These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
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This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
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To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
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Initially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\n
This collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\n
To celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\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:"10779",leadTitle:null,fullTitle:"21st Century Nanostructured Materials - Physics, Chemistry, Classification, and Emerging Applications in Industry, Biomedicine, and Agriculture",title:"21st Century Nanostructured Materials",subtitle:"Physics, Chemistry, Classification, and Emerging Applications in Industry, Biomedicine, and Agriculture",reviewType:"peer-reviewed",abstract:"Nanostructured materials (NMs) are attracting interest as low-dimensional materials in the high-tech era of the 21st century. Recently, nanomaterials have experienced breakthroughs in synthesis and industrial and biomedical applications. This book presents recent achievements related to NMs such as graphene, carbon nanotubes, plasmonic materials, metal nanowires, metal oxides, nanoparticles, metamaterials, nanofibers, and nanocomposites, along with their physical and chemical aspects. Additionally, the book discusses the potential uses of these nanomaterials in photodetectors, transistors, quantum technology, chemical sensors, energy storage, silk fibroin, composites, drug delivery, tissue engineering, and sustainable agriculture and environmental applications.",isbn:"978-1-80355-085-5",printIsbn:"978-1-80355-084-8",pdfIsbn:"978-1-80355-086-2",doi:"10.5772/intechopen.94802",price:139,priceEur:155,priceUsd:179,slug:"21st-century-nanostructured-materials-physics-chemistry-classification-and-emerging-applications-in-industry-biomedicine-and-agriculture",numberOfPages:388,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"72c67f97f9bef68200df115b5fd79884",bookSignature:"Phuong V. Pham",publishedDate:"April 20th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10779.jpg",numberOfDownloads:2697,numberOfWosCitations:0,numberOfCrossrefCitations:4,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:8,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:12,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 24th 2021",dateEndSecondStepPublish:"July 22nd 2021",dateEndThirdStepPublish:"September 20th 2021",dateEndFourthStepPublish:"December 9th 2021",dateEndFifthStepPublish:"February 7th 2022",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"236073",title:"Dr.",name:"Phuong",middleName:"Viet",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham",profilePictureURL:"https://mts.intechopen.com/storage/users/236073/images/system/236073.png",biography:"Phuong V. Pham is a pioneering scientist in materials science and electronic devices. He is currently a senior scientist at the School of Micro-Nano Electronics and Hangzhou Global Scientific and Technological Innovation Center (HIC), Zhejiang University, China. He earned a Ph.D. from SKKU Advanced Institute of Nanotechnology (SAINT), Sungkyunkwan University (SKKU), South Korea. Then, he spent a few years as a postdoctoral researcher and research fellow at the School of Advanced Materials Science and Engineering, SKKU and the Center for Multidimensional Carbon Materials (CMCM), Institute for Basic Science (IBS), South Korea, respectively. He is a recipient of the NSF Career Award and the National Postdoctoral Award for Excellent Young Scientists, China. His research interests include low-dimensional materials, 2D material synthesis, twistronics, straintronics, 2D heterostructures, doping technique development, nanocomposites, block copolymers, plasma engineering for flexible display, sensors, photodetectors, transistors, organic light-emitting diodes, and wearable electronics.",institutionString:"Zhejiang University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Zhejiang University",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"208",title:"Material Science",slug:"nanotechnology-and-nanomaterials-material-science"}],chapters:[{id:"79483",title:"Physics of Nanostructure Design for Infrared Detectors",doi:"10.5772/intechopen.101196",slug:"physics-of-nanostructure-design-for-infrared-detectors",totalDownloads:153,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Infrared detectors and focal plane array technologies are becoming ubiquitous in military, but are limited in the commercial sectors. The widespread commercial use of this technology is lacking because of the high cost and large size, weight and power. Most of these detectors require cryogenic cooling to minimize thermally generated dark currents, causing the size, weight, power and cost to increase significantly. Approaches using very thin detector design can minimize thermally generated dark current, but at a cost of lower absorption efficiency. There are emerging technologies in nanostructured material designs such as metasurfaces that can allow for increased photon absorption in a thin detector architecture. Ultra-thin and low-dimensional absorber materials may also provide unique engineering opportunities in detector design. This chapter discusses the physics and opportunities to increase the operating temperature using such techniques.",signatures:"Nibir Kumar Dhar, Samiran Ganguly and Srini Krishnamurthy",downloadPdfUrl:"/chapter/pdf-download/79483",previewPdfUrl:"/chapter/pdf-preview/79483",authors:[{id:"428664",title:"Prof.",name:"Nibir K.",surname:"Dhar",slug:"nibir-k.-dhar",fullName:"Nibir K. Dhar"},{id:"439626",title:"Dr.",name:"Samiran",surname:"Ganguly",slug:"samiran-ganguly",fullName:"Samiran Ganguly"},{id:"439627",title:"Dr.",name:"Srini",surname:"Krishnamurthy",slug:"srini-krishnamurthy",fullName:"Srini Krishnamurthy"}],corrections:null},{id:"79186",title:"Noise Analysis in Nanostructured Tunnel Field Devices",doi:"10.5772/intechopen.100633",slug:"noise-analysis-in-nanostructured-tunnel-field-devices",totalDownloads:70,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Tunnel Field Effect Transistors (TFETs) have appeared as an alternative candidate of “beyond CMOS” due to their advantages like very low leakage current and steep sub-threshold slope i.e. <60 mV/dec., etc. From past decades, researchers explored TFETs in terms of high ON current and steep subthreshold slope at low supply voltage i.e. < VDD = 0.5 V. The reliability issues of the device have profound impact on the circuit level design for practical perspectives. Noise is one of the important parameters in terms of reliability and very few research papers addressed this problem in comparison to other parameter study. Therefore, in this chapter, we discussed the impact of noise on Tunnel FET devices and circuits. The detail discussion has been done for the random telegraph noise, thermal noise, flicker noise, and shot noise for Si/Ge TFET and III-V TFETs. Recent research work for both low frequencies as well high frequency noise for different TFET device design has been discussed in details.",signatures:"Sweta Chander and Sanjeet Kumar Sinha",downloadPdfUrl:"/chapter/pdf-download/79186",previewPdfUrl:"/chapter/pdf-preview/79186",authors:[{id:"223387",title:"Dr.",name:"Sweta",surname:"Chander",slug:"sweta-chander",fullName:"Sweta Chander"},{id:"427030",title:"Dr.",name:"Sanjeet Kumar",surname:"Sinha",slug:"sanjeet-kumar-sinha",fullName:"Sanjeet Kumar Sinha"}],corrections:null},{id:"79872",title:"Plasmonic 2D Materials: Overview, Advancements, Future Prospects and Functional Applications",doi:"10.5772/intechopen.101580",slug:"plasmonic-2d-materials-overview-advancements-future-prospects-and-functional-applications",totalDownloads:196,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Plasmonics is a technologically advanced term in condensed matter physics that describes surface plasmon resonance where surface plasmons are collective electron oscillations confined at the dielectric-metal interface and these collective excitations exhibit profound plasmonic properties in conjunction with light interaction. Surface plasmons are based on nanomaterials and their structures; therefore, semiconductors, metals, and two-dimensional (2D) nanomaterials exhibit distinct plasmonic effects due to unique confinements. Recent technical breakthroughs in characterization and material manufacturing of two-dimensional ultra-thin materials have piqued the interest of the materials industry because of their extraordinary plasmonic enhanced characteristics. The 2D plasmonic materials have great potential for photonic and optoelectronic device applications owing to their ultra-thin and strong light-emission characteristics, such as; photovoltaics, transparent electrodes, and photodetectors. Also, the light-driven reactions of 2D plasmonic materials are environmentally benign and climate-friendly for future energy generations which makes them extremely appealing for energy applications. This chapter is aimed to cover recent advances in plasmonic 2D materials (graphene, graphene oxides, hexagonal boron nitride, pnictogens, MXenes, metal oxides, and non-metals) as well as their potential for applied applications, and is divided into several sections to elaborate recent theoretical and experimental developments along with potential in photonics and energy storage industries.",signatures:"Muhammad Aamir Iqbal, Maria Malik, Wajeehah Shahid, Waqas Ahmad, Kossi A. A. Min-Dianey and Phuong V. Pham",downloadPdfUrl:"/chapter/pdf-download/79872",previewPdfUrl:"/chapter/pdf-preview/79872",authors:[{id:"236073",title:"Dr.",name:"Phuong",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"},{id:"445754",title:"Dr.",name:"Muhammad Aamir",surname:"Iqbal",slug:"muhammad-aamir-iqbal",fullName:"Muhammad Aamir Iqbal"},{id:"445755",title:"Dr.",name:"Maria",surname:"Malik",slug:"maria-malik",fullName:"Maria Malik"},{id:"445756",title:"Dr.",name:"Wajeehah",surname:"Shahid",slug:"wajeehah-shahid",fullName:"Wajeehah Shahid"},{id:"445757",title:"Dr.",name:"Waqas",surname:"Ahmad",slug:"waqas-ahmad",fullName:"Waqas Ahmad"},{id:"464621",title:"Dr.",name:"Kossi A. A.",surname:"Min-Dianey",slug:"kossi-a.-a.-min-dianey",fullName:"Kossi A. A. Min-Dianey"}],corrections:null},{id:"80095",title:"Doping and Transfer of High Mobility Graphene Bilayers for Room Temperature Mid-Wave Infrared Photodetectors",doi:"10.5772/intechopen.101851",slug:"doping-and-transfer-of-high-mobility-graphene-bilayers-for-room-temperature-mid-wave-infrared-photod",totalDownloads:127,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"High-performance graphene-HgCdTe detector technology has been developed combining the best properties of both materials for mid-wave infrared (MWIR) detection and imaging. The graphene functions as a high mobility channel that whisks away carriers before they can recombine, further contributing to detection performance. Comprehensive modeling on the HgCdTe, graphene, and the HgCdTe-graphene interface has aided the design and development of this MWIR detector technology. Chemical doping of the bilayer graphene lattice has enabled p-type doping levels in graphene for high mobility implementation in high-performance MWIR HgCdTe detectors. Characterization techniques, including SIMS and XPS, confirm high boron doping concentrations. A spin-on doping (SOD) procedure is outlined that has provided a means of doping layers of graphene on native substrates, while subsequently allowing integration of the doped graphene layers with HgCdTe for final implementation in the MWIR photodetection devices. Successful integration of graphene into HgCdTe photodetectors can thus provide higher MWIR detector efficiency and performance compared to HgCdTe-only detectors. New earth observation measurement capabilities are further enabled by the room temperature operational capability of the graphene-enhanced HgCdTe detectors and arrays to benefit and advance space and terrestrial applications.",signatures:"Ashok K. Sood, John W. Zeller, Parminder Ghuman, Sachidananda Babu, Nibir K. Dhar, Randy N. Jacobs, Latika S. Chaudhary, Harry Efstathiadis, Samiran Ganguly, Avik W. Ghosh, Sheikh Ziauddin Ahmed and Farjana Ferdous Tonni",downloadPdfUrl:"/chapter/pdf-download/80095",previewPdfUrl:"/chapter/pdf-preview/80095",authors:[{id:"428664",title:"Prof.",name:"Nibir K.",surname:"Dhar",slug:"nibir-k.-dhar",fullName:"Nibir K. Dhar"},{id:"439626",title:"Dr.",name:"Samiran",surname:"Ganguly",slug:"samiran-ganguly",fullName:"Samiran Ganguly"},{id:"23657",title:"Dr.",name:"Ashok K.",surname:"Sood",slug:"ashok-k.-sood",fullName:"Ashok K. Sood"},{id:"210274",title:"Dr.",name:"John W.",surname:"Zeller",slug:"john-w.-zeller",fullName:"John W. Zeller"},{id:"444716",title:"Ms.",name:"Latika S.",surname:"Chaudhary",slug:"latika-s.-chaudhary",fullName:"Latika S. Chaudhary"},{id:"444719",title:"Dr.",name:"Randy N.",surname:"Jacobs",slug:"randy-n.-jacobs",fullName:"Randy N. Jacobs"},{id:"444720",title:"Dr.",name:"Parminder",surname:"Ghuman",slug:"parminder-ghuman",fullName:"Parminder Ghuman"},{id:"444721",title:"Dr.",name:"Sachidananda",surname:"Babu",slug:"sachidananda-babu",fullName:"Sachidananda Babu"},{id:"444724",title:"Prof.",name:"Harry",surname:"Efstathiadis",slug:"harry-efstathiadis",fullName:"Harry Efstathiadis"},{id:"444727",title:"Prof.",name:"Avik W.",surname:"Ghosh",slug:"avik-w.-ghosh",fullName:"Avik W. Ghosh"},{id:"451870",title:"Dr.",name:"Sheikh Ziauddin",surname:"Ahmed",slug:"sheikh-ziauddin-ahmed",fullName:"Sheikh Ziauddin Ahmed"},{id:"451871",title:"Dr.",name:"Farjana Ferdous",surname:"Tonni",slug:"farjana-ferdous-tonni",fullName:"Farjana Ferdous Tonni"}],corrections:null},{id:"79179",title:"Analysis of Heat Transfer in Non-Coaxial Rotation of Newtonian Carbon Nanofluid Flow with Magnetohydrodynamics and Porosity Effects",doi:"10.5772/intechopen.100623",slug:"analysis-of-heat-transfer-in-non-coaxial-rotation-of-newtonian-carbon-nanofluid-flow-with-magnetohyd",totalDownloads:145,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The study analyzed the heat transfer of water-based carbon nanotubes in non-coaxial rotation flow affected by magnetohydrodynamics and porosity. Two types of CNTs have been considered; single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs). Partial differential equations are used to model the problem subjected to the initial and moving boundary conditions. Employing dimensionless variables transformed the system of equations into ordinary differential equations form. The resulting dimensionless equations are analytically solved for the closed form of temperature and velocity distributions. The obtained solutions are expressed in terms of a complementary function error. The impacts of the embedded parameters are graphically plotted in different graphs and are discussed in detail. The Nusselt number and skin friction are also evaluated. The temperature and velocity profiles have been determined to meet the initial and boundary conditions. An augment in the CNTs’ volume fraction increases both temperature and velocity of the nanofluid as well as enhances the rate of heat transport. SWCNTs provides high values of Nusselt number compared to MWCNTs. For verification, a comparison between the present solutions and a past study is conducted and achieved excellent agreement.",signatures:"Wan Nura’in Nabilah Noranuar, Ahmad Qushairi Mohamad, Sharidan Shafie, Ilyas Khan, Mohd Rijal Ilias and Lim Yeou Jiann",downloadPdfUrl:"/chapter/pdf-download/79179",previewPdfUrl:"/chapter/pdf-preview/79179",authors:[{id:"190576",title:"Dr.",name:"Ilyas",surname:"Khan",slug:"ilyas-khan",fullName:"Ilyas Khan"},{id:"190595",title:"Dr.",name:"Sharidan",surname:"Shafie",slug:"sharidan-shafie",fullName:"Sharidan Shafie"},{id:"436205",title:"M.Sc.",name:"Wan Nura’in Nabilah",surname:"Noranuar",slug:"wan-nura'in-nabilah-noranuar",fullName:"Wan Nura’in Nabilah Noranuar"},{id:"436213",title:"Dr.",name:"Ahmad Qushairi",surname:"Mohamad",slug:"ahmad-qushairi-mohamad",fullName:"Ahmad Qushairi Mohamad"},{id:"436214",title:"Dr.",name:"Mohd Rijal",surname:"Ilias",slug:"mohd-rijal-ilias",fullName:"Mohd Rijal Ilias"},{id:"436215",title:"Dr.",name:"Lim Yeou",surname:"Jiann",slug:"lim-yeou-jiann",fullName:"Lim Yeou Jiann"}],corrections:null},{id:"79499",title:"Semiconductor