\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\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:"5411",leadTitle:null,fullTitle:"Fourier Transforms - High-tech Application and Current Trends",title:"Fourier Transforms",subtitle:"High-tech Application and Current Trends",reviewType:"peer-reviewed",abstract:"The main purpose of this book is to provide a modern review about recent advances in Fourier transforms as the most powerful analytical tool for high-tech application in electrical, electronic, and computer engineering, as well as Fourier transform spectral techniques with a wide range of biological, biomedical, biotechnological, pharmaceutical, and nanotechnological applications. The confluence of Fourier transform methods with high tech opens new opportunities for detection and handling of atoms and molecules using nanodevices, with potential for a large variety of scientific and technological applications.",isbn:"978-953-51-2894-6",printIsbn:"978-953-51-2893-9",pdfIsbn:"978-953-51-4114-3",doi:"10.5772/62751",price:119,priceEur:129,priceUsd:155,slug:"fourier-transforms-high-tech-application-and-current-trends",numberOfPages:262,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"5c45d1a91daef66093a42a82448a70f0",bookSignature:"Goran S. Nikolic, Milorad D. Cakic and Dragan J. Cvetkovic",publishedDate:"February 8th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5411.jpg",numberOfDownloads:26140,numberOfWosCitations:34,numberOfCrossrefCitations:21,numberOfCrossrefCitationsByBook:5,numberOfDimensionsCitations:44,numberOfDimensionsCitationsByBook:5,hasAltmetrics:1,numberOfTotalCitations:99,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 30th 2016",dateEndSecondStepPublish:"April 20th 2016",dateEndThirdStepPublish:"July 25th 2016",dateEndFourthStepPublish:"October 23rd 2016",dateEndFifthStepPublish:"November 22nd 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7,8",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"23261",title:"Prof.",name:"Goran",middleName:"S.",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic",profilePictureURL:"https://mts.intechopen.com/storage/users/23261/images/system/23261.jpg",biography:"Dr. Goran Nikolić was born in Knez Selo (Niš, Serbia) on 1 November 1966. He received his B.Sc. degree in Chemistry (1990), M.Sc. degree in Organic Chemical Technology and Polymer Engineering (1996), and finally his PhD degree in Chemical Engineering (2002) from the University of Niš. Currently, he is a full professor at the same university, on Pharmaceutical-cosmetic engineering group of subjects at Faculty of Technology in Leskovac. His research activities are: quality control and stability of drugs, development of new pharmaceutical products (antianemic, antiseptic), pharmaceutical ingredients (synthesis and characterization), polynuclear and biocomplexes, surfactants. His competences are experience: in team work as a researcher, in project management, and managing of academic institution at different levels (vice dean, department chairman, head of chromatographic and spectrosopic laboratories, president of the quality assurance at the Faculty, and a member of the Committee for the improvement of the quality of the University). He is a member of the several national projects in the technological development area (granted by the Ministry of Science and Technological Development, Republic of Serbia), and member of numerous TEMPUS Joint European projects of sustainable technologies, environmental application and management courses (JPHES 2013, JPHES 2010, MCHEM 2010, IB-JEP 19020). He is a member of Serbian Chemical Society and Physicochemical Association of Serbia, and member of the Editorial Board of the journal Advanced Technologies. He has authored more than 300 scientific papers (in international and national scientific journals, on international conferences), numerous technological solutions for pharmaceutical industry, national monographies, international patents, university textbooks, invitation lecturers. He is the referee in numerous international and national journals, and editor of two international monographs on FTIR spectroscopy (InTech Open).",institutionString:"University of Niš",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"University of Nis",institutionURL:null,country:{name:"Serbia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"195521",title:"Prof.",name:"Dragan",middleName:"J.",surname:"Cvetkovic",slug:"dragan-cvetkovic",fullName:"Dragan Cvetkovic",profilePictureURL:"https://mts.intechopen.com/storage/users/195521/images/5144_n.jpg",biography:"Prof. Dragan J. Cvetković was born on 26 June 1977 in Leskovac. He finished elementary and high school in Lebane, and then he completed his studies at the Faculty of Technology in Leskovac in the year 2002.He finished his PhD thesis in the year 2012 at the Faculty of Technology in Leskovac. Dragan Cvetković participated in the realization of numerous projects funded by the Ministry of Science, Republic of Serbia. He was engaged on the project “Folding and Stability of Phycobilisome Proteins” at the Institute of Biology and Technology of Saclay, France. He also participated in realization of the project entitled “Contribution of Chemical Quenching of Singlet Oxygen to Pro- and Antioxidant Activity of Carotenoids,” funded by the Polish Ministry of Science. He was elected as a teaching assistant in the year 2008on Physical Chemistry, Colloid Chemistry, and Instrumental Analysis, but in the year 2012, he was elected as an assistant professor on physicochemical group of subjects at the Faculty of Technology in Leskovac.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null},coeditorTwo:{id:"195519",title:"Dr.",name:"Milorad",middleName:null,surname:"Cakic",slug:"milorad-cakic",fullName:"Milorad Cakic",profilePictureURL:"https://mts.intechopen.com/storage/users/195519/images/5143_n.jpg",biography:"Prof. Milorad D. Cakić was born on 26 May 1951 in Leskovac, Serbia. He finished\b his studies at the Faculty of Chemistry in Skopje (Macedonia) in 1975. He completed his master studies in the field of molecular spectroscopy in 1978. His PhD thesis was defended at the same university in 1984. He was elected in 1985 as assistant professor at the University of Niš, Faculty of Technology in Leskovac, where he works today as a full professor. His main scientific interest is structure-spectral correlation investigations by different spectroscopic and chromatographic methods. He had published a number of articles in the field of synthesis and characterization of compounds with proven or potential pharmaceutical activity. He was an editor of many scientific publications and reviewer in a number of journals. His competences are experience in project management and managing of academic institution at different levels (dean, vice dean, head of the department, head of the laboratory, member of the senate, and deputy president of the Expert Board for Natural Sciences and Mathematics). Prof. Cakić is a member of the Board for the Accreditation of Scientific-Research Organizations of the Republic of Serbia.