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IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
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\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
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\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"72",leadTitle:null,fullTitle:"Ionic Liquids: Theory, Properties, New Approaches",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",reviewType:"peer-reviewed",abstract:"Ionic Liquids (ILs) are one of the most interesting and rapidly developing areas of modern physical chemistry, technologies and engineering. This book, consisting of 29 chapters gathered in 4 sections, reviews in detail and compiles information about some important physical-chemical properties of ILs and new practical approaches. This is the first book of a series of forthcoming publications on this field by this publisher. The first volume covers some aspects of synthesis, isolation, production, modification, the analysis methods and modeling to reveal the structures and properties of some room temperature ILs, as well as their new possible applications. The book will be of help to chemists, physicists, biologists, technologists and other experts in a variety of disciplines, both academic and industrial, as well as to students and PhD students. It may help to promote the progress in ILs development also.",isbn:null,printIsbn:"978-953-307-349-1",pdfIsbn:"978-953-51-4517-2",doi:"10.5772/603",price:159,priceEur:175,priceUsd:205,slug:"ionic-liquids-theory-properties-new-approaches",numberOfPages:750,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",bookSignature:"Alexander Kokorin",publishedDate:"February 28th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",numberOfDownloads:157214,numberOfWosCitations:488,numberOfCrossrefCitations:109,numberOfCrossrefCitationsByBook:56,numberOfDimensionsCitations:325,numberOfDimensionsCitationsByBook:91,hasAltmetrics:1,numberOfTotalCitations:922,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 12th 2010",dateEndSecondStepPublish:"June 9th 2010",dateEndThirdStepPublish:"September 14th 2010",dateEndFourthStepPublish:"November 13th 2010",dateEndFifthStepPublish:"January 27th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Semenov Institute of Chemical Physics",institutionURL:null,country:{name:"Russia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"935",title:"Fluid Dynamics",slug:"materials-science-fluid-mechanics-fluid-dynamics"}],chapters:[{id:"13911",title:"Thermodynamic Properties of Ionic Liquids - Measurements and Predictions -",doi:"10.5772/15222",slug:"thermodynamic-properties-of-ionic-liquids-measurements-and-predictions-",totalDownloads:8042,totalCrossrefCites:4,totalDimensionsCites:7,hasAltmetrics:0,abstract:null,signatures:"Zhi-Cheng Tan, Urs Welz-Biermann, Pei-Fang Yan, Qing-Shan Liu and Da-Wei Fang",downloadPdfUrl:"/chapter/pdf-download/13911",previewPdfUrl:"/chapter/pdf-preview/13911",authors:[{id:"20011",title:"Prof.",name:"Zhi-Cheng",surname:"Tan",slug:"zhi-cheng-tan",fullName:"Zhi-Cheng Tan"},{id:"20825",title:"Prof.",name:"Urs",surname:"Welz-Biermann",slug:"urs-welz-biermann",fullName:"Urs Welz-Biermann"},{id:"20826",title:"Prof.",name:"Pei-Fang",surname:"Yan",slug:"pei-fang-yan",fullName:"Pei-Fang Yan"},{id:"20827",title:"Dr.",name:"Qing-Shan",surname:"Liu",slug:"qing-shan-liu",fullName:"Qing-Shan Liu"},{id:"20828",title:"Prof.",name:"Da-Wei",surname:"Fang",slug:"da-wei-fang",fullName:"Da-Wei Fang"}],corrections:null},{id:"13912",title:"Thermal Properties of Ionic Liquids and Ionanofluids",doi:"10.5772/13920",slug:"thermal-properties-of-ionic-liquids-and-ionanofluids",totalDownloads:8839,totalCrossrefCites:10,totalDimensionsCites:23,hasAltmetrics:0,abstract:null,signatures:"A.P.C. 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He obtained his MS and Ph.D. from Louisiana State University, USA. His research focuses on system-level design for power optimization. His area of research encompasses different fields such as very-large-scale integration (VLSI), mixed-signal circuits/system development, the Internet of Things (IoT), and sensors. He published a book in the area of mixed-signal design and edited two books on carbon nanotubes and one book on micro-electro-mechanical system (MEMS) sensors. Dr. Yellampalli has also published more than 100 international journal papers and Institute of Electrical and Electronics Engineers (IEEE) conference papers. He has also delivered keynote speeches at international conferences in Canada, Dubai, and Spain including tutorials at various IEEE International conferences. He has been a consultant to various semiconductor companies.",institutionString:"SRM University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"SRM University",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"761",title:"Wireless Communication Network",slug:"electrical-and-electronic-engineering-wireless-communication-network"}],chapters:[{id:"76818",title:"Wireless Sensor Networks: Applications",slug:"wireless-sensor-networks-applications",totalDownloads:397,totalCrossrefCites:0,authors:[{id:"321152",title:"Prof.",name:"Bhargavi",surname:"Dalal",slug:"bhargavi-dalal",fullName:"Bhargavi Dalal"},{id:"331082",title:"Dr.",name:"Sampada",surname:"Kukarni",slug:"sampada-kukarni",fullName:"Sampada Kukarni"}]},{id:"73287",title:"Wireless Sensor Networks: Applications and Challenges",slug:"wireless-sensor-networks-applications-and-challenges",totalDownloads:742,totalCrossrefCites:2,authors:[{id:"322695",title:"Dr.",name:"Kingsley Eghonghon",surname:"Ukhurebor",slug:"kingsley-eghonghon-ukhurebor",fullName:"Kingsley Eghonghon Ukhurebor"},{id:"327049",title:"Dr.",name:"Ituabhor",surname:"Odesanya",slug:"ituabhor-odesanya",fullName:"Ituabhor Odesanya"},{id:"327050",title:"MSc.",name:"Silas Soo",surname:"Tyokighir",slug:"silas-soo-tyokighir",fullName:"Silas Soo Tyokighir"},{id:"327373",title:"Mr.",name:"Rout George",surname:"Kerry",slug:"rout-george-kerry",fullName:"Rout George Kerry"},{id:"327898",title:"Dr.",name:"Akinola Samson",surname:"Olayinka",slug:"akinola-samson-olayinka",fullName:"Akinola Samson Olayinka"},{id:"328545",title:"Dr.",name:"Ayodotun Oluwafemi",surname:"Bobadoye",slug:"ayodotun-oluwafemi-bobadoye",fullName:"Ayodotun Oluwafemi Bobadoye"}]},{id:"73741",title:"Design Model and Deployment Fashion of Wireless Sensor Networks",slug:"design-model-and-deployment-fashion-of-wireless-sensor-networks",totalDownloads:289,totalCrossrefCites:0,authors:[{id:"321533",title:"Ph.D.",name:"Sana",surname:"Akourmis",slug:"sana-akourmis",fullName:"Sana Akourmis"},{id:"328367",title:"Prof.",name:"Youssef",surname:"Fakhri",slug:"youssef-fakhri",fullName:"Youssef Fakhri"},{id:"328682",title:"Prof.",name:"Moulay Driss",surname:"Rahmani",slug:"moulay-driss-rahmani",fullName:"Moulay Driss Rahmani"}]},{id:"75056",title:"An Algorithmic Approach to the Node Selection Problem in Industrial Wireless Sensor Networks",slug:"an-algorithmic-approach-to-the-node-selection-problem-in-industrial-wireless-sensor-networks",totalDownloads:222,totalCrossrefCites:0,authors:[{id:"321148",title:"Dr.",name:"Veeramani",surname:"Sonai",slug:"veeramani-sonai",fullName:"Veeramani Sonai"},{id:"321150",title:"Ms.",name:"Indira",surname:"Bharathi",slug:"indira-bharathi",fullName:"Indira Bharathi"}]},{id:"73531",title:"Data Aggregation Scheme Using Multiple Mobile Agents in Wireless Sensor Network",slug:"data-aggregation-scheme-using-multiple-mobile-agents-in-wireless-sensor-network",totalDownloads:144,totalCrossrefCites:1,authors:[{id:"322462",title:"Ph.D.",name:"Mohamed",surname:"Younis Mohamed Alzarroug",slug:"mohamed-younis-mohamed-alzarroug",fullName:"Mohamed Younis Mohamed Alzarroug"},{id:"322468",title:"Prof.",name:"Wilson",surname:"Jeberson",slug:"wilson-jeberson",fullName:"Wilson Jeberson"}]},{id:"73535",title:"Data Collection Protocols in Wireless Sensor Networks",slug:"data-collection-protocols-in-wireless-sensor-networks",totalDownloads:382,totalCrossrefCites:2,authors:[{id:"321991",title:"Dr.",name:"Koppala",surname:"Guravaiah",slug:"koppala-guravaiah",fullName:"Koppala Guravaiah"},{id:"326404",title:"Dr.",name:"Rengaraj Leela",surname:"Velusamy",slug:"rengaraj-leela-velusamy",fullName:"Rengaraj Leela Velusamy"},{id:"326405",title:"Mrs.",name:"Kavitha",surname:"A.",slug:"kavitha-a.",fullName:"Kavitha A."}]},{id:"73540",title:"WSN for Event Detection Applications: Deployment, Routing, and Data Mapping Using AI",slug:"wsn-for-event-detection-applications-deployment-routing-and-data-mapping-using-ai",totalDownloads:186,totalCrossrefCites:0,authors:[{id:"326862",title:"Ph.D.",name:"Mohamed Hechmi",surname:"Jeridi",slug:"mohamed-hechmi-jeridi",fullName:"Mohamed Hechmi Jeridi"},{id:"329952",title:"Ph.D.",name:"Kamel",surname:"Abbassi",slug:"kamel-abbassi",fullName:"Kamel Abbassi"},{id:"331709",title:"Dr.",name:"Tahar",surname:"Ezzedine",slug:"tahar-ezzedine",fullName:"Tahar Ezzedine"}]},{id:"73250",title:"Swarm Intelligence-Based Bio-Inspired Framework for Wireless Sensor Networks",slug:"swarm-intelligence-based-bio-inspired-framework-for-wireless-sensor-networks",totalDownloads:378,totalCrossrefCites:0,authors:[{id:"142338",title:"Dr.",name:"Abdul Rahim",surname:"Naseer",slug:"abdul-rahim-naseer",fullName:"Abdul Rahim Naseer"},{id:"329249",title:"Dr.",name:"V.",surname:"Neelima",slug:"v.-neelima",fullName:"V. 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Narsimha"}]},{id:"74777",title:"Energy Saving Hierarchical Routing Protocol in WSN",slug:"energy-saving-hierarchical-routing-protocol-in-wsn",totalDownloads:164,totalCrossrefCites:0,authors:[{id:"321517",title:"Dr.",name:"Parvathi",surname:"C",slug:"parvathi-c",fullName:"Parvathi C"},{id:"322940",title:"Dr.",name:"Suresha",surname:"Talanki",slug:"suresha-talanki",fullName:"Suresha Talanki"}]},{id:"73191",title:"Research on Polling Control System in Wireless Sensor Networks",slug:"research-on-polling-control-system-in-wireless-sensor-networks",totalDownloads:271,totalCrossrefCites:0,authors:[{id:"322345",title:"Ph.D.",name:"Zhijun",surname:"Yang",slug:"zhijun-yang",fullName:"Zhijun Yang"},{id:"327260",title:"MSc.",name:"Lei",surname:"Mao",slug:"lei-mao",fullName:"Lei Mao"}]},{id:"73950",title:"Cross-Layer Inference in WSN: From Methods to Experimental Validation",slug:"cross-layer-inference-in-wsn-from-methods-to-experimental-validation",totalDownloads:355,totalCrossrefCites:0,authors:[{id:"321151",title:"Dr.",name:"Indrakshi",surname:"Dey",slug:"indrakshi-dey",fullName:"Indrakshi Dey"}]},{id:"74198",title:"Queries Processing in Wireless Sensor Network",slug:"queries-processing-in-wireless-sensor-network",totalDownloads:206,totalCrossrefCites:0,authors:[{id:"329952",title:"Ph.D.",name:"Kamel",surname:"Abbassi",slug:"kamel-abbassi",fullName:"Kamel Abbassi"},{id:"332253",title:"Dr.",name:"Taher",surname:"Ezzedine",slug:"taher-ezzedine",fullName:"Taher Ezzedine"}]},{id:"73173",title:"Interference Mapping in 3D for High-Density Indoor IoT Deployments",slug:"interference-mapping-in-3d-for-high-density-indoor-iot-deployments",totalDownloads:374,totalCrossrefCites:1,authors:[{id:"18206",title:"Dr.",name:"Vladimir",surname:"Poulkov",slug:"vladimir-poulkov",fullName:"Vladimir Poulkov"},{id:"322474",title:"Dr.",name:"Antoni",surname:"Ivanov",slug:"antoni-ivanov",fullName:"Antoni Ivanov"},{id:"322481",title:"Dr.",name:"Viktor",surname:"Stoynov",slug:"viktor-stoynov",fullName:"Viktor Stoynov"},{id:"328283",title:"Dr.",name:"Kliment",surname:"Angelov",slug:"kliment-angelov",fullName:"Kliment Angelov"},{id:"328284",title:"Mr.",name:"Radostin",surname:"Stefanov",slug:"radostin-stefanov",fullName:"Radostin Stefanov"},{id:"328285",title:"Dr.",name:"Dimitar",surname:"Atamyan",slug:"dimitar-atamyan",fullName:"Dimitar Atamyan"},{id:"328286",title:"Mr.",name:"Krasimir",surname:"Tonchev",slug:"krasimir-tonchev",fullName:"Krasimir Tonchev"}]},{id:"74058",title:"Applications of Prediction Approaches in Wireless Sensor Networks",slug:"applications-of-prediction-approaches-in-wireless-sensor-networks",totalDownloads:389,totalCrossrefCites:3,authors:[{id:"321798",title:"Mrs.",name:"Felicia",surname:"Engmann",slug:"felicia-engmann",fullName:"Felicia Engmann"},{id:"333585",title:"Dr.",name:"Kofi Sarpong",surname:"Adu-Manu",slug:"kofi-sarpong-adu-manu",fullName:"Kofi Sarpong Adu-Manu"},{id:"333586",title:"Prof.",name:"Ferdinand Apietu",surname:"Katsriku",slug:"ferdinand-apietu-katsriku",fullName:"Ferdinand Apietu Katsriku"},{id:"333587",title:"Dr.",name:"Jamal-Deen",surname:"Abdulai",slug:"jamal-deen-abdulai",fullName:"Jamal-Deen Abdulai"}]},{id:"73327",title:"Innovative Wearable Sensors Based on Hybrid Materials for Real-Time Breath Monitoring",slug:"innovative-wearable-sensors-based-on-hybrid-materials-for-real-time-breath-monitoring",totalDownloads:647,totalCrossrefCites:2,authors:[{id:"322542",title:"Prof.",name:"Younes",surname:"Messaddeq",slug:"younes-messaddeq",fullName:"Younes Messaddeq"},{id:"328390",title:"Ph.D.",name:"Mourad",surname:"Roudjane",slug:"mourad-roudjane",fullName:"Mourad Roudjane"}]},{id:"74888",title:"An Evolutionary Perspective for Network Centric Therapy through Wearable and Wireless Systems for Reflex, Gait, and Movement Disorder Assessment with Machine Learning",slug:"an-evolutionary-perspective-for-network-centric-therapy-through-wearable-and-wireless-systems-for-re",totalDownloads:275,totalCrossrefCites:1,authors:[{id:"2168",title:"Mr.",name:"Timothy",surname:"Mastroianni",slug:"timothy-mastroianni",fullName:"Timothy Mastroianni"},{id:"197088",title:"Dr.",name:"Robert",surname:"LeMoyne",slug:"robert-lemoyne",fullName:"Robert LeMoyne"}]},{id:"74540",title:"Challenges of WSNs in