Epitaxial Crystal Growth: Silicon Nanowires",doi:"10.5772/intechopen.100935",slug:"semiconductor-epitaxial-crystal-growth-silicon-nanowires",totalDownloads:100,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The topic of nanowires is one of the subjects of technological rapid-progress research. This chapter reviews the experimental work and the advancement of nanowires technology since the past decade, with more focus on the recent work. Nanowires can be grown from several materials including semiconductors, such as silicon. Silicon is a semiconductor material with a very technological importance, reflected by the huge number of publications. Nanowires made of silicon are of particular technological importance, in addition to their nanomorphology-related applications. A detailed description of the first successfully reported Vapor–Liquid–Solid (VLS) 1-D growth of silicon crystals is presented. The bottom-up approach, the supersaturation in a three-phase system, and the nucleation at the Chemical Vapor Deposition (CVD) processes are discussed with more focus on silicon. Positional assembly of nanowires using the current available techniques, including Nanoscale Chemical Templating (NCT), can be considered as the key part of this chapter for advanced applications. Several applied and conceptional methods of developing the available technologies using nanowires are included, such as Atomic Force Microscopy (AFM) and photovoltaic (PV) cells, and more are explained. The final section of this chapter is devoted to the future trend in nanowires research, where it is anticipated that the effort behind nanowires research will proceed further to be implemented in daily electronic tools satisfying the demand of low-weight and small-size electronic devices.",signatures:"Maha M. Khayyat",downloadPdfUrl:"/chapter/pdf-download/79499",previewPdfUrl:"/chapter/pdf-preview/79499",authors:[{id:"427861",title:"Associate Prof.",name:"Maha",surname:"Khayyat",slug:"maha-khayyat",fullName:"Maha Khayyat"}],corrections:null},{id:"79258",title:"Ultrathin Metal Hydroxide/Oxide Nanowires: Crystal Growth, Self-Assembly, and Fabrication for Optoelectronic Applications",doi:"10.5772/intechopen.101117",slug:"ultrathin-metal-hydroxide-oxide-nanowires-crystal-growth-self-assembly-and-fabrication-for-optoelect",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The fundamental understanding of transition metal oxides nanowires’ crystal growth to control their anisotropy is critical for their applications in miniature devices. However, such studies are still in the premature stage. From an industrial point of view, the most exciting and challenging area of devices today is having the balance between the performance and the cost. Accordingly, it is essential to pay attention to the controlled cost-effective and greener synthesis of ultrathin TMOS NWs for industrial optoelectronic applications. This chapter provides a comprehensive summary of fundamental principles on the preperation methods to make dimensionality controlled anisotropic nanowires, their crystal growth studies, and optical and electrical properties. The chapter particularly addresses the governing theories of crystal growth processes and kinetics that controls the anisotropy and dimensions of nanowires. Focusing on the oriented attachment (OA) mechanism, the chapter describes the OA mechanism, nanocrystal’s self-assembly, interparticle interactions, and OA-directed crystal growth to improve the state-of-the art kinetic models. Finally, we provide the future perspective of ultrathin TMOS NWs by addressing their current challenges in optoelectronic applications. It is our understanding that the dimension, and single crystallinity of nanowires are the main contributors for building all functional properties, which arise from quasi-1-D confinement of nanowire growth.",signatures:"Gayani Pathiraja and Hemali Rathnayake",downloadPdfUrl:"/chapter/pdf-download/79258",previewPdfUrl:"/chapter/pdf-preview/79258",authors:[{id:"323782",title:"Prof.",name:"Hemali",surname:"Rathnayake",slug:"hemali-rathnayake",fullName:"Hemali Rathnayake"},{id:"427650",title:"Dr.",name:"Gayani",surname:"Pathiraja",slug:"gayani-pathiraja",fullName:"Gayani Pathiraja"}],corrections:null},{id:"79858",title:"One-Dimensional Metal Oxide Nanostructures for Chemical Sensors",doi:"10.5772/intechopen.101749",slug:"one-dimensional-metal-oxide-nanostructures-for-chemical-sensors",totalDownloads:152,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The fabrication of chemical sensors based on one-dimensional (1D) metal oxide semiconductor (MOS) nanostructures with tailored geometries has rapidly advanced in the last two decades. Chemical sensitive 1D MOS nanostructures are usually configured as resistors whose conduction is altered by a charge-transfer process or as field-effect transistors (FET) whose properties are controlled by applying appropriate potentials to the gate. This chapter reviews the state-of-the-art research on chemical sensors based on 1D MOS nanostructures of the resistive and FET types. The chapter begins with a survey of the MOS and their 1D nanostructures with the greatest potential for use in the next generation of chemical sensors, which will be of very small size, low-power consumption, low-cost, and superior sensing performance compared to present chemical sensors on the market. There follows a description of the 1D MOS nanostructures, including composite and hybrid structures, and their synthesis techniques. And subsequently a presentation of the architectures of the current resistive and FET sensors, and the methods to integrate the 1D MOS nanostructures into them on a large scale and in a cost-effective manner. The chapter concludes with an outlook of the challenges facing the chemical sensors based on 1D MOS nanostructures if their massive use in sensor networks becomes a reality.",signatures:"Esther Hontañón and Stella Vallejos",downloadPdfUrl:"/chapter/pdf-download/79858",previewPdfUrl:"/chapter/pdf-preview/79858",authors:[{id:"425601",title:"Dr.",name:"Esther",surname:"Hontañón",slug:"esther-hontanon",fullName:"Esther Hontañón"},{id:"444852",title:"Dr.",name:"Stella",surname:"Vallejos",slug:"stella-vallejos",fullName:"Stella Vallejos"}],corrections:null},{id:"80152",title:"Energy Storage Properties of Topochemically Synthesized Blue TiO2 Nanostructures in Aqueous and Organic Electrolyte",doi:"10.5772/intechopen.102186",slug:"energy-storage-properties-of-topochemically-synthesized-blue-tio-sub-2-sub-nanostructures-in-aqueous",totalDownloads:103,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This book chapter discusses the topochemical synthesis of blue titanium oxide (b-TiO2) and their application as electrode material for supercapacitor devices in aqueous and organic electrolytes. The formation mechanism of b-TiO2 via topochemical synthesis and their characterization using X-ray diffraction, UV–visible, photoluminescence, electron spin resonance spectroscopy, laser Raman spectrum, X-ray photoelectron spectroscopy, and morphological studies (FESEM and HR-TEM) are discussed in detail. The supercapacitive properties of b-TiO2 electrode were studied using both aqueous (Na2SO4) and organic (TEABF4) electrolytes. The b-TiO2 based symmetric-type supercapacitor (SC) device using TEABF4 works over a wide voltage window (3 V) and delivered a high specific capacitance (3.58 mF cm−2), possess high energy density (3.22 μWh cm−2) and power density (8.06 mW cm−2) with excellent cyclic stability over 10,000 cycles. Collectively, this chapter highlighted the use of b-TiO2 sheets as an advanced electrode for 3.0 V supercapacitors.",signatures:"Parthiban Pazhamalai, Karthikeyan Krishnamoorthy and Sang-Jae Kim",downloadPdfUrl:"/chapter/pdf-download/80152",previewPdfUrl:"/chapter/pdf-preview/80152",authors:[{id:"81419",title:"Prof.",name:"Sang-Jae",surname:"Kim",slug:"sang-jae-kim",fullName:"Sang-Jae Kim"},{id:"278690",title:null,name:"Karthikeyan",surname:"Krishnamoorthy",slug:"karthikeyan-krishnamoorthy",fullName:"Karthikeyan Krishnamoorthy"},{id:"278691",title:"Dr.",name:"Parthiban",surname:"Pazhamalai",slug:"parthiban-pazhamalai",fullName:"Parthiban Pazhamalai"}],corrections:null},{id:"79227",title:"Silk Fibroin Nanoparticles: Synthesis and Applications as Drug Nanocarriers",doi:"10.5772/intechopen.100386",slug:"silk-fibroin-nanoparticles-synthesis-and-applications-as-drug-nanocarriers",totalDownloads:201,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The use of nanoparticles in biomedical fields is a very promising scientific area and has aroused the interest of researchers in the search for new biodegradable, biocompatible and non-toxic materials. This chapter is based on the features of the biopolymer silk fibroin and its applications in nanomedicine. Silk fibroin, obtained from the Bombyx mori silkworm, is a natural polymeric biomaterial whose main features are its amphiphilic chemistry, biocompatibility, biodegradability, excellent mechanical properties in various material formats, and processing flexibility. All of these properties make silk fibroin a useful candidate to act as nanocarrier. In this chapter, the structure of silk fibroin, its biocompatibility and degradability are reviewed. In addition, an intensive review on the silk fibroin nanoparticle synthesis methods is also presented. Finally, the application of the silk fibroin nanoparticles for drug delivery acting as nanocarriers is detailed.",signatures:"Guzmán Carissimi, Mercedes G. Montalbán, Marta G. Fuster and Gloria Víllora",downloadPdfUrl:"/chapter/pdf-download/79227",previewPdfUrl:"/chapter/pdf-preview/79227",authors:[{id:"187906",title:"Prof.",name:"Gloria",surname:"Víllora",slug:"gloria-villora",fullName:"Gloria Víllora"},{id:"194675",title:"Mrs.",name:"Mercedes G.",surname:"Montalbán",slug:"mercedes-g.-montalban",fullName:"Mercedes G. Montalbán"},{id:"245952",title:"MSc.",name:"Guzmán",surname:"Carissimi",slug:"guzman-carissimi",fullName:"Guzmán Carissimi"},{id:"429265",title:"MSc.",name:"Marta G.",surname:"Fuster",slug:"marta-g.-fuster",fullName:"Marta G. Fuster"}],corrections:null},{id:"78717",title:"Nanoparticles as Drug Delivery Systems",doi:"10.5772/intechopen.100253",slug:"nanoparticles-as-drug-delivery-systems",totalDownloads:633,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter presents a review on the design of nanoparticles which have been proposed as drug delivery systems in biomedicine. It will begin with a brief historical review of nanotechnology including the most common types of nanoparticles (metal nanoparticles, liposomes, nanocrystals and polymeric nanoparticles) and their advantages as drug delivery systems. These advantages include the mechanism of increased penetration and retention, the transport of insoluble drugs and the controlled release. Next, the nanoparticle design principles and the routes of administration of nanoparticles (parental, oral, pulmonary and transdermal) are discussed. Different routes of elimination of nanoparticles (renal and hepatic) are also analyzed.",signatures:"Guzmán Carissimi, Mercedes G. Montalbán, Marta G. Fuster and Gloria Víllora",downloadPdfUrl:"/chapter/pdf-download/78717",previewPdfUrl:"/chapter/pdf-preview/78717",authors:[{id:"187906",title:"Prof.",name:"Gloria",surname:"Víllora",slug:"gloria-villora",fullName:"Gloria Víllora"},{id:"194675",title:"Mrs.",name:"Mercedes G.",surname:"Montalbán",slug:"mercedes-g.-montalban",fullName:"Mercedes G. Montalbán"},{id:"245952",title:"MSc.",name:"Guzmán",surname:"Carissimi",slug:"guzman-carissimi",fullName:"Guzmán Carissimi"},{id:"429265",title:"MSc.",name:"Marta G.",surname:"Fuster",slug:"marta-g.-fuster",fullName:"Marta G. Fuster"}],corrections:null},{id:"79442",title:"Biological Synthesis of Metallic Nanoparticles from Different Plant Species",doi:"10.5772/intechopen.101355",slug:"biological-synthesis-of-metallic-nanoparticles-from-different-plant-species",totalDownloads:144,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Green chemistry for the synthesis of different nanoparticles (NPs) from metal has become a new and promising field of research in nanotechnology in recent years. The inspire applications of metal oxide NPs have attracted the interest of researchers around the world. Various physical, chemical and biological methods in material science are being adapted to synthesize different types of NPs. Green synthesis has gained widespread attention as a sustainable, reliable, and eco-friendly protocol for biologically synthesizing a wide range of metallic NPs. Green synthesis has been proposed to reduce the use of hazardous compounds and as a state of a harsh reaction in the production of metallic NPs. Plants extract used for biosynthesis of NPs such as silver (Ag), cerium dioxide (C2O2), copper oxide (CuO), Gold (Au), titanium dioxide (TiO2), and zinc oxide (ZnO). This review article gives an overview of the plant-mediated biosynthesis of NPs that are eco-friendly and have less hazardous chemical effects.",signatures:"Kalyan Singh Kushwah and Deepak Kumar Verma",downloadPdfUrl:"/chapter/pdf-download/79442",previewPdfUrl:"/chapter/pdf-preview/79442",authors:[{id:"334136",title:"Ph.D. Student",name:"Kalyan Singh",surname:"Kushwah",slug:"kalyan-singh-kushwah",fullName:"Kalyan Singh Kushwah"},{id:"426969",title:"Mr.",name:"Deepak Kumar",surname:"Verma",slug:"deepak-kumar-verma",fullName:"Deepak Kumar Verma"}],corrections:null},{id:"80585",title:"Nanofibers: Production, Characterization, and Tissue Engineering Applications",doi:"10.5772/intechopen.102787",slug:"nanofibers-production-characterization-and-tissue-engineering-applications",totalDownloads:80,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Among all nanostructured materials, nanofibers (NFs) are the one class that is widely used in tissue engineering (TE) and regenerative medicine (RM) areas. NFs can be produced by a variety of different methods, so they can be used almost for any tissue engineering process with appropriate modifications. Also, the variety of materials that can form nanofibers, production methods, and application fields increase the value of NFs greatly. They are almost suitable for any tissue engineering applications due to their tunable properties. Hopefully, this chapter will provide brief information about the production methods (electrospinning, wet spinning, drawing, etc.), characterization methods (Scanning Electron Microscopy, Transmission Electron Microscopy, Atomic Force Microscopy, etc.), and tissue engineering applications (core-shell fibers, antibacterial fibers, nanoparticle-incorporated fibers, drug-loaded fibers, etc.) of NFs.",signatures:"Ece Bayrak",downloadPdfUrl:"/chapter/pdf-download/80585",previewPdfUrl:"/chapter/pdf-preview/80585",authors:[{id:"427785",title:"Ph.D.",name:"Ece",surname:"Bayrak",slug:"ece-bayrak",fullName:"Ece Bayrak"}],corrections:null},{id:"79338",title:"Composite Metamaterials: Classification, Design, Laws and Future Applications",doi:"10.5772/intechopen.100861",slug:"composite-metamaterials-classification-design-laws-and-future-applications",totalDownloads:133,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The development of science and applications have reached a stage where the naturally existed materials are not meeting the required properties. Metamaterials (MMs) are artificial materials that obtain their properties from their accurately engineered meta-atoms rather than the characteristics of their constituents. The size of the meta-atom is small compared to light’s wavelength. A metamaterial (MM) is a term means beyond material which has been engineered in order to possess properties that does not exist in naturally-found materials. Currently, they are made of multiple elements such as plastics and metals. They are being organized in iterating patterns at a scale that is smaller than wavelengths of the phenomena it influences. The properties of the MMs are not derived from the forming materials but their delicate size, geometry, shape, orientation, and arrangement. These properties maintain MMs to manipulate the electromagnetic waves via promoting, hindering, absorbing waves to attain an interest that goes beyond the natural materials’ potency. The apt design of MMs maintains them of influencing the electromagnetic radiation or sound in a distinctive technique never found in natural materials. The potential applications of MMs are wide, starting from medical, aerospace, sensors, solar-power management, crowd control, antennas, army equipment and reaching earthquakes shielding and seismic materials.",signatures:"Tarek Fawzi and Ammar A.M. Al-Talib",downloadPdfUrl:"/chapter/pdf-download/79338",previewPdfUrl:"/chapter/pdf-preview/79338",authors:[{id:"425395",title:"Ph.D. Student",name:"Tarek",surname:"Fawzi",slug:"tarek-fawzi",fullName:"Tarek Fawzi"},{id:"437661",title:"Dr.",name:"Ammar",surname:"A.M. Al-Talib",slug:"ammar-a.m.