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"974",title:"Signal Processing",slug:"applied-mathematics-signal-processing"}],chapters:[{id:"53143",title:"Inversion-Based Fourier Transform as a New Tool for Noise Rejection",doi:"10.5772/66338",slug:"inversion-based-fourier-transform-as-a-new-tool-for-noise-rejection",totalDownloads:2064,totalCrossrefCites:4,totalDimensionsCites:4,hasAltmetrics:0,abstract:"In this study, a new inversion method is presented for performing two-dimensional (2D) Fourier transform. The discretization of the continuous Fourier spectra is given by a series expansion with the scaled Hermite functions as square-integrable set of basis functions. The expansion coefficients are determined by solving an overdetermined inverse problem. In order to define a quick algorithm in calculating the Jacobian matrix of the problem, the special feature that the Hermite functions are eigenfunctions of the Fourier transformation is used. In the field of inverse problem theory, there are numerous procedures for noise rejection, so if the Fourier transformation is formulated as an inverse problem, these tools can be used to reduce the noise sensitivity. It was demonstrated in many case studies that the use of Cauchy-Steiner weights could increase the noise rejection capability of geophysical inversion methods. Following this idea, the two-dimensional Fourier transform is formulated as an iteratively reweighted least squares (IRLS) problem using Cauchy-Steiner weights. The new procedure is numerically tested using synthetic data.",signatures:"Mihály Dobróka, Hajnalka Szegedi and Péter Vass",downloadPdfUrl:"/chapter/pdf-download/53143",previewPdfUrl:"/chapter/pdf-preview/53143",authors:[{id:"189265",title:"Prof.",name:"Mihály",surname:"Dobróka",slug:"mihaly-dobroka",fullName:"Mihály Dobróka"},{id:"194562",title:"MSc.",name:"Hajnalka",surname:"Szegedi",slug:"hajnalka-szegedi",fullName:"Hajnalka Szegedi"},{id:"194563",title:"Dr.",name:"Péter",surname:"Vass",slug:"peter-vass",fullName:"Péter Vass"}],corrections:null},{id:"54042",title:"Single Bin Sliding Discrete Fourier Transform",doi:"10.5772/66337",slug:"single-bin-sliding-discrete-fourier-transform",totalDownloads:2225,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The conventional method for spectrum analysis is the discrete Fourier transform (DFT), usually implemented using a fast Fourier transform (FFT) algorithm. However, certain applications require an online spectrum analysis only on a subset of M frequencies of an N-point DFT (M<N). In such cases, the use of single-bin sliding DFT (Sb-SDFT) is preferred over the direct application of FFT. The purpose of this chapter is to provide a concise overview of the Sb-SDFT algorithms, analyze their performance, and highlight advantages and limitations. Finally, a technique to mitigate the spectral leakage effect, which arises when using the Sb-SDFT in nonstationary conditions, is presented.",signatures:"Carlos Martin Orallo and Ignacio Carugati",downloadPdfUrl:"/chapter/pdf-download/54042",previewPdfUrl:"/chapter/pdf-preview/54042",authors:[{id:"187654",title:"Dr.",name:"Carlos",surname:"Orallo",slug:"carlos-orallo",fullName:"Carlos Orallo"},{id:"188926",title:"Dr.",name:"Ignacio",surname:"Carugati",slug:"ignacio-carugati",fullName:"Ignacio Carugati"}],corrections:null},{id:"53524",title:"Fourier Analysis for Harmonic Signals in Electrical Power Systems",doi:"10.5772/66733",slug:"fourier-analysis-for-harmonic-signals-in-electrical-power-systems",totalDownloads:4499,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The harmonic content in electrical power systems is an increasingly worrying issue since the proliferation of nonlinear loads results in power quality problems as the harmonics is more apparent. In this paper, we analyze the behavior of the harmonics in the electrical power systems such as cables, transmission lines, capacitors, transformers, and rotating machines, the induction machine being the object of our study when it is excited to nonsinusoidal operating conditions in the stator winding. For this, a model is proposed for the harmonic analysis of the induction machine in steady‐state regimen applying the Fourier transform. The results of the proposed model are validated by experimental tests which gave good results for each case study concluding in a model proper for harmonic and nonharmonic analysis of the induction machine and for “harmonic” analysis in an electrical power system.",signatures:"Emmanuel Hernández Mayoral, Miguel Angel Hernández López,\nEdwin Román Hernández, Hugo Jorge Cortina Marrero, José\nRafael Dorrego Portela and Victor Ivan Moreno Oliva",downloadPdfUrl:"/chapter/pdf-download/53524",previewPdfUrl:"/chapter/pdf-preview/53524",authors:[{id:"187793",title:"Dr.",name:"Emmanuel",surname:"Hernández",slug:"emmanuel-hernandez",fullName:"Emmanuel Hernández"},{id:"202757",title:"Dr.",name:"Miguel Angel",surname:"Hernández López",slug:"miguel-angel-hernandez-lopez",fullName:"Miguel Angel Hernández López"},{id:"202758",title:"Dr.",name:"Hugo Jorge",surname:"Cortina Marrero",slug:"hugo-jorge-cortina-marrero",fullName:"Hugo Jorge Cortina Marrero"},{id:"202759",title:"Dr.",name:"Edwin Román",surname:"Hernández",slug:"edwin-roman-hernandez",fullName:"Edwin Román Hernández"},{id:"202760",title:"Dr.",name:"Victor Iván Moreno",surname:"Oliva",slug:"victor-ivan-moreno-oliva",fullName:"Victor Iván Moreno Oliva"},{id:"202761",title:"Dr.",name:"José Rafael Dorrego",surname:"Portela",slug:"jose-rafael-dorrego-portela",fullName:"José Rafael Dorrego Portela"}],corrections:null},{id:"53909",title:"High Resolution Single-Chip Radix II FFT Processor for High- Tech Application",doi:"10.5772/66745",slug:"high-resolution-single-chip-radix-ii-fft-processor-for-high-tech-application",totalDownloads:2443,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Electrical motors are vital components of many industrial processes and their operation failure leads losing in production line. Motor functionality and its behavior should be monitored to avoid production failure catastrophe. Hence, a high‐tech DSP processor is a significant method for electrical harmonic analysis that can be realized as embedded systems. This chapter introduces principal embedded design of novel high‐tech 1024‐point FFT processor architecture for high performance harmonic measurement techniques. In FFT processor algorithm pipelining and parallel implementation are incorporated in order to enhance the performance. The proposed FFT makes use of floating point to realize higher precision FFT. Since floating‐point architecture limits the maximum clock frequency and increases the power consumption, the chapter focuses on improving the speed, area, resolution and power consumption, as well as latency for the FFT. It illustrates very large‐scale integration (VLSI) implementation of the floating‐point parallel pipelined (FPP) 1024‐point Radix II FFT processor with applying novel architecture that makes use of only single butterfly incorporation of intelligent controller. The functionality of the conventional Radix II FFT was verified as embedded in FPGA prototyping. For area and power consumption, the proposed Radix II FPP‐FFT was optimized in ASIC under Silterra 0.18 µm and Mimos 0.35 µm technology libraries.",signatures:"Rozita Teymourzadeh",downloadPdfUrl:"/chapter/pdf-download/53909",previewPdfUrl:"/chapter/pdf-preview/53909",authors:[{id:"188300",title:"Associate Prof.",name:"Rozita",surname:"Teymourzadeh",slug:"rozita-teymourzadeh",fullName:"Rozita Teymourzadeh"}],corrections:null},{id:"53607",title:"Memristor