Natural cardiotoxic toxins from plants: source, structure, receptors, mode of action, effects on heart and toxicity.
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More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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by"}},authors:[{id:"119775",title:"Prof.",name:"Osman",middleName:null,surname:"Babaarslan",fullName:"Osman Babaarslan",slug:"osman-babaarslan",email:"teksob@cu.edu.tr",position:null,institution:{name:"Cukurova University",institutionURL:null,country:{name:"Turkey"}}},{id:"178353",title:"Dr.",name:"Halil",middleName:"İbrahim",surname:"Çelik",fullName:"Halil Çelik",slug:"halil-celik",email:"hcelik@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"216179",title:"Dr.",name:"Esin",middleName:null,surname:"Sarıoğlu",fullName:"Esin Sarıoğlu",slug:"esin-sarioglu",email:"sarioglu@gantep.edu.tr",position:null,institution:{name:"Gaziantep University",institutionURL:null,country:{name:"Turkey"}}},{id:"245674",title:"Mrs.",name:"Münevver",middleName:null,surname:"Ertek Avci",fullName:"Münevver Ertek Avci",slug:"munevver-ertek-avci",email:"Munevver.ErtekAvci@calikdenim.com",position:null,institution:null}]},book:{id:"7242",title:"Engineered Fabrics",subtitle:null,fullTitle:"Engineered Fabrics",slug:"engineered-fabrics",publishedDate:"February 13th 2019",bookSignature:"Mukesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/7242.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"36895",title:"Dr.",name:"Mukesh Kumar",middleName:null,surname:"Singh",slug:"mukesh-kumar-singh",fullName:"Mukesh Kumar Singh"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},ofsBook:{item:{type:"book",id:"8807",leadTitle:null,title:"Organic Synthesis",subtitle:null,reviewType:"peer-reviewed",abstract:"
\r\n\tOrganic synthesis has always been one of the central topics of research for the scientific community in the academic laboratories and industrial world. Many striking journal articles and remarkable reviews and books have been published in the past year describing the practicability and applications of the subject demonstrating the importance of organic synthesis. In the present book, we will be putting together the topics in organic synthesis which may include but not limited to, (1) the basic terms and concepts, (2) various organic reactions including reduction, oxidation, addition, elimination, rearrangements, and cycloadditions, (3) Total Synthesis of Natural products, (4) transition metal catalysts, organocatalysts, enzymes and biotransformations, (5) applications in medicinal chemistry and drug design and development, (6) purification methods and characterization techniques, etc. To set a limit and to increase the scope of the book, author(s) are encouraged to send the chapters that include selected examples with practical applications and good yielding reactions reported within the past decade. Older topics with significant findings or their essence to prepare the foundation may be included in the chapter are welcomed as well.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"f3bbbd989d0896f142d317ccb8abcc35",bookSignature:"Dr. Prashant S Deore",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8807.jpg",keywords:"Natural Product Synthesis, Organic Reaction Mechanism, Stereoselective synthesis, Chirality, C-H Functionalization, Cross-Coupling Reactions, Heterogeneous Catalysis, Homogeneous Catalysis, Green Synthesis, Green Solvents and Reagents, Bioorganic synthesis, Click Chemistry",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 10th 2018",dateEndSecondStepPublish:"January 14th 2019",dateEndThirdStepPublish:"March 15th 2019",dateEndFourthStepPublish:"May 20th 2019",dateEndFifthStepPublish:"July 19th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"251769",title:"Dr.",name:"Prashant",middleName:"S",surname:"Deore",slug:"prashant-deore",fullName:"Prashant Deore",profilePictureURL:"https://mts.intechopen.com/storage/users/251769/images/system/251769.png",biography:"Dr. Prashant S. Deore was born in India. He received a Master’s degree in organic chemistry from Pune University in 2007. In the same year, he qualified with the SET and CSIR-NET (JRF) and joined in the group of Prof. Narshinha P. Argade for the doctoral studies in National Chemical Laboratory, India. In 2014, he awarded with a Ph. D. in Chemistry and was a recipient of the 2nd prize in “2014 Eli Lilly and Company Asia Outstanding Thesis Awards”. In July 2014 he moved to Canada and joined as a postdoctoral researcher in the group of Prof. Richard Manderville at the University of Guelph, Canada. Presently, Dr. Deore is working on the collaborative project between the University of Guelph and Aterica health Inc., and providing consulting to the company. His research interest includes organic synthesis, fluorescent probes development, nucleic acid synthesis and modifications, and aptasensor development for proteins and food toxins.",institutionString:"University of Guelph",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"8",title:"Chemistry",slug:"chemistry"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270935",firstName:"Rozmari",lastName:"Marijan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270935/images/7974_n.png",email:"rozmari@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"32608",title:"Cardiovascular Pathophysiology Produced by Natural Toxins and Their Possible Therapeutic Implications",doi:"10.5772/35079",slug:"cardiovascular-pathophysiology-produced-by-natural-toxins-and-their-possible-therapeutic-implication",body:'\n\t\tVenoms are complex concentrates of biologically highly active molecules known as toxins, and they exist mainly as peptides and proteins. Several natural toxins are produced by plants, bacteria, phytoplanktonic dinoflagellates, sea anemones, insects, fungi and animals. In nature, toxins have two main functions: to capture their preferred prey (e.g. spiders, snakes, scorpions, etc.) or to serve as defence (e.g. bee sting, frog poison, etc.). Toxins produced by micro-organisms are important virulence factors. On the other hand they are also tools to combat diseases. Some of them are used in low quantities as drugs, to prepare vaccines and as important tools in biomedical research. Toxins affecting heart physiology are very effective in the sense of defence and especially in capturing prey. They can disturb electrical (producing arrhythmias) and mechanical activity of the heart affecting pumping or leading even to cardiac arrest. The aim of this chapter is to describe most of the toxins affecting heart function, their targets in the heart tissue, mode of action and the most important clinical effects of envenomation.
\n\t\tVoltage-gated sodium channels are an essential part of excitable membranes and enable fast depolarisation, which is responsible for action potential (AP) generation in cardiomyocytes and in the some parts of the conduction system of the heart. Their density is very low in some parts of the heart\'s conductive system, e.g. sinoatrial node and atrioventricular node cells, and the highest in Purkinje cells and cardiomyocytes (Fozzard, 1996). Hence, they are targeted by several neurotoxins from plants and animals that use these molecules for defence and protection.
\n\t\t\tDifferent types of Ca2+-permeable channels have been described in the plasma membrane of heart cells: the L- and T-type channels, both voltage activated, and a background channel (for a review see Carmeliet et al., 1999). Inward current through L-type high voltage-gated calcium channels is responsible for prolonged AP in cardiac muscle cells and cardiac muscle contraction. L-type voltage-gated Ca2+-channels are especially target for some bacterial (saxitoxin) and animal toxins (atrotoxin, maitotoxin, -conotoxin, crotoxin).
\n\t\t\tThe role of potassium channels is to repolarize the membrane during the AP or to maintain hyperpolarizing potential. They are involved in the regulation of duration of the AP. Therefore, changes in the function of potassium channels may cause life-threatening arrhythmias (Carmeliet et al., 1999). Important potassium channels that can be the target of natural toxins are calcium-activated potassium channels (charybdotoxin, iberiotoxin, apamin) and voltage-gated potassium channels (some dendrotoxins).
