Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
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We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
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Throughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\n
We wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{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"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"9873",leadTitle:null,fullTitle:"Strategies of Sustainable Solid Waste Management",title:"Strategies of Sustainable Solid Waste Management",subtitle:null,reviewType:"peer-reviewed",abstract:"The world is currently experiencing increased environmental contamination with solid waste, which is one of the greatest environmental threats today. Although solid waste is harmful, proper management and profitable recycling can make it beneficial to the environment. In this regard, estimation of the true quantities of solid wastes generated annually in developed and developing countries is important for evaluating suitable strategies for economic and sustainable procedures of waste management. This book presents an interesting review of the economics of solid waste management in various developing and developed countries. It examines several economic applications of solid waste, such as innovative methods to generate bioelectricity from organic waste using microbial fuel cells and using solid waste as an alternative fuel in cement kilns.",isbn:"978-1-83962-560-2",printIsbn:"978-1-83962-559-6",pdfIsbn:"978-1-83962-561-9",doi:"10.5772/intechopen.87682",price:119,priceEur:129,priceUsd:155,slug:"strategies-of-sustainable-solid-waste-management",numberOfPages:170,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"59b5ceeeedaf7449a30629923569388c",bookSignature:"Hosam M. Saleh",publishedDate:"April 21st 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9873.jpg",numberOfDownloads:5955,numberOfWosCitations:5,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:22,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:34,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 12th 2020",dateEndSecondStepPublish:"July 3rd 2020",dateEndThirdStepPublish:"September 1st 2020",dateEndFourthStepPublish:"November 20th 2020",dateEndFifthStepPublish:"January 19th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"144691",title:"Prof.",name:"Hosam",middleName:null,surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh",profilePictureURL:"https://mts.intechopen.com/storage/users/144691/images/system/144691.png",biography:"Hosam Saleh is a Professor of Radioactive Waste Management at the Radioisotope Department, Atomic Energy Authority, Egypt. He was awarded with an MSc and PhD in Physical Chemistry from Cairo University. Saleh has more than 25 years of experience in hazardous waste management with an emphasis on treatment and developing new matrixes for immobilization of these wastes. He is also interested in studying innovative economic and environment-friendly techniques for the management of hazardous and radioactive wastes. He authored many peer-reviewed scientific papers and chapters and served as an editor of several books. He has been selected among the top 2% of scientists in the world according to the Stanford University report for 2020 and 2021.",institutionString:"Egyptian Atomic Energy Authority",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"13",totalChapterViews:"0",totalEditedBooks:"13",institution:{name:"Egyptian Atomic Energy Authority",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"891",title:"Solid Waste",slug:"solid-waste"}],chapters:[{id:"74478",title:"Introductory Chapter: Solid Waste",doi:"10.5772/intechopen.95327",slug:"introductory-chapter-solid-waste",totalDownloads:309,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Hosam M. Saleh and Amal I. Hassan",downloadPdfUrl:"/chapter/pdf-download/74478",previewPdfUrl:"/chapter/pdf-preview/74478",authors:[{id:"144691",title:"Prof.",name:"Hosam",surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"},{id:"218811",title:"Prof.",name:"Amal I.",surname:"Hassan",slug:"amal-i.-hassan",fullName:"Amal I. Hassan"}],corrections:null},{id:"73477",title:"Reflections on the Influence of Family Demographics on Food Waste Generation among the City of Tshwane Households, Republic of South Africa",doi:"10.5772/intechopen.93755",slug:"reflections-on-the-influence-of-family-demographics-on-food-waste-generation-among-the-city-of-tshwa",totalDownloads:304,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter presents the influence of households’ demographics on food waste generation. A mixed method research approach consisting of meta-analysis, survey (structured interviews), and experimental were used to collect opinions and weigh the amount of waste generated in each household. Although not all demographic variables were investigated, the influence of: (1) family size, (2) household monthly income, (3) employment status, (4) educational level, and (5) age of respondents on food waste generation were analyzed. The results of the study confirmed that age and family size are positive factors that influence the amount of food waste generated in households of the City of Tshwane, as opposed to the level of education, employment status, and monthly income levels. It should be noted, however, that this study does not conclusively exclude the other factors as not having an influence in food waste generations. However, their influence in the current food waste generation quantities was not conclusive. Further studies with larger sample size are thus recommended.",signatures:"Machate Machate",downloadPdfUrl:"/chapter/pdf-download/73477",previewPdfUrl:"/chapter/pdf-preview/73477",authors:[{id:"326045",title:"Prof.",name:"Machate",surname:"Machate",slug:"machate-machate",fullName:"Machate Machate"}],corrections:null},{id:"74039",title:"Sustainable Pathway for Closing Solid Waste Data Gaps: Implications for Modernization Strategies and Resilient Cities in Developing Countries",doi:"10.5772/intechopen.94384",slug:"sustainable-pathway-for-closing-solid-waste-data-gaps-implications-for-modernization-strategies-and-",totalDownloads:355,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter addresses three peculiar challenges in the solid waste management system of developing countries, namely: the chronic lack of reliable data for planning purposes, the absence of participatory engagement strategies in data gathering for wider ownership and usage, and the lack of monitoring of the climate change burden of existing waste disposal practices. A team of researchers has collaborated with system managers and a responsible philanthropic organization to engage key stakeholders to address these gaps in a sustainable manner. The strategy deployed has been to work in a participatory and evidenced-based frame to solicit support, enhance capacities, empower each other to understand the problems and find for ourselves the practical routes by which solid waste data gaps can be closed in the greater Accra region of Ghana. Stakeholders have participated in a comprehensive waste audit and landfill emission monitoring exercise to develop a baseline, and have used local resources and ideas to recommend steps to sustain reliable data flows and the development of a climate action plan for purposes of modernization. The methodological processes and research outcomes suggest that structural collaboration between researchers and system stakeholders is necessary to break the vicious circle of chronic data gaps and substitute virtuous circles of reliable data for planning purposes.",signatures:"Kwaku Oduro-Appiah and Abraham Afful",downloadPdfUrl:"/chapter/pdf-download/74039",previewPdfUrl:"/chapter/pdf-preview/74039",authors:[{id:"324899",title:"Dr.",name:"Kwaku",surname:"Oduro-Appiah",slug:"kwaku-oduro-appiah",fullName:"Kwaku Oduro-Appiah"},{id:"330032",title:"Mr.",name:"Abraham",surname:"Afful",slug:"abraham-afful",fullName:"Abraham Afful"}],corrections:null},{id:"73972",title:"Guide for Organising a Community Clean-up Campaign",doi:"10.5772/intechopen.94515",slug:"guide-for-organising-a-community-clean-up-campaign",totalDownloads:758,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"While it is the government’s and municipality’s mandate to ensure that its citizens stay in a clean and safe environment, it is of concern that waste management remains a big challenge in urban areas especially in developing countries. Increased economic development, rapid population growth and improvement of living standards are among the factors attributed to increased quantity and complexity of solid waste being generated. On the other hand, while people generate wastes, they continue to be looked at as passive recipients of municipality services. Ultimately, citizens fail to recognise their role in waste management and become unwilling to either pay for service delivery or participate in clean-up campaigns. Waste dumps are prime breeding sites for communicable disease vectors such as rodents, mosquitoes and houseflies, which can exacerbate the prevalence of water, food and waterborne diseases such as cholera and typhoid. This chapter thus describes the methodology of successfully conducting a community-led cleanup campaign. It is based on experience gained during implementation of an urban water, sanitation and hygiene (WASH) project. Ward level clean-up campaigns were organised and conducted by community members and local leaders. Besides clearing illegal dumpsites, the activity was also used to raise awareness on the consequence of waste dumping. The experience showed that organising a clean-up campaign only requires careful timeous planning. Overall, it was concluded that not only does the activity serve the practical purpose of cleaning, but it also creates a greater sense of unity and friendship among community members. Additionally, the power of beautification in a clean-up campaign wold naturally motivate residents to believe that their problems could be solved, resulting in a shared responsibility for sustainable management of waste and commons at local level.",signatures:"Innocent Rangeti and Bloodless Dzwairo",downloadPdfUrl:"/chapter/pdf-download/73972",previewPdfUrl:"/chapter/pdf-preview/73972",authors:[{id:"171647",title:"Mr.",name:"Innocent",surname:"Rangeti",slug:"innocent-rangeti",fullName:"Innocent Rangeti"},{id:"327929",title:"Dr.",name:"Bloodless",surname:"Dzwairo",slug:"bloodless-dzwairo",fullName:"Bloodless Dzwairo"}],corrections:null},{id:"74647",title:"Economics of Solid Waste Management: A Review",doi:"10.5772/intechopen.95343",slug:"economics-of-solid-waste-management-a-review",totalDownloads:721,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Solid Waste Management is one of the importance environmental issues at many developing countries. There is a lack of studies on economic analysis of solid waste management in the many cities at the national and international level. Most of the Municipal Corporation or city management is the major responsibility for better waste management. However, the local governments has been allocated budget for solid waste management without analysing cost and benefit of solid waste. Although, waste management budget is focusing on collected waste but, uncollected waste has been creating a number of socio, economic and health issues. Therefore, this chapter has presents a details review on economics of solid waste management at the various developing and developed countries. The main policy implication of the paper is to emphasis on better understanding of economic importance of solid waste management to the local policy makers.",signatures:"Muniyandi Balasubramanian",downloadPdfUrl:"/chapter/pdf-download/74647",previewPdfUrl:"/chapter/pdf-preview/74647",authors:[{id:"275432",title:"Dr.",name:"Muniyandi",surname:"Balasubramanian",slug:"muniyandi-balasubramanian",fullName:"Muniyandi Balasubramanian"}],corrections:null},{id:"73967",title:"Sustainable Solid Waste Management in Morocco: Co-Incineration of RDF as an Alternative Fuel in Cement Kilns",doi:"10.5772/intechopen.93936",slug:"sustainable-solid-waste-management-in-morocco-co-incineration-of-rdf-as-an-alternative-fuel-in-cemen",totalDownloads:319,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The management of municipal solid waste (MSW) is a major obstacle for the majority of municipalities in developing countries because of the impacts related to the landfilling of waste. Garbage is an energy-rich material. As a result, energy recovery is considered to be a sustainable waste management method. In Morocco, 7.4 million tons are produced annually; most of the waste is landfilled without any recovery despite the impacts related to this method of disposal. The objective of this chapter is to characterize combustible fractions (RDF) from household waste in Morocco and to study the economic and environmental benefits of their use as alternative fuels in cement kilns. The results of this research show that the combustible fractions contained in household waste in Morocco constitute a potential sustainable energy source with a high lower calorific value (4454 kcal/kg). The study of the advantages of co-incineration shows that the substitution of pet coke by 15% RDF reduces the pollution linked to gaseous emissions. In addition, the cement plant can make financial savings 389 USD/h by minimizing the use of fossil fuels.",signatures:"Aziz Hasib, Abdellah Ouigmane, Otmane Boudouch, Reda Elkacmi, Mustapha Bouzaid and Mohamed Berkani",downloadPdfUrl:"/chapter/pdf-download/73967",previewPdfUrl:"/chapter/pdf-preview/73967",authors:[{id:"166445",title:"Prof.",name:"Aziz",surname:"Hasib",slug:"aziz-hasib",fullName:"Aziz Hasib"},{id:"237725",title:"Prof.",name:"Reda",surname:"Elkacmi",slug:"reda-elkacmi",fullName:"Reda Elkacmi"},{id:"325462",title:"Dr.",name:"Abdellah",surname:"Ouigmane",slug:"abdellah-ouigmane",fullName:"Abdellah Ouigmane"},{id:"325463",title:"Prof.",name:"Otmane",surname:"Boudouch",slug:"otmane-boudouch",fullName:"Otmane Boudouch"},{id:"325528",title:"Prof.",name:"Mustapha",surname:"Bouzaid",slug:"mustapha-bouzaid",fullName:"Mustapha Bouzaid"},{id:"325529",title:"Prof.",name:"Mohammed",surname:"Berkani",slug:"mohammed-berkani",fullName:"Mohammed Berkani"}],corrections:[{id:"74392",title:"Corrigendum to: Sustainable Solid Waste Management in Morocco: Co-Incineration of RDF as an Alternative Fuel in Cement Kilns",doi:null,slug:"corrigendum-to-sustainable-solid-waste-management-in-morocco-co-incineration-of-rdf-as-an-alternativ",totalDownloads:null,totalCrossrefCites:null,correctionPdfUrl:null}]},{id:"74238",title:"Effectiveness of Anaerobic Technologies in the Treatment of Landfill Leachate",doi:"10.5772/intechopen.94741",slug:"effectiveness-of-anaerobic-technologies-in-the-treatment-of-landfill-leachate",totalDownloads:544,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Improper Solid Waste Management leads to the generation of landfill leachate at the landfills. To reduce the negative impacts of highly toxic and recalcitrant leachate on the environment, several techniques have been used. A lot of research is conducted to find suitable methods for the treatment of landfill leachate such as biological processes, chemical oxidation processes, coagulation, flocculation, chemical precipitation, and membrane procedures. The biological process is still being used widely for the treatment of leachate. The current system of leachate treatment consists of various unit processes which require larger area, energy and cost. In addition, the current aerobic treatment is not able to treat entirely the pollutants which require further treatment of the leachate. Anaerobic wastewater treatment has gained considerable attention among researchers and sanitary engineers primarily due to its economic advantages over conventional aerobic methods. The major advantages of anaerobic wastewater treatment in comparison to aerobic methods are: (a) the lack of aeration, which decreases costs and energy requirements; and (b) simple maintenance and control, which eliminates the need for skilled operators and manufacturers. Several anaerobic processes have been used for leachate treatment such as up-flow anaerobic sludge blanket (UASB) reactor, anaerobic filter, hybrid bed reactor, anaerobic sequencing batch reactor and Anaerobic baffled reactor. The following chapter provides an insight to the solid waste management at the landfills, generation of leachate and details of some of the highly efficient anaerobic treatment systems that are used for the overall treatment of landfill leachate.",signatures:"Imran Ahmad, Norhayati Abdullah, Shreeshivadasan Chelliapan, Ali Yuzir, Iwamoto Koji, Anas Al-Dailami and Thilagavathi Arumugham",downloadPdfUrl:"/chapter/pdf-download/74238",previewPdfUrl:"/chapter/pdf-preview/74238",authors:[{id:"237449",title:"Dr.",name:"Shreeshivadasan",surname:"Chelliapan",slug:"shreeshivadasan-chelliapan",fullName:"Shreeshivadasan Chelliapan"},{id:"324168",title:"Ph.D. Student",name:"Imran",surname:"Ahmad",slug:"imran-ahmad",fullName:"Imran Ahmad"},{id:"332462",title:"Dr.",name:"Norhayati",surname:"Abdullah",slug:"norhayati-abdullah",fullName:"Norhayati Abdullah"},{id:"338893",title:"Dr.",name:"Ali",surname:"Yuzur",slug:"ali-yuzur",fullName:"Ali Yuzur"},{id:"338894",title:"Dr.",name:"Iwamoto",surname:"Koji",slug:"iwamoto-koji",fullName:"Iwamoto Koji"},{id:"338895",title:"Dr.",name:"Anas",surname:"Al-Dailami",slug:"anas-al-dailami",fullName:"Anas Al-Dailami"},{id:"343758",title:"Dr.",name:"Thilagavathi",surname:"Arumugham",slug:"thilagavathi-arumugham",fullName:"Thilagavathi Arumugham"}],corrections:null},{id:"74004",title:"Hydrometallurgical Recovery of Gold from Mining Wastes",doi:"10.5772/intechopen.94597",slug:"hydrometallurgical-recovery-of-gold-from-mining-wastes",totalDownloads:666,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:1,abstract:"Gold is a highly required material for a wide range of personal and industrial applications. The high demand for gold, together with the shortage of natural resources and high pollution potential of wastes generated during mining and ore processing activities led to search for alternative sources of gold. A possible source is represented by mine wastes resulting from the processing of polymetallic or sulfidic ores. The reprocessing of wastes and old tailings with moderate to low content of gold offers not only a business opportunity, but also enhances the quality of the surrounding environment, changes the land use and offers a wide range of socio-economic benefits. Cyanidation, the most widespread Au leaching option, is progressively abandoned due to the high risk associated with its use and to the low public acceptance. Therefore, alternative methods such as thiocyanate, thiourea, thiosulphate and halide leaching gained more and more interest. This chapter presents the most important features of some Au leaching methods, emphasizing their advantages, limitations and potential applications.",signatures:"Emilia Neag, Eniko Kovacs, Zamfira Dinca, Anamaria Iulia Török, Cerasel Varaticeanu and Erika Andrea Levei",downloadPdfUrl:"/chapter/pdf-download/74004",previewPdfUrl:"/chapter/pdf-preview/74004",authors:[{id:"324453",title:"Dr.",name:"Erika Andrea",surname:"Levei",slug:"erika-andrea-levei",fullName:"Erika Andrea Levei"},{id:"335075",title:"Dr.",name:"Emilia",surname:"Neag",slug:"emilia-neag",fullName:"Emilia Neag"},{id:"335077",title:"MSc.",name:"Eniko",surname:"Kovacs",slug:"eniko-kovacs",fullName:"Eniko Kovacs"},{id:"335078",title:"Dr.",name:"Zamfira",surname:"Dinca",slug:"zamfira-dinca",fullName:"Zamfira Dinca"},{id:"335080",title:"Dr.",name:"Anamaria Iulia",surname:"Török",slug:"anamaria-iulia-torok",fullName:"Anamaria Iulia Török"},{id:"335081",title:"BSc.",name:"Cerasel",surname:"Varaticeanu",slug:"cerasel-varaticeanu",fullName:"Cerasel Varaticeanu"}],corrections:null},{id:"74827",title:"Bioelectricity from Organic Solid Waste",doi:"10.5772/intechopen.95297",slug:"bioelectricity-from-organic-solid-waste",totalDownloads:410,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Resource recovery and recycling of organic waste is a great challenge in the world. The unmanaged organic waste causes a great damage to the environment and the public health both in the developing countries and industrial parts of the world. In this research, an innovative method was adopted to generate bioelectricity from the organic waste by using the Microbial Fuel Cell (MFC). Various types of organic wastes such as livestock waste, food waste, fruit waste were used as the substrates of the microbial fuel cell. All the experiments were carried out in the same sized one chamber microbial fuel cell and the similar electrode materials. It was observed that all the organic wastes can be used to generate bioelectricity through microbial fuel cell. The generated electricity can be used in several environmental monitoring sensors and can be used as an alternate power source in the developing countries. The by-products of the bioelectricity generation can be used as soil conditioner in the organic depleted soil and agricultural fields.",signatures:"M. Azizul Moqsud",downloadPdfUrl:"/chapter/pdf-download/74827",previewPdfUrl:"/chapter/pdf-preview/74827",authors:[{id:"7199",title:"Dr.",name:"Md.Azizul",surname:"Moqsud",slug:"md.azizul-moqsud",fullName:"Md.Azizul Moqsud"}],corrections:null},{id:"73517",title:"Agricultural Solid Wastes: Causes, Effects, and Effective Management",doi:"10.5772/intechopen.93601",slug:"agricultural-solid-wastes-causes-effects-and-effective-management",totalDownloads:1577,totalCrossrefCites:5,totalDimensionsCites:14,hasAltmetrics:1,abstract:"The role of the agricultural sector in human development and economic development cannot be overemphasized. Awareness for increased agricultural production is on the increase, arising from the need to feed the ever-increasing human population. Interestingly, almost all agricultural activities generate wastes, which are generated in large quantities in many countries. However, these wastes may constitute a serious threat to human health through environmental pollution and handling them may result in huge economic loss. Unfortunately, in many developing countries where large quantities of these wastes are generated, they are not properly managed because little is known about their potential risks and benefits if properly managed. There are studies that address some of the challenges of agricultural solid wastes as well as suggestions on how they can be properly managed. In this chapter, we intend to explore the major sources of agricultural solid wastes, their potential risks, and how they can be properly managed.",signatures:"Isaac Oluseun Adejumo and Olufemi Adebukola Adebiyi",downloadPdfUrl:"/chapter/pdf-download/73517",previewPdfUrl:"/chapter/pdf-preview/73517",authors:[{id:"276527",title:"Dr.",name:"Isaac Oluseun",surname:"Adejumo",slug:"isaac-oluseun-adejumo",fullName:"Isaac Oluseun Adejumo"},{id:"328699",title:"Dr.",name:"O.A.",surname:"Adebiyi",slug:"o.a.-adebiyi",fullName:"O.A. Adebiyi"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8580",title:"Municipal Solid Waste Management",subtitle:null,isOpenForSubmission:!1,hash:"e3554c02569fe3ac8afa79cb02daae97",slug:"municipal-solid-waste-management",bookSignature:"Hosam El-Din Mostafa Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/8580.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam",surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2383",title:"Polyester",subtitle:null,isOpenForSubmission:!1,hash:"79fd9d6314f8e1abd60d7e21896ce878",slug:"polyester",bookSignature:"Hosam El-Din M. Saleh",coverURL:"https://cdn.intechopen.com/books/images_new/2383.jpg",editedByType:"Edited by",editors:[{id:"144691",title:"Prof.",name:"Hosam",surname:"Saleh",slug:"hosam-saleh",fullName:"Hosam Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6534",title:"Heavy Metals",subtitle:null,isOpenForSubmission:!1,hash:"a7573426a162c18f39acc575c1e69f67",slug:"heavy-metals",bookSignature:"Hosam El-Din M. Saleh and Refaat F. 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\r\n\tSediment transport is one of the most challenging topics in different fields of coastal, hydraulic and environmental engineering. Indeed, it appears in seas and oceans, lakes, rivers, harbors, and many other natural systems. \r\n\tIn the last decades, particular attention to this field has been paid to the coastal erosion problem all over the world. Indeed, the deployment of artificial reservoirs, modification of the runoff characteristics of internal areas, sand extraction from rivers, and harbor siltation, caused a decrease of sediment input on the coastal environments, and, therefore, a generalized deficit in the sediment budget. Often, dredging activities are required to collect sediment finalized to “soft” techniques to restore beaches or to move the sand trapped in the harbor (clean or contaminated). \r\n\tMoreover, the coastal protections induced hydrodynamics and morphodynamics modifications inducing sometimes strong variations to the sediment transport regime.