Threshold Logic FFT Circuits",doi:"10.5772/66583",slug:"memristor-threshold-logic-fft-circuits",totalDownloads:1818,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"One of the possible approaches to achieve more than Moore's law with signal processing circuits is to inspire from functioning of human brain to mimic neural functions by exploring emerging technologies such as memristor circuits. While fast Fourier transform (FFT) implementations are largely based on CMOS gates, they are limited by the computation speed and availability limits on the number of Boolean variables it can handle at a given time. Biological neurons and networks on the other hand are generalized in nature and can handle both analogue and digital signals. Through this chapter, memristor‐based resistive threshold logic family of gates that inspire from brain‐like large variable logic functions is introduced. This logic consists of a memristors acting as weights to the inputs followed by threshold operations emulating neuronal synapse. Using this Boolean logic, a processing unit that can compute Fourier transform of a given set of inputs was developed. Various comparisons of the circuit are found to be advantageous in implementing neuromorphic circuits. The existing logic families were carried out and the proposed logic family was found too advantageous in many ways.",signatures:"Alex Pappachen James",downloadPdfUrl:"/chapter/pdf-download/53607",previewPdfUrl:"/chapter/pdf-preview/53607",authors:[{id:"6992",title:"Prof.",name:"Alex",surname:"James",slug:"alex-james",fullName:"Alex James"}],corrections:null},{id:"53640",title:"Application of Fourier Series Expansion to Electrical Power Conversion",doi:"10.5772/66581",slug:"application-of-fourier-series-expansion-to-electrical-power-conversion",totalDownloads:2682,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Many power electronic applications demand generation of voltage of a rather good sinusoidal waveform. In particular, dc-to-ac voltage conversion could be done by multilevel inverters (MLI). A number of various inverter topologies have been suggested so far: diode-clamped (DC) MLI, capacitor-clamped (CC) MLI, cascaded H-bridge (CHB) MLI, and others. Fourier series expansions have been used to investigate and to form a basis of different topologies comparison, to discover their advantages and disadvantages, and to determine their control. In this chapter, we discuss modulation strategies of DCMLI and CHBMLI, solve their harmonics spectra analytically, and compare them using harmonic distortion indices.",signatures:"Irina Dolguntseva",downloadPdfUrl:"/chapter/pdf-download/53640",previewPdfUrl:"/chapter/pdf-preview/53640",authors:[{id:"188384",title:"Ph.D.",name:"Irina",surname:"Dolguntseva",slug:"irina-dolguntseva",fullName:"Irina Dolguntseva"}],corrections:null},{id:"52810",title:"Study of Green Nanoparticles and Biocomplexes Based on Exopolysaccharide by Modern Fourier Transform Spectroscopy",doi:"10.5772/65776",slug:"study-of-green-nanoparticles-and-biocomplexes-based-on-exopolysaccharide-by-modern-fourier-transform",totalDownloads:2004,totalCrossrefCites:2,totalDimensionsCites:6,hasAltmetrics:0,abstract:"The intention of this chapter is to contribute in clarification of nanoparticle synthesis and biocomplexes based on exopolysaccharide, green synthetic method development, their physico‐chemical characterization by modern spectroscopy, as well as testing of their antimicrobial activity. Silver nanoparticles of polysaccharide type have scientific interest, but practical importance too, because of their application in pharmaceutical and cosmetic product development due to proven antimicrobial and antioxidant activities. On the other hand, the biocomplexes based on exopolysaccharides are important in treatment of biometal deficiency in human and veterinary medicine, as well as in metal ion transporting in organism. Despite a number of studies of this kind of complexes, the investigations of effect of their structure to pharmaco‐biological activity are still interesting. It is important that question of interaction between reducing and stabilizing agents with metal ions is still opened. In this respect, the presented chapter offers further progress in the examination of silver nanoparticles and cobalt biocomplex synthesis with dextran oligosaccharides and its derivatives (such as dextran sulfate and carboxymethyl dextran). The complex structure, spectroscopic characterization, and the spectra‐structure correlation have been analyzed by different Fourier transform infrared (FTIR) spectroscopic techniques combined with energy‐dispersive X‐ray (EDX), X‐ray diffraction (XRD), scanning electron microscopy (SEM), and surface plasmon resonance UV‐Vis methods.",signatures:"Goran S. Nikolić, Milorad D. Cakić, Slobodan Glišić, Dragan J.\nCvetković, Žarko J. Mitić and Dragana Z. Marković",downloadPdfUrl:"/chapter/pdf-download/52810",previewPdfUrl:"/chapter/pdf-preview/52810",authors:[{id:"23261",title:"Prof.",name:"Goran",surname:"Nikolic",slug:"goran-nikolic",fullName:"Goran Nikolic"},{id:"195521",title:"Prof.",name:"Dragan",surname:"Cvetkovic",slug:"dragan-cvetkovic",fullName:"Dragan Cvetkovic"},{id:"195519",title:"Dr.",name:"Milorad",surname:"Cakic",slug:"milorad-cakic",fullName:"Milorad Cakic"},{id:"195520",title:"MSc.",name:"Slobodan",surname:"Glišić",slug:"slobodan-glisic",fullName:"Slobodan Glišić"},{id:"195522",title:"Dr.",name:"Žarko",surname:"Mitić",slug:"zarko-mitic",fullName:"Žarko Mitić"},{id:"195523",title:"MSc.",name:"Dragana",surname:"Marković-Nikolić",slug:"dragana-markovic-nikolic",fullName:"Dragana Marković-Nikolić"}],corrections:null},{id:"53409",title:"Fourier Transform Infrared and Two-Dimensional Correlation Spectroscopy for Substance Analysis",doi:"10.5772/66584",slug:"fourier-transform-infrared-and-two-dimensional-correlation-spectroscopy-for-substance-analysis",totalDownloads:1828,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The development of Fourier transform infrared (FTIR) has had widened its scope of perspective application on different types of substances in terms of technique of material analysis and identification. The tri-step infrared analysis has shown its powerful application in the analysis and interpretation of spectra from pure compound, fraction, raw material, natural product and complex mixture.",signatures:"Yew-Keong Choong",downloadPdfUrl:"/chapter/pdf-download/53409",previewPdfUrl:"/chapter/pdf-preview/53409",authors:[{id:"171079",title:"Dr.",name:"Yew Keong",surname:"Choong",slug:"yew-keong-choong",fullName:"Yew Keong Choong"}],corrections:null},{id:"53419",title:"Fourier Transform Infrared Spectroscopy in the Study of Hydrated Biological Macromolecules",doi:"10.5772/66576",slug:"fourier-transform-infrared-spectroscopy-in-the-study-of-hydrated-biological-macromolecules",totalDownloads:2450,totalCrossrefCites:3,totalDimensionsCites:15,hasAltmetrics:0,abstract:"The interaction between biological macromolecules (proteins, nucleic acids, lipids and other biomolecules in the cell) and environmental water is an important determining factor in their conformational properties, stability and function. The hydration processes of biopolymers have been extensively studied in the past 20 years with reference to a considerable variety of models and concepts. In all recent works, a distinction