IoT",slug:"challenges-of-wsns-in-iot",totalDownloads:386,totalCrossrefCites:0,authors:[{id:"321626",title:"Mr.",name:"Brijesh",surname:"Kundaliya",slug:"brijesh-kundaliya",fullName:"Brijesh Kundaliya"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"205697",firstName:"Kristina",lastName:"Kardum Cvitan",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/205697/images/5186_n.jpg",email:"kristina.k@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:"466",title:"Carbon Nanotubes",subtitle:"Synthesis, Characterization, Applications",isOpenForSubmission:!1,hash:null,slug:"carbon-nanotubes-synthesis-characterization-applications",bookSignature:"Siva Yellampalli",coverURL:"https://cdn.intechopen.com/books/images_new/466.jpg",editedByType:"Edited by",editors:[{id:"62863",title:"Dr.",name:"Siva",surname:"Yellampalli",slug:"siva-yellampalli",fullName:"Siva Yellampalli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"467",title:"Carbon Nanotubes",subtitle:"Polymer Nanocomposites",isOpenForSubmission:!1,hash:null,slug:"carbon-nanotubes-polymer-nanocomposites",bookSignature:"Siva Yellampalli",coverURL:"https://cdn.intechopen.com/books/images_new/467.jpg",editedByType:"Edited by",editors:[{id:"62863",title:"Dr.",name:"Siva",surname:"Yellampalli",slug:"siva-yellampalli",fullName:"Siva Yellampalli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6521",title:"MEMS Sensors",subtitle:"Design and Application",isOpenForSubmission:!1,hash:"0da20f1660250a3391770069a4655cc5",slug:"mems-sensors-design-and-application",bookSignature:"Siva Yellampalli",coverURL:"https://cdn.intechopen.com/books/images_new/6521.jpg",editedByType:"Edited by",editors:[{id:"62863",title:"Dr.",name:"Siva",surname:"Yellampalli",slug:"siva-yellampalli",fullName:"Siva Yellampalli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3341",title:"Sustainable Radio Frequency Identification Solutions",subtitle:null,isOpenForSubmission:!1,hash:"2adaeecfea5c7ebc03b4bb7764c3bdd3",slug:"sustainable-radio-frequency-identification-solutions",bookSignature:"Cristina Turcu",coverURL:"https://cdn.intechopen.com/books/images_new/3341.jpg",editedByType:"Edited by",editors:[{id:"9302",title:"Dr.",name:"Cristina",surname:"Turcu",slug:"cristina-turcu",fullName:"Cristina Turcu"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"26",title:"Wireless Mesh Networks",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"wireless-mesh-networks",bookSignature:"Nobuo Funabiki",coverURL:"https://cdn.intechopen.com/books/images_new/26.jpg",editedByType:"Edited by",editors:[{id:"15698",title:"Dr.",name:"Nobuo",surname:"Funabiki",slug:"nobuo-funabiki",fullName:"Nobuo Funabiki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"15",title:"Mobile Ad-Hoc Networks",subtitle:"Protocol Design",isOpenForSubmission:!1,hash:null,slug:"mobile-ad-hoc-networks-protocol-design",bookSignature:"Xin Wang",coverURL:"https://cdn.intechopen.com/books/images_new/15.jpg",editedByType:"Edited by",editors:[{id:"13802",title:"Prof.",name:"Xin",surname:"Wang",slug:"xin-wang",fullName:"Xin Wang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5480",title:"Towards 5G Wireless Networks",subtitle:"A Physical Layer Perspective",isOpenForSubmission:!1,hash:"da8d6b0a60a9c1ad989e111fde79785c",slug:"towards-5g-wireless-networks-a-physical-layer-perspective",bookSignature:"Hossein Khaleghi Bizaki",coverURL:"https://cdn.intechopen.com/books/images_new/5480.jpg",editedByType:"Edited by",editors:[{id:"21746",title:"Dr.",name:"Hossein",surname:"Khaleghi Bizaki",slug:"hossein-khaleghi-bizaki",fullName:"Hossein Khaleghi Bizaki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"384",title:"Mobile Ad-Hoc Networks",subtitle:"Applications",isOpenForSubmission:!1,hash:null,slug:"mobile-ad-hoc-networks-applications",bookSignature:"Xin Wang",coverURL:"https://cdn.intechopen.com/books/images_new/384.jpg",editedByType:"Edited by",editors:[{id:"13802",title:"Prof.",name:"Xin",surname:"Wang",slug:"xin-wang",fullName:"Xin Wang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5914",title:"Optical Fiber and Wireless Communications",subtitle:null,isOpenForSubmission:!1,hash:"d85edb2cf7e2780dc8f029a0f4021520",slug:"optical-fiber-and-wireless-communications",bookSignature:"Rastislav Roka",coverURL:"https://cdn.intechopen.com/books/images_new/5914.jpg",editedByType:"Edited by",editors:[{id:"112777",title:"Dr.",name:"Rastislav",surname:"Róka",slug:"rastislav-roka",fullName:"Rastislav Róka"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"913",title:"Advanced Transmission Techniques in WiMAX",subtitle:null,isOpenForSubmission:!1,hash:"007b8894fe253046bab7aadc41eb6bc4",slug:"advanced-transmission-techniques-in-wimax",bookSignature:"Roberto C. Hincapie and Javier E. Sierra",coverURL:"https://cdn.intechopen.com/books/images_new/913.jpg",editedByType:"Edited by",editors:[{id:"72042",title:"Dr.",name:"Roberto",surname:"Hincapie",slug:"roberto-hincapie",fullName:"Roberto Hincapie"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"42133",title:"Prolactin and Infertility",doi:"10.5772/55557",slug:"prolactin-and-infertility",body:'Prolactin (PRL) is one of several hormones that are produced by the pituitary gland. PRL has many different roles throughout the body, and most of those are clearly shown as clinical symptom. Perhaps the most important classical role of prolactin is to stimulate milk production in women after the delivery of a baby. Prolactin levels increase during pregnancy causing the mammary glands to enlarge in preparation for breastfeeding and ready to secrete colostrums closely after delivery. Later on the elevated prolactin levels help with the sustained production of milk during nursing. The somatomammotrop cells of the anterior pituitary gland synthesize and secrete prolactin, which is under the control of hypothalamic factors, mainly the tonic inhibition of Dopamine (DA). There are several other sources of PRL-like substances in the periphery such as placental lactogens, (similar to pituitary PRL), mammary gland (produced within the mammary epithelial cells), or PRL variants of immune cell origin (that modulates the immune system). (Gellersen,1989; Andersen 1990; Lkhider, 1996; Kurtz,1993; Gala, 1994, Montgomery,1990; Ben-Jonathan 1996; Yu-Lee LY 1997)
It is important to underline that serum PRL in normal individuals is considered as almost entirely pituitary PRL sources, the above mentioned extra pituitary-PRL may contribute significant amounts but either carries as specific function and target mainly to the local environment acting via paracrine/autocrine manner. (Yu-lee 1997; Bachelot 2007)
During the first several months of breastfeeding, the higher basal prolactin levels also serve to suppress ovarian cyclicity, through the inhibition of pituitary hormones, mainly via LH suppression (Taya 1982) This is the reason why women who are breastfeeding do not get their periods and therefore do not often become pregnant. In actively breastfeeding mothers the related hyperprolactinaemia persisting even over a year. It was observed that extended lactational amenorrhea is associated with low LH levels, and interestingly suckling induced PRL elevation as a response has a positive effect on prolongation. (Diaz 1991; Diaz 1995). Menstruation and ovulation may only occasionally occur before the drop of elevated basal PRL levels. As time goes on with less frequent breastfeeding, e.g. during weaning however, the PRL levels do not stay as high and the woman may start to ovulate. In cases of nonlactating/ nonbreastfeeding mothers, that may happen between 2-3 month after delivery. (Baird 1979)
Similarly, elevated PRL levels are shown during gestation, but mechanisms to inhibit ovulation is related to elevated estardiol and progesterone levels and a consequent depression of pituitary FSH secretion (Marrs 1981).
Generally, the lactogenic hormones play role also in regulation of reproductive function. On one hand, PRL is essential to maintain regular oestrus cycles. PRL knock out mice are completely infertile (Horsemann 1997). One of the other actions of PRL is to stimulate ovarian production of progesterone. That is required in the process of preparation for embryo implantation and it is dependent on a continued estrogen and progesterone secretion by the corpus luteum, which is supported by a functional pituitary during the first half of pregnancy in rodents. (Binart 2000)
On the other hand, high prolactin levels are associated with anovulation or may cause directly or indirectly infertility. In young women, hyperprolactinemia is probably one of the most common endocrine disorders related to pituitary function. Women who are not pregnant and are not breastfeeding should have lower levels of basal PRL (typically 10–28 μg/L in women and 5–10 μg/L in men are defined as “normal levels”) If a non-pregnant woman has abnormally high levels of PRL, it may cause her difficulty in becoming pregnant. It is considered as the most frequent cause of anovulatory sterility, although spontaneous pregnancy may occur occasionally. The prevalence of hyperprolactinemia varies in different patient populations, stays below 1% (0.4% in an unselected normal population) but can be as high as 17% of women with reproductive disorders shown at the clinics (Crosignani 1999)
The suppression of pituitary hormones by PRL, similar that described during lactation has an indirect anovulatory effect. PRL however, acts also directly on the ovary to inhibit the hCG-induced follicle rupture, resulting in the inhibition of ovulation. (Yoshimura 1989).
Clinically significant elevation of PRL levels may cause infertility in several different ways. First, prolactin may stop a woman from ovulating. If this occurs, a woman’s menstrual cycles will stop. In less severe cases, high prolactin levels may only disrupt ovulation once in a while. This would result in intermittent ovulation or ovulation that takes a long time to occur. Women in this category may experience infrequent or irregular periods. Women with the mildest cases involving high prolactin levels may ovulate regularly but not produce enough of the hormone progesterone after ovulation. This is known as a luteal phase defect. Deficiency in the amount of progesterone produced after ovulation may result in a uterine lining that is less able to have an embryo implant. Some women with this problem may see their period come a short time after ovulation (Shibli-Rahhal, 2011)
Hyperprolactinemia is commonly found in both female and male patients with abnormal sexual and/or reproductive function or with galactorrhea. If serum prolactin levels are above 200 μg/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause, but if levels are lower, differential diagnoses include the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia. When a pituitary tumour is present, patients often have pressure symptoms in addition to endocrine dysfunction, such as headaches, visual field defects, or cranial nerve deficits (Wang, 2012). The objectives of therapy are to improve the symptoms associated with high PRL levels and to reduce the size of a pituitary tumour.
Pharmacotherapy is available to reduce the tumour size and consequently decrease PRL levels. The large majority of patients with prolactinomas, both micro- and macroprolactinomas, can be successfully treated with dopamine D2 receptor agonists as first-line treatment, with normalization of prolactin secretion and gonadal function, and with significant tumour shrinkage in a high percentage of cases, to prevent the need for surgery. In cases when the only cause of infertility is chronic anovulation due to hyperprolactinemia, a 60-80% pregnancy rate can be achieved. Surgical resection of the prolactinoma is the option for patients who may refuse or do not respond to long-term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable choices if surgery fails. In patients with asymptomatic microprolactinoma no treatment needs to be given and a regular follow-up with serial prolactin measurements and pituitary imaging should be organized (Asa 2002; Crosignani 1999, Molitch 2003).
The most commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and cabergoline. When comparing the plasma half-life, efficacy and tolerability of these drugs are different, there is also important to evaluate the risk/ benefits profile of each product. As the current clinical practice, pharmacological treatment with dopamine agonist plays an important role. The recommendations on the most effective dosages and the advantages of a long term efficacy of products have been evaluated summarizing the results of case histories of the last decades.
A variety of etiological factors including disorders of the hypothalamo-pituitary axis, interruption of dopamine synthesis, stress, pituitary tumours, polycystic ovary syndrome, primary hypothyroidism, and various medications may lead to hyperprolactinemia (5). Hyperprolactinemia in girls causes delayed puberty, hypogonadotropic hypogonadism, primary or secondary amenorrhea, and galactorrhea (Fideleff, 2000). Hyperprolactinemia in men may result in as a first signs of decreased libido or impotence, however also cause inefficient sperm production and infertility (Colao, 2004).
As one of the fist signs in women with high prolactin levels may have irregular periods or no periods at all. Another common symptom is “galactorrhea”, which is the occurrence of a milky discharge from the breast in a woman who has not recently been pregnant. The discharge is the result of persistant high PRL levels stimulating the mammary gland for milk production. Some women may see galactorrhea occur spontaneously. Others may see it only if they squeeze their nipples.
