Characteristics of adrenergic receptors.
\r\n\tIn order to understand the detailed content, these parameters are also divided into different classes such as inert, readily biodegradable, soluble COD, etc. However, still we do not possess detailed knowledge on organics in water sources or wastewater streams. Therefore, during the last decade, scientists tried to divide organics into different classes and understand their treatment potential and natural pathways. This book aims to fill out a very significant gap in this research field. Different treatment processes, monitoring and water determination chapters on dissolved organics, emerging organic pollutants, endocrine disruptors, emerging disinfection by-products, microplastic etc. in water or wastewater are welcome to this book project.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"358ff11fd43b59f3a36498ef0494189d",bookSignature:"Associate Prof. Taner Yonar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8934.jpg",keywords:"COD, BOD, TOC, treatment, toxicity, fire retardents, bioacumulaion, treatment, pesticides, hormones, sources of microplastics, effects on health",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 11th 2019",dateEndSecondStepPublish:"July 2nd 2019",dateEndThirdStepPublish:"August 31st 2019",dateEndFourthStepPublish:"November 19th 2019",dateEndFifthStepPublish:"January 18th 2020",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:"190012",title:"Associate Prof.",name:"Taner",middleName:null,surname:"Yonar",slug:"taner-yonar",fullName:"Taner Yonar",profilePictureURL:"https://mts.intechopen.com/storage/users/190012/images/system/190012.png",biography:"Prof. Dr. Taner Yonar is a Professor of Uludag University, Engineering Faculty, Environmental Engineering Department. He has received his B.Sc. (1996) degree from the Environmental Engineering Department, Uludag University. He received his M.Sc. (1999) and Ph.D. (2005) degrees in Environmental Technology from Uludag University, Institute of Sciences. He did his post-doctoral research in the UK, at Newcastle University, Chemical Engineering and Advanced Materials Department (2011). He teaches graduate and undergraduate level courses in Environmental Engineering on water and wastewater treatment and advanced treatment technologies. He works on advanced oxidation, membrane processes, and electrochemical processes. He is the editor of three books (published by IntechOpen) and the author of over 80 research papers.",institutionString:"Uludağ University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Uludağ University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"12",title:"Environmental Sciences",slug:"environmental-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"270941",firstName:"Sandra",lastName:"Maljavac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/270941/images/7824_n.jpg",email:"sandra.m@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:"10026",title:"Electrodialysis",subtitle:null,isOpenForSubmission:!1,hash:"ffef55f8ffe48f096acaa5f6329ed76f",slug:"electrodialysis",bookSignature:"Taner Yonar",coverURL:"https://cdn.intechopen.com/books/images_new/10026.jpg",editedByType:"Edited by",editors:[{id:"190012",title:"Associate Prof.",name:"Taner",surname:"Yonar",slug:"taner-yonar",fullName:"Taner Yonar"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{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"}}]},chapter:{item:{type:"chapter",id:"29904",title:"Post-Myocardial Infarction Depression",doi:"10.5772/33408",slug:"post-myocardial-infarction-depression",body:null,keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/29904.pdf",chapterXML:null,downloadPdfUrl:"/chapter/pdf-download/29904",previewPdfUrl:"/chapter/pdf-preview/29904",totalDownloads:2050,totalViews:76,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,dateSubmitted:"April 19th 2011",dateReviewed:"September 27th 2011",datePrePublished:null,datePublished:"February 29th 2012",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/29904",risUrl:"/chapter/ris/29904",book:{slug:"novel-strategies-in-ischemic-heart-disease"},signatures:"Rousseau Guy, Thierno Madjou Bah and Roger Godbout",authors:[{id:"95306",title:"Prof.",name:"Guy",middleName:null,surname:"Rousseau",fullName:"Guy Rousseau",slug:"guy-rousseau",email:"Guy.Rousseau@umontreal.ca",position:null,institution:{name:"University of Montreal",institutionURL:null,country:{name:"Canada"}}},{id:"97203",title:"Dr.",name:"Roger",middleName:null,surname:"Godbout",fullName:"Roger Godbout",slug:"roger-godbout",email:"roger.godbout@umontreal.ca",position:null,institution:{name:"University of Montreal",institutionURL:null,country:{name:"Canada"}}}],sections:null,chapterReferences:null,footnotes:null,contributors:null,corrections:null},book:{id:"965",title:"Novel Strategies in Ischemic Heart Disease",subtitle:null,fullTitle:"Novel Strategies in Ischemic Heart Disease",slug:"novel-strategies-in-ischemic-heart-disease",publishedDate:"February 29th 2012",bookSignature:"Umashankar Lakshmanadoss",coverURL:"https://cdn.intechopen.com/books/images_new/965.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"13913",title:"Dr.",name:"Umashankar",middleName:null,surname:"Lakshmanadoss",slug:"umashankar-lakshmanadoss",fullName:"Umashankar Lakshmanadoss"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"29886",title:"Overview of Coronary Artery Disease",slug:"overview-of-ischemic-heart-disease",totalDownloads:2446,totalCrossrefCites:0,signatures:"Umashankar Lakshmanadoss",authors:[{id:"13913",title:"Dr.",name:"Umashankar",middleName:null,surname:"Lakshmanadoss",fullName:"Umashankar Lakshmanadoss",slug:"umashankar-lakshmanadoss"}]},{id:"29887",title:"Cardiac Biomarkers",slug:"biomarkers-in-ischemic-heart-disease",totalDownloads:10301,totalCrossrefCites:0,signatures:"Sadip Pant, Abhishek Deshmukh, Pritam Neupane, M.P. Kavin Kumar and C.S. Vijayashankar",authors:[{id:"84668",title:"Dr.",name:"Sadip",middleName:null,surname:"Pant",fullName:"Sadip Pant",slug:"sadip-pant"}]},{id:"29888",title:"Inflammatory Biomarkers in Ischemic Heart Disease",slug:"inflammatory-biomarkers-in-ischemic-heart-disease",totalDownloads:2442,totalCrossrefCites:0,signatures:"Mette Bjerre",authors:[{id:"97690",title:"Dr.",name:"Mette",middleName:null,surname:"Bjerre",fullName:"Mette Bjerre",slug:"mette-bjerre"}]},{id:"29889",title:"Measurement of Myocardial Contractility in the Ischemic Heart – A Disease Immanent Uncertainty",slug:"measurement-of-myocardial-contractility-in-the-ischemic-heart-a-disease-immanent-uncertainty",totalDownloads:2856,totalCrossrefCites:0,signatures:"Jens Broscheit",authors:[{id:"87908",title:"Dr.",name:"Jens",middleName:null,surname:"Broscheit",fullName:"Jens Broscheit",slug:"jens-broscheit"}]},{id:"29890",title:"Electrical Heart Instability Evaluation in Conditions of Diastolic Heart Failure Suffered by Coronary Heart Disease Patients",slug:"electrical-heart-instability-evaluation-in-conditions-of-diastolic-heart-failure-suffered-by-coronar",totalDownloads:1575,totalCrossrefCites:0,signatures:"E.P. Tatarchenko, N.V. Pozdnyakova, O.E. Morozova and E.A. Petrushin",authors:[{id:"88989",title:"Prof.",name:"Nadegda",middleName:null,surname:"Pozdnyakova",fullName:"Nadegda Pozdnyakova",slug:"nadegda-pozdnyakova"}]},{id:"29891",title:"Prehospital Thrombolysis: It’s All About Time",slug:"prehospital-thrombolysis-it-s-all-about-time",totalDownloads:5139,totalCrossrefCites:0,signatures:"Raveen Naidoo and Nicholas Castle",authors:[{id:"72301",title:"Mr.",name:"Nick",middleName:null,surname:"Castle",fullName:"Nick Castle",slug:"nick-castle"},{id:"73599",title:"Mr.",name:"Raveen",middleName:null,surname:"Naidoo",fullName:"Raveen Naidoo",slug:"raveen-naidoo"}]},{id:"29892",title:"Thrombolysis in Myocardial Infarction",slug:"thrombolysis-in-myocardial-infarction-",totalDownloads:4332,totalCrossrefCites:1,signatures:"Ajay Suri, Sophia Tincey, Syed Ahsan and Pascal Meier",authors:[{id:"73735",title:"Dr.",name:"Ajay",middleName:null,surname:"Suri",fullName:"Ajay Suri",slug:"ajay-suri"}]},{id:"29893",title:"Platelet Activation in Ischemic Heart Disease: Role of Modulators and New Therapies",slug:"platelets-activation-in-ischemic-heart-disease-role-of-modulators-and-new-therapies-",totalDownloads:2266,totalCrossrefCites:0,signatures:"Mahdi Garelnabi, Javier E. Horta and Emir Veledar",authors:[{id:"88368",title:"Prof.",name:"Mahdi",middleName:null,surname:"Garelnabi",fullName:"Mahdi Garelnabi",slug:"mahdi-garelnabi"},{id:"98032",title:"Dr.",name:"Javier",middleName:null,surname:"Horta",fullName:"Javier Horta",slug:"javier-horta"},{id:"98034",title:"Prof.",name:"Emir",middleName:null,surname:"Veledar",fullName:"Emir Veledar",slug:"emir-veledar"}]},{id:"29894",title:"Myocardial Ischemia-Reperfusion/Injury",slug:"myocardial-ischemia-reperfusion-injury",totalDownloads:1905,totalCrossrefCites:1,signatures:"Nermine Saleh and Magda Youssef",authors:[{id:"87897",title:"Dr.",name:"Nermine",middleName:null,surname:"Saleh",fullName:"Nermine Saleh",slug:"nermine-saleh"},{id:"97197",title:"Prof.",name:"Magda H. M.",middleName:null,surname:"Youssef",fullName:"Magda H. M. Youssef",slug:"magda-h.-m.-youssef"}]},{id:"29895",title:"Connexin 43 Hemichannels and Pharmacotherapy of Myocardial Ischemia Injury",slug:"connexin-43-hemichannels-and-pharmacotherapy-of-myocardial-ischemia-injury",totalDownloads:1633,totalCrossrefCites:0,signatures:"Ghayda Hawat and Ghayath Baroudi",authors:[{id:"90555",title:"Dr.",name:"Ghayath",middleName:null,surname:"Baroudi",fullName:"Ghayath Baroudi",slug:"ghayath-baroudi"},{id:"98487",title:"Dr.",name:"Ghayda",middleName:null,surname:"Hawat",fullName:"Ghayda Hawat",slug:"ghayda-hawat"}]},{id:"29896",title:"Myocardial Ischemia: Alterations in Myocardial Cellular Energy and Diastolic Function, a Potential Role for D-Ribose",slug:"myocardial-ischemia-alterations-in-myocardial-cellular-energy-and-diastolic-function-a-potential-rol",totalDownloads:1465,totalCrossrefCites:0,signatures:"Linda M. Shecterle and J. A. St. Cyr",authors:[{id:"87970",title:"Dr.",name:"John",middleName:null,surname:"St.Cyr",fullName:"John St.Cyr",slug:"john-st.cyr"},{id:"131599",title:"Dr.",name:"Linda",middleName:null,surname:"Shecterle",fullName:"Linda Shecterle",slug:"linda-shecterle"}]},{id:"29897",title:"Two Novel Approaches Providing Cardiac Protection Against Oxidative Stress",slug:"two-novel-approaches-providing-cardiac-protection-against-oxidative-stress-",totalDownloads:1862,totalCrossrefCites:0,signatures:"Howard Prentice and Herbert Weissbach",authors:[{id:"59770",title:"Prof.",name:"Howard",middleName:null,surname:"Prentice",fullName:"Howard Prentice",slug:"howard-prentice"},{id:"98675",title:"Prof.",name:"Herbert",middleName:null,surname:"Weissbach",fullName:"Herbert Weissbach",slug:"herbert-weissbach"}]},{id:"29898",title:"Hepatic Lipid Accumulation by High Cholesterol Diet is Inhibited by the Low Dose Fish Oil in Male C57BL/6J Mice",slug:"hepatic-lipid-accumulation-by-high-cholesterol-diet-is-inhibited-by-the-low-dose-fish-oil-in-male-c5",totalDownloads:1272,totalCrossrefCites:0,signatures:"Satoshi Hirako, Miki Harada, Hyoun-Ju Kim, Hiroshige Chiba and Akiyo Matsumoto",authors:[{id:"93685",title:"Dr.",name:"Hyounju",middleName:null,surname:"Kim",fullName:"Hyounju Kim",slug:"hyounju-kim"},{id:"98974",title:"Mr.",name:"Satoshi",middleName:null,surname:"Hirrako",fullName:"Satoshi Hirrako",slug:"satoshi-hirrako"}]},{id:"29899",title:"Cardiac Protection with Targeted Drug Delivery to Ischemic-Reperfused Myocardium",slug:"cardiac-protection-with-targeted-drug-delivery-to-ischemic-reperfused-myocardium",totalDownloads:2272,totalCrossrefCites:0,signatures:"Michael Galagudza",authors:[{id:"87829",title:"Dr.",name:"Michael",middleName:null,surname:"Galagudza",fullName:"Michael Galagudza",slug:"michael-galagudza"}]},{id:"29900",title:"Topical Negative Pressure, Applied onto the Myocardium, a Potential Alternative Treatment for Patients with Coronary Artery Disease in the Future",slug:"topical-negative-pressure-applied-onto-the-myocardium-a-potential-alternative-treatment-for-patients",totalDownloads:1450,totalCrossrefCites:0,signatures:"Sandra Lindstedt, Malin Malmsjö, Joanna Hlebowicz and Richard Ingemansson",authors:[{id:"90045",title:"PhD.",name:"Sandra",middleName:null,surname:"Lindstedt",fullName:"Sandra Lindstedt",slug:"sandra-lindstedt"},{id:"97151",title:"Dr.",name:"Malin",middleName:null,surname:"Malmsjö",fullName:"Malin Malmsjö",slug:"malin-malmsjo"},{id:"97152",title:"Dr.",name:"Richard",middleName:null,surname:"Ingemansson",fullName:"Richard Ingemansson",slug:"richard-ingemansson"},{id:"97173",title:"Dr.",name:"Joanna",middleName:null,surname:"Hlebowicz",fullName:"Joanna Hlebowicz",slug:"joanna-hlebowicz"}]},{id:"29901",title:"Ischemic Heart Disease, Diabetes and Mineralocorticoid Receptors",slug:"ischemic-heart-disease-diabetes-and-mineralocorticoid-receptors",totalDownloads:1762,totalCrossrefCites:0,signatures:"Anastasia Susie Mihailidou",authors:[{id:"90907",title:"Dr.",name:"Anastasia",middleName:"Susie",surname:"Mihailidou",fullName:"Anastasia Mihailidou",slug:"anastasia-mihailidou"}]},{id:"29902",title:"Cardiology Best Practice – Effective Health Education Meets Biomedical Advances: Reducing the Ultimate Knowledge Translation Gap",slug:"cardiology-best-practice-effective-health-education-meets-biomedical-advances-reducing-the-ultimate-",totalDownloads:1294,totalCrossrefCites:2,signatures:"Elizabeth Dean, Zhenyi Li, Wai Pong Wong and Michael E. Bodner",authors:[{id:"95246",title:"Prof.",name:"Elizabeth",middleName:null,surname:"Dean",fullName:"Elizabeth Dean",slug:"elizabeth-dean"},{id:"127701",title:"Dr.",name:"Zhenyi",middleName:null,surname:"Li",fullName:"Zhenyi Li",slug:"zhenyi-li"},{id:"127702",title:"Associate Prof.",name:"Wai Pong",middleName:null,surname:"Wong",fullName:"Wai Pong Wong",slug:"wai-pong-wong"},{id:"127703",title:"Dr.",name:"Michael E.",middleName:null,surname:"Bodner",fullName:"Michael E. Bodner",slug:"michael-e.