is made between intracellular water that maintains the ordinary liquid state (bulk water) and water ordered in extended hydrogen‐bonded lattices at the surface and structured in the internal grooves of macromolecules (hydration water) in dependence on the chemical properties of the macromolecule surface. FTIR spectroscopy has been implemented in this field both for the sensitivity in the conformational analysis of biological macromolecules and the reliability in the investigation of the water network. A perturbation technique such as dehydration‐rehydration treatment modifies the macromolecule structure and water distribution. It was applied to two structurally different proteins: lysozyme, a globular (α + β) protein and collagen, a fibrous protein characterized by the triple helix structure. Submitted to the treatment both of them display irreversible conformational changes.",signatures:"Maria Grazia Bridelli",downloadPdfUrl:"/chapter/pdf-download/53419",previewPdfUrl:"/chapter/pdf-preview/53419",authors:[{id:"108760",title:"Dr.",name:"Maria Grazia",surname:"Bridelli",slug:"maria-grazia-bridelli",fullName:"Maria Grazia Bridelli"}],corrections:null},{id:"53388",title:"Fourier Transform Hyperspectral Imaging for Cultural Heritage",doi:"10.5772/66107",slug:"fourier-transform-hyperspectral-imaging-for-cultural-heritage",totalDownloads:1781,totalCrossrefCites:1,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Hyperspectral imaging is a technique of analysis that associates to each pixel of the image the spectral content of the radiation coming from the scene. This content can be helpful to recognize the chemical nature of the materials within the scene or to calculate their colours under particular conditions. Different solutions of hyperspectral imager have been realized with different spatial resolution, spectral resolution and range in the electromagnetic spectrum. In particular, improving the spectral resolution allows discriminating smaller features in the spectrum and the unambiguous detection of the absorption bands characteristic of superficial materials. Hyperspectral imagers based on interferometers have the advantage of having a spectral resolution that can be varied according to the needs by changing the optical path delay of the interferometer. A spectrum for each pixel is obtained with an algorithm based on the Fourier transform of the calibrated interferogram. We present the results of the application of a hyperspectral imager based on Fabry‐Perot interferometers to the field of cultural heritage. On different artworks, the hyperspectral imager has been used for pigment recognition, for colour rendering elaborations of the image with different light sources or standard illuminants and for calculating the chromatic coordinates useful for specific purposes.",signatures:"Massimo Zucco, Marco Pisani and Tiziana Cavaleri",downloadPdfUrl:"/chapter/pdf-download/53388",previewPdfUrl:"/chapter/pdf-preview/53388",authors:[{id:"20909",title:"Dr.",name:"Marco Q.",surname:"Pisani",slug:"marco-q.-pisani",fullName:"Marco Q. Pisani"},{id:"20910",title:"Dr.",name:"Massimo E.",surname:"Zucco",slug:"massimo-e.-zucco",fullName:"Massimo E. Zucco"},{id:"194761",title:"Dr.",name:"Tiziana",surname:"Cavaleri",slug:"tiziana-cavaleri",fullName:"Tiziana Cavaleri"}],corrections:null},{id:"53366",title:"New Spectral Applications of the Fourier Transforms in Medicine, Biological and Biomedical Fields",doi:"10.5772/66577",slug:"new-spectral-applications-of-the-fourier-transforms-in-medicine-biological-and-biomedical-fields",totalDownloads:2347,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"This chapter reviews some recent spectral applications of the Fourier transform techniques as they are applied in spectroscopy. An overview about Fourier transform spectroscopy (FTS) used like a powerful and sensitive tool in medical, biological, and biomedical analysis is provided. The advanced spectroscopic techniques of FTS, such as Fourier transform visible spectroscopy (FTVS), Fourier transform infrared-attenuated total reflectance (FTIR-ATR), Fourier transform infrared-photoacoustic spectroscopy (FTIR-PAS), Fourier transform infrared imaging spectroscopy (FTIR imaging), and their biomedical applications are described. 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This book is intended to increase the readers' enthusiasm to explore the four sections of the contents: Section 1 begins with biochemistry, pathophysiology, histo-immunological study, and findings to assist in the diagnosis; Section 2 further investigates the role of vector in propagation of the parasite, the intensity on epidemiology, and the severity on clinical aspects, which help us to be well perceived on the course of disease; Section 3 is seeking beyond modern medicine and what lays in the nature that helps fight against this parasite; and the last section, Section 4, deals with the impacts of public health problem and the control strategies on Chagas disease.",isbn:"978-1-78923-659-0",printIsbn:"978-1-78923-658-3",pdfIsbn:"978-1-83881-369-7",doi:"10.5772/intechopen.69020",price:119,priceEur:129,priceUsd:155,slug:"chagas-disease-basic-investigations-and-challenges",numberOfPages:238,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"564a876f3d20c7740ede73057b5f6fa6",bookSignature:"Veeranoot Nissapatorn and Helieh S. 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Optimal dose selection is fundamental to appropriate clinical care. A comprehensive understanding of drug pharmacokinetics (PK) and pharmacodynamics (PD) and the factors that can influence the drug exposure-response (PK-PD) relationship is important to facilitate the optimization of dosage regimens. In the pediatric patient, though, normal growth and maturation complicates dose selection and optimization. Experience has demonstrated that the usual practice of adjusting dose size according to body weight often results in inappropriate pediatric doses as this practice ignores the impact of developmental changes on drug PK and PD processes. To ensure appropriate clinical care, then, dosing recommendations need to consider age-related changes in PK and PD. This becomes particularly important for new therapeutics, which have limited clinical trial data and experience of use in the pediatric population.
\nMedical
This chapter will mainly address issues of developmental maturation of PK and PD processes as key determinants of medical
Many studies report the use of
Limited information is available on the therapeutic use of
Commercially available medical
At present, age-appropriate formulations of
Medical
In the absence of pediatric PK and clinical trial data, adult data become a starting point for pediatric dose selection. For simplicity, doses may be normalized to body weight and, in some cases, to body surface area. Dose scaling by body weight (or body surface area) requires dose adjustment according to the patient’s clinical state and clinical response until a dose is titrated to appropriate effect. This process could take some time to identify an appropriate dosage regimen for the pediatric patient, if at all. Furthermore, given possible ceiling effects of the cannabinoids, where dosing beyond a certain amount per body weight may not yield further pharmacological benefit, this approach has risk of adverse therapeutic outcomes.