\r\n
\r\n\tHistorically, all these aspects are related to specific research areas ranging from engineering, geology, geomorphology, biology, etc, but it is difficult to find a comprehensive overview of these topics.
\r\n
\r\n\tThis book is intended to collect original works and review concerning numerical and experimental investigation, theoretical works, methodological approaches, and any other technique that allow giving the actual state-of-the-art in the field of sediment transport.
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\n
1. Introduction
\n
Drug repurposing (DR) is also known as drug repositioning, drug re-tasking, drug reprofiling, drug rescuing, drug recycling, drug redirection, and therapeutic switching. It can be defined as a process of identification of new pharmacological indications from old/existing/failed/investigational/already marketed/FDA approved drugs/pro-drugs, and the application of the newly developed drugs to the treatment of diseases other than the drug’s original/intended therapeutic use. It involves establishing new therapeutic uses for already known drugs, including approved, discontinued, abandoned and experimental drugs [1, 2, 3]. Traditional drug discovery is a time-consuming, laborious, highly expensive and high risk process. The novel approach of drug repositioning has the potential to be employed over traditional drug discovery program by mitigating the high monetary cost, longer duration of development and increased risk of failure. It confers reduced risk of failure where a failure rate of ~45% is associated due to safety or toxicity issues in traditional drug discovery program with additional benefit of saving up to 5–7 years in average drug development time [4, 5]. In recent years, the drug repositioning strategy has gained considerable momentum with about one-third of the new drug approvals correspond to repurposed drugs which currently generate around 25% of the annual revenue for the pharmaceutical industry [6]. It has been accounted that approximately 30% of the US Food and Drug Administration (FDA) approved drugs and biologics (vaccines) are repositioned drugs. According to recent estimates, pharmaceutical industries have significantly placed the market for repurposed drugs at $24.4 billion in 2015 with projected growth up to $31.3 billion in 2020. The first example of drug repositioning was an accidental discovery/serendipitous observations in the 1920s. After about a century of development, more approaches were developed for accelerating the process of drug repositioning. Some most successful and best-known drugs that have been emerged out of the DR approach are sildenafil, minoxidil, aspirin, valproic acid, methotrexate etc. [7]. For example, sildenafil originally developed for the treatment of hypertension and angina pectoris has currently been used to treat erectile dysfunction.
\n
\n
\n
2. Traditional drug discovery vs. drug repurposing
\n
The traditional approach to drug discovery involves de novo identification and of new molecular entities (NME), which include five stages: discovery and preclinical, safety review, clinical research, FDA review, and FDA post-market safety monitoring. It is a time-consuming and costly process with high risk of failure [8]. On the other hand, there are only four stages in drug repositioning, which include compound identification, compound acquisition, development, and FDA post-market safety monitoring [9] (Figure 1). With the advancement of bioinformatics/cheminformatics tools and availability of huge biological and structural database, drug repositioning has significantly decreased the time and cost of the drug development with reduction in risk of failure. In recent years, the use of in silico techniques along with the application of structure-based drug design (SBDD) and artificial intelligence (AI) technology has further accelerated the drug purposing process [10, 11].
\n
Figure 1.
Traditional drug discovery vs. drug repurposing.
\n
However, the repositioning strategy of using approved therapeutics for new therapeutic indications has demonstrated success particularly through prior serendipitous observations. The discovery of drugs by this approach is certainly advantageous as depicted above over traditional drug discovery program as described below. For example, sildenafil (Viagra), a phosphodiesterase-5 (PDE5) inhibitor initially developed for coronary artery disease (angina) by Pfizer (1985) has been repurposed for the treatment of erectile dysfunction. It potentially reduced the development cost at shorter development time. Metformin (Glucophage), an oral anti-diabetic medication used widely in type 2 diabetes mellitus has been developed as a cancer therapeutic which is currently under phase II/phase III clinical trials [1, 12].
\n
Drug repositioning has several advantages in comparison with traditional approaches to drug discovery. When comparing with traditional drug discovery program, a significant reduction of the time spent in R&D can be observed. In traditional approach, it is estimated that 10–16 years are spent for the development of a new drug, while in DR the estimated time is between 3 and 12 years. It only costs $1.6 billion to develop a new drug using a drug repositioning strategy, while the drug development through traditional strategy costs around $12 billion. Moreover, researchers only need 1–2 years to identify new drug targets and about an average of 8 years to develop a repositioned drug [6, 7]. A repositioned drug does not require the initial 6–9 years typically required for the development of new drugs by traditional process, but instead enters directly to preclinical testing and clinical trials, thus reducing the overall risk, time and cost of development. Reports suggest that repurposed drugs require approximately 3–12 years for gaining approval from FDA and/or European Medicines Agency (EMA) and at reduced 50–60% cost. At the beginning of a repositioning project, a range of pre-clinical (pharmacological, toxicological, etc.), and clinical efficacy and safety information is already available, as the candidate drug has already undergone through the early stages of drug development such as structural optimization, preclinical and/or clinical trials, in addition to the possibility of the candidate drug being an approved drug, having its clinical efficacy and safety profile. In this way, there is a reduction of the risks associated with failures in the early stages of development, which are high in traditional approaches, as well as a significant reduction of cost with the possible increase in clinical safety and therefore, high success rate [13, 14].
\n
Due to the availability of previously collected pharmacokinetic, toxicological, clinical and safety data at the start of a repurposing development project, the advantages that are encountered with drug repurposing over traditional drug discovery approach are reduced time of development, lower cost of development and reduced risks of failure in the clinical development.
\n
It has been estimated that the time required for development of a repositioned drug varies from 3 to 12 years (which is about 10–17 years in traditional discovery program) with substantially lower costs, which ensures the repositioning company’s significant savings in terms of time and capital. The average cost required to bring a new drug to market is USD 1.24 billion by traditional drug development process, whereas in drug repurposing it costs around ≤60% expenditure of traditional drug discovery. Some other advantages are as follow. The primary focus of traditional discovery program is to discover drugs to treat chronic and complex diseases, whereas by drug repositioning approach, development of drugs for rapidly emerging and re-emerging infectious diseases, difficult to treat diseases and neglected diseases (NTDs) are focused. Due to the availability of bioinformatics or cheminformatics approaches, huge omics (proteomics, transcriptomics, metabolomics, genomics etc.) data and database resources, disease targeted-based repositioning methods can be used to explore the unknown mechanisms of action (such as unknown targets for drugs, unknown drug–drug similarities, new biomarkers for diseases etc.) of known/existing drugs [13].
\n
\n
\n
3. Strategies of drug repurposing
\n
There are two main strategies of DR, viz., on-target and off-target (Figure 2). In on-target DR, the known pharmacological mechanism of a drug molecule is applied to a new therapeutic indication. In this strategy, the biological target of the drug molecule is same, but the disease is different [12].
\n
Figure 2.
On-target and off-target strategies of drug repositioning.
\n
For example, in the repositioning of minoxidil (Rogaine), an on-target profile is observed, since the drug acts on the same target and produces two different therapeutic effects. Minoxidil was transformed from an antihypertensive vasodilator anti hair loss drug. As an antihypertensive vasodilator, minoxidil has the property of widening blood vessels and opening potassium channels, which allows more oxygen, blood, and nutrients to the hair follicles and this pharmacological action helps its use in the treatment of male pattern baldness (androgenic alopecia). On the other hand, in the off-target profile, the pharmacological mechanism is unknown. Drugs and drugs candidates act on new targets, out of the original scope, for new therapeutic indications. Therefore, both the targets and the indications are new [1]. Aspirin (Colsprin) is good example of the off-target profile. Aspirin has been traditionally used as NSAID in the treatment of various pain and inflammatory disorders. It also suppresses blood coagulation (clot formation) by inhibiting the normal functioning of platelets (antiplatelet drug). It is, therefore, used in the treatment of heart attacks and strokes. Another new use of aspirin in the treatment of prostate cancer has also been reported.
\n
\n
\n
4. Approaches of drug repurposing
\n
Drug repositioning has two alternative and complementary approaches, one is experiment-based approach and the other is in silico-based approach.
\n
The experiment-based approach is also known as activity-based repositioning which refers to the screening of original drugs for new pharmacological indications based on experimental assays. It involves protein target-based and cell/organism-based screens in in vitro and/or in vivo disease models without requiring any structural information of target proteins. Several approaches of experimental repositioning are target screening approach, cell assay approach, animal model approach and clinical approach [15, 16].
\n
In contrast, in silico repositioning carries out virtual screening of public databases of huge drug/chemical libraries using computational biology and bioinformatics/cheminformatics tools. In this approach, the identification of potential bioactive molecules is achieved based upon the molecular interaction between drug molecule and protein target [17].
\n
The differences between activity- and in silico-based approaches of drug repositioning are summarized in Table 1.
\n
\n
\n
\n\n
\n
Activity-based approach
\n
\nIn silico-based approach
\n
\n\n\n
\n
Experimental (in vitro and in vivo) screening
\n
Computational (virtual) screening
\n
\n
\n
Target-based and cell/organism-based screening assay
\n
Protein target-based screening
\n
\n
\n
Requires no structural information of target proteins and drug-induced cell/disease phenotypic information
\n
Requires structural information of target proteins and drug-induced cell/disease phenotypic information
\n
\n
\n
Time and labor consuming
\n
Time and labor efficient
\n
\n
\n
Lower rate of false positive hits during the screening
\n
Higher rate of false positive hits during the screening
\n
\n\n
Table 1.
Differences between activity- and in silico- based approaches of drug repositioning [17, 18].
\n
Over the past few decades, the in silico approach has gained wide popularity with significant success in drug discovery program. Many pharmaceutical companies and drug discovery research laboratories have already successfully incorporated the in silico tools and techniques for the drug discovery from structurally diverse chemical spaces since a large amount of information on the chemical structure bioactive compounds, structure of proteins and pharmacophore models are available in the public domain. Moreover, in silico repositioning has some advantages over the experimental-based approach, which includes reduced time and cost of development and low risk of failure. The limitation of this method is that it requires precise structural information about drug targets and in case, the protein target is not available, disease specific phenotypic or genotypic profiles of drugs are required [19]. Figure 3 represents the approaches of drug repositioning.
\n
Figure 3.
Approaches of drug repositioning.
\n
In recent years, discovery scientists and researchers have combined in silico and experimental approaches to identify new therapeutic indications for existing drugs, called mixed approach. In the mixed approach, the result of computational methods is validated by pre-clinical biological experiments (in vitro and in vivo tests) and clinical studies. The simultaneous application of computational and experimental methodologies in a systematic manner offer a robust and logical approach to the discovery of new indications, demonstrating a greater efficiency than the discovery based on serendipity. Further, mixed approach offers opportunities for developing repositioned drugs more effectively and rapidly. This approach is credible and yet, reliable [20].
\n
\n
\n
5. Methodologies of drug repurposing
\n
The methodologies adopted in DR can be divided into three broad groups depending on the quantity and quality of the pharmacological, toxicological and biological activity information available. These are mainly (i) drug-oriented, (ii) target-oriented, and (iii) disease/therapy-oriented.
\n
In the drug-oriented methodology, the structural characteristics of drug molecules, biological activities, adverse effects and toxicities are evaluated. This strategy is meant for identifying molecules with biological effects based on cell/animal assays. This type of repositioning methodology is based on traditional pharmacology and drug discovery principles, where studies are usually conducted to determine the biological efficacy of drug molecules without really knowing about the biological targets. Significant successes in DR have been achieved with this orientation profile, through serendipity or clinical observation, such as discoveries with sildenafil [21].
\n
Target-based methodology comprise in silico screening or virtual high-throughput screening (vHTS) of drugs or compounds from drug libraries/compound databases such as ligand-based screening or molecular docking followed by in vitro and in vivo high-throughput and/or high-content screening (HTS/HCS) of drugs against a selective protein molecule or a biomarker of interest. In this method, there is a significant success rate in drug discovery as compared to drug-oriented method, because most biological targets directly represent the disease pathways/mechanisms [22].
\n
The application of disease/therapy-oriented methodology in DR is relevant when there is more information on the disease model is available. In this case, DR can be guided by the disease and/or treatment based upon availability of information given by proteomics (disease specific target proteins), genomics (disease specific genetic data), metabolomics (disease specific metabolic pathways/profile) and phenotypic data (off-target mechanism, pharmacological targets, disease pathways, pathological conditions, adverse and side effects etc.) concerning the disease process. It, therefore, requires construction of specific disease networks, recognizing genetic expression, considering key targets, identifying disease causing protein molecules related to cell and metabolic pathways of interest in the disease model [23].
\n
\nFigure 4 delineates the methodologies and steps involved in drug repositioning.
\n
Figure 4.
Methodologies and steps involved in drug repositioning.
\n
Drug-based phenotypic screening and target-based methods account for more than 50% of the FDA approved small drug molecules and biologics. Phenotypic drug screening methods identify drug candidates from small molecule libraries by serendipitous observations. Target-based methods discover drugs based upon known target molecules. The treatment/therapy-based repositioning methodology is similar to disease-based methodology [23].