\n\t\t\tAconitines are a group of very poisonous alkaloids derived from various aconite species. They are neurotoxins that open TTX-sensitive Na+ channels in the heart and other tissues (Wang & Wang, 2003). Some of them can bind to the high affinity receptor site 2 of sodium channels (Ki ~1.2 µM) and some of them to a low affinity binding site (Ki ~11.5 µM). The compounds of the high affinity group, which increases synaptosomal sodium and calcium activity (EC50 3 µM), are the most toxic and provoke tachyarrhythmia. Binding of aconitine to the site II of voltage-dependent Na+ channels prolongs the open state responsible for Na+ influx leading to the permanent depolarization. Now it is commonly accepted that aconitine produces arrhythmias by prolonging opening or delaying the inactivation of voltage-dependent Na+ channels. Low affinity alkaloids from aconitum species are less-toxic, reduce intracellular calcium activity and induce bradycardia (Friese et al., 1997).
\n\t\t\t\tAt least four grayanotoxins (GTXs) have been isolated from the leaves of Rhododendron decorum (Ericaceae). These toxins are responsible for so called "mad honey" intoxication. Early in the 1980s it was published that GTXs produce cardiac tachyarrhythmias. The pathophysiological mechanism, underlying tachyarrhythmia, is the triggered activity in the form of oscillatory afterpotentials, as it was shown in feline cardiac Purkinje fibres (Brown et al., 1981). After intoxication, GTXs can produce bradyarrhythmias in man and livestock (Koca & Koca, 2007). It was shown that GTXs-induced cardiac toxicity in rats is a consequence of increased sodium channel permeability and activated vagus nerve (Onat et al., 1991). Intoxication is associated with the fatal bradyarrhythmias that include second degree atrio-ventricular block and circulatory collapse (Okuyan et al., 2010).
\n\t\t\t\tVeratrum species plants contain more than 200 different alkaloids, which are the principal toxins. The opening of voltage-gated sodium channels is probably one of the most relevant pathophysiological mechanisms of its toxicity. Veratridine injected intravenously in rats induced the Bezold-Jarisch-like effect (transient hypotension) accompanied by bradicardia (Chianca et al., 1985). It is well known that persistent sodium current, which can be enhanced during heart ischemia, is one of the major contributors to ischemic arrhythmias. Prolonged cardiac AP, which can also be induced by veratridine, favours the occurrence of early afterdepolarizations that is one of the pathophysiological mechanisms of tachyarrhythmias. Increased Na+ uptake activates the Na+/Ca2+ exchanger that leads to cardomyocytes’ Ca2+ overload. The latter can trigger the late depolarization after-potentials (DAPs), which is another pathophysiological mechanism underlying arrhythmias. If the amplitude of the DAPs reaches the threshold potential, a new AP is triggered. Such large, late DAPs often occur in the case of oscillations of the cytosolic Ca2+ concentration (Pignier et al., 2010).
\n\t\t\t\t\tName | \n\t\t\t\t\t\t\t\tSource (produced by) | \n\t\t\t\t\t\t\t\tChemical structure | \n\t\t\t\t\t\t\t\tTarget | \n\t\t\t\t\t\t\t\tMode of action | \n\t\t\t\t\t\t\t\tEffects | \n\t\t\t\t\t\t\t\tAcute LD50 in mice | \n\t\t\t\t\t\t\t\tReference | \n\t\t\t\t\t\t\t
Cardiotoxic toxins from plants | \n\t\t\t\t\t\t\t|||||||
Aconitine | \n\t\t\t\t\t\t\t\tPlants from genus Aconitum | \n\t\t\t\t\t\t\t\tAlkaloid | \n\t\t\t\t\t\t\t\tVoltage-gated Na+ channels | \n\t\t\t\t\t\t\t\tDepolariza-tion, AP duration increase | \n\t\t\t\t\t\t\t\tArrhy-thmias | \n\t\t\t\t\t\t\t\t0.1 mg/kg | \n\t\t\t\t\t\t\t\tGutser, 1998 | \n\t\t\t\t\t\t\t
Grayanoto-xins (GTX) | \n\t\t\t\t\t\t\t\tSpecies from genus Rhododendron | \n\t\t\t\t\t\t\t\tPolyhydro-xylated cyclic diterpene | \n\t\t\t\t\t\t\t\tIncrease Na+ channel permeability and activate vagus nerve | \n\t\t\t\t\t\t\t\tAlteration of excitability | \n\t\t\t\t\t\t\t\tFatal cardiac bradyar-rhythmias | \n\t\t\t\t\t\t\t\t1.28 mg/kg i.p. | \n\t\t\t\t\t\t\t\tBrown et al., 1981; Okuyan et al., 2010 ; Scott et al., 1971 | \n\t\t\t\t\t\t\t
Veratridine | \n\t\t\t\t\t\t\t\tPlants in the family Liliaceae | \n\t\t\t\t\t\t\t\tSteroid-derived alkaloid | \n\t\t\t\t\t\t\t\tBinding to the activated Na+ ion channels | \n\t\t\t\t\t\t\t\tDepolariza-tion, AP duration increase | \n\t\t\t\t\t\t\t\tArrhy-thmias | \n\t\t\t\t\t\t\t\t1.35 mg/kg i.p. | \n\t\t\t\t\t\t\t\tChianca et al., 1985; Pignier et al., 2010; Swiss & Bauer, 1951 | \n\t\t\t\t\t\t\t
Natural cardiotoxic toxins from plants: source, structure, receptors, mode of action, effects on heart and toxicity.
Ostreolysin (Oly) is an acidic, 15 kDa protein isolated from the edible oyster mushroom (Pleurotus ostreatus) (Berne et al., 2002). It is a toxic, pore-forming cytolysin (Sepčić et al., 2003). When administered intravenously (i.v.), Oly causes electrocardiographic, arterial blood pressure and respiratory changes. Oly produces changes such as transient increase of arterial blood pressure followed by a progressive fall to mid-circulatory pressure accompanied by bradicardia, myocardial ischaemia and ventricular extrasystoles. Oly also induces lysis of rat erythrocytes in vitro and in vivo, resulting in hyperkalemia. Although direct action of the protein on the cardiomyocytes or heart circulation cannot be excluded (Oly is pore-forming toxin), the hyperkalemia resulting from the haemolytic activity seems to play an important role in its cardiotoxicity (Žužek et al., 2006). Additionally, an important mechanism of the cardiotoxic effect may also be its concentration-dependent contractile effect on elastic blood vessels, such as aorta (Rebolj et al., 2009) and coronary vessels (Juntes et al., 2009).
\n\t\t\t\t\tName | \n\t\t\t\t\t\t\t\tSource (produced by) | \n\t\t\t\t\t\t\t\tChemical structure | \n\t\t\t\t\t\t\t\tTarget | \n\t\t\t\t\t\t\t\tMode of action | \n\t\t\t\t\t\t\t\tEffects | \n\t\t\t\t\t\t\t\tAcute LD50 in mice | \n\t\t\t\t\t\t\t\tRefer-ence | \n\t\t\t\t\t\t\t
Cardiotoxic toxins derived from mushrooms | \n\t\t\t\t\t\t\t|||||||
Ostreolysin | \n\t\t\t\t\t\t\t\tOyster mushroom (Pleurotus ostreatus) | \n\t\t\t\t\t\t\t\tPore-forming protein | \n\t\t\t\t\t\t\t\tCell membranes | \n\t\t\t\t\t\t\t\tPore formation | \n\t\t\t\t\t\t\t\tBradycardia; myocardial ischaemia; ventricular extrasystoles, hyperkalemia | \n\t\t\t\t\t\t\t\t1.17 mg/kg | \n\t\t\t\t\t\t\t\tŽužek et al., 2006 | \n\t\t\t\t\t\t\t
Natural cardiotoxic toxins from mushrooms: source, structure, receptors, mode of action, effects on heart and toxicity.
\n\t\t\t\t\t\t\tVibrio parahemolyticus toxin is lethal for rats when injected i.v. in a dose of 5 g/kg or higher. It decreases intra-atrial and ventricular conductivity, and produces atrioventricular block. Before cardiac arrest occurs, ventricular flutter develops. The toxin is also toxic for cardiomyocytes in culture. Similar to the heart, the beating rhythm of cardiomyocytes exposed to the toxin increases and then abruptly stops (Honda et al., 1976).