-al-talib",fullName:"Ammar A.M. Al-Talib"}],corrections:null},{id:"79747",title:"Nanocomposite Material Synthesized Via Horizontal Vapor Phase Growth Technique: Evaluation and Application Perspective",doi:"10.5772/intechopen.101637",slug:"nanocomposite-material-synthesized-via-horizontal-vapor-phase-growth-technique-evaluation-and-applic",totalDownloads:116,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The synthesis of nanomaterials has been reported by many researchers using different methods. One of the methods that can be used with perfect pureness and have less pollution in the synthesized materials results is the vapor phase growth technique (VPGT). Several types of nano shapes materials were reported such as nanoparticles, nanorods, nano triangular, nanosphere, and nanocrystal. The synthesis method has a fundamental process where the nanomaterials evaporated and condensed based on the temperature difference. There are three important variables, i.e., stochiometric ratio of source materials, temperature and baking time. The synthesis was occured in the quartz tube and sealed in the vacuum condition. This create the material was synthesis in pure and isolated conditions. The application of the nanomaterials synthesized via Horizontal Vapor Phase Growth (HVPG) can be implemented in anti-pathogen, anti-bacterial, gas sensing and coating applications.",signatures:"Muhammad Akhsin Muflikhun, Rahmad Kuncoro Adi and Gil Nonato C. Santos",downloadPdfUrl:"/chapter/pdf-download/79747",previewPdfUrl:"/chapter/pdf-preview/79747",authors:[{id:"422388",title:"Assistant Prof.",name:"Muhammad",surname:"Akhsin Muflikhun",slug:"muhammad-akhsin-muflikhun",fullName:"Muhammad Akhsin Muflikhun"},{id:"446220",title:"Dr.",name:"Rahmad",surname:"Kuncoro Adi",slug:"rahmad-kuncoro-adi",fullName:"Rahmad Kuncoro Adi"},{id:"446221",title:"Dr.",name:"Gil Nonato",surname:"Santos",slug:"gil-nonato-santos",fullName:"Gil Nonato Santos"}],corrections:null},{id:"80747",title:"Recent Advances in Nano-Enabled Fertilizers towards Sustainable Agriculture and Environment: A Mini Review",doi:"10.5772/intechopen.103053",slug:"recent-advances-in-nano-enabled-fertilizers-towards-sustainable-agriculture-and-environment-a-mini-r",totalDownloads:55,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Food creation be directed expand uniquely to take care of the developing human populace; however, this should be accomplished while at the same time decreasing unfriendly natural effects. In such manner, there is expanding interest in the utilization of nanomaterials as composts for further developing plant mineral sustenances that are crippling Indian agriculture. To address these problems, there is a need to explore one of the frontier technologies like nano-technology to precisely detect and deliver correct quantity of nutrients that promote the productivity. Nano-technology uses synthesized materials that are 10–9 nm in size to improve the productivity, yield and crop quality. Research has proved beyond doubt that the nano-fertilizers that contain readily available nutrients in nano-scale have increased uptake, absorption and improved bioavailability in the plant body compared to the conventional bulk equivalents. This audit assesses the current writing on ENMs utilized as pesticides and manures, and features basic information holes that should be addressed to guarantee maintainable use of nanotechnology in horticulture to accomplish worldwide food security. Designing nanoparticles-based nanofertilizers offer advantages in crop nourishment of the board by upgrading abiotic stress resilience and improving farming efficiency towards the advancement of brilliant and supportable future horticulture.",signatures:"Challa Gangu Naidu, Yarraguntla Srinivasa Rao, Dadi Vasudha and Kollabathula Vara Prasada Rao",downloadPdfUrl:"/chapter/pdf-download/80747",previewPdfUrl:"/chapter/pdf-preview/80747",authors:[{id:"426790",title:"Assistant Prof.",name:"Dr Gangu Naidu",surname:"Challa",slug:"dr-gangu-naidu-challa",fullName:"Dr Gangu Naidu Challa"},{id:"452727",title:"Prof.",name:"Srinivasa Rao",surname:"Y",slug:"srinivasa-rao-y",fullName:"Srinivasa Rao Y"},{id:"452728",title:"Dr.",name:"Vasudha",surname:"D",slug:"vasudha-d",fullName:"Vasudha D"},{id:"452729",title:"Prof.",name:"Vara Prasada Rao",surname:"K",slug:"vara-prasada-rao-k",fullName:"Vara Prasada Rao K"}],corrections:null},{id:"79697",title:"Electrochemical Impedance Spectroscopy and Its Applications",doi:"10.5772/intechopen.101636",slug:"electrochemical-impedance-spectroscopy-and-its-applications",totalDownloads:157,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Electrochemistry has become an important and recognized field for the future since many of its approaches contemplate the establishment of stable energy supplies and the minimization of our impact on the environment. In this regard, electrochemistry can face both objectives by studying the electrode/solution interface. As a result, different electrochemical techniques can be used to study the interface to understand the electron transfer phenomena in different reactions. Considering this, one of the most useful techniques to understand the electrode/solution interface is electrochemical impedance spectroscopy. This technique allows us to describe the electrode behavior in the presence of a certain electrolyte in terms of electrical parameters such as resistances and capacitances, among others. With this information, we can infer the electrochemical behavior toward a specific reaction and the capacity of the electrode to carry on the electron transfer depending on its resistance (impedance) values. The aim of this chapter is to go from the theory, based on Ohm’s Law and its derivations, to actual applications. This will lead us to characterize the solution, electrode, and the interface between these two phases based on their electrical components by using an equivalent electrical circuit, such as the Randles equivalent circuit.",signatures:"Camila Pía Canales",downloadPdfUrl:"/chapter/pdf-download/79697",previewPdfUrl:"/chapter/pdf-preview/79697",authors:[{id:"428140",title:"Dr.",name:"Camila",surname:"Pía Canales",slug:"camila-pia-canales",fullName:"Camila Pía Canales"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10061",title:"21st Century Surface Science",subtitle:"a Handbook",isOpenForSubmission:!1,hash:"69253b3c7ba801a5fcd9c47827345f93",slug:"21st-century-surface-science-a-handbook",bookSignature:"Phuong Pham, Pratibha Goel, Samir Kumar and Kavita Yadav",coverURL:"https://cdn.intechopen.com/books/images_new/10061.jpg",editedByType:"Edited by",editors:[{id:"236073",title:"Dr.",name:"Phuong",surname:"Pham",slug:"phuong-pham",fullName:"Phuong Pham"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6408",title:"Novel Nanomaterials",subtitle:"Synthesis and Applications",isOpenForSubmission:!1,hash:"f3585d338d78e4d31c200d9991b03692",slug:"novel-nanomaterials-synthesis-and-applications",bookSignature:"George Z. 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Known indications, contraindications, diversity, comparative effects between subtypes, limits, allergies, treatments, adverse reactions, nonresponsiveness, and new investigations will be described. Botulinum toxin can be currently used in nearly every specialty. The main areas in this book are cosmetics and dermatology, as well as dentistry, urology, masseter hypertrophy, chronic pain treatment, and others. 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1. Introduction
Hyponatremia is the most frequent hydroelectrolytic disorder in clinical practice, both in hospital and outpatient settings [1]. Defined as a serum sodium concentration or sodium level < 135 mmol/L, its frequency varies according to its intensity, with severe and more severe hyponatremia in hospitalized patients. Hyponatremia is present in 15–20% of urgent hospital admissions and in up to 20% of critical patients. Although it estimates a daily incidence of 1% in hospitalized patients and a prevalence of 2.5%, its frequency is probably higher, since it is frequently underdiagnosed [2]. Some epidemiological studies report that only 30% of patients with hyponatremia are diagnosed, including the most serious ones [3]. Clinical manifestations of hyponatremia have a broad spectrum, from mild to severe or even potentially lethal. Hyponatremia is related to an increase in mortality, morbidity, duration of hospital stay and socio-health costs in patients with multiple pathologies. Some studies show that the presence of hyponatremia is an independent predictor of mortality rate, implying a relative risk of death between 1 and 2 times higher [4]; risk that is maintained per year and even 5 years after a hospital admission. Hyponatremia is related to a higher rate of hospitalization in Intensive Care Units and mechanical ventilation units.
Etiology of hyponatremia is multifactorial, highlighting the pharmacological origin. Some of the mechanisms involved in the development of pharmacological hyponatremia are the alteration of sodium and water homeostasis (diuretics), the increase in the production of the antidiuretic hormone (antidepressants, antipsychotics, antiepileptics, anticancer drugs, methrotrexate, interferon alfa, opiates) and the potentiation of the effects of antidiuretic hormone (antiepileptic, hypoglycemic, nonsteroidal anti-inflammatory drugs [NSAIDs], angiotensin-converting enzyme inhibitors [ACEIs] and anticancer drugs). Factors such as female sex, weight, advanced age, the presence of associated pathologies (cardiological, hepatic, neurological and endocrine), the concomitant use of drugs (especially thiazide diuretics, inhibitors of the reuptake of serotonin and carbamazepine) and basal sodium levels in the low threshold of normality have been related to the development of hyponatremia [5].
Prescription and use of psychotropic drugs is currently growing, both due to the increase in the incidence of mental illnesses and depression, which according to the WHO will be the second cause of disability in the world in 2020 [6]. Elderly patients have higher prevalences of mood disorders, which together with the greater frequency of polypathology and polypharmacy, makes them a risk group for presenting hyponatremia.
2. Hyponatremia
2.1. Definition of hyponatremia
2.1.1. Definition of hyponatremia based on biochemical severity
Mild (sodium between 130 and 135 mmol/L); moderate (sodium between 125 and 129 mmol/L); severe (sodium <125 mmol/L).
2.1.2. Definition of hyponatremia based on development time
Acute (<48 h) or chronic (greater or equal to 48 h). Current literature establishes the limit of 48 h to distinguish between acute and chronic hyponatremia, since cerebral edema appears more frequently when hyponatremia is established in less than 48 h. Experimental studies suggest that the brain needs approximately 48 h to adapt to a hypotonic environment; there is a risk of cerebral edema before such adaptation. However, once the adaptation is completed, a rapid rise in the serum sodium level can cause lesions of the myelin sheath, which is known as osmotic demyelination syndrome. Hence, the importance in clinical practice to distinguish between acute and chronic hyponatremia, evaluating whether a subject is at greater risk of cerebral edema or osmotic demyelination. If there are doubts about the development time of hyponatremia [7], it should be considered chronic, unless there are reasons to think otherwise.
2.1.3. Definition of hyponatremia based on symptoms
Moderate: any degree of hyponatremia associated with moderately severe symptoms of hyponatremia: nausea without vomiting, confusion, and headache.
Severe: any biochemical degree of hyponatremia associated with severe symptoms of hyponatremia: vomiting, cardiorespiratory distress, abnormal and deep drowsiness, seizures, and coma.
2.1.4. Definition of hyponatremia based on plasma osmolality
Hypotonic hyponatremia: the decrease in extracellular sodium is accompanied by hypotonia of the extracellular fluid and displacement of water from the extracellular space to the intracellular space, causing cellular edema. The most frequent cause is a syndrome of inappropriate secretion of antidiuretic hormone (SIADH). There are three types according to the volume status:
hypotonic hyponatremia with hypovolemia: occurs when there are losses of sodium and water, with partial supplementation of fluid losses without electrolytes. Losses can occur through the skin, digestive tract, renal pathway or leakage of fluids into a third space.
hypotonic hyponatremia with isovolemia: SIADH is the most common cause of hyponatremia.
hypotonic hyponatremia with hypervolemia: it occurs both in situations of increased vasopressin secretion in states of a relative decrease in effective intravascular volume (chronic heart failure, liver cirrhosis with ascites, nephrotic edema); excessive fluid intake without electrolytes and an altered excretion of free water (acute kidney injury, advanced chronic kidney disease).
Nonhypotonic hyponatremia (isotonic or hypertonic): increase in the plasma concentration of effective osmoles displaces the water from the intracellular to the extracellular space and generates a dilutional hyponatremia. Depending on the concentration of these compounds the plasma osmolality may be normal or increased. The most frequent cause is hyperglycemia.
Fictional hyponatremia or pseudohyponatremia occurs when a plasma concentration of sodium falsely decreases as a result of a high concentration of lipids or paraproteins, with normal plasma osmolality.
Isotonic or hypertonic: secondary to the presence of effective osmoles (glucose, mannitol, glycine, hyperosmolar radiological contrast, maltose).
Isotonic or hyperosmolar: secondary to presence of ineffective osmoles that elevate measured serum osmolality but do not cause hyponatremia because they do not change effective osmolality and does not attract water to extracellular compartment (urea, alcohol).
Isotonic: presence of endogenous solutes that cause pseudohyponatremia (triglycerides, cholesterol, proteins, intravenous immunoglobulins, monoclonal gammopathies).
Isovolemia: syndrome of inappropriate secretion of antidiuretic hormone (SIADH) which can be secondary to tumors (lung, oropharynx, stomach, duodenum, pancreas, ureter, bladder, prostate, endometrium, Ewing sarcoma, lymphomas, neuroblastoma), nervous system disorder (encephalitis, meningitis, abscess, infection by Rickettsia and Plasmodium, HIV, subdural hemorrhage, stroke, hydrocephalus, multiple sclerosis, Guillain-Barré syndrome, delirium tremens, acute porphyria), drugs (antidepressants, anticonvulsants, antipsychotics, anticancer drugs, antidiabetics, vasopressin analogs, opioids, interferon, NSAIDs, clofibrate, nicotine, proton pump inhibitors, amiodarone) [7].
2.2.4. Hyponatremia and psychotropic drugs
As we have previously described, in case of psychotropic drugs, hyponatremia is mediated by the inappropriate release of ADH. ADH or vasopressin is a hypothalamic hormone that is stored and released through the neurohypophysis in response to osmotic and nonosmotic stimuli:
Osmotic stimulus: the ADH is released or inhibited depending on the concentration of effective osmoles in the extracellular compartment. Osmotic threshold for ADH release is 280 – 290 mOsm/kg.
Nonosmotic stimulus:
Hemodynamics. In the presence of low effective circulating volume, the baroreceptors are activated. For example: hypovolemia, liver cirrhosis, arterial hypotension, congestive heart failure, nephrotic syndrome, primary adrenal insufficiency.
Nonhemodynamic: mediated by the release of corticotropin-releasing hormone (CRH, neurotransmitter involved in the response to stress and responsible for activating the pituitary secretion of ACTH) and angiotensin II. For example: pain, stress, nausea and vomiting, hypoglycemia, drugs, cancer, postoperative state, pulmonary or central nervous system pathology.
