Characteristics of the phenol used.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"6360",leadTitle:null,fullTitle:"New Horizons in Laparoscopic Surgery",title:"New Horizons in Laparoscopic Surgery",subtitle:null,reviewType:"peer-reviewed",abstract:"Approximately 100 years ago, after the first diagnostic laparoscopy and subsequent developments, the adventure began with laparoscopic appendectomy and cholecystectomy and reached a point where any surgical procedure could be performed easily. Today, many endoscopic surgical procedures have an important role not only in general surgery, but also in the daily practice of many surgical branches. This vertiginous development and change of speed make rapid replacement of the visual and printed materials necessary for training in this area. This book is prepared by surgeons who are very successful in their field.",isbn:"978-1-78923-733-7",printIsbn:"978-1-78923-732-0",pdfIsbn:"978-1-83881-427-4",doi:"10.5772/intechopen.69822",price:119,priceEur:129,priceUsd:155,slug:"new-horizons-in-laparoscopic-surgery",numberOfPages:116,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"f135ee4d1d0cc5f961b558004f073b07",bookSignature:"Murat Ferhat Ferhatoglu",publishedDate:"September 19th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/6360.jpg",numberOfDownloads:8028,numberOfWosCitations:5,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:17,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 29th 2017",dateEndSecondStepPublish:"June 19th 2017",dateEndThirdStepPublish:"September 15th 2017",dateEndFourthStepPublish:"December 14th 2017",dateEndFifthStepPublish:"February 12th 2018",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"200126",title:"M.D.",name:"Murat Ferhat",middleName:null,surname:"Ferhatoglu",slug:"murat-ferhat-ferhatoglu",fullName:"Murat Ferhat Ferhatoglu",profilePictureURL:"https://mts.intechopen.com/storage/users/200126/images/4973_n.png",biography:"Ferhatoglu M.D. has been working as an assistant professor in Okan University, General Surgery Clinic since 2016. M.Ferhat Ferhatoglu M.D has specialized in gastrointestinal system surgery. Presenting 51 presentations at national and international congresses. Ferhatoglu M.D. also has 4 articles and 1 book section.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Okan University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1146",title:"Laparoscopic Surgery",slug:"laparoscopic-surgery"}],chapters:[{id:"59815",title:"Laparoscopic Appendectomy",doi:"10.5772/intechopen.74192",slug:"laparoscopic-appendectomy-2018",totalDownloads:1077,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Appendectomy represents a fundamental step in the training course of a surgeon in so much that for several decades it has been the first surgical operation assigned to a training surgeon. Yet, laparoscopic appendectomy has not spread with the same characteristics as the operation of cholecystectomy for which laparoscopy has rapidly become the gold standard. We can moreover note that nowadays, in spite of a certain initial distrust, the laparoscopic methodology is fully employed in the treatment of acute appendicitis, even though the use of such technique is controversial in cases of acute complicated appendicitis.",signatures:"Paolo Ialongo, Giuseppe Carbotta and Antonio Prestera",downloadPdfUrl:"/chapter/pdf-download/59815",previewPdfUrl:"/chapter/pdf-preview/59815",authors:[{id:"213618",title:"Dr.",name:"Paolo",surname:"Ialongo",slug:"paolo-ialongo",fullName:"Paolo Ialongo"},{id:"213631",title:"Dr.",name:"Antonio",surname:"Prestera",slug:"antonio-prestera",fullName:"Antonio Prestera"},{id:"213778",title:"Dr.",name:"Giuseppe",surname:"Carbotta",slug:"giuseppe-carbotta",fullName:"Giuseppe Carbotta"}],corrections:null},{id:"62900",title:"Diastasis Recti and Other Midline Defects: Totally Subcutaneous Endoscopic Approach",doi:"10.5772/intechopen.75653",slug:"diastasis-recti-and-other-midline-defects-totally-subcutaneous-endoscopic-approach",totalDownloads:917,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Diastasis of the rectus is defined as the separation of the midline or alba line, which originates in a laxity of the interlocking fibers from the aponeurosis of both rectus muscles. At present, its surgical correction continues to be discussed. However, there is a multiplicity of factors that justify it.",signatures:"Pablo José Medina, Guido Luis Busnelli and Walter Sebastián Nardi",downloadPdfUrl:"/chapter/pdf-download/62900",previewPdfUrl:"/chapter/pdf-preview/62900",authors:[{id:"213193",title:"Dr.",name:"Jose Pablo",surname:"Medina",slug:"jose-pablo-medina",fullName:"Jose Pablo Medina"},{id:"213197",title:"Dr.",name:"Walter",surname:"Nardi",slug:"walter-nardi",fullName:"Walter Nardi"},{id:"215349",title:"Dr.",name:"Guido",surname:"Busnelli",slug:"guido-busnelli",fullName:"Guido Busnelli"}],corrections:null},{id:"61213",title:"Robotic Hysterectomy for Cancer and Benign Pathology",doi:"10.5772/intechopen.76466",slug:"robotic-hysterectomy-for-cancer-and-benign-pathology",totalDownloads:977,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The da Vinci Surgical System is an innovative technology that has advanced the laparoscopic treatment of benign and malignant diseases in gynecology. In this chapter, we will discuss the da Vinci Surgical System technology, including its history, utilization, surgical technique for benign and oncologic hysterectomy, future directions and surgical complications. Through a review of the literature, we aim to chronicle the current trends of application in both benign and oncologic gynecologic conditions and describe the current standards of care in this innovative and evolving operative technology. Although the future utility of robotic surgeries and robotic hysterectomies necessitates further research, the potential application of this surgical method affords great promise.",signatures:"Adrian Kohut, Leah Goldberg and Alexandre Buckley De Meritens",downloadPdfUrl:"/chapter/pdf-download/61213",previewPdfUrl:"/chapter/pdf-preview/61213",authors:[{id:"212008",title:"Dr.",name:"Alexandre",surname:"Buckley De Meritens",slug:"alexandre-buckley-de-meritens",fullName:"Alexandre Buckley De Meritens"},{id:"225697",title:"Dr.",name:"Adrian",surname:"Kohut",slug:"adrian-kohut",fullName:"Adrian Kohut"},{id:"225698",title:"Dr.",name:"Leah",surname:"Goldberg",slug:"leah-goldberg",fullName:"Leah Goldberg"}],corrections:null},{id:"58211",title:"Laparoscopic Surgery for Gastric Cancer",doi:"10.5772/intechopen.72852",slug:"laparoscopic-surgery-for-gastric-cancer",totalDownloads:865,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In patients with gastric cancer, surgical resection is the only treatment that can offer cure or increase long-term survival. With the accumulation of experience in laparoscopic radical gastrectomy and the progress in surgical instruments, laparoscopic surgery for gastric cancer has gained popularity despite initial concerns regarding safety and oncological adequacy. As a result, laparoscopic technique has been widely applied in gastric cancer. Different meta-analyses showed that laparoscopic procedures are associated with less blood loss but longer operation time. Many studies have reported outcomes of laparoscopic surgery for early gastric cancer, but several authors also have shown that a laparoscopic approach can also be used in cases of advanced gastric cancer. We therefore conducted this study to expand our experience and to evaluate laparoscopic gastrectomy step by step in the light of recent reports while defining key points and surgical technique.",signatures:"Talha Sarigoz, Inanc Samil Sarici, Ozgul Duzgun and Mustafa Uygar\nKalayci",downloadPdfUrl:"/chapter/pdf-download/58211",previewPdfUrl:"/chapter/pdf-preview/58211",authors:[{id:"213577",title:"Dr.",name:"Talha",surname:"Sarigoz",slug:"talha-sarigoz",fullName:"Talha Sarigoz"},{id:"213868",title:"Dr.",name:"Samil",surname:"Sarici",slug:"samil-sarici",fullName:"Samil Sarici"},{id:"214666",title:"Dr.",name:"Ozgul",surname:"Duzgun",slug:"ozgul-duzgun",fullName:"Ozgul Duzgun"},{id:"214667",title:"Dr.",name:"Mustafa Uygar",surname:"Kalayci",slug:"mustafa-uygar-kalayci",fullName:"Mustafa Uygar Kalayci"}],corrections:null},{id:"60143",title:"Total Laparoscopic Hysterectomy",doi:"10.5772/intechopen.75652",slug:"total-laparoscopic-hysterectomy",totalDownloads:1272,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The applications of minimally invasive pelvic surgery continue to grow. This chapter focuses primarily on the preoperative evaluation, surgical technique and post-operative care of total laparoscopic hysterectomy. Since laparoscopic assisted vaginal hysterectomy is a slight modification of the procedure it is not being discussed