As diagnostic practice, after signs and labtests have been evaluated the magnetic resonance imaging (MRI) of the pituitary gland should be performed in all patients. A pituitary adenoma with a diameter of less than 1 cm is defined as “microadenoma” and one above 1 cm in diameter as “macroadenoma”.
Prolactin can be measured with a simple blood test drawn at the fertility doctor\'s office. In order to get accurate results, prolactin should be drawn first thing in the morning. Since PRL may serve as a hormone to affect reproductive functions, sexual contact, stimulation of nipples in human may cause a not just immediate but also next-day-long alterations of the PRL secretory pattern. (Kruger 2012) These fluctuations are measured on the next day to produce a PRL elevation around noon, additional of the regular circadian rhythm of PRL levels, as the peak on the morning. Accordingly it is important to note that the woman should have the instructions to eat nothing from the night before and to avoid any stimulation of the breast and nipples, included sexual intercourse as well, from the day before also.
Since stimulation of the breast /nipples (stress such as physical exam) may cause immediate release of PRL one common mistake that doctors make is to draw a prolactin blood test immediately after a patient has had a breast exam in the office. These women will have high prolactin levels because of the exam and therefore they may show false (i.e. transient) increase of PRL levels. Prolactin should also be drawn early in the menstrual cycle - before ovulation. This is because prolactin levels are naturally higher after ovulation.
A prolactin level of 5-20 ng/mL is considered normal in both sexes, according to some laboratories and test references the male and female (a bit higher) normal range may differ. A level above 20 ng/mL in two successive measurements is defined as hyperprolactinemia (7). According to WHO standards: 1 μg/L = 21.2 mIU/L. PRL levels > 250 ng/mL usually indication for prolactinoma, when PRL > 500 ng/mL it is considered as diagnosis for macroprolactinoma. (Melmed, 2011)
There are cases when false positive and elevated PRL levels are measured: two high molecular mass forms of prolactin (PRL) in serum have been identified: macroprolactin (big-big PRL, > 100 kDa) and big PRL (40-60 kDa). Big PRL is a consistent “normal” component of total serum PRL but rarely cause of hyperprolactinemia. Macroprolactin is usually a complex of PRL and IgG in composition, it is formed in the circulation from monomeric PRL with a molecular mass of 150-170 kDa, but may have some additional variability in composition. In labor tests the PRL in the complex remains reactive to a variable extent in immunoassays. Individuals may show a different pattern of % of these variants, or even can be a predominant immunoreactive component of circulating PRL and the cause of apparent hyperprolactinemia, but it has minimal bioactivity in vivo and is not of pathological significance. As necessary the reference technique of gel filtration chromatography at the laboratory should be available for confirmation and request on investigation of samples to avoid confusion of diagnostics. (Fahie-Wilson 2005)
Pituitary adenomas are the most common tumour type in the pituitary gland. There is approximately 10% incidence was shown obtained by post-mortem autopsy, with similar ratio of male and female patients. The most frequently detected tumours (over 39%) are sparsely granulated PRL cell adenomas. The others types are GH cell or mixed PRL/GH adenoma, ACTH cell adenoma/Crooke’s cell adenoma (~14%) ; Gonadotroph cell adenoma (6.6%); Null cell adenoma/oncocytoma (~32%) and other or unclassified types (Buurman, 2006).
Invasive tumours with multiple recurrences are only classified as aggressive tumours or "atypical adenomas". Tumours with systemic metastasis must be considered as carcinomas, and “only” make up 0.1% to 0.2% of all pituitary tumours, but with very poor prognostics of 66% mortality (Oh, 2012). However it was suggested that a full picture inlcuded clinical signs (gender, DA-resistant hyperprolactinemia, etc), radiological status (invasive macro or giant tumour) and histological signs of angiogenesis, mitoses level, vascular invasion and molcular biology parameters (Ki-67 > 3 %, p53 positive, up-regulation of genes related to invasion and proliferation, and allelic loss of chromosome 11) should be taken into account considering the potential malignancy, prognosis of prolactin secreting tumours and identify the optimal therapy as early as possible. The key question is to identify factors associated with tumour aggressiveness. The approach combined genomic and transcriptomic analysis focus to the subtype of pituitary tumour able to identify molecular events associated with the aggressive and malignant phenotypes. Allelic loss in certain loci of chromosome 11 has been detected in tumours with signs of malignancy, potentially responsible for triggering the aggressive and malignant phenotypes. Within the recent years there are an increasing number of genes or molecular signs that has been associated with pituitary tumorigenesis to develop predictive and potential prognostic markers. (Zemmoura, 2012; Dworakowska, 2012; Wierinckx 2011)
About one-third of all pituitary tumours are not associated with hypersecretory syndromes but, rather, present with symptoms of an intracranial mass, such as headaches, nausea, vomiting or visual field disturbances. Only rare cases of pituitary tumours are considered as malignant prolactinoma. Tumours that produce growth hormone (GH) may also secrete prolactin in nearly 25% of cases. This is a common source of misdiagnosis, as the features of prolactin excess may capture attention while the more subtle features of GH excess go unnoticed.
In some people, a small group of cells may form a cyst in the pituitary gland which produces elevated levels of prolactin. These cysts are called prolactinomas or pituitary adenomas. It is unclear exactly how these cysts get started. Recent investigations on pituitary tumours reported that approximately 12% of pituitary glands (obtained by autopsy of 3048 patients) are shown histologically diagnosed but clinically inapparent adenoma. Among the mean tumour size is approx 1.9mm. According to published data two-thirds of adenomas has a tumour size <3 mm, half of them were smaller than 1 mm in diameter and ~23% was between 3-10mm. In this study only few (3/76) tumours were identified as macroadenomas corresponding to a tumour size >10 mm. (Buurman, 2006)
The prevalence of clinically apparent prolactinomas ranges from 6–50/ 100,000 in reported populations (Daly, 2006; Fernandez 2010). The prevalence of “ever-treated“ hyperprolactinemia is approximately 20 /100,000 in male patients and approximately 90 /100,000 in female patients. (Kars, 2009)
The adenomas can be seen and measured using MRI and classified based on their size.
Small adenomas are known as microadenomas. They measure less than one centimetre in diameter. This is the most common type of adenoma found. Microadenomas can even be present in healthy people who do not have high prolactin levels. Microadenomas can be treated with medication. They do not grow large and do not need to be treated if hormone levels are normal. Microprolactinomas usually follow a benign course and rarely progress to macroprolactinomas. However, in rare cases microadenoma may transform to other tumours.
A case history it was reported that a microadenoma transformed to macroprolactinoma within 10 month, probably due to estrogen therapy applied. The case report emphasizes the role of dopaminergic agonist in treatment of hyperprolactinemia. (Garcia, 1995)
A case history of a 22 -year-old woman with the signs of galactorrhea and slight hyperprolactinemia, showed 7-mm intrapituitary lesion which responded to treatment with cabergoline. This PRL-secreting microadenoma has a sudden change within 4 years of diagnose. The case represents a rapid evolution from a microprolactinoma initially responding to dopamine agonists to a fatal pituitary carcinoma. (Guastamacchia, 2007)
Adenomas larger than 1 centimetre are called macroadenomas. If untreated, macroadenomas can grow further and start to compress the nearby tissues and structures causing life-threatening events or even fatal outcome. The closest structures are the optic nerves, internal carotid arteries. If a macroadenoma causes compression of the optic nerves, partial blindness can result. For this reason, it is important to treat macroadenomas whether or not a woman is interested in getting pregnant. Medication can be used to treat them but if that fails, surgery may be necessary.
According to a recent clinical study in Japan, treatment with Cabergoline achieved a high pregnancy rate with uneventful outcomes in infertile women with prolactinoma, independent of tumour size and bromocriptine resistance or intolerance. Over 90% of patients in the study conceived pregnancies, and one-third of the macroprolactinomas disappeared. Cabergoline monotherapy could serve as an alternative of the conventional combination bromocriptine therapy with surgery or irradiation in macroprolactinomas. (Ono, 2010)
The hyperprolactinemia of hypothyroidism is related to several mechanisms. In response to the hypothyroid state, a compensatory increase in the discharge of central hypothalamic thyrotropin releasing hormone (TRH) results in increased stimulation of prolactin secretion.
Although TRH was originally named for its ability to trigger the release of thyroid-stimulating hormone (TSH) in mammals, it became apparent that TRH exerts multiple hypophysiotropic activities also in human. Stimulation with TRH will provide a diagnostic test to demonstrate a TSH release curve typical of the subclinic hypothyroidism. PRL is under tonic inhibition by the hypothalamus by way of the PRL inhibitory factor, DA. PRL-releasing factors include TRH., Increased release of TRH may also cause a sustained stimulation of prolactin release from the pituitary gland. There are several clinical reports presented the correlation between subclinic hypothyroidism-hyperprolactinemia and sterility. Treatment with thyroid hormone supplements will result in correction of both the thyroid feedback and the high prolactin levels.
Asymptomatic patients with intact gonadal and reproductive function and moderately elevated prolactin levels may have macroprolactinemia (Vallette-Kasic, 2002). Hypersecretion of PRL by lactotroph cells of the anterior pituitary cause hyperprolactinemia. Patients with hyperprolactinemia may have radiologically undetected microprolactinomas, but some of them may present other causes of hyperprolactinemia characterised as a symptom of macroprolactinemia, with a predominance of higher molecular mass prolactin forms (big-big prolactin, MW > 150 kDa). This term should not be confused with macroprolactinoma, which refers to a large pituitary tumour greater than 10 mm in diameter.
The prevalence of macroprolactinemia varies between 15-46% in hyperprolactinemic populations, and it may because confusing tests results that could not be differentiated from true hyperprolactinemic patients, on the basis of clinical features alone. The pathophysiology of macroprolactinemia is based on a mechanisms of the increased antigenicity of these molecules, leading to the appearance of autoantibodies against PRL, which can consequently reduce the bioactivity of PRL and provide extended half-life. Therefore macroprolactinemia is manifested with less frequent clinical symptoms in macroprolactinemic patients and the tests results mainly due to the delayed clearance of PRL. According to recent publications of Isik et al, evaluating over 300 hyperprolactinemic patients, over 26% of them resulted in elevated macroprolactin levels, with the less frequent signs of galactorrhea or abnormal MRI results compared those to patients with predominant monomer hyperprolactinemia. The other symptoms and frequency of amenorrhea, infertility, irregular menses, gynecomastia, and erectile dysfunction were similar in both groups. (Isik, 2012)
Macroprolactinemic patients have no clinical symptoms of hyperprolactinemia and may have no pituitary adenomas. It is still controversial whether macroprolactinemia is a benign condition that does not need further investigation and treatment. Patients can be screened for macroprolactinemia by PEG (polyethylene glycol) precipitation as a standard laboratory test with a results of recovery of ≤40% to normal monomeric PRL level is used as an indication of macroprolactinemia (Tamer, 2012). The clinical importance of this test is based on the lower prevalence of pituitary adenomas in this group, compared to “true hyperprolactinemic” patients.
PCOS is a common problem that can cause infertility by inhibiting ovulation, affecting 3.5-10% of the reproductive age of women. For unknown reasons, some women with PCOS may have slightly high PRL levels. PCOS similar to hypoprolactinemic are both common causes of secondary amenorrhoea in women. The relationship between PCOS and hyperprolactinemia so far has been reported still with controversial results: it seems that PCOS is very prevalent with hyperprolactinemia, nevertheless there are different reasons of altered regulation of gondotropin secretion, and suggests that these conditions have independent origins. Recent investigators using serial serum sampling have excluded transient elevations of PRL and have shown a less frequent association of these two disorders. According to clinical guidelines PCOS patients with increased PRL levels must be investigated for other causes of hyperprolactinemia, because hyperprolactinemia may be due to a reason of concomitant disease, but not proved the cause-relationship to PCOS. Treatment of infertility associated with PCOS has changed in the last decade due to the introduction of new medications such as insulin-sensitizing drugs, aromatase inhibitors, gonadotropin treatment etc. (Bracero 2001, Urman, 2006, Escobar-Morreale, 2004)
In a study conducted in Brazil, among the 82 PCOS women, 13 (16%) presented high PRL levels (over 100 microg/l). There were several reasons of hyperprolactinemia: pituitary adenoma; drug-induced hyperprolactinemia, or macroprolactinemia. The non-hyperprolactinemic PCOS patients (over 80%) represented normal PRL levels. The authors concluded that hyperprolactinemia is not a clinical manifestation of PCOS. (Filho, 2007)
Some medications can cause higher levels of prolactin to be produced. The most common medications that do this are known as anti-psychotic medications. The antipsychotics mostly act as dopaminergic neurotransmitters/ receptor blockers can also cause endocrine side effects, as hyperprolactinaemia and it is most common side effect of first-generation antipsychotics. The second- and thirdgeneration antipsychotics have a weaker affinity for D2 dopamine receptors, thus hyperprolactinemia is less common when such medication is used. (Uzun et al. 2005). The risk of side effects caused by antipsychotics is individual and it does not depend solely on the therapeutic dose and may have influence on some predisposing conditions. (Ružić 2011)
Other medications which may increase prolactin levels:
Some types of anti-depressants, serotonin reuptake inhibitors, SRIs (fluvoxamine; fluoxetine; paroxetine, duloxetine etc)
Some types of sedatives
Catecholamine depletor
Dopamine synthesis inhibitor
Neuropeptides
Anticonvulsants
Opiates and opiate antagonists
Estrogen Oral contraceptives (birth control pills)
Some types of blood pressure medications (methyldopa, verapamil)
A medication for nausea (Reglan, metoclopramide)
Antacids (cimetidine)
A high prolactin level can sometimes be related to physical stress. Even drawing blood can by itself cause someone to produce and immediate prolactin-release. PRL eleveation can also detected in response to strong or sudden external stimuli in general, such as stressful environmental conditions, or can be related to physchological reasons. This latter can be evaluated by stress profile or measured by experimental conditions, such as “Screamer Index”, which is shown resulting in values to be parallel to levels of hyperprolactinemia in women. (Harrison, 1988; Cepisky, 1992). On the other hand, anxiety and irritability maybe a result of hyperprolactinemia. In rat models PRL increased the stimulatory effect of ACTH-induced corticosterone secretion (Jaroenporn, 2007).