\nOther approaches exist to improve upon the simple extrapolation of body weight-adjusted adult doses. Allometric scaling approaches use body surface or body weight ratios and allometric models to extrapolate adult doses to the pediatric patient [16]. An important limitation of this approach is an assumption of a linear correlation between demographic covariates and the dose, which is not the case for the pediatric patient due to developmental maturation of PK and PD processes [16, 17, 18]. Children differ not only in body weight but also show changes in body composition, organ size, and maturation, which influence PK as well as result in differences in the therapeutic window (range of exposure concentrations that result in drug efficacy) due to PD changes with age. The use of exponential scaling factors adjusted by body size (and age) to predict dosages in pediatric patients is also limited by the complexity of these modeling approaches that precludes general application to many drugs [16, 17, 18]. Hence, we seem left with the current self-titration dosing model where doses, based on weight adjusted adult doses, begin low to moderate and are increased slowly, along with adjustments in dosing interval, until the desired effect is achieved [19]. This empirical “trial-and-error” approach will not likely result in optimal dosing guidelines for the different pediatric age strata due to diverse developmental periods within this population [20, 21].
\nChanges in body size and maturation of the physiological and biochemical processes determining PK and PD must be considered during dosage selection. Normal growth results in a decreasing ratio of body weight to body surface area with age making it difficult to recommend dosing according to patient body weight or body surface area consistent with adult guidelines [22]. For example, in an analysis of pediatric patients, dosing adjustments of hydrophobic drugs (cannabinoids are hydrophobic) based on body weight provided better clinical outcomes in patients between 1 month and 1 year of age, while dosing based on body surface area was best in older children [18]. As well, within and between the age strata maturational changes in PK and PD processes occur at considerably different rates and patterns suggesting that dosage adjustments with long-term therapy may be necessary to ensure efficacy and avoid risk of adverse events [23, 24]. Other clinical and demographic variables such as puberty, which bring hormonal changes known to influence PK in adolescents, and the patient’s clinical state, are known to influence dosing requirements [25]. Only with a greater understanding of the impact of such factors can we hope to rationally identify doses for different pediatric populations, particularly in the absence of robust clinical data. The following section addresses a key determinant of dosing requirements, the age-related changes in the PK processes acting upon a dose exposure.
\nFor many drugs, dosage regimens are designed to attain and maintain drug concentrations within a therapeutic window, the range of concentrations that produce a desired effect. Pediatric therapeutic windows may be quite different from the adult due to PD differences, such as receptor ontogeny (maturation of receptor number and functionality), and organ specific distributional differences resulting in different tissue concentrations of drug to elicit pharmacological activity. Such differences can result in differences in efficacy and toxicity which brings into question use of pediatric therapeutic ranges based on adult clinical data. However, the absence of dose-concentration-response data in children results in a void of evidence that risks the development of arbitrary therapeutic ranges. This was evident with theophylline for neonatal apnea where the therapeutic range adopted in the early 1980s was inadequate and a considerable number of neonates were under-dosed [26]. Understanding the therapeutic range of the cannabinoids for the different pediatric age-strata will be necessary to optimize dosing guidelines for
The attainment of plasma concentrations within the therapeutic window depends on route of administration, dosing frequency, size of dose, and the PK acting on the administered dose. Knowledge of the volume of distribution (Vd) is necessary in the design of a loading dose (the dose needed to quickly produce therapeutic concentrations, CTher), where Vd and the bioavailable dose (F × Dose) determine the plasma concentration (Eq. (1)). Following a chronic dosing regimen, the mean steady state therapeutic concentration (CSS,Ther) is the result of the bioavailable dose, dosing interval (τ), and systemic clearance (ClS) (Eq. (2)).
\nWith extravascular dosing (e.g., oral dosing), compounds must undergo absorption into the systemic circulation. Typically, less than 100% of the administered dose becomes available to the systemic circulation as presystemic mechanisms can limit the fraction of the oral dose that enters the systemic circulation as an unmodified compound (i.e., bioavailability (F)). Once absorbed into the blood supply, compounds distribute to the tissues of the body while systemic clearance mechanisms function to eliminate the compound. Hence, systemic exposure is determined by the extent of absorption (bioavailability) and by the efficiency of the systemic clearance mechanisms, while organ specific exposure additionally depends upon tissue distribution properties of the compound. Age-related changes occur with all these PK processes such that a standard dosage regimen will produce different systemic and tissue-specific exposure levels during pediatric development.
\nThe most common route of administration for pediatric patients is the oral route. The rate and extent of oral absorption is determined by the interaction of the physicochemical properties of the cannabinoid and its formulation with the physiological processes governing absorption. With oral ingestion of cannabinoids, time (Tmax) to maximum concentrations (Cmax) varies on average from 1 to 6 h, and bioavailability is low and quite variable (4–12%) in adults due to extensive first pass effects [27, 28]. As well, first-pass metabolism following an oral administration results in production of active metabolites (e.g., 11-hydroxy-THC, 7-hydroxy-CBD) with potent psychoactive effects that contribute to the pharmacology of the cannabinoids [27]. Age-related differences in Tmax, Cmax, and F may cause important differences in the onset and intensity of effect of an oral cannabinoid dose.
\nGrowth and maturation of gastrointestinal absorption processes variably influence both absorption rate and extent (i.e., bioavailability), a key determinant of the effective dose. pH dependent passive diffusion, biliary excretion, and gastrointestinal (GIT) transit times undergo considerable change with maturation [29]. Gastric pH is high at birth, becomes acidic in the first 24 h, returns to neutral pH values within the first 10 days of life, and subsequently decreases to adult pH levels within the first year or two of life [16]. Intestinal tract pH tends to be similar with the adult at all pediatric age groups [30]. Although impact of pH is likely limited on cannabinoid bioavailability (as these are neutral compounds), the higher gastric pH might reduce the extent of THC degradation [31]. Biliary excretion, though, is lower in the neonate (2–4 mM) than the adult (5–6 mM) in the first weeks of life, which is due to immaturity of the hepatic transporters responsible for their biliary excretion rather than ability to synthesize bile salts [32, 33]. As hydrophobic molecules, this may reduce cannabinoid bioavailability due to lower GIT solubilization in the first months of life. Gastrointestinal motility is also reduced at birth and gastric emptying and intestinal peristaltic function likely become similar to adults in the first weeks of life [34, 35]. This suggests Tmax is likely to be similar with adults within a month of birth, although differences in motility may not influence Cmax.