separately. The major physiologic obstacles to safe laparoscopy include pregnancy, increased intra cranial pressure, abnormalities of cardiac output and gaseous exchange in the lung, chronic liver diseases and coagulation disorders. In a redo surgery there may be problems of laparoscopic port entry.",signatures:"Nidhi Sharma and Vanusha Selvin",downloadPdfUrl:"/chapter/pdf-download/60143",previewPdfUrl:"/chapter/pdf-preview/60143",authors:[{id:"220214",title:"Prof.",name:"Nidhi",surname:"Sharma",slug:"nidhi-sharma",fullName:"Nidhi Sharma"},{id:"225521",title:"Dr.",name:"Vanusha",surname:"Selvin",slug:"vanusha-selvin",fullName:"Vanusha Selvin"}],corrections:null},{id:"61192",title:"Auto-tracking camera for dry-box laparoscopic training",doi:"10.5772/intechopen.76716",slug:"auto-tracking-camera-for-dry-box-laparoscopic-training",totalDownloads:768,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"While laparoscopic surgery is less invasive than open surgery and is now common in various medical fields, laparoscopic surgery often requires more time for the operator to achieve mastery. Dry box training is one of the most important methods for developing laparoscopic skill. However, the camera is usually fixed to a particular point, which is different from practical surgery, during which the operational field is constantly adjusted by an assistant. Therefore, we introduced a camera for dry box training that can be moved by surgeons as desired by using computer vision. By detecting the ArUco marker, the camera attached onto the servomotor successfully tracked the forceps automatically. This system could easily be modified and become operable by a foot switch or voice, and collaborations between surgeons and medical engineers are expected.",signatures:"Masakazu Sato, Minako Koizumi, Kei Inaba, Yu Takahashi, Natsuki Nagashima, Hiroshi Ki, Nao Itaoka, Chiharu Ueshima, Maki Nakata and Yoko Hasumi",downloadPdfUrl:"/chapter/pdf-download/61192",previewPdfUrl:"/chapter/pdf-preview/61192",authors:[null],corrections:null},{id:"59483",title:"Handheld Devices for Laparoscopic Surgery",doi:"10.5772/intechopen.74117",slug:"handheld-devices-for-laparoscopic-surgery",totalDownloads:1259,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:0,abstract:"Despite the well-known benefits of minimally invasive surgery (MIS) to the patients, this surgical technique implies some technical challenges for surgeons. These technical limitations are increased with the introduction of laparoendoscopic single-site (LESS) surgery. In order to overcome some of these technical difficulties, new handheld devices have been developed, providing improved functionalities along with precision-driven and articulating instrument tips. In this chapter, we will review the current status of handheld devices for laparoscopy and LESS surgery. Devices that provide additional and innovative functionalities in comparison with conventional surgical instruments will be considered. Results will be based on studies published in the scientific literature and our experience. These surgical devices will be organized into two main groups, mechanical devices and robotic-driven devices. In general, these instruments intend to simulate the dexterity of movements of a human wrist. Mechanical devices are cheaper and easier to develop, so most of the available handheld instruments fall into this category. The majority of the robotic-driven devices are needle holders with an articulating tip, controlled by an interface implemented on the instrument handle. In general, these handheld devices claim to offer an enhancement of dexterity, precision, and ergonomics.",signatures:"Francisco M. Sánchez-Margallo, Juan A. Sánchez-Margallo and Amir\nSzold",downloadPdfUrl:"/chapter/pdf-download/59483",previewPdfUrl:"/chapter/pdf-preview/59483",authors:[{id:"14715",title:"Prof.",name:"Francisco M.",surname:"Sánchez-Margallo",slug:"francisco-m.-sanchez-margallo",fullName:"Francisco M. Sánchez-Margallo"},{id:"188738",title:"Dr.",name:"Juan A.",surname:"Sánchez Margallo",slug:"juan-a.-sanchez-margallo",fullName:"Juan A. Sánchez Margallo"},{id:"214776",title:"Dr.",name:"Amir",surname:"Szold",slug:"amir-szold",fullName:"Amir Szold"}],corrections:null},{id:"60942",title:"How to Prevent Irregular Adsorption of Fatty Tissue into the Irrigation-Suction Instrument",doi:"10.5772/intechopen.76467",slug:"how-to-prevent-irregular-adsorption-of-fatty-tissue-into-the-irrigation-suction-instrument",totalDownloads:893,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Background: While using an irrigation-suction instrument for laparoscopic surgery, the irregular adsorption of fatty tissue may damage the tissue or obstruct continuous sucking. New devices of divided silicone drain tip and Count-on Q™ to prevent irregular adsorption of fatty tissue were reported. Materials and methods: A cigarette-type silicone drain was cut 4 cm in length, slipped over the instrument to cover the side holes, leaving 1.2 cm free from the end and fixed by means of 1-0 silk above the side holes. The free tip was divided vertically into four even pieces like octopus arms. Count-on Q™ was the irrigation-suction instrument equipped with multiple small side holes. Results: Divided silicon drain tip could prevent the irregular adsorption of fatty tissue (greater and lesser omentum or epiploic appendices) and could suck saline, fresh, and coagulated blood continuously. Count-on Q™ also could prevent the irregular adsorption of fatty tissue and could suck saline and fresh blood except coagulated blood continuously.",signatures:"Tokihito Nishida and Hajime Ikuta",downloadPdfUrl:"/chapter/pdf-download/60942",previewPdfUrl:"/chapter/pdf-preview/60942",authors:[{id:"215296",title:"Ph.D.",name:"Tokihito",surname:"Nishida",slug:"tokihito-nishida",fullName:"Tokihito Nishida"},{id:"215298",title:"Dr.",name:"Hjime",surname:"Ikuta",slug:"hjime-ikuta",fullName:"Hjime Ikuta"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1041",title:"Advanced Laparoscopy",subtitle:null,isOpenForSubmission:!1,hash:"dc4dd4e41e2604c5b585fb734757b0e8",slug:"advanced-laparoscopy",bookSignature:"Ali Shamsa",coverURL:"https://cdn.intechopen.com/books/images_new/1041.jpg",editedByType:"Edited by",editors:[{id:"32349",title:"Prof.",name:"Ali",surname:"Shamsa",slug:"ali-shamsa",fullName:"Ali Shamsa"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"714",title:"Advances in Laparoscopic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"2e517c04d6d192c2f823eadc2998ac58",slug:"advances-in-laparoscopic-surgery",bookSignature:"Arshad M. Malik",coverURL:"https://cdn.intechopen.com/books/images_new/714.jpg",editedByType:"Edited by",editors:[{id:"63407",title:"Dr.",name:"Arshad",surname:"Malik",slug:"arshad-malik",fullName:"Arshad Malik"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5390",title:"Laparoscopic Surgery",subtitle:null,isOpenForSubmission:!1,hash:"e4007519c91e2b804f5ef9039b691db5",slug:"laparoscopic-surgery",bookSignature:"Arshad M. 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Bentonite is characterized by high adsorption, ion exchange, and swelling capacity, as well as by specific rheological properties (thixotropy). It, therefore, has wide applications, ever more numerous and in different fields (drilling, foundry, ceramics, painting, pharmacy, bleaching earth, …). Bentonites play a significant role in a diverse range of environmental problems and their applications are steadily increasing. Among the few fields of application, bentonite can be used for the purification of gases [1], the elimination of radioactive elements [2, 3], the elimination of pesticides [4], and the elimination of phenol. This pollutant was removed by variety of clays and modified clay as the bentonite [5], the clinoptilolite [6], the composite of silica [7], the silica/hydrotalcite [8], the natural clay [9], the Montmorillonite, Clinoptilolite and Hydrotalcite [10], the hectorite [11], the untreated coffee wastes [12], the lignite [13], the zeolite X/activated carbon [14], the shells of eggs [15, 16] and the chitin/chitosan [16, 17, 18].
Zohra Dali and all [5] have studied the adsorption of phenol on two types of clays: sediment after chemical activation with ammonium chloride and bentonite which has undergone activation by sulfuric acid. They concluded that the acidified bentonite exhibits more affinity towards phenol with a limited adsorption capacity equal to 32.23 mg/g. Myroslav and al [6] studied the kinetics of phenol adsorption on clinoptilolite modified by hexa decyl trimethyl ammonium (HDTAM). They have shown that phenol can be fixed by this clay with a percentage of (85–90%). The adsorption process is fast. All phenol were fixed after one hour. The adsorption isotherm is described by the Langmuir model.