\n
A detailed enumeration of various methodologies employed in drug repositioning along with suitable examples is given in Table 2.
Drug omics data, disease pathway and protein interaction network
\n
Targeted- mechanism based, Network biology and Systems biology
\n
Elucidating targeted pathways
\n
Daunorubicin, clomifene (breast cancer)
\n
\n\n
Table 2.
Some available methods of drug repositioning [23, 24].
\n
Several available repositioning methods depicted above in Table 2 are described briefly as follows:
\n
Blinded search or screening methods involve serendipitous identification from biological tests/experimental screens aimed at specific disease models and drugs. The advantage of these methods is that they possess higher flexibility for screening a large number of drugs or diseases.
\n
Target-based methods carry out in vitro and in vivo high-throughput and/or high-content screening (HTS/HCS) of drug molecules for a protein target or a biomarker of interest and in silico screening of compounds or drugs from large compound libraries, such as ligand-based screening or molecular docking. In these methods, there is a higher possibility of finding useful drugs/drug leads as compared to blinded search methods. It also requires less time for the entire screening process to complete.
\n
Knowledge-based methods utilize bioinformatics or cheminformatics approaches to gather the available information of drug profile, chemical structures of targets and drugs, drug-target networks, clinical trial information including adverse effects, signaling or metabolic pathways. This information content of knowledge-based methods is rich enough as compared to blinded or target-based methods. The known information can be used to predict therefore, be used to predict the unknown new mechanisms, such as unknown targets for drugs, unknown drug–drug similarities, new biomarkers for diseases etc.
\n
Signature-based methods use gene signatures derived from disease omics data (genomics data) with or without treatments to discover unknown off-targets or unknown disease mechanisms. Genomics data are publicly available as databases. The advantage of these methods is that they are useful to explore unknown mechanisms of action of drugs. In comparison to knowledge-based methods, signature-based methods investigate drug mechanisms at more molecular-level, such as changes in expression of genes by using computational approaches.
\n
Pathway- or network-based methods make use of disease omics data, available signaling or metabolic pathways, and protein interaction networks to reconstruct disease-specific path- ways that provide the key targets for repositioned drugs. The advantage of these methods is that they can narrow down general signaling networks from a large number of proteins to a specific network with a few proteins (or target molecules).
\n
Targeted mechanism-based methods integrate treatment omics data, available signaling pathway information and protein interaction networks to describe the unknown mechanisms of action of drugs. The advantage of these methods is that they are not only used to discover the mechanisms related to diseases or drugs, but also to identify those directly related to treatments of drugs to specific diseases [23, 24, 25].
\n
\n
\n
6. Repositioned drugs
\n
Drug repositioning is an alternative approach to traditional drug discovery. With increasing market demand many pharmaceutical companies are developing new drugs or new therapeutic uses from existing/old/available drugs by drug repositioning approaches in less time, yet at low cost. In drug discovery program, the repositioning is usually essentially carried out in two stages as described follows. In the first stage, the in silico screening of approved drugs against a particular disease target is carried out, which is followed by the second step, in which the selected identified molecules are further experimentally investigated both in vitro and in vivo in specific disease models of interest. After successful preclinical studies in the second stage of repositioning, identified drug candidates enter the clinical trials in human subjects [24, 25]. Figure 5 delineates several potential strategies (with suitable examples) of drug repositioning.
\n
Figure 5.
Strategies of drug repositioning with examples. vHTS: virtual high-throughput screening; HTS/HCS: high-throughput and/or high-content screening; Strategy 1 (S1): serendipitous observation; Strategy 2 (S2): observance of novel activity (specific disease phenotype, rational approach); Strategy 3 (S3): new drug-target interaction; Strategy 4 (S4): new roles for existing protein target; Strategy 5 (S5): new biochemical pathways; Strategy 6 (S6): disease-specific repositioning; Strategy 7 (S7): unexpected side effects.
\n
\nTable 3 depicts examples of some repositioned drugs already developed or currently under development from various approved (FDA) or marketed drugs and investigational new drugs (IND). Some repositioned drugs currently under clinical trials in COVID-19 are also included in the list.
Colchicine, a well-known anti-inflammatory drug used in the treatment of gout and pericarditis, is currently under clinical trial for treating COVID-19 patients. This drug has been proved to be effective in preventing massive cytokine storm induced pneumonia caused by SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). The antiviral effect of an older antimalarial drug, chloroquine (used as phosphate salt) against SARS-CoV-2 infection has also been investigated worldwide. Studies suggest that chloroquine may be beneficial in preventing coronavirus induced pneumonia in COVID-19. As per recent reports from NIH (National Institutes of Health, US), the clinical trial of a combination of hydroxychloroquine/azithromycin for the treatment of COVID-19 patients has already been started. In this combination, both the drugs are FDA approved, where hydroxychloroquine is an antimalarial drug and azithromycin is an antibacterial antibiotic. An anti-viral drug, favipiravir intended for the treatment of influenza is currently under phase-2/phase-3 clinical trials on COVID-19 patients around the world (China, Japan, US, India). Glenmark has initiated phase-3 trial on favipiravir for the treatment of COVID-19 patients in India. An investigational anti-retroviral drug called remdesivir (originally developed by Gilead Sciences Inc. for the treatment of Ebola, but failed in clinical trial) is also under clinical trial for treating COVOD-19 patients in several countries like China, US, UK and India. In India, clinical trials on favipiravir, remdesivir and colchicine are currently underway by CSIR (Council of Scientific & Industrial Research) laboratories. A fixed dose drug combination called lopinavir/ritonavir earlier approved to treat HIV/AIDS under the brand name Kaletra is currently being studied to treat COVID-19 patients in several countries. This drug combination was investigated along with the flu drug, oseltamivir (Tamiflu) to cure infection caused by SARS-CoV-2 in Thailand. The clinical trial of an anti-parasitic drug called ivermectin (used traditionally as an approved treatment in worm infestations) for the treatment of COVID-19 is being undertaken in several parts of the world after a successful in vitro effectiveness against SARS-CoV-2 infection at Monash University in Melbourne, Australia. The clinical trial of toclizumab, an IL-6 receptor antagonist (marketed under the brand name Actemra) used for the treatment of inflammatory illness such as rheumatoid arthritis is also being conducted for the treatment of patients with COVID-19 [25, 26].
\n
\n
\n
7. Opportunities and challenges
\n
On contrary to traditional drug discovery program (a complex and time consuming process with high cost of development and risk of failure), drug repositioning, reduces the time and cost of drug development. Drug repositioning is also a low-risk strategy. Computational or machine learning approach has significantly improved the performance of drug repositioning. In comparison to computational approaches, using experimental approaches (such as target protein-based screening, cell-based assay, testing in animal model, and clinical testing) that provide direct evidence-based understanding of links between drugs and diseases are more reliable and credible. However, in recent years computational approaches are usually combined with the experimental approaches to identify new indications for old drugs, called mixed approaches. In this approach, computational methods are validated by biological experiments and clinical tests. Mixed approach of repositioning offers a rational and exhaustive exploration of all possible repositioning opportunities, taking into consideration improved access to available databases and technological advances. Furthermore, the R&D investment required for drug repositioning is lower than that for traditional drug discovery. Thus, drug repositioning offers an opportunity for many pharmaceutical companies to develop drugs with lower investments [27, 28]. Mixed approach of DR offers opportunities for developing repositioned drugs more effectively and rapidly. From the market perspective, a large number of diseases require new drugs to be treated with a potential market demand and economic impacts. For example, the discovery of drugs for rare/neglected diseases has a large potential market to explore. There is, therefore, an opportunity for repurposing of drugs for the treatment of rare, neglected, orphan diseases or difficult to treat diseases. There are over 6000 rare diseases that lack proper treatment. About 5% of them are being researched. Rare diseases have a large potential market to explore. Given the high attrition rates, substantial costs and slow pace of drug discovery and development, repurposing of old drugs to treat both common and rare diseases is increasingly becoming an attractive area of research because it involves the use of drug molecules with reduced risk of failure at shorter time and lower cost development [30, 31, 32, 33].
\n
With the advent of technologies such as genomics, proteomics, transcriptomics, metabolomics, etc., and availability of huge databases resources including drug omics data, disease omics data, etc., there are a plenty of opportunities to discover drugs by drug repositioning in a collective and integrated effort of all the above methods/approaches mentioned above. Researchers are currently equipped with the latest reliable tools and data to explore the novel unknown mechanism of actions/pathways based upon disease-specific target proteins/genes and/or specific biomarkers associated with the progression of the disease [34, 35].
\n
Various databases and software are available publicly for genomics, proteomics, metabolomics and pathway analysis. Several computational strategies are already developed to increase the speed and ease of the repurposing process. Some important databases used in drug repositioning studies are outlined in Table 4.
Databases used in repositioning studies [34, 35, 36].
\n
However, opportunities come often with many challenges in drug repositioning. The identification of a new therapeutic indication for an existing drug poses a major challenge in repositioning. However, drug repositioning is a complex process involving multiple factors such as technology, commercial models, patents, and investment and market demands. Some multiple challenges which include choosing the right therapeutic area for the drug under investigation, issues related to clinical trials such as need to run new trials from start if the data from clinical or preclinical trials for the original drug or drug product are outdated or are not satisfactory [34, 35].
\n
\n
\n
8. Regulatory and intellectual property issues
\n
Traditional drug development strategies are costly, failure prone and expensive ventures. Therefore, drug repositioning has recently drawn considerable attention to discover drugs with new therapeutic uses with the goal to bring drugs out at comparatively faster rate for clinical use. Some regulatory issues that are commonly encountered in drug repositioning are described as follows [37, 38]. As per regulatory guidelines, new preclinical and/or clinical trials may be required to be carried out if the available data are not satisfactory and do not comply with the requirements of regulatory agencies such as FDA or EMA. Another important issue is related to patent application and intellectual property rights (IPR). There are no provisions of IP protection of drug discovery by repositioning approach as per the IP and patent laws. For repositioned drugs, IP protection is limited. For repositioning drugs, IP protection is limited. For example, some novel drug-target disease associations found by repositioning researchers were confirmed by publications or online databases; however, it is difficult to seek IP protection for such associations because of the law. The IP issue prevents some repositioned drugs from entering even into the market [39, 40]. Moreover, some repositioning projects are forced to be abandoned, which is a waste of time, money and lot of efforts. Although many omics data and medical databases have been established, selecting the appropriate approach for repositioning is still a challenge due to the regulatory issues because massive amounts of data may not be valid if not obtained from reliable sources. It is, therefore, necessary that researchers or manufacturers must strictly adhere with standard regulatory guidelines for drug discovery by repositioning approaches [2, 41, 42, 43].
\n
\n
\n
9. Conclusion
\n
Traditionally, the dug repurposing has a long recorded history discovery of drug molecules particularly through serendipitous observations. In recent years, it has embarked a new avenue in the development of new therapies based upon existing/approved medicines. The strategic drug repositioning in a more systematic and rational way has brought innovation with the discovery of drug molecules with unknown therapeutic indications. As drug repositioning approach offers significant reduction in R&D costs, greater chances of success, shorter research time and lower investment risk, it has gained increasing market demands. Because these advantages are beneficial for discovery scientists, drug researchers, consumers and pharmaceutical companies, enabling the application of novel approaches of repositioning strategy in the drug discovery program for almost all human diseases. Moreover, the use of in silico techniques along with the application of structure-based drug design (SBDD) and pharmacophore modeling strategies and artificial intelligence (AI) technology can further accelerate the process of drug purposing in the drug discovery program. In the era of precision medicine, the drug repositioning strategy has become very much useful to establish the unknown mechanism of action of drugs through exploration of novel disease/metabolic/signaling pathways, or off-targets and target-specific mechanisms/ genetic expression profile for even genetic disorders. Advancement in genomics have provided us with genomic and transcriptomic data in huge quantities using technologies like next generation sequencing, microarray data and transcriptomics, etc. Network biology and systems biology approaches may add additional benefits to unveil such novel mechanisms of actions with through insights into drug-target interaction profile at molecular/genetic level. For better drug repositioning, more in-depth understanding are required to be executed with integrated approaches between computational and experimental methods to ensure high success rates of repositioned drugs. However, drug repurposing can be successfully utilized in the discovery and development of new drugs with novel and effective therapeutic indications for human diseases.
\n
\n
Conflict of interest
Authors declare that there is no conflict of interest.
\n',keywords:"drug repurposing, drug discovery, in silico repositioning, activity-based repositioning, target-based screening, therapeutic indication",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72744.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72744.xml",downloadPdfUrl:"/chapter/pdf-download/72744",previewPdfUrl:"/chapter/pdf-preview/72744",totalDownloads:2719,totalViews:0,totalCrossrefCites:17,totalDimensionsCites:30,totalAltmetricsMentions:317,impactScore:23,impactScorePercentile:100,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"April 26th 2020",dateReviewed:"June 16th 2020",datePrePublished:"July 13th 2020",datePublished:"December 2nd 2020",dateFinished:"July 7th 2020",readingETA:"0",abstract:"Drug repurposing (DR) (also known as drug repositioning) is a process of identifying new therapeutic use(s) for old/existing/available drugs. It is an effective strategy in discovering or developing drug molecules with new pharmacological/therapeutic indications. In recent years, many pharmaceutical companies are developing new drugs with the discovery of novel biological targets by applying the drug repositioning strategy in drug discovery and development program. This strategy is highly efficient, time saving, low-cost and minimum risk of failure. It maximizes the therapeutic value of a drug and consequently increases the success rate. Thus, drug repositioning is an effective alternative approach to traditional drug discovery process. Finding new molecular entities (NME) by traditional or de novo approach of drug discovery is a lengthy, time consuming and expensive venture. Drug repositioning utilizes the combined efforts of activity-based or experimental and in silico-based or computational approaches to develop/identify the new uses of drug molecules on a rational basis. It is, therefore, believed to be an emerging strategy where existing medicines, having already been tested safe in humans, are redirected based on a valid target molecule to combat particularly, rare, difficult-to-treat diseases and neglected diseases.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72744",risUrl:"/chapter/ris/72744",book:{id:"9086",slug:"drug-repurposing-hypothesis-molecular-aspects-and-therapeutic-applications"},signatures:"Mithun Rudrapal, Shubham J. Khairnar and Anil G. Jadhav",authors:[{id:"314279",title:"Dr.",name:"Mithun",middleName:null,surname:"Rudrapal",fullName:"Mithun Rudrapal",slug:"mithun-rudrapal",email:"rsmrpal@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314279/images/13834_n.jpg",institution:{name:"Dibrugarh University",institutionURL:null,country:{name:"India"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Traditional drug discovery vs. drug repurposing",level:"1"},{id:"sec_3",title:"3. Strategies of drug repurposing",level:"1"},{id:"sec_4",title:"4. Approaches of drug repurposing",level:"1"},{id:"sec_5",title:"5. Methodologies of drug repurposing",level:"1"},{id:"sec_6",title:"6. Repositioned drugs",level:"1"},{id:"sec_7",title:"7. Opportunities and challenges",level:"1"},{id:"sec_8",title:"8. Regulatory and intellectual property issues",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"},{id:"sec_13",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nAshburn TT, Thor KB. Drug repositioning: Identifying and developing new uses for existing drugs. Nature Reviews. Drug Discovery. 2014;3:673-683\n'},{id:"B2",body:'\nDey G. An overview of drug repurposing: Review article. Journal of Medical Science and Clinical Research. 2019;7(2):3-5\n'},{id:"B3",body:'\nDeotarse PP, Jain AS, Baile MB, Kolhe NS, Kulkarni AA. Drug repositioning: A review. 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Malaria Journal. 2013;12(359):1-11\n'},{id:"B29",body:'\nShim JS, Liu JO. Recent advances in drug repositioning for the discovery of new anticancer drugs. International Journal of Biological Sciences. 2014;10(7):654-663\n'},{id:"B30",body:'\nTalevi A, Bellera CL. Challenges and opportunities with drug repurposing: Finding strategies to find alternative uses of therapeutics. Expert Opinion on Drug Discovery. 2020;15(4):397-401\n'},{id:"B31",body:'\nPushpakom S, Iorio F, Eyers PA, Escott KJ, Hopper S, Wells A, et al. Drug repurposing: Progress, challenges and recommendations. Nature Reviews. Drug Discovery. 2019;18(1):41-58\n'},{id:"B32",body:'\nde Oliveira EAM, Lang KL. Drug repositioning: Concept, classification, methodology, and importance in rare/orphans and neglected diseases. Journal of Applied Pharmaceutical Science. 2018;8(8):157-165\n'},{id:"B33",body:'\nEkins S, Williams AJ, Krasowski MD, Freundlich JS. In silico repositioning of approved drugs for rare and neglected diseases. Drug Discovery Today. 2011;16(7-8):298-310\n'},{id:"B34",body:'\nNaylor S, Kauppi DM, Schonfeld JM. Therapeutic drug repurposing, repositioning and rescue. Part II: Business review. Drug Discovery World. 2015;16:57-72\n'},{id:"B35",body:'\nNaylor S, Schonfeld JM. Therapeutic drug repurposing, repositioning and rescue: Part I—Overview. Drug Discovery World. 2014;16:49-62\n'},{id:"B36",body:'\nJin G, Wong STC. Toward better drug repositioning: Prioritizing and integrating existing methods into efficient pipelines. Drug Discovery Today. 2014;19:637-644\n'},{id:"B37",body:'\nNaylor S, Kauppi DM, Schonfeld JM. Therapeutic drug repurposing, repositioning and rescue. Part III: Market exclusivity using intellectual property and regulatory pathways. Drug Discovery World. 2015;16:62-69\n'},{id:"B38",body:'\nJourdan JP, Bureau R, Rochais C, Dallemagne P. Drug repositioning: A brief overview. The Journal of Pharmacy and Pharmacology. 2020. DOI: 10.1111/jphp.13273\n'},{id:"B39",body:'\nLi YY, Jones SJ, Smith M. The importance of drug repositioning in the era of genomic medicine drug repositioning for personalized medicine. Review. Genome Medicine. 2012;4:27\n'},{id:"B40",body:'\nHernandez JJ, Pryszlak M, Smith L, et al. Giving drugs a second chance: Overcoming regulatory and financial hurdles in repurposing approved drugs as cancer therapeutics. Frontiers in Oncology. 2017;7:1-8\n'},{id:"B41",body:'\nBoguski MS, Mandl KD, Sukhatme VP. Repurposing with a difference. Science. 2019;324:1394-1395\n'},{id:"B42",body:'\nSimsek M, Meijer B, van Bodegraven AA, et al. Finding hidden treasures in old drugs: The challenges and importance of licensing generics. Drug Discovery Today. 2018;23:17-21\n'},{id:"B43",body:'\nGNS HS, GR S, Murahari M, Krishnamurthy M. An update on drug repurposing: Re-written saga of the drug’s fate. Biomedicine & Pharmacotherapy. 2019;110:700-716\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Mithun Rudrapal",address:"rsmrpal@gmail.com",affiliation:'
Sandip Institute of Pharmaceutical Sciences, Sandip Foundation, Mahiravani, Nashik, India
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Moumbock, Conrad V. Simoben, Ludger Wessjohann,\nWolfgang Sippl, Stefan Günther and Fidele Ntie‐Kang",authors:[{id:"177615",title:"Prof.",name:"Ludger",middleName:null,surname:"Aloisius Wessjohann",fullName:"Ludger Aloisius Wessjohann",slug:"ludger-aloisius-wessjohann"},{id:"197160",title:"Dr.",name:"Fidele",middleName:null,surname:"Ntie-Kang",fullName:"Fidele Ntie-Kang",slug:"fidele-ntie-kang"},{id:"197406",title:"Mr.",name:"Conrad Veranso",middleName:null,surname:"Simoben",fullName:"Conrad Veranso Simoben",slug:"conrad-veranso-simoben"},{id:"197408",title:"Prof.",name:"Wolfgang",middleName:null,surname:"Sippl",fullName:"Wolfgang Sippl",slug:"wolfgang-sippl"},{id:"199056",title:"Mr.",name:"Aurelien F. A.",middleName:null,surname:"Moumbock",fullName:"Aurelien F. A. Moumbock",slug:"aurelien-f.-a.-moumbock"},{id:"199057",title:"Prof.",name:"Stefan",middleName:null,surname:"Günther",fullName:"Stefan Günther",slug:"stefan-gunther"}]},{id:"54281",title:"Towards Metabolic Engineering of Podophyllotoxin Production",slug:"towards-metabolic-engineering-of-podophyllotoxin-production",signatures:"Christel L. C. Seegers, Rita Setroikromo and Wim J. Quax",authors:[{id:"196901",title:"Prof.",name:"Wim",middleName:null,surname:"Quax",fullName:"Wim Quax",slug:"wim-quax"},{id:"197867",title:"MSc.",name:"Christel L.C.",middleName:null,surname:"Seegers",fullName:"Christel L.C. 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\n
1. Introduction
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Biofilm is a population of cells growing on a surface and enclosed in an exopolysaccharide matrix [1]. The physiology, structure and chemistry of the biofilm vary with the nature of its resident microbes and local environment [2].