-bodner"}]},{id:"29903",title:"Inpatient Costs Associated with Ischemic Heart Disease Among Adults Aged 18-64 Years in the United States",slug:"inpatient-costs-associated-with-ischemic-heart-disease-among-u-s-adults-aged-18-64",totalDownloads:1626,totalCrossrefCites:1,signatures:"Guijing Wang, Zefeng Zhang, Carma Ayala, Diane Dunet and Jing Fang",authors:[{id:"90566",title:"Dr.",name:"Guijing",middleName:null,surname:"Wang",fullName:"Guijing Wang",slug:"guijing-wang"},{id:"90582",title:"Dr.",name:"Zefeng",middleName:null,surname:"Zhang",fullName:"Zefeng Zhang",slug:"zefeng-zhang"},{id:"90583",title:"Dr.",name:"Carma",middleName:null,surname:"Ayala",fullName:"Carma Ayala",slug:"carma-ayala"},{id:"90584",title:"Dr.",name:"Diane",middleName:null,surname:"Dunet",fullName:"Diane Dunet",slug:"diane-dunet"},{id:"90586",title:"Dr.",name:"Jing",middleName:null,surname:"Fang",fullName:"Jing Fang",slug:"jing-fang"}]},{id:"29904",title:"Post-Myocardial Infarction Depression",slug:"post-myocardial-infarction-depression",totalDownloads:2050,totalCrossrefCites:1,signatures:"Rousseau Guy, Thierno Madjou Bah and Roger Godbout",authors:[{id:"95306",title:"Prof.",name:"Guy",middleName:null,surname:"Rousseau",fullName:"Guy Rousseau",slug:"guy-rousseau"},{id:"97203",title:"Dr.",name:"Roger",middleName:null,surname:"Godbout",fullName:"Roger Godbout",slug:"roger-godbout"}]},{id:"29905",title:"Cytochrome P450 Epoxygenase CYP2J2 G-50T Polymorphism is an Independent Genetic Prognostic Risk Factor and Interacts with Smoking Cessation After Index Premature Myocardial Infarction",slug:"cytochrome-p450-epoxygenase-cyp2j2-7-polymorphism-is-an-independent-genetic-prognostic-risk-factor-a",totalDownloads:1507,totalCrossrefCites:0,signatures:"Ping-Yen Liu, Yi-Heng Li and Jyh-Hong Chen",authors:[{id:"109116",title:"Dr.",name:"Ping-Yen",middleName:null,surname:"Liu",fullName:"Ping-Yen Liu",slug:"ping-yen-liu"},{id:"116974",title:"Dr.",name:"Yi-Heng",middleName:null,surname:"Li",fullName:"Yi-Heng Li",slug:"yi-heng-li"},{id:"116975",title:"Prof.",name:"Jyh-Hong",middleName:null,surname:"Chen",fullName:"Jyh-Hong Chen",slug:"jyh-hong-chen"}]},{id:"29906",title:"Coronary Artery Aneurysms: An Update",slug:"coronary-artery-aneurysms-an-update",totalDownloads:5629,totalCrossrefCites:0,signatures:"Karina M. Mata, Cleverson R. Fernandes, Elaine M. Floriano, Antonio P. Martins, Marcos A. Rossi and Simone G. Ramos",authors:[{id:"74619",title:"Associate Prof.",name:"Simone",middleName:"Gusmão",surname:"Ramos",fullName:"Simone Ramos",slug:"simone-ramos"},{id:"98442",title:"Dr.",name:"Antonio",middleName:"Padua",surname:"Martins",fullName:"Antonio Martins",slug:"antonio-martins"},{id:"98449",title:"Prof.",name:"Marcos",middleName:null,surname:"Rossi",fullName:"Marcos Rossi",slug:"marcos-rossi"},{id:"127905",title:"Mrs.",name:"Elaine M.",middleName:null,surname:"Floriano",fullName:"Elaine M. Floriano",slug:"elaine-m.-floriano"},{id:"127906",title:"Dr.",name:"Karina M.",middleName:null,surname:"Mata",fullName:"Karina M. Mata",slug:"karina-m.-mata"},{id:"127907",title:"Dr.",name:"Cleverson R.",middleName:null,surname:"Fernandes",fullName:"Cleverson R. Fernandes",slug:"cleverson-r.-fernandes"}]},{id:"29907",title:"Cardiac Function and Organ Blood Flow at Early Stage Following Severe Burn",slug:"the-heart-function-and-organ-blood-flow-at-early-stage-following-severe-burn",totalDownloads:2185,totalCrossrefCites:0,signatures:"Rong Xiao and Yue-Sheng Huang",authors:[{id:"98192",title:"Prof.",name:"Yue-Sheng",middleName:null,surname:"Huang",fullName:"Yue-Sheng Huang",slug:"yue-sheng-huang"},{id:"135404",title:"Dr.",name:"Rong",middleName:null,surname:"Xiao",fullName:"Rong Xiao",slug:"rong-xiao"}]},{id:"29908",title:"Aging, Reactive Nitrogen Species and Myocardial Apoptosis Induced by Ischemia/Reperfusion Injury",slug:"aging-reactive-nitrogen-species-and-myocardial-apoptosis-induced-by-ischemia-reperfusion-injury",totalDownloads:1552,totalCrossrefCites:0,signatures:"Huirong Liu, Ke Wang, Xiaoliang Wang, Jue Tian, Jianqin Jiao, Kehua Bai, Jie Yang and Haibo Xu",authors:[{id:"92110",title:"Prof.",name:"Huirong",middleName:null,surname:"Liu",fullName:"Huirong Liu",slug:"huirong-liu"},{id:"97762",title:"Ms.",name:"Ke",middleName:null,surname:"Wang",fullName:"Ke Wang",slug:"ke-wang"},{id:"97767",title:"Dr.",name:"Xiaoliang",middleName:null,surname:"Wang",fullName:"Xiaoliang Wang",slug:"xiaoliang-wang"},{id:"97769",title:"Dr.",name:"Jue",middleName:null,surname:"Tian",fullName:"Jue Tian",slug:"jue-tian"},{id:"97775",title:"Dr.",name:"Kehua",middleName:null,surname:"Bai",fullName:"Kehua Bai",slug:"kehua-bai"},{id:"97818",title:"Dr.",name:"Jianqin",middleName:null,surname:"Jiao",fullName:"Jianqin Jiao",slug:"jianqin-jiao"},{id:"97822",title:"Ms.",name:"Jie",middleName:null,surname:"Yang",fullName:"Jie Yang",slug:"jie-yang"},{id:"97824",title:"Mr.",name:"Haibo",middleName:null,surname:"Xu",fullName:"Haibo Xu",slug:"haibo-xu"}]}]},relatedBooks:[{type:"book",id:"5166",title:"Echocardiography in Heart Failure and Cardiac Electrophysiology",subtitle:null,isOpenForSubmission:!1,hash:"cb992fb172cb9aa79234394e1704ecc2",slug:"echocardiography-in-heart-failure-and-cardiac-electrophysiology",bookSignature:"Umashankar Lakshmanadoss",coverURL:"https://cdn.intechopen.com/books/images_new/5166.jpg",editedByType:"Edited by",editors:[{id:"13913",title:"Dr.",name:"Umashankar",surname:"Lakshmanadoss",slug:"umashankar-lakshmanadoss",fullName:"Umashankar Lakshmanadoss"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"52405",title:"Introductory Chapter: Practical Approach to the Use of Intracardiac Echocardiography in Invasive Electrophysiology Procedures",slug:"introductory-chapter-practical-approach-to-the-use-of-intracardiac-echocardiography-in-invasive-elec",signatures:"Umashankar Lakshmanadoss",authors:[{id:"13913",title:"Dr.",name:"Umashankar",middleName:null,surname:"Lakshmanadoss",fullName:"Umashankar Lakshmanadoss",slug:"umashankar-lakshmanadoss"}]},{id:"51713",title:"The Role of Electrocardiographic Markers in the Prevention of Atrial and Ventricular Arrhythmias",slug:"the-role-of-electrocardiographic-markers-in-the-prevention-of-atrial-and-ventricular-arrhythmias",signatures:"Veronika Sebestyén and Zoltán Szabó",authors:[{id:"179148",title:"Ph.D.",name:"Zoltan",middleName:null,surname:"Szabo",fullName:"Zoltan Szabo",slug:"zoltan-szabo"},{id:"179158",title:"Dr.",name:"Veronika",middleName:null,surname:"Sebestyen",fullName:"Veronika Sebestyen",slug:"veronika-sebestyen"}]},{id:"51963",title:"Echocardiography and Other Noninvasive Imaging Techniques in the Selection and Management of Patients with Cardiac Resynchronization Therapy",slug:"echocardiography-and-other-noninvasive-imaging-techniques-in-the-selection-and-management-of-patient",signatures:"Silvia Lupu, Lucia Agoston-Coldea and Dan Dobreanu",authors:[{id:"185084",title:"Dr.",name:"Silvia",middleName:null,surname:"Lupu",fullName:"Silvia Lupu",slug:"silvia-lupu"},{id:"185100",title:"Prof.",name:"Dan",middleName:null,surname:"Dobreanu",fullName:"Dan Dobreanu",slug:"dan-dobreanu"},{id:"185101",title:"Dr.",name:"Lucia",middleName:null,surname:"Agoston-Coldea",fullName:"Lucia Agoston-Coldea",slug:"lucia-agoston-coldea"}]},{id:"51894",title:"Multimodality Echocardiographic Assessment of Patients Undergoing Atrial Fibrillation Ablation",slug:"multimodality-echocardiographic-assessment-of-patients-undergoing-atrial-fibrillation-ablation",signatures:"Mariana Floria and Maria Daniela Tanase",authors:[{id:"185089",title:"Dr.",name:"Tanase",middleName:null,surname:"Daniela Maria",fullName:"Tanase Daniela Maria",slug:"tanase-daniela-maria"},{id:"185115",title:"Dr.",name:"Mariana",middleName:null,surname:"Floria",fullName:"Mariana Floria",slug:"mariana-floria"}]},{id:"51931",title:"Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists",slug:"speckle-tracking-imaging-principles-and-clinical-applications-a-review-for-clinical-cardiologists",signatures:"Iacopo Fabiani, Nicola Riccardo Pugliese, Veronica Santini, Lorenzo\nConte and Vitantonio Di Bello",authors:[{id:"184730",title:"Prof.",name:"Vitantonio",middleName:null,surname:"Di Bello",fullName:"Vitantonio Di Bello",slug:"vitantonio-di-bello"},{id:"184733",title:"Dr.",name:"Iacopo",middleName:null,surname:"Fabiani",fullName:"Iacopo Fabiani",slug:"iacopo-fabiani"},{id:"184734",title:"Dr.",name:"Nicola Riccardo",middleName:null,surname:"Pugliese",fullName:"Nicola Riccardo Pugliese",slug:"nicola-riccardo-pugliese"},{id:"184736",title:"Dr.",name:"Lorenzo",middleName:null,surname:"Conte",fullName:"Lorenzo Conte",slug:"lorenzo-conte"},{id:"185432",title:"Dr.",name:"Santini",middleName:null,surname:"Veronica",fullName:"Santini Veronica",slug:"santini-veronica"}]},{id:"51729",title:"Cardiac Imaging in Hypertrophic Cardiomyopathy",slug:"cardiac-imaging-in-hypertrophic-cardiomyopathy",signatures:"Dai-Yin Lu and Ming-Chong Hsiung",authors:[{id:"184766",title:"Dr.",name:"Ming-Chon",middleName:null,surname:"Hsiung",fullName:"Ming-Chon Hsiung",slug:"ming-chon-hsiung"},{id:"184767",title:"Dr.",name:"Dai-Yin",middleName:null,surname:"Lu",fullName:"Dai-Yin Lu",slug:"dai-yin-lu"}]},{id:"51873",title:"Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography",slug:"noninvasive-measurement-of-pulmonary-capillary-wedge-pressure-by-speckle-tracking-echocardiography",signatures:"Masanori Kawasaki",authors:[{id:"50603",title:"Dr.",name:"Masanori",middleName:null,surname:"Kawasaki",fullName:"Masanori Kawasaki",slug:"masanori-kawasaki"}]},{id:"52572",title:"The Role of Echocardiography in the Management of Patients Undergoing a Ventricular Assist Device Implantation and/or Transplantation",slug:"the-role-of-echocardiography-in-the-management-of-patients-undergoing-a-ventricular-assist-device-im",signatures:"Tomoko Kato, Takashi Nishimura, Shunei Kyo, Kenji Kuwaki,\nHiroyuki Dada and Atsushi Amano",authors:[{id:"19711",title:"Dr.",name:"Tomoko",middleName:"Sugiyama",surname:"Kato",fullName:"Tomoko Kato",slug:"tomoko-kato"},{id:"193920",title:"Dr.",name:"Takashi",middleName:null,surname:"Nishimura",fullName:"Takashi Nishimura",slug:"takashi-nishimura"},{id:"193927",title:"Prof.",name:"Shunei",middleName:null,surname:"Kyo",fullName:"Shunei Kyo",slug:"shunei-kyo"},{id:"193928",title:"Dr.",name:"Kenji",middleName:null,surname:"Kuwaki",fullName:"Kenji Kuwaki",slug:"kenji-kuwaki"},{id:"193929",title:"Prof.",name:"Hiroyuki",middleName:null,surname:"Dada",fullName:"Hiroyuki Dada",slug:"hiroyuki-dada"},{id:"193930",title:"Prof.",name:"Atsushi",middleName:null,surname:"Amano",fullName:"Atsushi Amano",slug:"atsushi-amano"}]},{id:"52656",title:"Assessment of Right Ventricle by Echocardiogram",slug:"assessment-of-right-ventricle-by-echocardiogram",signatures:"Gunjan Choudhary, Arushi A. Malik, Dwight Stapleton and Pratap\nC. Reddy",authors:[{id:"183647",title:"Dr.",name:"Gunjan",middleName:null,surname:"Choudhary",fullName:"Gunjan Choudhary",slug:"gunjan-choudhary"},{id:"192261",title:"Dr.",name:"Arushi A",middleName:null,surname:"Malik",fullName:"Arushi A