Vasopressin has three receptors coupled to G proteins: V1 (presents vasopressor effect), V2 (responsible for the reabsorption of water in the collecting tubule of the nephron) and V3 (responsible for the release of ACTH). Vasopressin or ADH has several functions:
Renal. ADH acts on V2 receptors on collecting duct in the nephron. Its action increases the reabsorption of water, but not of solute, through the increased expression of aquaporin 2 channels (AQP2). Aquaporins are proteins that are part of the water channel. AQP2 is expressed exclusively in collecting duct principal cells and is responsible for the apical water permeability of this region of the nephron. Its activity is dependent on ADH, which is released in response to hyperosmolar and hypovolemic stimuli. There is a type of inherited nephrogenic diabetes insipidus associated with mutations in AQP2 [8].
Vascular smooth muscle. It produces vasoconstriction and increases peripheral vascular resistance.
2.3. Symptomatology
The symptomatology of hyponatremia varies depending on the biochemical severity and the speed of the establishment. It can be classified as mild, moderate and severe.
2.3.1. Mild symptoms
(Na 130–135 mEq/L): headache, attention deficit, memory alterations, irritability, depression.
2.3.2. Moderate symptoms
(Na 120–130 mEq/L): nausea, vomiting, bradypsychia, confusion, disorientation.
2.3.3. Severe symptoms
(Na < 120 mEq/L): stupor, seizures, coma, respiratory depression.
2.3.4. Hyponatremic encephalopathy
In hyponatremia, low serum osmolarity causes an osmotic gradient between the extracellular space and the intracellular space, with the consequent passage of free water into the interior of the cell. This accumulation of water in the brain cells causes cerebral edema. The cellular edema produces an increase in the size of the various organs, however in the case of brain, expansion is not possible due to the limitation of the cranial cavity. Thus, increases in brain volume of 8–10% can cause coma and compromise the condition of the individual due to intracranial hypertension and transtentorial herniation. However, hyponatremia activates a series of compensatory mechanisms to decrease the volume of intracellular fluid, to reduce the risk of cerebral edema and the risks derived from it [9]. Adequate regulation of brain volume is an essential factor in the prognosis of hyponatremic encephalopathy. Some of these compensatory mechanisms are:
The increase in intracranial pressure favors the increase of hydrostatic pressure and subsequent passage of water to the ventricular and venous system.
After an initial osmotic edema, the cells quickly expel electrolytes (potassium, chloride and sodium) into the extracellular space, with the subsequent release of water by osmotic gradient, restoring brain volume. This phenomenon allows to restore cell volume in hours but is energy dependent and requires the operation of sodium-potassium ATPase system.
Role of the astrocytes. Act as regulators of brain water content, its swelling in hyposmolar situations protect and spare neurons. Its extensions form the blood-brain barrier and they have high number of pores called aquaporins (AQP) particularly AQP1 and AQP4, allowing the passage of water into astrocytes in hyposmolar situations which selectively swell, whereas neurons are relatively spared.
Studies in animals have shown that brain osmolytes (glycine, taurine, creatine myo-inositol) leave the cell in hypoosmolar states and accumulate in the hyperosmolar states. Studies in humans with magnetic resonance imaging show that the osmolytes output is parallel to the changes in sodium concentration, which takes approximately 48 h.
Brain adaptation to hyponatremia is related to the speed of its establishment. In chronic hyponatremia (that lasts more than 48 h) the slow and progressive decrease of sodium allows a compensatory regulation of the whole volume, limiting the degree of cerebral edema and being asymptomatic or slightly symptomatic. However, in cases of acute hyponatremia, adaptive mechanisms are exceeded and symptoms are more likely to occur even with mild hyponatremia.
There are some risk factors for the development of hyponatremic cerebral edema:
Menstruating women. Estrogens inhibit the sodium-potassium ATPase, making intracellular sodium leakage difficult; and affect the expression of AQP4 channels. In this patient profile, cases of hyponatremic encephalopathy with cerebral herniation have been documented even with serum sodium of 128 mEq/L.
Children. They are a risk group for unfavorable evolution in hyponatremic encephalopathy. It is postulated that the high ratio of brain size to that of the skull after the closure of the fontanelles, as well as the lower activity of the sodium-potassium ATPase pump than in adults can limit the adaptation to cerebral edema.
Hypoxia It has been postulated that hypoxia is a factor for death and brain damage in patients with hyponatremia, after adjustment for other comorbidities. It alters the regulation of the energy-dependent astrocyte volume, since the active transport of sodium requires oxygen. In addition, in patients with hyponatremic encephalopathy, cranial hypertension and incipient brain herniation may favor the development of a neurogenic pulmonary edema and hypercapnic respiratory failure that worsens hypoxia.
Hormonal factors: vasopressin and estrogen make it difficult to adapt to cellular edema. On the one hand, vasopressin acts by decreasing brain flow and oxygen consumption through arterial vasoconstriction, as well as facilitating the displacement of water in brain cells through AQP4. On the other hand, estrogens increase the secretion of vasopressin.
Risk factors to develop hyponatremia: as we have previously commented, the establishment of the hyponatremia and the severity of it is associated with multiple factors such as polypathology and polymedication, among others. For this reason, literature recommends the identification of those risk factors to perform an adequate prevention and early detection of those cases of hyponatremia.
2.3.5. Age
Elderly patients are a vulnerable population and at risk of developing hyponatremia due to various causes. In the first place, the physiological changes characteristic of aging, such as the decrease in volume and body weight, pose a risk to develop hyponatremia. On the other hand, they are a population often with multi co-morbidities, exposed to diets without salt, to forced hydration (oral or intravenous) and with the use of polytherapy, which makes them candidates for risk.
2.3.6. Institutionalization
Some studies have shown a higher incidence of hyponatremia in subjects older than 60 years institutionalized in residences than in patients of the same age living at home (18 versus 8%) [10].
2.3.7. Female sex
Female sex has been associated with an increased risk of hyponatremia and the development of hyponatremic encephalopathy [11]. Some hypothesis proposed for this difference are based on hormonal factors and cellular transport of sodium and volume of distribution of body water different from men.
2.3.8. Comorbidity
Hyponatremia has been associated with multiple pathologies (infectious, oncological, neurological, renal, metabolic, etc.).
2.3.9. Polytherapy
Multiple drugs have been associated with an increased risk of hyponatremia, especially antipsychotics, antidepressants and antiepileptic [12], diuretics (mainly thiazides), ACEIs and NSAIDs. Other drugs have been related to hyponatremia, such as vasopressin analogs, interferon, antidiabetics, anticancer drugs, proton pump inhibitors and monoclonal antibodies, among others.
Basal levels of sodium in low range of normality
Low weight
Exposure to high temperatures
2.4. Treatment
It is important to remember that despite of the severity of the neurological signs and symptoms of acute hyponatremia, the correction of hyponatremia in a rapid and uncontrolled way can generate chronic neurological lesions due to osmotic demyelination. When there is a decrease in sodium, cells excrete organic solutes and other molecules to maintain homeostasis, in a process that can last between 48 and 72 h, so hyponatremia can be classified as acute or chronic if the duration is shorter or greater than 48 h, respectively.
It is recommended that sodium correction rate does not exceed 8 mmol/L in any 24-h period, being even lower in those patients susceptible to osmotic demyelination (as in the case of advanced cirrhosis, alcoholism or severe malnutrition). Even in patients with severe hyponatremia that are accompanied by severe neurological symptoms, 4 – 6 mEq/L rise in serum sodium is sufficient in the first 24-h (this target can be achieved in first few hours in severely symptomatic patients and then maintained at that level for the first 24-h). Three percent sodium chloride solution can be used to achieve this. It is important to remember that the recommended correction rates of 24 h should not be exceeded.
There is a series of formulas that allow to calculate in a quantitative way the effect of the prescribed fluid therapy on patient’s serum sodium.
The Adrogue-Madias Formula (AMF) [13] helps to estimate the effect of a given fluid on serum sodium. It takes into account the sodium concentration and the total body weight (TBW) adjusted by a correction factor that varies according to age and sex. However, the AMF does not take into account the losses and the pathophysiology that underlies them and requires that sodium levels be monitored frequently during the infusion of the fluid.
Infusate formula: Adrogue-Madias formula.
E1
However, this formula has the limitation of being approximate as rise in sodium level is often greater than that predicted by the formula.
Fluid restriction should be the first therapeutic measure in cases of euvolemic or hypervolemic hyponatremia. Depending on the severity of the hyponatremia and symptomatic severity, the fluid should be restricted to provide a negative fluid balance of approximately 500 ml per day.
There are several therapeutic options for the treatment of hyponatremia secondary to SIADH:
Demeclocycline. It is a tetracyclic antibiotic whose mechanism of action is the inhibition of ADH receptors in the renal distal tubule, inducing nephrogenic diabetes insipidus. It is administered in doses of (300 – 600 mg twice a day). Side effects include photosensitivity, nephrotoxicity and nausea.
Antagonists of the vasopressin receptor (“vaptans”). ADH or vasopressin acts at the level of various receptors: V1a (causes vasoconstriction), V1b (secretion of ACTH) and V2 (water reabsorption and release of von Willebrand factor and factor VIII). Drugs that act on V2 receptors at the tubular level increase the excretion of water (aquaresis).
Tolvaptan: It has an action as a selective antagonist of the V2 receptors of vasopressin at the level of the renal tubule, increasing the free elimination of water. It has been used in patients with congestive heart failure, cirrhosis and SIADH. Although it has not shown a reduction in the rates of rehospitalization or death due to congestive heart failure, it improves sodium levels, fluid balance and symptoms of congestion. It is approved for the treatment of hypervolemic and euvolemic hyponatremia.
Conivaptan: Antagonist of the V1a-V2 receptors with approval for the treatment of euvolemic and hypervolemic hyponatremia. Its use is limited to intravenous use at the hospital level.
Lixivaptan: V2 receptor antagonist of vasopressin, used in euvolemic and hypervolemic hyponatremia.
3. Hyponatremia and antipsychotics
Antipsychotics are a family of drugs used primarily in the treatment of schizophrenia, bipolar disorder and other affective psychoses, but also in other neuropsychiatric disorders (such as dementia and autism), symptomatic treatment of acute confusional symptoms and other conditions not psychiatric (nausea, hiccups, migraine). Some studies show stability in the prevalence (2.05%) and incidence (0.66%) in the use of antipsychotics in the last decade, although showing an increase in its use in the infant-juvenile population and higher employment of second generation antipsychotics (SGAPs) [14]. Its mechanism of action is dopaminergic blocking. They are classified into two main groups: the classic or typical antipsychotics, which present a blockade of the D2 dopaminergic receptor and are effective in the positive symptoms of schizophrenia (hallucinations and delusions) but show extrapyramidal symptoms as the most notable side effects; and the atypical or second generation antipsychotics, in addition to blocking the D2 receptor, exhibit muscarinic, adrenergic, serotonergic and histamergic receptor activity, showing a broader spectrum of action (including positive and negative symptoms) and a different side effect profile of the typical ones (minor extrapyramidal symptoms, but weight gain, dry mouth, orthostatic hypotension, constipation, urinary retention, narrow-angle glaucoma, sedation).
Hyponatremia is an adverse effect described both in the case of classical and atypical antipsychotics. It is postulated that the etiopathogenesis of hyponatremia in atypical antipsychotics is mediated by the action of serotonin, both by the release of ADH induced by the stimulation of central receptors 5-HT2 and 5-HT1c and by the increase in the effects of ADH at the renal medullary level [15]. In the case of typical antipsychotics, prolonged blockade of dopamine D2 receptors stimulates the release of ADH and increases its peripheral response [16]. The occurrence of hyponatremia occurs in the first 3 weeks of treatment in up to 50% of cases, although cases have also been reported in patients undergoing long-term chronic treatments. On the other hand, in the case of antipsychotics, neither age nor female sex are risk factors. The chemical structure and receptor affinity profiles of the dopamine D2 receptor and serotonin 5-HT2A have not shown a variation with respect to the risk of hyponatremia [17]. Several studies describe that hyponatremia at admission is associated with greater medical deterioration in hospitalized psychiatric patients [18], therefore adequate clinical monitoring should be performed to identify and treat somatic pathologies and concomitant use of drugs. Also, it is recommended to measure serum sodium in those patients on antipsychotic treatment who present with seizures.
In a follow-up study over 15 years with a sample of 2051 patients diagnosed with schizophrenia [19] from 1998 to 2013, an incidence of hyponatremia of 6.7% was observed. The study showed that the use of antipsychotics, both typical and atypical, was associated with an elevated risk of hyponatremia with respect to the nonuse of antipsychotics, even after adjusting for age, sex and physical comorbidity. Age of diagnosis of the disease, low income, physical comorbidity, psychiatric admissions and concomitant treatment with carbamazepine were also associated with an increased risk of hyponatremia. Another retrospective study showed that treatment with atypical antipsychotics in the elderly was associated with a modest but statistically significant increase in the risk of hospitalization for hyponatremia in 30 days, an association that was smaller than other psychotropic drugs [20]. A systematic review on hyponatremia and the use of antipsychotics, published in 2010 [16], which includes 4 studies and 91 cases and series of cases, showed that the diagnosis of schizophrenia and male sex were more frequently associated with hyponatremia. Using the Naranjo Scale of Adverse Drug Reaction Probability Scale, in 80% of the cases possible causality was determined, in 19% probable causality and in 1% impossible causality. No significant association was found between daily doses of drugs and serum sodium or time to onset of hyponatremia. Currently, tolvaptan is positioned as a drug approved by the FDA in the treatment of euvolemic and hypervolemic hyponatremia, and useful in the management of hyponatremia associated with the use of antipsychotics [21].
3.1. First generation antipsychotics (FGAS)
In recent decades the use of typical antipsychotics has been progressively replaced by atypical ones, by the receptor profile and side effects. Nonetheless, haloperidol continues to be the drug of choice in the management of agitation and acute confusional syndrome. Haloperidol-related hyponatremia has been reported for decades [22, 27], but also with other first-generation antipsychotics such as chlorpromazine, perphenazine, and fluphenazine [23, 24, 25]. In the majority of cases there were other intercurrent factors involved in the development of hyponatremia (concomitant treatment with ACE inhibitors, diuretics and other psychotropic drugs).
3.2. Second generation antipsychotics (SGAS)
3.2.1. Aripiprazole
Aripiprazole is a partial agonist of dopamine, frequently used for its efficacy in cognitive and affective symptoms in psychosis. There are currently presentations for oral, parenteral and prolonged release treatment. Literature collects cases of aripiprazole-induced hyponatremia both in patients who developed the symptoms at the start of treatment [15] and in increasing the dose [26], improving in all of them the clinical symptoms with interruption of treatment and water restriction.
3.2.2. Olanzapine
It is an atypical antipsychotic, antagonist of D2 and 5HT2A receptor. It is commonly used in clinical practice to control agitation and positive symptoms. Cases of olanzapine-induced hyponatremia have been reported together with the concomitant use of other psychoactive drugs [5, 27]. In 2014, a case of death was described in a young schizophrenic male who presented with hyponatremia secondary to excessive water intake and which was related to the increase in the dose of olanzapine, which could have acted aggravating the intoxication itself [28].
3.2.3. Quetiapine
Synthesized in 1985, it is used in the treatment of schizophrenia, bipolar disorder, Alzheimer’s disorder and major depression. There are few cases of SIADH induced by quetiapine, something that could be related to underdiagnosis and underreporting of this situation. Nonetheless, some cases are collected where quetiapine, together with other factors such as advanced age and polytherapy, is involved in the development of hyponatremia [29, 30, 31].