\n\t\t\t\t\tStreptolisin O is a pore-forming toxin released in the extracellular medium by the majority of group A and some of group C and G Streptococci. It belongs to the sulphydryl- or thiol-activated toxins. It is a protein with a molecular weight of about 67 kDa. Streprolysin O is capable of forming cation permeable pores in cholesterol-rich membranes. Administered i.v. in high doses it produces sudden cardiac arrest, probably due to a non-specific binding to the lipid bilayers of cardiac cells (for a review see Harvey, 1990).
\n\t\t\t\t\tSaxitoxin (STX) is produced by certain marine species of dinoflagellates (Alexandrium sp., Gymnodinium sp.) and cyanobacteria species (Anabaena sp., some Aphanizomenon spp., Cylindrospermopsis sp.). STX, usually administered through shellfish ingestion, is responsible for the human illness known as paralytic shellfish poisoning (PSP). STX acts primarily as a sodium channel blocker; it binds to the binding site 1 (Mebs & Hucho, 1990). Additionally it was found that STX also inhibits L-type Ca2+ currents in adult mouse ventricular myocytes (Su et al., 2003).
\n\t\t\t\t\tTetrodotoxin (TTX) is a toxin of microbial origin. A number of marine bacteria probably produce TTX, especially members of the genus Vibrio (most common species is Vibrio alginolyticus). The link between this species and production of TTX in animals has not been definitely confirmed as it is not clear whether the source of TTX in animals is the above-mentioned bacteria. TTX has been isolated from many animal species (pufferfish, toads of the genus Atelopus, octopuses of the genus Hapalochlaena, etc. (Mebs & Hucho, 1990). It was shown that both high and low affinity receptors (sodium channels) for TTX exist on the rat cardiomyocytes. Only a low affinity binding site is functional on the cardiac cells, which has dissociation constant for TTX about three orders of magnitude higher compared to the reported dissociation constant for TTX receptors in muscle and nerve. The concentration needed to block cardiac sodium channels is very high (Renaud et al., 1983). The myocytes in the heart express fast voltage-gated sodium channel and therefore the generation of AP and
\n\t\t\t\t\t\tName | \n\t\t\t\t\t\t\t\t\tSource (produced by) | \n\t\t\t\t\t\t\t\t\tChemical structure | \n\t\t\t\t\t\t\t\t\tTarget | \n\t\t\t\t\t\t\t\t\tMode of action | \n\t\t\t\t\t\t\t\t\tEffects | \n\t\t\t\t\t\t\t\t\tAcute LD50 in mice | \n\t\t\t\t\t\t\t\t\tReference | \n\t\t\t\t\t\t\t\t
Microbial toxins | \n\t\t\t\t\t\t\t\t|||||||
Bacterial toxins | \n\t\t\t\t\t\t\t\t|||||||
Hemolysin TDH, TRH | \n\t\t\t\t\t\t\t\t\tVibrio parahaemolyticus | \n\t\t\t\t\t\t\t\t\tProtein | \n\t\t\t\t\t\t\t\t\tHeart | \n\t\t\t\t\t\t\t\t\tAlteration in conductance of the conductive system | \n\t\t\t\t\t\t\t\t\tArrhy-thmias, cardiac arrest | \n\t\t\t\t\t\t\t\t\tBetween 2.5 and 5 g/kg in rats | \n\t\t\t\t\t\t\t\t\tHonda et al., 1976 | \n\t\t\t\t\t\t\t\t
Streptolysin O | \n\t\t\t\t\t\t\t\t\tStreptococci group A, C and G | \n\t\t\t\t\t\t\t\t\tProtein | \n\t\t\t\t\t\t\t\t\tNonspecific binding (membranes rich on cholesterol) | \n\t\t\t\t\t\t\t\t\tPore formation | \n\t\t\t\t\t\t\t\t\tBradycardia, atrio-ventricular conduction block | \n\t\t\t\t\t\t\t\t\t8 g/kg i.v. | \n\t\t\t\t\t\t\t\t\tGill, 1982; Harvey, 1990 | \n\t\t\t\t\t\t\t\t
Tetrodotoxin (TTX) | \n\t\t\t\t\t\t\t\t\tBacteria: Pseudoalteromo-nas tetraodonis, certain species of Pseudomonas and Vibrio | \n\t\t\t\t\t\t\t\t\theterocyclic, organic, water-soluble non-protein molecule | \n\t\t\t\t\t\t\t\t\tVoltage dependent Na+ channels | \n\t\t\t\t\t\t\t\t\tShorten the AP duration and decrease the initial depolarizing phase of the AP | \n\t\t\t\t\t\t\t\t\tCardiac arrest | \n\t\t\t\t\t\t\t\t\t10.7 g/kg i.p.; 12.5 g/kg s.c.; 532 g/kg i.g. | \n\t\t\t\t\t\t\t\t\tMebs & Hucho, 1990; Xu et al., 2003 | \n\t\t\t\t\t\t\t\t
Saxitoxin | \n\t\t\t\t\t\t\t\t\tMarine dinoflagellates (Alexandrium sp., Gymnodinium sp.) and cyanobacteria (Anabaena sp., some Aphanizomenon spp., Cylindrospermopsis sp.) | \n\t\t\t\t\t\t\t\t\tHeterocy-clic guanidine | \n\t\t\t\t\t\t\t\t\tVoltage-gated Na+ channels- block L-type Ca2+ channels- partial block | \n\t\t\t\t\t\t\t\t\tShorten the AP duration and decrease the initial depolarizing phase of the AP | \n\t\t\t\t\t\t\t\t\tProlongation of P-Q interval, first degree of atrio-ventricular block, ventricular fibrilation | \n\t\t\t\t\t\t\t\t\t3 – 10 µg/kg i.p. | \n\t\t\t\t\t\t\t\t\tAnderson, 2000; Su et al., 2003 | \n\t\t\t\t\t\t\t\t
Natural cardiotoxic toxins from microbes: source, structure, receptors, mode of action, effects on heart and toxicity; i.g.- intra-gastric administration
electrical activity is blocked leading to blockade of myocardium excitability and cardiac arrest, although sodium channels are usually not affected in case of intoxication.
\n\t\t\t\t\tAlgae are ubiquitous micro-organisms in aqueous environments. Some of them will periodically form harmful “blooms.” Karenia brevis is a dinoflagellate that can form harmful blooms known as “Florida red tides”. Blooms are associated with the production of a group of powerful neurotoxins known as brevetoxins.
\n\t\t\t\t\tBrevetoxin (PbTx) is produced by marine dinoflagellates. It is polyether neurotoxin that targets the voltage-gated sodium channels present in all excitable membranes including heart tissues. Brevetoxins open voltage-gated sodium ion channels in cell membranes and cause uncontrolled sodium influx into the cell leading to the depolarization (Purkerson et al., 1999). Humans can be exposed to PbTx by ingesting brevetoxin-contaminated shellfish or through other environmental exposures. Its affinity for the rat heart tissue is much lower in contrast to the heart tissue of marine animals, but comparable with the skeletal muscle and brain (Dechraoui et al., 2006). At least 10 different brevetoxins have been isolated from seawater blooms and K. brevis cultures. PbTx in a dose higher than 25 µg/kg produces heart block, ventricular extrasystoles and idioventricular rhythms in conscious rats. It was concluded that brevetoxin causes changes in the cardiac conduction system and multiple changes in the function of the nervous system (Templeton et al., 1989). Systemic accumulation of the toxin in artificially respirated cats injected with PbTx leads to cardiovascular collapse and death (Borison et al., 1985).
