experimental Therapeutics 138230/3358916 JPET 326:604–613, 2008 Printed in U.S.A. Influence of Lipid-Soluble Gating Modifier Toxins on Sodium Influx in Neocortical Neurons Zhengyu Cao, Joju George, William H. Gerwick, Daniel G. Baden, Jon D. Rainier, and Thomas F. Murray Creighton University, School of Medicine, Department of Pharmacology, Omaha, Nebraska (Z.C., J.G., T.F.M.); Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California at San Diego, La Jolla, California (W.H.G.); University of North Carolina, Center for Marine Science Research, Wilmington, North Carolina (D.G.B.); and Department of Chemistry, University of Utah, Salt Lake City, Utah (J.D.R.) Received February 20, 2008; accepted April 25, 2008 Downloaded from ABSTRACT The electrical signals of neurons are fundamentally dependent tridine and aconitine, and the pyrethroid deltamethrin were ϩ on voltage-gated sodium channels (VGSCs), which are respon- somewhat lower with maximal [Na ]i increments of less than 40 sible for the rising phase of the action potential. An array of mM. The rank order of efficacy of sodium channel gating mod- jpet.aspetjournals.org naturally occurring and synthetic neurotoxins have been iden- ifiers was brevetoxin (PbTx)-1 Ͼ PbTx-desoxydioxolane Ͼ tified that modify the gating properties of VGSCs. Using murine batrachotoxin Ͼ antillatoxin Ͼ PbTx-2 ϭ PbTx-3 Ͼ PbTx- neocortical neurons in primary culture, we have compared the 3␣-naphthoate Ͼ veratridine Ͼ deltamethrin Ͼ aconitine Ͼ ability of VGSC gating modifiers to evoke Naϩ influx.
    [Show full text]
  • Concurrent Sessions Abstracts
    20th World Congress of the International Society on Toxinology "Toxinology in the 21st century: Public health impact from basic, translational and clinical sciences" CONCURRENT SESSION ABSTRACTS 08 – 13 September, 2019 Buenos Aires, Argentina INDEX Page Concurrent Session I 1A. Public Health and Toxinology 2 1B. New Developments in Basic Toxinology I. 7 Concurrent Session II 2A. New Developments in Antivenoms 14 2B. New Developments in Basic Toxinology II. 20 Concurrent Session III 3A. Emerging Technologies in Toxinology 28 3B. Organ Systems and Toxins I 35 Concurrent Session IV 4A. Non-antibody and Adjuvant – Based Therapeutics 41 4B. Organ Systems and Toxins II 47 Concurrent Session V 5A. North American Society on Toxinology 55 Concurrent Session VI 6A. North American Society on Toxinology 60 Concurrent Session VII 7A. Clinical I 66 Concurrent Session VIII 8A. New Biology and Evolution of Venomous Organisms I 77 8B. Clinical II. Emerging Clinical Topics: Safety and Effectiveness of Current Antivenoms; Clinical Presentations of Intoxication and Management; 83 Epidemiology. Concurrent Session IX 9A. New Biology and Evolution of Venomous Organisms II 89 9B. SBTX: Innovation in Clinical and Basic Research in Toxinology 96 1 Concurrent Session I 1A. Public Health and Toxinology. Chairs: José M. Gutiérrez/Fan Hui Wen 1. Abdulrazaq Habib (Bayero University, Nigeria): Burden of Snakebite and Antivenom Supply Challenges in Africa. [email protected] 2. Mohammad Afzal Mahmood: A framework for shifting the paradigm and developing coalitions to address neglected public health problems: Lessons from the Myanmar Snakebite Project. [email protected] 3. Fan Hui Wen: (Instituto Butantan, Brazil): Public health policies to better manage the burden of scorpion sting envenoming.