3.2.4. Risperidone
Approved by the FDA in 1993 for the use of schizophrenia, exists in oral presentation and depot. Like the other antipsychotics, risperidone has also been associated with the risk of developing hyponatremia, although some cases have been described in which the use of risperidone improved polydipsia in the schizophrenic patient [32, 33]. However, the results in the literature are inconclusive and controversial regarding the improvement of certain atypical antipsychotics (olanzapine and risperidone) on primary polidipsia.
3.2.5. Paliperidone
Paliperidone is an active metabolite of risperidone, indicated in the management of schizophrenia and schizoaffective disorder. In 2016, a case of rhabdomyolysis, malignant neuroleptic syndrome and SIADH associated with paliperidone prolonged release in a 35-year-old man hospitalized for psychotic decompensation was described. Two days after the administration of the treatment, the patient presented with a tonic-clonic seizure that was attributed to hypoosmolar hyponatremia [34]. It is important to remember that in all patients receiving antipsychotic treatment, serum sodium should be measured in the presence of epileptic seizures.
3.2.6. Ziprasidone
Ziprasidone is an atypical antipsychotic indicated in psychotic agitation, schizophrenia and manic and mixed episodes in bipolar disorder. The literature includes a series of cases in which hyponatremia is observed in the context of the use of ziprasidone, concomitantly with other psychopharmaceuticals such as duloxetine [35] and with comitial symptoms in the debut of the hyponatremia [36], as a neurological symptom present in cases of hyponatremia.
3.2.7. Clozapine
Synthesized in the late 1950s, clozapine is considered the first atypical antipsychotic. It emphasizes its low rate of extrapyramidal effects and its antipsychotic potency, being currently indicated in the management of resistant psychosis and psychotic symptoms in Parkinson’s disease. Literature collects controversial data on its relationship with hyponatremia, although some authors defend its use in Syndrome of Psychosis, Intermittent Hyponatremia and Polydipsia (PIP syndrome) [37].
3.3. Syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP syndrome)
Hyponatremia in psychotic patients is a relatively frequent complication, both due to the osmotic dysregulation of the disease and the secondary effect of antipsychotics. The PIP syndrome is characterized clinically by the presence of acute confusional symptoms derived from symptomatic hyponatremia and water intoxication. Between 6 and 20% of psychotic patients presents with polydipsia. In psychotic patients, in addition to xerostomia and consequent compulsive water intake, the role of supra-optic and paraventricular hypothalamic nuclei, responsible for the regulation of thirst and secretion of antidiuretic hormone (ADH) in the pathophysiology of hyponatremia, is postulated, as well as dopamine and endogenous opioids as neurotransmitters involved in the ingestion of water. Neuroimaging studies in schizophrenic patients show a ventricular dilation in basal conditions, however under conditions of hyponatremia cerebral edema and ventricular contraction are observed. Some studies show that the MDR1 C3435T polymorphism may increase the susceptibility to polydipsia in schizophrenia [38].
Despite its prevalence, morbidity and mortality, it is an underestimated entity in its prevention and early diagnosis. One of the diagnostic challenges is the differentiation between hyponatremia induced by antipsychotics and PIP, since often the treatment of one of the entities worsens the other. Some studies show that urine concentration measurements are useful to differentiate both situations, detecting more frequently concentrated urine in pharmacological hyponatremia and dilute urine secondary to psychotic decompensation [39]. While some studies show that clozapine can generate polydipsia and hyponatremia, others show that it improves the symptoms of polydipsia, so clozapine is postulated as a therapeutic option [37], especially as an alternative to electroconvulsive therapy in cases of catatonia [40].
4. Antidepressants
The consumption of antidepressants has increased significantly in most Organization for Economic Co-operation and Development (OECD) countries since the year 2000. There is significant variation in consumption of antidepressants between countries. For example, in Germany, antidepressant use had risen 46% in just 4 years, in case of Spain and Portugal, it rose about 20% during the same period and Iceland led the pack in overall use with about one in 10 people taking a daily antidepressant [41]. The new generation of antidepressant drugs are widely used as the first line of treatment for major depressive disorders and are considered to be safer than tricyclic agents due to a profile of better tolerability and lower rate of side effects [42]. Several side effects are transient and may disappear after a few weeks following treatment initiation, but potentially serious adverse events may persist or ensue later.
Hyponatramia is the most common electrolyte disorder in ambulatory outpatients, especially in the elderly, and is one of the many well-known side effects of antidepressants [43]. Most of the evidence pointing toward an increased risk of hyponatremia with the use of antidepressant medications is based on multiple case reports and a few observational studies. It is important to remember that mild hyponatremia is associated with instability and falls, reduced cognitive function, osteoporosis and increased morbidity and mortality [44]. Most studies are small and observational and only few have had the power to examine whether specific antidepressants carry a higher or lower risk of hyponatremia.
Hyponatremia, usually, is not dose dependent and the patient recovers when treatment with antidepressant is interrupted. For this reason, early detection as well as the evaluation of concomitant risk factors in all patients starting antidepressant are important. Besides, it seems necessary to supervise sodium plasma levels periodically when patients are in treatment with antidepressants and to choose safe drugs between all possibilities [45].
The selective serotonin reuptake inhibitors (SSRIs) and venlafaxine appear to be the antidepressants most commonly associated with hyponatremia. Between the SSRIs, the incidence of hyponatremia varies based on the definition of hyponatremia used. On the one hand, studies which defined hyponatremia as serum sodium levels <135 mmol/l, the incidence ranged from 9 to 40%. On the other hand, the incidence decreased to 0.06–2.6% when hyponatremia was defined as serum sodium levels <130 mmol/l. The number of case reports and small observational studies with hyponatremia concerning SSRI is substantially higher than the number of case reports and observational studies with other antidepressants, but it is not clear whether this is due to a true difference in incidence of hyponatremia. A review concluded that current evidence suggests a relatively higher risk of hyponatremia with SSRIs and venlafaxine compared to tricyclic antidepressants (TCA) and mirtazapine, but for several antidepressants, data were insufficient to determine the risk of hyponatremia [46]. We found that there were no consistent difference in the incidence of hyponatremia among different SSRI members, but available data indicate that the incidence could be slightly higher for citalopram, fluoxetine and escitalopram, whereas incidence rates may be lower for sertraline and paroxetine [47, 48, 49].
Nevertheless, according to national and international pharmacovigilance committees, 1/3 of the reports of drug induced hyponatremia are severe, with the greatest frequency involving paroxetine, fluoxetine, fluvoxamine, citalopram, venlafaxine, escitalopram and sertraline [50].
The data looking at the risk of hyponatremia associated with the use of serotonin–norepinephrine reuptake inhibitors (SNRIs) are even more limited. Most studies have found incidence rates of hyponatremia comparable to the ones reported for SSRIs. Incidence figures for mirtazapine and tricyclic antidepressants (TCAs) appear to be lower [46, 51].
The mechanisms of antidepressants induced hyponatremia remain incompletely elucidated, but these agents can act by either increasing the release of antidiuretic hormone (ADH) or increasing the sensitivity to ADH resulting in a clinical picture similar to the syndrome of inappropriate secretion of ADH [12]. It must be clarified that the precise mechanism is not known but today it is known that antidepressants are thought to cause the syndrome of inappropriate antidiuretic hormone release (SIADH) by direct or indirect stimulation of vasopressin release from the posterior pituitary gland. SIADH can be produced by multiple causes (hyponatremia with plasma hyposmolality and increased urinary excretion of sodium, increase in urinary osmolality, hypotension, heart failure, nephropathy, liver disease…) and lead to retention of water and to hyponatremia [52]. The prevalence of SIADH in patients using antidepressants has been described in several case reports and a case series and is estimated to occur in five of every 1000 patients treated per year [44, 46, 53, 54]. If we take into account the genetic factor, it is known that most antidepressants are metabolized by the hepatic enzyme cytochrome P450 2D6 (CYP2D6), which is highly polymorphic with >60 variant alleles (http://www.cypalleles.ki.se). In case of individuals carrying two functional CYP2D6 alleles (*1, *2) have “normal” enzyme activity and are classified as extensive metabolizers. However, 5–10% of the population lack enzyme activity due to inheritance of two nonfunctional alleles (*3, *4, *5, *6) and form the so-called poor metabolizers. CYP2D6*4 is the most common variant allele in Caucasians (allele frequency of 20%) [55]. Poor metabolizers have higher plasma concentrations of antidepressants metabolized by CYP2D6 and are therefore more likely to suffer from adverse drug events [56]. It has been hypothesized that hyponatraemia or low serum sodium concentration may be one of these adverse events [57]. This review evaluated the literature on association of hyponatremia and the different families of antidepressants.
The phenomenon of recurrent hyponatremia induced by the use of SSRI has been described in the literature by some authors in subjects who were exposed to it.
Sertraline: In 2013 there were over 41 million prescriptions, making it the most prescribed antidepressant and second most prescribed psychiatric medication in the United States [58] and is used for a number of conditions. There are many publications with patient cases that take this treatment and suffer from hyponatremia [59, 60].
Paroxetine: Paroxetine is primarily used for many mental disorders, has a well-known discontinuation syndrome and shares many of the common adverse effects of SSRIs such as hyponatremia [61, 62, 63].
Fluoxetine: It is a widely used antidepressant, with a multitude of indications and has been assessed as the most effective and safe medicine needed in a health system [64]. There are many cases of patients with hyponatremia taking this treatment [65].
Citalopram: This antidepressant has a good anxiolytic profile but some cases of hyponatremia were recorded [66, 67].
Escitalopram: Is the (S)-stereoisomer of the earlier medication citalopram, used in clinical practice and is related with cases of hyponatremia [68, 69].
Fluvoxamine: Antidepressant with some uses and some analgesic properties. Many cases of hyponatremia were related [70, 71].
Data looking at the risk of hyponatremia associated with the use of SNRIs are even more limited but some cases were described.
Venlafaxine: Drug widely used in daily clinical practice, with indications for mental disorders and painful pathology. Cases of hyponatremia were registered [72, 73, 74].
Duloxetine: Recommended as a first line agent for the treatment of chemotherapy-induced neuropathy and for fibromyalgia in the presence of mood disorders, in addition to other disorders. There are patient cases that take this treatment and suffer from hyponatremia [75, 76].
Desvenlafaxine: Desvenlafaxine is a synthetic form of the major active metabolite of venlafaxine and some cases of hyponatremia were registered [77].
4.3. Mirtazapine
It has noradrenergical and specific serotonergical antidepressant effect and it is more likely to cause weight gain and sleepiness than other treatments. Some cases of hyponatremia were described [14, 53, 54, 55], however, this antidepressant has not been associated with hyponatremia in all cases or with less power of association to this side effect [46, 49, 53, 60, 76, 78].
4.4. Bupropion
Is a norepinephrine-dopamine reuptake inhibitor (NDRI) primarily used as an antidepressant and smoking cessation aid and related with cases of hyponatremia [79, 80], but less than other antidepressants and that does not happen in all cases [51, 61].
4.5. Tricyclic antidepressants
Discovered in the early 1950s, they have number of uses, many of their side effects may be related to the antimuscarinic properties and cases of hyponatremia were registered [81], but with fewer registered cases than with other antidepressants [47, 49, 82].
4.6. Vortioxetine
New antidepressant so-called serotonin modulator and stimulator and two cases of patients with hyponatremia were registered [83].
4.7. Trazodone
Is a serotonin antagonist and reuptake inhibitor that is widely used for the treatment of depression and insomnia. We found controversial results for relationship between trazodone and hyponatremia: case reports in patients on treatment [84], some cases were reported in overdose [85] or articles which describe less power of association to this side effect [51].
4.8. Agomelatine
Agomelatine is a potent agonist at melatonin receptors and an antagonist at serotonin-2C (5-HT2C) receptors. Given the limited references of hyponatremia associated with agomelatine, it has been postulated as a therapeutic alternative in those patients with risk or a history of hyponatremia that require antidepressant treatment [5].
4.9. Mianserine
Mianserin is a tetracyclic antidepressant with serotonergic (5HT2, 5HT1c), histaminergic and adrenergic (α1,α2) inhibitory activity. Some studies report that the association of hyponatremia and mianserin is low [86].
5. Antiepileptics
Epilepsy is a group of neurological disorders characterized by epileptic seizures. It is estimated that nearly 40 million people have epilepsy [86], with differences between countries and age groups. The median incidence of epilepsy is around 50.4/100,000/year: 45.0 for high-income countries and 81.7 for low- and middle-income countries [87]. Incidence is highest in old age (>60 years of age), with an estimated 60–135 new cases per 100,000 older adults each year [87]. Antiepileptics are, usually, initiated as monotherapy for the treatment of epilepsy [88]. However, these drugs are also often used in treatment of nonepileptic conditions such as pain and psychiatric disorders, for this reason it is very common in clinical practice that we find antiepileptics associated with other drugs [89].
As with antidepressants, many cases of hyponatremia are associated with the use of antiepileptic drugs and have been reported and published. However, there are great differences between them [90]. Besides all this, it is important to differentiate cases of antiepileptic that induce asymptomatic hyponatremia and can be easily corrected [91] from cases of severe or symptomatic hyponatremia. Last ones are associated with various types of neurological damage: seizures, altered mentality, brain stem herniation, death, etc., [92]. Because hyponatremia frequently goes undiagnosed and untreated with associated risks, next we will talk about the effect of different antiepileptics in this electrolyte abnormality.
5.1. Phenytoin
This drug was approved by the FDA in 1953. It works by blocking voltage-sensitive sodium channels. It is one of the most used and affordable antiepileptics, with several presentations. Some cases of hyponatremia related to the use of this drug have been described [93], but with less intensity than with other antiepileptic drugs [94].
5.2. Carbamazepine
Is used primarily in the treatment of epilepsy, neuropathic pain, schizophrenia along with other medications and as a second line agent in bipolar disorder. Carbamazepine is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system World Health Organization [70]. It has sodium channel blocking effect. There are many publications with patient cases that take this treatment and suffer from hyponatremia, so it is one of the antiepileptics most frequently associated with this side effect [90, 93, 95, 96, 97].
5.3. Oxcarbazepine
Is a structural derivative of carbamazepine and acts by blocking voltage-sensitive sodium channels. Its use can reduce the occurrence of epileptic episodes, and in psychiatry, has been shown to improve mood (option for add-on therapy in the treatment of bipolar disorder) and reduce anxiety. There is approximately a 25–30% chance of cross-reactivity between carbamazepine and oxcarbazepine. Number of cases of hyponatremia have been recorded with this treatment and with greater strength of association [49, 84, 90, 92, 98, 99].
5.4. Eslicarbazepine acetate
The active component, eslicarbazepine, stabilizes the inactive state of voltage-gated sodium channels (same mechanism of action as oxcarbazepine). This new antiepileptic has potential uses for the treatment of trigeminal neuralgia and bipolar disorder. Cases of hyponatremia were recorded [91, 100, 101].
5.5. Topiramate
Its therapeutic activity and medical indications are very extensive, probably related to multireceptorial effects: voltage-gated sodium channels, GABA-A, AMPA/kainate, high-voltage-activated calcium channels and carbonic anhydrase isoenzymes. Some cases of hyponatremia are related [85], but with less frequency than with other antiepileptic drugs [102].
5.6. Lamotrigine
Is a sodium channel blocking drug (inhibits voltage-sensitive sodium channels), suppress the release of glutamate and aspartate (two dominant excitatory neurotransmitters) and blocks L-, N-, and P- type calcium channels, among other receptor effects. It is used in several neurological and psychiatric disorders and patients with hyponatremia has been notified [90, 103].