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Most important feature among biofilms is that their structural integrity critically depends upon the extracellular matrix produced by their constituent cells. They are notoriously difficult to eradicate and are a source of many recalcitrant infections [2]. Biofilms are associated with serious health issues stemming from persistent infections due to the contamination of medical devices (intravenous and urinary catheters), artificial implants and drinking water pollution among others [3].
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Intercellular signaling, often referred to as quorum sensing (QS), has been shown to be involved in biofilm development [4]. Quorum sensing relies on small, secreted signaling molecules; much like hormones in higher organisms, to initiate coordinated responses across a population and it contributes to behaviors that enable microbes to resist antimicrobial compounds [5]. Quorum sensing signaling activation can lead to antimicrobial resistance of the pathogens, thus increasing the therapy difficulty of diseases [4].
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The key concern about biofilms is their contribution to the development of resistance against antimicrobial agents, and with the on-going emergence of antibiotic-resistant pathogens, there is a current need for development of alternative therapeutic strategies [6].
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An anti-virulence approach by which quorum sensing is impeded could be a viable means to manipulate bacterial processes, especially pathogenic traits that are harmful to human and animal health and agricultural productivity [7]. Further research into the identification and development of chemical compounds and enzymes that facilitate quorum-sensing inhibition (QSI) by targeting signaling molecules, signal biogenesis, or signal detection are required [7]. Anti-QS agents can abolish the QS signaling and prevent the biofilm formation, therefore reducing bacterial virulence without causing drug-resistant to the pathogens, suggesting that anti-QS agents could be potential alternatives for antibiotics [8]. An effective clinical strategy for treating bacterial diseases in the near future will be to combine anti-QS agents with conventional antibiotics since this can significantly improve the efficacy of therapeutic drugs and decrease the cost of human healthcare [9].
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2. Microbial biodiversity in biofilm systems
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Biofilms are mixed microbial cultures normally consisting predominantly of prokaryotes with some eukaryotes. Thus, in addition to microbial cells, the surrounding environment contains a range of macromolecular products in which exopolysaccharide secreted by the cells is the dominant macromolecular component, while the water content is probably about 90–97% [10, 11]. Secreted products also include enzymes and other proteins, bacteriocins, and low mass solutes and nucleic acid released through cell lysis. The lysis may occur either naturally with cell aging or through the action of phage and bacteriocins.
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Opportunistic pathogens, viruses, parasitic protozoa, toxin releasing algae and fungi and enteric bacteria e.g. Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter agglomerans, Helicobacter pylori, Shigella spp., Campylobacter spp., Salmonella spp., Clostridium perfringens, Enterococcus faecium, Enterococcus faecalis and environmental pathogenic bacteria like Legionella pneumophila, Pseudomonas aeruginosa, Pseudomonas fluorescens, Aeromonas hydrophila, Aeromonas caviae, Mycobacterium avium, Mycobacterium xenopi etc. are associated with biofilms present in drinking water [12, 13].
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Biofilms present complex assemblies of microorganisms attached to surfaces. They are dynamic structures in which various metabolic activities and interactions between the component cells occur [10]. Studies on microorganisms and biofilm formation have revealed diverse complex social behavior including cooperation in foraging, building, reproduction, dispersion and communication among microorganisms [14]. The organisms within a biofilm setup may include a single or diverse species of microorganisms. In the biofilm, bacteria can share nutrients and are sheltered from harmful factors in the environment, such as desiccation, antibiotics, and a host body’s immune system.
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Bacteria, fungi, viruses, protozoa and cyanobacteria that are common pathogens are all involved in biofilm formation [15].
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2.1 Bacterial biofilms
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About 99.9% of all bacteria live in biofilm communities [16]. A biofilm usually begins to form when a free-swimming bacterium attaches to a surface. Pathogenic organisms are found on most food items including seafoods and biofilm forming pathogens are found on such seafoods as crabs [17], pacific oysters [18], shrimps [19] etc. Public health and clinical microbiologists recognize that biofilms are present everywhere in nature and are responsible for a number of human infections. Infectious caused by microbial communities include urinary tract infections, middle-ear infections, dental plaque, gingivitis, endocarditis, cystic fibrosis. Biofilms on persistent indwelling devices such as catheter, contact lenses, heart valves and joint prostheses are also responsible for many recurrent infections [20, 21]. Biofilms on indwelling medical devices may be composed of Gram-positive or Gram-negative bacteria. Bacteria commonly isolated from these devices include the Gram-positive Enterococcus faecalis, Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus viridans; and the Gram-negative Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa [22]. It has been shown that virtually all indwelling central venous catheters are colonized by microorganisms embedded in a biofilm matrix. Among these S. epidermidis and S. aureus are commonly present on cardiovascular devices [23], causing about 40–50% of infections related to heart valve [14].
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The organisms that form biofilms on medical devices originate from patient’s skin microflora, exogenous microflora from health-care personnel, or contaminated infusates. Biofilms associated with catheters may initially be composed of single species, but with the passage of time they become multi-specie communities. Some urinary tract and bloodstream infections are also caused by biofilm-associated indwelling medical devices with 50–70% of infections related to catheter [12]. Chronic infections, inflammation and tissue damage caused by many strains of single species are often found in polymicrobial communities [24].
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Bacteria that reside in a biofilm community usually will not grow when cultured, a situation normally referred to as “viable, but not culturable”. The reason is that to change to the planktonic state from a biofilm-producing phenotype, bacteria require complex and specific environmental and signaling factors that are not available in a culture plate [25]. This therefore suggests that analyzing biofilm samples for bacterial infective agents during infections may show negative results and the real cause of the infections may not be detected if culturing is the only investigative procedure.
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2.2 Fungal biofilms
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Many medically important fungi produce biofilms and they include Candida, Aspergillus, Cryptococcus, Trichosporon, Coccidioides, and Pneumocystis. Candida albicans biofilms are primarily made up of yeast-form and hyphal cells, both of which are required for biofilm formation [26]. The formation of Candida albicans biofilm follows a sequential process that involves adherence to a substrate (either abiotic or mucosal surface), proliferation of yeast cells over the surface, and induction of hyphal formation [27]. As the biofilm matures extracellular matrix (ECM) accumulates. Many other Candida spp. form ECM-containing biofilms but do not produce true hyphae and they include Candida tropicalis, Candida parapsilosis, and Candida glabrata [28]. Aspergillus biofilms can form both on abiotic and biotic surfaces and the initial colonizing cells that adhere to the substrate are conidia. Mycelia (the hyphal form) develop as the biofilm matures [29]. Aspergillus fumigatus produces two forms of biofilm infections: Aspergilloma and Aspergillosis. Aspergilloma infections present an intertwined ball of hyphae while aspergillosis infections present individual separated hyphae [30].
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\nTrichosporon asahii forms biofilms comprised of yeast and hyphal cells embedded in matrix, as do those of Coccidioides immitis. Cryptococcus neoformans forms biofilms consisting of yeast cells on many abiotic substrates [31]. Although Cryptococcus neoformans forms hyphae in the course of mating, no hyphae have been observed in Cryptococcus neoformans biofilms. Similarly, Pneumocystis species do not produce hyphal structures as part of their biofilms [32]. Hyphal formation is therefore, not a uniform feature of fungal biofilms.
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2.3 Protozoan biofilms
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Free-living protozoans are single celled eukaryotic organisms and are divided into amoebae, flagellates and ciliates. All the three protozoan groups have been found in fresh water biofilms. Although many different species are found in association with biofilms, their level of association differs. The protozoans Cyclospora cayetanensis, Cryptosporidium spp., and Toxoplasma gondii have all been found in biofilm communities [22].
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2.4 Virus involvement in biofilms
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Viruses are obligatory intracellular parasites and are found in communities where cells in which they live are found. Viruses are, thus, found in biofilms communities associated with the bacteria, fungi and protozoa they infect.
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Many phages may produce polysaccharases or polysaccharide lyases. Some phages are also known to produce enzymes that degrade the poly-Q-glutamic acid capsule of Bacillus spp. [33]. Various structures including extracellular polymers and heterologous microbial cells may impede viral access to the bacterial cell surface. Phage may carry on their surfaces enzymes that degrade bacterial polysaccharides including those of biofilm structures. These enzymes are very specific and seldom act on more than a few closely related polysaccharide structures [34]. Numerous phages have been isolated which induce enzymes capable of degrading the exopolysaccharide of various Gram-negative bacterial genera. These include phage for biofilm-forming bacteria. It has been observed that the extracellular matrix of the biofilms does not protect the bacterial cells from infection with phage T4 [35].
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Many biofilms possess an open architecture with water-filled channels, which would allow the phage access to the biofilm interior [36]. As biofilms age and cells die and slough off, potential new viral receptor sites may become available. As bacteria excel at adapting to differing nutrient conditions, changes to the host cell surface could be expected with either loss or gain of possible phage receptors. A further factor which might influence phage retention within biofilms lies in the role of hydrophobic and electrostatic interactions. In the interaction of a coliphage with both hydrophobic and hydrophilic membranes, a critical factor in the retention of the phage was its iso-electric point [37].
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In complex biofilms in natural environments, eukaryotic algae may also be present [38]. Under these circumstances algal cell lysis through viral action is also possible as many viruses for algal species have now been isolated and identified [39].
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3. Biofilms in respiratory tract infections
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It is becoming progressively more accepted that biofilm formation is an important cause of morbidity in respiratory tract infections [40]. Biofilms may be involved in some respiratory infections, including ventilator-associated pneumonia, bronchiectasis, bronchitis, cystic fibrosis and upper respiratory airway infections [41].
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3.1 Upper respiratory tract infections
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Infectious diseases that affect the upper respiratory tract include otitis media, sinusitis, tonsillitis, adenoiditis, pharyngotonsillitis, adenoiditis and chronic rhinosinusitis [42]. In otitis media, infections may be as a result of both respiratory viruses and bacteria such as non-capsulated Haemophilus influenza, Streptococcus pneumonia, Streptococcus pyogenes, Moraxella catarrhalis and Staphylococcus aureus, triggering the appearance of polymicrobial biofilms [43].
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The most cited reason for childhood visits to physicians is otitis media with effusion (OME) and is again one of the most reasons for antibiotic therapy in children. Even though OME is regarded as a sterile inflammatory process, current data using a chinchilla model suggest that viable bacteria are present in intricate communities referred to as mucosal biofilms [44]. It is interesting to know that intracellular Haemophilus influenzae, Streptococcus pneumoniae, Staphylococcus aureus and Moraxella catarrhalis in situ are found in adenoids from children going through adenoidectomy for the treatment of hypertrophic adenoids or chronic otitis media using Fluorescence in situ hybridization [45]. Haemophilus influenzae and intracellular S. pneumoniae have also been in middle ear mucosal biopsies in children with chronic otitis media [46].
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Biofilms were seen in the sinus tissues of 72% of patients affected by chronic rhinosinusitis and the cultured organisms identified included H. influenzae (28%), P. aeruginosa (22%), S. aureus (50%), and fungi (22%). The presence of bacterial biofilms was linked to persistent mucosal inflammation after endoscopic sinus surgery [47]. Assessment of some chronic infections in the upper respiratory tract including recurrent tonsillitis and chronic rhinosinusitis in human clinical specimens suggests that both attachment and aggregated bacteria are present [48]. For instance, electron microscopy and culture were used to show that biofilms were associated with the mucosal epithelium of tonsils in 73% of tonsils removed for tonsillitis and 75% of those tonsils removed due to hypertrophic tonsils alone [49]. Calo et al. [42] found bacterial biofilms in recurrent and chronic infectious diseases of the upper respiratory tract (adenoiditis, tonsillitis, and chronic rhinosinusitis) and concluded that biofilms formation plays a role in upper airway infections.
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3.2 Tissue-related infections
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3.2.1 Cystic fibrosis (CF)
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Cystic fibrosis (CF) is a protracted disease of the lower respiratory tract. The most frequent serious clinical complication in CF today is chronic endobronchial infection with Pseudomonas aeruginosa. Pseudomonas aeruginosa is a microorganism characterized by the capacity to produce large amounts of alginate and developed as a biofilm where micro-colonies of bacteria embedded in a matrix of alginate attack the lower respiratory tract [42]. Cystic fibrosis occurs as a result of a mutation in the CF transmembrane conductance regulator gene that encodes a cyclic AMP-regulated chloride ion channel. The mutation causes defective ion transport across epithelial cell surfaces in the upper airways, interfering with the removal of particles and microbial cells trapped in the overlying mucus and causing increased susceptibility to bacterial infection. Therefore, the airways of patients with CF are almost always infected with different bacterial species, but P. aeruginosa infection causes the greatest problem of morbidity and mortality [43]. Pseudomonas aeruginosa is the most common bacterial species that causes respiratory tract infection in CF patients and can be seen in about half of all cases and in up to 70% of adults [44]. Other pathogens such as Staphylococcus aureus, Achromobacter xylosoxidans, Burkholderia cepacia complex and Stenotrophomonas maltophilia have also been found to cause CF and are linked to biofilm formation [45].
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3.2.2 Cystic fibrosis with chronic lung infections
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A major difficulty in this type of infection is contamination of lower respiratory secretions with the normal oropharyngeal flora, particularly as members of the normal flora (e.g. Haemophilus influenzae, Staphylococcus aureus, Streptococcus pneumonia and Moraxella catarrhalis) are common lung pathogens in CF [46, 47]. The incidence of bacterial lung infections in CF is high because the mucoid polysaccharidic material that accumulates on the respiratory epithelium due to the fact that impaired mucociliary removal in the bronchi of such patients favors biofilm formation. The capacity of Pseudomonas aeruginosa to form biofilms is believed to be the primary reason for its survival in the CF lung, despite a high inflammatory response and intensive antibiotic treatment [48]. Chronic airway infections cause an increase deterioration of lung tissue, a decline in pulmonary function and, finally, respiratory failure and death in cystic fibrosis (CF) patients [49].
The role of biofilms in patients with COPD has not been directly validated but has been hypothesized considering the evidence showing that the respiratory tracts of these patients are frequently colonized by pathogens. Murphy and Kirkham [50] have recently confirmed that biofilms do play a role in COPD where they identified major outer membrane proteins of Non-typeable H. influenzae during its growth as a biofilm. Even if direct proof of biofilm formation in vivo is lacking, biofilms may reasonably be considered to be involved in the vicious cycle of infection/inflammation leading to disease development in patients with COPD [51].