Endocrine abnormalities are frequently associated with a wide range of psychological symptoms. These symptoms may reach the level of psychiatric illness (mainly mood and anxiety disorders) or just being identified by the subclinical forms of assessment provided by the Diagnostic Criteria for Psychosomatic Research (DCPR). In a population study reported by Sonino et al, (2007), the majority of patients suffered from at least one of the three DCPR syndromes considered: irritable mood (over 45%), demoralization, persistent somatization. Long-standing endocrine disorders may imply a degree of irreversibility of the pathological process. Endocrine treatment may cause even the worsening of psychological symptoms. The methodology and assessment score provided by DCPR tests have been demonstrated to be a valuable tool for psychological assessment in endocrine disease from diagnostic to follow-up periods. (Sonino 2007)
In clinical environment the variability of PRL concentration in random estimations underline the need for special testing to rule out stress-related hyperprolactinemia and diagnostic pitfalls. It was recommended by the results, that two or three serial PRL determinations in resting conditions provide more reliable results (Muneyyirci-Delale, 1989).
In experimental conditions, hyperprolactinemia and stress interact differentially according to the length of the stimuli and that is connected to the immune response modulated by PRL. Surgical or restraint stress induce marked (2x- 4x) increase of plasma PRL of control rats, but interestingly did not change the PRL levels of hyperprolactinemic rats. In both cases the plasma glucose levels reported elevated (Reis, 1996).
It is suggested as a result of a retrospective observational study, that life events such as changes in subject’s social or personal environment indicated that these stressful conditions may provoke hyperprolactinemia. Even an exposure during childhood to a stressful environment maybe associated with hyperprolactinemia and/or galactorrhea later in life as a response to specific environmental changes (Sobrinho, 1984). Patients with hyperprolactinemia reported significantly more life events, these events rated as being of „moderate”, marked or severe „negative” impact compared with control subjects (Sonino, 2004).
There is evidence that several external stress-factors may contribute to the occurrence of hyperprolactinemia. In theory, stress might have been involved in facilitation of a clonal proliferation of a single mutated cell and cause prolactinomas. Patients in functional hyperprolactinemic status, stress might trigger neuroendocrine changes involving DA and/or serotonin, which both can consequently affect PRL release. (Verhelst, 2003; Freeman, 2000; Fava, 1981.)
Prolactin is a pituitary-derived hormone that plays an important role in a variety of reproductive functions. It is an essential factor for normal production of breast milk following childbirth. Additionally, prolactin negatively modulates the secretion of pituitary hormones responsible for gonadal function, including luteinizing hormone and follicle-stimulating hormone. Clnincally significant hyperprolactinemia may result in hypogonadism, infertility, and galactorrhea, or in some cases it may remain asymptomatic for a long period. (Klibanski 2010) The most commonly cited indications for treatment of microprolactinomas is infertility and hypogonadism. Hypogonadism and infertility associated closely with the treatment: DA agonists can restore normal PRL levels and consequently the normal gonadal function. According to the date of a meta-analyis, patients treated with bromocriptine had normalization of prolactin levels and it was successful in 53% of patients with infertility. Studies with cabergoline showed similar results: cabergoline was shown more effective than bromocriptine reducing PRL levels, or in symptoms of amenorrhea/oligomenorrhea, or in some of the patient-important outcomes. (Gillam 2006; Wang 2012)
Prolactin is under dual regulation by hypothalamic hormones delivered through the hypothalamic–pituitary portal circulation. The differential diagnosis and causes of pathological hyperprolactinemia are summarized in Figure 1.
The predominant signal is inhibitory, preventing prolactin release, and is mediated by the neurotransmitter dopamine. The stimulatory signal is mediated by the hypothalamic TRH. The balance between the two opposite signals determines the amount of prolactin released from the anterior pituitary gland (Verhelst; 2003).
Prolactin is under dual control from the hypothalamus.
The first steps in cases of signs of hyperprolactinemia should be a critical diagnosis, as discussed above, may involve dynamic testings, assessment for macroprolactinemia and further laboratory tests to eliminate false positive or negative results.
Consider other underlying causes, such as suspected drug-induced hyperprolactinemia, hypothyroidism, elimination/renal failure, other persistent pituitary and parasellar tumours, etc.
Identify the size of pituitary tumour and other anatomical circumstances.
Apply pharmacotherapy treatment specified to patient
The major steps of diagnosis of hyperprolactinemia is summarized in Figure 2.
Approach to diagnosis of hyperprolactinemia.
Specific recommendations for diagnosis of hyperprolactinemia include the following (Melmed 2011):
A single measurement of serum prolactin level can confirm the diagnosis if the level is above the upper limit of normal and the serum sample was obtained without excessive venipuncture stress. Dynamic testing of prolactin secretion is not recommended to diagnose hyperprolactinemia.
Macroprolactin evaluation is recommended in patients with asymptomatic hyperprolactinemia.
When there is a discrepancy between a very large pituitary tumour and a mildly elevated prolactin level, serial dilution of serum samples is recommended to eliminate the "hook effect," or an artifact that can occur with some immunoradiometric assays leading to a falsely low prolactin value.
Specific recommendations for management of drug-induced hyperprolactinemia are as follows (Melmed 2011):
In a symptomatic patient with suspected medication-induced hyperprolactinemia, the drug should be discontinued for 3 days or an alternative drug substituted, and the serum prolactin measurement should then be repeated. However, the patient\'s physician should be consulted before an antipsychotic agent is discontinued or substituted. If the drug cannot be discontinued and the onset of the hyperprolactinemia does not coincide with starting therapy, magnetic resonance imaging (MRI) of the pituitary gland may distinguish medication-induced hyperprolactinemia from symptomatic hyperprolactinemia caused by a pituitary or hypothalamic mass.
Patients with asymptomatic medication-induced hyperprolactinemia should not be treated. Estrogen or testosterone can be used in patients with long-term hypogonadism (hypogonadal symptoms or low bone mass) caused by medication-induced hyperprolactinemia.
If it is not possible to stop the drug causing medication-induced hyperprolactinemia, cautious administration of a dopamine agonist should be considered, in consultation with the patient\'s physician.
As noted above, prolactin levels can often be corrected by stopping suspected medication or switching to a different medication type. Correction of hypothyroidism is also effective and specific to reduce PRL levels. If prolactin levels are persistently high, they can be effectively treated with a group of medications known as dopamine agonists.
According to our clinical practice patients with macroadenoma suggested to undergo transsphenoidal pituitary surgery. Medical treatment is given to the subjects with microadenoma, persistent postoperative hyperprolactinemia, and to those cases of hyperprolactinemia when it is caused by other medications.
From the available mediactions Bromocriptine 2.5 mg (Parlodel®, Novartis) once or twice a day or cabergoline 0.5 mg (Dostinex®, Pharmacia) once or twice a week is given as prolactin-lowering drug.
Parlodel is an effective and inexpensive medication for high prolactin levels. Parlodel is usually taken at bedtime with a snack. This is because Parlodel will occasionally cause dizziness or stomach upset, so taking it before sleep and with food will reduce those side effects. Generally with time, the side effects stop anyway.
The prolactin levels can be rechecked in about three weeks. If the levels are still elevated the dose can be increased or a different medication can be tried. The administration of Parlodel can be stopped upon diagnosis of pregnancy. However, if a woman has a macroadenoma, Parlodel should be continued through pregnancy and delivery.
Due to the side effects, some women can not tolerate Parlodel. For these women, they may try alternatives, e.g. vaginal bioadhesive suppositories or inserted the pills vaginally instead of taking them orally.
Because it is more expensive, cabergoline is not usually the first choice for treatment of high prolactin levels. It is usually used when Parlodel is ineffective or a woman cannot tolerate the side effects. Cabergoline is a longer acting medication. It is usually given twice a week instead of every day.
The Endocrine Society has released a new clinical practice guideline for the diagnosis and treatment of patients with hyperprolactinemia (Melmed, 2011). The new recommendations for management of elevated levels of the PRL, which is associated with infertility, low sex drive, and bone loss, are listed.
Specific recommendations for management of prolactinoma are as follows (Melmed 2011)::
Dopamine agonist therapy is recommended to reduce prolactin levels and tumor size and to restore gonadal function in patients with symptomatic prolactin-secreting microadenomas or macroadenomas. Compared with other dopamine agonists, cabergoline is more effective in normalizing prolactin levels and in shrinking pituitary tumours.
Dopamine agonists are not recommended for asymptomatic patients with microprolactinomas. However, patients with microadenomas who have amenorrhea can be treated with a dopamine agonist or oral contraceptives.
In patients treated with dopamine agonists for at least 2 years who no longer have elevated serum prolactin levels or visible tumour on MRI, careful clinical and biochemical follow-up therapy may be tapered and perhaps discontinued.
Specific recommendations for management of resistant and malignant prolactinoma are as follows (Melmed 2011):
For symptomatic patients in whom normal prolactin levels are not achieved or who have significant shrinking of the tumour size while receiving standard doses of a dopamine agonist, the dose should be increased rather than referring the patient for surgery.
Patients resistant to bromocriptine should be switched to cabergoline.
Symptomatic patients with prolactinomas who cannot tolerate high doses of cabergoline or who are unresponsive to dopamine agonist therapy should be offered trans-sphenoidal surgery. Patients intolerant of oral bromocriptine may respond to intravaginal administration. Radiation therapy is recommended for patients in whom surgical treatment fails or for those with aggressive or malignant prolactinomas.
Temozolomide therapy is recommended for patients with malignant prolactinomas.
Specific recommendations for management of prolactinoma during pregnancy are as follows (Melmed 2011):
Women with prolactinomas should discontinue dopamine agonist therapy as soon as pregnancy is recognized, except for selected patients with invasive macroadenomas or adenomas abutting the optic chiasm.
Serum prolactin measurements should not be performed during pregnancy.
Unless there is clinical evidence for tumour growth, such as visual field impairment, routine use of pituitary MRI during pregnancy is not recommended in patients with microadenomas or intrasellar macroadenomas.
Women with macroprolactinomas that do not shrink during dopamine agonist therapy or women who cannot tolerate bromocriptine or cabergoline should be counselled regarding the potential benefits of surgical resection before attempting pregnancy.
Pregnant women with prolactinomas who experience severe headaches and/or visual field changes should have formal visual field assessment followed by MRI without gadolinium.
Bromocriptine therapy is recommended in patients who experience symptomatic growth of a prolactinoma during pregnancy.
Hyperprolactinemia has been proposed to block ovulation through inhibition of GnRH release. Kisspeptin neurons, which express prolactin receptors, were recently identified as major regulators of GnRH neurons. A recently published study demonstrated that hyperprolactinemia in mice induced anovulation, reduced GnRH and gonadotropin secretion, and diminished kisspeptin expression. Kisspeptin administration restored gonadotropin secretion and ovarian cyclicity, suggesting that kisspeptin neurons play a major role in hyperprolactinemic anovulation. This study indicate that administration of kisspeptin may serve as an alternative therapeutic approach to restore the fertility of hyperprolactinemic women who are resistant or intolerant to dopamine agonists (Sonigo, 2012).
To sum up, the systematic reviews and meta-analyses affirm the use of dopamine agonists in treating hyperprolactinemia and reducing associated morbidity. Cabergoline was found to be more effective than bromocriptine in achieving normoprolactinemia and resolving amenorrhea/oligomenorrhea and galactorrhea. Radiotherapy and surgery are efficacious in patients with resistance or intolerance to dopamine agonists (Wang, 2012).
Prolactin-secreting pituitary tumours are a common cause of amenorrhea and infertility in premenopausal women. The goals of therapy are to normalize prolactin, restore gonadal function and fertility, and reduce tumour size, and dopamine agonists are the preferred therapy. Clinically significant tumour enlargement during pregnancy is uncommon and dependent on tumour size and pre-pregnancy treatment.
Accroding to over 180 clinical study reports (across 3000 patients) treatment with bromocriptine or with cabergoline are both effective in normalization of prolactin levels and also successful in restoration of fertility over 53% of patients. Cabergoline was shown more effective than bromocriptine in persistent hyperprolactinemia, and reducing the symptoms of amenorrhea/oligomenorrhea. At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line approach. In the small group of patients who do not respond to this treatment, or who refuse long-term therapy, surgery is offered. Radiotherapy is given if both pharmacologic therapy and surgery fail.
Consciousness remains the hall mark defining human intelligence and interactive life and the true demarcation line between being and not being. In spite of being the most practical experience of self identity and intelligent life reactions in this life that we live, its nature remains an area of great debate and sometimes conflicting opinions between philosophers, biologist and intellectualists since the dawn of human scientific history. The twentieth century is known as the century of brain as there was exaggerated materialistic inflation of brain role in human functions but mainly consciousness. There is compelling scientific and rational evidence to convince scientific communities that the nature of consciousness involves dynamics inside the skull but essentially much beyond it in extreme dimensions between the skull and the sky. In addition to discussing the sophisticated neurobiological dynamics within the cerebral cortex, the main aim of this chapter is to open channels for holistic perception and understanding of human consciousness incorporating other scientific disciplines like the central role of human heart contribution to consciousness, quantum physics, as well as astrobiologigcal aspects of consciousness are going to be discussed.
Since the dawn of humanity the ability of human beings to be alert, responsive and behave intelligently with emotions and identity were the subject of huge concerns in the philosophical, medical, psychological and religious communities. The explosive nature of diagnostic modalities in neuroimaging, medical physics and neurocardiology since world war 2 but more specifically in the last 20 years created revolutionary perspective of our understanding of the nature and origin of consciousness. Those advances were paralleled with numerous publications and selective conferences concerned with the brain and mind. We established unique conceptual congress, the King of Organs for Advanced Cardiac Sciences where heart and brain communications were discussed in unconventional ways in five international conferences (2006,2008,2010, 2012 and 2019) founded and chaired by the author of this chapter. One of the most challenging controversial and still ongoing scientific issues is the debate on how to define consciousness. The words
Comprehensive understandings of scientific etymology demands the linguistic power in combination with the practical meanings as it is accepted and understood in the mainstream language. In this regard we suggest approaching consciousness with broad visionary perspective. For this reason we will define consciousness by referring to three major domains: First: the state of alertness and being vigilant, the opposite of which is coma as measured by Glasgow Coma Scale. This is predominantly of neurological nature. Second is the experience or the content of experience from time to time or ‘what something looks like’ and the inward connotation and feelings. This is predominantly of philosophical nature. Third is referred to the mental state with propositional content like fear, anger or appreciation. Most research in medical literature has natural tendency to neglect this third meaning of consciousness. This state of continuous historical uncertainty and debate about consciousness is in our opinion justified because of lack of knowledge of the origin, dimension and fate of our current life consciousness. The fact that the nature of consciousness cannot be explained as deduction from pathological alterations in the brain led to the fact that the mysterious mission of understanding human consciousness will be impossible without involving dimensions out of cerebral cortex. It can be looked as property of highly complex dependent biological systems which is adaptive, and highly interconnected.