Malik",slug:"arushi-a-malik"},{id:"192262",title:"Dr.",name:"Dwight",middleName:null,surname:"Stapleton",fullName:"Dwight Stapleton",slug:"dwight-stapleton"},{id:"192263",title:"Dr.",name:"Pratap C",middleName:null,surname:"Reddy",fullName:"Pratap C Reddy",slug:"pratap-c-reddy"}]},{id:"52583",title:"Role of Echocardiography in the Critically Ill Patients",slug:"role-of-echocardiography-in-the-critically-ill-patients",signatures:"Manivannan Veerasamy",authors:[{id:"185477",title:"Dr.",name:"Manivannan",middleName:null,surname:"Veerasamy",fullName:"Manivannan Veerasamy",slug:"manivannan-veerasamy"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"64530",title:"Adrenergic Receptors as Pharmacological Targets for Neuroinflammation and Neurodegeneration in Parkinson’s Disease",doi:"10.5772/intechopen.81343",slug:"adrenergic-receptors-as-pharmacological-targets-for-neuroinflammation-and-neurodegeneration-in-parki",body:'\nThere are a number of neurological disorders that fall under the umbrella of neurodegeneration, with the major ones including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), spinal cord injury (SCI), and others. Currently, there are no generally effective treatments available to slow down or reverse the debilitating effects of these diseases, and the long-term effects of these diseases are the progressive degeneration and death of neurons. A majority of the neurodegenerative diseases are linked with inflammation in CNS [1], and the presence of activated glial cells, infiltration and activation of adaptive and innate immune cells, increased presence of inflammatory molecules such as cytokines and chemokines, and increased oxidative stress and reactive oxygen species (ROS) are the main neuroinflammatory characteristics present in lesions associated with these neurodegenerative disorders. Recent approaches found to be effective in the treatment of Parkinson’s disease involve the use of anti-inflammatory agents and cytokines such as agonists to the β2-adrenergic receptors (β2-AR) to inhibit neuroinflammation and the progression of dopaminergic neurodegeneration. In this chapter, we will address the current understanding of therapeutic approaches targeting neuroinflammation linked with PD and the use of β2-AR agonists as an effective treatment for PD.
\nParkinson’s disease (PD) is a progressive neurodegenerative disorder which leads to impaired motor skills. The major pathological feature of PD is the degeneration of dopaminergic (DA) neurons which project from substantia nigra (SN) to the striatum in the midbrain (nigro-striatal pathway) [2]. Another neuropathological feature of PD is the cytoplasmic inclusion of misfolded α-synuclein protein in degenerating dopaminergic neurons called Lewy bodies [3]. The primary motor symptoms of PD, such as tremor, rigidity, and bradykinesia, are caused by inadequate formation and neurotransmission of dopamine within the nigro-striatal pathway [4, 5]. Dementia is reported in 28% of PD cases with the prevalence rising to 65% in those aged 85 years and above. Patients with PD also show non-motor-related symptoms such as olfactory deficits, depression, cognitive deficits, sleep disorders, and autonomic dysfunction [6]. The majority of PD cases are idiopathic Parkinson’s, and the disease mechanism that ultimately causes idiopathic PD is largely unknown. In the remainder of the cases of PD, about 10–15% of patients do have a family history and those patients are referred to as having the familial form of PD. For these patients, their PD appears to be caused by a mutation in one of a few selected genes (such as SNCA, Parkin, LRRK2, DJ-1, etc.) [7, 8]. Although the etiology of the idiopathic form of the disease remains elusive, there are some risk factors associated with the development of the disease. These risk factors include exposure to environmental toxins, severe cranial trauma, systemic or localized infections, and inherited genetic risk factors. These genetic and nongenetic risk factors have the potential to initiate neurodegeneration and subsequent chronic inflammation in the brain which eventually contributes to the pathophysiology of PD [9]. In addition, several cellular and molecular pathways such as oxidative stress [10], proteosomal dysfunction [11], excitotoxicity [12], and mitochondrial dysfunction [13] have also been identified which contributes to neuronal death.
\nThe presence of activated glial cells, increased inflammatory molecules such as cytokines/chemokines, and increased oxidative stress and ROS are the main neuroinflammatory characteristics present in PD [14]. PD is now not only characterized as loss of DA-neurons and motor impairment, but also recognized to have an inflammatory component which plays a crucial role in the progression of the disease. Several inflammatory mediators such as TNF-α, IL-1β, ROS, and nitric oxide (NO), released from nonneuronal cells exacerbate the disease pathology [3, 15]. It has been suggested that α-synuclein released from dying neurons also activate the microglia via TLR2 activation [16]. Furthermore, the elevated levels of inflammatory cytokines such as TNF-α, IL-1β, and IL-6 have been reported in serum, cerebrospinal fluid (CSF), and striatum of PD patients [17]. The influx of peripheral macrophages has been reported in brains of patients with PD, but the role of these cells in disease pathology remains to be tested [18]. Additionally, activation and increased number of glial cells and infiltrating peripheral lymphocytes such as cytotoxic CD4+ and CD8+ cells in SN also support the role of adaptive immunity in the etiology of the disease [8]. Overall, these studies and others suggest the contribution of the immune system in the pathophysiology of PD.
\nMicroglia originate from erythromyeloid progenitors in the yolk sac which migrate and differentiate during development to form the central nervous system (CNS). Fully differentiated microglial cells are also considered to be the resident macrophages of the CNS [19], although some phenotypic and functional differences between microglia and macrophages have been found [20]. Growing evidence suggests that the activation of microglia in CNS plays an important role in the pathogenesis of PD. It is not well understood how microglia activation is either beneficial or detrimental to the neuron or how microglial activity is regulated. It has been found that microglial activation is required for neuronal survival by the removal of toxic substances through innate immunity [21]. On the other hand, it has been found that over-activated microglial cells are detrimental and neurotoxic [22]. Research studies of post-mortem brain tissue from patients with PD and related parkinsonian syndromes suggest the presence of activated microglia around degenerating DA-neurons in the SN [23] and these activated microglia are not only limited to the SN but also present in extended brain areas such as hippocampus, putamen, trans-entorhinal cortex, cingulate cortex, and temporal cortex [24]. Imaging of activated microglia in the striatum could be used as a biomarker for detecting neuroinflammation in neurodegenerative parkinsonian disorders [25]. The resting microglia switches to an activated microglia phenotype in response to pathogen invasion or release of toxic or inflammatory mediators and thereby promotes an inflammatory response [1]. Once activated, microglial cells produce a wide range of inflammatory mediators which serve to initiate an innate immune response or glial cell-propagated inflammation termed as neuroinflammation [26]. Also, the degenerating DA-neurons release many toxic factors that activate microglia and these degenerating neurons are vulnerable to inflammatory insult. Degenerating neurons will co-localize or attract an even larger population of microglia in the SN [27]. Collectively, these activated microglia and damaged neurons form a repetitive and vicious cycle that leads to chronic inflammation and continued extensive DA neurodegeneration over time, leading to the progression of PD [27]. These findings confirm neuroinflammation as a pivotal process in the progression of neurodegenerative disorders and the central role of microglia in this process [22]. Targeting neuroinflammatory pathways within microglia could be a significant step in the development of new therapeutics for neurodegenerative diseases, including PD.
\nTreatment for PD normally involves medications such as Levodopa to enhance the dopamine levels and deal with movement symptoms [28]. While none of our current treatments are able to stop the disease, medication and surgery can be helpful for managing the symptoms [29]. These treatments work well in patients initially, but they are also associated with unwanted side-effects and reduced efficacy over time [30]. On the other hand, many studies suggest that inflammatory mediators such as TNF, PGE2, NO, free radicals, and other immune mediators play role in the pathogenesis of PD and degeneration of dopamine-producing neurons and that targeting these mediators can be an effective treatment for PD. This opens up the potential of using anti-inflammatory drugs as an effective and long-term treatment in PD. These anti-inflammatory drugs can act by arresting the disease onset (primary prevention) or by interrupting or even reversing the disease progression (secondary prevention). Epidemiological and observational studies suggest that the use of anti-inflammatory drugs lower the risk of developing PD [31]. Observations which demonstrated that inflammation in SN plays a role in PD have led many investigators to initially consider the potential use of both steroidal and nonsteroidal anti-inflammatory drugs for the treatment of PD. Steroidal anti-inflammatory drugs (SAIDs), such as dexamethasone, have shown neuroprotective effects in LPS-induced neurotoxicity in the SN in LPS models of PD [32]. Nonsteroidal anti-inflammatory drugs (NSAIDs) have also been used as analgesics and antipyretics to suppress the adverse effects of inflammation [33]. The neuroprotective effects of Ibuprofen have been studied in PD pathogenesis and these studies demonstrate the protective effect on dopaminergic neurons against glutamate toxicity in vitro [34, 35]. Previously, we have established several therapies targeting neuroinflammation and neurodegeneration in an animal model of PD and these therapies include D-morphinan-related compounds [36], anti-inflammatory cytokines such as TGF-β (transforming growth factor-beta) [37] and IL-10 [38, 39], IKK (inhibitor of kappa B (IκB) kinase) inhibitors [40], NADPH (nicotinamide adenine dinucleotide phosphate) oxidase inhibitors [41], and β2-AR (beta 2-adrenergic receptor) agonists [42, 43].
\nWe have conducted a number of experiments using different classes of anti-inflammatory compounds to determine their efficacy in preventing dopaminergic neurotoxicity by activated microglial cells both in vitro and in vivo. First, it was found that morphinan compounds and their stereoisomers (L-morphine and its D stereo enantiomers) can inhibit microglial activation and LPS- or MPP+-induced neurotoxicity in rat primary mesencephalic cultures. We and others observed that several dextrorotatory isomers of morphine compounds, including D-morphine, dextromethorphan, and sinomenine, showed neuroprotective effects against LPS and MPP+ (1-methyl-4-phenylpyridinium) which were mediated through the inhibition of microglial PHOX activity [36, 44, 45]. Furthermore, these studies also suggest that these morphinan compounds bind to the catalytic subunit of PHOX, inhibit its activity, and reduce the production of superoxide and other pro-inflammatory cytokines [44]. In another set of studies using a different anti-inflammatory approach, a specific inhibitor of IKK-β (IkappaB kinase-beta) protects dopaminergic neurons against LPS-induced neurotoxicity both in vitro and in vivo through inhibition of NF-κB activation, resulting in the decreased production of ROS and inflammatory cytokines [40]. We have also developed therapies targeting neuroinflammation in PD models by using anti-inflammatory cytokines such as IL-10 and TGF-β1, and found that treatment with IL-10 on rat mesencephalic neuron-glia culture protects against LPS-induced neurotoxicity via suppression of pro-inflammatory mediators and superoxide production [38]. Similarly, the neuroprotective effect of TGFβ1 is primarily due to its ability to inhibit ERK phosphorylation, the serine phosphorylation on p47\nphox\n, and the production of ROS from microglia during activation by LPS [37].