\nOther gastrointestinal physiological factors that have importance on the extent of absorption (i.e., bioavailability) include gastrointestinal permeability and first pass effects. All cannabinoids undergo passive permeation across the gastrointestinal epithelium. Intestinal permeability is initially high at birth given the leakiness of the epithelial tight junctions, but with junction closure within the first week of birth overall permeability becomes lower than adult due to a smaller intestinal absorptive surface area [36]. Passive transport mechanisms likely reach adult values within 4 months of birth. First-pass effects have a longer maturational trajectory. First pass effects include the activity of microbiota and gut luminal enzymes, enzymes and transporters of the gastrointestinal epithelia and liver. In adults, the low and variable bioavailability of CBD and THC is due to pre-systemic elimination by cytochrome P450 enzymes, principally CYP3A4 and CYP2C’s, expressed in the intestinal and hepatic epithelium [37]. Intestinal and hepatic CYP3A4 expression and hepatic CYP2C expression principally contribute to considerable first-pass metabolism and the low oral bioavailability of cannabinoids [38]. With development, hepatic CYP2C expression reaches adult levels by 6 months, exceeds adult levels in childhood, and returns to adult levels after puberty [39]. CYP3A4 undergoes a slower maturation with considerable increases in the first 6 months but does not reach adult levels until after 2 years of age [40, 41]. CYP3A4 activity also exceeds the adult in early childhood and returns to adult levels after puberty. Their developmental maturation suggests bioavailability is likely to be higher in neonates and infants until these enzymes reach adult expression levels. The xenobiotic transporters also contribute to first-pass effects. THC is a substrate of efflux transporters including p-glycoprotein (MDR1) and BCRP, while CBD only inhibits these efflux transporters. These transporters undergo rapid ontogeny in the first 6 months of life to reach adult values by 2 years of age, but may not contribute to age-related differences in bioavailability beyond 6 months of age [42]. The immaturity of these transporters can further enhance THC bioavailability relative to the adult.
\nBacterial activity within the gastrointestinal tract lumen may influence first pass metabolism. Whether cannabinoids undergo bacterial metabolism is unknown, but glucuronide metabolites may undergo deconjugation in the gut lumen. Children from 3 to 15 years of age showed no differences in activity of bacterial enzymes such as beta-glucuronidase, beta-glucosidase, and other enzymes and intestinal bacterial colonies approach adult characteristics by 1–4 years of age [43]. The gastrointestinal microbiome also influences the regulation of drug metabolizing enzymes and transporters, but information in the pediatric patient is lacking. A multitude of factors can influence the microbiome including age, disease, diet, and drug exposure, and our understanding of their impact during development is limited.
\nOverall, postnatal development of pH, gastrointestinal motility, and first-pass mechanisms should reach maturity by 5 years of age [17] at which time the rate and extent of oral absorption should have similarity to adult estimates. The variable rate and pattern of maturation, though, will lead to large ranges in Tmax, Cmax, and bioavailability estimates between the different pediatric age classes. Since variability in blood concentrations is principally inversely proportional to oral bioavailability, we may expect important differences in the oral dose requirements needed to attain equivalent plasma concentrations and therapeutic responses. Variable bioavailability will challenge treating caregivers on advising doses indicated by age, and individualization of dosage regimens will remain necessary. This expectation, though, creates opportunity for development of pediatric dosage formulations that considers both the potential age influences on cannabinoid liberation from the dosage formulation and the need to provide higher and more consistent oral bioavailability. Effective oral formulations promise more consistent dosage recommendations and reductions in the risk of under- or overdosing.
\nAge-related differences in the extent of tissue distribution (i.e., volume of distribution, Vd) will impact intensity and duration of cannabinoid activity. In adults, the high plasma protein binding characteristics (>97% bound in the adult) [44] of the cannabinoids result in a small central Vd (2.5–3 L). The cannabinoids undergo rapid and extensive distribution into lipophilic tissues (e.g., brain and adipose) and the highly perfused tissues (e.g., heart, lung, and liver) resulting in a large steady state Vd with reports ranging from 2.5–3 to 10 L/kg [27, 45]. The slow redistribution of cannabinoids from tissues, in particular adipose, as well as enterohepatic recirculation lead to long half-lives ranging from 1.5 to 5 days or longer for THC and 1–2 days for CBD, and even longer for the metabolites [27, 45]. Since the Vd is an important determinant of half-life, which, in turn, is used to guide the dosing interval, the expected age-related differences in cannabinoid Vd are likely to lead to differences in half-lives between the pediatric age strata and a possible need to consider such differences in the dosing interval.
\nBody composition, plasma and tissue protein binding, and physicochemical characteristics of the cannabinoids will influence the extent of their distribution (i.e., Vd). For many compounds, Vd demonstrates a linear relationship with body size. In the pediatric population, body size can change from less than 1 kg to up to 100 kg or more with development. Consequently, Vd expressed on a per body weight basis will show tremendous variability in the pediatric population. Ratio of fat, muscle, and intracellular and extracellular water also changes with maturation. At birth, total body water is 75%, and total body water-to-fat ratio is the highest in neonates and young infants with total body water reaching adult values by 6 months [46]. However, older infants and toddlers tend to have the highest fat-to-body water ratio only to reach adult ratios in later childhood [46]. Although higher body fat to water ratio may suggest higher Vd for the hydrophobic cannabinoids in these age groups, studies with other highly lipophilic drugs suggest that the Vd was not different between adults and infants [47]. Past infancy, then, the Vd might be similar between children and adults for the cannabinoids [47]. The lipophilic nature of the cannabinoids, though, raise concerns with childhood obesity and whether obese children should be dosed based on actual or ideal body weights [48].
\nPlasma protein binding is an important physiological determinant of Vd and the unbound fraction in the blood. In adults, cannabinoids bind extensively to lipoproteins and albumin where the unbound fraction can range from 1 to 5% [44, 45]. In the pediatric population, the plasma levels of albumin and alpha1-acid glycoprotein, the two major plasma binding proteins, are lower at birth and increase gradually to reach adult values by 1–3 years of age [49]. Lipoprotein and triglyceride levels also rise gradually during the first year of life, with further increases in childhood and adolescence [50]. Consequently, neonates and infants might exhibit lower bound fractions of the cannabinoids due to lower lipoprotein and albumin concentrations. These age dependent increases in plasma proteins might also mean higher distribution volumes in the neonate and infant and a lower Cmax.
\nWith high binding characteristics, seemingly small differences in binding, though, may result in large differences in the availability of cannabinoids to bind to their therapeutic targets. The unbound concentration is known to better reflect the pharmacodynamics of highly bound drugs [51], and a greater unbound fraction coupled with a lower elimination capacity for the cannabinoids (see section below) would enhance the availability of cannabinoids at their pharmacological sites of action. This can result in more intense pharmacological or toxicological responses and possibly a need to adjust doses to ensure equivalent PD responses. In addition to the amount of protein available for binding, binding affinity shows age-related changes. The presence of endogenous competitors for plasma protein binding sites, such as bilirubin and free fatty acids, is higher in the neonate [52], and along with exogenous competitors (e.g., co-administered drugs) may further increase the unbound cannabinoid concentration with subsequent enhancements in their pharmacological or adverse effects. Either way this might necessitate a dose reduction.