The phenomena of access consciousness where information are accessed to the brain from different energetic cosmic levels is a major gate to explore in the comprehensive science of consciousness although by itself, it is unconscious. What increase complexity is the historical believe in different civilizations and religions that consciousness will never disappear but transform from one realm to another. Recently consciousness research refers to the
Agreement in definition and overlapping terms is important to navigate safely and target the phenomenology of human consciousness as precisely as possible. To recapitulate the wide spectrum of meanings and domains the author define Consciousness as
The following discussions in this chapter will expand the understanding in those directions.
The level of human consciousness is the collective activity of widespread areas of bilateral association of cortical and subcortical structures and possibly other interconnected biological and astrophysical systems. Due to the complex nature of consciousness origin and dimensions, it would be too artificial and nonrealistic to confined consciousness discussion in cortical, subcortical dimensions as is the product of interaction and connections of complex biological and non-biological networks.
Cortical components consisting medially of the medial frontal, anterior cingulate, posterior cingulate, and medial parietal (precuneus, retrosplenial) cortex. On the lateral surface, it includes the lateral frontal, anterior insula, orbital frontal, and lateral temporal–parietal association cortex. The major subcortical networks that regulate level of consciousness including the thalamus and subcortical arousal nuclei acting through multiple neurotransmitters (glutamate, acetylcholine, gamma amino butyric acid (GABA), norepinephrine, serotonin, dopamine, histamine, orexin) that arise from the upper brainstem, basal forebrain, and hypothalamus are going to be discussed.
The consciousness experience remains more complex than simple understanding of possible structure or network functions. The content of consciousness at certain time period is interdependent on the substrate of structure(s) and network(s) activated during that time to yield the specific conscious experience as will be discussed in this section.
In spite of the developments in the field of consciousness in the last two decades it is not clear how any physical process, such as neural activity, can give rise to a subjective phenomenon such as conscious awareness of an experience. For this reason, very important observation for researchers in the field of neurobiology of consciousness is to know that the causal relationship of the objective detection of neuronal activation and the subjective awareness of conscious experience is uncertain. Neuroscientist suggested the idea of the Neuronal Correlates of Consciousness (NCC) to be able to study the possible minimal model or the smallest possible building components of conscious percept or explicit memory.
Revising history of arousal in modern medicine document (ARAS) as one of the first described structures responsible of enhanced arousal [11]. After decades of researchers efforts we know that what was described as (ARAS) is not a structure of brain stem nuclei per se but is a group of specialized nodes in a complex network and pathways that controls arousal. This network includes the cholinergic nuclei in the upper brainstem and basal forebrain, The posterior hypothalamus histamine projection, and noradrenergic nuclei, especially the locus coeruleus. The dopamine and serotonin pathways that arise from brain stem are thought to be part of (ARAS). The thalamus which constitute crucial synaptic relay for most sensory and intracerebral pathways is located strategically at the apex of (ARAS) and have mediated major control on most of its activities [12, 13]. Thalamic burst discharges are generated through extensive inhibitory axon collaterals, produced by special thalamic, ARAS coordination. Those discharges are responsible for gating specific reticular information which is in turn transmitted back to the cortex, and this reverts the information back to the brainstem [14]. Positron emission tomography (PET) investigation during slow-wave sleep [15] and anesthesia [16] documented selective thalamic and ARAS hypometabolism through studying functional neuroimaging of normal human sleep and studying the neurophysiologic basis of anesthetic induced unconsciousness.
Amygdala, the brain’s center for emotions, occupies major position in the neurology and biology research concerned with working memory, long-term memory, and attention. It is strongly linked with social interactions region in the brain, namely, the orbital cortex. Tight tripartite network constitutes robust pathways from amygdala connected to neurons in the thalamus which in turn connect directly to the orbital cortex. The pathways from the amygdala to the orbital cortex and to the thalamus are dual and distinct by function, morphology, neurochemistry [17]. This highly sophisticated and specialized pathways provide strong evidence that emotions influence higher cortical areas concerned with affective reasoning. In addition, Investigating the neurobiological bases of executive functions suggest that amygdala facilitates cognitive performance during challenging tasks between the amygdala and cognitive systems. For this reason neurotransmitters like dopamine and noradrenaline may contribute important role between the amygdala and higher cognition [18, 19]. In our opinion, the well-established role of amygdala in emotions and the additional relation to cognition are both integral to each other and support the establishment of comprehensive intelligent emotional model as a cornerstone of human consciousness experience.
Functions related to movement, gait, posture and balance were the traditional functions related to cerebellum. In the last two decades cerebellum was found to have regulatory functions concerned with emotion processing, cognition, behavior, and collectively consciousness experience [20, 21]. The cognitive role of the cerebellum can be understood by looking at its afferent and efferent connections. The most important of the central afferent circuits is the corticopontocerebellar pathway which emanates from the motor and sensory cortical areas. The pontocerebellar tracts connect with the pontine nuclei then it connect with the contralateral cerebellar hemisphere in a somatotopic manner -which denotes feeling or consciousness experience- of point to point correspondence of an area of the body to a specific point on the cortex. Peripheral cerebellar pathways originate from the brainstem. Via the red nucleus and ventrolateral nucleus of the thalamus, the cerebellum exerts most of its output to the brain stem and the cerebral motor cortex [22]. Efferent cerebellar pathways are four and ultimately connects to the following critical structures: pons, medulla oblongata a, reticular formation, basal ganglia, corticospinal and reticulospinal pathways and limbic cortices (cingulate and parahippocampal gyri). Those sophisticated networks and connections of afferent (corticopontocerebellar) and efferent (cerebellothalamocortical) pathways, the cerebellum can exert highly complex regulatory role and integrate information to the cortical cerebral areas related to cognition and ultimately the consciousness experience [23]. The ongoing collective data from different discipline in genetics, neuropsychological research, structural and functional brain imaging studies will provide better perspective of the integral role of cerebellum in consciousness [22].
Thalami are pair of large ovoid organs that form most of the lateral walls of the third ventricle of the brain in humans. Thalamic main nuclear divisions and nuclei are: midline thalamic nuclei, anterior nuclear group, medial nuclear group (mediodorsal nucleus), lateral nuclear group, thalamic reticular nucleus and intralaminar nuclei. Nearly all information directed to the cortex first reaches the thalamus. The thalamus transmits this information and reciprocally receives an even greater number of connections back from the cerebral cortex. For this reason, the thalamus is considered as a major player in all forebrain functions including consciousness. The thalamus relays the content of consciousness, and also controls its level via specialized circuits that act as regulator of arousal level and are critical for selective attention. The specific thalamic relay nuclei communicate with the cerebral cortex regarding each sensory and motor function. For this reason the thalamus with its extensive nuclei connections is thought to be responsible for all the individual contents of consciousness [24]. Corticothalamic rhythms are thought to be generated by The reciprocal connections between thalamic relay nuclei and the thalamic reticular nucleus during normal sleep and waking activity, as well as in pathological rhythms such as epilepsy [25]. the intralaminar thalamus plays an important role in transmitting arousal influences from strategic location, namely, the midbrain and upper pontine cholinergic and glutamatergic systems to the cortex.
The contribution of frontoparietal activity to conscious perception was suggested by neuroimaging studies. In addition to visual perception due to activity in the ventral visual cortex, the parietal and prefrontal areas contribution seems to be essential for awareness [26, 27]. The network nodes for correlates of consciousness are thought to be divided to primary and secondary. Early activity in the occipital lobe correlates with the perceptual processes, which is detrimental for later process, namely, the activity in the frontoparietal areas. Access consciousness, in comparison to the phenomenal subjective consciousness due to mainly activation of sensory regions, refers to the direct control of experience through reasoning, reporting, or action. This type of higher functioning needs the involvement of the frontoparietal areas [28].
The PFC constitutes a large portion of the frontal lobe that includes most of the cortical tissue anterior to the central sulcus which can be divided to five main areas. The role of the prefrontal cortex (PFC) as an NCC is the source of debate between prefrontal theories and posterior theories of consciousness. The strongest argument point of posterior theories of advocates is the preservation of consciousness in patients with PFC lesions. Apparently, they limit their definition of consciousness to the state of alertness and vigilance, which is too deficient definition. In our view, adopting our comprehensive definition of consciousness, mentioned earlier, will make both conflicting parties complementary rather than competitive. The five main areas of the PFC –namely The anterior prefrontal cortex the caudal prefrontal cortex; the dorsolateral prefrontal cortex; the ventrolateral prefrontal cortex; and the medial prefrontal cortex -are extensively connected with sensory areas, which conceivably denotes that PFC is essential part of the consciousness experience although the exact mechanism of how the sensory information could become conscious is still not well understood. NCCs involving PFC might be subtle neurological activity. The fact that common neuroimaging techniques are not sufficiently sensitive to detect subtle differences in neural activity should be considered in future research discussing the role of OFC in consciousness [29].
Precumues or the mesial extent of Brodmann’s area is a cortical region located in the posteromedial portion of the parietal lobe. It is well known with its widespread connections with both cortical and the subcortical structures. Recent Functional imaging findings in healthy subjects suggest a central role for the precuneus in a wide spectrum of higher functions, including visuo-spatial imagery, episodic memory retrieval and self-processing operations. Precuneus and surrounding posteromedial areas are among the most hot spots of the brain as it is displaying high resting metabolic rates. It is characterized by transient decreases in the tonic activity during engagement in non-self-referential goal-directed actions [28]. It is thought that precuneus is involved in the interwoven network of the neural correlates of self-consciousness, engaged in self-related mental representations during rest. The evidence is supportive of the involvement of precunues in the endogenous signaling function during conscious resting state. This hypothesis is consistent with the selective hypometabolism in the posteromedial cortex reported in a wide range of altered conscious states, such as sleep, drug-induced anesthesia and vegetative states [30].
The most prevalent excitatory neurotransmitter in the central nervous system is Glutamate. It functions seems to be critical in initiation and maintaining of sleep and wakefulness. Arousal system pathways arising from the midbrain and upper pontine reticular formation that project to the thalamus and basal forebrain as well as the widespread projections from the thalamic intralaminar nuclei to the cortex are thought to be mediated by glutamate [31]. Through interaction with other types of neurons, the glutamatergic neurons can regulate sleep stages. With this type of arrangement, complex sleep–wake regulation network in the brain is made [32].
Acetylcholine, although being, the major neurotransmitter of the peripheral nervous system, plays neuromodulatory function in the central nervous system (CNS). The brainstem pontomesencephalic reticular formation and the basal forebrain are the two main sources of cholinergic projections neurons in CNS. Brain stem arousal is thought to act in a synergistic manner with the noncholinergic putative glutamatergic pontomesencephalic neurons which project to intralaminar thalamus and basal forebrain [24, 31, 33]. The brainstem and basal forebrain cholinergic systems work together to abolish The cortical slow wave activity which is known to be enhanced with pathological brain function as in stroke, schizophrenia, depression, Morbus Alzheimer, and post-traumatic stress disorder are abolished by the brainstem and basal forebrain cholinergic systems and this ultimately will promote an alert state [31, 34] Muscarinic acetylcholine receptors are the major receptor type operating in cholinergic arousal in the CNS, although nicotinic receptors may also play an important role [24]. The result of pharmacological blockage of cholinergic neurons in the CNS can be deduced from its functional areas connections, resulting in acute state of delirium and memory loss. In the contrary, the miracle of human brain creation is shown in the preservation of consciousness with experimental selective damage to cholinergic neurotransmission [35]. This can be explained by the multiple parallel neurotransmitter systems are participating in maintaining the consciousness.
The most prevalent inhibitory neurotransmitter in the CNS is GABA. It is known for its major role in regulating arousal. Several long-range GABAergic projection systems also contribute to controlling arousal. Arousal is promoted by some GABAergic neurons in the basal forebrain as these inhibitory neurons in turn project to cortical inhibitory interneurons [24, 36]. On the other hand the overall effects of basal forebrain GABAergic neurons on arousal process is variable with variable firing patterns on cortex and sleep awake cycle. Long GABAergic projections have their overall function as inhibitors for arousal process. These include neurons like ventral lateral preoptic nucleus which is known for its widespread inhibitory projections to almost all subcortical arousal systems [37]; forebrain and hypothalamus inhibitory neurons namely lateral septal GABAergic neurons [38]; and the GABAergic containing neurons nucleus namely the thalamic reticular nucleus that is projecting to the remainder of the thalamus and projecting to the brainstem reticular formation [39]. Regions of the thalamus including the intralaminar nuclei are inhibited by GABAergic neurons in the globus pallidus internal segment. It is thought that the inhibition of the globus pallidus to remove the tonic inhibition of the intralaminar thalamus with medications like zolpidem in minimally conscious state, or benzodiazepines in catatonia is the possible mechanism for the paradoxical arousal effects of those GABA agonist [24, 40]. The loss of consciousness in partial seizures is thought to be due to activation of these multiple GABAergic inhibitory projections converging on the subcortical arousal.
In proximity to the fourth ventricle, in the rostral pons the locus ceruleus contains the norepinephrine (noradrenaline) neurons. Inhibition of locus ceruleus neurons with drugs like selective α-2 agonists such as clonidine or the anesthetic agent dexmedetomidine is the possible mechanism of action yielding profound depression of arousal. In contrary selective blockage or removal of noradrenergic neurons will impair arousal but will not end up in deep coma. This can be explained, like the situation mentioned in cholinergic arousal systems, by multiple parallel neurotransmitter systems are participating in maintaining the consciousness. Norepinephrine neurons type are also found in the lateral tegmental area extending into the more caudal pons and medulla [24, 41]. Sleep–wake cycles, attention, and mood are regulated via ascending noradrenergic projections that reach the cortex, thalamus and hypothalamus. Modulation of autonomic nervous system function and pain gating is operated through descending projections to the brainstem, cerebellum, and spinal cord.
