Some recent findings on drug-induced liver toxicity.
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"6150",leadTitle:null,fullTitle:"Flight Physics - Models, Techniques and Technologies",title:"Flight Physics",subtitle:"Models, Techniques and Technologies",reviewType:"peer-reviewed",abstract:"The book focuses on the synthesis of the fundamental disciplines and practical applications involved in the investigation, description, and analysis of aircraft flight including applied aerodynamics, aircraft propulsion, flight performance, stability, and control. The book covers the aerodynamic models that describe the forces and moments on maneuvering aircraft and provides an overview of the concepts and methods used in flight dynamics. Computational methods are widely used by the practicing aerodynamicist, and the book covers computational fluid dynamics techniques used to improve understanding of the physical models that underlie computational methods.",isbn:"978-953-51-3808-2",printIsbn:"978-953-51-3807-5",pdfIsbn:"978-953-51-4047-4",doi:"10.5772/intechopen.68297",price:119,priceEur:129,priceUsd:155,slug:"flight-physics-models-techniques-and-technologies",numberOfPages:240,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"fa5828a4ee518adf719c68c1e533f3b7",bookSignature:"Konstantin Volkov",publishedDate:"February 14th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6150.jpg",numberOfDownloads:25986,numberOfWosCitations:16,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:32,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:61,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 14th 2017",dateEndSecondStepPublish:"April 4th 2017",dateEndThirdStepPublish:"July 20th 2017",dateEndFourthStepPublish:"September 29th 2017",dateEndFifthStepPublish:"December 20th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"118184",title:"Dr.",name:"Konstantin",middleName:null,surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov",profilePictureURL:"https://mts.intechopen.com/storage/users/118184/images/system/118184.jpeg",biography:"Dr. Volkov is a senior lecturer in Thermofluids at Kingston University (London, UK). He holds a Ph.D. in fluid mechanics. After completing his Ph.D., Dr. Volkov worked at the Baltic State Technical University (Russia), University of Central Lancashire (UK), University of Surrey (UK). His areas of expertise cover multidisciplinary areas: from design and optimization of energy systems to fundamental problems focused on modeling and simulation of turbulent multiphase flows. He is a Chartered Engineer and member of the Institute of Physics, Institution of Mechanical Engineers, and Combustion Institute in the UK. He is the author of more than 120 scientific papers and a member of the editorial board and the scientific committee of a number of journals and conferences.",institutionString:"Kingston University London",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"Kingston University",institutionURL:null,country:{name:"United Kingdom"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"683",title:"Aeronautics",slug:"aeronautics"}],chapters:[{id:"58784",title:"Learning from Nature: Unsteady Flow Physics in Bioinspired Flapping Flight",doi:"10.5772/intechopen.73091",slug:"learning-from-nature-unsteady-flow-physics-in-bioinspired-flapping-flight",totalDownloads:1987,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"There are few studies on wing flexibility and the associated aerodynamic performance of insect wings during free flight, which are potential candidates for developing bioinspired microaerial vehicles (MAVs). To this end, this chapter aims at understanding wing deformation and motions of insects through a combined experimental and computational approach. Two sets of techniques are currently being developed to make this integration possible: first, data acquisition through the use of high-speed photogrammetry and accurate data reconstruction to quantify the wing and body motions in free flight with great detail and second, direct numerical simulation (DNS) for force measurements and visualization of vortex structures. Unlike most previous studies that focus on the near-field vortex formation mechanisms of a single rigid flapping wing, this chapter presents freely flying insects with full-field vortex structures and associated unsteady aerodynamics at low Reynolds numbers. Our chapter is expected to lead to valuable insights into the underlying physics about flow mechanisms of low Reynolds number flight in nature, which will have great significance to flapping-wing MAV design and optimization research in the future.",signatures:"Haibo Dong, Ayodeji T. Bode-Oke and Chengyu Li",downloadPdfUrl:"/chapter/pdf-download/58784",previewPdfUrl:"/chapter/pdf-preview/58784",authors:[{id:"208608",title:"Dr.",name:"Haibo",surname:"Dong",slug:"haibo-dong",fullName:"Haibo Dong"},{id:"222158",title:"MSc.",name:"Ayodeji",surname:"Bode-Oke",slug:"ayodeji-bode-oke",fullName:"Ayodeji Bode-Oke"},{id:"222159",title:"Dr.",name:"Chengyu",surname:"Li",slug:"chengyu-li",fullName:"Chengyu Li"}],corrections:null},{id:"57483",title:"Helicopter Flight Physics",doi:"10.5772/intechopen.71516",slug:"helicopter-flight-physics",totalDownloads:8169,totalCrossrefCites:3,totalDimensionsCites:8,hasAltmetrics:1,abstract:"This chapter is dedicated to present the principles that constitute the fundamentals of helicopter flight physics, starting from the basics of the main rotor aerodynamics and of the component parts related to flight control. The chapter opens with a short history of helicopter development, taking the date of 13th November 1907 for a reference point; this is the date when the first helicopter flight occurred, having the French man, Paul Cornu, for a pilot. The main constructive solutions for helicopters are presented and the basic equations of fluid mechanics are applied on a helicopter model with one main rotor and tail rotor. Helicopter hovering, vertical flight, and forward flight are approached, too, one by one. Furthermore, the ground effect, autorotation, stability, and helicopter control are focused on. At the end of the chapter, the main factors that determine the helicopter performances are mentioned.",signatures:"Constantin Rotaru and Michael Todorov",downloadPdfUrl:"/chapter/pdf-download/57483",previewPdfUrl:"/chapter/pdf-preview/57483",authors:[{id:"206857",title:"Prof.",name:"Constantin",surname:"Rotaru",slug:"constantin-rotaru",fullName:"Constantin Rotaru"},{id:"209010",title:"Prof.",name:"Michael",surname:"Todorov",slug:"michael-todorov",fullName:"Michael Todorov"}],corrections:null},{id:"57517",title:"Flight Dynamic Modelling and Simulation of Large Flexible Aircraft",doi:"10.5772/intechopen.71050",slug:"flight-dynamic-modelling-and-simulation-of-large-flexible-aircraft",totalDownloads:2709,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:0,abstract:"The drive for aircraft efficiency and minimum environmental impact is requiring the aerospace industry to generate technologically innovative and highly integrated aircraft concepts. This has changed the approach towards conceptual design and highlighted the need for modular low fidelity aircraft simulation models that not only capture conventional flight dynamics but also provide insight into aeroservoelasticity and flight loads. The key aspects that drive the need for modularity are discussed alongside integration aspects related to coupling aerodynamic models, flight dynamic equations of motion and structural dynamic models. The details of developing such a simulation framework are presented and the utility of such a tool is illustrated through two test cases. The first case focuses on aircraft response to a gust that has a spanwise varying profile. The second investigates aircraft dynamics during control surface failure scenarios. The Cranfield Accelerated Aeroplane Loads Model (CA2LM) forms the basis of the presented discussion.",signatures:"Gaétan Dussart, Vilius Portapas, Alessandro Pontillo and Mudassir\nLone",downloadPdfUrl:"/chapter/pdf-download/57517",previewPdfUrl:"/chapter/pdf-preview/57517",authors:[{id:"206753",title:"Dr.",name:"Mudassir",surname:"Lone",slug:"mudassir-lone",fullName:"Mudassir Lone"},{id:"206955",title:"Mr.",name:"Vilius",surname:"Portapas",slug:"vilius-portapas",fullName:"Vilius Portapas"},{id:"220349",title:"Mr.",name:"Gaetan",surname:"Dussart",slug:"gaetan-dussart",fullName:"Gaetan Dussart"},{id:"220350",title:"Mr.",name:"Alessandro",surname:"Pontillo",slug:"alessandro-pontillo",fullName:"Alessandro Pontillo"}],corrections:null},{id:"56528",title:"Aerodynamic Characteristics and Longitudinal Stability of Tube Launched Tandem-Scheme UAV",doi:"10.5772/intechopen.70228",slug:"aerodynamic-characteristics-and-longitudinal-stability-of-tube-launched-tandem-scheme-uav",totalDownloads:1692,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Tube launched unmanned aerial vehicles (UAV) are often implemented with aerodynamic scheme with forward and rear wings (so-called tandem-scheme). Specificity of such UAV is that immediately after launch, they have a flight path in which wings are turned from position along the fuselage to flight position in which sweep angles are about zero. UAV aerodynamic characteristics for different wing rotation angles were researched by computational fluid