By studying the interposed action of two kinds of clay (bentonite and kaolinite) by both the surfactant hexa decyl trimethyl ammonium (HDTAM) and the phenyl methyl ammonium bromide (PTMA), Uday and all [19], have shown that the kinetics of adsorption on both clays follows the model of the pseudo-second-order and the adsorption isotherm following the model Freundlich and Langmuir. The parameters thermodynamics shows that adsorption was exothermic and spontaneous. In another research, Jin and al [20], chose to intercalate a Na-montmorillonite with dihydroxy ethyl methyl ammonium bromide (ODEM). The results obtained showed that the adsorption kinetic of phenol by (Na-Mt) modified was pseudo-second-order. The adsorption isotherm described by the Langmuir model gave an adsorption capacity of (384.61 mg/g at 308 K). The parameters thermodynamics indicate that the adsorption process was exothermic and spontaneous. Richards and all [21], for their part, have studied the phenol adsorption kinetics on two clay (basaltic clay and bentonite) changes organically by hexa decyl trimethyl ammonium (HDTAM) and phenyl trimethyl ammonium. The results obtained shows that the adsorption kinetics of (HDTAM) -basaltic and (TMPA) -Bentonite was pseudo-second-order. For its part, Jianfeng and all [22] have studied the adsorption kinetics of phenol and ap-nitro-phenol and β - naphthol on organobentonite (Bentonite-TAB). They showed that phenol can be fixed by this organobentonite after 25 min at 69% and 92% for p-nitrophenol and 99% for β - naphthol. The treatment of phenol by adsorption flocculation using an organobentonite was studied by Yun Hwei [23]. The process consists of dispersing the bentonite in water by adding a cationic surfactant that has a short chain (BTMA). The result showed that BTMA bentonite had a high affinity for phenol and 90% of phenol was removed and 100% bentonite was recovered by the process of adsorption flocculation. The study by Basri and all [24] on bentonite modified by the surfactant cetyl trimethyl ammonium bromide (CTAB) as the adsorbent of phenol taking into account several parameters such as the pH of the solution, the contact time. At the initial concentration and temperature, we showed that the adsorption is maximal at pH = 9. The equilibrium was reached after 1 hour with a kinetic adsorption second order. The calculation of the thermodynamic parameter (∆G°), enthalpy (∆H°) and entropy (∆S°) has shown that the adsorption on the organobentonite is possible spontaneous and exothermic in the range of temperature 0-40C °. The adsorption of phenol and 2-chlorophenol and 2,4,6 trichlorophenol by organo-clays (Na-montmorillonite) modified by transition metal complexes was undertaken by Boufatit and al [25]. The results showed that the adsorption capacity of organophilic clay is not obeyed in a logical order, but depends on the nature of the complex. The work carried out by SYuening and all [26] allowed the study of the elimination of phenol using Na-montmorillonite modified with two new Gemini surfactants containing hydroxyl groups, 1,3-bis (hexa decyl dimethyl ammonio) -2-hydroxy-dichloride (BHHP) and1,3-bis (octyl dimethyl ammonio) - 2-hydroxy-dichloride (BOHP) as adsorbent. The effects of contact time, pH, temperature, and concentration of adsorbate on the adsorption performance of phenol by the Na - modified montmorillonite were examined by tests in batch. The results have shown that the kinetics follows the pseudo-second-order model, and the adsorption equilibrium data are described by the Langmuir model. The thermodynamic study has shown that the adsorption of phenol is a spontaneous and exothermic process.
The present chapter is interested in the study of the elimination of phenol as a very toxic pollutant using commercial bentonite (BTC) and treated bentonite. The treatment of the clay was carried out with acid solutions of different concentrations. Before starting the pollution treatment, physicochemical characterization of the bentonite was undertaken. The elimination of the pollutant was carried out by studying kinetic and isothermal adsorption process.
In the form of white crystals at ambient temperature, it is of GMBH origin. It has a purity of 99.5%. Phenol solutions were prepared with distilled laboratory water. The main characteristics of phenol are grouped in Table 1.
TF (temperature of melting in °C) | TE (temperature of boiling in °C) | S/H2O (gL −1) (20 °C) | μ (D) | pKa (acidity constant) |
---|---|---|---|---|
41 | 181 | 93 | 1.59 (pH → OH) | 9.9 |
Characteristics of the phenol used.
Phenol is weakly acidic and transforms in a basic medium into a phenolate anion according to the reaction:
Phenol is very toxic: VA = 19 mg.m −3.
The various phenol adsorption experiments on bentonite are carried out at room temperature. A fixed mass m 0 = 0.1 g of bentonite is contacted with the aqueous solution of phenol with an initial concentration of C0 = 2.10−3 M. The mixture is then stirred at 500 rpm for an adsorption time t (tads). For each experiment, the solution pH is adjusted, as necessary, by the addition of HCl (0.1 N) or NaOH (0.1 N).
After the time required for adsorption (tads), the solutions are filtered through a 0.45 μm microporous membrane, and then the filtrates obtained are analyzed by UV/Visible spectrophotometry and the bentonite by IRTF spectrophotometry.
Commercial bentonite (BTC) was treated with HCl 3 N (BTC3N) and HCl 12 N (BT12N) overnight. The objective of these treatments is to determine the effect of acid on the capacity of adsorption by BTC. The study of the adsorption kinetics of phenol and its isotherms was carried out by UV / visible and IRTF.
IR and UV / Visible spectrophotometry are two analysis techniques, based on the principle of absorption by the sample of a beam in IR [400–4000] cm−1 or UV / Visible [200–800] nm range.
Scanning electron microscopy is a spectroscopic technique, based on the principle of electron-matter interaction. An electron beam scans the surface of the powdered solid, deposited on a sample holder, which in response re-emits certain particles (electrons). Different detectors make it possible to analyze these particles and fully reconstruct the image or cartography of the surface of the solid analyzed. Combined with the EDX technique, it provides access to the chemical composition of the solid. This technique is used for the characterization of the texture of bentonite and its chemical composition.
Commercial bentonite (BTC) in the form of a very fine white powder was purchased from Rhône Poulenc. Its origin is a volcanic clay rock, strongly colloidal. It is identical to montmorillonite of the smectite group, consisting mainly of alumina silicate. Its crystalline structure is in the form of a sheet of alumina octahedron, placed between two sheets of silica tetrahedron. The percentage of silica is 50 to 60% and that of alumina is between 15 and 20%, the rest is in the form of metal oxides (Fe, Mg, Ti) and oxides of alkaline elements and alkaline earth (Na, K, and Ca) [3]. The amount of interstitial H 2 O and the nature of the exchangeable cations present in the interleaf space determine the Physico-chemical properties of bentonite. These essential properties enhance bentonite in its field of use and application.
Before performing the phenol removal experiments, the commercial bentonite BTC and treated with 3 N and 12 N HCl acid were characterized by the techniques of BET, IRTF, and SEM / EDX to evaluate the surface and active functions of clay.
The specific surface of the bentonite was evaluated at 19 m2/ g by the BET method using an automatic device of the ASAP type from the European Institute of Membranes (IEM) in Montpellier. Figure 1 shows the adsorption/desorption isotherm of N 2 at −196° C on the solid and in the Table 2 the parameters characterizing its texture. The isotherm thus obtained is of type IV, according to the IUPAC classification, exhibiting a hysteresis characteristic of mesoporous solids of type H3.
Adsorption/desorption isotherm of N2 on bentonite.
Methods | Values | Units |
---|---|---|
Point B method | 18.5351 | Specific area (m2 / g) |
BET | 19.4377 | |
BJH adsorption | 20.2408 | |
BJH desorption | 28.9052 | |
BET | 0.058366 | Volume (cm3 / g) |
BJH adsorption | 0.070829 | |
BJH desorption | 0.072696 | |
BET | 120.1091 | Diameter (Å) |
BJH adsorption | 139.9721 | |
BJH desorption | 100.5997 |
Textural characteristics of bentonite.
With BJH indicates pore size.
For BTC 3 N and BTC 12 N, the specific surface areas are equal to 96 m2/g, greater than the surface area of BTC, indicating an increase in nitrogen adsorption sites.
For many technical applications, raw bentonites must be subjected to a preparation adapted to the requirements of their use (activation). Activation with acids such as hydrochloric acid increases porosity by the peripheral dissolution of Smectites. This results in a product with a high adsorption capacity. They are used for clarification or protein stabilization operations in musts and wines [27].
Scanning electron microscopy images, taken at different scales and two different locations, under the energy of 30 keV, are shown in Figure 2 for BTC, BTC 3 N, and BTC 12 N. They show that BTC is not treated with HCl, which has a mesoporous sheet structure and variable particle size. Their values are in perfect agreement with the results of BET and BJH. On the other hand, for treated BTC, the SEM images show an increase in the number of pores and a decrease in their size with the concentration of HCl. The surface of BTC 12 N becomes very compact indicating the formation of several micro-pores.
Microscopic images of BTC, BTC 3 N, and BTC 12 N.
The IR spectrum of Figure 3 shows the absorption bands of commercial bentonite before its contact with phenol. The bands thus observed are characteristic of the structure of clays belonging to the smectite class, such as montmorillonite and bentonite. Table 3 shows the different frequencies and their attributions to the different vibration modes [28, 29].
IRTF spectrum of commercial bentonite.