\nRelevant to the cannabinoids is the possible influence of age-related differences in the volume of the brain and the permeability of the blood-brain-barrier. Brain volume is larger in younger children and approaches adult values at 4–6 years of age [53]. THC but not CBD is a substrate for P-glycoprotein (P-gp, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) [54], while both cannabinoids inhibit P-gp and BCRP activity [55, 56]. These transporters function to limit permeation of THC and other drug substrates across the blood-brain-barrier and expedite their elimination from the brain, while CBD brain uptake and removal is not influenced by these transporters [54]. This might suggest a longer residence time of CBD in brain tissue relative to THC and a potential disconnect between plasma levels and the psychoactive effects of these compounds. As an inhibitor of efflux transporters, CBD might also modulate brain disposition of THC, which could explain, in part, its known ability to modulate THC psychoactive effects [57]. Important cannabinoid-drug interactions might ensue with co-administration of other efflux transporter substrates with a concomitant risk for brain accumulation of these drugs and potential adverse effects. Finally, known pharmacogenetic polymorphisms in these transporters result in reduced activity, which may enhance brain penetration and residence, increase the psychoactive effects, and, in turn, risk
The lipophilic cannabinoids are eliminated primarily through hepatic metabolic clearance. Hepatic clearance depends on three physiological determinants, plasma protein binding, hepatic blood flow, and intrinsic clearance (the overall ability of the liver to metabolize a compound). The cannabinoids appear to fall within the class of intermediate to high extraction ratio compounds (systemic clearance ranging from 600 to 1190 mL/min for THC and 960 to 1560 mL/min for CBD) [59, 60], suggesting that hepatic clearance is influenced variably by hepatic blood flow, intrinsic clearance, and plasma protein binding or predominantly by the hepatic blood flow at the highest hepatic clearance values. All determinants undergo developmental maturation. Hepatic metabolic clearance of the cannabinoids principally involves cytochrome P450 enzyme-mediated metabolism. The metabolites generated from P450 enzyme reactions may undergo further phase II enzyme conjugation reactions for their subsequent renal or biliary excretion. An understanding of the contribution of Phase I and II enzymes is important as the rate and pattern of their maturation tend to follow different developmental trajectories.
\nCannabinoids are principally metabolized by CYP3A4, CYP2C9, and CYP2C19 [45, 61]. As a superfamily of enzymes, the developmental trajectories of P450 enzymes are grouped into three characteristic classes [62]. CYP3A4 and CYP2C enzymes are class II enzymes, where enzymes are expressed at low levels at birth and gradually increase postnatally to achieve adult values within a year or two of age [62]. For instance, CYP2C19 activity is less than one-third adult values at birth, surges to 50% of adult activity in the first month of postnatal life, and reaches adult values at 1 year of age [39]. After 1 year, the hepatic clearance of CYP2C19 substrates show similarity to adult values [62]. Although CYP3A4 is the most abundant hepatic P450 enzyme in the adult, the predominant CYP3A isoform at birth is CYP3A7, while CYP3A4 expression is only 10% of adult levels [62, 63]. A developmental switch is observed such that CYP3A4 activity increases concomitantly with reductions in CYP3A7 activity. By 1 year of age, CYP3A4 activity is 75% adult levels, while CYP3A7 activity is considerably reduced [62, 63]. Although the two isoforms share 95% identity in their nucleotide sequence, differences in substrate specificities are noted for the two isoforms as well as a lower metabolism rate by CYP3A7 [64]. No study has evaluated the metabolic activity of CYP3A7 against CBD and THC, but CBD was identified as an inhibitor of this CYP3A isoform [65].
\nCBD, THC, and their respective metabolites also undergo phase II metabolism principally by the UDP-glucuronosyltransferase (UGT) enzymes. UGT1 and UGT2 families are involved in drug metabolism and typically more than one isoform contributes to the metabolism of a single compound [66]. Generally, the UGT enzymes have 25% activity in young infants relative to adult levels with adult levels achieved within 6–30 months of birth [66]. However, individual UGT enzymes undergo different maturation patterns leading to considerable variability reported in the glucuronidation capacity of newborns and infants.
\nThe developmental pattern of the major cannabinoid metabolizing enzymes suggests that systemic clearance and oral bioavailability may change throughout the pediatric period. Neonates and infants may demonstrate lower systemic clearance and higher oral bioavailability due to reductions in hepatic metabolism, but adolescents may have similar values to the adult. Interesting children ages 2–12 may require larger weight adjusted doses. In a mechanistic-based analysis, for drugs almost solely eliminated by CYP3A4 children required higher (~2 times) doses corrected for body weight relative to the younger child and adult, although similar weight-corrected doses between children and adults were required for drugs eliminated solely by CYP2C19 or UGT isoforms to achieve equivalent plasma concentrations [17]. Given the contribution of both P450 enzymes to the elimination of cannabinoids, higher weight adjusted doses may be required in children relative to the adult due to higher systemic clearance or first-pass metabolism.
\nQuantitatively and qualitatively P450 and UGT enzymes show considerable variation in their developmental maturation both within and between the age strata. A consequence of this variation may be altered cannabinoid metabolite profiles relative to the adult. After oral administration in the adult, extensive first-pass metabolism results in the production of high circulating levels of bioactive hydroxylated metabolites of CBD and THC [27]. These active metabolites contribute to the pharmacology of
Renal and biliary excretion mediates the elimination of the cannabinoid phase I and II enzyme metabolites. Elimination by the kidney occurs by glomerular filtration and tubular secretion. Neonates are born with reduced glomerular and tubular function, which is further compromised in the preterm neonate due to incomplete nephrogenesis [68]. Profound anatomical and functional changes in the kidney occur following birth that include enhancements in renal blood flow, redistribution of blood flow in the kidney, improvements in glomerular filtration efficiency, and the growth and maturation of renal tubules and tubular processes. These changes result in rapid attainment of renal elimination function within the first year of age [68]. Maturation of glomerular filtration processes precedes tubular processes, such that glomerular filtration rate reaches adult levels by 6 months of age and tubular reabsorption and excretion processes mature to adult levels by 1 year of age [68]. The excretion rate in toddlers and preschool children, though, can exceed adult levels but subsequently returns to adult levels in childhood [68]. The anatomical and functional immaturity of the kidney and the discordance in the maturation of glomerular and tubule function can contribute to considerable interindividual variability in renal elimination in pediatric patients.