The midline raphe nuclei of the midbrain, pons, and medulla contains most of the serotonergic neurons. Projections to the entire forebrain are received from the more frontal serotonergic neurons in the midbrain and upper pontine raphe nuclei, participating in regulation of sleep–wake cycle. Serotonergic systems occupies major position in psychiatric practice as dysfunction of which is thought to play a role in a number of psychiatric disorders including, anxiety, depression, obsessive–compulsive disorder, aggressive behavior, and eating disorders. Modulation of breathing, pain, cardiovascular system, temperature control,, and motor function is attributed to the caudal serotonergic neurons in the pons and medulla. The dorsal raphe and median raphe are thought to be the most important rostral raphe nuclei participating in arousal process [42]. The contribution of serotonergic neurons to the arousal process with either promotion or inhibition, is complex due to the wide diversity of serotonin receptors in different regions of the brain [43, 44]. The lifesaving arousal response to hypoventilation and high carbon dioxide tension is thought to be promoted by brainstem serotonergic neurons located rostrally [45].
The substantia nigra pars compacta and the adjacent ventral tegmental area of the mid brain are the regions where dopaminergic neurons are mostly found. Three ascending dopaminergic projection systems will emanate from those nuclei projecting to vital cortical and subcortical regions with substantial contribution to consciousness process: (1) the mesostriatal (nigrostriatal) pathway (2) the mesolimbic pathway (3) the mesocortical pathway. Those three projections arise from substantia nigra (pathway 1) and ventral tegmental area (pathway 2 and 3) reaching to the caudate and putamen (pathway 1), limbic structures including the medial temporal lobe, amygdala, cingulate gyrus, septal nuclei, and nucleus accumbens (pathway 2), the prefrontal cortex and the thalamus (pathway 3). Dopamine can have dual effect on the thalamus and cortex either activation or inhibitory [46]. Schizophrenia related apathy and the reduction of motivation and initiative, seen in frontal lob pathologies, abulia, and akinetic mutism are thought to be due to impaired dopaminergic transmission to the prefrontal cortex [47].
In the posterior hypothalamusan an important nucleus is called tuberomamillary nucleus where most of the Histamine-containing neurons are found. In addition a few scattered histaminergic neurons can be seen in the midbrain reticular formation. The entire forebrain including cortex and thalamus receives extensive ascending projections emanating from the tuberomamillary nucleus, while the brainstem and spinal cord receives descending projections [48]. Anti-histamine medications are intended to act on peripheral histamine release from mast cells, but are well-known to induce drowsiness presumably through central actions (White and Rumbold, 1988). Anti histamine medications are thought to act centrally inhibiting the arousal function of histamine on cortex [49] and thalamus [50] resulting in drowsness. In addition other hypothalamic nuclei, the basal forebrain, brainstem cholinergic and noradrenergic nuclei may contribute to the arousal actions of histamine. Histamine effect is thought to be receptor specific as activation of H1 receptors will facilitate alertness where H3 receptors activation will result in drowsiness.
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Hydrolysis of Adenosine Mono phosphate (AMP) and S adenosyl- homocysteine (SAH) will result in adenosine production which is known as a somnogenic substance that has control on normal sleep–wake patterns. The neuroanatomical sources of adenosine are not well known, but functionally it is well known neuromodulator contributing to the conscious arousal The adenosine system can affect the gating of Slow Wave System-Slow Wave Activity expression. Adenosine affect is through modulating of the arousal level, thereby altering the duration of time during which sleep homeostasis and function can occur [52]. Adenosine receptor stimulation is expected theoretically to act as a potential treatment for insomnia. In spite of the fact that A2AR agonists strongly induce sleep, classical A2AR agonists have adverse cardiovascular effects that restrict its use clinically. In addition the passage of adenosine across the blood–brain barrier (BBB) is known to be poor with evidence of rapid degradation inside endothelial BBB cells. Infusing of selective A2AR agonist CGS21680 increases the release of GABA in the tuberomammillary nucleus (TMN), but not in the frontal cortex and decreases histamine release in the frontal cortex and medial preoptic area. Adenosine arousal effect can be blocked by coffee and theophylline.
The last 7 decades conceptual model of the consciousness scientific dilemma in general human knowledge as well as in scientific specialties in psychiatry, neurology, clinical neuroscience and all related disciplines was based on reductionist concepts that aimed at naturalizing all phenomena of mind including memory and other higher functions, to solely, cellular and molecular mechanisms of the human nervous system [53]. This dogma occupied the scientific understanding of the twentieth century. As a matter of fact those reductionist ideas as well as their opponents extended few thousands of years deep in the human history. Example of the opponents are the phrenologicals as documented by work of the Austrian anatomist Franz Joseph Gall (1758–1828), [54]. In fact in ancient Egyptian wisdom the role of human brain as the source of wisdom and consciousness was not of value. In fact, when creating a mummy, the Egyptians scooped out the brain through the nostrils and threw it away [55]. The ancient Egyptians believed that the heart, rather than the brain, was the source of human wisdom, as well as emotions, memory, the soul and the personality itself. The father of the reductionist theory of brain functioning in todays medicine is Wilder Penfield’s (1891–1976) who adopt the concept that electrical stimulations in certain brain areas produce experiential phenomena [56]. The originality and innovative level of Penfield’s contributions to the field of neurophysiological localization of the higher psychological functions in the human cortex as well as the purity of his operational research approaches was questioned and criticized. Now a days, Penfield approach with his neurological and psychiatric patients is of considerable academic debate in the scientific communities [57]. In historical appraisal R. Nitsch and F. W. Stahnisch in the journal Cerebral Cortex challenged Penfield original concept of experiential phenomena elicited by electrical Stimulation of the human cortex. They revisited Penfield clinical work and found that the actual results obtained from electrical stimulation studies of the brain are far less conclusive, than his firm assertions made during Penfield Gordon Wilson Lecture in 1950. They stated clearly “In-depth comparison with the original stimulation map shows clearly that the original stimulation protocol did not support this repetitive account by stimulation at the same point”. There was no consistent response of defined experiential phenomena observed upon stimulation of an individual stimulation point of the original work. In addition there was no full memory repertoire could be elicited. Patient’s stimulation records did not yield stream of an individual’s consciousness [58]. The heaviness of the scientific evidence emphasizing that consciousness is a complex reconstructive process, not merely limited to electrophysiological stimulation and recordings is beyond the stage of simply overlooking the situation.
The thalamocortical complex does not seem to be critically essential for consciousness experience. Brainstem mechanisms by its own can create adequate consciousness state. This means that Consciousness without a cerebral cortex is possible [59]. Penfield and Jasper note that a cortical removal even as radical as hemispherectomy deprived their patients certainly from of information and discriminative capacities but not consciousness [60]. An explicit reference to the midbrain reticular formation was always included in Penfield and Jasper definition of their proposed centrencephalic system. Sprague in 1966 contribute significantly to consciousness research after performing complete removal of the posterior visual areas of one hemisphere in the cat. Agrees well with the Penfield and Jasper perspective that without cognizance of potential subcortical contributions to cortical damage deficit, the cortical functions will be counterfactually inflated [61]. Striking scientific agreement arguing strongly against the necessity of cerebral cortex for consciousness experience is seen in children born without cortex, namely Hydranenecephalic children. It is a congenital anomaly of the brain where for genetic or acquired reasons the cerebral cortex is drastically under developed and replaced by cerebrospinal fluid (Figure 1).
Sagittal MRI section for a child demonstrating drastic underdevelopment of cerebral cortex with only remnants of occipital and temporal lobes. Cerebellum and brainstem are intact.
Neurological evaluation reveals they are responsiveness to their surroundings and conscious. Personal observations reported by hundreds of families of affected children stressed on the fact that their responsiveness is most readily to sounds, but also to salient visual stimuli. To the surprise a paradox phenomena in this regard is rarity for any auditory cortex to be spared in those children in spite of their impressive sound responsiveness. Bjorn Merker wrote a unique chapter entitled “Consciousness without a cerebral cortex: A challenge for neuroscience and medicine” which appeared in Behavioral and Brain Sciences and was able to spent seven days of observation with 5 families in a visits to Disney World. He stated that “They express pleasure by smiling and laughter, and aversion by “fussing,” arching of the back and crying (in many gradations), their faces being animated by these emotional states. The children respond differentially to the voice and initiatives of familiars, and show preferences for certain situations and stimuli over others, such as a specific familiar toy, tune, or video program, and apparently can even come to expect their regular presence in the course of recurrent daily routines. “[62] It is woeful that many medical institutes label hydranenecephalic children to be in a vegetative state. On the other hand
44 years old french man with 90% absence of his cerebral cortex. His consciousness, mentality as well as social life were otherwise normal. LV=lateral ventricle. III=third ventricle. IV=fourth ventricle. Arrow=Magendie’s foramen.
Thinking of intelligence from the point of computer and artificial intelligence language will denote the fact that the higher the capacity and intellectual power of a computer requires larger hard ware and more sophisticated computers. The comparisons is not valid in case of human brain as the anatomical study of the most intelligent human in the 20 century Albert Einstein’s brain was not showing any convincing anatomical difference than any body brain. Witelson and colleagues’ claim that Einstein’s brain lacks a parietal operculum on the left and right sides. A M Galaburda from Harvard Medical School -and others- argues strongly against this and documented that Einstein’s brain is no exception to the most common of patterns, showing a parietal operculum on the left and the typical posteriorly rising Sylvian fissure on the right (Figure 3) [64, 65].
Einstein’s brain is no exception to the most common of patterns, showing (A): Typical posteriorly rising Sylvian fissure on the right (arrow) and (B): A parietal operculum on the left (asterisk).
It is conspicuous for the ingenious observer in the consciousness scientific arena that the inability to explain and match facts and observations and the failure to reproduce the exact consciousness experience incorporating current knowledge in the field implies presence of deficient rings in the long chain that demand more comprehensive perspective. In this regard we established the King of Organs International Congress for Advanced Cardiac Sciences and held five international congresses (2006,2007,2008,20,101,2012 and 2019). The King of Organs congresses are an international collaborative efforts between international renewed scientists in cardiac sciences, psychologists, astrophysicist, mathematicians, geologists, space engineers, signal analysis specialists and other related disciplines. It is chaired by us in Prince Sultan Cardiac Center (Alhasa, Saudi Arabia). Our academic partners are the HeartMath Institute and the Global Coherence Initiative (Boulder Creek, CA, USA), American Institute of Stress (NY, USA), The Global Consciousness Project (Institute of Noetic Sciences, USA), and other western and eastern reputable universities and collaborators.
The field of neurocardiology is relatively new discipline which was discussed first time in a scientific conference in King of Organs 2006,Saudi Arabia. The meticulous and sophisticated neurological afferent pathways (Figure 4) as well as energetic dominance of the heart over the brain was astonishing for the modern scientific communities. The amplitude of the cardiac electrical signal is about 60 times greater in amplitude compared to the brain while the electromagnetic field of the heart is approximately 5000 times stronger than the brain and can be detected six feet away from the body with sensitive magnetometers. Other ways the heart communicate the brain are hormonal and biophysical.
The currently known afferent pathways by which information from the heart and cardiovascular system modulates brain activity. The nucleus of tractus solitarius (NTS) direct connection to the amygdala, hypothalamus and thalamus is shown. In addition there is emerging evidence of the presence of a pathway from the dorsal vagal complex that travels directly to the frontal cortex.
John and Beatrice Lacey during 1960s and 1970s created a massive drift in the modern psychophysiological research with their publications on human heart –brain communication [66, 67]. An important land mark in the field was there observations that afferent input from the heart and cardiovascular system could significantly affect perception, cognitive functions and behavior. This was neurophysiological evidence signifying that sensory and motor integration could be modified by cardiovascular activity. The heart behaves as if it had a mind of its own. In contradiction to Cannon theory of homeostasis, Laceys showed that patterns of physiological responses were affected as much by the context of a specific task and its requirements as by emotional stimuli. A phenomenon called by Laceys the
One of the strategic scientific, philosophical, as well as conceptual turning points that emanates from the basic science and neuroscientific arena is the accumulating evidence of the precedence of the heart detection of sensory stimulus before the brain. Hyeong-Dong Park in nature neuroscience, documented neural events locked to heartbeats before stimulus onset predict the detection of a faint visual grating in two regions that have multiple functional correlates and that belong to the same resting-state network:the posterior right inferior parietal lobule and the ventral anterior cingulate cortex Figure 5 [73].
Neural events locked to heartbeats before stimulus onset predict the conscious detection of a faint visual grating in the posterior right inferior parietal lobule and the ventral anterior cingulate cortex [
There is compelling evidence to suggest the physical heart is coupled to a field of information not bound by the classical limits of time and space [74]. Rigorous experimental study demonstrated the heart receives and processes information about a future event before the event actually happens. The study’s results provide surprising data showing that both the heart and brain receive and respond to pre-stimulus information about a future event before it occurs but the heart proceeded the brain by 1.3 seconds which is truly too long time in the scale of neural impulse transmission which is counted with milliseconds (Figure 6).