5.7. Valproate
Acts through blockade of voltage-gated sodium channels and increased brain levels of gamma-aminobutyric acid (GABA). It is used as primary option to treat epilepsy, bipolar disorder and to prevent migraine headaches, and is included in the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system [64]. Many cases of hyponatremia with Valproate’s treatment were identified [90, 93, 104, 105, 106].
5.8. Gabapentin
Is used primarily to treat seizures and neuropathic pain, and is commonly used to treat anxiety and other disorders. Gabapentin bind to the α2δ-1 subunit of voltage-gated calcium channels, interacts with NMDA receptors, protein kinase C and inflammatory cytokines. There is little relationship between hyponatremia and the use of this drug [90].
5.9. Levetiracetam
This antiepileptic is used to treat epilepsy and different types of seizures. It also associates a multitude of indications for its use: Tourette syndrome, anxiety disorder, neuropathic pain… It acts as a neuromodulator binding to a synaptic vesicle glycoprotein (SV2A) and by inhibiting presynaptic calcium channels. Association of some cases of hyponatremia and use of levetiracetam has been documented [90, 107].
5.10. Pregabalin
It is useful when added to other treatments for many indications. It is an analog of GABA and increases the density of GABA transporter proteins, the rate of functional GABA transport and the extracellular GABA concentrations. Few cases of hyponatremia with use of pregabalin were reported [108].
6. Conclusions
Hyponatremia is a frequent clinical situation in clinical practice, both in outpatient and inpatient settings. Clinical manifestations have a broad spectrum with effect on different indicators such as morbidity and mortality. Nevertheless, this side effect is avoidable and reversible. Given the wide use of psychotropic drugs (antidepressants, antipsychotics and antiepileptics) and its current growing use, it is important to know those pharmacological options with lower risk of hyponatremia such as bupropion, trazodone, mianserin, pregabalin or gabapentin.
We have seen that etiology of hyponatremia is multifactorial and involves pharmacological origin (increase in the production or potentiation of the effects of antidiuretic hormone, alteration of the homeostasis of sodium and water), but many other factors such as advanced age, associated pathologies, female sex, weight or use of concomitant drugs also contribute to the development of hyponatremia. It is important to identify vulnerable patients and to measure sodium levels frequently, especially in the first few days after initiating treatment to help prevent or correct hyponatremia and its undesirable effects.
Conflict of interest
The authors declare no conflict of interests.
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Although hyponatremia has been especially associated with serotonergic antidepressants (SSRIs), there is also an elevated risk with tricyclics, duals and heterocyclic antidepressants, due to the different mechanisms of action at the renal tubular level and the release of ADH. Hyponatremia secondary to tricyclics with slow CYP2D6 metabolizers have higher plasma concentrations of antidepressants metabolized by CYP2D6. Hyponatremia secondary to SSRIs appears in the first week of treatment, it is “not dose-dependent” and normalization of natremia occurs between 2 and 20 days after stopping the medication. Bupropion, trazodone, mianserin, reboxetine and agomelatine are a safe alternative. Also antiepileptics have been related to hyponatremia. Both typical and atypical antipsychotics have been exposed to an increased risk of hyponatremia, even after adjusted factors such as age, sex and comorbidity. Other factors that favor the onset of hyponatremia act synergistically with psychotropic drugs, such as: advanced age, female sex, concomitant diuretic intake, low body weight and low sodium levels; NSAID, ACEIs, and warm.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/62184",risUrl:"/chapter/ris/62184",book:{id:"6790",slug:"fluid-and-electrolyte-disorders"},signatures:"Mireia Martínez Cortés and Pedro Gurillo Muñoz",authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Hyponatremia",level:"1"},{id:"sec_2_2",title:"2.1. Definition of hyponatremia",level:"2"},{id:"sec_2_3",title:"2.1.1. Definition of hyponatremia based on biochemical severity",level:"3"},{id:"sec_3_3",title:"2.1.2. Definition of hyponatremia based on development time",level:"3"},{id:"sec_4_3",title:"2.1.3. Definition of hyponatremia based on symptoms",level:"3"},{id:"sec_5_3",title:"2.1.4. Definition of hyponatremia based on plasma osmolality",level:"3"},{id:"sec_7_2",title:"2.2. Etiology",level:"2"},{id:"sec_7_3",title:"2.2.1. Acute hyponatremia",level:"3"},{id:"sec_8_3",title:"2.2.2. Nonhypotonic hyponatremia",level:"3"},{id:"sec_9_3",title:"2.2.3. Hypotonic hyponatremia",level:"3"},{id:"sec_10_3",title:"2.2.4. Hyponatremia and psychotropic drugs",level:"3"},{id:"sec_12_2",title:"2.3. Symptomatology",level:"2"},{id:"sec_12_3",title:"2.3.1. Mild symptoms",level:"3"},{id:"sec_13_3",title:"2.3.2. Moderate symptoms",level:"3"},{id:"sec_14_3",title:"2.3.3. Severe symptoms",level:"3"},{id:"sec_15_3",title:"2.3.4. Hyponatremic encephalopathy",level:"3"},{id:"sec_16_3",title:"2.3.5. Age",level:"3"},{id:"sec_17_3",title:"2.3.6. Institutionalization",level:"3"},{id:"sec_18_3",title:"2.3.7. Female sex",level:"3"},{id:"sec_19_3",title:"2.3.8. Comorbidity",level:"3"},{id:"sec_20_3",title:"2.3.9. Polytherapy",level:"3"},{id:"sec_22_2",title:"2.4. Treatment",level:"2"},{id:"sec_24",title:"3. Hyponatremia and antipsychotics",level:"1"},{id:"sec_24_2",title:"3.1. First generation antipsychotics (FGAS)",level:"2"},{id:"sec_25_2",title:"3.2. Second generation antipsychotics (SGAS)",level:"2"},{id:"sec_25_3",title:"3.2.1. Aripiprazole",level:"3"},{id:"sec_26_3",title:"3.2.2. Olanzapine",level:"3"},{id:"sec_27_3",title:"3.2.3. Quetiapine",level:"3"},{id:"sec_28_3",title:"3.2.4. Risperidone",level:"3"},{id:"sec_29_3",title:"3.2.5. Paliperidone",level:"3"},{id:"sec_30_3",title:"3.2.6. Ziprasidone",level:"3"},{id:"sec_31_3",title:"3.2.7. Clozapine",level:"3"},{id:"sec_33_2",title:"3.3. Syndrome of psychosis, intermittent hyponatremia and polydipsia (PIP syndrome)",level:"2"},{id:"sec_35",title:"4. Antidepressants",level:"1"},{id:"sec_35_2",title:"4.1. SSRI: selective serotonin reuptake inhibitors",level:"2"},{id:"sec_36_2",title:"4.2. SNRI: serotonin-norepinephrine reuptake inhibitors",level:"2"},{id:"sec_37_2",title:"4.3. Mirtazapine",level:"2"},{id:"sec_38_2",title:"4.4. Bupropion",level:"2"},{id:"sec_39_2",title:"4.5. Tricyclic antidepressants",level:"2"},{id:"sec_40_2",title:"4.6. Vortioxetine",level:"2"},{id:"sec_41_2",title:"4.7. Trazodone",level:"2"},{id:"sec_42_2",title:"4.8. Agomelatine",level:"2"},{id:"sec_43_2",title:"4.9. Mianserine",level:"2"},{id:"sec_45",title:"5. Antiepileptics",level:"1"},{id:"sec_45_2",title:"5.1. Phenytoin",level:"2"},{id:"sec_46_2",title:"5.2. Carbamazepine",level:"2"},{id:"sec_47_2",title:"5.3. Oxcarbazepine",level:"2"},{id:"sec_48_2",title:"5.4. Eslicarbazepine acetate",level:"2"},{id:"sec_49_2",title:"5.5. Topiramate",level:"2"},{id:"sec_50_2",title:"5.6. Lamotrigine",level:"2"},{id:"sec_51_2",title:"5.7. Valproate",level:"2"},{id:"sec_52_2",title:"5.8. Gabapentin",level:"2"},{id:"sec_53_2",title:"5.9. Levetiracetam",level:"2"},{id:"sec_54_2",title:"5.10. Pregabalin",level:"2"},{id:"sec_56",title:"6. 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DOI: 10.1111/j.1528-1167.2006.00585.x'},{id:"B89",body:'Geller AI, Nopkhun W, Dows-Martinez MN, et al. Polypharmacy and the role of physical medicine and rehabilitation. PMR. March 2012;4(3):198-219. DOI: 10.1016/j.pmrj.2012.02.012'},{id:"B90",body:'Lu X, Wang X. Hyponatremia induced by antiepileptic drugs in patients with epilepsy. Expert Opinion on Drug Safety. 2017;16(1):77-87. DOI: 10.1080/14740338.2017.1248399'},{id:"B91",body:'Gupta DK, Bhoi SK, Kalita J, et al. Hyponatremia following esclicarbazepine therapy. Seizure-European Journal of Epilepsy. 2015;29:11-14. DOI: 10.1016/j.seizure.2015.03.005'},{id:"B92",body:'Kim YS, Kim DW, Jung KH, et al. Frequency of and risk factors for oxcarbazepine-induced severe and symptomatic hyponatremia. Seizure-European Journal of Epilepsy. 2014;23(3):208-212. DOI: 10.1016/j.seizure.2013.11.015'},{id:"B93",body:'Gandhi S, McArthur E, Mamdani MM, et al. Antiepileptic drugs and hyponatremia in older adults: Two population-based cohort studies. 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Sodium valproate–induced hyponatremia: A case report. Primary Care Companion to the Journal of Clinical Psychiatry. 2010;12(5): PCC.09l00941'},{id:"B107",body:'Rosca EC, Simu M. Levetiracetam-induced hyponatremia. Acta Neurologica Belgica. 28 Jul 2017;118(1):123-124. DOI: 10.1007/s13760-017-0825-4'},{id:"B108",body:'Jung YJ, Lee DY, Kim HW, et al. A case report of syndrome of inappropriate antidiuretic hormone induced by Pregabalin. Electrolytes & Blood Pressure. 2016;14(2):31-34. DOI: 10.5049/EBP.2016.14.2.31'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mireia Martínez Cortés",address:"mireia.martinez.cortes@gmail.com",affiliation:'
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1. Introduction
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The Pomegranate fruit (Punica granatum L.) is a perineal fruit of the family punicaceae, the fruit comprises of white to deep purple seeds covered in a spongy membrane which is further covered by the pericarp. It is available across the globe as a well-established folklore medicine owing to its anti-oxidant and anti-inflammatory properties. Various useful medicinally active components are present in the peel, seed, flower and even the leaves. The phenolic components comprise the major medicinally active part of the pomegranate extract along with minerals like magnesium, phosphorous, sodium and potassium [1, 2, 3]. There are four groups of phenolic compounds present in pomegranate namely the groups with anthocyanin pigments, hydrolysable tannins like punicalagin, ellagic acid and hydrolysable tannins. All of which contribute to the antioxidant activity. Moreover, it is rich in flavonoids and tannic acids which further adds to its the medicinal value. The antioxidant and anti-inflammatory potential of pomegranate juice and pomegranate extracts puts it apart from other fruits owing to the high concentrations of hydrolysable tannins and anthocyanins along with the polyphenols [4]. Among the various parts of the fruit, the peel and lamella which are the main on edible parts of the fruit has majority of the phenolic contents compared to the other edible parts. The peel accounts for more than half of the total antioxidative potential of the fruit and their anti-proliferative activity [5, 6]. The seed coat of the fruit also presents with numerous organic acids including citric acid and ascorbic acid [7]. Among the major biomedical advantages of pomegranate is the anti-cancer activity since pomegranate and its various components has been prove to assist the treatment of cancer and show immunomodulatory activity [8]. This chapter will be discussing on the anti-cancer activity of pomegranate and its antioxidant activity.
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Cancer is one of the most common disease conditions which is becoming the leading cause of death even when detected in its early stages. In the year of 2021, almost 2 million new cancer cases are expected to happen just in the united states. The cancer death is reducing with each decade comparing to the initial few decades since its peak. With each passing year, there is rapid improvement in the cancer treatment strategies [9]. Pomegranate components can be used for treatment of many ailments as such or as an adjuvant in the treatment. One of the common problems related to cancer therapy is the lack of specificity in differentiating the cancer cells from the normal cells which manifests problems in the oral cavities as mucositis or candidiasis. This shows the prospect of using pomegranate extracts as an adjuvant in normal cancer chemotherapy in order to improve the quality of life of the people undergoing treatment. Also, the rind extract rich in the tannin punicalagin when used in combination with zinc is shows healing activity in the oral cavity due to the anti-inflammatory activity [10, 11].
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2. Pomegranate and prostate cancer
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Prostate cancer is the most prevalent type of cancer in men with an incidence rate above 30 worldwide [12]. From the multicenter studies conducted in human prostate cancer using pomegranate extracts rich in polyphenols, the extracts were found to cause an inhibition in the proliferation of the cells in both in vivo and in vitro studies. Hence the study demonstrated a significant anticancer activity through the inhibition of invasion and proliferation of the cancer cells [13]. The initial stages of prostate cancer will be testosterone dependent and this can be treated with normal radiation or chemotherapy but not in the late stages which shows no dependence with testosterone. The Further studies on the extracts from different parts of pomegranate showed a synergic activity in the anti-proliferative activity of other components of pomegranate. The seed oil from pomegranate acts as a synergistic when used in conjunction with the juice rich in polyphenols in the prevention of proliferation even though it does not have any anti-proliferative effect alone [14].
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The studies on LNCaP cell lines which are modified to over express androgen receptors so that a situation similar to that of androgen independent prostate cancer. By using the different pomegranate extracts rich in polyphenols, the study later on showed a decrease in expression of the gene for the androgen synthesizing enzymes. Since the down regulation of androgen receptors is evident from the study, pomegranate extracts can be of use in the treatment of prostate cancer with an up-regulation of androgen receptors [15]. In androgen independent prostate cancer, there is an observed activation of the nuclear factor NF-κB. The activation of this nuclear factor is a common event in many types of cancer including breast cancer and cervical cancer [16]. In the molecular studies conducted using pomegranate extracts on the activity of NF-κB. It was found that the pomegranate extracts were able inhibit the NF-κB activity which was shown in the androgen independent cells, DU145 with increasing doses. Congruent results were obtained from the electro mobility shift assay conducted on the same cells using pomegranate extracts. In the DU145 and CL-1 cells which are the androgen independent cell lines, the activity of NF-κB was found to be activated through the TNF-α. Pomegranate extracts showed promising activity in the inhibition of NF-κB cells activated in this way as well. In the LAPC4 xenograft induced model of cancer, the extracts from pomegranate was found to delay the initiation of prostate cancer through prevention of proliferation of the cells [17].
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Punicalagin is an important polyphenol constituent of pomegranate and as discussed before, the antioxidant activity of which is very evident in the cancer cells. The antiproliferative activity of punicalagin was examined in previous studies using the DPPH assay and the lipid peroxidation inhibition assays. Along with this, the study checked the cytotoxic activity and viability effects were also determined using punicalagin. It was found that punicalagin inhibited proliferation of cancer cells in prostate cancer and that the prostate cancer cells remained intact in the presence of punicalagin which was further supported by evidences from cell viability assays. The antioxidant activity of the polyphenol was further shown in the DPPH free radical scavenging assay which showed that it scavenged the free radicals in a dose dependent manner. The lipid peroxidation was also inhibited in the presence of punicalagin. PC-3 is another major cell line which is involved in prostate cancer and the polyphenol was found to reduce the PC-3 cells through apoptosis with higher concentrations [18, 19].