\n\t\t\t\t\tYessotoxins (YTXs) are polycyclic ether compounds produced by phytoplanktonic dinoflagellates (algal toxins). They can accumulate in shellfish which are a source of human intoxication through contaminated seafood ingestion. YTX, homoyessotoxin and 45-hydroxy-homoyessotoxin are lethal when administered intraperitonealy (i.p.) to mice. Although the mechanisms of the cardiotoxicity of YTX and homoyessotoxins are not well understood, some data from in vitro experiments, such as changes of intracellular calcium and cyclic AMP concentrations, alteration of cytoskeletal and adhesion molecules, caspases activation and opening of the permeability transition pore of mitochondria, support their cardiotoxic action (Dominguez et al., 2010; for a review see Tubaro et al., 2010). They induce microscopically visible ultrastructural changes in heart tissue after intraperitoneal and oral exposure. Noticeable intracytoplasmic oedema of cardiac muscle cells was observed within three hours after the i.p. administration of YTX at a dose of 300 g/kg or higher (Terao et al., 1990). In mice YTX produces swelling of cardiomyocytes and separation of organelles in the area near capillaries after oral (10 mg/kg) and i.p. (1 mg/kg) toxin administration (Aune et al., 2002).
\n\t\t\t\t\tCiguatera caused by fish poisoning is a foodborne disease caused by eating certain fishes whose meat is contaminated with ciguatoxins produced by dinoflagellates such as Gambierdiscus toxicus. These toxins include ciguatoxin (CTX), maitotoxin, scaritoxin and palytoxin. Ciguatera fish poisoning is primarily endemic in tropical regions of the world. On neuroblastoma cells, CTX induces a membrane depolarization which is due to an action that increases Na+ permeability and is prevented by voltage-gated sodium channel blocker TTX (Bidard et al., 1984). Intravenous injections of ciguatoxin evoke dose-dependent effects: bradycardia and atrioventricular conduction block at low doses, ventricular tachycardia at sublethal doses, and heart failure at high doses (up to 160 µg/kg) (Legrand et al., 1982). The Caribbean ciguatoxin (C-CTX-1) stimulates the release of acetylcholin (ACh) and produces muscarinic effect on frog atrial fibres (Sauviat, 1999; Sauviat et al., 2002).
\n\t\t\t\t\t\tName | \n\t\t\t\t\t\t\t\t\tSource (produced by) | \n\t\t\t\t\t\t\t\t\tChemical structure | \n\t\t\t\t\t\t\t\t\tTarget | \n\t\t\t\t\t\t\t\t\tMode of action | \n\t\t\t\t\t\t\t\t\tEffects | \n\t\t\t\t\t\t\t\t\tAcute LD50 in mice | \n\t\t\t\t\t\t\t\t\tReference | \n\t\t\t\t\t\t\t\t
Algal toxins | \n\t\t\t\t\t\t\t\t|||||||
Brevetoxin | \n\t\t\t\t\t\t\t\t\tDinoflagellate Karenia brevis \n\t\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\t\tCyclic polyether \n\t\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\t\tVoltage-gated Na+ channels | \n\t\t\t\t\t\t\t\t\tDepolari-zation, AP duration increase | \n\t\t\t\t\t\t\t\t\tHeart block, ventricular extrasystoles and idioventricular rhythms | \n\t\t\t\t\t\t\t\t\t250 µg/kg i.p. | \n\t\t\t\t\t\t\t\t\tPurkerson et al., 1999; Templeton et al., 1989; Selwood et al., 2008 | \n\t\t\t\t\t\t\t\t
Yes-sotoxins | \n\t\t\t\t\t\t\t\t\tAlgae | \n\t\t\t\t\t\t\t\t\tPolycyclic ether compo-unds | \n\t\t\t\t\t\t\t\t\tVoltage gated Ca2+ channels | \n\t\t\t\t\t\t\t\t\tReduction of the firing and biting frequency of rat cardiac cells | \n\t\t\t\t\t\t\t\t\tChanges of intracellular Ca2+ and cyclic AMP concentrations, alteration of cytoskeletal and adhesion molecules, caspases activation and opening of the permeability transition pore of mitochondria | \n\t\t\t\t\t\t\t\t\t444-512 µg/kg i.p. | \n\t\t\t\t\t\t\t\t\tTubaro et al., 2003; Dell’Ovo et al., 2008 | \n\t\t\t\t\t\t\t\t
Ciguatoxin | \n\t\t\t\t\t\t\t\t\tDinoflagellate Gambierdiscus toxicus | \n\t\t\t\t\t\t\t\t\tPolyether toxins | \n\t\t\t\t\t\t\t\t\tVoltage-gated Na+ channels | \n\t\t\t\t\t\t\t\t\tDepolari-zation, AP duration increase, arrhythmias | \n\t\t\t\t\t\t\t\t\tBiphasic inotropic and chronotropic excitatory, and inhibitory effects | \n\t\t\t\t\t\t\t\t\t0.3 – 10 µg/kg i.p. | \n\t\t\t\t\t\t\t\t\tDechraoui et al., 1999 | \n\t\t\t\t\t\t\t\t
Maitotoxin | \n\t\t\t\t\t\t\t\t\tDinoflagellate Gambierdiscus toxicus | \n\t\t\t\t\t\t\t\t\tN/A | \n\t\t\t\t\t\t\t\t\tCa2+ channels | \n\t\t\t\t\t\t\t\t\tAgonist | \n\t\t\t\t\t\t\t\t\tAP amplitude increase | \n\t\t\t\t\t\t\t\t\t0.17 mg/kg i.p. | \n\t\t\t\t\t\t\t\t\tIgarashi et al., 1999; Mebs & Hucho, 1990 | \n\t\t\t\t\t\t\t\t
Natural cardiotoxic toxins from algae: source, structure, receptors, mode of action, effects on heart and toxicity. (N/A - not applicable).
Maitotoxin (MTX) plays an important role in the syndrome named ciguatera poisoning. The toxin is derived from Gambierdiscus toxicus, a marine dinoflagellate species (for a review see Mebs & Hucho, 1990). MTX causes dose-dependent effects on the heart. It has positive inotropic effects on heart preparations and causes irreversible contracture of isolated rat cardiomyocytes that can be prevented by specific voltage-dependent Ca2+ channel blocker verapamil (Kobayashi et al., 1986). MTX increases dose-dependent increase in Ca2+ activity in freshly dispersed cardiomyocytes. This effect of MTX may be inhibited by reducing Ca2+ concentration in the culture medium or by the calcium-channel blocker verapamil. Therefore, it has been concluded that MTX specifically activates voltage-dependent Ca2+ channels. This influx of Ca2+ into the cells is considered an important mechanism for cardiotoxicity of the MTX (Santostasi et al., 1990).
\n\t\t\t\t\tAnimal venoms are usually a complex mixture of polypeptides, enzymes and molecules which can cause cell injury. Polypeptides exert their effect through action on ion channels and in a cell\'s plasma membrane. Enzymes can cause membrane lysis, pore formation, etc.
\n\t\t\tPalytoxin (PTX) was first toxin isolated from the soft coral Palythoa toxica. PTX is one of the most powerful marine biotoxins of a high molecular weight ( 3.3 kDa). It is the most potent non-proteinic and non-peptidic toxic substance known, with a lethal dose LD50 of 0.15 g/kg in mice by the i.v. route (Moore & Scheuer, 1971).
\n\t\t\tIberiotoxin (IbTX) is derived from the venom of Eastern Indian red scorpion Buthus tamulus. IbTX selectively inhibits current through the calcium-activated potassium channels. IbTX in a 2 M concentration increased the stimulation-induced ACh release (Kawada et al., 2010). It was reported that some patients who had been stung by a scorpion had signs such as hypertension and supraventricular tachycardia (Bawaskar & Bawaskar, 1992), to which may contribute also IbTX.