Temporal dynamics of heart and brain pre-stimulus responses. Sharp downward shift about 4.8 seconds prior to the stimulus (arrow 1) is seen. The emotional trials ERP showed a sharp positive shift about 3.5 seconds prior to the stimulus (arrow 2). This positive shift in the ERP denotes the time the brain “knew” the nature of the future stimulus. The time difference between these two events suggests that the heart received the intuitive information about 1.3 seconds before the brain. Heartbeat-evoked potential analysis confirmed that a different afferent signal was sent by the heart to the brain during this period. (ERP) is event-related potential at EEG site FP2.HRV is heart rate variability [
Astonishing fact of the vagus nerve (means the nerve with unknown role) called sometimes, the tenth cranial nerve is the fact that it has very significant afferent neurons beside what we taught about its efferent neurons in our medical schools. 85–90% of the fibers in the vagus nerve are afferent [75]. The majority of higher brain centers, as well as emotional experience and cognitive processes are operated by Cardiovascular related afferent neural traffic [76]. Numerous brain centers including the thalamus, hypothalamus, and amygdala are connected to cardiovascular afferents. Range of frequencies of complex afferent information related to mechanical and chemical factors is continuously sent to the brain and is over time scales ranging from milliseconds to minutes [77]. Vagal afferent nerve stimulation causing increases traffic over the normal intrinsic levels in the thalamic pain pathways in the spinal cord will inhibit those pathways. In addition, vagal afferent nerve stimulation was shown to reduces migraine and cluster headaches and to improve cognitive processing and memory [78]. Activating afferent input with vagal nerve stimulation (VNS) is apparently heralding a new era in medical therapeutics as it proves effective in many psychophysiological disorders including epilepsy, obesity, depression, anxiety, autism, alcohol addiction, mood disorders, as well as multiple sclerosis, and traumatic brain injury [79, 80]. The cardiac coherence training is known to intensify afferent vagal neuronal inputs to cortical and subcortical systems and to Neuronal Correlates of Consciousness (NCC) with long term capabilities to reset the reference set up points resulting in increased afferent nerve activity noninvasively and ultimately improves psychophysiological parameters and the consciousness experience. There is thus a need to explore novel ways of repairing lost consciousness. Vagus nerve stimulation (VNS) may also contribute to breaking advances in awakening the unconscious vegetative state patient as approved by improvement in behavioral responsiveness and enhanced brain connectivity patterns. The vagus nerve carries afferent connections to the deep nuclei of the brain via the nucleus solitaries (see Figure 4). These afferent connections have multiple consciousness related targets, which include the thalamus, amygdala, reticular formation, hippocampus, raphe nucleus, and the locus coeruleus. VNS will create improved global neurostimulation state leading to promoted spread of cortical signals and caused an increase of metabolic activity leading to behavioral improvement as measured with the Coma Recovery Scale-Revised (CRS-R) scale [81]. Theta waves dominance were shown in the right inferior parietal and the parieto-temporal-occipital border, a region known to be instrumental in conscious awareness.
McCraty and colleagues introduced the term physiological coherence to describe the degree of order, harmony, and stability in the various rhythmic activities within living systems over any given time period [82]. This harmonious order signifies a coherent system that has an efficient or optimal physiological functioning which will be reflected in more resilient personality and higher consciousness. Physiological coherence (also referred to as cardiac coherence) can be measured by HRV analysis where more ordered sine like HRV pattern will be seen around frequency of 0.1 Hz (10 seconds) which will be seen as very narrow, high-amplitude peak in the low frequency (LF) region of the HRV power spectrum with no major peaks in the VLF or HF regions [83].
Ground breaking discovery emphasizing the ability of afferent cardiac signals to reprogram the cortical and subcortical neural networks is what we describe as the
Heart activity affects brain function. The ascending heart signals impact autonomic regulatory centers in the brain and cascade up to higher brain centers involved in emotional and cognitive processing, including the thalamus, amygdala, and cortex [
Heartbeat evoked potentials (HEPs) are segments of electroencephalogram (EEG) that are synchronized to the heartbeat. The ECG R-wave is used as a timing source for signal averaging, resulting in waveforms known as HEPs. Based on animal studies, Those cardiac afferents are transmitted to cortical areas including the insula, amygdala, somatosensory cortex and cingulate cortex, through subcortical relays such as the nucleus of the solitary tract, parabrachial nucleus, and thalamus Changes in these evoked potentials associated with the heart’s afferent neurological input to the brain are detectable between 50 and 550 ms after each heartbeat [70].
Initiation of negative or positive emotion conditions by recalling past events reduced HRV and N250 amplitude. In contrast, resonance frequency breathing with HRV frequency around the 0.1 Hz peak increased HRV and HRV coherence above baseline and increased N250 amplitude [90]. We and others thought of HEPs as a neural marker of cardiac-related cortical processing in in consciousness and other diverse cognitive functions. Different afferent input mechanisms from the heart to the brain during different emotions and HRV can be identified using HEPs. Hyeong-Dong Park et al., found that neural responses to heartbeats can be recorded mainly in the insula (i.e., anterior, posterior) and operculum (i.e., frontal, central, posterior)., although it can be found in other regions distributed across the brain including the amygdala and fronto-temporal cortex [91]. It is known that insula is the primary cortical projection site of interoceptive signals. It is interesting to know that the HBEP is significantly higher during interoceptive compared to exteroceptive attention, in a time window of 524–620 ms after the R-peak [92].
Similarities of basic frequencies, harmonics, magnetic field intensities, voltages, band widths, and energetic solutions between the Schumann resonances in the space between earth and ionosphere and the activity within the human cerebral cortices suggest the capacity for direct interaction [93]. Every cell in our body is bathed in an internal and external environment of fluctuating invisible magnetic forces that can affect virtually every cell and circuit in biological systems [94]. Therefore, it should not be surprising that numerous physiological rhythms in humans heart and brain and global collective behaviors are not only synchronized with solar and geomagnetic activity, but disruptions in these fields can create adverse effects on human health and behavior. The most sensitive body systems to those fluctuating electromagnetic environments are the heart and brain [95]. The heart is the largest dynamic organ in the human body. No surprise that the heart magnetic field is the strongest rhythmic field produced by the human body. The second strongest magnetic generator is the brain. The primary source of the electromagnetic activity of the brain measured from the scalp and emerges from the cerebral cortices because of the parallel arrangement of the dendrite-soma-axo orientations perpendicular to the surface for most of the approximately 20 billion neurons. Superimposed upon the steady potential are fluctuating voltages that define the electroencephalogram (EEG). It is not surprising that the heart’s electrical field is about 60 times greater in amplitude than the electrical activity generated by the brain. There is a direct mathematical relationship between the HRV
Resonance refers to vibration of large amplitude in electrical or mechanical system caused by a relatively small periodic stimulus of the same or nearly the same period as the natural vibration period of the system. The concept of resonance and its implementations in physiological as well as astrophysical rhythms is of critical significance for life on earth and to human consciousness experience. All biological systems on the planet are exposed to an external and internal environment of fluctuating invisible wide range of magnetic fields frequencies. These fields can affect virtually every cell and circuit to a greater or lesser degree. Numerous physiological rhythms have been shown to be synchronized with solar and geomagnetic activity. Geomagnetic and solar influences affect a wide range of human rhythmic systems with the nervous and cardiovascular systems, with their significant contribution to consciousness, being the most clearly impacted [70]. Sharp variations of sudden and sharp nature of geomagnetic, solar activity and its resultant geomagnetic storms can act as stressors, which has the capacity to alter body regulatory processes and rhythmic systems such as melatonin/serotonin balance, blood pressure, breathing, reproductive, immune, neurological, and cardiac system processes [98, 99, 100, 101]. In the clinical arena significant increases in hospital admissions for depression, mental disorders psychiatric admission, homicides, suicide attempts, and traffic accidents are associated with planetary geomagnetic disturbances [102, 103, 104, 105, 106, 107, 108]. Increase incidence of myocardial infarctions, vascular variability disorders, local and global communication between humans during geomagnetic disturbances are all denotes that brain and cardiovascular systems are clear targets for the planetary geomagnetic disturbances [109, 110, 111, 112, 113, 114]. Exacerbation of present disease like development of cardiac arrhythmias and epilepsy is well known during disturbed geomagnetic activity. Low frequency magnetic oscillations, around 3 Hz, was observed to cause Altered EEG rhythms with sedative effect [115]. Applying the lowest Schumann Resonance (SR) frequency of 7.8 Hz with 90 nano Tesla for 1.5 hours was found to be cardioprotective from stress conditions with reduction of the amount of CK released to the buffer, during normal conditions, hypoxic conditions and oxidative stress induced by 80 μM H2O2 [116]. The longest record in human history of human heart rate variability (HRV) synchronized with Solar Wind indices, Shumann Resonances (SR) and Galactic Cosmic Rays (GCR) monitoring was achieved by our group [117]. Schumann resonance frequency is 7.83 hertz (Hz), with a (day/night) variation of around ±0.5 Hz. The higher frequencies are ~14, 20, 26, 33, 39 and 45 Hz, all of which closely overlay with alpha (8–12 Hz), beta (12–30 Hz) and gamma (30–100 Hz) brain waves. The delicate orchestration of this universal symphony and vibrations with the human autonomic nervous system (ANS) that interacts with cerebral cortex and control heart rhythm, respiration, digestive functions and other involuntary activities was investigated. We were able to confirm that changes in solar and geomagnetic activity during periods of normal undisturbed activity affect daily ANS activity. In an other publication, we were able to document significant correlations between the group’s HRV and solar wind speed, Kp, Ap, solar radio flux, cosmic ray counts, Schumann resonance power, and the total variations in the magnetic field [110] This affect is initiated at different times after the changes in the various environmental factors and persist over varying time periods. Peaks of increased solar activity occurs every 10.5 to 11 years. During those peaks, the sun emits increased ultraviolet (UV) energy and solar radio flux, which is measured by the 2.8 GHz signal (F10.7) [110] We considered Solar wind intensity as biological stressor as increase in its intensity is well correlated to increase heart rate. Galactic Cosmic Rays (GCR) are highly energetic particles that originate outside the solar system and are likely formed by nuclear explosive events in supernova and other mega giant galaxies. These highly energetic particles consist of fully ionized nuclei ranging from hydrogen, accounting for approximately 89% of the GCR spectrum, to trace amounts of uranium. The planetary magnetic field and the solar winds are protective for life on earth from this extremely ionized rays. We documented that human HRV with its modulatory effect on the consciousness pillars through ascending neuronal input to cortical and sub cortical structures increases with rise of the three major universal vibrations that we examined: Solar Winds, Shumann Resonances (SR), and the Galactic Cosmic Rays (GCR). This complex interaction between HRV and those environmental energetic fields may contribute to the human knowledge about the pathomechanistic effects on human psychphysiological homeostasis and the consciousness experience.
It is conspicuous from the previous sections that the neuronal firing of brain structures is not enough to explain subjective consciousness experience. Quantum physicists Larissa Brizhik and Emilio DelGiudice suggested that the most likely physical agent that can continuously provide an exchange of information between living systems within the larger ecosystem is the magnetic fields. According to the quantum field theory, potentials of the magnetic field, governs the dynamics of biological systems and the whole ecosystem. As a matter of fact, the planetary magnetic field is ubiquitous and involved in the deep behavior of biology. Animals can detect the Earth’s magnetic field through magnetoreception-related photoreceptor cryptochromes [118] through which the planetary magnetic field guides the different species in their thousands of miles migration in land and oceans. The field causes the emergence of the coherent structures, which, in view of their coherence, openness and nonlinearity, are able to self-organize and form a chain of hierarchical levels of ecosystems [119] Coherence in the quantum language implies correlations, connectedness, consistency, efficient energy utilization, and the concept of global order, where the whole is greater than the sum of its individual parts. In medicine we refer to coherence to implies a harmonious relationship, correlations and connections between the various parts of a system. The Wight of evidence towards new evolutionary paradigm of the origin and effect of human consciousness with mutual effect to the environment is prevailing.
Evidence is accumulating supporting the hypothesis that our consciousness can even influences our physical world. Random number generators (RNGs) are one tool used to evaluate micro-psychokinesis or our ability to affect the physical world with our consciousness. Research conducted by the Global Consciousness Project (GCP) (which maintains a worldwide network of random number generators running constantly at about 60 locations around the world, sending streams of 200-bit trials generated each second to be archived as parallel random sequences), has found that human emotionality affects the randomness of these electronic devices in globally correlated manner. Roger Nelson who is the founder of GCP reported in a recent publication multiple examples of striking similarity between event-related brain potentials and event-related correlations in random data [119] (Figure 8). If all living systems are indeed interconnected and communicate with each other via biological and electromagnetic fields, it stands to reason that humans can work together in a co-creative relationship to consciously increase global coherence and raise the global consciousness. It is conspicuous that classical mechanics cannot explain consciousness. Quantum consciousness is the science that incorporate conceptual discussion of phenomenon of quantum mechanics like entanglement and superposition to explore the deep science of human consciousness.
Striking similarity between evoked potential (EP) from an auditory stimulus (the black) and composite of GCP data from nine 6 hour events (the red) [
The idea that quantum mechanics has something to do with the workings of the mind was developed by Eugene Wigner, Hungarian-American theoretical physicist and Nobel Prize Laurete in Physics in 1963,who proposed that the wave function collapses due to its interaction with consciousness. Freeman Dyson argued that “mind, as manifested by the capacity to make choices, is to some extent inherent in every electron. David Bohm is theoretical physicists who contributed significantly to quantum theory, neuropsychology and the philosophy of mind. He stimulated new era of conceptual approach to consciousness with more fundamental level in the universe. He claimed both quantum theory and relativity pointed to this deeper theory, which he formulated as a quantum field theory. Bohm’s proposed implicate order which applies both to matter and consciousness. He suggested that it could explain the relationship between them. Bohm’s views mind and matter as projections into our explicate order from the underlying implicate order This more fundamental level was proposed to represent an undivided wholeness and an implicate order, from which arises the explicate order of the universe as we experience it. Holonomic brain theory is a branch of neuroscience investigating the idea that human consciousness is formed by quantum effects in or between brain cells. This specific theory of quantum consciousness was developed by neuroscientist Karl Pribram initially in collaboration with David Bohm. In addition to the neuroanatomical components of the human brain including the large fiber tracts in the brain, neurotransmissions also occurs in dendrites and other webs of fine fiber branche, that form webs. Due to the billions of action potentials and neural impulse formations, dynamic electrical fields will result around these dendritic trees. Those dendritic trees can affect other surrounding neurons without physical contact between them by entanglement. In this way, processing in the brain can occur in a non-localized manner. An energy-based concept of information was described by Dennis Gabor, who invented the hologram in 1947,which he described as quanta of information. Later on, he won Nobel prize in physics for this invention in 1971.Kal H.Pribram’s holonomic model of brain processing was described in his 1991
In this chapter we investigate the elusive issue of human consciousness. We introduce revolutionary paradigm in the time line of consciousness science, where we discuss a comprehensive perspective of the process of consciousness of neurobiological and astrophysical bases. Our new perspective is built on our work confirming the symphony interplay of human ANS represented by HRV on one hand and Shumann Resonances, Solar Wind Indices and Cosmic Rays on the other hand. In addition to up to date discussion on the neuroanatomical aspects of consciousness, the delicate and powerful contribution of cardiac afferent input to brain consciousness related cortical and subcortical structures and pathways and heartbeat evoked potentials (HEP) is discussed. The role of the quantum principles and magnetic potentials in the universal information processing is emphasized. Our new perspective is complementary but never competitive to the quantum consciousness theories discussed especially the theories of Karl Primbram-David Bohem, Penrose and Stuart Hameroff, and Pierce Stapp. This new comprehensive understanding of human consciousness should bring many scientific disciplines closer to illustrate the necessity of the intelligent blend of science branches to solve historical human issues in medicine, science, philosophy, and religion.