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Further, it was found that pomegranate extracts affect the bio synthesis of androgens from the studies conducted using prostate cancer models. In the in vivo study conducted on the animal model using PTEN (Phosphatase and tensin homolog) knockout mouse which represents prostate cancer, there was observable reduction in the levels of steroids in the serum and in the case of in vitro studies using prostate cancer cell lines LNCaP and 22RV1, pomegranate extracts were found to cause a fall in the production of androgens. The in vitro and in vivo date obtained from various studies further shows the possible activity of pomegranate extracts in the treatment of Prostate cancer [20].
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3. Pomegranate and breast cancer
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Breast cancer is the most common type of cancer diagnosed in women and the leading cause of death due to cancer in women with over 2 million cases being diagnosed from recent studies [21]. The major causative factor for the cancer proliferation in breast cancer proliferation is estrogen and the enzymes which catalyzes the production of estrogen. The enzyme aromatase aids in the conversion of androgen into estrogen. So, the inhibition of this enzyme can further aid in the treatment of breast cancer. In vitro studies conducted on one of the major constituents of the pomegranate namely extract ellagic acid and urolithins A and B showed promising results on the inhibition of aromatase enzyme. The placental microsome aromatase assay conducted on ellagitannin derived compounds from pomegranate extracts namely, methylated urolithin B, methylated urolithin A and urolithin A further showed the aromatase inhibiting activity of pomegranate extracts. Which in turn inhibits the proliferation of cancer cells [22].
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From the in vivo studies conducted on mammary organ culture in mice using the pomegranate seed oil rich in punicic acid and the fermented fruit extracts, it was found that the extracts of pomegranate caused a reduction in the number of lesions obtained and supports the activity of pomegranate extracts in the treatment of breast cancer [23].
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The in vitro studies conducted on cancer stem cells derived from MMTV-Wnt-1, pomegranate extract was found to inhibit the proliferation of cancer cell by arresting the cell cycle at an early phase and induced apoptosis of the cancer cells. Pomegranate extracts caused an elevation I the levels of the enzyme caspase 3 which aids in the apoptosis. Among the various extracts, ellagic acid and ursolic acid along with luteolin were found to cause the inhibition of cell proliferation. Also, pomegranate extracts showed promising results in the molecular studies conducted on the MCF-7 cells of breast cancer through the inhibition of proliferation of the cancer cells. In the MCF-7 cells, the anti-cancer activity was found to be due to the cell cycle arrest, down regulation of genes which proliferate the cancer cells and also through the upregulation of the genes which aids in the regulation of proliferation and apoptosis. Hence, pomegranate extracts are relevant in the treatment of breast cancer therapy in the cases which are relatively resistant to the existing agents of treatment [24, 25].
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4. Pomegranate and colon cancer
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Colorectal cancer is currently one of the most common diagnosed cancer in men and women and it manifests with the uncontrolled proliferating of the epithelial cells and the suppression of their apoptosis [26]. One of the major constituents of pomegranate, the ellagitannin urolithin A plays a key role in the inhibition of proliferation of colon cancer cells through cell cycle arrest and the inhibition of mitogen activated protein kinase signaling (MAPK) [27].
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The action of ellagitannins and urolithin on the CYP1 enzymes is important as these enzymes lead to the activation of inactive carcinogens into active carcinogenic chemicals in colon cancer. In the cell line study using HT-29 colon cancer cells, the evaluation of activity of CYP1 enzyme by employing EROD assay (ethoxy resorufin-O-deethylase assay) showed a reduction of CYP1 enzymes which were induced in the cell line. The extracts were found to show selective inhibition of proliferation of the cells omitting the non-cancer cells in a dose dependent fashion. Further, ellagitannin and urolithin was found to cause an increase in the apoptosis of the cell lines resulting in a reduction of the cell colony [28].
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From the animal studies conducted on rats which were induced with colon cancer using N-methylnitrosourea which caused an increase in antigens which were specific to colon cancer along with and increase in plasma levels of Bcl2 and TGF-β, it was found that pomegranate peel extracts caused a fall in the cancer specific parameters which were induced in the mice. The in vivo study further suggests the efficacy of pomegranate in the treatment of colon cancer through the inhibition of proliferation and increased apoptosis which was evident from the fall in CEA and CCSA-4 prostate cancer cell markers along with the down regulation of β-catenin genes which has a pivotal role in the advancement of colon cancer. The down regulation of the specific gene disrupts the signaling pathway involving Wnt/β-catenin [29, 30].
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From the cell line studies using HCT116 and HT-29 colon cancer cell lines, pomegranate extracts comprising of punicalagin, ellagic acid and tannins showed a drastic antiproliferative activity which led to complete inhibition of proliferation depending on the dose. The extract was found to cause apoptosis in the selected cell lines. Further, the extracts were found to have effect on the colon cancer cells which were not metastatic. The cell line studies further cement the role of punicalagin, ellagic acid and pomegranate tannins in the cancer protective activity in colon cancer [31].
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5. Pomegranate and head and neck cancer
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Head and neck cancers are one of the prevalent type of cancer which usually includes squamous cell carcinomas found in the epithelial cells of the pharynx, larynx and the oral cavity [32]. Due to the underdeveloped methods of screening of the disease, the chances of predicting the cancer at an early stage is less. This condition further leads to the increase in number of people who are diagnosed at a late stage of disease progression. In the current scenario, the treatment strategy of the disease mainly involves chemoradiation and surgery. The therapeutic approach to head and neck cancer comes with the common side effects of mucositis and dermatitis. Pomegranate extracts were studied for its protective effect in ameliorating the side effects of the treatment. In the clinical setup of a cohort containing patients with head and neck cancer, it was found that the extracts reduced the extend of damage caused by radiation induced dermatitis as well as mucositis [33].
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Radiation therapy is applied in the cancer therapy for a long time because of its ability to kill the tumor cells but this will also lead to the production of reactive oxygen species that will damage the normal adjacent cells. Pomegranate extract has been studied in the amelioration of cellular damage induced by these reactive oxidants. From a study conducted using the extracts from pomegranate fruit and seeds, it was found that the treatment with the extracts increased the levels of antioxidant and the enzymes which has antioxidant property. Further the extracts were found to cause a decline in the lipid peroxidation levels suggesting the protective effect of pomegranate extracts in the cancer treatment as an adjuvant to reduce the unwanted side effects [34].
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Other than in chemoradiation, pomegranate fruit extracts rich in punicalagin has been found useful in acting as a protective agent for the skin fibroblast cells namely the SKU-1064 from possible apoptosis due to UV-A and UV-B exposure. The extracts were found to suppress the NF- κB activation and through the downregulation of caspase-3 which is proapoptotic. Further studies found an increase in DNA repair through the increase in G0/G1 phase [35]. All these findings further supports the fact that pomegranate extracts can be applied in the treatment of cancer as an adjuvant also as a protective for radiation induced cellular damage.
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6. Pomegranate and lung cancer
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Lung cancer is one of the leading causes of death related to cancer worldwide in both men and women. Cigarette smoking is attributed to e the major cause of the condition. Along with lung cancer, cigarette smoke causes an increase in oxidative stress and DNA damage. From the animal studies conducted on the formation of lung nodules associated with lung cancer and other cancer related factors like the attenuation of mitosis and the levels of hypoxia inducible factor-1α or HIF1 α because of cigarette smoke, it was found that pomegranate juice supplements wee able to reduce the formation of lung nodules which is a common observation in the case of cigarette smoke exposure along with the reduction of mitosis and HIF-1 α [36].
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Further, pomegranate fruit extract treatment in the cell line study using human carcinoma cell associated with lung cancer namely the A549 cells showed an inhibition of the markers of cell proliferation and angiogenesis such as MAPK, NIF-kappa B and PI3K/Akt. The treatment with the extracts further arrested the growth of tumor cells. Thus, pomegranate may be useful as a chemo preventive or as a chemotherapeutic agent against cancer affecting lungs [37]. Methotrexate is a widely used chemotherapeutic agent but it causes injuries in the lung cells due to oxidative stress. In the animal studies employed to study the effect of pomegranate extracts on the protective action against the lung injury caused due to methotrexate, it was found that the use of pomegranate extracts as a prophylactic significantly reduced the total oxidant status and the oxidative stress index along with elevating the total antioxidant capacity. This in turn shows the application of pomegranate extracts as an adjuvant as well in the therapy of lung cancer [38, 39].
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7. Pomegranate and skin cancer
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Pomegranate extracts from seed, peel and the whole fruit have been proven to be beneficial in the treatment of many cancer treatments. Skin cancer is the most common cancer among the Caucasian population and it varies depending on the type of cells affected. UV radiation is the major cause of skin cancer since it initiates and promotes tumor [40]. The in vivo and in vitro studies has shown the efficacy of pomegranate as a protectant in the UVB radiation induced skin damage. The oral treatment of pomegranate juice and extract in the Fitzpatrick II-IV skin type showed the possibility of enhancement in the protective from UV damage since it is able to increase the threshold of the UV dose required to cause erythema of skin [41].
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The oil extracted from seed of pomegranate fruit was studied on animals as a topical prophylactic in the mice which was induced with skin cancer using 12-O-tetradecanoylphorbol 13-acetate and 7,12-dimethylbenzanthracene and it was found that the pre-treated animals had a significant less incidence of skin cancer which tells the protective effect of pomegranate in skin cancer [42]. From the studies conducted on the human skin fibroblasts SKU-1064 which were irradiated with UV, it was found that the pomegranate extracts rich in punicalagin was able to prevent the skin cell death showing the effect of pomegranate as a topical protective agent against skin cancer [35].
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8. Conclusion
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Pomegranate and the products derived from it has been proven to show various medicinal properties. Even though it has been in use in various traditional medical folklore since ages, the medicinal property of pomegranate is not explored much to be of use in the current medical scenario. Pomegranate is still being used as just a fruit and from the studies which are conducted so far on the fruit, it is to be noted that the extracts of the fruit rather than the whole fruit as such possesses many medicinal properties.
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The role of pomegranate in the therapy of cancer as such and as an adjuvant in therapy is explored very less as there are very few studies has been conducted on humans, even though there are a handful of studies which are conducted on animal models or cell line studies which deems the fruit and its extracts effective in the therapy of cancer. The studies conducted so far shows the potency of pomegranate and its components in the treatment of cancer relating to prostate, breast, head and neck, colon, lungs and skin or as an adjuvant in the treatment to minimize the unwanted side effects. The various components of pomegranates because of its antioxidant and anti-inflammatory property can be applied to various treatment strategies in numerous types of cancer in one way or the other.
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Hence it can be concluded that pomegranate extracts can be made to much use for humans in improving the treatment strategies in turn improving the quality of life, for which there has to be more human, animal and cell line studies so that the complete potency of pomegranate can be uncovered.