\nOne of the most potent and successful therapeutic treatments for inflammation-mediated dopaminergic neurotoxicity is the use of long-acting agonists to the β2-AR. Adrenergic receptors (AR) are seven-transmembrane proteins that serve as adrenoreceptors for catecholamines such as norepinephrine and epinephrine on multiple cell types, and cells within the CNS that express AR include neurons, immune cells, and astrocytes. Pharmacological classification of the adrenergic receptor was first introduced in 1948 and broadly classified as α and β adrenergic receptors [46] by Ahlquist. The classification was based on the order of potency and specificity of natural and synthetic agonist and blocking agents. The α-AR response corresponds to mainly excitatory response, while β-AR responses were correlated mainly with the inhibitory response. The α-AR response showed the order of potency: norepinephrine > epinephrine > isoproterenol and β-AR-mediated response exhibited order of potency: isoproterenol > epinephrine > norepinephrine [47, 48]. After the discovery of new drugs which have a high affinity to adrenergic receptors, these receptors were sub-classified. α-AR were subdivided into α1 and α2 adrenergic receptors [49]. Further studies subdivided β-AR into β1 and β2 which are normally present on immune cells, cardiac muscles, and airway smooth muscles, respectively [50]. A third β-AR, now called as β3-AR was identified on adipose tissues [51]. Tissue distribution, physiological effects, mechanism of action, and the major agonists/antagonists of ARs are summarized in \nTable 1\n. Pharmacological compounds that serve as short, long, and ultra-long-acting agonists for these receptors have now been developed, and they are normally thought to stimulate adrenergic receptors by four different mechanisms: (1) by direct receptor binding, the most common mechanism where drugs activate peripheral adrenergic receptors via direct binding to receptor and mimic the actions of endogenous agonists (NE, epinephrine), (2) by ameliorating NE release, where drugs act on sympathetic nerve terminals and results into NE release, (3) by inhibition of NE reuptake, where these drugs can cause NE to accumulate within synaptic gaps at sympathetic nerve terminals, (4) by blockade of NE inactivation where drugs inhibit the activity of monoamine oxidase (MAO) which inhibits the activity of monoamines such as NE and dopamine [52].
\nCharacteristics of adrenergic receptors.
The β2-ARs belong to a diverse superfamily of human cell surface seven transmembrane receptors for hormones and neurotransmitters called G-protein-coupled receptors (GPCRs). GPCRs are divided into six classes on basis of sequence homology: class A (Rhodopsin-like), class B (Secretin receptor family), class C (Metabotropic glutamate), class D (Fungal mating pheromone receptor), class E (Cyclic AMP receptor), and class F (Frizzled/smoothened) [53]. GPCRs are one of the most extensively studied proteins for the development of pharmaceutical drugs and target for approximately 50% of the marketed pharmaceutical drugs [54]. The adrenergic receptor family belongs to the rhodopsin-like subfamily, the largest class of the GPCR. The β2-AR is an intron-less gene is present on the long arm of chromosome 5 (5q31) and encodes for 413 amino acid polypeptide of 46kD [55]. Similar to all GPCRs, β2-AR is composed of seven transmembrane spanning α-helices with an intracellular C-terminus and an extracellular N-terminus. The β2-AR was the first GPCR to be cloned [56] and the first GPCR structure to be solved [57]. The β2-AR has been studied extensively and also serves as a model system for investigating the regulation and signal transduction of GPCRs. The study of the 3D protein structure of this family of GPCRs took a giant leap forward when rhodopsin was first crystallized in 2000 and this crystalline structure has been used as an important template for modeling other GPCRs in this family [58]. The crystalline structure of human β2-AR was not solved until 2007, when a nonactive structure of β2-AR was identified [57]. Post-translational modifications such as glycosylation, pamitoylation, disulfide bond formation, and phosphorylation have now been found to affect receptor functions. Interestingly, β2-AR is glycosylated at amino acid 6, 15, and 187 which is important for the trafficking of the β2-AR from the endoplasmic reticulum to the plasma membrane [59]. Mutation in these sites also results in reduced expression of receptor on the cell membrane, suggesting a role for glycosylation in cell surface expression [60]. Conversely, the cysteine amino acid in the cytoplasmic tail at position 341 is palmitoylated, and is now found to be an important residue for the adequate coupling of the receptor to the Gs-protein [61]. Finally, β2-ARs have disulfide bonds which are essential for agonist binding and also for maintaining their tertiary structure [62].
\nAdrenergic receptors are widely distributed on human body organs and regulate physiologic functions such as bronchodilation [63], vasodilation, glycogenolysis in the liver, and relaxation of uterine and bladder muscles [64]. The human β2-AR are widely expressed not only on airway smooth muscles, but also on the wide variety of cells such as epithelial cells, endothelial cells, brain cells, and immune cells including mast cells, macrophages, adaptive immune cells, and eosinophils [65]. The expressions of β1- and β2-AR have also been found on microglial cells, suggesting that microglia, the brain’s resident immune cell, is predominantly regulated by NE since NE is the predominant catecholamine in the CNS. Conversely, peripheral immune cells such as macrophages and T cells, which also express high levels of β1 and β-2 AR, are thought to be regulated primarily by epinephrine [66].
\nActivation of adrenergic receptors could result into both pro- and anti-inflammatory actions, depending on certain parameters such as the type of cell, duration of ligand exposure to the receptor, and type of the adrenergic receptor [67]. It is the diversity of the β2-AR that leads to the complexity of signaling mechanisms and to this duality of function. Activation of β2-AR by receptor agonists initiate intracellular signaling pathways that function either via G-proteins or through β-arrestins. Like other GPCR, β2-AR can activate either canonical (traditional) or noncanonical (nontraditional) signal transduction pathway. In the canonical pathway, similar to a typical GPCR the β2-AR signals via a heterotrimeric G-protein complex, and when the receptor is coupled to inactive GDP-bound G-protein, it appears to have high affinity to the agonist or ligand. After ligand binding, the transmembrane domains of the receptor undergo conformational change with the exchange of GDP to GTP. Further, this conformational change reduces the affinity of the ligand to its receptor, increasing the possibility of retraction of ligand from the receptor, thereby preventing the over-activation of G-protein. This provides evidence that β2-AR appear to oscillate between an active and inactive form under normal conditions. After the exchange of GDP to GTP, the Gα-subunit dissociates from Gβγ-subunit which remains associated with plasma membrane and the Gα-subunit activates effector proteins. The downstream signaling of this process normally results in the production of intracellular second messengers which further activates the cAMP-PKA-mediated intracellular signaling pathway. The activated β2-AR binds with the α-subunit of the G-protein together with a guanosine triphosphate (GTP) molecule. Further, the receptor coupled with adenylate cyclase (AC) which catalyzes the conversion of ATP into cAMP (a second messenger for β2-AR) by hydrolysis of GTP into GDP. The cAMP activates and regulates protein kinase A (PKA) which further mediates the transcription of genes and degradation of cAMP by phosphodiesterase (PDE) leading to termination of signaling [68].
\nEarlier it was determined that β2-AR exhibits their inhibitory signals in immune cells via the canonical (PKA) signaling pathway. It has now been found that GPCR can also signal through a noncanonical pathway in addition to their classical signaling pathway [69]. Activation through the noncanonical signaling pathway is cell type dependent and G-protein independent, but rather the G-protein-coupled receptor kinases (GRKs) and β-arrestins are involved in activation of this noncanonical signaling pathway. Various types of GRKs phosphorylate specifically serine and threonine at C-terminal of the β2-AR which further determines whether receptors undergo desensitization or initiate noncanonical signaling [70]. For example, phosphorylation of receptor by GRK5/6 initiates β-arrestin-mediated noncanonical signaling, while phosphorylation by GRK2 leads to β-arrestin-mediated desensitization of the receptor [71]. During noncanonical signaling, β-arrestin2 couples β2-AR to MAPK signaling pathways which induces activation of transcription factors and allows their nuclear translocation. Activation of β2-AR with high agonist concentration can lead to sustained activation of ERK1/2 via β-arrestin2. This explains why β2-AR activation can either enhance or suppress the proliferation of immune cells and cytokine production particularly at a high concentration of agonists [67, 72]. Studies suggest that during inflammatory conditions immune cells can switch from canonical to the noncanonical pathway [67, 68]. Engagement of β2-AR receptors by agonists can result in immunomodulatory actions. Depending on the type of immune stimuli and timing of β2-AR activation relative to immune activation, β2-AR stimulation can positively or negatively regulate the response of immune activator [67, 73]. The initial data obtained in animal models of dopaminergic neurotoxicity suggests that the primary immunomodulatory mechanism of β2-AR activation that regulates CNS inflammation in microglial cells occurs through the noncanonical β-arrestin2 pathway of activation.
\nβ-agonists are a group of pharmaceutical compounds or sympathomimetic drugs that mimic the effects of endogenous catecholamines such as epinephrine, norepinephrine, and dopamine. These drugs do not comprise a similar structure to catecholamines but still directly or indirectly activate the β2-adrenergic receptor. The first β-agonist was used around 5000 years ago in Chinese medicine where an ephedrine containing plant, Ma-huang, was used to treat respiratory problems [74]. Further research in the twentieth century has led to increased use of β-agonists for the treatment of respiratory diseases. The first β2-AR selective agonist, Salbutamol was synthesized by Glaxo in 1968 [75]. Later, the same team at Glaxo modified Salbutamol into Salmeterol with long-lasting effects and reduced side effects. Recently, they have synthesized β2-agonists with ultra-long-lasting effects such as Indacaterol [76]. After successful trials, these β2-agonists were approved by the US Food and Drug Administration (FDA) for the treatment of respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD). Since 1968, a number of companies have labored to develop β2-AR agonists, and some have now been commercialized for use in the treatment of COPD. A list of some of these agonists is given below and in \nTable 1\n.
\nA pharmacogenetic study of β2-agonists has summarized the relationship between polymorphisms in the β2-adrenoreceptor (ADRB2) gene and the effects of select β2-agonists [77]. Two hypotheses aim to account for the differences in functioning and in vivo half-lives of these compounds: exosite/exoreceptor or plasmalemma diffusion microkinetics. Briefly, the exosite hypothesis focuses on the ability of the side-chain of these compounds to interact with a distinct site on the receptor such that it allows the active component to “swing back-and-forth” to activate the receptor. The plasmalemma diffusion microkinetic hypothesis suggests that high concentrations of agonists are achieved in close proximity to the receptor and allows for a longer duration of action [78]. Both of these hypotheses require further investigation and need to be studied within the CNS. Depending upon their mechanism and duration of action, all β2-agonists are grouped into three major classes: short-acting, long-acting, and ultra-long-acting β2-agonists.
\nThese drugs are mostly hydrophilic in nature, access the active site of β-AR directly from the aqueous extracellular area and show the fast onset of action [79]. These SABAs bind to the receptor for short time; therefore, their duration of action is short. Some of the more common SABAs include Salbutamol (Ventolin), Albuterol (AccuNeb), Pirbuterol (Maxair), and Levalbuterol (Xopenex).
\nThese drugs are a frontline treatment for COPD, and usually prescribed alone or in combination with inhaled corticosteroids. LABAs are lipophilic in nature and taken up by cell membrane as a reservoir, progressively seep out and interact with the active site of the receptor [79]. They diffuse in the plasma membrane, where they interact with the active site of the β2-AR which allows for the close proximity with the receptor and longer duration of action. The onset of action of these drugs is slower as compared to SABAs, but the duration of action is prolonged thereby, called as LABAs. The duration of action is also dependent on the concentration of the agonist. Salmeterol, Salmeterol with an inhaled corticosteroid, Formoterol, and Formoterol with an inhaled corticosteroid are commercially available LABAs and used in medication for asthma and COPD [80].
\nThese agonists are also lipophilic in nature and onset of action is similar to LABAs, but the duration of action lasts longer than LABAs. Vilanterol with an inhaled corticosteroid and Indacaterol are ultra-LABAs, approved by FDA for the treatment of COPD [81].
\nDisease Condition | \nDesign | \nDoses | \nDrug | \nReferences | \n
---|---|---|---|---|
Spinal Cord Injury | \nRandomized controlled | \n4mg twice/day for 1st week then 8mg twice/day for 15 weeks | \nAlbuterol | \n[129] | \n
Alzheimer’s Disease | \nRandomized controlled | \n20mg/2ml for 12 months | \nFormoterol | \n[130] | \n
Multiple Sclerosis | \nBlinded controlled | \n4mg/day | \nAlbuterol | \n[131] | \n
Neuropathic pain | \nControlled, double blinded | \n5mg twice/day for 28 days | \nTerbutaline | \n[132] | \n
Memory and Cognition | \nRandomized controlled | \n4mg, single oral administration | \nSalbutamol | \n[133] | \n
SMA | \nUncontrolled | \n3-8mg/day for 6 months | \nAlbuterol | \n[134] | \n
ALS | \nUncontrolled | \n60ug/day for 6 months | \nClenbuterol | \n[135] | \n
SBMA | \nUncontrolled | \n20ug/day for 2days, then 40ug/day | \nClenbuterol | \n[136] | \n
Clinical trials using β2-agonist in neurological conditions.
\nSMA: Spinal Muscular Atrophy, SBMA: Spinal and Bulbar Muscular Atrophy, ALS: Amyotrophic Lateral Sclerosis.
The majority of adrenergic neurons are present in brainstem locus coeruleus (LC) nuclei, which is a predominant site for the production of norepinephrine (NE) in the brain. LC neurons play a key role in the regulation of cognitive behavior such as attention, mood, and arousal [82]. These neurons also play role in the development of the brain, mainly the neocortex [83]. The degeneration of LC-neurons has been identified in patients with PD and AD [84]. Also, the classical “monoamine hypothesis of depression” says that the deficiency of NE is a culprit for the cognitive impairment [85]. NE/noradrenaline, the primary neurotransmitter released by the LC neurons targets the adrenergic receptors present on the microglia and astrocytes in the brain [86]. NE-activated ARs on glial cells stimulate the second messenger system and maintain the homeostasis in the brain. Activation of AR on glial cells elicits anti-inflammatory actions, inhibits neuroinflammation, and thereby limits the degeneration of neurons [87]. Moreover, drugs that stimulate the release of NE/NA have potential to reduced inflammation and amyloid pathology in a mouse model of AD [88]. According to Braak’s hypothesis, early stage of progression starts in LC before it spreads to SN [89]. Overall, these and many other studies suggest the role of the adrenergic signaling in neurodegeneration. Therefore, enhancing NE/NA signaling, transplanting noradrenergic neurons, or use of drugs that mimic the activity of NA/NE on glial cells have great potential to reverse or halt the progressive degeneration of neurons [90]. The endogenous agonist/ligand for β2-AR is norepinephrine which acts as a neurotrophic factor and can influence protein/DNA synthesis in developing adult brain [91, 92]. NE protects cholinergic and dopaminergic cultured neurons against oxidative stress and catechol moiety of NE plays role in neuroprotection [93, 94]. It suggests that a compound containing catechol moiety, such as β-agonists, can mimic the neuroprotective effects of NE. Treatment with NE stimulates the synthesis of BDNF in astrocytes and neuron in vitro and in vivo [95, 96] and these neuroprotective effects were reversed by the antagonist of α1, β1, and β2-AR [97].