dynamics (CFD) methods (Ansys 16 software). Quantitative results prove that UAV is unstable with wings rotation angles up to 60° because rear wings produce lift ahead of center of gravity. Therefore, low time of wings unfolding is required. For high angles of wings rotation (low sweep angles), UAV model is stable in a wide range of angles of attack. Local aerodynamic defects were found in the area of the rotation units of both wings. Longitudinal vortex along the left side of fuselage was observed, but it does not result in significant roll moment. Further research might include UAV dynamics modelling based on calculated aerodynamics characteristics or flight tests.",signatures:"Illia S. Kryvokhatko and Oleksandr M. Masko",downloadPdfUrl:"/chapter/pdf-download/56528",previewPdfUrl:"/chapter/pdf-preview/56528",authors:[{id:"207157",title:"Ph.D.",name:"Illia",surname:"Kryvokhatko",slug:"illia-kryvokhatko",fullName:"Illia Kryvokhatko"},{id:"208137",title:"Mr.",name:"Oleksandr",surname:"Masko",slug:"oleksandr-masko",fullName:"Oleksandr Masko"}],corrections:null},{id:"57229",title:"Airfoil Boundary Layer Optimization Toward Aerodynamic Efficiency of Wind Turbines",doi:"10.5772/intechopen.70895",slug:"airfoil-boundary-layer-optimization-toward-aerodynamic-efficiency-of-wind-turbines",totalDownloads:1475,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter describes the method of airfoil optimization considering boundary layer for aerodynamic efficiency increment. The advantages of laminar boundary layer expansion in airfoil of horizontal axis wind turbine (HAWT) blades are presented as well. The genetic algorithm (GA) optimization interfaced with the flow solver XFOIL was used with multi-objective function. The power performance of turbine with optimized airfoil was calculated by using blade element method (BEM) in software QBlade. The CFD simulation from OpenFOAM® with Spalart-Allmaras turbulence model showed the visualized airflow. The optimized airfoil shows enlarged laminar boundary layer region in all flow regime with a higher aerodynamic efficiency and the increased gliding ratio (GR). The power velocity and annual energy production (AEP) curves show the performance improvement of wind turbine with the optimized airfoil. The boundary layer thickness and skin-friction coefficient values support the decreased drag of the optimized airfoil. The smaller laminar separation bubbles and reduced stall regime of CFD simulations illustrate the desirable aerodynamics of the resulted airfoil.",signatures:"Youjin Kim, Ali Al-Abadi and Antonio Delgado",downloadPdfUrl:"/chapter/pdf-download/57229",previewPdfUrl:"/chapter/pdf-preview/57229",authors:[{id:"208318",title:"M.Sc.",name:"Youjin",surname:"Kim",slug:"youjin-kim",fullName:"Youjin Kim"},{id:"208320",title:"Dr.",name:"Ali",surname:"Al-Abadi",slug:"ali-al-abadi",fullName:"Ali Al-Abadi"},{id:"208321",title:"Prof.",name:"Antonio",surname:"Delgado",slug:"antonio-delgado",fullName:"Antonio Delgado"}],corrections:null},{id:"57091",title:"LES of Unsteady Aerodynamic Forces on a Long-Span Curved Roof",doi:"10.5772/intechopen.70880",slug:"les-of-unsteady-aerodynamic-forces-on-a-long-span-curved-roof",totalDownloads:1474,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The present paper discusses the unsteady aerodynamic forces on long-span curved roofs by using large eddy simulation (LES). The forced vibration test in a turbulent boundary layer is simulated. The models are force vibrated in the first anti-symmetric mode to investigate the influences of a roof’s vibration on the wind pressure and flow field around a vibrating roof. The characteristics of unsteady aerodynamic forces in a wider range of reduced frequency of vibration are also investigated. A comparison between the wind tunnel experiment and the LES indicates that the LES can be used effectively to evaluate the unsteady aerodynamic force.",signatures:"Wei Ding",downloadPdfUrl:"/chapter/pdf-download/57091",previewPdfUrl:"/chapter/pdf-preview/57091",authors:[{id:"214111",title:"Dr.",name:"Wei",surname:"Ding",slug:"wei-ding",fullName:"Wei Ding"}],corrections:null},{id:"57441",title:"Wake Topology and Aerodynamic Performance of Heaving Wings",doi:"10.5772/intechopen.71517",slug:"wake-topology-and-aerodynamic-performance-of-heaving-wings",totalDownloads:1372,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Simulating the three-dimensional flow features generated by heaving wings constitutes a great challenge due to the computational effort required to compute the complex three-dimensional flow produced as a function of the kinematics parameters, wing geometry, and Reynolds number. Hereafter, we study the wake topology generated by oscillating rigid wings and the validity of the Strouhal number as the fundamental parameters used to assess the aerodynamic performance of heaving wings. The unsteady laminar incompressible Navier-Stokes equations are solved on moving overlapping structured grids using a second-order accurate in space and time finite-difference numerical method. The numerical simulations are performed at a Reynolds number of Re = 250 and at different values of Strouhal number and heaving frequency.",signatures:"Joel E. Guerrero",downloadPdfUrl:"/chapter/pdf-download/57441",previewPdfUrl:"/chapter/pdf-preview/57441",authors:[{id:"61098",title:"Dr.",name:"Joel",surname:"Guerrero",slug:"joel-guerrero",fullName:"Joel Guerrero"}],corrections:null},{id:"56629",title:"Aeroelastic Stability of Turboprop Aircraft: Whirl Flutter",doi:"10.5772/intechopen.70171",slug:"aeroelastic-stability-of-turboprop-aircraft-whirl-flutter",totalDownloads:1890,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter is focused on a specific type of dynamic aeroelastic stability phenomenon—whirl flutter. Whirl flutter is caused by the effect of rotating parts of a turboprop power plant (propeller and, gas turbine engine rotor). The chapter presents fundamental facts regarding the whirl flutter phenomenon, including a historical overview and information regarding the occurrence of whirl flutter in aerospace practice. After that, the physical principles of whirl flutter are explained using a simple mechanical system with two degrees of freedom. Next, an analytical solution to determine the aerodynamic forces caused by the gyroscopic motion on each of the propeller blades is provided and the influences of the main structural parameters on the whirl flutter stability are discussed. The second, practical part is focused on the experimental research of the whirl flutter phenomenon and on the certification-related issues. The methodology of certification according to the FAR/CS 23 regulation standard is demonstrated on the example of a twin wing mounted tractor engine commuter aircraft.",signatures:"Jiří Čečrdle",downloadPdfUrl:"/chapter/pdf-download/56629",previewPdfUrl:"/chapter/pdf-preview/56629",authors:[{id:"207285",title:"Dr.",name:"Jiri",surname:"Cecrdle",slug:"jiri-cecrdle",fullName:"Jiri Cecrdle"}],corrections:null},{id:"58577",title:"Goal- and Object-Oriented Models of the Aerodynamic Coefficients",doi:"10.5772/intechopen.71419",slug:"goal-and-object-oriented-models-of-the-aerodynamic-coefficients",totalDownloads:1922,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nowadays, aeronautics discovers new ways of flights near the critical regimes, unconventional aircraft forms, utilizing the micro–electro-mechanical technologies in flow and aircraft control, adaptive and morphing structures, using the structures and controls based on the biological principles, developing highly flexible structures, etc. Before deployment, these new technologies and solutions must be evaluated, tested in wide aerodynamic, flight dynamic simulations that require improved and new type of aerodynamic coefficient models. The chapter overviews the applicable models of the aerodynamic coefficients, introduces some new models and demonstrates how the different models can be applied in different goal- and object-oriented solutions. The following will be shortly explained: (i) how the aerodynamic forces and moments are generating, (ii) how the linear, nonlinear, steady, and nonsteady aerodynamic coefficient structures and forms might be modeled, and (iii) how to harmonize the model with the goal and object of investigations.",signatures:"Jozsef Rohacs",downloadPdfUrl:"/chapter/pdf-download/58577",previewPdfUrl:"/chapter/pdf-preview/58577",authors:[{id:"208115",title:"Prof.",name:"Jozsef",surname:"Rohacs",slug:"jozsef-rohacs",fullName:"Jozsef Rohacs"}],corrections:null},{id:"56231",title:"The Effects of Storage on Turbine Engine Fuels",doi:"10.5772/intechopen.69897",slug:"the-effects-of-storage-on-turbine-engine-fuels",totalDownloads:1653,totalCrossrefCites:2,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Modern aviation requires reliable and safe sources of fuel which means fuel is frequently stored for extended periods. In addition, as fuel is used, new fuel is added which is not always compatible with the fuel in the tank. The incompatibility and long-term storage leads to a number of problems that will be addressed in this chapter. Some of the possible changes over time include formation of biofilms, deposit formation, water incorporation and additive depletion. The chemistry and biochemistry of each of these areas will be