    [Show full text]
  • Innovative Mode of Action Based in Vitro Assays for Detection of Marine Neurotoxins
    Innovative mode of action based in vitro assays for detection of marine neurotoxins Jonathan Nicolas Thesis committee Thesis advisor Prof. Dr I.M.C.M. Rietjens Professor of Toxicology Wageningen UR Thesis co-supervisors Dr P.J.M. Hendriksen Project leader, BU Toxicology and Bioassays RIKILT - Institute of Food Safety, Wageningen UR Dr T.F.H. Bovee Expertise group leader Bioassays & Biosensors, BU Toxicology and Bioassays RIKILT - Institute of Food Safety, Wageningen UR Other members Prof. Dr D. Parent-Massin, University of Western Brittany, Brest, France Dr P. Hess, French Research Institute for Exploitation of the Sea (IFREMER), Nantes, France Prof. Dr A.J. Murk, Wageningen UR Prof. Dr A. Piersma, National Institute for Public Health and the Environment (RIVM), Bilthoven This research was conducted under the auspices of the Graduate School VLAG (Avanced studies in Food Technology, Agrobiotechnology, Nutrition and Health Sciences). Innovative mode of action based in vitro assays for detection of marine neurotoxins Jonathan Nicolas Thesis submitted in fulfilment of the requirements for the degree of doctor at Wageningen University by the authority of the Rector Magnificus Prof. dr. ir. A.P.J. Mol, in the presence of the Thesis Committee appointed by the Academic Board to be defended in public on Wednesday 07 October 2015 at 11 a.m. in the Aula. Jonathan Nicolas Innovative mode of action based in vitro assays for detection of marine neurotoxins, 214 pages, PhD thesis, Wageningen UR, Wageningen, NL (2015) With references, with summary in
    [Show full text]
  • Ciguatera Mini Review: 21St Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them
    International Journal of Environmental Research and Public Health Review Ciguatera Mini Review: 21st Century Environmental Challenges and the Interdisciplinary Research Efforts Rising to Meet Them Christopher R. Loeffler 1,2,* , Luciana Tartaglione 2,3, Miriam Friedemann 4, Astrid Spielmeyer 1, Oliver Kappenstein 1 and Dorina Bodi 1 1 National Reference Laboratory of Marine Biotoxins, Department Safety in the Food Chain, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany; [email protected] (A.S.); [email protected] (O.K.); [email protected] (D.B.) 2 Department of Pharmacy, School of Medicine and Surgery, University of Napoli Federico II, Via D. Montesano 49, 80131 Napoli, Italy; [email protected] 3 CoNISMa—National Inter-University Consortium for Marine Sciences, Piazzale Flaminio 9, 00196 Rome, Italy 4 Department Exposure, German Federal Institute for Risk Assessment, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany; [email protected] * Correspondence: Christopher.Loeffl[email protected] Abstract: Globally, the livelihoods of over a billion people are affected by changes to marine ecosys- tems, both structurally and systematically. Resources and ecosystem services, provided by the Citation: Loeffler, C.R.; Tartaglione, marine environment, contribute nutrition, income, and health benefits for communities. One threat L.; Friedemann, M.; Spielmeyer, A.; to these securities is ciguatera poisoning; worldwide, the most commonly reported non-bacterial Kappenstein, O.; Bodi, D. Ciguatera seafood-related illness. Ciguatera is caused by the consumption of (primarily) finfish contaminated Mini Review: 21st Century with ciguatoxins, potent neurotoxins produced by benthic single-cell microalgae. When consumed, Environmental Challenges and the ciguatoxins are biotransformed and can bioaccumulate throughout the food-web via complex path- Interdisciplinary Research Efforts ways.