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3.2.4 Non-cystic fibrosis bronchiectasis
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In bronchiectasis not due to cystic fibrosis, infections result in changes in the muscular and elastic components of the bronchial wall, which become distorted and expanded. Airways gradually become unable to clear mucus, leading to serious lung infections, which in turn cause more damage to the bronchi [52]. Recently biofilm formation has been demonstrated in vivo and is assumed to play a significant role in the pathophysiological cascade of the disease [53]. Bacterial biofilm formation by Pseudomonas aeruginosa or Klebsiella pneumoniae is common in bronchiectasis and could be an essential factor that makes infections in bronchiectasis obstinate. Other pathogens such as Prevotella sp., Veillonella sp. and Neisseria sp. have also been identified recently in patients with bronchiectasis to form biofilms [54].
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3.2.5 Bronchitis
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Prolonged bacterial bronchitis may be caused by chronic infections of the respiratory tract. In children especially, the condition appears to be secondary to impaired mucociliary removal that produces an environment favorable for bacteria to become established, usually in the form of biofilms. The most commonly involved bacteria include Haemophilus influenzae (30–70%), Moraxella catarrhalis and Streptococcus pneumonia [55].
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3.2.6 Diffuse pan-bronchiolitis
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Diffuse pan-bronchiolitis (DPB) is an unusual inflammatory lung disease of unknown etiology found in adult Japanese patients. With this disease, chronic endobronchial infection with Pseudomonas aeruginosa biofilms leading to respiratory failure is common. It is a severe, progressive form of bronchiolitis (Inflammation and congestion in the bronchioles of the lung) [56].
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3.3 Device-related infections
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In device-related infections such as ventilator-associated pneumonia (VAP), biofilms result in microbial persistence and reduced response to treatment. Biofilm formation within the first 24 h after intubation has been reported in 95% of endotracheal tubes [57]. Pathogens in both endotracheal tube biofilm and secretions accrued within the airways/endotracheal tubes in 56 to 70% of patients with VAP have been reported. Pseudomonas aeruginosa and Acinetobacter baumannii are the most common bacteria that colonize these devices [57].
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3.4 Biofilm forming organisms associated with respiratory tract infections
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This section presents the role of biofilms in respiratory tract infections, with specific emphasis on the biofilms formed by Pseudomonas, Staphylococcus, and Haemophilus, the primary pathogens associated with respiratory tract infections [58] although additional important pathogens, including Streptococcus pneumoniae, Bordetella and Mycobacterium species do play a role [59].
\n
\n
3.4.1 Biofilms formed by Pseudomonas aeruginosa\n
\n
\nPseudomonas aeruginosa is a recognized common pathogen in respiratory tract infections although other members of the genus Pseudomonas are able to form biofilms [7]. Respiratory infections caused by P. aeruginosa are a major globally clinical issue, especially for patients with chronic pulmonary disorders, such as those with cystic fibrosis (CF), non-CF bronchiectasis, severe chronic obstructive pulmonary disease (COPD) and ventilator-associated pneumonia [60]. This bacterium is a difficult opportunistic pathogen that readily forms biofilms on most surfaces [5]. The intricate steps of biofilm formation by P. aeruginosa are considered to be a developmental process. The stages of P. aeruginosa biofilm formation can be seen by several strategies. One easy technique is the scanning electron microscope (SEM) of P. aeruginosa grown on glass surfaces or tracheal explants. Biofilms form when planktonic P. aeruginosa bacteria get attached to a surface using adhesins such as type IV fimbriae and flagella, and begin to colonize. In this regard type IV fimbriae and flagella P. aeruginosa mutants are severely compromised in initiation of biofilm formation [58, 61]. Additionally, the process of surface translocation mediated by type IV fimbriae (twitching motility) is essential for initiation of biofilm formation by P. aeruginosa [58]. Most probable, twitching motility confers synchronized cell movement along the surface as well as cell–cell communications that lead to the formation of micro-colonies. The coordination of events for the initiation and formation of biofilms requires cell–cell interactions that are mediated by quorum sensing [62]. Following this, the micro-colonies mature into distinctive three-dimensional structures that pose the most severe scenario for clinical treatment. This structure is typically trapped in a matrix material that may be composed of protein, polysaccharide, or nucleic acid. Nonetheless, it has been proposed guluronic and mannuronic acids [63] are the major constituents of the biofilm matrix [64]. Recent data also suggest that DNA also contributes to this matrix [60].
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3.4.2 Biofilms formed by Staphylococcus species\n
\n
The adherence of Staphylococcus directly to an implanted device (intravascular catheters, prosthetic devices, and other indwelling medical devices) or indirectly via host proteins is the first step in the development of a biofilm. This is followed by a buildup of multilayered cell clusters on the polymer surface [65]. When Staphylococcus bacteria get within 50 nm of a surface, they adhere through hydrophobic interactions, van der Waal’s forces, and when present, fimbriae and pili also contribute to its adhesion [66]. A biofilm-associated protein (Bap) is reported to contribute to S. aureus biofilm formation. The second phase of Staphylococcus biofilm formation is the accumulation of complex cell clusters mediated by intercellular adhesion. A 140 kDa extracellular protein, known as the accumulation associated protein (AAP), appears responsible for accumulative growth on polymer substances [67]. It has been hypothesized that AAP is involved in anchoring the polysaccharide adhesion PIA (polysaccharide intercellular adhesion) to the cell surface [63]. The extracellular polysaccharide adhesion antigen PIA is a well-described polysaccharide antigen that is linked to cellular aggregation or clustering. Lastly, the generation of a slime glycocalyx is believed to be the climaxing event in the staphylococcal biofilm developmental process. This slime layer is not essential for surface colonization and appears variable between strains. However, when present, the slime layer protects the bacteria from host defenses and some antibiotics. As in P. aeruginosa, organization of complex communities within Staphylococcus biofilms is a coordinated effort and requires cell–cell communication [68].
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3.4.3 Biofilms formed by Haemophilus influenzae\n
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Non-typeable H. influenzae (NTHI) strains are members of the normal human nasopharyngeal flora, as well as frequent opportunistic pathogens of both the upper and lower respiratory tracts. It is an important cause of otitis media in children and lower respiratory tract infection in adults with chronic obstructive pulmonary disease (COPD). Recently, it has been shown that NTHI can form biofilms both in vitro and in vivo [69]. Considerable diversity in the ability of NTHi isolates to form biofilms has also been reported. A NTHi pilus defective strain was reduced three-to four fold in biofilm formation compared with its isogenic parental NTHi isolate, signifying a role of the pilus in biofilm development. Although this is the case for other gram-negative bacteria [70], nonetheless, it is quite clear that NTHi strains have the ability to form biofilms both in vitro and in vivo [69]. Earlier studies of cell envelopes during growth of H. influenzae as a biofilm established an increased abundance of a ~30 kDa protein [58], peroxiredoxin-glutaredoxin (PGdx) [71], that is expressed by H. influenzae during biofilm growth and this probably contributes to its persistence in the upper respiratory tract infections.
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3.4.4 Biofilms formed by other microorganisms
\n
\nStreptococcus pneumoniae: Streptococcus pneumoniae is a frequent colonizer of the human nasopharynx and a significant human respiratory pathogen that causes a variety of diseases such as community-acquired pneumonia and otitis media in children [72]. Colonizing pneumococci form well-ordered biofilm communities in the nasopharyngeal environment, but the exact role of biofilms and their interaction with the host during colonization and disease is not yet explicit [73]. However, investigators have speculated that pneumococci form biofilms in the nasopharynx in vivo [74]. Recently, pneumococci have been reported for the first time to form highly structured biofilms during colonization of the murine nasopharynx [75]. Mice were also inoculated intranasally with the pneumococcal strain EF3030, a clinical isolate known to be non-invasive and an efficient colonizer in murine models, and found to form biofilms [76].
\n
\nBordetella species: Bordetellae are respiratory pathogens that infect both humans and animals. Bordetella bronchiseptica causes asymptomatic and long-term to life-long infections in animal nasopharynges while the human pathogen, B. pertussis is the etiological agent of the acute disease whooping cough in infants and young children. One proposed hypothesis to explain the survival and continued persistence of Bordetella spp. in the mammalian nasopharynx is that these organisms produce surface-adherent communities known as biofilms [77]. Researchers have recently established the ability of the three classical Bordetella species (Bordetella pertussis, Bordetella bronchiseptica, and Bordetella parapertussis) to form biofilms on abiotic surfaces [78]. It is assumed that Bordetella biofilm formation may play a role in the pathogenic cycle, precisely in persistence within the nasopharynx [79]. The capacity to form biofilms in mice suggests a role for Bordetella mode of existence during human infections. Clusters and tangles (reminiscent of biofilms) of Bordetella pertussis adherent to ciliated cells in explant cultures and tissue biopsies of pertussis patients have been documented [79]. As reported for other biofilm-forming organisms, extracellular DNA and exopolysaccharide are vital for biofilm formation by Bordetella bronchiseptica. The observation of biofilm-like structures in vivo in the nasal epithelium of Bordetella bronchiseptica infected mice showed that these communities expressed a polysaccharide essential for in vivo biofilm development [75, 76]. In Bordetella, BvgAS-regulated factors, including the filamentous hemagglutinin and adenylate cyclase, may also contribute to biofilm formation [79].
\n
\nMycobacterium species: Mycobacterial infections have been shown to form biofilms, most notably Mycobacterium tuberculosis, which under the conducive environments, can self-assemble. Among the non-tuberculous mycobacteria, Mycobacterium avium complex (MAC) and the rapidly growing mycobacteria, including Mycobacterium abscessus complex, have been reported to produce biofilms either in vitro or in environmental reservoirs [80], but in vivo conditions have not been investigated. Mycobacterium abscessus complex is an evolving threat to patients with cystic fibrosis [81], that become infected at an early stage and worsens clinically as the persistent infection results in inflammation and tissue damage.
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4. Quorum sensing
\n
In the control of microbial infections, two strategies are normally envisaged; killing the organisms or attenuation of the organisms’ virulence such that they fail to adapt to the host environment. The former approach is what is generally favored; the latter lacks specific targets for rational drug design. It has, however, been realized that Gram-negative bacteria use small molecules known as acyl homoserine lactones to regulate the production of secondary metabolites and virulence factors, and this could offer a novel target to address the strategy of attenuating the organisms’ virulence thereby impairing their adaptation to the host system. Recent research has highlighted the importance of cell-to-cell interactions or communications, referred to as Quorum Sensing (QS), in microorganisms. Many bacterial species employ a complex mechanistic communication system to transmit information among themselves. Bacteria can act in response to a variety of chemical signals produced by the same species along with others produced by other species, and this provides a way for intraspecies and interspecies cross-communication and interruption of signals. The ability of bacteria to dispatch, pull together, and process information allow them to act as “multicellular” organisms and enhance their survival in complex environments [82].
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Any mechanism capable of disrupting QS signals can be used to reduce survival of the microorganism thereby preventing or reducing virulence in the host environment. Such methods of interruption of the QS include:
Disruption of biosynthesis of signal molecules,
Application of QS antagonists (e.g. use of extracts from higher plants and algae and other chemical compounds),
Chemical inactivation of quorum sensing signals,
Biodegradation of signal molecule.
\n\n
Agents capable of inhibiting the growth of microorganisms or disrupting the quorum sensing mechanisms of the microorganisms or interrupting the biofilm formation may be useful in the fight against microbial pathogenicity.
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4.1 Anti-quorum sensing activity
\n
It has now become apparent that different types of microorganisms have evolved the ability to recognize and act in response to the presence of other microorganisms in their neighborhood. Most Gram-negative bacteria produce and respond to N-acyl homoserine lactone (AHLs) signal molecules to regulate production of secondary metabolites in order to monitor their own population density. These molecules, at a threshold population density, act together with cellular receptors and elicit the expression of target genes such as those involved in virulence, antimicrobial production, motility and swarming, sporulation, bioluminescence and biofilm formation. The concept of quorum sensing (QS) was initially described in Vibrio fischeri, a luminescent marine bacterium. It was observed that the organisms express genes controlling light emission (the luciferase enzyme) when in symbiotic association with its hosts, the squid [83]. At low population densities (i.e. free-living in seawater) Vibrio fischeri does not express luciferase and so is non-luminescent. However, when cultured in the laboratory to high cell densities, they express bioluminescence with a blue-green light. They do not emit light unless they detect a concentration high enough of their own AHL. These organisms usually form symbiotic relationships with some fish and squid species such as Euprymna scolopes. Euprymna scolopes appears bioluminescent in dark surroundings because of high-population of the cells (Vibrio fischeri) in a specialized light organ. Euprymna scolopes, in return, offers nutrients to the Vibrio fischeri population. The QS system originally identified in Vibrios involved two genes, luxl and luxR. The Luxl codes for an enzyme, which synthesizes 3-oxo-C6-homoserine lactone (an auto-inducer as they are produced by the same cells whose metabolism they regulate) [82].
\n
The unpleasant side effects of antibiotics (such as ototoxicity and nephrotoxicity associated with the aminoglycosides) have led to preference for preventive rather than curative approach towards fighting infectious diseases. Inhibition of quorum sensing activity has been hypothesized as one approach that can be useful in preventing bacterial infection. It could provide an additional approach to antibiotic mediated bactericidal or bacteriostatic activity thereby reducing the risk of successful establishment of infections or resistance development in the bacteria. This is supported by the protective effect of QS inhibition demonstrated in animal infection models. A simple animal infection model on QS was launched in Caenorhabditis elegans, a nematode that feeds on bacteria. When fed on opportunistic pathogens such as P. aeruginosa, the worm was mostly destroyed within a short time after taking in the bacteria; presumably annihilated by the actions of cyanide and phenazines produced by the bacteria [84]. However, in instances where the worms ingested P. aeruginosa with mutations in the QS-controlling systems, they were not killed but were rather sustained on the bacteria. This model highlights the involvement of QS-regulated virulence factors in pathogenicity of Pseudomonas aeruginosa. It is obvious from such models that interruption of the QS apparatus of bacteria by plant extracts or other chemical compounds may offer a novel and an exciting approach to fight the existing problems associated with antimicrobial chemotherapy.
\n
Many bacteria produce AHL molecules in response to QS and so could be used as biomonitor organisms in screening of compounds for anti-QS activity. Such bacteria include Chromobacterium violaceum, Erwinia carotovora and Pseudomonas aeruginosa.
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5. Medicinal plants with biofilm inhibition activity
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Natural products have been identified to inhibit biofilm formation in microorganisms. The exact mechanism for most of the agents is yet to be elucidated. Medicinal plants have been identified as rich source of bioactive compounds that have the capability of interfering with biofilm formation but most of these studies are still in the early stages of drug development. The anti-biofilm effects of medicinal plants have been proposed to be due to the inhibition of formation of polymer matrix, suppression of cell adhesion and attachment, interruption of extracellular matrix formation and reduction in virulence factors production and activation, thereby blocking QS network and biofilm development [85].
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Medicinal plants belonging to various plant families reported to have biofilm inhibitory activity are listed in Table 1; the part of the plant (leaves, fruits, stem bark, rhizome) used, the various solvents used for extraction and their ability to inhibit cell adhesion or to eradicate biofilm formed by different pathogens have been mentioned.
\n
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\n
\n
\n
\n\n
\n
Plant name
\n
Family
\n
Part used
\n
Solvent
\n
Biofilm inhibition activity
\n
Reference
\n
\n\n\n
\n
\nPunica granatum L
\n
Lythraceae
\n
Fruit
\n
Methanol
\n
Inhibit biofilm formation in E. coli by 70% at 150 μg/mL
Combatting biofilm and quorum sensing is a good strategy to reduce microbial pathogenicity and thus fight infections. This can be achieved by finding effective agents that can inhibit biofilm formation and disrupt quorum sensing mechanisms. Natural products particularly medicinal plants are a rich source of bioactive compounds that have served as useful leads in the development of drugs. Rigorous evaluation of medicinal plants can therefore lead to novel anti-biofilm and anti-quorum sensing agents.