discussed along with how they might be prevented. New areas of research on low temperature oxidation of trace fuel components and the prevention of bacterial growth will be presented. Other problems are related to the reaction of trace components in the fuel which can lead to oxidation and deposit formation. Trace components also vary based on fuel source and lead to problems in compatibility of different fuels. In addition some of the reactions of fuel additives will be discussed.",signatures:"David W. Johnson",downloadPdfUrl:"/chapter/pdf-download/56231",previewPdfUrl:"/chapter/pdf-preview/56231",authors:[{id:"178441",title:"Dr.",name:"David",surname:"Johnson",slug:"david-johnson",fullName:"David Johnson"}],corrections:null},{id:"57125",title:"12-Pulse Active Rectifier for More Electric Aircraft Applications",doi:"10.5772/intechopen.70882",slug:"12-pulse-active-rectifier-for-more-electric-aircraft-applications",totalDownloads:1645,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The Aircraft industry is moving very quickly towards what it known as More Electric Aircraft (MEA). In a modern aircraft power technology system instead of using a fixed 400 Hz supply, a variable frequency supply (360 to 800 Hz) is used, which is dependent on the aircraft speed. In MEA electrical energy feeds the aircraft subsystems such as the flight control actuation, environmental control system, and utility function instead of mechanical, hydraulic and pneumatic energy. Although the new technology of MEA goes towards variable frequency supply, one of the essential parts of the power distribution systems require DC power sources to feed different DC loads, and a portion of load may require a fixed 400 Hz supply. This chapter simulation model of 12-pulse active rectifier for More Electric Aircraft applications.",signatures:"Mohamad Taha",downloadPdfUrl:"/chapter/pdf-download/57125",previewPdfUrl:"/chapter/pdf-preview/57125",authors:[{id:"207348",title:"Ph.D.",name:"Mohamad",surname:"Taha",slug:"mohamad-taha",fullName:"Mohamad Taha"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5801",title:"Turbulence Modelling Approaches",subtitle:"Current State, Development Prospects, Applications",isOpenForSubmission:!1,hash:"806f8c12f61aee260f439635c576baf8",slug:"turbulence-modelling-approaches-current-state-development-prospects-applications",bookSignature:"Konstantin Volkov",coverURL:"https://cdn.intechopen.com/books/images_new/5801.jpg",editedByType:"Edited by",editors:[{id:"118184",title:"Dr.",name:"Konstantin",surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6631",title:"Heat Transfer",subtitle:"Models, Methods and Applications",isOpenForSubmission:!1,hash:"18bd3ce3b071e4f0cb9d4f58ac33c2fa",slug:"heat-transfer-models-methods-and-applications",bookSignature:"Konstantin Volkov",coverURL:"https://cdn.intechopen.com/books/images_new/6631.jpg",editedByType:"Edited by",editors:[{id:"118184",title:"Dr.",name:"Konstantin",surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5447",title:"Aerosols",subtitle:"Science and Case Studies",isOpenForSubmission:!1,hash:"33d07546861d6fdb403e55c5f5e460b5",slug:"aerosols-science-and-case-studies",bookSignature:"Konstantin Volkov",coverURL:"https://cdn.intechopen.com/books/images_new/5447.jpg",editedByType:"Edited by",editors:[{id:"118184",title:"Dr.",name:"Konstantin",surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2202",title:"Efficiency, Performance and Robustness of Gas Turbines",subtitle:null,isOpenForSubmission:!1,hash:"12d1e92c0759e7c24b281e557e6d357e",slug:"efficiency-performance-and-robustness-of-gas-turbines",bookSignature:"Konstantin Volkov",coverURL:"https://cdn.intechopen.com/books/images_new/2202.jpg",editedByType:"Edited by",editors:[{id:"118184",title:"Dr.",name:"Konstantin",surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7678",title:"Computational Models in Engineering",subtitle:null,isOpenForSubmission:!1,hash:"26e40818fe70b418deffb63c33d47d6d",slug:"computational-models-in-engineering",bookSignature:"Konstantin Volkov",coverURL:"https://cdn.intechopen.com/books/images_new/7678.jpg",editedByType:"Edited by",editors:[{id:"118184",title:"Dr.",name:"Konstantin",surname:"Volkov",slug:"konstantin-volkov",fullName:"Konstantin Volkov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1992",title:"Recent Advances in Aircraft Technology",subtitle:null,isOpenForSubmission:!1,hash:"67fa903d68a094013f66d01b38882107",slug:"recent-advances-in-aircraft-technology",bookSignature:"Ramesh K. 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Chlamydia’s life cycle depends on the establishment of its intracellular niche called the inclusion. In addition to secreting soluble effector proteins into the host cytoplasm, Chlamydia inserts proteins called ‘Incs’ (for inclusion membrane proteins) on the cytosolic face of the inclusion membrane. This localization is ideal for Incs to interact with host proteins and enables Chlamydia to hijack the host cell to promote bacterial replication and inclusion growth.
\r\n\tThe recent expansion of the genetic toolbox for Chlamydia, including the creation of knockout and mutant Chlamydia strains, has enabled a new wave of discoveries regarding the role of chlamydial effectors in manipulating the host cell. This book intends to provide an updated overview on how Chlamydia targets its host cell at the molecular level, to support its intracellular lifestyle and pathogenicity.
The liver is a reddish-brown multifunctional organ that lies beneath the diaphragm in the abdomen’s right upper quadrant and overlies the gallbladder. It performs varieties of biological and metabolic functions, but one significant of them is xenobiotic metabolism/detoxification, in which exogeneous lipophilic xenobiotics (drugs and herbal supplements) are converted to hydrophilic compounds via biochemical processes catalysed by cytochrome P450 enzyme systems. The metabolic products obtained are then actively transported by hepatocyte transporter proteins into the plasma or bile for excretion by the kidney or gastrointestinal tract [1, 2]. However, sometimes, these xenobiotics produce reactive (or toxic) metabolites or electrophiles that bind covalently to hepatocytes, resulting to changes in protein conformation, DNA mutation or induce lipid peroxidation respectively, thereby leading to hypersensitivity reaction or liver necrosis. This is known as drug-induced injury (or hepatogenous poisoning, toxic-liver disease, chemical-driven injury). This situation often leads to hospitalisation and/or liver transplantation, depending on the magnitude of the liver injury [3]. There are over 1000 hepatotoxic agents available, however, drugs account for about 20–40% of the cases associated with liver failure/injury [4]. Notably, there are two categories of drug-induced liver injury (DILI) namely: intrinsic (or pharmacological) and idiosyncratic DILI respectively. Intrinsic DILI, refer to a form of liver toxicity caused by a drug in a projectable and dose-dependent manner (e.g. acetaminophen). In this circumstance, liver injury sets-in after an elevated concentration of the drug is attained. On the other hand, idiosyncratic DILI (which occurs relatively), is a non-projectable, non-dose-dependent response to drug and differs in the period of latency (e.g. Trovafloxacin and Troglitazone). It is worthy of note, that approximately 75–80% cases of idiosyncratic reactions end up in death or liver transplantation and as such precautionary measures should be observed in the use of drugs [5, 6]. The dreadful incidences of DILI can be checked by creating drug pharmacovigilant awareness, in which cases of adverse side effects after drug administration should be withdrawn or stopped abruptly to avoid further harm to the body. Besides the harmful effects of acetaminophen (APAP) overdose that has been well documented, studies provide us with wide spectrum of drug inducible agents like, Atypical antipsychotic (AAP), D-galactosamine ((D-GalN)), N-nitrosodiethylamine (NDEA), thioacetamide, Anti- Tuberculosis Drugs (ATD), Anti- Retroviral Drugs (ARDs), Antimalarial Drugs, NSAIDs (Non-Steroidal Anti-inflammatory Drugs), azacytidine, to mention but a few [3]. Therefore, this chapter focuses on discussing the mechanism of action and toxicological implications of drug-induced hepatotoxicity of the aforementioned drugs to human health.
As much as there are several analgesic drugs consumed by man as pain killer agents, paracetamol seems to be the commonly used and contains acetaminophen - the active ingredient, which has been shown to be well-tolerated in prescribed dose but in the event of overdose, liver damage occurs. This is because, acetaminophen metabolism catalysed by cytochrome P450 enzymes in the liver produces N-acetyl-p-benzoquineimine (NAPBQI) – a highly reactive (toxic) intermediate metabolite [7]. In the normal sense, this metabolite gets detoxified by glutathione conjugation in phase II reaction. Nevertheless, during acetaminophen’s overdose, a high concentration of the toxic metabolite is produced, and thus overwhelms the detoxification process, leading to hepatocellular necrosis. Reports have shown that liver injury caused by this metabolite can be reduced by the administration of acetylcysteine - a precursor of glutathione, by scavenging the toxic metabolite from the system [8].