ν (cm −1) | Vibrations | Vibration type |
---|---|---|
477 | Si-O-Si | vibration of distortion out of plane |
525 | Si-O-Al or Mg, Fe | vibration of distortion out of plane |
630 | Al-O and Si-O | vibration of distortion out of plane |
795 | Quartz | Si-O vibration |
845 | Al-Mg-OH | Vibration of valence |
875 | Al-Fe-OH | The vibration of valence (Al; Mg) |
917 | Al- AlO -H | The vibration of valence OH (Fe, Mg) |
1035 | Si-O- Si tetrahedron | Asymmetric vibration in the plane |
1084 | Al-OH | Vibration in the plane |
1494 | OH (H 2 O) | H 2 O deformation vibration |
1640 | CH 2: alkanes | The vibration of deformation CH bond of |
2920 2847 | H 2 O | H bond or of combination (2x1640) |
3252 | Interfoliar H 2 O | Asymmetric and symmetrical vibration |
3444 | Si-OH; Al-Al-OH | Free OH elongation vibration |
3634 |
IR bands of commercial bentonite.
The comparison between raw and treated bentonite has been illustrated in Figure 4. This figure represents a comparison of the IR spectra of the three samples: BTC, BTC 3 N, and BTC 12 N, before adsorption of the phenol. It can be observed that the acid treatment of BTC with 3 N HCl leads to a slight increase in the bands initially identified on BTC in the [3700–1600] cm−1 domain compared to BTC 12 N and BTC 6 N. However, in the [400–1500] cm−1 domain, this evolution is not observed since the intensities of the bands decrease in the following order: BTC 3 N > BTC 6 N > BTC 12 N, the treatment of alumino-silicates with concentrated acids generates a change in the Si / Al ratio, the major element in the composition of bentonite and on the occasion of new MO bonds (M: Al, Si, or Mg) of the same type as those characterized for BTC can appear and contribute to the increase of these intensities. These bonds (MO) can combine in an acidic medium with the H + protons to form hydroxyl groups, which would explain the increase in the band at 3630 cm−1 (isolated or terminal OH). The increase in the band at 3435 cm−1, linked to the interfoliar H2 O, may be due to its adsorption and that at 3252 cm−1 to the strengthening of the hydrogen bond between water and OH groups [28].
IR spectra of BTC, BTC 3 N, and BTC 12 N.
On the other hand, these results are in good agreement with the increase in the specific surface which goes from 19 m2 /g for BTC to 96 m2/g for BTC 3 N and BTC 12 N.
The phenol adsorption kinetics were studied on commercial bentonite (BTC) and bentonite had undergone treatment for 12 hours with 3 N HCL (BT3N) and 12 N HCl (BT12N). To determine the time necessary for obtaining the adsorption equilibrium, phenol adsorption experiments (C0 = 2.10−3 M) were carried out for different contact times with a mass m = 0.1 g of commercial and treated bentonite.
It can be observed from the UV spectra of the residual phenol in Figure 5, the presence of two peaks of phenol, successively at max = 210 nm and 270 nm. Their position does not change concerning that of the pure phenol, which indicates that there is no reaction in solution between the phenol and the species released by the bentonite. The presence of two shoulders at λmax = 230 nm and λmax = 287 nm, is linked to the formation of the phenolate anion, which is favored in a basic medium. An increase in the pH value of the solutions from 8.9 to the value 10, which is equal to the pKa of phenol, was recorded for the stirring times. This increase in pH is explained by the release of the basic species by the BTC, in particular the Na+ cations.
(A and B) Evolution of the residual concentration of phenol after different adsorption times on bentonite.
On the other hand, the intensities of the peaks gradually decrease with the contact time, which indicates that the adsorption of phenol on BTC is favored in a basic medium.
By taking into account the deconvolution of the spectra, the exact intensities of the two peaks can be determined. The residual concentration of phenol Cr is in this case represented by the maximum absorbance of the first peak (Ar) in the calibration curve. This will allow the determination of the amount of phenol adsorbed Cards for different contact times using (Eq. (1)), namely:
where A 0 is the maximum absorbance of the peak at 270 nm for a concentration of phenol alone (C 0 = 2.10−3 M; A 0 = 2.71). The use of the above spectra leads to the phenol adsorption kinetics curve given in Figure 6. This curve shows that the adsorbed quantity of phenol rises rapidly as a function of time (t < 5 h) and then keeps a practically constant value for longer times. The saturation value of the surface corresponds to a concentration of the adsorbed phenol Cad = 8.10−4 M, which indicates, for C 0 = 2.10−3 M, a rate of elimination of the phenol of 40%. The linear rise observed may indicate the adsorption of phenol on equivalent sites, and the plateau obtained reflects a limited number of adsorption sites.
Adsorption kinetics of phenol (C0 = 2.10−3 M) on BTC / BTC3N / BTC12N.
The same evolution is observed for the adsorption of phenol on BT3N and BT12N with a significant drop in the quantity of phenol adsorbed at saturation. The acid treatment of BTC resulted in a significant loss of adsorption sites (Figure 6), following the results of SEM analysis, which showed a significant decrease in the pore size of the solids treated, which prevents access to the solids adsorption sites.
To elucidate the process of adsorption of phenol on BTC, several kinetic models have been proposed by Lagergren et al. [30], Ho et al. [31] and Boukhlifi et al. [32, 33] by considering pseudo-first--first-order and pseudo-second-order kinetics. The results obtained in this work can be subject to equations resulting from these models [30, 31, 32, 33].
Either phenol adsorption reaction on BTC:
Cr: residual concentration of phenol, S and S0 are, respectively, the area occupied by phenol and the total area of BTC.
The differential equation that results from the adsorption reaction is as follows (Eq. (2)):
where qt, in (mg / g) is the amount of phenol adsorbed at t; QE, in (mg / g) is the quantity of phenol at adsorption equilibrium and K ‘(min−1), the pseudo-rate constant.
Using the initial conditions (at, t = 0; qt = 0) and (at, t; qt), its rearrangement after integration gives (Eq. (3)):
The plot of ln (qe - qt) as a function of a (t), given in Figure 7, does not lead to a straight line as provided by the model equation. The curve obtained from the experimental data seems rather formed of two portions of straight lines. The first before t = 5 h (Figure 7) of negative slope can conform with the kinetic model of pseudo-first-order where the adsorption of phenol occurs in a very fast way (kinetic figure). However, the second portion, with a positive slope (Figure 7), is in contradiction with the equation of the proposed model. The linear regression coefficients R2 of the two lines are not close to 1, which makes it possible to conclude that the kinetics of adsorption of phenol on BTC cannot be described by a pseudo-first-order speed. In addition, the calculated value of qe (qe = 47 mg / g) is much higher than the experimental value (≈14.5 mg / g).
Kinetics modeling according to the pseudo-first-order model ln (q e - q t) as a function of a (t).
Kinetics modeling according to the pseudo second order model t/qt = f (t).
The same treatment can be carried out for the pseudo-second-order kinetics (Eq. (4)), namely:
The application of this equation to the experimental result of Figure 8, leads in this case to plotting t / qt = f (t)) to the right of Figure 8, with a linear regression coefficient (R2 = 0.995) very close to 1. The parameters K′2 and qe, determined from the slope (1 / qe) and the y-intercept (1 / K′2.qe2) of the equation of the line, are respectively equal to 0.532 g / (mg.h) and 13.7 mg / g. The value of qe obtained is in perfect agreement with the experimental value (≈14.5 mg / g), which indicates that the adsorption of phenol on bentonite obeys pseudo-second-order kinetics for the entire time range studied.
Intra-particle diffusion model.
The diffusion phenomenon (adsorbate ⇒adsorbent) also plays a determining role in the adsorption kinetics. The equation resulting from the treatment of the intra-particle diffusion model is given by the following relation (Eq. (5)) [34, 35, 36]:
where Kd is the intraparticle diffusion constant and C a constant. In the case where C = 0, the intra-particulate diffusion step is the step that controls the adsorption process, if C is nonzero this step is not limiting.
The plot
IR spectra of phenol adsorption on BTC.
The masses of the solids resulting from the BTC/phenol contact were analyzed by IRTF. Figure 10 shows the evolution of the spectra obtained after t = 1 hour and 17 hours of contact. The overall analysis of these spectra shows a clear decrease in the absorption bands of BTC, located at 477, 525, 1035, 1084, and 3634 cm−1 and related to the vibrations of the M-O bonds where M can represent the atoms of Si, Al, or Fe (Table 2). The decrease in these bands can be explained by their direct involvement in the adsorption of phenol on different sites of BTC. Their positions, which remain unchanged, meaning that the adsorption of phenol occurs at superficial sites. Indeed, for these two contact times, the intensities of these bands are practically equal, following the quantities of the adsorbed phenol, determined previously (Figure 6).
IR spectra of phenol adsorption on BTC 3 N.
On the other hand, the bands located at 3430 and 1634 cm−1, attributed to the OH vibrations of the interfoliar water and the shoulder at 3225 cm−1, attributed to the OH group linked by the hydrogen bonds (H…OH), increase slightly in intensity. For the first band, there is probably the formation of interfoliar water by dehydroxylation and for the last band, the formation of hydrogen bonds during the adsorption of phenol. The formation of H2O during the adsorption of phenol on clay solids have already been mentioned by several authors according to the following process:
This proposition is in good agreement with our results which simultaneously show the increase in the H2O bands and the decrease in the vibration band of the O -H groups at 3634 cm−1. Moreover, the mechanism of adsorption of phenol by hydrogen bonding has also been mentioned by SYuening and al [26]. This bond, characterized by the band at 3225 cm−1, results from an interaction between phenol and the oxygen atoms of the surface. It appears more marked for t = 17 h than t = 1 h of adsorption, following the intensities of the OH (3636 cm−1) and interfoliar H2O (3430 cm−1) vibration bands.