\nThe use of β2-agonists as an adjunct therapy to L-DOPA in PD was first described in 1994 [98]. Chai et al. showed that the β2-AR activation enhances hippocampal neurogenesis, ameliorates memory deficits, and increases dendritic branching and spine density in a mouse model of Alzheimer’s disease [99]. Recently, Mittal et al. have found that β2-AR activation regulates the gene expression of α-synuclein in various animal and in vitro models of PD. Salbutamol, a blood-brain-barrier-permeable β2-agonist, reduces expression of SNCA gene via histone-3-lysine-27 acetylation of its promoter and enhancer. They also analyzed the pharmacological history of 4 million Norwegians over 11 years and found that Salbutamol was also associated with reduced risk of developing PD [100]. In a mouse model of Down syndrome, Formoterol, a long-acting β2-AR agonist, causes significant improvement in synaptic density and cognitive functions [101]. Salmeterol (Sal) is an inhaled long-acting highly selective β2-AR agonist which is currently being used as the active ingredient in Advair@ as a bronchodilator. Our previous studies and others have shown that Salmeterol has anti-inflammatory and DA-neuroprotective activities, even at very low doses. Pre-treatment with Salmeterol protects DA neurons against LPS- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity in both in vitro and in vivo animal models of PD [42, 102]. The mechanism how Salmeterol regulates the activation of microglia is described in \nFigure 1\n. Collectively, these studies suggest that β2-AR agonists not only protect neurons against degeneration, but also have anti-inflammatory effects, and therefore, hold significant promise for the treatments of a wide variety of neurodegenerative conditions including PD [43]. The clinical efficacy of β2-AR agonists have been examined in various neurological disorders and few of them are summarized in \nTable 2\n.
\nSchematic of microglia-mediated neurotoxicity and inhibitory effects of Salmeterol on microglial activation.
Extensive previous investigations into the etiology of PD demonstrate a central role for the inflammatory microglial cell in the progression of PD. Thus, targeting neuroinflammation mediated by microglia may serve as a potential therapeutic benefit in the treatment of PD. Since traditional treatment for PD is aimed only at controlling the disease symptoms, the search for more effective neuroprotective therapies which target the cause of the disease is now receiving significant attention. Studies targeting neuroinflammation are aimed to promote the development of a novel therapeutic approach and aid in the drug discovery for neurodegenerative conditions such as PD.
\nOne such anti-inflammatory approach that has been found to be effective in protection against dopaminergic neurodegeneration is accomplished by natural and therapeutic compounds that activate the β2-AR. Brain cells including neurons, microglia, and astrocytes as well as immune cells express a high density of β2-AR on their surface [66, 103]. Catecholamines such as epinephrine (adrenaline), norepinephrine (noradrenaline), and dopamine are the most abundant catecholamines found in the nervous system. As evidenced by many unrelated studies, catecholamines can modulate the immune response [87, 104]. Further studies have found that the endogenous agonist of β2-AR, norepinephrine (NE), controls microglial motility and functions during pathogenic conditions [105]. NE also protects cortical neurons against microglia-mediated inflammation, while decreased levels of NE enhance microglial activation [106]. One study showed that β2-AR negatively regulates NF-κB activation and stabilizes the NF-κB/IκBα complex via β-arrestin 2 in LPS activated murine macrophages [107]. Interestingly, activation of β2-AR in astrocytes modulates TNF-α-induced inflammatory gene expression in vitro and in vivo. In addition, an in vivo study demonstrated increased expression of β2-AR in glial cells in response to neuronal injury. This suggests that β2-AR may provide a therapeutic target for regulation of glial cell functioning and the inflammatory response in the brain [108]. Activation of β2-AR on astrocytes stimulates the release of trophic factors such as BDNF, bFGF, NGF-1, and TGF-β1 via canonical signaling, showing anti-apoptotic and neuroprotective effects in animal models of cerebral ischemia and excitotoxicity [109, 110]. It has also been shown that noradrenaline acting on β2-AR enhances the expression of anti-inflammatory and neurotrophic cytokine IL-10 in the brain. This suggests an endogenous ligand of β2-AR is neuroprotective during inflammatory conditions in CNS disease pathology [108, 111]. Both canonical and noncanonical signaling of β2-AR can selectively regulate the adaptive immune response [67], since β2-AR are expressed by naïve CD4+ T (T-helper (Th0)) and Th1 cells but absent on Th2 cells [112, 113]. Naïve CD4+ T-cell treated with a β2-AR agonist or NE suppresses the production of interferon (IFN)-γ and IL-2 and affects their differentiation [114]. Collectively, these studies and several others suggest the role of β2-AR in the regulation of immune response.
\nWe have characterized and examined the effects of β2-AR agonists including Salbutamol, Salmeterol, Indacaterol, and Vilanterol on neuroinflammation in models of PD in vitro and in vivo. However, the short-acting agonists were neuroprotective and able to reduce inflammation in vitro at higher doses, but the long-acting agonist showed beneficial effects at low concentration (10−9 M) in neurotoxicity and inflammatory models of PD. Salmeterol, a β2-AR agonist, can effectively serve as a therapeutic treatment for PD by inhibiting microglia-mediated inflammatory responses in vivo. We have found that Salmeterol functions to inhibit innate pro-inflammatory response in both murine macrophages and microglia through its inhibition of the NF-κB signaling pathways [42]. We have also investigated whether Salmeterol is specific to neuroinflammation in PD or if it can be used as a universal anti-inflammatory drug against other chronic inflammatory diseases. To test this, we used murine macrophages stimulated with LPS from Porphyromonas gingivalis (PgLPS), an oral pathogen as an in vitro model for the periodontal disease. We have found that Salmeterol shows similar anti-inflammatory effects on PgLPS-stimulated macrophages [115]. Additionally, Feng et al. have also shown neuroprotective effects of β-arrestin2 via endogenous opioid arrest in inflammatory microglial cells [116].
\nThe agonist-activated β2-AR stimulates MAPK signaling pathway via noncanonical and G-protein independent pathway. Agonist-activated β2-AR reduces phosphorylation of ERK1/2 and p38 MAPK in macrophages stimulated with LPS. In contrast, β2-AR activation stimulates MAPK signaling and TNF-α, IL-12, and NO production in murine macrophages treated with PMA (phorbol 12-myristate-13-acetate) [73]. Similarly, our previous studies have shown that activation of β2-AR with the high concentration of agonist (up to 10−5 M) leads to sustained phosphorylation of ERK1/2 and enhanced production inflammatory mediators in murine microglia and macrophages [117]. High-dose treatment of β2-AR agonists on mixed neuroglia culture enhances neurotoxicity via NADPH oxidase activity in the ERK-dependent manner [118]. Like others, we have found that the low-doses of the β2-AR agonist Salmeterol reduces the MAPK activity, NF-κB activation and production of TNF-α in LPS-activated primary microglia [42]. We have also found that low-dose Salmeterol inhibits the phosphorylation of TAK1 (TGF-β-activated kinase1) which is an upstream regulator of NF-κB signaling in LPS-stimulated microglia. We have also found that Salmeterol increases the expression of β-arrestin2 and enhances the interaction between β-arrestin2 and TAB1 (TAK1-binding protein), reduced TAK1/TAB1 mediated activation of NFκB and expression of pro-inflammatory genes. Furthermore, silencing of β-arrestin2 abrogates the anti-inflammatory effects of Salmeterol in LPS-stimulated BV2 cells [119]. These studies suggest that the anti-inflammatory effects of Salmeterol work through the inhibition of pro-inflammatory pathways in microglial cells.
\nPrevious findings show that high dose Salmeterol enhances the expression of IL-1β and IL-6 mRNA and protein in unstimulated human monocytes and murine macrophages. These effects were β-arrestin2-dependent but PKA and NF-κB independent, while treatment with ERK1/2 and p38 MAPK inhibitor could reverse this effect [117]. This finding and several others suggest Salmeterol or other long-acting agonist have β-arrestin “biased” signaling of β2-AR. These agonists activate receptors via β-arrestin signaling with a much greater extent than their effect on G-protein-dependent signaling [120]. Our studies suggest that a very low concentration of Salmeterol does not enhance cAMP signaling and its downstream mediators, while it activates the β-arrestin2-mediated signaling events [42]. β-arrestin2 has been shown as a novel regulator of IκB stability via the direct interaction of β-arrestin2 and IκB in HEK293 cells [121]. In addition, β-arrestin2 negatively regulates the activation of NF-κB via direct binding with IκBα [122]. One study showed that overexpression of β-arrestin2 significantly reduces L-DOPA-induced dyskinesia in animal models of PD [123]. Collectively, these studies suggest that β2-AR agonists can be used therapeutically not only to inhibit chronic inflammation and progressive degeneration of neurons, but also to treat some of the most debilitating neurologic symptoms in PD.
\nAfter binding with an agonist or endogenous ligand, β2-AR normally activates the classical cAMP-dependent signaling pathway. The downstream effect of the cAMP/PKA pathway is the phosphorylation and nuclear translocation of the CREB transcription factor which further enhances the expression of cAMP-inducible genes [79]. Activation of CREB via this pathway regulates the synthesis of proteins which are mandatory for neuronal homeostasis [124]. The classical signaling of β2-AR also increases the activity of PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha), which is a key regulator of mitochondrial biogenesis and ROS metabolism [125]. Activation of β2-AR also elevated the release of neurotrophic factors via cAMP/PKA/CREB pathway and provides neuroprotective benefits against degeneration [126]. An endogenous agonist of β2-AR (NE) affects immune cell functions, production of cytokines, and antibody secretion [112]. β2-AR agonists have anti-inflammatory activity and inhibit release of pro-inflammatory mediators via cAMP/PKA/CREB pathway and also by alternate cAMP-dependent pathway (cAMP/Epac1/2) [42, 127, 128]. We have also found that pro-inflammatory effects of high-dose of Salmeterol are through cAMP/Epac pathway, while the anti-inflammatory effects of low-dose of Salmeterol are independent on cAMP and Epac activation [42, 118].
\nThe β2-AR agonists discussed above are FDA-approved for the treatment of respiratory diseases such as asthma and COPD, but none of these β2-AR agonists are specifically developed for PD. Although, Mittal et al. have found in a Norwegian population that using Salbutamol, a SABA, lower the risk of developing PD whereas the use of Propranolol, a β2-AR antagonist (commonly used to treat hypertension and certain other forms of heart disease) was associated with increased risk of PD [100]. Furthermore, this risk of developing PD was dependent on the duration of Salbutamol intake in those patients. In the patient population who used Salbutamol for at least 6 months, it was expected that 43 would develop PD, but only 23 patients were ultimately diagnosed with the disease (rate ratio 0.66). On the other hand, in the cohort who used Salbutamol for 2 months or less, there was no decreased risk of developing PD in this population [100]. In contrast, patients on Propranolol (which is also used as therapeutic for tremors in PD) for at least 1 year showed a significantly increased risk of developing PD compared to patients not on propranolol (rate ratio 2.2). Therefore, it is clear that patients on long-term Salbutamol (a β2-AR agonist) had significantly decreased the risk of developing PD, while patients on long-term propranolol (a β2-AR antagonist) therapy had significantly higher rates of PD, suggesting that β2-AR inhibition is a highly significant risk factor in developing PD. When we compared the effectiveness of Salbutamol to Salmeterol (a more lipophilic drug) in animal models of PD, Salmeterol was much more effective both in vitro and in vivo in dopaminergic neuroprotection [42]. More importantly, we found that animals given Salmeterol treatment well before the appearance of symptoms in a long-term model of PD showed little evidence of dopaminergic neurodegeneration compared to untreated animals. Taken together, this data suggests that administration of β2-AR agonists may have a profound preventative effect on the development of PD. Since the blood-brain-barrier penetration is a major obstacle in the development of therapeutics targeting CNS disorders, it will be important to consider the importance of lipophilic properties, concentration within the CNS, as well as the specificity, half-life and safety in using β2-AR agonists in older patients before and after the initial appearance of symptoms associated with PD. Consequently, these drugs require further investigation in a large cohort study to assess their utility as a potential therapeutic for PD and other neurodegenerative diseases.
\nNatural or synthetic activation or inhibition of the β2-AR can have profound effects on the development and progression of Parkinson’s disease, a chronic neurodegenerative disorder which involves both neuroinflammatory and cellular mechanisms in dopaminergic neurotoxicity. It is now clear that the therapeutic use of β2-AR agonists can both inhibit the cause of neurodegeneration and activate a mechanism that can enhance recovery of patients with this disease, and serves as an important new therapeutic approach to the treatment of chronic neurodegenerative disorders.
\nAuthors declare no “conflict of interest.”
\n"I work with IntechOpen for a number of reasons: their professionalism, their mission in support of Open Access publishing, and the quality of their peer-reviewed publications, but also because they believe in equality. Throughout the world, we are seeing progress in attracting, retaining, and promoting women in STEMM. IntechOpen are certainly supporting this work globally by empowering all scientists and ensuring that women are encouraged and enabled to publish and take leading roles within the scientific community." Dr. Catrin Rutland, University of Nottingham, UK
",metaTitle:"Advantages of Publishing with IntechOpen",metaDescription:"We have more than a decade of experience in Open Access publishing. \n\n ",metaKeywords:null,canonicalURL:null,contentRaw:'[{"type":"htmlEditorComponent","content":"We have more than a decade of experience in Open Access publishing. The advantages of publishing with IntechOpen include:
\\n\\nOur platform – IntechOpen is the world’s leading publisher of OA books, built by scientists, for scientists.