Antipsychotic drugs are detoxified via the cytochrome-P450 system in the phase 1 and phase 11 reactions. In its metabolism, the enzyme known as mono-oxygenase converts the drugs into less toxic metabolites through hydrolysis, oxido-reduction and dealkylation processes. However, sometimes, the phase products may display high level of toxicity, hence, phase 11 reaction becomes inevitable. The phase II reaction mainly involves a biochemical process called conjugation reaction which makes use of glucuronic acid, sulphate, acetate, amino acids and glutathione to convert phase 1 products to a more body friendly form and subsequently for excretion. Many antipsychotic drugs beside antisulpride, risperidone, and paliperidone are catabolised primarily via the CYP2D6 and CYP3A4 systems while clozapine and olanzapine use the CYP1A2 system for its drug metabolism. Experimentation shows that antipsychotic drugs potentially damages liver cells through three mechanisms (i) By increasing bile secretion and excretion leading to cholestasis which relates to immune-mediated hypersensitivity (a typical mechanism of chlorpromazine) (ii) Accumulation of toxic or reactive intermediates (or metabolites) that eventually attacks liver cells (iii) By Increasing the risk of metabolic idiosyncratic syndrome leading to high risk of non-alcoholic fatty liver diseases which is typical of olanzapine and clozapine. Indiscriminate consumption of antipsychotic drugs presents some clinical manifestations (or side effects) and this can be encapsulated into four categories namely:
Hepatocellular disorder in which hepatic bio-indicators such as aminotransferases, ALP (alkaline phosphatase) and γ-glutamyl transferase (GGT) activities as well as the levels of albumin and total bilirubin are found to increase significantly in the serum.
Gastrointestinal disorders ranging from fatigue, appetite loss, excruciating pains in the liver region and epigastric discomfort
Cholestasis and steatosis like coloured stool
Immunological or hypersensitivity disorders including eosinophilia, anthralgia, rashes, acute liver failure (ALF), auto-immune diseases among others [9, 10].
Galactosamine, one of the commonly used experimental model for hepatotoxicity study in animals, is an amino sugar derivative found majorly as glycoprotein in living cells. In addition, it forms a component of some hormonal systems like Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) respectively. Biochemical investigation into the hepatotoxic effect of D-galactosamine revealed that it induces liver damage by interfering with the products of galactosamine metabolism via Leloir pathway of galactose metabolism. Firstly, galactosamine is transformed to galactosamine-1-phosphate (Gal-1-P) catalysed by galactokinase while the second phase involves the conversion of galactosaminr-1-phosphate to Uridine diphosphate-galactosamine (UDPG) by galactose uridyltransferase. At low substrate specificity, UDPG inhibits the activity of UDP-galactose-41-epimerase, thereby causing a significant accumulation in the hepatic cells and others like UDP-N-acetylglucosamine and UDP-N-acetyl galactosamine with corresponding depletions of uridine triphosphate (UTP), uridine diphosphate (UDP), uridine monophosphate (UMP) as well as uridine diphosphate-glucose (UDP-Glu) and uridine diphosphate-galactose (UDP-Gal), respectively. The outcome of this process then causes the loss of intracellular Ca2+ homeostasis, inhibits hepatocyte ATP metabolism and hepatitis which invariably affects cell membrane, inhibits mRNA, protein and nucleic acid biosynthesis. These effects increase protein gene (p53) expression and decreases Bcl-2 mRNA levels in the liver. It is noteworthy, that the hepatoxic action of galactosamine is effective when in combination with lipopolysaccharide (GalN/LPS). This combination induces the Kupffer cells to secrete pro-inflammatory mediators that leads to liver cell apoptosis [11]. Experimental design that involves the treatment of animals with D-GalN alters albumin mRNA, glucose-6-phosphatase, histone-3 mRNA, alpha fetoprotein mRNA (αFP mRNA), gamma-glutamyl transpeptidase (GGTP) expressions. Furthermore, it also upregulates expression of tumour nuclear factor (TNF-α mRNA) that has activity of necrotic factor-kappa B (NF- κB10) and alter membrane cofactor protein (MCP-1) level in serum. Also, serum ALT and AST activities increases substantially [12, 13].
N-nitrosodiethylamine (NDEA), is a member of the nitrosamine family and are found in various foodstuff and underground water with high nitrate level. It has hepatocarcinogenic property by yielding adducts of DNA carcinogen in the liver and induces hepatic cancer. NDEA’s mechanism of hepatic damage is such that after treatment, it stimulates increase in liver mitochondrial transitional permeability (MTP), leading to increase hydrogen peroxide (H2O2) production, resulting in peroxidative stress [14, 15]. Alternatively, cytochrome P450 activates NDEA, generating reactive electrophilic molecules capable of increasing oxidative stress and liver cytotoxicity and carcinogenicity [16].
Thioacetamide (TAA), is a white crystalline, organosulfur compound with high affinity for water and alcohol. It is chemically designated as C2H5NS and generally classified as class 2B human carcinogenic agent. NDEA exhibits wide range of relevance such as serve as sulphide source in the synthesis of compounds (organic and inorganic), controls the deterioration of orange fruits (fungicidal role), precipitates cadmium sulphide from acidic solutions, drug development, pesticide production, serve as cross-linking agent but to mention a few. However, scientific reports documented that long-term oral consumption of TAA causes liver cell adenomas, cholangiomas and hepatocarcinomas as well as affects protein, nuclei acid synthesis and GGTP activity. The bio-transformation of TAA via oxidative bioactivation in the liver microsomes catalysed by flavin-containing mono-oxygenases (FMOs) and cytochrome P450 systems produce two toxic metabolites. Firstly, TAA is catalysed by thioacetamide-S-oxygenase to form a reactive intermediate, thioacetamide-S-oxide (TAASO) adduct through oxidation process, which then induces hepatocytic oxidative stress, resulting to increase in nucleoli and Ca2+ concentrations as well as inhibit mitochondrial activity, thereby leading to hepatotoxicity with a resultant effect of centrilobular necrosis. However, the action of CYP2E1 inhibitors (such as 4-methylpyrazole and diallyl sulphide) and TAA, block TAASO toxicity in a relative and absolute manner respectively. The second phase of metabolism involves the conversion of TAASO to thioacetamide-S-S-dioxide (TAASO2 - a reactive species) by the action of thioacetamide-S-oxide-S-oxygenase and then covalently binds with protein and nucleic acid causing hepatotoxicity with consequential effect of liver damage/injury [17, 18]. The characteristic validation of the hepatotoxic effect of TAA includes decrease in microRNA gene expression (miR-122, miR-192 and miR-194) and increase in AST and ALT activities, mitochondrial membrane protein gene expression (MMP-9 and MMP-2) as well as myeloperoxidase, interleukin-10 (IL-10) and tumour nuclear factor (TNFα) respectively [19, 20, 21].
This is a fluorine derivative compound with carcinogenic tenacity. Its incorporation in diet and subsequent administration induces increased incidences of liver and urinary bladder carcinomas in animal model. Acetylaminofluorene, a by-product of diethyl nitrosamine (DEN) initiates carcinogenesis by increasing reactive oxygen species (ROS) production and facilitate hyperproliferation [22]. Acetylaminofluorene metabolism by cytochrome P450 produces metabolites like 2-aminofluorene (AF), 2-glycoloylaminofluorene (2-GAF), N-hydroxy-2-acetylaminofluorene (NH-2-AAF), 2-acetylaminofluoren-3-,-7-,-9-ol (3-, 7-, 9-hydroxy-AAF) and 2-acetylaminofluoren-9-one (AAF-9-one) respectively and exhibits different toxicity pathway. For instance, N-hydroxy-2-acetylaminofluorene and AAF binds covalently at Carbon - 8th positions in guanine; causing single strand breaks in DNA with resultant effect of severe apoptosis. Sometimes, AAF exposure increases expression of genes implicated in p53-signalling pathway, mRNA genes [encode mitochondria drug resistance proteins (Mdr1b, Mrp1 and Mrp3)] and microRNA genes respectively, thereby resulting in apoptosis [23, 24, 25]. Studies showed that at small dose of 2-AAF for long (2.24 or 22.4 mg/kg, 3 times/week for 31 days) or high dose (448 mg/kg BW, i.g., 5 days/week for 8 weeks) produces maximum hepatocellular carcinogenesis through AAF- DNA adducts [26, 27]. Interestingly, lower dose of 2-AAF (50 mg/kg BW, i.p.) was reported to increase lipid peroxidation, deplete GSH level while the activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT), and glutathione-S-transferase (GST) were significantly reduced [28].