Adsorption of phenol on bentonite treated with 3 N and 12 N HCl was also monitored by IR. The spectra obtained are illustrated in Figures 11 and 12. It can be noted first that the bands detected on BTC (spectrum A) are also observed at the same positions on BTC 3 N (spectrum B) with an increase in their intensities. This means that the acid treatment leads, in the range [300–1100] cm−1, to the creation of MO bonds of the same type as those observed in BTC (Metal: Si, Al, and Fe) probably by breaking the OMO bonds or MOM. This explanation is confirmed on the one hand, by the increase in the intensity of the band to 3626 cm−1, often attributed to the vibration of the MOH (free OH) bond and on the other hand, by the increase in the specific surface area which goes from 19 m2 / g for BTC to 96 m2 / g for BTC 3 N. The band at 3436 cm−1, linked to the formation of the hydrogen bond increases in intensity under the effect of the acid treatment of BTC.
IR spectra of adsorption of phenol on BTC 12 N.
Furthermore, the adsorption of phenol on BTC 3 N leads to a reduction in the intensities of the characterized bands, except for the bands located at 3436, 3225, and at 1640 cm−1. Taking into account the kinetic curve of Figure 6, it was found that the amount of phenol adsorbed by BTC 3 N is lower than that adsorbed by BTC.
The adsorption isotherm was obtained at T = 25° C, by bringing different initial concentrations of C0 of phenol into contact with BTC for a period t = 5 hours at pH = 6. The study of this isotherm is essential since it makes it possible, from known models, to obtain information on the adsorption parameters characterizing the adsorbate/adsorbent interaction.
The plot of the amount of adsorbed phenol (Cads) as a function of Cr gives the curve of the corresponding isotherm, represented by Figure 13. Several models are used to exploit the adsorption isotherms, the most commonly adapted to the adsorption of liquids are the isotherms of Langmuir (homogeneous sites) and Freundlich (heterogeneous sites). The latter is used to determine the parameters giving information on the nature of the interaction (adsorbate/adsorbent).
Phenol adsorption isotherm.
This model assumes that the adsorption sites are energetically equivalent and there is no interaction between the adsorbates at two neighboring sites. The equation that governs this model is as follows (Eq. (6)):
Its linearization makes it possible to determine the constants Qmax and b (Eq. (7)), namely:
It can be observed in Figure 14 that the experimental results do not verify the Langmuir model since the plot of 1 / qe = f (1 / Ce) does not give a straight line. Besides, the theoretical line obtained by linear regression of the experimental points gives a correlation coefficient R2 = 0.938, less than 1. The constants Qmax and b deduced from the ordinate at the origin and the slope of this line are, respectively, equal at Qmax = 10.42 mg / g and b = 1.05 m/g. Another parameter noted RL given by the relation below (Eq. (8)), characterizes a constant of the equilibrium of the Langmuir model. It makes it possible to predict whether such a model is favorable or not according to certain conditions on the values of RL:
Langmuir isotherm for the adsorption of phenol on BTC.
If 0 < RL <1: the isotherm is favorable; if RL = 1: the isotherm is linear and if RL > 1: the isotherm is not favorable and if RL = 0: the isotherm is irreversible.
The calculation of RL is carried out for C0 (max) = 6.10-3 M = 11.28 mg, which gives for RL a value of 0.08. This value is very close to 0 if one takes into account the uncertainties on b and C0, which confirms that the Langmuir model is not favorable.
This model is often applied in liquid / solid adsorption, it takes as the main assumption a heterogeneity of the solid adsorption sites. The empirical equation established by Freundlich is as follows (Eq. (9)):
where K, F, and n are the Freundlich constants, related, respectively, to the adsorption capacity and its intensity. Applying this equation in its logarithmic form to the experimental data leads to the values of these constants from the y-intercept and the slope of the following line (Eq. (10)):
Figure 15 shows the obtaining of a perfect line with a correlation coefficient very close to 1 (R2 = 0.998), for the initial concentrations used, between 10 −3 M and 6.10−3 M. The values found for the constants KF and n are, respectively, equal to 5.68 mg / g and 4.06. The low value of (1 / n = 0.246), indicates that the Freundlich model is more suitable for describing the adsorption isotherm of phenol on a BTC surface having very heterogeneous sites, the number of which is low if the value of KF is taken into account.
Freundlich isotherm for the adsorption of phenol on BTC.
The study of the adsorption of phenol on commercial BTC has shown that this pollutant can be eliminated from liquid effluents with a fairly large percentage (40%). This encouraging result allows us to extend this study to real industrial discharges. The treatment of bentonite with concentrated HCl (3 N) and (12 N) did not give satisfactory results, although it led to an increase in the specific surface from 35 m2/g for bentonite not treated to 96 m2/g for bentonite treated with acid. This is due to a decrease in the number of phenol adsorbing sites and the decrease in the pore diameters as shown by the analyzes by BET and SEM. The modeling of the experimental results of the adsorption isotherm made it possible to specify the most appropriate kinetic model, the adsorption is fast before two hours. It is the Freundlich model which is favorable for a surface having heterogeneous sites. The adsorption capacity was evaluated at 5.68 mg/g. The mechanism of phenol adsorption by hydrogen bonding has also been proven by spectroscopic analyzes. This bond, characterized by the band at 3225 cm−1, results from an interaction between phenol and the free oxygen doublet of the surface.
About 7% of the population >65 years suffer from a painful heel, even though younger people are often affected, too [1]. The most common cause of this symptom is the so‐called “plantar fasciitis” [2]. This term is widely used, although “plantar fasciopathy” or “plantar fasciosis” would be a better description to point out the degenerative nature of the disease. However, as more than 1100 citations in Pubmed quote “plantar fasciitis” (in comparison with only 50), we will use the traditional term in the following.
Plantar fasciitis has been associated with obesity, with acute or chronic work overload, or with work on hard surfaces [2, 3]. It seems that physiological degeneration of the fascia at the calcaneal insertion exacerbates due to repetitive microtraumas caused by vertical compression [4]. This causes inflammatory tissue reactions. As a result, the fascia is thickened with an associated fluid collection to 4.0 mm and more in ultrasonography [5]. Furthermore, this inflammation may trigger bone formation, the so‐called “plantar heel spur.” This process has been studied intensively by Kumai and Benjamin [6]. They proposed three stages of spur growth: “(a) an initial formation of cartilage cell clusters and fissures at the plantar fascia enthesis; (b) thickening of the subchondral bone plate at the enthesis as small spurs form; and (c) development of vertically oriented trabeculae buttressing the proximal end of larger spurs” [6]. The first description of this spur formation and correlation with the clinical symptoms was carried out by Plettner in 1900 [7]. However, not every heel spur is associated with heel pain, as these spurs are found in 11–16% of the normal asymptomatic population [4]. On the other hand, some patients with painful plantar fasciitis do not have a radiographic confirmation of a spur formation.
A similar mechanism (although caused by longitudinal traction and not by vertical compression) of bone formation has been described at the insertion of the Achilles tendon [8].
According to the American clinical practice guidelines from 2010, diagnosis is established by the typical anamnesis and the characteristic localizations of tenderness. Still, weight‐bearing radiographs are also recommended [9].
Single doses of external beam radiotherapy (EBRT) in the range of 0.3–1 Gy are called “low dose EBRT” (LD‐EBRT). These single fractions are applied two or three times a week until a total dose of about 3–6 Gy is reached. Such radiotherapeutic concepts are used for diverse nonmalignant conditions, e.g., osteoarthrosis, tendinopathy, epicondylitis, or bursitis. A comprehensive review of the historical developments in LD‐EBRT for benign diseases is given by Trott [10].
In contrast, EBRT in oncology is characterized by much higher single and total doses. “Normofractionation” describes single doses of 1.8–2 Gy, applied about five times a week. To treat breast cancer, the total doses of about 62 Gy are necessary, in prostate cancer even more than 72 Gy. From a radiobiological point of view, these high cumulative doses are used to induce DNA double strand breaks. Due to errors in a repair mechanism (nonhomologous end joining), dicentric chromosomes can occur. These can result in unfinished mitoses, the so‐called “mitotic catastrophe,” the main mechanism to reduce clonogenic survival in tumor cells [11]. High doses of EBRT induce local inflammation and tissue reactions.
The much lower doses of LD‐EBRT act via different mechanisms. In the last two decades, several anti‐inflammatory effects have been discovered, contrary to the effects of the above‐mentioned high EBRT doses.