\n
\n\n',keywords:"biofilm, quorum sensing, bacteria, acyl homoserine lactone",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69590.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69590.xml",downloadPdfUrl:"/chapter/pdf-download/69590",previewPdfUrl:"/chapter/pdf-preview/69590",totalDownloads:977,totalViews:0,totalCrossrefCites:1,dateSubmitted:"April 26th 2019",dateReviewed:"August 17th 2019",datePrePublished:"October 16th 2019",datePublished:"October 7th 2020",dateFinished:"October 16th 2019",readingETA:"0",abstract:"Biofilms are structured aggregates of bacterial cells that are embedded in self-produced extracellular polymeric substances. Various pathogens initiate a disease process by creating organized biofilms that enhance their ability to adhere, replicate to accumulate, and express their virulence potential. Quorum sensing, which refers to the bacterial cell-to-cell communication resulting from production and response to N-acyl homoserine lactone signal molecules, also plays an important role in virulence and biofilm formation. Attenuation of microorganisms’ virulence such that they fail to adapt to the hosts’ environment could be a new strategic fight against pathogens. Thus, agents or products that possess anti-biofilm formation and/or anti-quorum sensing activities could go a long way to manage microbial infections. The incidence of microbial resistance can be reduced by the use of anti-biofilm formation and anti-quorum sensing agents.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69590",risUrl:"/chapter/ris/69590",signatures:"Cynthia Amaning Danquah, Samuel Osei-Djarbeng, Theresah Appiah, Yaw Duah Boakye and Francis Adu",book:{id:"8967",type:"book",title:"Bacterial Biofilms",subtitle:null,fullTitle:"Bacterial Biofilms",slug:"bacterial-biofilms",publishedDate:"October 7th 2020",bookSignature:"Sadik Dincer, Melis Sümengen Özdenefe and Afet Arkut",coverURL:"https://cdn.intechopen.com/books/images_new/8967.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-900-3",printIsbn:"978-1-78985-899-0",pdfIsbn:"978-1-83968-819-5",isAvailableForWebshopOrdering:!0,editors:[{id:"188141",title:"Prof.",name:"Sadik",middleName:null,surname:"Dincer",slug:"sadik-dincer",fullName:"Sadik Dincer"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"186987",title:"Dr.",name:"Yaw Duah",middleName:null,surname:"Boakye",fullName:"Yaw Duah Boakye",slug:"yaw-duah-boakye",email:"yawduahb@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"262750",title:"Dr.",name:"Cynthia",middleName:null,surname:"Amaning Danquah",fullName:"Cynthia Amaning Danquah",slug:"cynthia-amaning-danquah",email:"cadanquah.pharm@knust.edu.gh",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"262752",title:"Dr.",name:"Francis",middleName:null,surname:"Adu",fullName:"Francis Adu",slug:"francis-adu",email:"franceadu@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"297439",title:"Dr.",name:"Theresa",middleName:null,surname:"Appiah",fullName:"Theresa Appiah",slug:"theresa-appiah",email:"theresaappiah22@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"309609",title:"Dr.",name:"Samuel",middleName:null,surname:"Osei-Djarbeng",fullName:"Samuel Osei-Djarbeng",slug:"samuel-osei-djarbeng",email:"osdjarb@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Microbial biodiversity in biofilm systems",level:"1"},{id:"sec_2_2",title:"2.1 Bacterial biofilms",level:"2"},{id:"sec_3_2",title:"2.2 Fungal biofilms",level:"2"},{id:"sec_4_2",title:"2.3 Protozoan biofilms",level:"2"},{id:"sec_5_2",title:"2.4 Virus involvement in biofilms",level:"2"},{id:"sec_7",title:"3. Biofilms in respiratory tract infections",level:"1"},{id:"sec_7_2",title:"3.1 Upper respiratory tract infections",level:"2"},{id:"sec_8_2",title:"3.2 Tissue-related infections",level:"2"},{id:"sec_8_3",title:"3.2.1 Cystic fibrosis (CF)",level:"3"},{id:"sec_9_3",title:"3.2.2 Cystic fibrosis with chronic lung infections",level:"3"},{id:"sec_10_3",title:"3.2.3 Chronic obstructive pulmonary disease (COPD)",level:"3"},{id:"sec_11_3",title:"3.2.4 Non-cystic fibrosis bronchiectasis",level:"3"},{id:"sec_12_3",title:"3.2.5 Bronchitis",level:"3"},{id:"sec_13_3",title:"3.2.6 Diffuse pan-bronchiolitis",level:"3"},{id:"sec_15_2",title:"3.3 Device-related infections",level:"2"},{id:"sec_16_2",title:"3.4 Biofilm forming organisms associated with respiratory tract infections",level:"2"},{id:"sec_16_3",title:"3.4.1 Biofilms formed by Pseudomonas aeruginosa\n",level:"3"},{id:"sec_17_3",title:"3.4.2 Biofilms formed by Staphylococcus species\n",level:"3"},{id:"sec_18_3",title:"3.4.3 Biofilms formed by Haemophilus influenzae\n",level:"3"},{id:"sec_19_3",title:"3.4.4 Biofilms formed by other microorganisms",level:"3"},{id:"sec_22",title:"4. Quorum sensing",level:"1"},{id:"sec_22_2",title:"4.1 Anti-quorum sensing activity",level:"2"},{id:"sec_24",title:"5. Medicinal plants with biofilm inhibition activity",level:"1"},{id:"sec_25",title:"6. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nDavey ME, O’Toole GA. Microbial biofilms: From ecology to molecular genetics. Microbiology and Molecular Biology Reviews. 2000;64:847-867\n'},{id:"B2",body:'\nDonlan RM. Biofilms: Microbial life on surfaces. Emerging Infectious Diseases. 2002;8:881-890\n'},{id:"B3",body:'\nBjarnsholt T. The role of bacterial biofilms in chronic infections. APMIS. 2013;121:1-58\n'},{id:"B4",body:'\nSifri CD. Quorum sensing: Bacteria Talk Sense. Clinical Infectious Diseases. 2008;47:1070-1076\n'},{id:"B5",body:'\nDavies DG, Parsek MR, Pearson JP, Iglewski BH, Costerton JW, Greenberg EP. The involvement of cell-to-cell signals in the development of a bacterial biofilm. Science. 1998;280:295-298\n'},{id:"B6",body:'\nLewis K. 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Genetic control of Candida albicans biofilm development. Nature Reviews Microbiology. 2011;9:109-118\n'},{id:"B28",body:'\nSilva S, Negri M, Henriques M, Oliveira R, Williams DW, Azeredo J. Adherence and biofilm formation of non-Candida albicans Candida species. Trends in Microbiology. 2011;19:241-247\n'},{id:"B29",body:'\nMowat E, Williams C, Jones B, McChlery S, Ramage G. The characteristics of Aspergillus fumigatus mycetoma development: Is this a biofilm? Medical Mycology. 2009;47:S120-S126\n'},{id:"B30",body:'\nLoussert C, Schmitt C, Prevost MC, Balloy V, Fadel E, Philippe B, et al. In vivo biofilm composition of Aspergillus fumigatus. Cellular Microbiology. 2010;12:405-410\n'},{id:"B31",body:'\nMartinez LR, Casadevall A. Cryptococcus neoformans biofilm formation depends on surface support and carbon source and reduces fungal cell susceptibility to heat, cold, and UV light. Applied and Environmental Microbiology. 2007;73:4592-4601\n'},{id:"B32",body:'\nCushion MT, Collins MS, Linke MJ. Biofilm formation by Pneumocystis spp. Eukaryotic Cell. 2009;8:197-206\n'},{id:"B33",body:'\nKimura K, Itoh Y. Characterization of poly-Q-glutamate hydrolase encoded by a bacteriophage genome: Possible role in phage infection of Bacillus subtilis encapsulated with poly-Q-glutamate. Applied and Environmental Microbiology. 2003;69:2491-2497\n'},{id:"B34",body:'\nSutherland IW. Polysaccharases for microbial polysaccharides. Carbohydrate Polymers. 1999;116:319-328\n'},{id:"B35",body:'\nDoolittle MM, Cooney JJ, Caldwell DE. Lytic infection of Escherichia coli biofilms by bacteriophage T4. Canadian Journal of Microbiology. 1995;41:12-18\n'},{id:"B36",body:'\nWood SR, Kirkham J, Marsh PD, Shore RC, Nattress B, Robinson C. Architecture of intact natural human plaque biofilms studied by confocal laser scanning microscopy. Journal of Dental Research. 2000;79:21-27\n'},{id:"B37",body:'\nVan Voorthuizen EM, Ashbolt NJ, Schafer AI. Role of hydrophobic and electrostatic interactions for initial enteric virus retention by MF membranes. Journal of Membrane Science. 2001;194:69-79\n'},{id:"B38",body:'\nVan Etten JL, Lane LC, Meints RH. Viruses and virus-like particles of eukaryotic algae. Microbiological Reviews. 1991;55:586-620\n'},{id:"B39",body:'\nWilson WH, Tarran GA, Schroder D, Cox M, Oke J, Malin G. Isolation of viruses responsible for the demise of Emiliania huxleyi bloom in the English Channel. Journal of the Marine Biological Association. 2002;82:369-377\n'},{id:"B40",body:'\nAnderson MJ, Patrick J, Parks MLP. A mucosal model to study microbial biofilm development and anti-biofilm therapeutics. Journal of Microbiological Methods. 2012;92:201-208\n'},{id:"B41",body:'\nBlasi F, Page C, Maria G, Pallecchi L, Gabriella M, Rogliani P, et al. The effect of N-acetylcysteine on biofilms : Implications for the treatment of respiratory tract infections. Respiratory Medicine. 2016;117:190-197\n'},{id:"B42",body:'\nCalo L, Passàli GC, Galli J, Fadda G, Paludetti G. Role of biofilms in chronic inflammatory diseases of the upper airways. Advances in Oto-Rhino-Laryngology. 2011;72:93-96\n'},{id:"B43",body:'\nHamilos DL. Host-microbial interactions in patients with chronic rhinosinusitis. Journal of Allergy and Clinical Immunology. 2014;133(3):640-653\n'},{id:"B44",body:'\nEhrlich GD, Veeh R, Wang XJ, Costerton W, Hayes JD, Hu FZ, et al. Mucosal biofilm formation on middle-ear mucosa in the chinchilla model of otitis media. JAMA. 2002;287:1710-1715\n'},{id:"B45",body:'\nForsgren J, Samuelson A, Ahlin A, Jonasson J, Rynnel-Dagöö B, Lindberg A. Haemophilus influenzae resides and multiplies intracellularly in human adenoid tissue as demonstrated by in situ hybridization and bacterial viability assay. Infection and Immunity. 1994;62:673-679\n'},{id:"B46",body:'\nCoates H, Thornton R, Langlands J, Filion P, Keil AD, Vijayasekaran S, et al. The role of chronic infection in children with otitis media with effusion: Evidence for intracellular persistence of bacteria. Otolaryngology-Head and Neck Surgery. 2008;138:778-781\n'},{id:"B47",body:'\nGoddard AF, Staudinger BJ, Dowd SE, Joshi-Datar A, Wolcott RD, Aitken ML, et al. Direct sampling of cystic fibrosis lungs indicates that DNA-based analyses of upper-airway specimens can misrepresent lung microbiota. Proceedings of the National Academy of Sciences of the USA. 2012;109:13769-13774\n'},{id:"B48",body:'\nKoch C, Hoiby N. Pathogenesis of cystic fibrosis. Lancet. 1993;341:165-1069\n'},{id:"B49",body:'\nSibley CD, Rabin H, Surette MG. Cystic fibrosis: A polymicrobial infectious disease. Future Microbiology. 2006;1:53-61\n'},{id:"B50",body:'\nMurphy TF, Kirkham C. Biofilm formation by non-typeable Haemophilus influenzae: Strain variability, outer membrane antigen expression and role of pili. FEMS Microbiology Letters. 2002;2:81-89\n'},{id:"B51",body:'\nChalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. European Respiratory Journal. 2015;45:1446-1462\n'},{id:"B52",body:'\nRogers GB, van der Gast CJ, Serisier DJ. Predominant pathogen competition and core microbiota divergence in chronic airway infection. International Society for Microbial Ecology. 2014;9:217-225\n'},{id:"B53",body:'\nPriftis KN, Litt D, Manglani S, Anthracopoulos MB, Thickett K, Tzanakaki G, et al. Bacterial bronchitis caused by Streptococcus pneumoniae and non-typable Haemophilus influenzae in children: The impact of vaccination. Chest. 2013;143:152-157\n'},{id:"B54",body:'\nFolkesson A, Jelsbak L, Yang L, Johansen HK, Ciofu O, Høiby N, et al. Adaptation of Pseudomonas aeruginosa to the cystic fibrosis airway: An evolutionary perspective. Nature Reviews Microbiology. 2012;10:841-851\n'},{id:"B55",body:'\nMietto C, Pinciroli R, Patel N, Berra L. Ventilator associated pneumonia: Evolving definitions and preventive strategies. Respiratory Care. 2013;58:990-1007\n'},{id:"B56",body:'\nJackson K, Keyser R, Wozniak DJ. The role of biofilms in airway disease. Thieme. 2003;24:663-670\n'},{id:"B57",body:'\nLipuma J. The changing microbial epidemiology in cystic fibrosis. Clinical Microbiology Reviews. 2010;23:299-323\n'},{id:"B58",body:'\nO’Toole GA. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceeds via multiple convergent signalling pathways: A genetic analysis. Molecular Microbiology. 1998;28:449-461\n'},{id:"B59",body:'\nGrimwood K, Kyd JM, Owen SJ, Massa HM, Cripps AW. Vaccination against respiratory Pseudomonas aeruginosa infection. Human Vaccines & Immunotherapeutics. 2014;11:14-20\n'},{id:"B60",body:'\nWhitchurch CB, Tolker-Nielsen T, Ragas PC, Mattick JS. Extracellular DNA required for bacterial biofilm formation. Science. 2002;295:1487\n'},{id:"B61",body:'\nEvans LR, Linker A. Production and characterization of the slime polysaccharide of Pseudomonas aeruginosa. Journal of Bacteriology. 1973;116:915-924\n'},{id:"B62",body:'\nDavies DG, Chakrabarty AM, Geesey GG. Exopolysaccharide production in biofilms: Substratum activation of alginate gene expression by Pseudomonas aeruginosa. Applied and Environmental Microbiology. 1993;59:1181-1186\n'},{id:"B63",body:'\nvon Eiff C, Peters G, Heilmann C. Pathogenesis of infections due to coagulase-negative staphylococci. Lancet Infectious Diseases. 2002;2:677-685\n'},{id:"B64",body:'\nSchierholz JM, Beuth J. Implant infections: A haven for opportunistic bacteria. Journal of Hospital Infection. 2001;49:87-93\n'},{id:"B65",body:'\nHussain M, Herrmann M, von Eiff C, Perdreau-Remington F, Peters G. A 140-kilodalton extracellular protein is essential for the accumulation of Staphylococcus epidermidis strains on surfaces. Infection and Immunity. 1997;65:519-524\n'},{id:"B66",body:'\nBalaban N, Goldkorn T, Gov Y, Hirshberg M, Koyfman N, Matthews HR, et al. Regulation of Staphylococcus aureus pathogenesis via target of RNAIII-activating protein (TRAP). Journal of Biological Chemistry. 2001;276:2658-2667\n'},{id:"B67",body:'\nJurcisek JA, Bakaletz LO. Biofilms formed by non-typeable Haemophilus influenzae in vivo contain both double-stranded DNA and type IV pilin protein. Molecular Biology of Pathogens. 2007;189:3868-3875\n'},{id:"B68",body:'\nO’Toole GA, Kolter R. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Molecular Microbiology. 1998;30:295-304\n'},{id:"B69",body:'\nHoiby N, Johansen HK, Moser C, Song Z, Ciofu O, Kharazmi A. Pseudomonas aeruginosa and the in vitro and in vivo biofilm mode of growth. Microbes and Infection. 2001;3:23-35\n'},{id:"B70",body:'\nHoa M, Tomovic S, Nistico L, Hall-Stoodley L, Stoodley P, Sachdeva L, et al. Identification of adenoid biofilms with middle ear pathogens in otitis-prone children utilizing SEM and FISH. International Journal of Pediatric Otorhinolaryngology. 2009;73:1242-1248\n'},{id:"B71",body:'\nChao Y, Marks LR, Pettigrew MM, Hakansson AP. Streptococcus pneumoniae biofilm formation and dispersion during colonization and disease. Frontiers in Cellular and Infection Microbiology. 2015;4:194\n'},{id:"B72",body:'\nSanchez CJ, Shivshankar P, Stol K, Trakhtenbroit S, Sullam PM, Sauer K, et al. The pneumococcal serine-rich repeat protein is an intra-species bacterial adhesin that promotes bacterial aggregation in vivo and in biofilms. PLoS Pathogens. 2010;6:e1001044\n'},{id:"B73",body:'\nMarks LR, Parameswaran GI, Hakansson AP. Pneumococcal interactions with epithelial cells are crucial for optimal biofilm formation and colonization in vitro and in vivo. Infection and Immunity. 2012;80:2744-2760\n'},{id:"B74",body:'\nPalaniappan R, Singh S, Singh UP, Sakthivel SK, Ades EW, Briles DE, et al. Differential PsaA-PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage. Infection and Immunity. 2005;73:1006-1013\n'},{id:"B75",body:'\nSloan GP, Love CF, Sukumar N, Mishra M, Deora R. The Bordetella bps polysaccharide is critical for biofilm development in the mouse respiratory tract. Jorunal of Bacteriology. 2007;189:8270-8276\n'},{id:"B76",body:'\nConover MS, Mishra M, Deora R. Extracellular DNA is essential for maintaining Bordetella biofilm integrity on abiotic surfaces and in the upper respiratory tract of mice. PLoS One. 2011;6:e16861\n'},{id:"B77",body:'\nPaddock CD, Sanden GN, Cherry JD, Gal AA, Langston C, Tatti KM, et al. Pathology and pathogenesis of fatal Bordetella pertussis infection in infants. Respiratory Medicine. 2008;47:328-338\n'},{id:"B78",body:'\nParise G, Mishra M, Itoh Y, Romeo T, Deora R. Role of a putative polysaccharide locus in Bordetella biofilm development. Journal of Bacteriology. 