Anti-tubercular drugs are the most auspicious prescription medication used for the treatment of cases of tuberculosis - an infectious disease with high mortality rate [29]. However, long- term administration of anti-tubercular drugs like rifampicin (RIF), isoniazid (INH) and pyrazinamide (PZA) (first line anti-tubercular drugs), significantly increase hepatotoxicity and induces liver injury in mammals [30]. The mechanism that precipitates anti-tubercular drug’s liver damage maybe unclear, nevertheless, studies show significant increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activities. Furthermore, lipid peroxidation, intracellular calcium (Ca2+) level and CYP4502EI activity also increases while GSH level, GPx and catalase activities decreases [31]. Recently, research shows that acetylators generate high level of acetylated drug which undergo further metabolism to yield other toxic intermediates which causes liver disruption, for instance, Isoniazid acetylation by N-acetyltransferase (NTA2) enzyme produces mono-acetyl hydrazine (MAH) that increases liver toxicity [32]. Notably, polymorphism at gene loci of NTA2, CYP2E1 and GST (detoxifying enzymes) modulate the activities of these enzymes and hence increases the risk of hepatotoxicity [33]. Studies have shown some administrable dose regimen of anti-tubercular drugs that can be used for biochemical evaluation, for example, intraperitoneal administration of 50 mg/kg BW of isoniazid, 100 mg/kg BW of rifampicin and intragastric administration of 350 mg/kg BW of pyrazinamide respectively. Also, when they are in combined form such as INH and RIF as well as INH, RIF and PZA induces hepatotoxicity. This observation was in agreement with previous work as reported by [34] that daily oral administration of isoniazid (15 mg/kg BW), rifampicin (20 mg/kg BW) and pyrazinamide (35 mg/kg BW) in combined form for 45 days, increases malondialdehyde level (MDA).
The therapeutic action of highly active antiretroviral drugs (HAART) like Protease inhibitors (PI), non-Nucleoside reverse transcriptase inhibitors (nNRTI) and Nucleoside/Nucleotide reverse transcriptase inhibitors (NRTI) used in the management of human immunodeficiency virus (HIV) undergo various pathways, nonetheless, their adverse effects are targeted/localised at the hepatic cells [35, 36]. Take for example, all anti-retroviral therapy-native (ART-naïve) like atazanavir or ritonavir and NRTIs (such as zidovudine or didanosine) alongside N-Apostolova Efavirenz (nNRTI) causes hepatic mitochondrial dysfunction and acute mitotoxic effect and oxidative stress respectively [37, 38]. Furthermore, administration of 50 μM of Efavirenz (EFV) can activate the activities of caspase-3 and caspase −9, trigger apoptotic mitochondrial intrinsic pathway and directly inhibit mitochondrial complex 1 subunit (MC1s) expression [39, 40]. The therapeutic efficacy of antiretroviral drugs is seen when used in combinations such as nNRTI and NRTIs but reports have documented that this combination produces deleterious effects on the mitochondria and also cause hepatic steatosis [41]. Another typical mechanism of action of some antiretroviral drug like stavudine (NRTI) is its ability to arrest cell cycle in growth phase (G1 phase) through upregulation of cyclic-dependent kinase inhibitor (CDKN2A) as well as p21 genes and inhibiting mitochondrial DNA replication [42].
Amodiaquine (an anti-malarial drug) hepatotoxic effect is achieved in humans when it is being oxidised by liver microsomes and peroxidases, produces iminoquinone, (a reactive metabolite) which binds to proteins irreversibly, causing direct liver toxicity by disrupting the hepatocyte function [43].
This class of drugs act mainly by hepatocellular or mixed reactions and rarely by cholestatic reaction. The Niacin and Statin are the commonly used drugs in the treatment of hyperlipidemic conditions, however, they have potential to induce liver injury. Studies revealed that the administration of Lovastatin and Simvastatin in animal model (rabbits or Guinea pig) resulted in hepatocellular necrosis while Atorvastatin produced a mixed pattern of liver injury. It is noteworthy, that Simvastatin in combination with other drugs like flutamide, troglitazone and diltiazem gives a more pronounced hepatic effect and this has been attributed to the drug–drug interaction mechanism [1].
The liver damaging effects of NSAIDs like acetylsalicylic acid ranges from elevated ALT, AST and ALP activities to acute cytolytic, cholestatic or mixed hepatitis as well as increases in bilirubin and prothrombin time. The mechanistic action of NSAID-induced hepatotoxicity is unclear but both intrinsic (Aspirin and phenylbutazone) and idiosyncratic (Ibuprofen, sulindac, phenylbutazone, piroxicam, diclofenac and indomethacin) reactions have been documented [44]. Suggestively, hypersensitivity and metabolic aberrations are thought to responsible for liver injury. Unlike hypersensitivity reactions that are characterised by considerable anti-nuclear factor or anti-smooth muscle antibody titres as well as lymphadenopathy and eosinophilia, metabolic aberrations are caused by genetic polymorphisms, altering susceptibility to variety of drugs [45]. Diclofenac hepatotoxicity in humans and rats, for example, is linked to mitochondrial ATP synthesis impairment and the production of N-5-dihydroxydiclofenac (active metabolites), which causes cytotoxicity. Also, diclofenac-induced liver injury results in mitochondrial transition permeability (MTP), causing ROS formation, protein thiols production, mitochondrial swelling and oxidation of NADP+ (Nicotinamide adenine dinucleotide phosphate) respectively [45].
This anti-hypertensive drug called methyl dopa metabolises in the liver by Cytochrome P450, however, the oxidative reaction of methyl dopa by CYP450 produces superoxide anions (free radicals) to a reactive quinone or semi-quinone that binds tightly to the hepatic cells causing liver injury such as acute/chronic hepatitis and cholestasis with clinical evidence of elevated activities of ALT, AST and ALP respectively in the blood system [1].
Azacytidine (or Azacitidine), is a pyrimidine nucleoside analogue of cytidine which is metabolised to a triphosphate molecule in the intracellular domain and then introduced into the RNA and DNA molecule firmly held together covalently by DNA methyltransferase 1(DNMT 1) - an enzyme that adds methyl to DNA molecule at the carbon 5 position of cytosine. Azacitidine has an anticancer effect but at low doses, it inhibits DNA methylation resulting in its deactivation leading to DNA hypomethylation shortly after cell division in the absence of DNMT1. The antineoplastic activity of this drug comes from its hypomethylation, leading to tumour suppressor gene (TSG) reactivation which is rapidly lost in myelodysplastic syndrome (MDS) – a disorder associated with clonal haematopoietic stem cell, caused mainly due to ineffective cellular maturation with side effects as peripheral blood cytopenia and abnormalities in functional blood cell. The cytotoxic effect of azacytidine is achieved when the product of its phosphorylation is incorporated into RNA molecule, thereby leading to an elevated level of CDKN2B - a gene that encodes the protein p15 (a cell growth inhibitor responsible for myeloid differentiation as well as tumour suppression) in their bone marrow [46, 47].
Administration of tacrine (a reversible cholinesterase inhibitor) in the treatment of Alzheimer disease, gives rise to an elevated ALT activity in the bloodstream, inferring that there is disruption in the integrity of the hepatocytes. Tacrine’s mechanism of liver toxicity may be probably due to the inhibition of cholinesterase activity, resulting in the stimulation of cholinergic coeliac ganglion sensory (or afferent) sympathetic pathway, in which blood constricts, leading to impaired perfusion of the sinusoids and reperfusion injury-mediated by ROS [1].
Despite the basic biochemical indicators discussed above that are associated with drug-induced hepatotoxicity, recent studies have further identified other indicators and these are represented in Table 1 as shown below:
Drug-induced hepatotoxicity | Biomarkers of Liver toxicity | References |
---|---|---|
Acetaminophen (APAP) | Upregulation of mRNA expression of IL-10, IL-36, HO-1, TNFα, MT 1 and 2 and MMP 12 genes. | [48] |
D-Galactosamine | Increase in the expressions of NLRP3, NF-kBp65, IL-6, IL-1β and TNFα genes. | [49] |
N-nitrosodiethylamine (NDEA) | Increase MDA level and decrease SOD, CAT, GST, GR, GPx activity. | [50] |
Thioacetamide (TAA) | Increase in Anti-PLT Ig level, Increase in the expression of TNFα, HMGB-1 and IL-6 genes. Increase in AST and ALT activity. | [51] |
2-Acetylaminofluorene (2-AAF) | Overexpression of iNOS, COX-2, NF-KB, PCNA genes. Increase in xanthine oxidase (XO) activity. Decrease in the activity of SOD, CAT, GST, GR and GPx. Increase in AST and ALT activity. High density of mast cell infiltration. | [52] |
Anti-Tuberculosis drugs | Over-expression of NAT2, CYP2E1, ABCB1 genes. Increase in NAD and Bilirubin levels and decrease in HAT activity. Decrease in GST, SOD, CAT activity. | [53] |
Anti-retroviral drugs | Increase in ABCB1 gene expression (that is c3435C > T of ABCB1) and CYPs genes (CYP2B6, CYP3A4 and CYP3A5). Increase in IL-1RN, IL-1β, IL-10, HLA-B and C and HLA-DRB1 genes. ALP activity and Total bilirubin (TBil) level increases. | [54, 55] |
Anti-hyperlipidemic drugs | Increase in the expression of HLA-DRB1 and SREBP2 genes while CK and HMG-CoA reductase activities increases. | [56] |
Some recent findings on drug-induced liver toxicity.