\nTransporters are categorized into ATP-Binding Cassette (ABC) and Solute Carrier (SLC) families. ABC proteins are efflux transporters expressed apically at tissue-blood interfaces and function to limit penetration of compounds into these tissues. Maturation of ABC transporters can result in a developmental vulnerability to THC use. ABC transporter ontogeny as well as genetic variation (polymorphisms) is known to influence treatment response to drugs and increase risk for psychiatric disorders in pediatric populations as a result of altered disposition to the brain [69]. For example, the common P-glycoprotein (ABCB1) genetic variant C3435T, which results in altered p-glycoprotein expression, was associated with increased risk of
Dosing considerations of the pediatric patient not only need to acknowledge the impact of age-related changes in PK processes, but also the maturation of the endocannabinoid system and how this will influence PD and the relationship between exposure and response. Very little data, though, are available from human clinical studies on the developmental maturation of the endocannabinoid system and how these may influence cannabinoid pharmacology. What is known is that the endocannabinoid system is expressed early in fetal life and plays a critical role in normal neurological development. Cannabinoid receptor populations and levels of the enzyme systems and endocannabinoids are dynamic in pediatric development particularly during adolescence [70]. Some data suggest daily high dose exposure to THC may pose a risk to normal neurological development, although the data are not available for CBD [71].
\nThe lack of data on PD ontogeny and age-specific exposure-response relationships risks development of inappropriate therapeutic ranges. In the absence of any data, the treating caregiver may apply therapeutic ranges in adults or older pediatric age groups to younger pediatric age classes on the assumption of a similar exposure-response relationship to help inform dose selection [72]. Yet drawing from examples with other drugs, changes in receptor density expression with maturation have altered the efficacy and safety of drugs in children, such as reduced PD sensitivity to propofol resulting in overdosing and subsequently myocardial failure, metabolic acidosis, multiorgan failure, and death [73]. Given that the endocannabinoid system undergoes continued development, therapeutic windows are likely to be different among the different pediatric age strata.
\nThe toxicity of cannabinoids is generally considered quite low. In adults, cannabinoids have a number of central nervous system effects that include intoxication, appetite stimulation, disruption of psychomotor behavior, short-term memory impairment, antinociceptive actions, and anti-emesis. Lethal doses are unknown, but the size of a single lethal dose is likely to be very high. The apparent low toxicity in adults, though, cannot necessarily translate to a low adverse effect potential in pediatric patients. Very little information exists on the pediatric specific adverse effects of
In pediatric patients, medical
Other PK and PD interactions of concern include interactions at efflux transporters and impact of disease. The exposure-response relationship can be affected by clinically relevant interactions at the efflux transporters expressed at the blood brain barrier. Such interactions can alter the brain distribution of the pharmacologically active cannabinoid fraction to enhance cannabinoid response at a given
We face a clinical and ethical dilemma in the use of medical
IntechOpen - where academia and industry create content with global impact
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\\n\\nBut, one thing we have in common is -- we are all scientists at heart!
\\n\\nSara Uhac, COO
\\n\\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
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\\n\\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\\n\\nDr Alex Lazinica
\\n\\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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\n\nBut, one thing we have in common is -- we are all scientists at heart!
\n\nSara Uhac, COO
\n\nSara Uhac was appointed Managing Director of IntechOpen at the beginning of 2014. She directs and controls the company’s operations. Sara joined IntechOpen in 2010 as Head of Journal Publishing, a new strategically underdeveloped department at that time. After obtaining a Master's degree in Media Management, she completed her Ph.D. at the University of Lugano, Switzerland. She holds a BA in Financial Market Management from the Bocconi University in Milan, Italy, where she started her career in the American publishing house Condé Nast and further collaborated with the UK-based publishing company Time Out. Sara was awarded a professional degree in Publishing from Yale University (2012). She is a member of the professional branch association of "Publishers, Designers and Graphic Artists" at the Croatian Chamber of Commerce.
\n\nAdrian Assad De Marco
\n\nAdrian Assad De Marco joined the company as a Director in 2017. With his extensive experience in management, acquired while working for regional and global leaders, he took over direction and control of all the company's publishing processes. Adrian holds a degree in Economy and Management from the University of Zagreb, School of Economics, Croatia. A former sportsman, he continually strives to develop his skills through professional courses and specializations such as NLP (Neuro-linguistic programming).
\n\nDr Alex Lazinica
\n\nAlex Lazinica is co-founder and Board member of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his Ph.D. in Robotics at the Vienna University of Technology. There, he worked as a robotics researcher with the university's Intelligent Manufacturing Systems Group, as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and, most importantly, co-founded and built the International Journal of Advanced Robotic Systems, the world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career since it proved to be the pathway to the foundation of IntechOpen with its focus on addressing academic researchers’ needs. Alex personifies many of IntechOpen´s key values, including the commitment to developing mutual trust, openness, and a spirit of entrepreneurialism. Today, his focus is on defining the growth and development strategy for the company.
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\r\n\tPollution is caused by a wide variety of human activities and occurs in diverse forms, for example biological, chemical, et cetera. In recent years, significant efforts have been made to ensure that the environment is clean, that rigorous rules are implemented, and old laws are updated to reduce the risks towards humans and ecosystems. However, rapid industrialization and the need for more cultivable sources or habitable lands, for an increasing population, as well as fewer alternatives for waste disposal, make the pollution control tasks more challenging. Therefore, this topic will focus on assessing and managing environmental pollution. It will cover various subjects, including risk assessment due to the pollution of ecosystems, transport and fate of pollutants, restoration or remediation of polluted matrices, and efforts towards sustainable solutions to minimize environmental pollution.
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",annualVolume:11967,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/39.jpg",editor:{id:"137040",title:"Prof.",name:"Jose",middleName:null,surname:"Navarro-Pedreño",fullName:"Jose Navarro-Pedreño",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRAXrQAO/Profile_Picture_2022-03-09T15:50:19.jpg",institutionString:"Miguel Hernández University of Elche, Spain",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"177015",title:"Prof.",name:"Elke Jurandy",middleName:null,surname:"Bran Nogueira Cardoso",fullName:"Elke Jurandy Bran Nogueira Cardoso",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRGxzQAG/Profile_Picture_2022-03-25T08:32:33.jpg",institutionString:"Universidade de São Paulo, Brazil",institution:null},{id:"211260",title:"Dr.",name:"Sandra",middleName:null,surname:"Ricart",fullName:"Sandra Ricart",profilePictureURL:"https://mts.intechopen.com/storage/users/211260/images/system/211260.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}}]},{id:"40",title:"Ecosystems and Biodiversity",keywords:"Ecosystems, Biodiversity, Fauna, Taxonomy, Invasive species, Destruction of habitats, Overexploitation of natural resources, Pollution, Global warming, Conservation of natural spaces, Bioremediation",scope:"