Furthermore, doses between 0.1 and 0.5 Gy reduced the adhesion of PBMC significantly to endothelial cells (ECs)
A third mechanism was the suppression of nitric oxide (NO) production in activated macrophages by LD‐EBRT between 0.3 and 1.25 Gy [18]. As the expression of inducible nitric oxide synthases (iNOS) proteins was not altered, the LD‐EBRT seemed to act at the translational or posttranslational level. Furthermore, a dose of 0.5 Gy significantly reduced oxidative burst and superoxide production of stimulated macrophages [19]. A diminished release of reactive oxygen species (ROS) can also contribute to the anti‐inflammatory effects of LD‐EBRT.
Taken together, all of these pathways and mechanisms showed a similar dose dependence with a maximum effect between 0.3 and 0.7 Gy regarding a discontinuous dose‐effect relation [20].
There are several
Since 1937 [21] for decades, large retrospective studies on the efficacy of LD‐EBRT in calcaneodynia have been published (overview in 22). In 1970, one negative randomized trial was reported and heavily criticized but had not been repeated [23]. Starting in the 1980s, patients were systematically clinically examined and interrogated in a structured manner to try to control for diverse risk factors and to compare the efficacy of different fractionation schemes and total doses [24].
It took until the past decade to perform and report prospectively randomized trials to proof the efficacy of LD‐EBRT and to identify the optimal dose fractionation schedule. In the following, we report the design and the results of these trials. Table 1 gives a short overview of the studied dose concepts and the results. Due to methodological reasons, we will describe the studies not following their publications dates, but according to a systematic order.
Since the publication of the first randomized trial on LD-EBRT in 1970, the efficacy of LD‐EBRT was questioned [23]. Goldie et al. randomized 399 patients, however, only nine patients suffered from calcaneodynia. This is why these results cannot be extrapolated to LD‐EBRT of a painful heel spur. Furthermore, endpoints were not clearly defined, and therapy was started in an acute stage of the disease [25].
The landmark study to prove the efficacy of LD‐EBRT was performed by the German cooperative group on the radiotherapy for benign diseases (GCGBD) under the responsibility of Niewald et al. [26]. A very low dose EBRT (6 × 0.1 Gy applied twice a week up to a total dose of 0.6 Gy) was randomized to a standard dose LD‐EBRT (6 × 1 Gy twice a week up to a total dose of 6 Gy). In the case of an unfavorable response after 3 months, the patient was offered a second treatment series (“reirradiation”) applying a standard dose. The dosage of the experimental arm was chosen to examine if very low doses are effective at all. Second, it acted as a placebo irradiation, as a sham irradiation was regarded unethical. LD‐EBRT was applied using a linear accelerator (4‐ to 6‐MV photons) using lateral parallel opposing fields.
Inclusion criteria were tenderness of the calcaneus with a limitation of the painless walking distance and duration of the symptoms for more than 6 months. Furthermore, a radiological proof of a heel spur was required, and the patients had to be least 40 years of age. Patients with previous traumata to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, or breastfeeding were excluded. Concomitant therapy with oral analgesics was not limited. However, local injections with steroids during the study period were not permitted.
Initially, 200 patients were planned [27] to detect a difference of 10% in the quality of life (QOL) sum score (SF‐12) [28] and calcaneodynia sum score (CS) [29] (Table 2) with a power of 80% and an error probability of 5%. Furthermore, the visual analogue scale (VAS) to evaluate pain intensity was used. However, after randomization of 66 patients and interim analysis of 62 patients (4 had to be excluded due to a withdrawal of informed consent or violation of the inclusion criteria), the differences in efficacy between the two treatment arms were so pronounced, that the trial was closed early.
Author | Year | N | Standard arm | Experimental arm | Results | Conclusions |
---|---|---|---|---|---|---|
2012 | 66 | 6 × 1 Gy twice a week | 6 × 0.1 Gy | 3 months: VAS/CS/SF12 sig. better with standard | 1. Dose‐response relationship | |
1 year: less second treatment series with standard | 2. Proof of therapeutic effect of LD‐EBRT | |||||
2007 | 130 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 months: CS no sig. differences | 6 × 0.5 Gy as standard fractionation | |
2014 | 457 | 6 × 1 Gy twice a week | 6 × 0.5 Gy | 6 weeks, 2.5 years: VAS/CS no sig. differences | 6 × 0.5 Gy as standard confirmed | |
2015 | 127 | 6 × 1 Gy twice a week | 12 × 0.5 Gy thrice a week | 3 months: VAS/CS/SF12 no sig. differences | Efficacy not increased with 12 × 0.5 Gy standard still 6 × 0.5 Gy |
Summary of contemporary randomized trials on LD‐EBRT of painful heel spurs: tested schedules, results, and conclusions.
Criteria | Extent of symptoms/alteration | Points |
---|---|---|
S = Pain at | 6 / 4 / 2 / 0 | |
(total: 30%) | N = Pain during D = Pain during R = Pain at I = Pain at none = 6 ; slight = 4 ; moderate = 2 ; severe = 0 points ⇨ | 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 6 / 4 / 2 / 0 |
per single criterion | ||
(total: 15%) | None Orthopedic shoe, insoles, heel cushion One cane or crutch Two canes or crutches ⇨ | 15 10 5 0 |
(total: 20%) | No limitation, maximum professional strain possible Slight limitation, normal professional work possible Moderate limitation, reduced professional activity Severe limitation, daily professional work impossible ⇨ | 20 10 5 0 |
(total: 15%) | No limitation of daily and leisure activities and sports Slightly limitation/reduced leisure activities and sports Moderate limitation/no leisure activities and sports Complete limitation of any daily and leisure activities ⇨ | 15 10 5 0 |
(total: 20%) | No limp, normal walking is possible without a limitation Slightly altered, limp after walking Moderately altered, limp after walking Severely altered, normal walking is impossible ⇨ | 20 10 5 0 |
The mean age of patients was 54 years in the standard dose group and 58 years in the 6 × 0.1 Gy group. Sixty‐one patients had a plantar, one patient a dorsal heel spur. In mean, patients in the standard dose group suffered for 15.3 months before the start of LD‐EBRT, in the 6 × 0.1 Gy group for 18.8 months. Twenty‐one patients had symptoms on both sides. In 28 patients the pain irradiated into the calf, only in 18 patients it was localized to the sole of the foot. Two patients had received surgery for LD‐EBRT.
Three months after therapy VAS values, CS‐ and QOL‐scores were significantly better after the standard dose in comparison with the very low dose treatment arm. The higher pain relief resulted in a better QOL. Twelve months after therapy about 64% of the patients after 6 × 0.1 Gy had to receive a second treatment series due to insufficient treatment results, in comparison with only 17% of the patients in the standard dose treatment group. As the second series was applied with a standard dose (6 × 1 Gy), patients in the 6 × 0.1 Gy group who were reirradiated showed equally favorable results compared with those in the standard‐dose group who did not receive a second course [26]. This is why the second treatment series in this clinical setting acted as a “salvage therapy.” Another interesting finding was that patients with a good response already at 3 months remained stable or even improved at 12 months. Furthermore, this underlines the long‐lasting efficacy of LD‐EBRT.
Acute side effects or long‐term toxicity did not occur.
In conclusion, this randomized trial established a dose‐response‐relationship of the analgesic effect of LD‐EBRT, thus providing a clinical and methodological proof of the efficacy of 6 × 1 Gy LD‐EBRT on the clinical course of painful heel spurs. The early termination of the study was justified due the interim analysis showing significant differences in the clinical outcome between both treatment arms. Still, the trial was not blinded, so both the patients and the staff were aware of the received dose. With modern linear accelerators, a complete blinding of the staff is nearly impossible. The only option would be a shame irradiation with closed collimator jaws, reducing the dose to the unavoidable “leakage” radiation. A much easier and straight forward way was used in the above‐mentioned study by application of a minimal physical dose with 0.1 Gy. Another critical point might be that only half of the patients were examined 12 months after therapy (
Another potential confounder not only in this study but also in all other published prospective and retrospective case series might be that a lot of the patients had received diverse and other conservative therapies before being referred to LD‐EBRT. An interaction between one of these other treatments and LD‐EBRT cannot be ruled out due to methodological reasons. This reflects clinical reality. Still, an interaction between one of these therapies and LD‐EBRT is rather unlikely and counter‐intuitive, as patients were referred to LD‐EBRT after the clinical failure of all the other conservative treatments.
Two randomized studies investigated the efficacy of 0.5 Gy single dose in comparison to 1 Gy.
The first trial was conducted by Heyd et al. [30]. They randomized 130 patients between 6 × 0.5 Gy twice weekly (low dose) and 6 × 1 Gy (standard dose). A linear accelerator was used, applying a single field technique.
Inclusion criteria were clinical signs of a painful heel spur, radiological evidence of spur formation, patient age ≥30 years and a relapse after previous conservative treatments, in patients >45 years LD‐EBRT could be used as the primary treatment. Endpoints of the study were changes in the “original” calcaneodynia score [31], that was documented before LD‐EBRT, at the end of the course, and 6 weeks and 6 months afterward.