Drugs primarily serve as therapeutic agents in the treatment and management of various diseases, but over dependent or illicit consumption of drugs, results in hepatotoxicity which confers a detrimental effect on the liver’s architecture and functions respectively. Our findings showed that drug-induced hepatotoxicity can cause liver inflammation (associated with excruciating pains), liver transplantation (economically burdensome) as well as death. As a result of these frightening effects outlined above, we hereby conclude that doctor’s prescription guideline should be adhered to strictly, indiscriminate use of illicit drugs should be discouraged while regulatory bodies and law enforcement agencies should be empowered to prosecute drug offenders promptly.
The expertise of Professor Iheanacho Kizito, Department of Biochemistry, Federal University of Technology, Owerri is well appreciated.
The authors declare no conflict of interest in this work.
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pH, Fibre Degradation, and Microbiota According to the Diet",slug:"use-of-yeast-probiotics-in-ruminants-effects-and-mechanisms-of-action-on-rumen-ph-fibre-degradation-",totalDownloads:7902,totalCrossrefCites:17,totalDimensionsCites:38,abstract:null,book:{id:"2991",slug:"probiotic-in-animals",title:"Probiotic in Animals",fullTitle:"Probiotic in Animals"},signatures:"Frédérique Chaucheyras-Durand, Eric Chevaux, Cécile Martin and Evelyne Forano",authors:[{id:"151065",title:"Dr.",name:"Frederique",middleName:null,surname:"Chaucheyras-Durand",slug:"frederique-chaucheyras-durand",fullName:"Frederique Chaucheyras-Durand"},{id:"151068",title:"Mr.",name:"Eric",middleName:null,surname:"Chevaux",slug:"eric-chevaux",fullName:"Eric Chevaux"},{id:"151069",title:"Dr.",name:"Evelyne",middleName:null,surname:"Forano",slug:"evelyne-forano",fullName:"Evelyne Forano"},{id:"160177",title:"Dr.",name:"Cécile",middleName:null,surname:"Martin",slug:"cecile-martin",fullName:"Cécile Martin"}]},{id:"28679",doi:"10.5772/32100",title:"Values of Blood Variables in Calves",slug:"values-of-blood-variables-in-calves",totalDownloads:9601,totalCrossrefCites:16,totalDimensionsCites:36,abstract:null,book:{id:"1667",slug:"a-bird-s-eye-view-of-veterinary-medicine",title:"A Bird's-Eye View of Veterinary Medicine",fullTitle:"A Bird's-Eye View of Veterinary Medicine"},signatures:"Martina Klinkon and Jožica Ježek",authors:[{id:"90171",title:"Prof.",name:"Martina",middleName:null,surname:"Klinkon",slug:"martina-klinkon",fullName:"Martina Klinkon"}]},{id:"16107",doi:"10.5772/16563",title:"Effect of Cryopreservation on Sperm Quality and Fertility",slug:"effect-of-cryopreservation-on-sperm-quality-and-fertility",totalDownloads:15471,totalCrossrefCites:10,totalDimensionsCites:35,abstract:null,book:{id:"185",slug:"artificial-insemination-in-farm-animals",title:"Artificial Insemination in Farm Animals",fullTitle:"Artificial Insemination in Farm Animals"},signatures:"Alemayehu Lemma",authors:[{id:"25594",title:"Dr.",name:"Alemayehu",middleName:null,surname:"Lemma",slug:"alemayehu-lemma",fullName:"Alemayehu Lemma"}]},{id:"57645",doi:"10.5772/intechopen.71780",title:"Antibiotics in Chilean Aquaculture: A Review",slug:"antibiotics-in-chilean-aquaculture-a-review",totalDownloads:1931,totalCrossrefCites:17,totalDimensionsCites:29,abstract:"Aquaculture in Chile has been practiced since the 1920s; however, it was not until the 1990s that aquaculture became an important sector here. Important species in Chilean aquaculture include salmonids, algae, mollusks, and turbot. Salmonids are the dominant species in Chilean aquaculture for both harvest volume and export value, their production reaching greater than 800-thousand tons in 2015. However, this growth has been accompanied by an increase in disease presence, requiring greater drug use to control. This increase in drug use is an environmental and public health concern for the authorities, the salmon industry itself, and the destination markets. In this chapter, we review the literature on drug use, antibiotic resistance, regulatory framework, and alternatives, with focus on Chile.",book:{id:"6179",slug:"antibiotic-use-in-animals",title:"Antibiotic Use in Animals",fullTitle:"Antibiotic Use in Animals"},signatures:"Ivonne Lozano, Nelson F. Díaz, Susana Muñoz and Carlos Riquelme",authors:[{id:"208847",title:"Dr.",name:"Ivonne",middleName:null,surname:"Lozano",slug:"ivonne-lozano",fullName:"Ivonne Lozano"},{id:"208895",title:"Dr.",name:"Nelson F.",middleName:null,surname:"Díaz",slug:"nelson-f.-diaz",fullName:"Nelson F. Díaz"},{id:"208897",title:"Dr.",name:"Carlos",middleName:null,surname:"Riquelme",slug:"carlos-riquelme",fullName:"Carlos Riquelme"},{id:"208898",title:"MSc.",name:"Susana",middleName:null,surname:"Muñoz",slug:"susana-munoz",fullName:"Susana Muñoz"}]}],mostDownloadedChaptersLast30Days:[{id:"56612",title:"Reproduction in Goats",slug:"reproduction-in-goats",totalDownloads:2892,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Reproductive activity of the goat begins when the females reach puberty, which happens at 5 months of age. The ovarian or estrous cycle is the period between two consecutive estrus. It is also the time that lasts the development of the follicle in the ovary, until rupture occurs and ovulation takes place, which coincides with the appearance of estrus. This chapter will describe the physiological and endocrinological bases of estrus in the goat. Likewise, factors affecting the presence of estrus and ovulation will be described. At another point, synchronization of estrus and ovulation, factors affecting the presence of estrus and external symptoms of estrus, will be described. To achieve synchronization of estrus or induction of ovulation within or outside the breeding season, it may be necessary to manage light hours, male effect, and/or use of hormones. The importance of artificial insemination is described, as well as the current situation of this technique worldwide. Currently, the techniques of artificial insemination in goats have been limited worldwide, due to the lack of resources of producers and trained technicians. The techniques of artificial insemination with estrous synchronization programs and ovulation with current research results will be described.",book:{id:"5987",slug:"goat-science",title:"Goat Science",fullTitle:"Goat Science"},signatures:"Fernando Sánchez Dávila, Alejandro Sergio del Bosque González\nand Hugo Bernal Barragán",authors:[{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila"},{id:"206127",title:"Dr.",name:"Alejandro Sergio",middleName:null,surname:"Del Bosque-Gonzalez",slug:"alejandro-sergio-del-bosque-gonzalez",fullName:"Alejandro Sergio Del Bosque-Gonzalez"},{id:"206128",title:"Dr.",name:"Hugo",middleName:null,surname:"Bernal-Barragán",slug:"hugo-bernal-barragan",fullName:"Hugo Bernal-Barragán"}]},{id:"58095",title:"The Innovative Techniques in Animal Husbandry",slug:"the-innovative-techniques-in-animal-husbandry",totalDownloads:3766,totalCrossrefCites:4,totalDimensionsCites:8,abstract:"Technology is developing rapidly. In this development, the transfer of computer systems and software to the application has made an important contribution. Technologic instruments made farmers can work more comfortable and increased animal production efficiency and profitability. Therefore, technologic developments are the main research area for animal productivity and sustainability. Many technologic equipment and tools made animal husbandry easier and comfortable. Especially management decisions and applications are effected highly ratio with this rapid development. In animal husbandry management decisions that need to be done daily are configured according to the correctness of the decisions to be made. At this point, smart systems give many opportunities to farmers. Milking, feeding, environmental control, reproductive performance constitute everyday jobs most affected by correct management decisions. Human errors in this works and decisions made big effect on last product quality and profitability are not able to be risked. This chapter deal with valuable information on the latest challenges and key innovations affecting the animal husbandry. Also, innovative approaches and applications for animal husbandry are tried to be summarized with detail latest research results.",book:{id:"6384",slug:"animal-husbandry-and-nutrition",title:"Animal Husbandry and Nutrition",fullTitle:"Animal Husbandry and Nutrition"},signatures:"Serap Göncü and Cahit Güngör",authors:[{id:"215579",title:"Prof.",name:"Serap",middleName:null,surname:"Goncu",slug:"serap-goncu",fullName:"Serap Goncu"},{id:"218971",title:"Dr.",name:"Cahit",middleName:null,surname:"Güngör",slug:"cahit-gungor",fullName:"Cahit Güngör"}]},{id:"58486",title:"Quality of Chicken Meat",slug:"quality-of-chicken-meat",totalDownloads:3290,totalCrossrefCites:18,totalDimensionsCites:26,abstract:"Chicken meat is considered as an easily available source of high-quality protein and other nutrients that are necessary for proper body functioning. In order to meet the consumers’ growing demands for high-quality protein, the poultry industry focused on selection of fast-growing broilers, which reach a body mass of about 2.5 kg within 6-week-intensive fattening. Relatively low sales prices of chicken meat, in comparison to other types of meat, speak in favor of the increased chicken meat consumption. In addition, chicken meat is known by its nutritional