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\n\n',keywords:"Pomegranate, cancer, antioxidants",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/76671.pdf",chapterXML:"https://mts.intechopen.com/source/xml/76671.xml",downloadPdfUrl:"/chapter/pdf-download/76671",previewPdfUrl:"/chapter/pdf-preview/76671",totalDownloads:258,totalViews:0,totalCrossrefCites:0,dateSubmitted:"September 14th 2020",dateReviewed:"March 12th 2021",datePrePublished:"May 14th 2021",datePublished:null,dateFinished:"May 8th 2021",readingETA:"0",abstract:"Pomegranate (Punica granatum) has been used since ages as a folk medicine. Studies have shown that pomegranate extracts have a role in various signaling pathways involved in inflammation, cellular transformation, hyperproliferation, angiogenesis, initiation of tumorigenesis, and eventually suppressing the final steps of tumorigenesis and metastasis. In this chapter, we have discussed some of the polyphenolic constituents present in pomegranate and their medical value, and we then discussed studies on chemopreventive/chemotherapeutic properties of pomegranate against various types of cancer, such as skin, prostate, colon, head and neck and lung cancers in cell culture systems, animal models and humans.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/76671",risUrl:"/chapter/ris/76671",signatures:"Amulya Thotambailu, Deepu Cheriamane, Manjula Santhepete, Satheesh Kumar Bhandary, Jiju Avanippully and Prakash Bhadravathi",book:{id:"10171",type:"book",title:"Pomegranate",subtitle:null,fullTitle:"Pomegranate",slug:null,publishedDate:null,bookSignature:"Dr. Vasiliki Lagouri",coverURL:"https://cdn.intechopen.com/books/images_new/10171.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-83968-464-7",printIsbn:"978-1-83968-447-0",pdfIsbn:"978-1-83968-465-4",isAvailableForWebshopOrdering:!0,editors:[{id:"232589",title:"Dr.",name:"Vasiliki",middleName:null,surname:"Lagouri",slug:"vasiliki-lagouri",fullName:"Vasiliki Lagouri"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Pomegranate and prostate cancer",level:"1"},{id:"sec_3",title:"3. Pomegranate and breast cancer",level:"1"},{id:"sec_4",title:"4. Pomegranate and colon cancer",level:"1"},{id:"sec_5",title:"5. Pomegranate and head and neck cancer",level:"1"},{id:"sec_6",title:"6. Pomegranate and lung cancer",level:"1"},{id:"sec_7",title:"7. Pomegranate and skin cancer",level:"1"},{id:"sec_8",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nSharma J, Chandra R, Sharma K, Babu D, Meshram D, Maity A, et al. POMEGRANATE: Cultivation, Marketing and Utilization. 2014. https://doi.org/10.13140/RG.2.1.1286.4088\n'},{id:"B2",body:'\nNaz S, Siddiqi R, Ahmad S, Rasool SA, Sayeed SA. Antibacterial Activity Directed Isolation of Compounds from Punica granatum. J Food Sci 2007;72:M341–M345. https://doi.org/10.1111/j.1750-3841.2007.00533.x\n'},{id:"B3",body:'\nViuda-Martos M, Fernández-López J, Pérez-Álvarez JA. Pomegranate and its Many Functional Components as Related to Human Health: A Review. Compr Rev Food Sci Food Saf 2010;9:635-654. https://doi.org/10.1111/j.1541-4337.2010.00131.x\n'},{id:"B4",body:'\nGil MI, Tomás-Barberán FA, Hess-Pierce B, Holcroft DM, Kader AA. Antioxidant Activity of Pomegranate Juice and Its Relationship with Phenolic Composition and Processing. J Agric Food Chem 2000;48:4581-4589. https://doi.org/10.1021/jf000404a\n'},{id:"B5",body:'\nOrgil O, Schwartz E, Baruch L, Matityahu I, Mahajna J, Amir R. The antioxidative and anti-proliferative potential of non-edible organs of the pomegranate fruit and tree. LWT - Food Sci Technol 2014;58:571-577. https://doi.org/10.1016/j.lwt.2014.03.030\n'},{id:"B6",body:'\nMutahar S. S, Mutlag M. A-O, Najeeb S. A. Antioxidant Activity of Pomegranate (Punica granatum L.) Fruit Peels. Food Nutr Sci 2012;2012. https://doi.org/10.4236/fns.2012.37131\n'},{id:"B7",body:'\nViladomiu M, Hontecillas R, Lu P, Bassaganya-Riera J. Preventive and Prophylactic Mechanisms of Action of Pomegranate Bioactive Constituents. Evid Based Complement Alternat Med 2013;2013:789764. https://doi.org/10.1155/2013/789764\n'},{id:"B8",body:'\nXu Y-Y, Wang W-W, Huang J, Zhu W-G. Ellagic acid induces esophageal squamous cell carcinoma cell apoptosis by modulating SHP-1/STAT3 signaling. Kaohsiung J Med Sci 2020;36:699-704. https://onlinelibrary.wiley.com/doi/abs/10.1002/kjm2.12224 (accessed February 1, 2021)\n'},{id:"B9",body:'\nSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Statistics, 2021. CA Cancer J Clin 2021;71:7-33. https://doi.org/10.3322/caac.21654\n'},{id:"B10",body:'\nSANTOS MGC dos, NÓBREGA DR de M, ARNAUD RR, SANTOS RC dos, GOMES DQ de C, PEREIRA JV. Punica granatum Linn. prevention of oral candidiasis in patients undergoing anticancer treatment. Rev Odontol UNESP 2017;46:33-38\n'},{id:"B11",body:'\nCeliksoy V, Moses RL, Sloan AJ, Moseley R, Heard CM. Evaluation of the In Vitro Oral Wound Healing Effects of Pomegranate (Punica granatum) Rind Extract and Punicalagin, in Combination with Zn (II). Biomolecules 2020;10:1234. https://doi.org/10.3390/biom10091234\n'},{id:"B12",body:'\nCancer today n.d. http://gco.iarc.fr/today/home (accessed February 5, 2021)\n'},{id:"B13",body:'\nAlbrecht M, Jiang W, Kumi-Diaka J, Lansky EP, Gommersall LM, Patel A, et al. Pomegranate Extracts Potently Suppress Proliferation, Xenograft Growth, and Invasion of Human Prostate Cancer Cells. J Med Food 2004;7:274-283. https://doi.org/10.1089/jmf.2004.7.274\n'},{id:"B14",body:'\nLansky EP, Jiang W, Mo H, Bravo L, Froom P, Yu W, et al. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest New Drugs 2005;23:11-20. https://doi.org/10.1023/B:DRUG.0000047101.02178.07\n'},{id:"B15",body:'\nHong MY, Seeram NP, Heber D. Pomegranate polyphenols down-regulate expression of androgen-synthesizing genes in human prostate cancer cells overexpressing the androgen receptor. J Nutr Biochem 2008;19:848-855. https://doi.org/10.1016/j.jnutbio.2007.11.006\n'},{id:"B16",body:'\nBaldwin AS Jr. Series Introduction: The transcription factor NF-κB and human disease. J Clin Invest 2001;107:3-6. https://doi.org/10.1172/JCI11891\n'},{id:"B17",body:'\nRettig MB, Heber D, An J, Seeram NP, Rao JY, Liu H, et al. Pomegranate extract inhibits androgen-independent prostate cancer growth through a nuclear factor-κB-dependent mechanism. Mol Cancer Ther 2008;7:2662. https://doi.org/10.1158/1535-7163.MCT-08-0136\n'},{id:"B18",body:'\nAdaramoye O, Erguen B, Nitzsche B, Höpfner M, Jung K, Rabien A. Punicalagin, a polyphenol from pomegranate fruit, induces growth inhibition and apoptosis in human PC-3 and LNCaP cells. Chem Biol Interact 2017;274:100-106. https://doi.org/10.1016/j.cbi.2017.07.009\n'},{id:"B19",body:'\nTai S, Sun Y, Squires JM, Zhang H, Oh WK, Liang C-Z, et al. PC3 is a cell line characteristic of prostatic small cell carcinoma. The Prostate 2011;71:1668-1679. https://doi.org/10.1002/pros.21383\n'},{id:"B20",body:'\nMing D-S, Pham S, Deb S, Chin MY, Kharmate G, Adomat H, et al. Pomegranate extracts impact the androgen biosynthesis pathways in prostate cancer models in vitro and in vivo. J Steroid Biochem Mol Biol 2014;143:19-28. https://doi.org/10.1016/j.jsbmb.2014.02.006\n'},{id:"B21",body:'\nBray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424. https://doi.org/10.3322/caac.21492\n'},{id:"B22",body:'\nAdams LS, Zhang Y, Seeram NP, Heber D, Chen S. Pomegranate Ellagitannin–Derived Compounds Exhibit Antiproliferative and Antiaromatase Activity in Breast Cancer Cells In vitro. Cancer Prev Res (Phila Pa) 2010;3:108-113. https://doi.org/10.1158/1940-6207.CAPR-08-0225\n'},{id:"B23",body:'\nMehta R, Lansky EP. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur J Cancer Prev 2004;13:345-348. https://doi.org/10.1097/01.cej.0000136571.70998.5a\n'},{id:"B24",body:'\nDai Z, Nair V, Khan M, Ciolino HP. Pomegranate extract inhibits the proliferation and viability of MMTV-Wnt-1 mouse mammary cancer stem cells in vitro. Oncol Rep 2010;24:1087-1091. https://doi.org/10.3892/or_00000959\n'},{id:"B25",body:'\nShirode AB, Kovvuru P, Chittur SV, Henning SM, Heber D, Reliene R. Antiproliferative effects of pomegranate extract in MCF-7 breast cancer cells are associated with reduced DNA repair gene expression and induction of double strand breaks. Mol Carcinog 2014;53:458-470. https://doi.org/10.1002/mc.21995\n'},{id:"B26",body:'\nZhao Y, Miao G, Li Y, Isaji T, Gu J, Li J, et al. Microrna 130b Suppresses Migration and Invasion of Colorectal Cancer Cells through Downregulation of Integrin β1. PLOS ONE 2014;9:1-10. https://doi.org/10.1371/journal.pone.0087938\n'},{id:"B27",body:'\nGonzález-Sarrías A, Espín J-C, Tomás-Barberán FA, García-Conesa M-T. Gene expression, cell cycle arrest and MAPK signalling regulation in Caco-2 cells exposed to ellagic acid and its metabolites, urolithins. Mol Nutr Food Res 2009;53:686-698. https://doi.org/10.1002/mnfr.200800150\n'},{id:"B28",body:'\nKasimsetty SG, Bialonska D, Reddy MK, Ma G, Khan SI, Ferreira D. Colon Cancer Chemopreventive Activities of Pomegranate Ellagitannins and Urolithins. J Agric Food Chem 2010;58:2180-2187. https://doi.org/10.1021/jf903762h\n'},{id:"B29",body:'\nAhmed HH, El-Abhar HS, Hassanin EAK, Abdelkader NF, Shalaby MB. Punica granatum suppresses colon cancer through downregulation of Wnt/β-Catenin in rat model. Rev Bras Farmacogn 2017;27:627-635. https://doi.org/10.1016/j.bjp.2017.05.010\n'},{id:"B30",body:'\nAshihara E, Takada T, Maekawa T. Targeting the canonical Wnt/β-catenin pathway in hematological malignancies. Cancer Sci 2015;106:665-671. https://doi.org/10.1111/cas.12655\n'},{id:"B31",body:'\nSeeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, et al. In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 2005;16:360-367. https://doi.org/10.1016/j.jnutbio.2005.01.006\n'},{id:"B32",body:'\nLeemans CR, Braakhuis BJM, Brakenhoff RH. The molecular biology of head and neck cancer. Nat Rev Cancer 2011;11:9-22. https://doi.org/10.1038/nrc2982\n'},{id:"B33",body:'\nThotambailu AM, Bhandary BSK, Sharmila KP. Protective Effect of Punica granatum Extract in Head and Neck Cancer Patients Undergoing Radiotherapy. Indian J Otolaryngol Head Neck Surg 2019;71:318-320. https://doi.org/10.1007/s12070-018-1297-4\n'},{id:"B34",body:'\nBhandary S, Sherly S, Kumari S, Bhat V, Sanjeev G. Ameliorative Activity of Punica granatum Extracts and Ellagic acid against Radiation Induced Biochemical Changes in Swiss Albino Mice. Res J Pharm Biol Chem Sci 2014;5:1097\n'},{id:"B35",body:'\nPacheco-Palencia LA, Noratto G, Hingorani L, Talcott ST, Mertens-Talcott SU. Protective Effects of Standardized Pomegranate (Punica granatum L.) Polyphenolic Extract in Ultraviolet-Irradiated Human Skin Fibroblasts. J Agric Food Chem 2008;56:8434-8441. https://doi.org/10.1021/jf8005307\n'},{id:"B36",body:'\nHusari A, Hashem Y, Zaatari G, El Sabban M. Pomegranate Juice Prevents the Formation of Lung Nodules Secondary to Chronic Cigarette Smoke Exposure in an Animal Model. Oxid Med Cell Longev 2017;2017:e6063201. https://doi.org/10.1155/2017/6063201\n'},{id:"B37",body:'\nKhan N, Mukhtar H. Pomegranate fruit as a lung cancer chemopreventive agent. Drugs Future - DRUG FUTURE 2007;32. https://doi.org/10.1358/dof.2007.032.06.1097137\n'},{id:"B38",body:'\nSelimoğlu Sen H, Sen V, Bozkurt M, Türkçü G, Güzel A, Sezgi C, et al. Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats. Med Sci Monit Int Med J Exp Clin Res 2014;20:1983-1990. https://doi.org/10.12659/MSM.890972\n'},{id:"B39",body:'\nMukherjee S, Ghosh S, Choudhury S, Adhikary A, Manna K, Dey S, et al. Pomegranate reverses methotrexate-induced oxidative stress and apoptosis in hepatocytes by modulating Nrf2-NF-κB pathways. J Nutr Biochem 2013;24:2040-2050. https://doi.org/10.1016/j.jnutbio.2013.07.005\n'},{id:"B40",body:'\nD’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV Radiation and the Skin. Int J Mol Sci 2013;14:12222-12248. https://doi.org/10.3390/ijms140612222\n'},{id:"B41",body:'\nHenning SM, Yang J, Lee R-P, Huang J, Hsu M, Thames G, et al. Pomegranate Juice and Extract Consumption Increases the Resistance to UVB-induced Erythema and Changes the Skin Microbiome in Healthy Women: a Randomized Controlled Trial. Sci Rep 2019;9:14528. https://doi.org/10.1038/s41598-019-50926-2\n'},{id:"B42",body:'\nHora JJ, Maydew ER, Lansky EP, Dwivedi C. Chemopreventive Effects of Pomegranate Seed Oil on Skin Tumor Development in CD1 Mice. J Med Food 2003;6:157-161. https://doi.org/10.1089/10966200360716553\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Amulya Thotambailu",address:"amulyathotambailu@gmail.com",affiliation:'
Department of ENT, JSS Medical College and Hospital, JSS Academy of Higher Education and Research, India
JSS Academy of Higher Education and Research, India
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Open Access publication costs can often be designated directly in the grants or in specific budgets allocated for that purpose. Many of the most important funding organisations encourage, and even request, that the projects they fund are made available at no cost to the wider public. IntechOpen strives to maintain excellent relationships with these funders and ensures compliance with mandates.
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In order to help Authors identify appropriate funding agencies and institutions, we have created a list, based on extensive research on various OA resources (including ROARMAP and SHERPA/JULIET) of organizations that have funds available. Before consulting our list we encourage you to petition your own institution or organization for Open Access funds or check the specifications of your grant with your funder to ascertain if publication costs are included. Where you are in receipt of a grant you should clarify:
\n\n
\n\t
Does your institution already have a budget for covering Open Access publication costs?
\n\t
Does your grant list Open Access publication fees as legitimate direct/indirect costs?
\n
\n\n
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Here the word “asymmetric” means that the available information of the follower is some sub-\n\nσ\n\n-algebra of that available to the leader, though they play as different roles in the classical literatures. Stackelberg equilibrium is represented by the stochastic versions of Pontryagin’s maximum principle and verification theorem with partial information. A linear-quadratic (LQ) leader-follower stochastic differential game with asymmetric information is studied as applications. If some system of Riccati equations is solvable, the Stackelberg equilibrium admits a state feedback representation.",book:{id:"6756",slug:"game-theory-applications-in-logistics-and-economy",title:"Game Theory",fullTitle:"Game Theory - Applications in Logistics and Economy"},signatures:"Jingtao Shi",authors:[{id:"147959",title:"Dr.",name:"Jingtao",middleName:null,surname:"Shi",slug:"jingtao-shi",fullName:"Jingtao Shi"}]},{id:"62516",title:"The Game Theory: Applications in the Wireless Networks",slug:"the-game-theory-applications-in-the-wireless-networks",totalDownloads:1444,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Recent years have witnessed a lot of applications in the computer science, especially in the area of the wireless networks. The applications can be divided into the following two main categories: applications in the network performance and those in the energy efficiency. The game theory is widely used to regulate the behavior of the users; therefore, the cooperation among the nodes can be achieved and the network performance can be improved when the game theory is utilized. On the other hand, the game theory is also adopted to control the media access control protocol or routing protocol; therefore, the energy exhaust owing to the data collision and long route can be reduced and the energy efficiency can be improved greatly. In this chapter, the applications in the network performance and the energy efficiency are reviewed. The state of the art in the applications of the game theory in wireless networks is pointed out. Finally, the future research direction of the game theory in the energy harvesting wireless sensor network is presented.",book:{id:"6756",slug:"game-theory-applications-in-logistics-and-economy",title:"Game Theory",fullTitle:"Game Theory - Applications in Logistics and Economy"},signatures:"Deyu Lin, Quan Wang and Pengfei Yang",authors:[{id:"258432",title:"Dr.",name:"Deyu",middleName:null,surname:"Lin",slug:"deyu-lin",fullName:"Deyu Lin"},{id:"259049",title:"Prof.",name:"Quan",middleName:null,surname:"Wang",slug:"quan-wang",fullName:"Quan Wang"},{id:"261098",title:"Dr.",name:"Pengfei",middleName:null,surname:"Yang",slug:"pengfei-yang",fullName:"Pengfei Yang"}]},{id:"63373",title:"Infinite Supermodularity and Preferences",slug:"infinite-supermodularity-and-preferences",totalDownloads:967,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter studies the ordinal content of supermodularity on lattices. 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In such smart deregulated market environment, cooperative game theory can play a vital role for analyzing various smart deregulated market problems. As an optimization tool, cooperative game theory is very useful in smart energy logistics and economy analysis problem. The economy associated with smart deregulated structure can be better optimized and allocated with the help of cooperative game theory. Initially, due to regulated structure, there is no cooperation between different entities of energy sector. But after new market structure, all the entities are free to take their own decisions as an independent entity. Transmission open access of energy logistics is also comes into the picture, as all the generators and demands have the same right to access the transmission system. In this market situation, multiple utilities are using the same energy logistic network. This situation can be formulated as a cooperative game in which generators and demands are represented by players. This chapter deals with energy logistic cost allocation problems for a smart deregulated energy market. 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\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. 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In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[{type:"book",id:"11672",title:"Chemokines Updates",subtitle:null,isOpenForSubmission:!0,hash:"c00855833476a514d37abf7c846e16e9",slug:null,bookSignature:"Prof. Murat Şentürk",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",editedByType:null,submissionDeadline:"May 6th 2022",editors:[{id:"14794",title:"Prof.",name:"Murat",middleName:null,surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk",profilePictureURL:"https://mts.intechopen.com/storage/users/14794/images/system/14794.jpeg",biography:"Dr. Murat Şentürk obtained a baccalaureate degree in Chemistry in 2002, a master’s degree in Biochemistry in 2006, and a doctorate degree in Biochemistry in 2009 from Atatürk University, Turkey. 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:"profile.detail",path:"/profiles/24251",hash:"",query:{},params:{id:"24251"},fullPath:"/profiles/24251",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)}()