    [Show full text]
  • Lessons Learned
    Prevention and Reversal of Chronic Disease Copyright © 2019 RN Kostoff PREVENTION AND REVERSAL OF CHRONIC DISEASE: LESSONS LEARNED By Ronald N. Kostoff, Ph.D., School of Public Policy, Georgia Institute of Technology 13500 Tallyrand Way, Gainesville, VA, 20155 [email protected] KEYWORDS Chronic disease prevention; chronic disease reversal; chronic kidney disease; Alzheimer’s Disease; peripheral neuropathy; peripheral arterial disease; contributing factors; treatments; biomarkers; literature-based discovery; text mining ABSTRACT For a decade, our research group has been developing protocols to prevent and reverse chronic diseases. The present monograph outlines the lessons we have learned from both conducting the studies and identifying common patterns in the results. The main product of our studies is a five-step treatment protocol to reverse any chronic disease, based on the following systemic medical principle: at the present time, removal of cause is a necessary, but not necessarily sufficient, condition for restorative treatment to be effective. Implementation of the five-step treatment protocol is as follows: FIVE-STEP TREATMENT PROTOCOL TO REVERSE ANY CHRONIC DISEASE Step 1: Obtain a detailed medical and habit/exposure history from the patient. Step 2: Administer written and clinical performance and behavioral tests to assess the severity of symptoms and performance measures. Step 3: Administer laboratory tests (blood, urine, imaging, etc) Step 4: Eliminate ongoing contributing factors to the chronic disease Step 5: Implement treatments for the chronic disease This individually-tailored chronic disease treatment protocol can be implemented with the data available in the biomedical literature now. It is general and applicable to any chronic disease that has an associated substantial research literature (with the possible exceptions of individuals with strong genetic predispositions to the disease in question or who have suffered irreversible damage from the disease).
    [Show full text]
  • Neuroprotective Natural Products Neuroprotective Natural Products
    Neuroprotective Natural Products Neuroprotective Natural Products Clinical Aspects and Mode of Action Edited by Goutam Brahmachari Editor All books published by Wiley-VCH are carefully produced. Nevertheless, authors, Dr. Goutam Brahmachari editors, and publisher do not warrant the Visva-Bharati (a Central University) information contained in these books, including Department of Chemistry, Laboratory this book, to be free of errors. Readers are of Natural Products and Organic Synthesis, advised to keep in mind that statements, data, Santiniketan illustrations, procedural details or other items West Bengal 731 235 may inadvertently be inaccurate. India Cover Library of Congress Card No.: applied for Neurons: © fotolia_ktsdesign British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library. Bibliographic information published by the Deutsche Nationalbibliothek The Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at http:// dnb.d-nb.de. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are
    [Show full text]
  • Inhibition of Kv Channels by Gambierol Through an Interaction with the Voltage-Sensing Domain
    This item is the archived peer-reviewed author-version of: Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels Reference: Kopljar Ivan, Grottesi Alessandro, de Block Tessa, Rainier Jon D., Tytgat Jan, Labro Alain, Snyders Dirk.- Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels Neuropharmacology - ISSN 0028-3908 - 107(2016), p. 160-167 Full text (Publisher's DOI): http://dx.doi.org/doi:10.1016/J.NEUROPHARM.2016.03.010 To cite this reference: http://hdl.handle.net/10067/1330540151162165141 Institutional repository IRUA *Title page Voltage-sensor conformation shapes the intra-membrane drug binding site that determines gambierol affinity in Kv channels. Authors: Ivan Kopljar1Ψ, Alessandro Grottesi2, Tessa de Block1, Jon D. Rainier3, Jan Tytgat4, Alain J. Labro1, Dirk J. Snyders1* Affiliations: 1Laboratory for Molecular Biophysics, Physiology and Pharmacology, University of Antwerp, 2610 Antwerp, Belgium 2CINECA – Sede di Roma – Via dei Tizii 6, 00185 – Rome, Italy 3Department of Chemistry, University of Utah, Salt Lake City, UT 84112-0850, USA 4Toxicology and Pharmacology, University of Leuven Campus Gasthuisberg, 3000 Leuven, Belgium ΨCurrent affilation: Global Safety Pharmacology, PD&S, Discovery Sciences, Janssen Research and Development, Beerse, Belgium *Corresponding Author: Dirk J. Snyders, M.D., Ph.D. Laboratory for Molecular Biophysics, Physiology and Pharmacology Department of Biomedical Sciences University of Antwerp Universiteitsplein 1, T5.35 2610 Antwerp, Belgium Phone: +32-(3)-820-2335 Fax: +32-(3)-820-2326 Email: [email protected] *Abstract Abstract Marine ladder-shaped polyether toxins are implicated in neurological symptoms of fish-borne food poisonings.
    [Show full text]