quality, as it contains significant amount of high-quality and easily digestible protein and a low portion of saturated fat. Therefore, chicken meat is recommended for consumption by all age groups. The technological parameters of chicken meat quality are related to various factors (keeping conditions, feeding treatment, feed composition, transport, stress before slaughter, etc.). Composition of chicken meat can be influenced through modification of chicken feed composition (addition of different types of oils, vitamins, microelements and amino acids), to produce meat enriched with functional ingredients (n-3 PUFA, carnosine, selenium and vitamin E). By this way, chicken meat becomes a foodstuff with added value, which, in addition to high-quality nutritional composition, also contains ingredients that are beneficial to human health.",book:{id:"6384",slug:"animal-husbandry-and-nutrition",title:"Animal Husbandry and Nutrition",fullTitle:"Animal Husbandry and Nutrition"},signatures:"Gordana Kralik, Zlata Kralik, Manuela Grčević and Danica Hanžek",authors:[{id:"207236",title:"Dr.",name:"Gordana",middleName:null,surname:"Kralik",slug:"gordana-kralik",fullName:"Gordana Kralik"},{id:"227281",title:"Prof.",name:"Zlata",middleName:null,surname:"Kralik",slug:"zlata-kralik",fullName:"Zlata Kralik"},{id:"227283",title:"Dr.",name:"Manuela",middleName:null,surname:"Grčević",slug:"manuela-grcevic",fullName:"Manuela Grčević"},{id:"227284",title:"BSc.",name:"Danica",middleName:null,surname:"Hanžek",slug:"danica-hanzek",fullName:"Danica Hanžek"}]},{id:"56453",title:"Goat System Productions: Advantages and Disadvantages to the Animal, Environment and Farmer",slug:"goat-system-productions-advantages-and-disadvantages-to-the-animal-environment-and-farmer",totalDownloads:4328,totalCrossrefCites:5,totalDimensionsCites:21,abstract:"Goats have always been considered very useful animals. Goats success is related to its excellent adaptability to the difficult mountain conditions, extreme weather and low value feed acceptance, versatile habits and high production considering their size. These are some reasons because goats are among the first animals to be domesticated. In terms of evolution, goats could be separated by their dispersion area in three large groups: the European, the Asian, and the African. Global goat populations, mainly in Africa and in Asia, have increased for centuries but very strongly in the past decades, well above the world population growth. They are also used for forest grazing, an integrated and alternative production system, very useful to control weed growth reducing fire risk. Despite some exceptions, no large‐scale effort to professionalize this industry has been made so far. There are consumers for goat dairy products and there is enough global production, but misses a professional network between both. Regarding goat meat, the world leadership also stays in Africa and Asia, namely in China, and there is a new phenomenon, the spreading of goat meat tradition through Europe due to migrants from Africa and other places with strong goat meat consumption.",book:{id:"5987",slug:"goat-science",title:"Goat Science",fullTitle:"Goat Science"},signatures:"António Monteiro, José Manuel Costa and Maria João Lima",authors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"},{id:"203680",title:"Prof.",name:"Maria João",middleName:null,surname:"Lima",slug:"maria-joao-lima",fullName:"Maria João Lima"},{id:"203683",title:"MSc.",name:"José Manuel",middleName:null,surname:"Costa",slug:"jose-manuel-costa",fullName:"José Manuel Costa"}]},{id:"70760",title:"Induction and Synchronization of Estrus",slug:"induction-and-synchronization-of-estrus",totalDownloads:1716,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Estrus cycle is a rhythmic change that occur in the reproductive system of females starting from one estrus phase to another. The normal duration of estrus cycle is 21 days in cow, sow, and mare, 17 days in ewe, and 20 days in doe. The species which exhibit a single estrus cycle are known as monstrous and species which come into estrus twice or more are termed polyestrous animals. Among them some species have estrus cycles in a particular season and defined as seasonal polyestrous. It includes goats, sheep, and horses. On the other hand, cattle undergo estrus throughout the year. The estrus inducers can grossly be divided into two parts, that is, non-hormonal and hormonal. Non-hormonal treatments include plant-derived heat inducers, mineral supplementation, uterine and ovarian massage, and use of Lugol’s iodine. The hormones that are used in estrus induction are estrogen, progesterone, GnRH, prostaglandin, insulin, and anti-prolactin-based treatment. Synchronization can shorten the breeding period to less than 5 days, instead of females being bred over a 21-day period, depending on the treatment regimen. The combination of GnRH with the prostaglandin F2α (PGF2α)- and progesterone-based synchronization program has shown a novel direction in the estrus synchronization of cattle with the follicular development manipulation.",book:{id:"8545",slug:"animal-reproduction-in-veterinary-medicine",title:"Animal Reproduction in Veterinary Medicine",fullTitle:"Animal Reproduction in Veterinary Medicine"},signatures:"Prasanna Pal and Mohammad Rayees Dar",authors:[{id:"299126",title:"Dr.",name:"Mohammad Rayees",middleName:null,surname:"Dar",slug:"mohammad-rayees-dar",fullName:"Mohammad Rayees Dar"},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal"}]}],onlineFirstChaptersFilter:{topicId:"25",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82457",title:"Canine Hearing Management",slug:"canine-hearing-management",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.105515",abstract:"The United States military employs multipurpose canines as force multipliers. A newly developed baseline audiology program applicable to noise effects on the hearing threshold for these dogs has just been developed by the University of Cincinnati FETCHLAB using brainstem auditory evoked potentials to detect estimated threshold shifts in this population. Dogs that are routinely deployed are subject to consistent exposure to noise in the field. Few investigations have focused on the effects of transport noise on the auditory system in multipurpose dogs. The consequence of these dogs having a significant hearing threshold shift is a failure of the dog to properly respond to voice commands and to miss critical acoustic cues while on target. This chapter specifically discusses the baseline protocol for audiological testing of special operations’ multipurpose canines related to helicopter transport.",book:{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg"},signatures:"Peter M. Skip Scheifele, Devan Marshall, Stephen Lee, Paul Reid, Thomas McCreery and David Byrne"},{id:"82285",title:"Parvovirus Vectors: The Future of Gene Therapy",slug:"parvovirus-vectors-the-future-of-gene-therapy",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.105085",abstract:"The unique diversity of parvoviral vectors with innate antioncogenic properties, autonomous replication, ease of recombinant vector production and stable transgene expression in target cells makes them an attractive choice as viral vectors for gene therapy protocols. Amongst various parvoviruses that have been identified so far, recombinant vectors originating from adeno-associated virus, minute virus of mice (MVM), LuIII and parvovirus H1 have shown promising results in many preclinical models of human diseases including cancer. The adeno-associated virus (AAV), a non-pathogenic human parvovirus, has gained attention as a potentially useful vector. The improved understanding of the metabolism of vector genomes and the mechanism of transduction by AAV vectors is leading to advancement in the development of more sophisticated AAV vectors. The in-depth studies of AAV vector biology is opening avenues for more robust design of AAV vectors that have potentially increased transduction efficiency, increased specificity in cellular targeting, and an increased payload capacity. This chapter gives an overview of the application of autonomous parvoviral vectors and AAV vectors, based on our current understanding of viral biology and the state of the platform.",book:{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg"},signatures:"Megha Gupta"},{id:"81793",title:"Canine parvovirus-2: An Emerging Threat to Young Pets",slug:"canine-parvovirus-2-an-emerging-threat-to-young-pets",totalDownloads:17,totalDimensionsCites:0,doi:"10.5772/intechopen.104846",abstract:"Canine parvovirus-2 (CPV-2) is a highly contagious and key enteropathogen affecting the canine population around the globe by causing canine parvoviral enteritis (CPVE) and vomition. CPVE is one of the the leading causes of morbidity and mortality in puppies and young dogs. Over the years, five distinct antigenic variants of CPV-2, namely CPV-2a, CPV-2b, new CPV-2a, new CPV-2b, and CPV-2c, have emerged throughout the world. CPV-2 infects a diverse range of wild animals, and the newer variants of CPV-2 have expanded their host range to include felines. Despite the availability of highly specific diagnostics and efficacious vaccines, CPV-2 outbreaks have been reported globally due to the emergence of newer antigenic variants, expansion of the viral host range, and vaccination failures. The present chapter describes the latest information pertaining to virus properties