\\n\\nOur reputation – Everything we publish goes through a two-stage peer review process. We’re proud to count Nobel laureates among our esteemed authors. We meet European Commission standards for funding, and the research we’ve published has been funded by the Bill and Melinda Gates Foundation and the Wellcome Trust, among others. IntechOpen is a member of all relevant trade associations (including the STM Association and the Association of Learned and Professional Society Publishers) and has a selection of books indexed in Web of Science's Book Citation Index.
\\n\\nOur expertise – We’ve published more than 4,500 books by more than 118,000 authors and editors.
\\n\\nOur reach – Our books have more than 130 million downloads and more than 146,150 Web of Science citations. We increase citations via indexing in all the major databases, including the Book Citation Index at Web of Science and Google Scholar.
\\n\\nOur services – The support we offer our authors and editors is second to none. Each book in our program receives the following:
\\n\\nOur end-to-end publishing service frees our authors and editors to focus on what matters: research. We empower them to shape their fields and connect with the global scientific community.
\\n\\n"In developing countries until now, advancement in science has been very limited, because insufficient economic resources are dedicated to science and education. These limitations are more marked when the scientists are women. In order to develop science in the poorest countries and decrease the gender gap that exists in scientific fields, Open Access networks like IntechOpen are essential. Free access to scientific research could contribute to ameliorating difficult life conditions and breaking down barriers." Marquidia Pacheco, National Institute for Nuclear Research (ININ), Mexico
\\n\\nInterested? Contact Ana Pantar (book.idea@intechopen.com) for more information.
\\n"}]'},components:[{type:"htmlEditorComponent",content:'We have more than a decade of experience in Open Access publishing. The advantages of publishing with IntechOpen include:
\n\nOur platform – IntechOpen is the world’s leading publisher of OA books, built by scientists, for scientists.
\n\nOur reputation – Everything we publish goes through a two-stage peer review process. We’re proud to count Nobel laureates among our esteemed authors. We meet European Commission standards for funding, and the research we’ve published has been funded by the Bill and Melinda Gates Foundation and the Wellcome Trust, among others. IntechOpen is a member of all relevant trade associations (including the STM Association and the Association of Learned and Professional Society Publishers) and has a selection of books indexed in Web of Science's Book Citation Index.
\n\nOur expertise – We’ve published more than 4,500 books by more than 118,000 authors and editors.
\n\nOur reach – Our books have more than 130 million downloads and more than 146,150 Web of Science citations. We increase citations via indexing in all the major databases, including the Book Citation Index at Web of Science and Google Scholar.
\n\nOur services – The support we offer our authors and editors is second to none. Each book in our program receives the following:
\n\nOur end-to-end publishing service frees our authors and editors to focus on what matters: research. We empower them to shape their fields and connect with the global scientific community.
\n\n"In developing countries until now, advancement in science has been very limited, because insufficient economic resources are dedicated to science and education. These limitations are more marked when the scientists are women. In order to develop science in the poorest countries and decrease the gender gap that exists in scientific fields, Open Access networks like IntechOpen are essential. Free access to scientific research could contribute to ameliorating difficult life conditions and breaking down barriers." Marquidia Pacheco, National Institute for Nuclear Research (ININ), Mexico
\n\nInterested? Contact Ana Pantar (book.idea@intechopen.com) for more information.
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"58592",title:"Dr.",name:"Arun",middleName:null,surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58592/images/1664_n.jpg",biography:"Arun K. Shanker is serving as a Principal Scientist (Plant Physiology) with the Indian Council of Agricultural Research (ICAR) at the Central Research Institute for Dryland Agriculture in Hyderabad, India. He is working with the ICAR as a full time researcher since 1993 and has since earned his Advanced degree in Crop Physiology while in service. He has been awarded the prestigious Member of the Royal Society of Chemistry (MRSC), by the Royal Society of Chemistry, London in 2015. Presently he is working on systems biology approach to study the mechanism of abiotic stress tolerance in crops. His main focus now is to unravel the mechanism of drought and heat stress response in plants to tackle climate change related threats in agriculture.",institutionString:null,institution:{name:"Indian Council of Agricultural Research",country:{name:"India"}}},{id:"4782",title:"Prof.",name:"Bishnu",middleName:"P",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4782/images/system/4782.jpg",biography:"Bishnu P. Pal is Professor of Physics at Mahindra École\nCentrale Hyderabad India since July 1st 2014 after retirement\nas Professor of Physics from IIT Delhi; Ph.D.’1975 from IIT\nDelhi; Fellow of OSA and SPIE; Senior Member IEEE;\nHonorary Foreign Member Royal Norwegian Society for\nScience and Arts; Member OSA Board of Directors (2009-\n11); Distinguished Lecturer IEEE Photonics Society (2005-\n07).",institutionString:null,institution:{name:"Indian Institute of Technology Delhi",country:{name:"India"}}},{id:"69653",title:"Dr.",name:"Chusak",middleName:null,surname:"Limsakul",slug:"chusak-limsakul",fullName:"Chusak Limsakul",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Prince of Songkla University",country:{name:"Thailand"}}},{id:"75563",title:"Dr.",name:"Farzana Khan",middleName:null,surname:"Perveen",slug:"farzana-khan-perveen",fullName:"Farzana Khan Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75563/images/system/75563.png",biography:"Dr Farzana Khan Perveen (FLS; Gold-Medallist) obtained her BSc (Hons) and MSc (Zoology: Entomology) from the University of Karachi, MAS (Monbush-Scholar; Agriculture: Agronomy) and from the Nagoya University, Japan, and PhD (Research and Course-works from the Nagoya University; Toxicology) degree from the University of Karachi. She is Founder/Chairperson of the Department of Zoology (DOZ) and Ex-Controller of Examinations at Shaheed Benazir Bhutto University (SBBU) and Ex-Founder/ Ex-Chairperson of DOZ, Hazara University and Kohat University of Science & Technology. \nShe is the author of 150 high impact research papers, 135 abstracts, 4 authored books and 8 chapters. She is the editor of 5 books and she supervised BS(4), MSc(50), MPhil(40), and Ph.D. (1) students. She has organized and participated in numerous international and national conferences and received multiple awards and fellowships. She is a member of research societies, editorial boards of Journals, and World-Commission on Protected Areas, International Union for Conservation of Nature. Her fields of interest are Entomology, Toxicology, Forensic Entomology, and Zoology.",institutionString:"Shaheed Benazir Bhutto University",institution:{name:"Shaheed Benazir Bhutto University",country:{name:"Pakistan"}}},{id:"23804",title:"Dr.",name:"Hamzah",middleName:null,surname:"Arof",slug:"hamzah-arof",fullName:"Hamzah Arof",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/23804/images/5492_n.jpg",biography:"Hamzah Arof received his BSc from Michigan State University, and PhD from the University of Wales. Both degrees were in electrical engineering. His current research interests include signal processing and photonics. Currently he is affiliated with the Department of Electrical Engineering, University of Malaya, Malaysia.",institutionString:null,institution:{name:"University of Malaya",country:{name:"Malaysia"}}},{id:"41989",title:"Prof.",name:"He",middleName:null,surname:"Tian",slug:"he-tian",fullName:"He Tian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"East China University of Science and Technology",country:{name:"China"}}},{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/33351/images/168_n.jpg",biography:null,institutionString:null,institution:{name:"Institut Teknologi Bandung",country:{name:"Indonesia"}}},{id:"11981",title:"Prof.",name:"Hiroshi",middleName:null,surname:"Ishiguro",slug:"hiroshi-ishiguro",fullName:"Hiroshi Ishiguro",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Osaka University",country:{name:"Japan"}}},{id:"45747",title:"Dr.",name:"Hsin-I",middleName:null,surname:"Chang",slug:"hsin-i-chang",fullName:"Hsin-I Chang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"National Chiayi University",country:{name:"Taiwan"}}},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61581/images/237_n.jpg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"94249",title:"Prof.",name:"Junji",middleName:null,surname:"Kido",slug:"junji-kido",fullName:"Junji Kido",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Yamagata University",country:{name:"Japan"}}},{id:"12009",title:"Dr.",name:"Ki Young",middleName:null,surname:"Kim",slug:"ki-young-kim",fullName:"Ki Young Kim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12009/images/system/12009.jpg",biography:"Http://m80.knu.ac.kr/~doors",institutionString:null,institution:{name:"National Cheng Kung University",country:{name:"Taiwan"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5763},{group:"region",caption:"Middle and South America",value:2,count:5227},{group:"region",caption:"Africa",value:3,count:1717},{group:"region",caption:"Asia",value:4,count:10365},{group:"region",caption:"Australia and Oceania",value:5,count:897},{group:"region",caption:"Europe",value:6,count:15784}],offset:12,limit:12,total:10365},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{topicId:"6"},books:[{type:"book",id:"8977",title:"Protein Kinase - New Opportunities, Challenges and Future Perspectives",subtitle:null,isOpenForSubmission:!0,hash:"6d200cc031706a565b554fdb1c478901",slug:null,bookSignature:"Dr. Rajesh Kumar Singh",coverURL:"https://cdn.intechopen.com/books/images_new/8977.jpg",editedByType:null,editors:[{id:"329385",title:"Dr.",name:"Rajesh",surname:"Singh",slug:"rajesh-singh",fullName:"Rajesh Singh"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9659",title:"Fibroblasts - Advances in Cancer, Autoimmunity and Inflammation",subtitle:null,isOpenForSubmission:!0,hash:"926fa6446f6befbd363fc74971a56de2",slug:null,bookSignature:"Ph.D. Mojca Frank Bertoncelj and Ms. Katja Lakota",coverURL:"https://cdn.intechopen.com/books/images_new/9659.jpg",editedByType:null,editors:[{id:"328755",title:"Ph.D.",name:"Mojca",surname:"Frank Bertoncelj",slug:"mojca-frank-bertoncelj",fullName:"Mojca Frank Bertoncelj"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10797",title:"Cell Culture",subtitle:null,isOpenForSubmission:!0,hash:"2c628f4757f9639a4450728d839a7842",slug:null,bookSignature:"Prof. Xianquan Zhan",coverURL:"https://cdn.intechopen.com/books/images_new/10797.jpg",editedByType:null,editors:[{id:"223233",title:"Prof.",name:"Xianquan",surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10800",title:"Ligase",subtitle:null,isOpenForSubmission:!0,hash:"1f10ff112edb1fec24379dac85ef3b5b",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10800.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10801",title:"Uric Acid",subtitle:null,isOpenForSubmission:!0,hash:"d947ab87019e69ab11aa597edbacc018",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10837",title:"Peroxisomes",subtitle:null,isOpenForSubmission:!0,hash:"0014b09d4b35bb4d7f52ca0b3641cda1",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10838",title:"Ion Channels",subtitle:null,isOpenForSubmission:!0,hash:"048017b227b3bdfd0d33a49bac63c915",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10838.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10840",title:"Benzimidazole",subtitle:null,isOpenForSubmission:!0,hash:"9fe810233f92a9c454c624aec634316f",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10840.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10841",title:"Hydrolases",subtitle:null,isOpenForSubmission:!0,hash:"64617cf21bf1e47170bb2bcf31b1fc37",slug:null,bookSignature:"",coverURL:"https://cdn.intechopen.com/books/images_new/10841.jpg",editedByType:null,editors:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:13},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:3},{group:"topic",caption:"Business, Management and Economics",value:7,count:1},{group:"topic",caption:"Chemistry",value:8,count:6},{group:"topic",caption:"Computer and Information Science",value:9,count:6},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:7},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:3},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:27},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:2},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:4},{group:"topic",caption:"Social Sciences",value:23,count:2},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:1}],offset:12,limit:12,total:9},popularBooks:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.png",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9864",title:"Hydrology",subtitle:null,isOpenForSubmission:!1,hash:"02925c63436d12e839008c793a253310",slug:"hydrology",bookSignature:"Theodore V. Hromadka II and Prasada Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9864.jpg",editors:[{id:"181008",title:"Dr.",name:"Theodore V.",middleName:"V.",surname:"Hromadka II",slug:"theodore-v.