\n\t\t\tBatrachotoxins (BTXs) are neurotoxic steroidal alkaloids first isolated from a Colombian poison-dart frog. BTXs are lipid-soluble toxins that bind with a high affinity to the type 2 receptor site of voltage-gated sodium channels in nerve and muscle membranes, keeping them in an open state (Albuquerque et al., 1971; Huang et al., 1984). This results in cell depolarization since BTXs inhibit inactivation of sodium channels. BTXs seem to play the most important role in cardiotoxicity. The cardiotoxic effects of BTXs accompanied by arrhythmia and cardiac arrest are connected to the activation of voltage-gated sodium channels in cardiac cells (Mebs & Hucho, 1990). It can evoke premature heart beat and fatal ventricular fibrillation associated with the haemodynamic arrest (Albuquerque et al., 1971).
\n\t\t\tAtrotoxin (ATX) is isolated from a venomous rattlesnake species Crotalus atrox found in the United States and Mexico. ATX binds reversibly to the voltage-gated calcium channels, leading to the increase of voltage-dependent calcium currents in single, dispersed guinea pig ventricular cells. ATX acts as a specific Ca2+ channel agonist (Hamilton et al., 1985).
\n\t\t\tEquinatoxins are pore-forming proteins isolated from the sea anemone Actinia equine. First evidence that equinatoxins are cardiotoxic was provided by Sket et al. (1974) by administration of tentacle extract of sea anemone i.v. into rats. Later, the isolation of three cardiotoxic proteins named Equinatoxin I, II and III with median lethal doses of 23, 35 and 83 µg/kg in mice, respectively (Macek & Lebez, 1988), was reported. EqT II is a pore forming toxin that through de novo formed pores evokes significant increase of intracellular Ca2+ activity, which cannot be blocked by conventional sodium and calcium channel blockers and probably plays an important role in direct (cytotoxic) or indirect cardiotoxicity through coronary vessel contraction and drop of the coronary perfusion rate (Frangež et al., 2000; Frangež et al., 2008; Zorec et al., 1990). All three equinatoxins are highly haemolytic and can cause a dose-dependent increase in potassium activity in blood plasma, leading to arrhythmias and cardiac arrest. Administered i.v. they produce dose-dependent disturbances in electrical activity of the heart accompanied by blood pressure changes. Additional information about direct dose-dependent cardiotoxic effects of EQT IIs were provided from the experiments on Langendorff\'s heart preparations. It causes a concentration-dependent drop of the perfusion rate, decreases left ventricular pressure and produces arrhythmias followed by cardiac arrest (Bunc et al., 1999).
\n\t\t\tA cytolytic protein was isolated from the Indian monocellate cobra (Naja kaouthia) venom. Intraperitoneal median lethal dose was estimated to be 2.5 mg/kg in Balb/C in male mice. In vitro the toxin produces auricular blockade as shown on isolated guinea pig auricle (Debnath et al., 2010).
\n\t\t\tTaicatoxin (TCX) is a snake toxin derived from the Australian taipan snake Oxyuranus scutellatus scutellatus. TCX reversibly and specifically blocks voltage-dependent L-type calcium channels in nanomolar concentrations (Brown et al., 1987). TCX decreases the plateau of AP in cardiomyocytes leading to a decrease in contractility. TCX has a negative chronotropic effect and evokes arrhythmias (Fantini et al., 1996). Electrocardiographic abnormalities were described in patients envenomed with a number of different species including Oxyuranus spp. Electrocardiographic changes include septal T wave inversion and bradycardia, and atrioventricular block. One of possible mechanisms which might be responsible for such clinical signs is a calcium channel blockade on cardiomyocytes (Lalloo et al., 1997).
\n\t\t\tConotoxins are peptides derived from the marine snail Conus geographus and consist of 10 to 30 amino acid residues. Many of these peptides modulate the activity of different ion channels. ω-conotoxin inhibits N-type voltage-dependent Ca2+ channels. It decreases the magnitude of cardiac AP and possesses a negative inotropic effect (Nielsen, 2000).
\n\t\t\tCrotoxin (CTX) is derived from the venom of the South American rattlesnake, Crotalus durissus terrificus. In vitro, CTX decreases contractile force, increases the P-R interval and displaces the S-T segment. Arrhythmias are uncommon. The reduction of the contractile force and the increase in creatine kinase (CK) activity are ascribed to the release of free fatty acids and lysophospholipids, and to a cellular lesion (Santos et al., 1990; Zhang et al., 2010).
\n\t\t\tSarafotoxins (SRTs) and bibrotoxins are a group of extremely poisonous cardiotoxic snake venom peptides that show a striking structural similarity to endothelins (Becker et al., 1993; Kloog et al., 1988). SRTs are highly lethal peptides: in mice, the LD50 is 15 µg/kg body weight equalling the LD50 for endothelin (Bdolah et al., 1989), which is quite surprising for a peptide naturally occurring in the plasma of healthy humans. Sarafotoxin S6C, the most acidic endothelin-like peptide, shows reduced vasoconstrictive potency and is a highly selective natural ETBR agonist (over 100 000 times higher affinity for the ETBR vs. the ETAR; [Williams et al., 1991]).
\n\t\t\tGs-Mtx-4 is an amfipathic peptide toxin derived from the venom of the tarantula spider (Grammostola spatulata) with a molecular weight of 4 kDa (Hodgson & Isbister, 2009). It is the only toxin known that specifically affects cationic stretch activated ion channels and is therefore able to inhibit atrial fibrillation (Bowman et al., 2007).
\n\t\t\tSome of the natural toxins acting on the cardiovascular system are very potent and highly specific for some receptors in cardiac and neuronal tissue. They can block, activate and even modulate the ion channels activity in excitable membranes. Although they are very stable molecules and possess high receptors specificity, they are seldom used as therapeutic drugs. Information about their three dimensional structure and data from structure-function studies of protein toxins may provide useful information for synthesis of smaller analogues with lower toxicity. Few natural toxins have potential in clinical use for treatment of cardiovascular dysfunction. Some of them have a positive inotropic effect, i.e. grayanotoxin, veratridine (Brill & Wasserstrom, 1986; Tirapelli et al., 2008). Due to their high toxicity, none of the described natural cardiotoxic substances are used as therapeutic drugs for treating cardiovascular diseases. Recently, sarafotoxins have been utilized to develop new, low molecular weight substances with metalloproteinase inhibitory activity. The modified molecule of the sarafotoxin 6b is used as a starting point, which has retained metalloproteinase inhibitory activity and removed vasoconstrictor activity. From this, the peptide (STX-S4-CT) was developed, which will hopefully provide a foundation for further development of improved candidate molecules (Hodgson & Isbister, 2009). Some promising