and replication, disease manifestations in animals, and an additional recent updates on diagnostic, prevention and control strategies of CPV-2.",book:{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg"},signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy"},{id:"81271",title:"The Diversity of Parvovirus Telomeres",slug:"the-diversity-of-parvovirus-telomeres",totalDownloads:38,totalDimensionsCites:0,doi:"10.5772/intechopen.102684",abstract:"Parvoviridae are small viruses composed of a 4–6 kb linear single-stranded DNA protected by an icosahedral capsid. The viral genes coding non-structural (NS), capsid, and accessory proteins are flanked by intriguing sequences, namely the telomeres. Telomeres are essential for parvovirus genome replication, encapsidation, and integration. Similar (homotelomeric) or different (heterotelomeric) at the two ends, they all contain imperfect palindromes that fold into hairpin structures. Up to 550 nucleotides in length, they harbor a wide variety of motifs and structures known to be recognized by host cell factors. Our study aims to comprehensively analyze parvovirus ends to better understand the role of these particular sequences in the virus life cycle. Forty Parvoviridae terminal repeats (TR) were publicly available in databases. The folding and specific DNA secondary structures, such as G4 and triplex, were systematically analyzed. A principal component analysis was carried out from the prediction data to determine variables signing parvovirus groups. A special focus will be put on adeno-associated virus (AAV) inverted terminal repeats (ITR), a member of the genus Dependoparvovirus used as vectors for gene therapy. This chapter highlights the diversity of the Parvoviridae telomeres regarding shape and secondary structures, providing information that could be relevant for virus-host interactions studies.",book:{id:"11580",title:"Recent Advances in Canine Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg"},signatures:"Marianne Laugel, Emilie Lecomte, Eduard Ayuso, Oumeya Adjali, Mathieu Mével and Magalie Penaud-Budloo"},{id:"79209",title:"Virtual Physiology: A Tool for the 21st Century",slug:"virtual-physiology-a-tool-for-the-21st-century",totalDownloads:153,totalDimensionsCites:0,doi:"10.5772/intechopen.99671",abstract:"Veterinary physiology is a basic curricular unit for every course within the veterinary field. It is mandatory to understand how the animal body works, and what to expect of a healthy body, in order to recognize any misfunction, and to be able to treat it. Classic physiology teaching involves wet labs, much equipment, many reagents, some animals, and a lot of time. But times are changing. In the 21st century, it is expected that the teaching and learning process can be more active and attractive, motivating students to learn better. It is necessary to understand what students like, and to introduce novelties into the school routine. The use of a game-based learning, using “new” technologies, creating virtual experiences and labs, reducing the costs of reagents, equipment, and especially reducing the use of animals, will be the future for physiology teaching.",book:{id:"10665",title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg"},signatures:"Carmen Nóbrega, Maria Aires Pereira, Catarina Coelho, Isabel Brás, Ana Cristina Mega, Carla Santos, Fernando Esteves, Rita Cruz, Ana I. Faustino-Rocha, Paula A. Oliveira, João Mesquita and Helena Vala"},{id:"78543",title:"Pulmonary Vein: Embryology, Anatomy, Function and Disease",slug:"pulmonary-vein-embryology-anatomy-function-and-disease",totalDownloads:183,totalDimensionsCites:0,doi:"10.5772/intechopen.100051",abstract:"Four pulmonary veins come from respective lung lobes drain oxygen-rich blood back to the left atrium. Failure of incorporation with the left atrium can lead to a condition, called Cor triatriatum sinister, that the left atrium is separated into two chambers by an abortive fibrous tissue. The venous system of lung and whole body communicate with each other in the earlier time and they will be disconnected in the following developmental process. Total or partial anomalous pulmonary venous connection refers to that there is/are some degree of the communication exists after birth, which can occur in different sites. In the veterinary field, retrospective studies and several case reports have been published to describe these rare congenital cardiovascular diseases in several species. More cases are need for better understanding their clinical manifestation, treatment options and outcomes.",book:{id:"10665",title:"Updates on Veterinary Anatomy and Physiology",coverURL:"https://cdn.intechopen.com/books/images_new/10665.jpg"},signatures:"Chan I-Ping and Hsueh Tung"}],onlineFirstChaptersTotal:13},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. In the last five years, he has published more than 60 papers in international journals indexed in the JCR (around 70% of them belonging to first quartile journals) and he has edited some Springer books “Supervised Descriptive Pattern Mining” (2018), “Multiple Instance Learning - Foundations and Algorithms” (2016), and “Pattern Mining with Evolutionary Algorithms” (2016). He has also been involved in more than 20 research projects supported by the Spanish and Andalusian governments and the European Union. He currently belongs to the editorial board of PeerJ Computer Science, Information Fusion and Engineering Applications of Artificial Intelligence journals, being also associate editor of Applied Computational Intelligence and Soft Computing and IEEE Transactions on Cybernetics. Finally, he is editor-in-chief of Progress in Artificial Intelligence. He is a Senior Member of the IEEE Computer, the IEEE Computational Intelligence, and the IEEE Systems, Man, and Cybernetics Societies, and the Association of Computing Machinery (ACM). Finally, his main research interests include data science, computational intelligence, and their applications.",institutionString:null,institution:{name:"University of Córdoba",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"26",title:"Machine Learning and Data Mining",coverUrl:"https://cdn.intechopen.com/series_topics/covers/26.jpg",isOpenForSubmission:!0,editor:{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null},{id:"27",title:"Multi-Agent Systems",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",isOpenForSubmission:!0,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:19,paginationItems:[{id:"82196",title:"Multi-Features Assisted Age Invariant Face Recognition and Retrieval Using CNN with Scale Invariant Heat Kernel Signature",doi:"10.5772/intechopen.104944",signatures:"Kamarajugadda Kishore Kumar and Movva Pavani",slug:"multi-features-assisted-age-invariant-face-recognition-and-retrieval-using-cnn-with-scale-invariant-",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"82063",title:"Evaluating Similarities and Differences between Machine Learning and Traditional Statistical Modeling in Healthcare Analytics",doi:"10.5772/intechopen.105116",signatures:"Michele Bennett, Ewa J. Kleczyk, Karin Hayes and Rajesh Mehta",slug:"evaluating-similarities-and-differences-between-machine-learning-and-traditional-statistical-modelin",totalDownloads:6,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Machine Learning and Data Mining - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11422.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"81791",title:"Self-Supervised Contrastive Representation Learning in Computer Vision",doi:"10.5772/intechopen.104785",signatures:"Yalin Bastanlar and Semih Orhan",slug:"self-supervised-contrastive-representation-learning-in-computer-vision",totalDownloads:28,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Pattern Recognition - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11442.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}},{id:"79345",title:"Application of Jump Diffusion Models in Insurance Claim Estimation",doi:"10.5772/intechopen.99853",signatures:"Leonard Mushunje, Chiedza Elvina Mashiri, Edina Chandiwana and Maxwell Mashasha",slug:"application-of-jump-diffusion-models-in-insurance-claim-estimation-1",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Data Clustering",coverURL:"https://cdn.intechopen.com/books/images_new/10820.jpg",subseries:{id:"26",title:"Machine Learning and Data Mining"}}}]},overviewPagePublishedBooks:{paginationCount:9,paginationItems:[{type:"book",id:"7723",title:"Artificial Intelligence",subtitle:"Applications in Medicine and Biology",coverURL:"https://cdn.intechopen.com/books/images_new/7723.jpg",slug:"artificial-intelligence-applications-in-medicine-and-biology",publishedDate:"July 31st 2019",editedByType:"Edited by",bookSignature:"Marco Antonio Aceves-Fernandez",hash:"a3852659e727f95c98c740ed98146011",volumeInSeries:1,fullTitle:"Artificial Intelligence - Applications in Medicine and Biology",editors:[{id:"24555",title:"Dr.",name:"Marco Antonio",middleName:null,surname:"Aceves Fernandez",slug:"marco-antonio-aceves-fernandez",fullName:"Marco Antonio Aceves Fernandez",profilePictureURL:"https://mts.intechopen.com/storage/users/24555/images/system/24555.jpg",biography:"Dr. Marco Antonio Aceves Fernandez obtained his B.Sc. (Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. 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He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. 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