-hromadka-ii",fullName:"Theodore V. Hromadka II"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9083",title:"Rodents",subtitle:null,isOpenForSubmission:!1,hash:"480148de5ecf236b3e0860fc3954b2d4",slug:"rodents",bookSignature:"Loth S. Mulungu",coverURL:"https://cdn.intechopen.com/books/images_new/9083.jpg",editors:[{id:"108433",title:"Dr.",name:"Loth S.",middleName:null,surname:"Mulungu",slug:"loth-s.-mulungu",fullName:"Loth S. Mulungu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5220},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9385",title:"Renewable Energy",subtitle:"Technologies and Applications",isOpenForSubmission:!1,hash:"a6b446d19166f17f313008e6c056f3d8",slug:"renewable-energy-technologies-and-applications",bookSignature:"Tolga Taner, Archana Tiwari and Taha Selim Ustun",coverURL:"https://cdn.intechopen.com/books/images_new/9385.jpg",editors:[{id:"197240",title:"Associate Prof.",name:"Tolga",middleName:null,surname:"Taner",slug:"tolga-taner",fullName:"Tolga Taner"}],equalEditorOne:{id:"186791",title:"Dr.",name:"Archana",middleName:null,surname:"Tiwari",slug:"archana-tiwari",fullName:"Archana Tiwari",profilePictureURL:"https://mts.intechopen.com/storage/users/186791/images/system/186791.jpg",biography:"Dr. Archana Tiwari is Associate Professor at Amity University, India. Her research interests include renewable sources of energy from microalgae and further utilizing the residual biomass for the generation of value-added products, bioremediation through microalgae and microbial consortium, antioxidative enzymes and stress, and nutraceuticals from microalgae. She has been working on algal biotechnology for the last two decades. She has published her research in many international journals and has authored many books and chapters with renowned publishing houses. She has also delivered talks as an invited speaker at many national and international conferences. Dr. Tiwari is the recipient of several awards including Researcher of the Year and Distinguished Scientist.",institutionString:"Amity University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Amity University",institutionURL:null,country:{name:"India"}}},equalEditorTwo:{id:"197609",title:"Prof.",name:"Taha Selim",middleName:null,surname:"Ustun",slug:"taha-selim-ustun",fullName:"Taha Selim Ustun",profilePictureURL:"https://mts.intechopen.com/storage/users/197609/images/system/197609.jpeg",biography:"Dr. Taha Selim Ustun received a Ph.D. in Electrical Engineering from Victoria University, Melbourne, Australia. He is a researcher with the Fukushima Renewable Energy Institute, AIST (FREA), where he leads the Smart Grid Cybersecurity Laboratory. Prior to that, he was a faculty member with the School of Electrical and Computer Engineering, Carnegie Mellon University, Pittsburgh, PA, USA. His current research interests include power systems protection, communication in power networks, distributed generation, microgrids, electric vehicle integration, and cybersecurity in smart grids. He serves on the editorial boards of IEEE Access, IEEE Transactions on Industrial Informatics, Energies, Electronics, Electricity, World Electric Vehicle and Information journals. Dr. Ustun is a member of the IEEE 2004 and 2800, IEC Renewable Energy Management WG 8, and IEC TC 57 WG17. He has been invited to run specialist courses in Africa, India, and China. He has delivered talks for the Qatar Foundation, the World Energy Council, the Waterloo Global Science Initiative, and the European Union Energy Initiative (EUEI). His research has attracted funding from prestigious programs in Japan, Australia, the European Union, and North America.",institutionString:"Fukushima Renewable Energy Institute, AIST (FREA)",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Institute of Advanced Industrial Science and Technology",institutionURL:null,country:{name:"Japan"}}},equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8985",title:"Natural Resources Management and Biological Sciences",subtitle:null,isOpenForSubmission:!1,hash:"5c2e219a6c021a40b5a20c041dea88c4",slug:"natural-resources-management-and-biological-sciences",bookSignature:"Edward R. Rhodes and Humood Naser",coverURL:"https://cdn.intechopen.com/books/images_new/8985.jpg",editors:[{id:"280886",title:"Prof.",name:"Edward R",middleName:null,surname:"Rhodes",slug:"edward-r-rhodes",fullName:"Edward R Rhodes"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9027",title:"Human Blood Group Systems and Haemoglobinopathies",subtitle:null,isOpenForSubmission:!1,hash:"d00d8e40b11cfb2547d1122866531c7e",slug:"human-blood-group-systems-and-haemoglobinopathies",bookSignature:"Osaro Erhabor and Anjana Munshi",coverURL:"https://cdn.intechopen.com/books/images_new/9027.jpg",editors:[{id:"35140",title:null,name:"Osaro",middleName:null,surname:"Erhabor",slug:"osaro-erhabor",fullName:"Osaro Erhabor"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7841",title:"New Insights Into Metabolic Syndrome",subtitle:null,isOpenForSubmission:!1,hash:"ef5accfac9772b9e2c9eff884f085510",slug:"new-insights-into-metabolic-syndrome",bookSignature:"Akikazu Takada",coverURL:"https://cdn.intechopen.com/books/images_new/7841.jpg",editors:[{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8558",title:"Aerodynamics",subtitle:null,isOpenForSubmission:!1,hash:"db7263fc198dfb539073ba0260a7f1aa",slug:"aerodynamics",bookSignature:"Mofid Gorji-Bandpy and Aly-Mousaad Aly",coverURL:"https://cdn.intechopen.com/books/images_new/8558.jpg",editors:[{id:"35542",title:"Prof.",name:"Mofid",middleName:null,surname:"Gorji-Bandpy",slug:"mofid-gorji-bandpy",fullName:"Mofid Gorji-Bandpy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9668",title:"Chemistry and Biochemistry of Winemaking, Wine Stabilization and Aging",subtitle:null,isOpenForSubmission:!1,hash:"c5484276a314628acf21ec1bdc3a86b9",slug:"chemistry-and-biochemistry-of-winemaking-wine-stabilization-and-aging",bookSignature:"Fernanda Cosme, Fernando M. Nunes and Luís Filipe-Ribeiro",coverURL:"https://cdn.intechopen.com/books/images_new/9668.jpg",editors:[{id:"186819",title:"Prof.",name:"Fernanda",middleName:null,surname:"Cosme",slug:"fernanda-cosme",fullName:"Fernanda Cosme"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7847",title:"Medical Toxicology",subtitle:null,isOpenForSubmission:!1,hash:"db9b65bea093de17a0855a1b27046247",slug:"medical-toxicology",bookSignature:"Pınar Erkekoglu and Tomohisa Ogawa",coverURL:"https://cdn.intechopen.com/books/images_new/7847.jpg",editors:[{id:"109978",title:"Prof.",name:"Pınar",middleName:null,surname:"Erkekoglu",slug:"pinar-erkekoglu",fullName:"Pınar Erkekoglu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8620",title:"Mining Techniques",subtitle:"Past, Present and Future",isOpenForSubmission:!1,hash:"b65658f81d14e9e57e49377869d3a575",slug:"mining-techniques-past-present-and-future",bookSignature:"Abhay Soni",coverURL:"https://cdn.intechopen.com/books/images_new/8620.jpg",editors:[{id:"271093",title:"Dr.",name:"Abhay",middleName:null,surname:"Soni",slug:"abhay-soni",fullName:"Abhay Soni"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9660",title:"Inland Waters",subtitle:"Dynamics and Ecology",isOpenForSubmission:!1,hash:"975c26819ceb11a926793bc2adc62bd6",slug:"inland-waters-dynamics-and-ecology",bookSignature:"Adam Devlin, Jiayi Pan and Mohammad Manjur Shah",coverURL:"https://cdn.intechopen.com/books/images_new/9660.jpg",editors:[{id:"280757",title:"Dr.",name:"Adam",middleName:"Thomas",surname:"Devlin",slug:"adam-devlin",fullName:"Adam Devlin"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9122",title:"Cosmetic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"207026ca4a4125e17038e770d00ee152",slug:"cosmetic-surgery",bookSignature:"Yueh-Bih Tang",coverURL:"https://cdn.intechopen.com/books/images_new/9122.jpg",editors:[{id:"202122",title:"Prof.",name:"Yueh-Bih",middleName:null,surname:"Tang",slug:"yueh-bih-tang",fullName:"Yueh-Bih Tang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"9550",title:"Entrepreneurship",subtitle:"Contemporary Issues",isOpenForSubmission:!1,hash:"9b4ac1ee5b743abf6f88495452b1e5e7",slug:"entrepreneurship-contemporary-issues",bookSignature:"Mladen Turuk",coverURL:"https://cdn.intechopen.com/books/images_new/9550.jpg",editedByType:"Edited by",editors:[{id:"319755",title:"Prof.",name:"Mladen",middleName:null,surname:"Turuk",slug:"mladen-turuk",fullName:"Mladen Turuk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10065",title:"Wavelet Theory",subtitle:null,isOpenForSubmission:!1,hash:"d8868e332169597ba2182d9b004d60de",slug:"wavelet-theory",bookSignature:"Somayeh Mohammady",coverURL:"https://cdn.intechopen.com/books/images_new/10065.jpg",editedByType:"Edited by",editors:[{id:"109280",title:"Dr.",name:"Somayeh",middleName:null,surname:"Mohammady",slug:"somayeh-mohammady",fullName:"Somayeh Mohammady"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9313",title:"Clay Science and Technology",subtitle:null,isOpenForSubmission:!1,hash:"6fa7e70396ff10620e032bb6cfa6fb72",slug:"clay-science-and-technology",bookSignature:"Gustavo Morari Do Nascimento",coverURL:"https://cdn.intechopen.com/books/images_new/9313.jpg",editedByType:"Edited by",editors:[{id:"7153",title:"Prof.",name:"Gustavo",middleName:null,surname:"Morari Do Nascimento",slug:"gustavo-morari-do-nascimento",fullName:"Gustavo Morari Do Nascimento"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9888",title:"Nuclear Power Plants",subtitle:"The Processes from the Cradle to the Grave",isOpenForSubmission:!1,hash:"c2c8773e586f62155ab8221ebb72a849",slug:"nuclear-power-plants-the-processes-from-the-cradle-to-the-grave",bookSignature:"Nasser Awwad",coverURL:"https://cdn.intechopen.com/books/images_new/9888.jpg",editedByType:"Edited by",editors:[{id:"145209",title:"Prof.",name:"Nasser",middleName:"S",surname:"Awwad",slug:"nasser-awwad",fullName:"Nasser Awwad"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8098",title:"Resources of Water",subtitle:null,isOpenForSubmission:!1,hash:"d251652996624d932ef7b8ed62cf7cfc",slug:"resources-of-water",bookSignature:"Prathna Thanjavur Chandrasekaran, Muhammad Salik Javaid, Aftab Sadiq",coverURL:"https://cdn.intechopen.com/books/images_new/8098.jpg",editedByType:"Edited by",editors:[{id:"167917",title:"Dr.",name:"Prathna",middleName:null,surname:"Thanjavur Chandrasekaran",slug:"prathna-thanjavur-chandrasekaran",fullName:"Prathna Thanjavur Chandrasekaran"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9644",title:"Glaciers and the Polar Environment",subtitle:null,isOpenForSubmission:!1,hash:"e8cfdc161794e3753ced54e6ff30873b",slug:"glaciers-and-the-polar-environment",bookSignature:"Masaki Kanao, Danilo Godone and Niccolò Dematteis",coverURL:"https://cdn.intechopen.com/books/images_new/9644.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10432",title:"Casting Processes and Modelling of Metallic Materials",subtitle:null,isOpenForSubmission:!1,hash:"2c5c9df938666bf5d1797727db203a6d",slug:"casting-processes-and-modelling-of-metallic-materials",bookSignature:"Zakaria Abdallah and Nada Aldoumani",coverURL:"https://cdn.intechopen.com/books/images_new/10432.jpg",editedByType:"Edited by",editors:[{id:"201670",title:"Dr.",name:"Zak",middleName:null,surname:"Abdallah",slug:"zak-abdallah",fullName:"Zak Abdallah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9671",title:"Macrophages",subtitle:null,isOpenForSubmission:!1,hash:"03b00fdc5f24b71d1ecdfd75076bfde6",slug:"macrophages",bookSignature:"Hridayesh Prakash",coverURL:"https://cdn.intechopen.com/books/images_new/9671.jpg",editedByType:"Edited by",editors:[{id:"287184",title:"Dr.",name:"Hridayesh",middleName:null,surname:"Prakash",slug:"hridayesh-prakash",fullName:"Hridayesh Prakash"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8415",title:"Extremophilic Microbes and Metabolites",subtitle:"Diversity, Bioprospecting and Biotechnological Applications",isOpenForSubmission:!1,hash:"93e0321bc93b89ff73730157738f8f97",slug:"extremophilic-microbes-and-metabolites-diversity-bioprospecting-and-biotechnological-applications",bookSignature:"Afef Najjari, Ameur Cherif, Haïtham Sghaier and Hadda Imene Ouzari",coverURL:"https://cdn.intechopen.com/books/images_new/8415.jpg",editedByType:"Edited by",editors:[{id:"196823",title:"Dr.",name:"Afef",middleName:null,surname:"Najjari",slug:"afef-najjari",fullName:"Afef Najjari"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9731",title:"Oxidoreductase",subtitle:null,isOpenForSubmission:!1,hash:"852e6f862c85fc3adecdbaf822e64e6e",slug:"oxidoreductase",bookSignature:"Mahmoud Ahmed Mansour",coverURL:"https://cdn.intechopen.com/books/images_new/9731.jpg",editedByType:"Edited by",editors:[{id:"224662",title:"Prof.",name:"Mahmoud Ahmed",middleName:null,surname:"Mansour",slug:"mahmoud-ahmed-mansour",fullName:"Mahmoud Ahmed Mansour"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"112",title:"Biomedical Engineering",slug:"engineering-biomedical-engineering",parent:{title:"Engineering",slug:"engineering"},numberOfBooks:63,numberOfAuthorsAndEditors:1947,numberOfWosCitations:3297,numberOfCrossrefCitations:1685,numberOfDimensionsCitations:4225,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"engineering-biomedical-engineering",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10107",title:"Artificial