\n\t\t\tName | \n\t\t\t\t\t\tSource (produced by) | \n\t\t\t\t\t\tChemical structure | \n\t\t\t\t\t\tTarget | \n\t\t\t\t\t\tMode of action | \n\t\t\t\t\t\tEffects | \n\t\t\t\t\t\tAcute LD50 in mice | \n\t\t\t\t\t\tSource | \n\t\t\t\t\t
Animal toxins | \n\t\t\t\t\t|||||||
Palytoxin | \n\t\t\t\t\t\tSoft coral: Palythoa toxica | \n\t\t\t\t\t\tAliphatics carbon chain containing a series of heterocyclic rings | \n\t\t\t\t\t\tNa+/K+-ATPase; Hemolysin | \n\t\t\t\t\t\tVoltage-dependent K+ channels | \n\t\t\t\t\t\tHaemolysis, arrhythmias | \n\t\t\t\t\t\t0.15 µg/kg | \n\t\t\t\t\t\tSosa et al., 2009 | \n\t\t\t\t\t
Equinatoxin I, II, II | \n\t\t\t\t\t\tSea anemone: Actinia equina | \n\t\t\t\t\t\tProteins | \n\t\t\t\t\t\tHaemolysin | \n\t\t\t\t\t\tNew cation non-selective pore formation | \n\t\t\t\t\t\tDose-dependent arrhythmias, cardiac arrest, haemolysis | \n\t\t\t\t\t\t25,30 and 83 µg/kg i.v. | \n\t\t\t\t\t\tMaček & Lebez, 1988; Sket et al., 1974 | \n\t\t\t\t\t
Batrachotoxins (BTX) | \n\t\t\t\t\t\tSome frogs species (poison-dart frog), melyrid beetles and birds (Ifrita kowaldi, Colluricincla megarhyncha) | \n\t\t\t\t\t\tSteroidal alkaloids | \n\t\t\t\t\t\tNa+ channels | \n\t\t\t\t\t\tDepolarize, lengthen the AP | \n\t\t\t\t\t\tArrhythmias, extrasystoles, ventricular fibrillation | \n\t\t\t\t\t\t2 µg/kg s.c. | \n\t\t\t\t\t\tAlbuquerque et al., 1971; Mebs & Hucho, 1990 | \n\t\t\t\t\t
Atrotoxin | \n\t\t\t\t\t\tSnake: Crotalus atrox | \n\t\t\t\t\t\tN/A | \n\t\t\t\t\t\tCa2+ channels | \n\t\t\t\t\t\tAgonist, AP amplitude increase | \n\t\t\t\t\t\tArrhythmias | \n\t\t\t\t\t\t89.4 – 137 µg i.v. | \n\t\t\t\t\t\tHamilton et al., 1985; Barros et al., 1998 | \n\t\t\t\t\t
Cardiotoxic-cytotoxic protein (MW 6.76 kDa) | \n\t\t\t\t\t\tIndian monocellate cobra (Naja kaouthia) | \n\t\t\t\t\t\tProtein | \n\t\t\t\t\t\tHeart | \n\t\t\t\t\t\tSinuauricular blockade | \n\t\t\t\t\t\tArrhythmias | \n\t\t\t\t\t\t2.5 mg/kg i.p. | \n\t\t\t\t\t\tDebnath et al., 2010 | \n\t\t\t\t\t
Taicatoxin (TCX) | \n\t\t\t\t\t\tAustralian taipan snake Oxyuranus scutellatus | \n\t\t\t\t\t\tN/A | \n\t\t\t\t\t\tCa2+ channels | \n\t\t\t\t\t\tAntagonist | \n\t\t\t\t\t\tBradycardia, atrioventricular block | \n\t\t\t\t\t\tN/A | \n\t\t\t\t\t\tBrown et al., 1987; Lalloo et al., 1997 | \n\t\t\t\t\t
Omega-conotoxin | \n\t\t\t\t\t\tCone snail from genus Conus | \n\t\t\t\t\t\tPeptide | \n\t\t\t\t\t\tN-type voltage-dependent Ca2+ channels | \n\t\t\t\t\t\tAntagonist | \n\t\t\t\t\t\tDecreases the magnitude of AP plateau, negative inotropic effects | \n\t\t\t\t\t\tN/A | \n\t\t\t\t\t\tNielsen, 2000 | \n\t\t\t\t\t
Crotoxin (CTX) | \n\t\t\t\t\t\tSouth American rattlesnake (Crotalus durissus terrificus) | \n\t\t\t\t\t\tProtein; crotapotin basic phospolipase A2 | \n\t\t\t\t\t\tL-type Ca2+ channels | \n\t\t\t\t\t\tAgonist | \n\t\t\t\t\t\tElongation of AP duration, an increase of its amplitude | \n\t\t\t\t\t\t55.5 – 70.5 µg/kg i.p. | \n\t\t\t\t\t\tRangel-Santos et al., 2004 | \n\t\t\t\t\t
Sarafotoxin (SRTs) and bibrotoxin | \n\t\t\t\t\t\tSnake: Atractaspis engaddensis | \n\t\t\t\t\t\tPeptide | \n\t\t\t\t\t\tEndothelin receptors | \n\t\t\t\t\t\tAgonist | \n\t\t\t\t\t\tArrhythmias | \n\t\t\t\t\t\t15 µg/kg | \n\t\t\t\t\t\tBdolah et al., 1989 | \n\t\t\t\t\t
GsMtx-4 | \n\t\t\t\t\t\tSpider – tarantula: Grammostola spatulata | \n\t\t\t\t\t\tPeptide | \n\t\t\t\t\t\tStretch activated ion channels (SACs) | \n\t\t\t\t\t\tAntagonist | \n\t\t\t\t\t\tInhibits atrial fibrillation | \n\t\t\t\t\t\tN/A | \n\t\t\t\t\t\tBowman et al., 2007 | \n\t\t\t\t\t
Natural cardiotoxic toxins from animals: source, structure, receptors, mode of action, effects on heart and toxicity. (N/A - not applicable).
results in the treatment of cardiovascular disorders were also obtained with GsMtx-4 toxin isolated from tarantula Grammostola spatulata venom. This toxin is able to inhibit the stretch activated ion channels (SACs) and consequently inhibits atrial fibrillation. Due to its described properties, it can be used as a framework for developing a new class of anti-arrhythmic drugs, which would be directed against pathophysiologic mechanisms of atrial fibrillation, instead of just dealing with the symptoms as with many current therapies (Hodgson & Isbister, 2009).
\n\t\tSevere acute toxic insult caused by natural toxins can cause functional changes in heart tissue physiology or even cardiac cell death. Most of the natural toxins derived from plants, bacteria, phytoplanktonic dinoflagellates, fungi and animals target ionic channels in excitable membranes of cardiac cells or cardiac cell membranes itself, produce alteration in AP (e.g. depolarization, repolarization, alterations in its duration) or significant changes in intracellular ion activity. These changes may lead to reversible or even irreversible life threatening cardiac arrhythmias and eventually heart failure.
\n\t\t“Any sufficiently advanced technology is indistinguishable from magic.”
-Arthur C Clarke
Today, 55% of the world’s population lives in urban areas, and this proportion is expected to reach 68% by 2050 [1]. City governments face the challenge of producing wealth, innovation, health, and sustainability [2], but with an increase in urban populations, these challenges become harder for city governments to manage. For this reason, instead of continuing to use old-fashioned methods, some cities have applied updated, innovative methods to manage such issues in smarter ways [3], much as we do in our daily lives. We have moved from using “dumb” technologies (e.g., a road atlas or telephone) to interacting with “smart” technologies (e.g., personalized journey planning apps on smart phones) that “exist to help us, serve us, to make our lives easier and more interesting” [4].
As internationalization has become a widely discussed topic in recent years [5], the problem of overcrowding of cities is considered a global issue, and smart city applications have spread rapidly worldwide [2]. These applications not only enable city governments to facilitate the routine functions of individuals, buildings, and traffic systems but also enable them to monitor, understand, analyze, and plan cities to improve their efficiency, equity, and quality of life in real time [6]. The concept “smart,” therefore, means the ability to manage the complexity through Big Data, which comes from a variety of sources in a huge volume and in a rapid way. As an example, in their daily lives, individuals check their social media accounts from mobile devices and share or like posts. They also read personalized news and check traffic jams. They then check their e-mail when they arrive at their offices. At lunchtime, they order food using online applications, and they watch personalized videos during free time. In other words, individuals produce a great deal of personal data and consume many more services based on that data. Thus, they also desire cities that support this lifestyle [7].