2007;189:750-760\n'},{id:"B79",body:'\nSerra DO, Conover MS, Arnal L, Sloan GP, Rodriguez ME, Yantorno OM, et al. FHA-mediated cell-substrate and cell-cell adhesions are critical for Bordetella pertussis biofilm formation on abiotic surfaces and in the mouse nose and the trachea. PLoS One. 2011;6:e28811\n'},{id:"B80",body:'\nFalkinham JO. Surrounded by mycobacteria: Non-tuberculous mycobacteria in the human environment. Journal of Applied Microbiology. 2009;107:356-367\n'},{id:"B81",body:'\nLeung JM, Olivier KN. Non-tuberculous mycobacteria: The changing epidemiology and treatment challenges in cystic fibrosis. Current Opinion in Pulmonary Medicine. 2013;19:662-669\n'},{id:"B82",body:'\nSwift S, Downie JA, Whitehead WA. Quorum sensing as a population-density-dependent determinant of bacteria physiology. Advances in Microbial Physiology. 2001;45:199-200\n'},{id:"B83",body:'\nWagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH. Microarray analysis of Pseudomonas aeruginosa. Quorum-sensing regulons: Effects of growth phase and environment. Journal of Bacteriology. 2003;185:2080-2095\n'},{id:"B84",body:'\nNealson KH, Platt T, Hastings JW. Cellular control of the synthesis and activity of the bacterial luminescent system. Journal of Bacteriology. 1970;104:313-322\n'},{id:"B85",body:'\nLu L, Hu W, Tian Z, Yuan D, Yi G, Zhou Y, et al. Developing natural products as potential anti-biofilm agents. Chinese Medicine. 2019;14:11\n'},{id:"B86",body:'\nBakkiyaraj D, Nandhini J, Malathy B, Pandian S. The anti-biofilm potential of pomegranate (Punica granatum L.) extract against human bacterial and fungal pathogens. Biofouling. 2013;29:929-937\n'},{id:"B87",body:'\nAl-Bakri A, Othman G, Afifi F. Determination of the antibiofilm, antiadhesive, and anti-MRSA activities of seven Salvia species. Pharmacognosy Magazine. 2010;6:2640-2670\n'},{id:"B88",body:'\nSilva S, Costa E, Costa M, Pereira M, Pereira J, Soares J, et al. Aqueous extracts of Vaccinium corymbosum as inhibitors of Staphylococcus aureus. Food Control. 2015;51:314-320\n'},{id:"B89",body:'\nChusri S, Phatthalung P, Voravuthikunchai S. Anti-biofilm activity of Quercus infectoria G. Olivier against methicillin-resistant Staphylococcus aureus. Letters in Applied Microbiology. 2012;54:511-517\n'},{id:"B90",body:'\nPerumal S, Mahmud R. Chemical analysis, inhibition of biofilm formation and biofilm eradication potential of Euphorbia hirta L. against clinical isolates and standard strains. BMC Complementary and Alternative Medicine. 2013;13:346\n'},{id:"B91",body:'\nYadav S. Antibiofilm formation activity of Terminalia bellerica plant extract against clinical isolates of Streptococcus mutans and Streptococcus sobrinus implication in oral hygiene. International Journal of Pharmaceutical & Biological Archive. 2012;3:6\n'},{id:"B92",body:'\nSyed H, Khalid A, Sikander KS, Nazia B, Shahana U. Detection of Mycobacterium smegmatis biofilm and its control by natural agents. International Journal of Current Microbiology and Applied Sciences. 2014;3:801-812\n'},{id:"B93",body:'\nTrentin D, Giordani R, Zimmer K, da Silva A, da Silva M, Correia MT, et al. Potential of medicinal plants from the Brazilian semi-arid region (Caatinga) against Staphylococcus epidermidis planktonic and biofilm lifestyles. Journal of Ethnopharmacology. 2011;137:327-335\n'},{id:"B94",body:'\nLimsong J, Benjavongkulchai E, Kuvatanasuchati J. Inhibitory effect of some herbal extracts on adherence of Streptococcus mutans. Journal of Ethnopharmacology. 2004;92:281-289\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Cynthia Amaning Danquah",address:"cadanquah.pharm@knust.edu.gh",affiliation:'
Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Ghana
Department of Pharmaceutical Microbiology, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Ghana
'}],corrections:null},book:{id:"8967",type:"book",title:"Bacterial Biofilms",subtitle:null,fullTitle:"Bacterial Biofilms",slug:"bacterial-biofilms",publishedDate:"October 7th 2020",bookSignature:"Sadik Dincer, Melis Sümengen Özdenefe and Afet Arkut",coverURL:"https://cdn.intechopen.com/books/images_new/8967.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-900-3",printIsbn:"978-1-78985-899-0",pdfIsbn:"978-1-83968-819-5",isAvailableForWebshopOrdering:!0,editors:[{id:"188141",title:"Prof.",name:"Sadik",middleName:null,surname:"Dincer",slug:"sadik-dincer",fullName:"Sadik Dincer"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"170125",title:"Dr.",name:"Jeane",middleName:"Eliete Laguila",surname:"Visentainer",email:"jelvisentainer@gmail.com",fullName:"Jeane Visentainer",slug:"jeane-visentainer",position:null,biography:null,institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/170125/images/5935_n.jpg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"3",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:{name:"State University of Maringa",institutionURL:null,country:{name:"Brazil"}}},booksEdited:[],chaptersAuthored:[{id:"46247",title:"HLA and Infectious Diseases",slug:"hla-and-infectious-diseases",abstract:null,signatures:"Daniela Maira Cardozo, Amanda Vansan Marangon, Ana Maria Sell,\nJeane Eliete Laguila Visentainer and Carmino Antonio de Souza",authors:[{id:"162164",title:"Dr.",name:"Amanda",surname:"Marangon",fullName:"Amanda Marangon",slug:"amanda-marangon",email:"amanda_vansan@hotmail.com"},{id:"162165",title:"MSc.",name:"Daniela",surname:"Cardozo",fullName:"Daniela Cardozo",slug:"daniela-cardozo",email:"danielamcardozo@gmail.com"},{id:"170124",title:"Dr.",name:"Ana Maria",surname:"Sell",fullName:"Ana Maria Sell",slug:"ana-maria-sell",email:"anamsell@gmail.com"},{id:"170125",title:"Dr.",name:"Jeane",surname:"Visentainer",fullName:"Jeane Visentainer",slug:"jeane-visentainer",email:"jelvisentainer@gmail.com"}],book:{id:"3824",title:"HLA and Associated Important Diseases",slug:"hla-and-associated-important-diseases",productType:{id:"1",title:"Edited Volume"}}},{id:"60014",title:"Immunogenetics of MHC and KIR in the Leprosy",slug:"immunogenetics-of-mhc-and-kir-in-the-leprosy",abstract:"Several genetic polymorphisms in immune response genes have been associated to leprosy. This fact converges on the main hypothesis that genetic factors are involved in the disease susceptibility in two distinct steps: leprosy per se and their clinical forms. These genes play an important role in the recognition process, in the activation of the main metabolic pathway of the immune response and in the evolution of the disease. The scope of this project was to highlight the role of the immune response genes in the context of leprosy, emphasizing the participation of some of them in the signaling and targeting processes in response to bacillus infection and on disease evolution, such as HLA, KIR and MIC genes. Some environmental and genetic factors are important when the exposure to the bacillus occurs, leading to cure or not. Factors that favor a cellular or humoral immune response may influence the clinical manifestations after the infection inducting to one of extreme poles. Furthermore, some genetic factors were associated to the type of reaction that some individuals present during the disease development. 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Human milk fat has an important position as energy source, structural and regulatory functions, being one of the most important components of breast milk. It provides approximately 50–60% of the energy of the human milk, and its composition in fatty acids defines its nutritional and physico-chemical properties. Furthermore, human milk contains the long-chain polyunsaturated essential fatty acids (LCPUFA) eicosapentaenoic acid (EPA), arachidonic acid (AA) and docosahexaenoic acid (DHA), which is important for appropriate development of baby’s organs, tissues and nervous system. This chapter will address the benefits associated with the consumption of human milk (health, nutritional, immunological and developmental benefits) as well as the analysis applied to determine the lipid quality of this powerful food.",signatures:"Jesui Vergilio Visentainer, Oscar Oliveira Santos, Liane Maldaner, Caroline Zappielo, Vanessa Neia, Lorena Visentainer, Luciana Pelissari, Jessica Pizzo, Adriela Rydlewski, Roberta Silveira, Marilia Galuch and Jeane Laguila Visentainer",authors:[{id:"170125",title:"Dr.",name:"Jeane",surname:"Visentainer",fullName:"Jeane Visentainer",slug:"jeane-visentainer",email:"jelvisentainer@gmail.com"},{id:"256644",title:"Dr.",name:"Oscar",surname:"Santos",fullName:"Oscar Santos",slug:"oscar-santos",email:"oosjunior@uem.br"},{id:"258900",title:"Ph.D.",name:"Jesui",surname:"Vergilio Visentainer",fullName:"Jesui Vergilio Visentainer",slug:"jesui-vergilio-visentainer",email:"jesuiv@gmail.com"},{id:"267803",title:"MSc.",name:"Caroline",surname:"Zappielo",fullName:"Caroline Zappielo",slug:"caroline-zappielo",email:"carolzappi@hotmail.com"},{id:"267804",title:"MSc.",name:"Vanessa",surname:"Javera Neia",fullName:"Vanessa Javera Neia",slug:"vanessa-javera-neia",email:"nutrivanjavera@hotmail.com"},{id:"267807",title:"MSc.",name:"Luciana",surname:"Pelissari",fullName:"Luciana Pelissari",slug:"luciana-pelissari",email:"lucianapmanin@hotmail.com"},{id:"267808",title:"MSc.",name:"Jessica",surname:"Pizzo",fullName:"Jessica Pizzo",slug:"jessica-pizzo",email:"jehspizzo@gmail.com"},{id:"267812",title:"Dr.",name:"Liane",surname:"Maldaner",fullName:"Liane Maldaner",slug:"liane-maldaner",email:"lmaldaner@uem.br"},{id:"267813",title:"MSc.",name:"Lorena",surname:"Visentainer",fullName:"Lorena Visentainer",slug:"lorena-visentainer",email:"lo.visentainer@gmail.com"},{id:"267814",title:"MSc.",name:"Adriela",surname:"Rydlewski Ito",fullName:"Adriela Rydlewski Ito",slug:"adriela-rydlewski-ito",email:"adrielaar@hotmail.com"},{id:"267815",title:"MSc.",name:"Roberta",surname:"Silveira",fullName:"Roberta Silveira",slug:"roberta-silveira",email:"dasilveira.roberta@gmail.com"},{id:"267816",title:"MSc.",name:"Marilia",surname:"Galuch",fullName:"Marilia Galuch",slug:"marilia-galuch",email:"mariliagaluch@gmail.com"}],book:{id:"7006",title:"Biochemistry and Health Benefits of Fatty Acids",slug:"biochemistry-and-health-benefits-of-fatty-acids",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"34102",title:"Dr.",name:"Isabel",surname:"Torres",slug:"isabel-torres",fullName:"Isabel Torres",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Jaén",institutionURL:null,country:{name:"Spain"}}},{id:"40574",title:"Dr.",name:"Masahito",surname:"Katahira",slug:"masahito-katahira",fullName:"Masahito Katahira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"EDUCATION:\r\n1984–1990 \tMD, Nagoya University School of Medicine, Nagoya, Japan\r\n1995–1998 \tPhD, Nagoya University School of Medicine, Nagoya, Japan\r\nAPPOINTMENTS:\r\n1990–1992 \tResident in Internal Medicine,\r\nNagoya First Red Cross Hospital, Nagoya, Japan\r\n1992–1994 \tFellow in Endocrinology,\r\nNagoya First Red Cross Hospital, Nagoya, Japan\r\n1994–1995\tPhysician-in-Chief of Internal Medicine, Hekinan Municipal Hospital, Hekinan, Japan\r\n1997–2002\tCo-director of Endocrinology, Okazaki City Hospital, Okazaki, Japan\r\n2002–2005\tPhysician-in-Chief of Internal Medicine, Kyoritsu General Hospital, Nagoya, Japan\r\n2005–present Director, Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, Ichinomiya, Japan",institutionString:null,institution:{name:"Aichi Prefectural University",institutionURL:null,country:{name:"Japan"}}},{id:"68881",title:"Dr.",name:"Jacome",surname:"Bruges-Armas",slug:"jacome-bruges-armas",fullName:"Jacome Bruges-Armas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/68881/images/2495_n.jpg",biography:"Jácome Bruges Armas is a Senior Specialist in Internal Medicine and is currently the Director of the Genetics and Arthritis Research Group (GARG) at the Institute for Molecular and Cell Biology (IBMC), University of Porto, PortugaL. He is also the Director of the Epidemiology and Molecular Biology Service (SEEBMO) at the Hospital de Santo Espirito de Angra do Heroismo, Terceira Island, The Azores, Portugal. His research interests are mainly the epidemiology and molecular genetics of Spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Chondrocalcinosis (CC). He is a member of several scientific organizations and a member of the editorial board of several scientific journals.",institutionString:null,institution:{name:"University of Porto",institutionURL:null,country:{name:"Portugal"}}},{id:"78755",title:"Dr.",name:"Attapon",surname:"Cheepsattayakorn",slug:"attapon-cheepsattayakorn",fullName:"Attapon Cheepsattayakorn",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/78755/images/3963_n.jpg",biography:"Education:\r\nMD-1986\r\nFRCP (London)-2007\r\nFRCP (Edinburgh)-2005\r\nFRCP (Glasgow)-2005\r\nFACP (USA)-2004\r\nMembership of the American College of Physicians-2003\r\nFCCP (USA)-2001\r\nFRCP (Thai)-2004\r\nFRCFP (Thai)-2001\r\nFRCR (Thai)-1991\r\nDiplomate: Thai Board of Preventive Medicine (Public Health Science)-2010\r\nDiplomate : Thai Board of General Practice-1992\r\nCertificate of Leadership Training in Tuberculosis Program Management (RIT, Tokyo, Japan)-2002\r\nCertificate of Training of Tuberculosis in Medical School (Aga Khan University and International Union Against Tuberculosis and Lung Disease )-2004",institutionString:null,institution:null},{id:"161075",title:"Distinguished Prof.",name:"Yongzhi",surname:"Xi",slug:"yongzhi-xi",fullName:"Yongzhi Xi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/161075/images/4053_n.jpg",biography:"Dr. Yongzhi Xi graduated from BINZHOU Medical College and Academy of Military Medical Sciences, P.R. 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Our business values are based on those any scientist applies to their research. The values of our business are based on the same ones that all good scientists apply to their research. We have created a culture of respect and collaboration within a relaxed, friendly, and progressive atmosphere, while maintaining academic rigour.
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Please check out our job board for open positions.
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Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
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Disruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
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What makes IntechOpen a great place to work?
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IntechOpen is a dynamic, vibrant company, where exceptional people are achieving great things. We offer a creative, dedicated, committed, and passionate environment but never lose sight of the fact that science and discovery is exciting and rewarding. We constantly strive to ensure that members of our community can work, travel, meet world-renowned researchers and grow their own career and develop their own experiences.
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If this sounds like a place that you would like to work, whether you are at the beginning of your career or are an experienced professional, we invite you to drop us a line and tell us why you could be the right person for IntechOpen.
Integrity - We are consistent and dependable, always striving for precision and accuracy in the true spirit of science.
\n\n
Openness - We communicate honestly and transparently. We are open to constructive criticism and committed to learning from it.
\n\n
Disruptiveness - We are eager for discovery, for new ideas and for progression. We approach our work with creativity and determination, with a clear vision that drives us forward. We look beyond today and strive for a better tomorrow.
\n\n
What makes IntechOpen a great place to work?
\n\n
IntechOpen is a dynamic, vibrant company, where exceptional people are achieving great things. We offer a creative, dedicated, committed, and passionate environment but never lose sight of the fact that science and discovery is exciting and rewarding. We constantly strive to ensure that members of our community can work, travel, meet world-renowned researchers and grow their own career and develop their own experiences.
\n\n
If this sounds like a place that you would like to work, whether you are at the beginning of your career or are an experienced professional, we invite you to drop us a line and tell us why you could be the right person for IntechOpen.