One hundred and thirty patients were randomized. Mean age was 58.4 years. A 102 patients suffered from a plantar, one patient from a dorsal, and 27 patients from combined spurs. In mean, patients had been suffering from symptoms for 9.8 months. The symptoms had been present in 58 patients for less than 6 months, in 72 patients for a longer time. In 7 heels LD‐EBRT was the first therapeutic approach.
At the end of LD‐EBRT, 66% in the low dose group vs. 59% in the standard dose experienced an improvement in symptoms, 6 weeks later 80 vs. 85%. At this time point, 1.5% in each group reported an increase in symptoms, 19 vs. 14% no change. No statistically significant differences were noted. In case of insufficient treatment results patients were offered a second EBRT series. Thus 26 vs. 37% were treated a second time. Six weeks after that, 71 vs. 79% of these patients reported a further improvement. Six months after LD‐EBRT 88% of the patients in both groups had an amelioration of their symptoms, the remaining patients reported no change. During the EBRT series a slight increase in pain was reported by 26 vs. 29% of the patients. No other acute or late toxicity occurred.
In conclusion, 6 × 0.5 Gy twice weekly was as effective as 6 × 1 Gy.
These results were confirmed by a second randomized trial [32, 33]. Ott et al. randomized 457 patients between 6 × 0.5 Gy (low dose) and 6 × 1 Gy (standard dose). In contrast to the above‐cited “Heyd‐study” [30] an X‐ray unit (orthovoltage) and not linear accelerators was used. Patients received a single field (6 × 8 cm on the plantar calcaneus) with 150 kV, 15 mA, 1 mm Cu‐filter, with source‐to‐skin distance (SSD) of 40 cm. Six weeks after the LD‐EBRT a second series was offered to patients with an insufficient response. The endpoint was pain reduction. CS score and VAS values were measured before and at the end of LD‐EBRT (early response), 6 weeks (delayed), and 2.5 years (long‐term) afterward.
With a median follow‐up of 32 months the mean VAS values before treatment, for early, delayed, and long‐term response for the 0.5 and 1.0 Gy groups were 65.5 ± 22.1 and 64.0 ± 20.5 (
Taken together, the above‐mentioned studies proofed an equivalent clinical efficacy of 6 × 0.5 Gy in comparison to 6 × 1 Gy, thus defining a new clinical treatment standard with six times 0.5 Gy twice weekly as the minimum effective dose.
Before proofing 0.5 Gy as the new standard single dose, another randomized study tried to increase efficacy in reaching the “old” cumulative dose of 6 Gy with a single dose of 0.5 Gy. Niewald et al. randomized between 6 × 1 Gy twice a week (old “standard dose”) and 12 × 0.5 Gy three times a week (“experimental dose”) [25]. The aim was not just to get comparable results, but to further improve the analgesic effects. Linear accelerators (6 MV photons) applying a lateral opposing field technique were used.
Inclusion and exclusion criteria were quite similar to the ones used in the landmark study [26]: Clinical evidence of a painful heel spur, and duration of the symptoms for more than 6 months; radiological proof of a spur formation; age at least 40 years; Karnofsky‐Index at least 70%. Patients with previous radiotherapy or previous trauma to the foot, rheumatic or vascular diseases, lymphatic edema, pregnancy, breastfeeding, or severe psychiatric disorders were excluded. Concomitant therapy with analgesics was allowed. However, patients receiving surgery or shock wave therapy after randomization were excluded.
Endpoints were the SF‐12 sum score, the CS sum score (Table 2), and VAS. Follow‐up was scheduled every 6 weeks for 1 year.
Two‐hundred and forty patients were calculated to detect a difference of 15% in the VAS and CS score, with a power of 80%, and an error probability of 5%. After randomization of 127 patients and an interim analysis of 107 patients, the study was closed early, as the intended increase in analgesic efficacy by the experimental treatment was very unlikely to be achieved.
The mean age of the patients in the standard group was 56.1 Gy in comparison with 58.1 Gy in the experimental group. The mean duration of symptoms before initiation of LD‐EBRT was 17 vs. 16 months. In 98% of the standard group and 93% of the experimental group a plantar spur was treated, in 2 and 7% a combined (plantar and dorsal) spur.
Results after 3 months have been issued so far [25], longer follow‐up has yet to be published. After 3 months, there were no significant differences neither in the VAS (standard 42.3 vs. experimental 44.4) nor the CS sum score (28 vs. 28.4) nor in the QOL (SF‐12) scores. Although longer follow‐up has to be awaited, a further increase in the analgesic effect by applying 12 × 0.5 Gy three times a week is unlikely. This is why this fractionation schedule is currently not recommended, as it does not follow the “as low as reasonable achievable” principle of radiation protection.
Further reduced single doses in LD‐EBRT (with the exception of 0.1 Gy [26]) have never been tested in a prospectively randomized clinical trial. In radiotherapy of degenerative joint disorders, single doses of about 0.3–0.4 Gy were established by von Pannewitz in the late 1920s and published in 1933 and 1970 [34, 35]. However, two studies on calcaneodynia have raised serious concerns on single doses as low as 0.3 Gy.
Seegenschmiedt et al. analyzed treatment efficacy in 141 patients (170 irradiated heels), who were treated from 1984–1994 with X‐ray units (250 kV/200 kV, 20 mA, 40 cm SSD), applying a single field of 6 × 8 cm [24]. Seventy‐two heels received 12 Gy with 6 × 1 Gy (three times a week) –6 weeks break – 6 × 1 Gy (group A), 50 heels were treated with 10 × 0.3 Gy every day (group B1), and 38 heels 10 × 0.5 Gy every day (group B2). The endpoint was the value of a semiquantitative pain score 3 months and in mean 4 years after LD‐EBRT.
The median age of patients was 55 years in group A and 59 years in group B1/B2. The mean duration of symptoms before LD‐EBRT was 8 months, in one‐third, the symptoms persisted for more than 6 months.
Complete pain remission was achieved in 68–71% of the patients without significant differences between the treatment groups. However, there were differences in the clinical course of patients with partial remission of the symptoms: The best results in these patients were achieved during longer follow‐up in group B1 (10 × 0.5 Gy), followed by group A (6 × 1–6 × 1 Gy), followed by group B2 (10 × 0.3 Gy). The latter group showed a significantly worse amelioration of symptoms than the other groups.
A reduced efficacy was also reported in another retrospective case series, comprising 673 heels treated with a single dose of 0.3 Gy three times weekly up to 1.5 Gy (X‐ray) [36]. In case of insufficient treatment results the patients were offered a second course. After the first treatment, only 13% reported CR, nearly all patients had undergone a second LD‐EBRT.
Taken together, to the best of our current knowledge a single dose of 0.5 Gy is standard of care and should only be modified in controlled clinical trials.
In Table 3 selected contemporary randomized trials and patient series are shown broken down into several factors that might be correlated with treatment efficacy. For a better overview, we did not differentiate between univariate and multivariate analyses. We did not try to collect all ever published data.
Duration of symptoms before start of LD‐EBRT has been shown to be correlated with treatment efficacy in numerous studies.
Muecke et al. analyzed in a retrospective multicenter study 502 patients [22]. Duration of symptoms ≤6 months was associated with 76% treatment success vs. 44% after a history >6 months. Also Seegenschmiedt et al. found in their large collectives a correlation between the duration of heel pain and treatment outcome [24]. A significant influence of duration of symptoms before LD‐EBRT was also reported in 73 heels by Schneider et al. [37]. With a history of 3–6 months, the VAS value was reduced by 85%, 28 months after LD‐EBRT in comparison with a reduction of 58% with a history > 6 months. Similar results were obtained by Hermann et al. in 285 heels comparing <12 month history of pain vs. >12 months [38].
In contrary, another study could not confirm these results [30].
To the best of our knowledge, in no study, an influence of gender on treatment outcome has been confirmed [22, 24, 30, 38, 39]. In contrast to radiotherapy for oncological indications with high doses, efficacy and tolerability of LD‐EBRT seems to be the same concerning gender.
Several studies described a correlation between older age and better treatment results, at least 6 weeks after LD‐EBRT [37]. Age somewhat over 50 years seems to be important: >50 years [40], > 53 [38], or > 58 [22]. For a possible explanation see Section 2.3.7.
However, other studies found no influence of this patient characteristic on treatment outcome [24, 30, 39].
A very precise registration of changes in pain intensity (VAS) was done by Schneider at al. [37]. Sixty‐two patients (73 treated heels) were prospectively scored every week during LD‐EBRT, at the end of therapy, 6 weeks, 28 months, and 40 months later. Additionally, subjective mechanical heel stress during LD‐EBRT was estimated. A linear accelerator (10 MV) was used, applying one single field with a size of 12 × 17 cm. Patients were treated twice a week to a total dose of 5 Gy, with increasing single fraction doses (0.25 – 0.25 – 0.5 – 1 – 1 – 1 – 1 Gy). Mean patient age was 54 years, and all had a radiologically proven plantar spurn, mean symptom duration before LD‐EBRT was 6.5 months. Nearly all patients had received other conservative therapies before LD‐EBRT with insufficient results.