For instance, in Milton Keynes, a large town in the middle of England, the rapid expansion of the Internet together with young and technically inclined population gave rise to the concept of “smart cities.” This included the application of technology, especially Big Data principles, to improve residents’ quality of life. Such applications ranged from waste management to public transportation [8]. Now, many more cities, such as London, Stockholm, Amsterdam, Vienna, Luxembourg, Turku, Eindhoven, and Montpellier, have adopted a “smart” approach. The smart city theme also provides a city more stable and higher brand equity than green and creative themes [9]. In a project conducted at the Vienna University of Technology, six indicators of smart cities were identified:
“Smart economy,” including competitive components, such as innovation, entrepreneurship, and productivity
“Smart people,” which is the result of ethnic or social diversity and related to online education to raise social capital and qualification
“Smart governance,” such as e-government, which can include all parties in transparent decision-making processes
“Smart mobility,” which includes transportation planned using information and communications technologies (ICT)
“Smart environment,” which encourages cities to use energy efficiently by employing innovative technologies, such as solar energy and other renewable sources
“Smart living,” which refers to systems that improve quality of life, such as services and public safety tools [10]
These components are associated with different aspects of urban life: (1) industry, (2) education, (3) e-democracy, (4) logistics and infrastructure, (5) efficiency and sustainability, and (6) security and quality, respectively [11, 12].
This study is focused on smart mobility and examines the case of Istanbul New Airport, which officially opened on 29 October 2018. With a capacity of 200 million annual passengers and 3500 flights per day, Istanbul New Airport is the first smart airport of its size [13].
As an indicator of smart cities in terms of logistics and infrastructure, smart mobility requires urban planning that shifts the focus of transportation modes from individual to collective through the extensive use of ICT [14]. Smart mobility is concerned with local and global accessibility, ICT infrastructure, and innovative and sustainable transport systems [15]. Moreover, it should serve individuals’ needs by reducing time spent traveling and helping travelers avoid unnecessary travel altogether [16]. To provide these outputs, smart mobility should [17] accomplish the following goals:
Use technology to generate and share data, information, and knowledge that influence decisions.
Use technology to enhance vehicles, infrastructure, and services.
Derive improvements for transport system operators, users, and shareholders.
In certain situations, IT-supported service experiences can enhance customer satisfaction significantly [18]. Therefore, customer journey maps can be analyzed to observe the effects of technologies on customers’ experiences with the provided services.
Shorter life cycles make products and services more commoditized. Therefore, the differentiation has shifted from the offerings themselves to their providers that create experiences related with the acquisition, use, and maintenance of these offerings. People are naturally inclined to prefer pleasant, special experiences that have important lasting effects [19]. Thus, the opportunity for new revenue growth depends not only on driving sales of existing goods and services but on creating experiences for which customers are willing to pay [20]. Experiences can be conceptualized as “events that engage individuals in a personal way” [21] or as “enjoyable, engaging, memorable encounters for those consuming these events” [22], so creating strong customer experiences is a leading objective for management [23] to create competitive advantage [24].
Given the current progress of technology, it is possible to use it to develop customer experiences. For instance, in the fashion industry, information technologies enhance customer experiences by creating interactive and exciting shopping experiences [25]. In the banking industry, the increase of the Internet services and automated teller machines (ATMs) in various locations provides more services and more comfortable customer experiences than before [26]. In addition to B2C context, technology is used also to create B2B customer experiences, such as salespeople’s use of information technology [27].
In addition to enhancing experiences, technology advancement also provides multiple ways for customers to interact with product and service providers. These interactions are crucial to creating superior customer experiences [28]. To depict the events through which customers may interact with a service organization, academics and practitioners use a strategic management tool called customer journey mapping (CJM) [29].
Cities are considered smart when “investments in human and social capital and traditional (transport) and modern (ICT) communication infrastructure fuel sustainable economic growth and a high quality of life, with a wise management of natural resources, through participatory governance” [30]. As a dimension of smart city planning, smart mobility is considered in this study. Smart mobility can be summarized as planning and controlling transport systems through the extensive use of ICT. This kind of system has recently been applied in the building of Istanbul New Airport.
Airport information systems are divided into seven sections [31]:
Flight planning and operation
Passenger process
Business administration
Security
Facility management
Business center and airport management
Contact and information
Recently, airports in the Middle East and in Istanbul have begun to compete with European airports to create a “global hub” for connecting (transfer) passengers [32]. With the increased capacity and technologies developed at Istanbul New Airport, an improved customer experience would provide a competitive advantage. Thus, CJM is proposed in this study to depict customer experiences based on the technologies adapted at Istanbul New Airport.
The format used by Rosenbaum et al. was considered when creating the CJM [29]. On the CJM’s horizontal axis, the customer touch points take place according to a process timeline. The timeline is also divided into three periods: pre-service, service, and post-service. The pre-service period refers to customer experiences that occur before a service begins. The service period refers to customer experiences during the actual service. Finally, the post-service period refers to customer experiences occurring after the service [29]. In parallel with this process, a CJM can represent customer experiences prior to going to the airport, at the airport, and after leaving the airport, respectively.
To develop a CJM for Istanbul New Airport, customer touch points are determined first to build the CJM’s horizontal axis. The general limitation of CJM indicated by Rosenbaum et al. was that a common underlying assumption for customer touch points was the consideration that each touch point was equally important to the planning process; however, not all customers experience all touch points [29]. Thus, 62 students with previous flight experiences were recruited from two undergraduate marketing classes at Marmara University using a convenience sampling method. As the Istanbul New Airport was not operating at full capacity at the time of the study, the selection criterion was limited to participants’ previous flight experience at other airports in Istanbul (Istanbul Atatürk Airport or Istanbul Sabiha Gökçen Airport). To determine a unique CJM, only flights departing from the airports were considered. The main assumption for this approach was that passengers spend more time—or, in other words, they experience more—at the departure airport.
As discussed previously, the main assumption of CJM is that each passenger’s touch points are considered to be of equal importance. To address this limitation, the students were asked to indicate the first touch points that came to mind regarding the departure airports in Istanbul. As they all experienced different touch points, all the steps gathered from the students are listed in Table 1 to create a complete list of customer journey touch points. The percentages of listed touch points are indicated next to them. At the end of this step, a total of 33 touch points was identified by the respondents. Of the steps, 7 occurred during the pre-service period (before passengers arrive to the airport), 20 occurred during the service period (when passengers are at the airport), and 6 occurred during the post-service period (after passengers leave the airport). After the collection of the touch points for Istanbul Airport as a departure airport, two marketing professors from Marmara University checked them for a potential missing point.
(% listed) | |
---|---|
Pre-service period (before passengers arrive at the airport) | |
Please list your pre-service (before going to the airport) touch points with the airport (such as “seeing an advertisement on a street billboard about the airport”) | |
1. Preparing luggage | 1.61 |
2. Buying tickets (online or through agencies) | 37.10 |
3. Transportation (public or private) to the airport | 41.94 |
4. Checking in online | 9.68 |
5. Visiting the airport’s website or mobile application | 9.68 |
6. Searching for information about facilities at the airport | 1.61 |
7. Seeing advertising (on a street billboard, a website, or a social media service) about the airport | 40.32 |
Service period (when passengers are at the airport) | |
Please list your during-service (when you are at the airport) touch points with the airport (such as “using the parking lot of the airport”) | |
1. Using the parking lot | 16.13 |
2. Security screening process | 9.68 |
3. Checking in at the airport | 19.35 |
4. Delivering luggage | 8.06 |
5. Asking for help from airport personnel (such as asking for general information or for a wheelchair) | 1.61 |
6. Eating or drinking in the cafés at the airport (including smoking rooms) | 56.45 |
7. Using an ATM to withdraw money | 1.61 |
8. Exchanging money | 1.61 |
9. Using lounge services | 9.68 |
10. Using the toilets | 9.68 |
11. Shopping at the airport | 11.29 |
12. Paying for stamp fees | 3.23 |
13. Passport control | 0 |
14. Tracking flight gates on the screens | 1.61 |
15. Going to flight gates | 4.84 |
16. Visiting duty-free stores | 11.29 |
17. Waiting in the waiting areas (such as reading a book or listening to music) | 16.13 |
18. Connecting to Wi-Fi | 8.06 |
19. Taking photos in the airport | 1.61 |
20. Boarding | 3.23 |
Post-service period (after passengers leave the airport) | |
Please list your after service (when you leave the airport) touch points with the airport (such as “talking to friends or family about the airport”) | |
1. Baggage collection (at the destination airport) | 9.68 |
2. Calling (informing) family about arrival | 12.90 |
3. Talking to friends or family about experiences at the airport | 48.39 |
4. Communicating with the airport post-services (completing a survey about experiences at the airport) | 3.23 |
5. Writing about the airport on the Internet | 1.61 |
6. Sharing photos taken at the airport on social media | 1.61 |
Istanbul New Airport’s key horizontal axis customer touch points.