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Alméciga-Díaz",authors:[{id:"47504",title:"MSc",name:"Oscar",middleName:null,surname:"Sanchez",slug:"oscar-sanchez",fullName:"Oscar Sanchez"},{id:"56842",title:"Dr.",name:"Rocio",middleName:null,surname:"Sierra",slug:"rocio-sierra",fullName:"Rocio Sierra"},{id:"56843",title:"Dr.",name:"Carlos",middleName:"Javier",surname:"Almeciga-Diaz",slug:"carlos-almeciga-diaz",fullName:"Carlos Almeciga-Diaz"}]},{id:"40527",doi:"10.5772/50241",title:"Solid Waste Management in African Cities – East Africa",slug:"solid-waste-management-in-african-cities-east-africa",totalDownloads:16198,totalCrossrefCites:19,totalDimensionsCites:33,abstract:null,book:{id:"2781",slug:"waste-management-an-integrated-vision",title:"Waste Management",fullTitle:"Waste Management - An Integrated Vision"},signatures:"James Okot-Okumu",authors:[{id:"141924",title:"Dr.",name:"James",middleName:null,surname:"Okot-Okumu",slug:"james-okot-okumu",fullName:"James Okot-Okumu"}]},{id:"17589",doi:"10.5772/23176",title:"Performance and Emission Characteristics of Spark Ignition Engine Fuelled with Ethanol and Methanol Gasoline Blended Fuels",slug:"performance-and-emission-characteristics-of-spark-ignition-engine-fuelled-with-ethanol-and-methanol-",totalDownloads:12126,totalCrossrefCites:16,totalDimensionsCites:29,abstract:null,book:{id:"325",slug:"alternative-fuel",title:"Alternative Fuel",fullTitle:"Alternative Fuel"},signatures:"Ioannis Gravalos, Dimitrios Moshou, Theodoros Gialamas, Panagiotis Xyradakis, Dimitrios Kateris and Zisis Tsiropoulos",authors:[{id:"50923",title:"Prof.",name:"Ioannis",middleName:null,surname:"Gravalos",slug:"ioannis-gravalos",fullName:"Ioannis Gravalos"},{id:"57241",title:"Prof.",name:"Theodoros",middleName:null,surname:"Gialamas",slug:"theodoros-gialamas",fullName:"Theodoros Gialamas"},{id:"57242",title:"MSc.",name:"Panagiotis",middleName:null,surname:"Xyradakis",slug:"panagiotis-xyradakis",fullName:"Panagiotis Xyradakis"},{id:"57244",title:"Dr.",name:"Dimitrios",middleName:null,surname:"Kateris",slug:"dimitrios-kateris",fullName:"Dimitrios Kateris"},{id:"57245",title:"MSc",name:"Zisis",middleName:null,surname:"Tsiropoulos",slug:"zisis-tsiropoulos",fullName:"Zisis Tsiropoulos"},{id:"101768",title:"Prof.",name:"Dimitrios",middleName:null,surname:"Moshou",slug:"dimitrios-moshou",fullName:"Dimitrios Moshou"}]},{id:"17585",doi:"10.5772/21905",title:"Biodiesel Fuel Production by Enzymatic Transesterification of Oils: Recent Trends, Challenges and Future Perspectives",slug:"biodiesel-fuel-production-by-enzymatic-transesterification-of-oils-recent-trends-challenges-and-futu",totalDownloads:11056,totalCrossrefCites:13,totalDimensionsCites:26,abstract:null,book:{id:"325",slug:"alternative-fuel",title:"Alternative Fuel",fullTitle:"Alternative Fuel"},signatures:"Nevena Luković, Zorica Knežević-Jugović and Dejan Bezbradica",authors:[{id:"45320",title:"MSc",name:"Nevena",middleName:null,surname:"Lukovic",slug:"nevena-lukovic",fullName:"Nevena Lukovic"},{id:"57079",title:"Prof.",name:"Dejan",middleName:null,surname:"Bezbradica",slug:"dejan-bezbradica",fullName:"Dejan Bezbradica"},{id:"57080",title:"Dr.",name:"Zorica",middleName:null,surname:"Knežević-Jugović",slug:"zorica-knezevic-jugovic",fullName:"Zorica Knežević-Jugović"}]}],mostDownloadedChaptersLast30Days:[{id:"73517",title:"Agricultural Solid Wastes: Causes, Effects, and Effective Management",slug:"agricultural-solid-wastes-causes-effects-and-effective-management",totalDownloads:1576,totalCrossrefCites:5,totalDimensionsCites:14,abstract:"The role of the agricultural sector in human development and economic development cannot be overemphasized. Awareness for increased agricultural production is on the increase, arising from the need to feed the ever-increasing human population. Interestingly, almost all agricultural activities generate wastes, which are generated in large quantities in many countries. However, these wastes may constitute a serious threat to human health through environmental pollution and handling them may result in huge economic loss. Unfortunately, in many developing countries where large quantities of these wastes are generated, they are not properly managed because little is known about their potential risks and benefits if properly managed. There are studies that address some of the challenges of agricultural solid wastes as well as suggestions on how they can be properly managed. In this chapter, we intend to explore the major sources of agricultural solid wastes, their potential risks, and how they can be properly managed.",book:{id:"9873",slug:"strategies-of-sustainable-solid-waste-management",title:"Strategies of Sustainable Solid Waste Management",fullTitle:"Strategies of Sustainable Solid Waste Management"},signatures:"Isaac Oluseun Adejumo and Olufemi Adebukola Adebiyi",authors:[{id:"276527",title:"Dr.",name:"Isaac Oluseun",middleName:null,surname:"Adejumo",slug:"isaac-oluseun-adejumo",fullName:"Isaac Oluseun Adejumo"},{id:"328699",title:"Dr.",name:"O.A.",middleName:null,surname:"Adebiyi",slug:"o.a.-adebiyi",fullName:"O.A. Adebiyi"}]},{id:"64270",title:"Decentralization and Solid Waste Management in Urbanizing Ghana: Moving beyond the Status Quo",slug:"decentralization-and-solid-waste-management-in-urbanizing-ghana-moving-beyond-the-status-quo",totalDownloads:2045,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Waste management is competing with more pressing economic and social issues such as social protection programs, education, and health. The government of Ghana has therefore decentralized the waste management system in the country. With this development, local government authorities and private sector actors are now playing key roles in waste management in the country. This study sought to examine decentralized solid waste management in the Berekum and Dormaa Municipalities in the Brong Ahafo Region of Ghana. Specifically, it analyzed the involvement of the private sector in solid waste management, and the quality of waste management services in the two selected municipalities. Through a survey of 312 households, the study analyzed the performance improvement, regulatory policy, and sustainable service delivery of solid waste management in the municipalities. The study found that there were no mechanisms for full cost recovery to include majority of the residents, who patronize communal collection service. The study therefore recommends the adherence to normative standards and agreed rules, adoption, and use of appropriate cost recovery strategies for low-income groups as well as the restructuring of institutional arrangements to ensure user involvement and enforcement of legislation to improve municipal solid waste management in Ghana.",book:{id:"8580",slug:"municipal-solid-waste-management",title:"Municipal Solid Waste Management",fullTitle:"Municipal Solid Waste Management"},signatures:"Richard Kyere, Michael Addaney and Jonas Ayaribilla Akudugu",authors:[{id:"273978",title:"Ph.D. Student",name:"Michael",middleName:null,surname:"Addaney",slug:"michael-addaney",fullName:"Michael Addaney"},{id:"273981",title:"Mr.",name:"Richard",middleName:null,surname:"Kyere",slug:"richard-kyere",fullName:"Richard Kyere"},{id:"273982",title:"Dr.",name:"Jonas Ayaribilla",middleName:null,surname:"Akudugu",slug:"jonas-ayaribilla-akudugu",fullName:"Jonas Ayaribilla Akudugu"}]},{id:"65314",title:"Municipal Solid Waste Disposal in Mangrove Forest: Environmental Implication and Management Strategies in the Niger Delta, Nigeria",slug:"municipal-solid-waste-disposal-in-mangrove-forest-environmental-implication-and-management-strategie",totalDownloads:1031,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"Niger Delta is an oil rich region situated in the southern part of Nigeria. It is made up of nine states which hosts oil industries. There are a handful of businesses (super market, manufacturing companies, etc.) that service the over 40 million people living in the cities. This situation had led to the increase in solid waste in the city. Because of the problem of over population, and poor waste management strategies (e.g., lack of recycling habit and lack of equipment) the mangrove forest had become a dumping ground for waste. This action has impacted the health of aquatic and terrestrial organisms, and has created a public health disaster for citizens because of increase in heavy metal concentration up the food chain. This chapter therefore, identifies poverty, lack of planning, poor behavior and poor technology as key factors affecting effective waste management in the Niger Delta. It suggests that good waste management system can be worked out if there is coordination between research institution and government in the implementation of recommendation by research institutes. Attitudinal change is also necessary on the part of citizens and government to enable a healthy interaction for the purpose of managing waste effectively.",book:{id:"8580",slug:"municipal-solid-waste-management",title:"Municipal Solid Waste Management",fullTitle:"Municipal Solid Waste Management"},signatures:"Aroloye O. Numbere",authors:[{id:"215285",title:"Dr.",name:"Aroloye O.",middleName:null,surname:"Numbere",slug:"aroloye-o.-numbere",fullName:"Aroloye O. Numbere"}]},{id:"51114",title:"Overview of Hazardous Waste Management Status in Malaysia",slug:"overview-of-hazardous-waste-management-status-in-malaysia",totalDownloads:6188,totalCrossrefCites:4,totalDimensionsCites:14,abstract:"This chapter reviews the status of hazardous waste management in Malaysia. It highlights the sources of the hazardous waste, government policies on waste generation and management, the involvement of the stakeholders, and the various management procedures adopted in Malaysia. Currently, the manufacturing sector is the major contributor in hazardous waste generated in Malaysia. Other sectors that contribute include household, agriculture, medical, and other industrial sectors. Malaysian government’s resolve on human health protection and safeguarding the environment prompted various acts, regulations, and orders such as the popular Environmental Quality Act (EQA) 1974. The regulations made pursuant to the Environmental Quality Act have continuously improved to address the issues on the definition and classifications of hazardous waste and the management process in Malaysia. The management of hazardous waste in Malaysia is effectively growing as a result of continuous review of the regulations and enforcement of the acts. The stakeholders in the industries have also been active in keeping to the EQA regulations to keep the environment safe as much as possible.",book:{id:"5242",slug:"management-of-hazardous-wastes",title:"Management of Hazardous Wastes",fullTitle:"Management of Hazardous Wastes"},signatures:"Ogboo Chikere Aja, Hussain H. Al-Kayiem, Mesfin Gizaw Zewge and\nMeheron Selowara Joo",authors:[{id:"181768",title:"Dr.",name:"Ogboo Chikere",middleName:null,surname:"Aja",slug:"ogboo-chikere-aja",fullName:"Ogboo Chikere Aja"},{id:"181769",title:"Dr.",name:"Mesfin Gizaw",middleName:null,surname:"Zewge",slug:"mesfin-gizaw-zewge",fullName:"Mesfin Gizaw Zewge"},{id:"182433",title:"Mr.",name:"Meheron",middleName:null,surname:"Selowara Joo",slug:"meheron-selowara-joo",fullName:"Meheron Selowara Joo"},{id:"184186",title:"Prof.",name:"Hussain H.",middleName:null,surname:"Al-Kayiem",slug:"hussain-h.-al-kayiem",fullName:"Hussain H. Al-Kayiem"}]},{id:"40529",title:"Solid Waste Management in Malaysia – A Move Towards Sustainability",slug:"solid-waste-management-in-malaysia-a-move-towards-sustainability",totalDownloads:10054,totalCrossrefCites:11,totalDimensionsCites:25,abstract:null,book:{id:"2781",slug:"waste-management-an-integrated-vision",title:"Waste Management",fullTitle:"Waste Management - An Integrated Vision"},signatures:"Jayashree Sreenivasan, Marthandan Govindan, Malarvizhi Chinnasami and Indrakaran Kadiresu",authors:[{id:"154427",title:"Dr.",name:"Sreenivasan",middleName:null,surname:"Jayashree",slug:"sreenivasan-jayashree",fullName:"Sreenivasan Jayashree"}]}],onlineFirstChaptersFilter:{topicId:"146",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"79771",title:"Global Fertilizer Contributions from Specific Biogas Coproduct",slug:"global-fertilizer-contributions-from-specific-biogas-coproduct",totalDownloads:6,totalDimensionsCites:0,doi:"10.5772/intechopen.101543",abstract:"The impact of Haber-Bosch process on modern agriculture is prodigious. Haber-Bosch process led to invention of chemical fertilizers that powered green revolution, minimized food scarcity, and improved human and animal nutrition. Haber–Bosch process facilitated agricultural productivity in many parts of the world, with up to 60% of crop yield increase attributed solely to nitrogen fertilizer. However, Haber-Bosch fertilizers are expensive, and their poor use efficiency exerts adverse external consequences. In European Union for example, the annual damage of up to € 320 (US$ 372.495) billion associated with chemical fertilizers outweighs their direct benefit to farmers, in terms of crops grown, of up to € 80 (US$ 93.124) billion. A substitute for chemical fertilizers is therefore needed. In this chapter, external costs of chemical fertilizers are highlighted. The capability of liquid fraction of cassava peeling residue digestate to supplant and mitigate pecuniary costs of chemical fertilizers required for production of cassava root is also analyzed and presented. Results indicate that about 25% of fund used to purchase chemical fertilizers required for cassava root production could be saved with the use of liquid fraction of cassava peeling residue digestate. The pecuniary value is estimated at US$ 0.141 (≈ € 0.121) billion for the 2019 global cassava root output. This saving excludes external costs associated with Haber-Bosch fertilizers such as ammonia air pollution, eutrophication, greenhouse gasses emissions, and contamination of potable water supply reserves. Consequently, liquid fraction digestate could reduce the cost of cassava root production, as well as minimize adverse health and environmental consequences attributed to chemical fertilizers.",book:{id:"10980",title:"Biogas - Basics, Integrated Approaches, and Case Studies",coverURL:"https://cdn.intechopen.com/books/images_new/10980.jpg"},signatures:"Sammy N. Aso, Simeon C. Achinewhu and Madu O. Iwe"},{id:"80783",title:"Role of Microbial and Organic Amendments for the Enrichment of Methane Production in Bioreactor",slug:"role-of-microbial-and-organic-amendments-for-the-enrichment-of-methane-production-in-bioreactor",totalDownloads:32,totalDimensionsCites:0,doi:"10.5772/intechopen.102471",abstract:"Studies were carried out on lab-scale levels for biogas production using two different wastewaters, that is, herbal pharmaceutical wastewater and food processing wastewater. A total of eight methane bacteria were isolated from cattle dung and mass culturing was carried out to study their feasibility in biogas escalation. Optimization of methane bacteria that could increase biogas production was identified. Among the methane bacteria, two species Bacillus sk1 and Bacillus sk2 were found to enhance the biogas production to a maximum level. Gas analysis showed CH4 content of 63% in the case of food processing wastewater and around 67% with herbal pharmaceutical wastewater. Bacillus sk1 was found to be more suitable for both wastewater and biogas production and was found to be 46.4% in food processing wastewater and 43.3% in herbal pharmaceutical wastewater. Amendment of Bacillus sk2 in food processing wastewater produces 39.7% and 30.3% of biogas in herbal pharmaceutical wastewater was observed. Enzyme Bacillidine™ (P-COG-concentrate aqueous base) was also tried but results were not very encouraging. Comparative studies on both the wastewater have been discussed in detail in this article.",book:{id:"10980",title:"Biogas - Basics, Integrated Approaches, and Case Studies",coverURL:"https://cdn.intechopen.com/books/images_new/10980.jpg"},signatures:"Sharda Dhadse and Shanta Satyanarayan"},{id:"79776",title:"Biogas Production: Evaluation and Possible Applications",slug:"biogas-production-evaluation-and-possible-applications",totalDownloads:99,totalDimensionsCites:0,doi:"10.5772/intechopen.101544",abstract:"Biogas is an excellent example of renewable feedstock for energy production enabling closure of the carbon cycle by photosynthesis of the existing vegetation, without charging the atmosphere with excessive carbon dioxide. The present review contains traditional as well as new methods for the preparation of raw materials for biogas production. These methods are compared by the biogas yield and biogas content with the possible applications. Various fields of biogas utilization are discussed. They are listed from simple heating, electricity production by co-generation, fuel cell applications to catalytic conversions for light fuel production by the Fischer-Tropsch process. The aspects of carbon dioxide recycling reaching methane production are considered too.",book:{id:"10980",title:"Biogas - Basics, Integrated Approaches, and Case Studies",coverURL:"https://cdn.intechopen.com/books/images_new/10980.jpg"},signatures:"Venko Beschkov"},{id:"79715",title:"Case Studies in Biogas Production from Different Substrates",slug:"case-studies-in-biogas-production-from-different-substrates",totalDownloads:92,totalDimensionsCites:0,doi:"10.5772/intechopen.101622",abstract:"The present paper involves applicative research in the field of biogas production with the accent on small laboratory scale installations built for biogas production, preliminary testing of substrate for biogas production and combustion applications for biogas-like mixtures. The interconnected aspect of the presented material involves cumulative expertise in multidisciplinary fields of interest and continuous development of possibilities to determine the energetic potential of substrates subjected to biodegradable fermentation conversion for further applications. The research analyzed the combustion behavior of biogas with different methane/carbon dioxide ratio without and in the presence of specific catalysts. Also, laboratory analysis on biomass substrates for determining their physical and chemical potential for different applications was performed. The main conclusions are drawn revolve around the untapped potential of the different types of biomasses that are not commonly used in the production of renewable energy carriers, like biogas, and also the potential use of residual biomass in combustion processes for an enclosed life cycle from cradle to the grave. The study involving the use of catalysts in biogas combustion processes present possible solutions which can be developed and implemented for increasing the combustion quality by using relatively cost-effective materials for the production of catalytic materials.",book:{id:"10980",title:"Biogas - Basics, Integrated Approaches, and Case Studies",coverURL:"https://cdn.intechopen.com/books/images_new/10980.jpg"},signatures:"Adrian Eugen Cioabla and Francisc Popescu"}],onlineFirstChaptersTotal:4},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:105,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:null,scope:"
\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\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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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\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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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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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"April 24th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:0,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. 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. Her publications cover a wide range of scientific and technical research publications that include edited books, book chapters, refereed journals, refereed conference papers and reports for local, state and federal government clients. She has also produced podcasts for various organisations and participated in media interviews. She has received state, national and international funding worth over USD $25 million. Usha has been awarded the Quarterly Franklin Membership by London Journals Press (UK). Her biography has been included in the Marquis Who's Who in the World® 2018, 2016 (33rd Edition), along with approximately 55,000 of the most accomplished men and women from around the world, including luminaries as U.N. Secretary-General Ban Ki-moon. 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Buchholz and Erik J. Behringer",hash:"e373a3d1123dbd45fddf75d90e3e7c38",volumeInSeries:1,fullTitle:"Calcium and Signal Transduction",editors:[{id:"89438",title:"Dr.",name:"John N.",middleName:null,surname:"Buchholz",slug:"john-n.-buchholz",fullName:"John N. Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Plant Physiology",value:13,count:1},{group:"subseries",caption:"Human Physiology",value:12,count:2},{group:"subseries",caption:"Cell Physiology",value:11,count:8}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:1},{group:"publicationYear",caption:"2020",value:2020,count:4},{group:"publicationYear",caption:"2019",value:2019,count:5},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. 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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:[],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:"May 15th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:286,numberOfPublishedBooks:27,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:"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://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRqB9QAK/Profile_Picture_1626163237970",institutionString:null,institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/170125",hash:"",query:{},params:{id:"170125"},fullPath:"/profiles/170125",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)}()