Intelligence in Oncology Drug Discovery and Development",subtitle:null,isOpenForSubmission:!1,hash:"043c178c3668865ab7d35dcb2ceea794",slug:"artificial-intelligence-in-oncology-drug-discovery-and-development",bookSignature:"John W. Cassidy and Belle Taylor",coverURL:"https://cdn.intechopen.com/books/images_new/10107.jpg",editedByType:"Edited by",editors:[{id:"244455",title:"Dr.",name:"John",middleName:null,surname:"Cassidy",slug:"john-cassidy",fullName:"John Cassidy"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9575",title:"Recent Advances in Biomechanics",subtitle:null,isOpenForSubmission:!1,hash:"97edc53b612c683e4c79a995a9f379c0",slug:"recent-advances-in-biomechanics",bookSignature:"Redha Taiar",coverURL:"https://cdn.intechopen.com/books/images_new/9575.jpg",editedByType:"Edited by",editors:[{id:"81693",title:"Prof.",name:"Redha",middleName:null,surname:"Taiar",slug:"redha-taiar",fullName:"Redha Taiar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9236",title:"Cheminformatics and its Applications",subtitle:null,isOpenForSubmission:!1,hash:"3fed97d1719b8a321190c86985494a34",slug:"cheminformatics-and-its-applications",bookSignature:"Amalia Stefaniu, Azhar Rasul and Ghulam Hussain",coverURL:"https://cdn.intechopen.com/books/images_new/9236.jpg",editedByType:"Edited by",editors:[{id:"213696",title:"Dr.",name:"Amalia",middleName:null,surname:"Stefaniu",slug:"amalia-stefaniu",fullName:"Amalia Stefaniu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8569",title:"Intraocular Lens",subtitle:null,isOpenForSubmission:!1,hash:"2c184a80e647c0e74df5bc34318a2d8b",slug:"intraocular-lens",bookSignature:"Xiaogang Wang and Felicia M. Ferreri",coverURL:"https://cdn.intechopen.com/books/images_new/8569.jpg",editedByType:"Edited by",editors:[{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7945",title:"Cryopreservation",subtitle:"Current Advances and Evaluations",isOpenForSubmission:!1,hash:"0fe037813f921f4136cd393b7ff8dfe1",slug:"cryopreservation-current-advances-and-evaluations",bookSignature:"Marian Quain",coverURL:"https://cdn.intechopen.com/books/images_new/7945.jpg",editedByType:"Edited by",editors:[{id:"72151",title:"Dr.",name:"Marian",middleName:"Dorcas",surname:"Quain",slug:"marian-quain",fullName:"Marian Quain"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7439",title:"Photoacoustic Imaging",subtitle:"Principles, Advances and Applications",isOpenForSubmission:!1,hash:"05982e7eb4c7f3f165306f9b136a8ae4",slug:"photoacoustic-imaging-principles-advances-and-applications",bookSignature:"Reda R. Gharieb",coverURL:"https://cdn.intechopen.com/books/images_new/7439.jpg",editedByType:"Edited by",editors:[{id:"225387",title:"Prof.",name:"Reda",middleName:null,surname:"Gharieb",slug:"reda-gharieb",fullName:"Reda Gharieb"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6835",title:"Computer Methods and Programs in Biomedical Signal and Image Processing",subtitle:null,isOpenForSubmission:!1,hash:"19f08ef15d97900c94dc8fb04f9afb5f",slug:"computer-methods-and-programs-in-biomedical-signal-and-image-processing",bookSignature:"Lulu Wang",coverURL:"https://cdn.intechopen.com/books/images_new/6835.jpg",editedByType:"Edited by",editors:[{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7869",title:"Advanced Endoscopy",subtitle:null,isOpenForSubmission:!1,hash:"92f6ce51b737e9086a6059ab7470eee9",slug:"advanced-endoscopy",bookSignature:"Qiang Yan and Xu Sun",coverURL:"https://cdn.intechopen.com/books/images_new/7869.jpg",editedByType:"Edited by",editors:[{id:"247970",title:"Prof.",name:"Qiang",middleName:null,surname:"Yan",slug:"qiang-yan",fullName:"Qiang Yan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8691",title:"Ultrasound Elastography",subtitle:null,isOpenForSubmission:!1,hash:"fdbf5197352ca0294bfc963ef83d1e00",slug:"ultrasound-elastography",bookSignature:"Monica Lupsor-Platon",coverURL:"https://cdn.intechopen.com/books/images_new/8691.jpg",editedByType:"Edited by",editors:[{id:"208594",title:"Associate Prof.",name:"Monica",middleName:null,surname:"Lupsor-Platon",slug:"monica-lupsor-platon",fullName:"Monica Lupsor-Platon"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7728",title:"Synthetic Biology",subtitle:"New Interdisciplinary Science",isOpenForSubmission:!1,hash:"cc50b31cb749d94a5aa38999a712ae2f",slug:"synthetic-biology-new-interdisciplinary-science",bookSignature:"Madan L. Nagpal, Oana-Maria Boldura, Cornel Baltă and Shymaa Enany",coverURL:"https://cdn.intechopen.com/books/images_new/7728.jpg",editedByType:"Edited by",editors:[{id:"182681",title:"Dr.",name:"Madan L.",middleName:null,surname:"Nagpal",slug:"madan-l.-nagpal",fullName:"Madan L. Nagpal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8125",title:"Medical Imaging",subtitle:"Principles and Applications",isOpenForSubmission:!1,hash:"e0fa3875d6f66d5ccd8cd3f1444c3fb9",slug:"medical-imaging-principles-and-applications",bookSignature:"Yongxia Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/8125.jpg",editedByType:"Edited by",editors:[{id:"259308",title:"Dr.",name:"Yongxia",middleName:null,surname:"Zhou",slug:"yongxia-zhou",fullName:"Yongxia Zhou"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6875",title:"Bio-Inspired Technology",subtitle:null,isOpenForSubmission:!1,hash:"074fba986c7ba872f1af99c4fb65337e",slug:"bio-inspired-technology",bookSignature:"Ruby Srivastava",coverURL:"https://cdn.intechopen.com/books/images_new/6875.jpg",editedByType:"Edited by",editors:[{id:"185788",title:"Dr.",name:"Ruby",middleName:null,surname:"Srivastava",slug:"ruby-srivastava",fullName:"Ruby Srivastava"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:63,mostCitedChapters:[{id:"17237",doi:"10.5772/24553",title:"Hydrogels: Methods of Preparation, Characterisation and Applications",slug:"hydrogels-methods-of-preparation-characterisation-and-applications",totalDownloads:64259,totalCrossrefCites:61,totalDimensionsCites:210,book:{slug:"progress-in-molecular-and-environmental-bioengineering-from-analysis-and-modeling-to-technology-applications",title:"Progress in Molecular and Environmental Bioengineering",fullTitle:"Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications"},signatures:"Syed K. H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]},{id:"26368",doi:"10.5772/23927",title:"Poly(Lactic Acid)-Based Biomaterials: Synthesis, Modification and Applications",slug:"poly-lactic-acid-based-biomaterials-synthesis-modification-and-applications",totalDownloads:35069,totalCrossrefCites:54,totalDimensionsCites:128,book:{slug:"biomedical-science-engineering-and-technology",title:"Biomedical Science, Engineering and Technology",fullTitle:"Biomedical Science, Engineering and Technology"},signatures:"Lin Xiao, Bo Wang, Guang Yang and Mario Gauthier",authors:[{id:"52500",title:"Prof.",name:"Guang",middleName:null,surname:"Yang",slug:"guang-yang",fullName:"Guang Yang"}]},{id:"18658",doi:"10.5772/19033",title:"Metals for Biomedical Applications",slug:"metals-for-biomedical-applications",totalDownloads:47348,totalCrossrefCites:63,totalDimensionsCites:119,book:{slug:"biomedical-engineering-from-theory-to-applications",title:"Biomedical Engineering",fullTitle:"Biomedical Engineering - From Theory to Applications"},signatures:"Hendra Hermawan, Dadan Ramdan and Joy R. P. Djuansjah",authors:[{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan"},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah"},{id:"61582",title:"Dr.",name:"Dadan",middleName:null,surname:"Ramdan",slug:"dadan-ramdan",fullName:"Dadan Ramdan"}]}],mostDownloadedChaptersLast30Days:[{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:5746,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"10042",title:"Superhydrophobicity, Learn from the Lotus Leaf",slug:"superhydrophobicity-learn-from-the-lotus-leaf",totalDownloads:16768,totalCrossrefCites:3,totalDimensionsCites:10,book:{slug:"biomimetics-learning-from-nature",title:"Biomimetics",fullTitle:"Biomimetics Learning from Nature"},signatures:"Mengnan Qu, Jinmei He and Junyan Zhang",authors:null},{id:"67331",title:"Research in Medical Imaging Using Image Processing Techniques",slug:"research-in-medical-imaging-using-image-processing-techniques",totalDownloads:2424,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"medical-imaging-principles-and-applications",title:"Medical Imaging",fullTitle:"Medical Imaging - Principles and Applications"},signatures:"Yousif Mohamed Y. Abdallah and Tariq Alqahtani",authors:[{id:"274452",title:"Dr.",name:"Yousif Mohamed Y.",middleName:"Mohamed Yousif",surname:"Abdallah",slug:"yousif-mohamed-y.-abdallah",fullName:"Yousif Mohamed Y. Abdallah"},{id:"294009",title:"Dr.",name:"Tariq",middleName:null,surname:"Alqahtani",slug:"tariq-alqahtani",fullName:"Tariq Alqahtani"}]},{id:"48226",title:"Biomedical Sensor, Device and Measurement Systems",slug:"biomedical-sensor-device-and-measurement-systems",totalDownloads:5399,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"advances-in-bioengineering",title:"Advances in Bioengineering",fullTitle:"Advances in Bioengineering"},signatures:"Gaofeng Zhou, Yannian Wang and Lujun Cui",authors:[{id:"37425",title:"Dr.",name:"Gaofeng",middleName:null,surname:"Zhou",slug:"gaofeng-zhou",fullName:"Gaofeng Zhou"}]},{id:"17237",title:"Hydrogels: Methods of Preparation, Characterisation and Applications",slug:"hydrogels-methods-of-preparation-characterisation-and-applications",totalDownloads:64249,totalCrossrefCites:61,totalDimensionsCites:210,book:{slug:"progress-in-molecular-and-environmental-bioengineering-from-analysis-and-modeling-to-technology-applications",title:"Progress in Molecular and Environmental Bioengineering",fullTitle:"Progress in Molecular and Environmental Bioengineering - From Analysis and Modeling to Technology Applications"},signatures:"Syed K. H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]},{id:"59741",title:"Active Contour Based Segmentation Techniques for Medical Image Analysis",slug:"active-contour-based-segmentation-techniques-for-medical-image-analysis",totalDownloads:2480,totalCrossrefCites:10,totalDimensionsCites:18,book:{slug:"medical-and-biological-image-analysis",title:"Medical and Biological Image Analysis",fullTitle:"Medical and Biological Image Analysis"},signatures:"R.J. Hemalatha, T.R. Thamizhvani, A. Josephin Arockia Dhivya,\nJosline Elsa Joseph, Bincy Babu and R. Chandrasekaran",authors:[{id:"238868",title:"Prof.",name:"Hemalatha",middleName:null,surname:"R.J",slug:"hemalatha-r.j",fullName:"Hemalatha R.J"},{id:"242385",title:"Dr.",name:"Chandrasekaran",middleName:null,surname:"R",slug:"chandrasekaran-r",fullName:"Chandrasekaran R"},{id:"242386",title:"Ms.",name:"Thamizhvani",middleName:null,surname:"T.R",slug:"thamizhvani-t.r",fullName:"Thamizhvani T.R"},{id:"242388",title:"Dr.",name:"Josephin Arockia Dhivya",middleName:null,surname:"A",slug:"josephin-arockia-dhivya-a",fullName:"Josephin Arockia Dhivya A"},{id:"242389",title:"Ms.",name:"Josline Elsa",middleName:null,surname:"Joseph",slug:"josline-elsa-joseph",fullName:"Josline Elsa Joseph"},{id:"242390",title:"Ms.",name:"Bincy",middleName:null,surname:"Babu",slug:"bincy-babu",fullName:"Bincy Babu"}]},{id:"18658",title:"Metals for Biomedical Applications",slug:"metals-for-biomedical-applications",totalDownloads:47343,totalCrossrefCites:63,totalDimensionsCites:119,book:{slug:"biomedical-engineering-from-theory-to-applications",title:"Biomedical Engineering",fullTitle:"Biomedical Engineering - From Theory to Applications"},signatures:"Hendra Hermawan, Dadan Ramdan and Joy R. P. Djuansjah",authors:[{id:"33351",title:null,name:"Hendra",middleName:null,surname:"Hermawan",slug:"hendra-hermawan",fullName:"Hendra Hermawan"},{id:"61581",title:"Dr.",name:"Joy Rizki Pangestu",middleName:null,surname:"Djuansjah",slug:"joy-rizki-pangestu-djuansjah",fullName:"Joy Rizki Pangestu Djuansjah"},{id:"61582",title:"Dr.",name:"Dadan",middleName:null,surname:"Ramdan",slug:"dadan-ramdan",fullName:"Dadan Ramdan"}]},{id:"63949",title:"A Survey on 3D Ultrasound Reconstruction Techniques",slug:"a-survey-on-3d-ultrasound-reconstruction-techniques",totalDownloads:1165,totalCrossrefCites:2,totalDimensionsCites:3,book:{slug:"artificial-intelligence-applications-in-medicine-and-biology",title:"Artificial Intelligence",fullTitle:"Artificial Intelligence - Applications in Medicine and Biology"},signatures:"Farhan Mohamed and Chan Vei Siang",authors:null},{id:"9927",title:"Digitizing Literacy: Reflections on the Haptics of Writing",slug:"digitizing-literacy-reflections-on-the-haptics-of-writing",totalDownloads:10143,totalCrossrefCites:39,totalDimensionsCites:91,book:{slug:"advances-in-haptics",title:"Advances in Haptics",fullTitle:"Advances in Haptics"},signatures:"Anne Mangen and Jean-Luc Velay",authors:null},{id:"43462",title:"Current Applications of Optical Coherence Tomography in Ophthalmology",slug:"current-applications-of-optical-coherence-tomography-in-ophthalmology",totalDownloads:3266,totalCrossrefCites:2,totalDimensionsCites:4,book:{slug:"optical-coherence-tomography",title:"Optical Coherence Tomography",fullTitle:"Optical Coherence Tomography"},signatures:"Nadia Al Kharousi, Upender K. Wali and Sitara Azeem",authors:[{id:"130480",title:"Dr.",name:"Nadiya",middleName:null,surname:"Al Kharousi",slug:"nadiya-al-kharousi",fullName:"Nadiya Al Kharousi"}]}],onlineFirstChaptersFilter:{topicSlug:"engineering-biomedical-engineering",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/135437/daniel-machado",hash:"",query:{},params:{id:"135437",slug:"daniel-machado"},fullPath:"/profiles/135437/daniel-machado",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()