The vertical axis for CJM reflects the managerial practices that enable passengers to experience each touch point in a satisfactory way [29]. As the purpose of this study is to reveal customer experiences with technology applications, only the corresponding technological application is considered regarding passenger touch points at Istanbul New Airport.
Turkish Airlines’ move from Istanbul Atatürk Airport to the Istanbul New Airport coincides with the time of this study (5–7 April 2019), so it was not possible to meet with authorities at Istanbul New Airport. However, secondary data were used to list the corresponding technological applications. A meeting was held with Ms. Hülya Zerener Gürbaşak, the corporate account manager of Technopc, which provides more than 4000 hardware products to Istanbul New Airport. These products include desktop, mini, integrated, industrial, and kiosk computers used at check-in, security, card access, and passport control points. In addition, Mr. Mertcan Tanaydı, the communication chief of İGA Istanbul Airport, provided several documents and a video [33] in which the technologies of the airport are explained in detail from a customer’s point of view.
In terms of technological infrastructure at Istanbul New Airport, three data centers support artificial intelligence (AI) and smart systems. There are 647 servers, 3267 flight displays, 4549 computers, and more than 3000 card access points. To integrate these systems, 1740 km fiber and 4500 km copper cables were used. Data from all systems can reach up to 209 million GB. A total of 708 employees works in technology support roles [33].
The main focus of the technology was a mobile application developed to assist passengers. The airport mobile application can be used before, during, and after service. It guides passengers from home to the airport, assisting with time management by considering the traffic on the road (corresponding to the pre-service touch point). Its “Where is my car?” service also helps passengers find their cars in the parking lot among 19,000 cars in the closed area and 40,000 cars in the open area (corresponding to the post-service touch point). All corresponding technological applications for the service period are listed in Table 2.
Passenger touch points during the service period | Corresponding technological applications |
---|---|
1. Using the parking lot | A total of 4500 cameras tracks the cars in the parking lot; they take photos of the cars and upload them on the airport mobile application. Visitors may find their cars by writing their license plate on the application |
2. To be controlled by security | Electronic screens at the airport entrance show wait times at the security points (based on sensors and cameras that produce heat maps showing the density of people). Accordingly, the number of security points increases or decreases. In addition, the security cameras with AI use facial recognition systems and warn security if they detect unfavorable movements in the airport |
3. Checking in at the airport | Self-check-in points allow passengers to check in for their flights and leave their luggage |
4. Delivering luggage | |
5. Asking airport personnel for help (asking for general information or for a wheelchair) | An interactive passenger assistant located at the airport enables passengers to connect to customer service and make a video call with a responsible party who can see the passenger’s flight details; the customer opens the e-ticket’s QR code and puts the mobile phone to the device. The cameras and sensors on the top scan the e-ticket’s QR code, enabling the responsible party to see both the passenger and the ticket. In this way, the responsible party can generate a personal map for the passenger from the current location to the flight gate |
6. Eating and drinking in the cafés at the airport (including lounge services and smoking rooms) | The airport location guide provided by the airport mobile application lists all facilities and stores at the airport |
7. Using an ATM to withdraw money | |
8. Exchanging money | |
9. Using lounge services | |
10. Using the toilets | |
11. Shopping at the airport | |
12. Paying for stamp fees | |
13. Passport control | The iGate-fast passport control system includes two steps. The first door is opened when the passport is scanned by a device, and the second door is opened when a passenger’s face and hand are scanned by a device and matched to the passport |
14. Tracking flight gates on screens | Flight information screens and the airport mobile application provide flight information |
15. Going to flight gates | Personalized direction is provided by the airport mobile application to the gate for the selected destination |
16. Visiting duty-free stores | Pre-ordering is available in duty-free stores, where salespeople can reserve passengers’ pre-ordered items |
17. Waiting in the waiting areas (reading a book and listening to music) | USB inputs between the seats enable passengers to charge their mobile devices |
18. Connecting to Wi-Fi | Up to 1 h of free Wi-Fi is available at the airport |
19. Taking photos in the airport | |
20. Boarding | Boarding time can be seen in the airport mobile application |
Corresponding technological applications during the service period at Istanbul New Airport.
In addition to existing technologies, new ones are planned for the airport. There will be a store offering inventions and technological products where visitors may have such experiences as flying a drone. Moreover, three types of robots will work in the airport. Service robots will assist passengers and will reply to their questions about such topics as flight gates and ticket offices. The other robots will be responsible for cleaning and safety. They will be called “İGAbots.” Another innovation will be autonomous vehicles, which will be called “İGAbus.” They will carry passengers to various places at the airport [33].
City governments today must manage increasing urban populations in smart ways. In other words, large amounts of data produced by the population should be used to create sustainable places by decreasing the chaos of overcrowding, such as traffic, pollution, and waste. One smart city dimension is smart mobility, which refers to enhancing individuals’ mobility using innovation and technology. Technology is also essential to creating customer experiences. CJM can be used to analyze touch points and their corresponding created experiences.
In this study, an attempt was made to use CJM as a tool to analyze Istanbul New Airport, one of the largest smart airports in the world, which promises memorable customer experiences. In this way, Istanbul New Airport aims to compete with other airports defined as hubs in Europe. Therefore, a customer journey was created based on a survey of 62 undergraduate students who were asked which touch points came to mind first. The corresponding technologies were indicated based on secondary data.
According to the results, the most indicated touch point from the participants was “talking to friends or family about experiences at the airport” (48.39%). However, the question should be considered to evaluate this high rate. To make the questions clear and to get more touch points, an example was provided for pre-service, service, and post-service periods. Therefore, these three questions were recalls rather than the points coming to the respondents’ minds first. Nevertheless, the findings provide evidence that touch points do not have equal importance for all passengers. Different passengers experience different touch points during their journeys, so they perceive different experiences with the technological applications.
As can be seen from the touch point-technology match, Istanbul New Airport provides experiences through technological applications for most passenger touch points. Of these technologies, the main focus is on the mobile application created to affect various points of a customer journey, including time management and considering the traffic on the road to the airport, car location in the parking lot, guides listing all the facilities and stores in the airport, flight information for the selected destination, and personalized directions to the flight gate. In addition, various technologies are used to enhance passenger experiences, such as self-check-in points, interactive passenger assistants, AI-integrated security cameras, fast passport control system, and free Wi-Fi. According to the CJM, customer experience creators should also consider passengers’ use of social media and create a strategy accordingly. Passengers like to take photos at the airport and share them on their social media accounts, so there may be several photo opportunities when they experience a new technology. In this way, passengers may share and transfer their experiences with their surroundings, leading to positive word-of-mouth communication about the airport.
Regarding the limitations of this study, as the airport was not running at full capacity, the CJM was created based on participants’ experiences at other airports in Istanbul. Therefore, a new CJM should be created after the airport begins to run at full capacity by considering the airport from both departure and arrival perspectives to extend customers’ experiences. In addition to technological applications, other managerial practices can be also included in the CJM’s vertical axis.
IntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
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\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
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\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
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