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It is currently affected by different pressures, mainly driven by human activities such as climate change and bioinvasions. This Sea, also due to its geographic position (wedged between the temperate climate of central Europe and the arid climate of northern Africa), seems to be one of the regions most susceptible to global climate change. The increased rates of introduction and spread of marine alien species may represent a supplementary stress factor to Mediterranean marine native biota already challenged by climatic abnormalities. The Suez Canal is considered to be the main vector of introduction of non‐indigenous marine species into the Mediterranean Sea. Due to the dramatically accelerating rate of such introductions and due to the sheer magnitude of shipping traffic, the Mediterranean Sea may be considered as a true hotspot of marine bioinvasions. The complexity of interactions between native and invasive species and the associated resulting impacts make environmental management of such an issue particularly difficult. A collaboration between researchers, resource management agencies and policy makers is called for to bolster the effectiveness of invasive species management procedures.",book:{id:"5995",slug:"mediterranean-identities-environment-society-culture",title:"Mediterranean Identities",fullTitle:"Mediterranean Identities - Environment, Society, Culture"},signatures:"Anna M. 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The effects in regard to the time trends, vegetation, and soil will be reflected in the species distribution, forest composition, and soil potential productivity. In general, it can be said that the larger the fire and the shorter the time between two consecutive occurrences, the higher the probability to originate shifts in vegetation and soil degradation. In the Mediterranean region, the number of fire ignitions does not reflect the burnt area due to the occurrence of very large fires. The latter occur in a very small proportion of the number of ignitions, but result in very large burnt areas. Also there seems to be an increasing trend toward larger fires in the Mediterranean region due mainly to climatic and land use changes. This case study highlights the importance of vegetation regrowth a short time after the fire to maintain both forest systems and soil conservation.",book:{id:"5995",slug:"mediterranean-identities-environment-society-culture",title:"Mediterranean Identities",fullTitle:"Mediterranean Identities - Environment, Society, Culture"},signatures:"Ana Cristina Gonçalves and Adélia M.O. 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This inspired a study to assess the role of eco-village practices in strengthening climate change adaptive capacity and mitigating desertification in semi-arid areas of Chololo village, Dodoma region in central Tanzania. Data were collected using mixed methods, that is, household survey (92), focus group discussions (21), key informants interviews (6), field observation and documentary review. Statistical Package for Social Sciences (SPSS) and content analysis were used in analyzing quantitative and qualitative data respectively. The study found a relatively high level of community awareness on the eco-village initiative; the initiative rehabilitated village forest reserve; improved land productivity for sorghum and pearl millet; increased number of planted trees; and strengthening communities’ adaptation to climate change through improved households’ nutrition, income and reduced water stress.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Fredy S. Mswima and Abiud L. Kaswamila",authors:[{id:"115390",title:"Prof.",name:"Abiud L.",middleName:"Lucas",surname:"Kaswamila",slug:"abiud-l.-kaswamila",fullName:"Abiud L. Kaswamila"},{id:"415117",title:"Dr.",name:"Fredy S.",middleName:null,surname:"Mswima",slug:"fredy-s.-mswima",fullName:"Fredy S. Mswima"}]},{id:"77741",title:"Characteristic on the Stability of Haloxylon ammodendron Plantation in the Southern Fringe of Gurbantunggut Desert, Northwest China",slug:"characteristic-on-the-stability-of-em-haloxylon-ammodendron-em-plantation-in-the-southern-fringe-of-",totalDownloads:165,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Using chronosequence theory and method, the characteristics of vegetation-soil coupling and structure stability of Haloxylon ammodendron plantations in the southern fringe of Gurbantunggut Desert were analyzed. The results showed, the canopy storey of H. ammodendron plantation experienced three stages, rapid growth (the age of 7 to 20), then slow growth (the age of 20 to 28) and last decline (over the age of 28). The best natural regeneration started from 17-yr-old plantation. Vegetation-soil system coupling degree (C) and coupling coordinative degree (D) of plantations with different age were not one-to-one correspondence. The system of H. ammodendron plantations always stayed in disorder recession, vegetation and soil were prone to loss type during the process of sand-fixation. Five principal components evaluated that the first rank was 42-yr-old plantation. It was inferred that the trend of the vegetation and soil system was from senescence to harmonious development. So the trend of coordinated development between vegetation and soil would be promoted, if the artificial tending and management measures strengthened.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Qinghong Luo, Qimin Chen, Miao He and Na Li",authors:[{id:"340564",title:"Dr.",name:"Qinghong",middleName:null,surname:"Luo",slug:"qinghong-luo",fullName:"Qinghong Luo"},{id:"347848",title:"Mr.",name:"Qimin",middleName:null,surname:"Chen",slug:"qimin-chen",fullName:"Qimin Chen"},{id:"348214",title:"Associate Prof.",name:"Miao",middleName:null,surname:"He",slug:"miao-he",fullName:"Miao He"},{id:"348215",title:"Associate Prof.",name:"Na",middleName:null,surname:"Li",slug:"na-li",fullName:"Na Li"}]},{id:"77086",title:"Bowing Sand, Dust, and Dunes, Then and Now–A North American Perspective",slug:"bowing-sand-dust-and-dunes-then-and-now-a-north-american-perspective",totalDownloads:94,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Dune fields of the present day, the Dust Bowl disaster of the 1930s U.S. Great Plains, and contemporary efforts to forecast, simulate, and understand dust storms have a striking, uniform commonality. What these apparently diverse phenomena have in common is that they all result from blowing sand and dust. This review paper unifies these three disparate but related phenomena. Its over-arching goal is to clearly explain these manifestations of windblown sand and dust. First, for contemporary dune fields, we offer reviews of two technical papers that explain the eolian formation and the continuing development of two major dune fields in southeastern California and northwestern Sonora, Mexico: the Algodones Dunes and the Gran Desierto de Altar. Second, historical, geological, meteorological, and socioeconomic aspects of the 1930s Great Plains Dust Bowl are discussed. Third, and last, we return to the present day to summarize two lengthy reports on dust storms and to review two technical papers that concern their forecasting and simulation. The intent of this review is to acquaint the interested reader with how eolian transport of sand and dust affects the formation of present-day dune fields, human agricultural enterprises, and efforts to better forecast and simulate dust storms. Implications: Blowing sand and dust have drastically affected the geological landscape and continue to shape the formation of dune fields today. Nearly a century ago the U.S. Great Plains suffered through the Dust Bowl, yet another consequence of blowing sand and dust brought on by drought and mismanagement of agricultural lands. Today, this phenomenon adversely affects landscapes, transportation, and human respiratory health. A more complete understanding of this phenomenon could (and has) led to more effective mitigation of dust sources, as well as to a more accurate predictive system by which the public can be forewarned.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Peter Hyde and Alex Mahalov",authors:[{id:"348247",title:"Dr.",name:"Peter",middleName:null,surname:"Hyde",slug:"peter-hyde",fullName:"Peter Hyde"},{id:"419631",title:"Dr.",name:"Alex",middleName:null,surname:"Mahalov",slug:"alex-mahalov",fullName:"Alex Mahalov"}]},{id:"61738",title:"Assessment of the Riparian Vegetation Changes Downstream of Selected Dams in Vhembe District, Limpopo Province on Based on Historical Aerial Photography",slug:"assessment-of-the-riparian-vegetation-changes-downstream-of-selected-dams-in-vhembe-district-limpopo",totalDownloads:1571,totalCrossrefCites:0,totalDimensionsCites:2,abstract:"Dams have been associated with various impacts on downstream river ecosystems, including a decrease in stream flow, species biodiversity, water quality, altered hydrology and colonisation of the area by invasive alien plant species. The impacts normally interfere with the ecosystem functioning of riparian and aquatic environments, thereby leading to decreased biodiversity. This study aims to assess the impacts of dams on downstream river ecosystems, using data from aerial photographs and orthophotos, supplemented by field work. Five dams in Limpopo Province, South Africa, were selected (Albasini, Damani, Mambedi, Nandoni and Vondo), and photographs from different years were used. The area devoid of trees of certain species both downstream and upstream of the dams was calculated using grids of predetermined square sizes on each available photograph. Aerial photographs and orthophoto data were supplemented by field work. The nearest-individual method was used in the field to determine tree density of particular tree species. The environments downstream of the dams show a loss of obligate riparian vegetation and an increase of obligate terrestrial vegetation (Acacia Karroo, Acacia Ataxacantha and Bauhinia galpinii). Treeless area increased in all cases, especially in the case of Mambedi and Vondo dams, indicating lower resilience and higher fragility there.",book:{id:"6706",slug:"environmental-risks",title:"Environmental Risks",fullTitle:"Environmental Risks"},signatures:"John M. Mokgoebo, Tibangayuka A. Kabanda and Jabulani R.\nGumbo",authors:[{id:"224099",title:"Prof.",name:"Jabulani",middleName:null,surname:"Gumbo",slug:"jabulani-gumbo",fullName:"Jabulani Gumbo"},{id:"250766",title:"Mr.",name:"M.J.",middleName:null,surname:"Mokgoebo",slug:"m.j.-mokgoebo",fullName:"M.J. Mokgoebo"},{id:"250767",title:"Prof.",name:"T.A.",middleName:null,surname:"Kabanda",slug:"t.a.-kabanda",fullName:"T.A. Kabanda"}]},{id:"78428",title:"Jojoba - The Gold of Desert",slug:"jojoba-the-gold-of-desert",totalDownloads:247,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Jojoba [Simmondsia chinensis (Link) Schneider] is evergreen, perennial and drought resistant shrub belongs to the family of Simmondsiaceae. It is a multipurpose oil seed crop mainly grown in desert regions of world. This plant has unique oil among plant kingdom which is chemically a liquid-wax. The liquid-wax is made up of an ester of long chain fatty acids and alcohols. The liquid-wax is unique in nature because have no traces of glycerine and easily modified via hydrolysis, hydrogenation, halogenation, sulfurization, phosphosulfurization and ozonization techniques. The main uses of liquid-wax in various industries like cosmetics, pharmaceuticals, petrochemicals and lubricants. It is a potential seed oil crop for desert region so it is well known as the gold of desert. The main purpose of this chapter is to review the complete information about this plant so that it can produce and utilized maximally. Moreover, the review focuses on biology, biogeography, physico-chemical properties of jojoba oil and propagation techniques of the plant of desert regions.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Raman Bala",authors:[{id:"347678",title:"Dr.",name:"Raman",middleName:null,surname:"Bala",slug:"raman-bala",fullName:"Raman Bala"}]}],onlineFirstChaptersFilter:{topicId:"135",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:319,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:133,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:16,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. She is an author of about 90 publications (According to Scopus: H-Index: 23; According to WOS: H-Index: 20) on peer-reviewed journals, a member of the “Società Italiana di Biochimica e Biologia Molecolare,“ and a Consultant Reviewer for International Journal of Molecular Science, Journal of Chromatography A, COPD, Plos ONE and Nutritional Neuroscience.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null}]},overviewPageOFChapters:{paginationCount:37,paginationItems:[{id:"82291",title:"The Role of Oxidative Stress in the Onset and Development of Age-Related Macular Degeneration",doi:"10.5772/intechopen.105599",signatures:"Emina Čolak, Lepša Žorić, Miloš Mirković, Jana Mirković, Ilija Dragojević, Dijana Mirić, Bojana Kisić and Ljubinka Nikolić",slug:"the-role-of-oxidative-stress-in-the-onset-and-development-of-age-related-macular-degeneration",totalDownloads:0,totalCrossrefCites:null,totalDimensionsCites:null,authors:null,book:{title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",subseries:{id:"15",title:"Chemical Biology"}}},{id:"82195",title:"Endoplasmic Reticulum: A Hub in Lipid Homeostasis",doi:"10.5772/intechopen.105450",signatures:"Raúl Ventura and María Isabel Hernández-Alvarez",slug:"endoplasmic-reticulum-a-hub-in-lipid-homeostasis",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82409",title:"Purinergic Signaling in Covid-19 Disease",doi:"10.5772/intechopen.105008",signatures:"Hailian Shen",slug:"purinergic-signaling-in-covid-19-disease",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:10,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}}]},overviewPagePublishedBooks:{paginationCount:32,paginationItems:[{type:"book",id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7006.jpg",slug:"biochemistry-and-health-benefits-of-fatty-acids",publishedDate:"December 19th 2018",editedByType:"Edited by",bookSignature:"Viduranga Waisundara",hash:"c93a00abd68b5eba67e5e719f67fd20b",volumeInSeries:1,fullTitle:"Biochemistry and Health Benefits of Fatty Acids",editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. 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Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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Dr. Şentürk currently works as an professor of Biochemistry in the Department of Basic Pharmacy Sciences, Faculty of Pharmacy, Ağri Ibrahim Cecen University, Turkey. \nDr. Şentürk published over 120 scientific papers, reviews, and book chapters and presented several conferences to scientists. \nHis research interests span enzyme inhibitor or activator, protein expression, purification and characterization, drug design and synthesis, toxicology, and pharmacology. \nHis research work has focused on neurodegenerative diseases and cancer treatment. Dr. Şentürk serves as the editorial board member of several international journals.",institutionString:"Ağrı İbrahim Çeçen University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Ağrı İbrahim Çeçen University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"July 5th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:319,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",fullName:"Abdulsamed Kükürt",profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",institutionString:null,institution:{name:"Kafkas University",institutionURL:null,country:{name:"Turkey"}}},{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/42133",hash:"",query:{},params:{id:"42133"},fullPath:"/chapters/42133",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)}()