Interestingly, VAS scores decreased continuously during LD‐EBRT: before treatment the mean value was 6.3 ± 1.5, after the first week of LD‐EBRT 6.2 ± 1.8, after the second week 5.5 ± 2 (
In standard schedules with fixed single doses a slight increase in pain during the treatment series was reported by 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) of the patients [30]. Unfortunately, a possible correlation of this phenomenon with definite treatment results was not investigated.
Without further quantification, another study (6 × 1 vs. 6 × 0.1 Gy) stated, that this initial increase in symptoms “had no influence on the final pain relief 3 and 12 months after treatment” [26]. Older studies postulated a temporary reduction of the pH value in the irradiated tissues at the beginning of the treatment series, without consequences for the long‐term efficacy of LD‐EBRT [41].
This is contrasted by observations of LD‐EBRT in peritendinitis humeroscapularis [42]. In 73 patients (86 shoulders) initial increase of pain during the treatment course was significantly associated with a good response.
Muecke et al. analyzed in a retrospective multicenter study the influence of different treatment techniques in 502 patients [22]. Treatment failure was defined as pain persistence after LD‐EBRT and recurrence of pain during follow‐up. Treatment with MV (6–10 MV) was a significant prognostic factor for pain relief in multivariate analysis, as MV was associated with an eight‐year event‐free probability of 68 vs. 61% after X‐ray beams (175 kV). There are two possible explanations for this finding: besides the possibility of a random result, the authors postulate a more homogenous dose distribution with MV treatment in comparison with KV [22].
Schneider et al. reported an efficacy of just one‐third after a second LD‐EBRT course (so‐called “re‐irradiation”) in comparison with the effects of the first course [37]. Out of 73 heels treated with 5 Gy LD‐EBRT 18 heels received reirradiation due to insufficient treatment response. However, pain reduction measured by means of changes in VAS shortly after the second course and during long‐term follow‐up was significantly diminished in comparison with the efficacy of the first course (about 30% reduction in pain at the last evaluation vs. 86%).
Similar results were obtained in the large retrospective series (502 patients) by Muecke et al. [22]. Treatment failure was significantly associated with the number of treatment series: eight‐year event‐free probability was about 70% after the first course in comparison with just about 30% after reirradiation.
A systematic study on the efficacy of a reirradiation has been published by Hautmann et al. [43]. Eighty‐three patients (101 heels) with insufficient response to the first course or recurrent pain afterward due to plantar fasciitis (83 heels), or achillodynia (28 heels) received a second LD‐EBRT course in median 10 weeks (range 4 weeks to 63 months) after the first LD‐EBRT. About 75% of the patients were treated with 6 × 1 Gy, the others 6 × 0.5 Gy. The pain was assessed using the numeric rating scale (NRS) before and at the end of LD‐EBRT, 6, and 12 weeks, and 6, 12, and 24 months thereafter.
Before reirradiation NRS values were 6 (interquartile range 5–8), at the end of LD‐EBRT 5 (2–6), 6 weeks later 2 (1–4), at 12 weeks 1 (0–3), at 6 months 0 (0–2), at 12 and 24 months 0 (0–1). Interestingly, not only the patients with recurrent pain after the first course but also patients with insufficient responses to the first course experienced a profound and long‐lasting amelioration of their symptoms after the second course.
This is why a second treatment course should be recommended in case of insufficient efficacy of the first course.
A significant correlation between avoidance of heel stress during LD‐EBRT and efficacy of LD‐EBRT 6 weeks after therapy was reported by Schneider et al. in 73 heels [37]. With a Pearson\'s correlation coefficient of -0.467 (
An intuitive explanation is given by the authors [37]: As patient age was associated with positive treatment results, too, they proposed that older patients are often retired, thus being able to take more care of their heels.
Interestingly, all randomized trials required the radiological proof of a heel spur before including patients into the studies. Furthermore, most of the prospective and retrospective series warranted such an objective sign. However, as a substantial part of the patients suffers from plantar heel pain without having developed a heel spur, LD‐EBRT should be effective in these patients, too.
Hermann et al. analyzed treatment efficacy in 250 patients (285 heels), who received LD‐EBRT predominantly with 6 × 1 Gy [38]. In this series, 33% of the treated heels were without radiological evidence of a spur. In 185 patients a spur was confirmed with a mean length of 6.5 mm (range 0.6–25 mm). Patients without evidence of a plantar heel spur had a significantly higher chance of CR after LD‐EBRT (43 vs. 35%). Furthermore, the length of the spurs correlated directly with treatment outcome. Spurs >6.5 mm had just a 30% chance of experiencing CR in comparison with shorter ones. No statistical differences were found between treatment results of heels without spurs and those with spurs ≤6.5 mm.
Miszczyk et al. reported on 327 patients (623 LD‐EBRT series) mostly treated with X‐ray (180 kV, usually 1mm Cu filters) with single doses of 1.5 Gy (range 1–3 Gy) up to a total dose between 9 and 12 Gy (range 1–45 Gy) [39]. Mean spur size was 9 mm (range 1–30 mm). With a mean follow‐up of 74 months, no correlation between spur size and duration of pain relief was found. Analysis concerning spur length and treatment outcome in itself were unfortunately not reported.
Multivariate logistic regression enables the identification of factors independently predicting treatment outcome. By combining these factors, models can be calculated, that predict treatment outcome with a high probability. An example from the study of Hermann et al. is given in Table 4: in 285 heels treated with 6 × 1 Gy/6 × 0.5 Gy the influences of the patient characteristics age, spur length, and duration of symptoms before LD-EBRT alone and in combination were calculated [38]. The best results were obtained for patients > 53 years, spur length <6 mm, and a duration of symptoms <12 months with a probability for CR of 55% (CI 36–73%) and PR of 38% (CI 22–58%). Without these characteristics, the chance for CR was just 18% (CI 9–33%), for PR 31% (17–48%).
Study (citation) | [30] | [26] | [24] | [37] | [39] | [22] | [38] | [40] | [83] |
---|---|---|---|---|---|---|---|---|---|
Rand | Rand | Prospect | Prospect | Retrospect | Retrospect | Retrospect | Retrospect | Retrospect | |
130 | 66 | 170 | 73 | 623 | 502 | 285 | 161 | 7947 | |
MV | MV | KV | MV | KV | MV, KV | MV | KV | MV, KV | |
calcaneus | calcaneus | calcaneus | entire dorsal and middle foot | insertion of plantar fascia | calcaneus | calcaneus vs. insertion of calcaneus | calcaneus | entire dorsal foot vs. calcaneus vs. insertion of plantar fascia | |
6 × 1 vs. 6 × 0.5 Gy | 6 × 1 Gy vs. 6 × 0.1 Gy | 12, 3, 5 Gy | 5 Gy (increasing single dose) | 1.5 (1–3) up to 9–12 Gy (1–45) | 5–10 × 0.5–1 Gy | 6 × 1 Gy6 × 0.5 Gy | 6 × 1 Gy | 0.3–1.5 Gy; 2–3x weekly 2.5–18.76 Gy | |
History of symptoms | 0 | n.i. | + | + | 0 | + | + | + | + |
Gender | 0 | n.i. | 0 | n.i. | 0 | 0 | 0 | n.i. | n.i. |
Patient\'s age | 0 | n.i. | 0 | + | 0 | + | + | + | n.i. |
Initial worsening of pain during LD‐EBRT | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. | n.i. |
MV vs. KV | n.i. | n.i. | n.i. | n.i. | n.i. | + | n.i. | n.i. | 0 |
Number of therapy series | n.i. | n.i. | n.i. | + | n.i. | + | n.i. | n.i. | + |
Heel stress during LD‐EBRT | n.i. | 0 | n.i. | + | n.i. | n.i. | n.i. | n.i. | n.i. |
Factors associated with treatment efficacy in contemporary studies.
Patient\'s age >53 | No spur or spur ≤6.5 mm | Duration of symptoms <12 months | Probability of | ||
---|---|---|---|---|---|
No change | Partial remission | Complete remission | |||
1 | 1 | 1 | 0.07 (0.03–0.14) | 0.38 (0.22–0.58) | 0.55 (0.36–0.73) |
1 | 1 | 0 | 0.13 (0.07–0.28) | 0.37 (0.21–0.57) | 0.50 (0.30–0.70) |
1 | 0 | 1 | 0.15 (0.06–0.24) | 0.53 (0.33–0.72) | 0.32 (0.17–0.53) |
1 | 0 | 0 | 0.25 (0.13–0.45) | 0.48 (0.27–0.69) | 0.27 (0.13–0.48) |
0 | 1 | 1 | 0.17 (0.10–0.31) | 0.33 (0.19–0.50) | 0.50 (0.33–0.66) |
0 | 1 | 0 | 0.34 (0.20–0.53) | 0.40 (0.24–0.59) | 0.26 (0.13–0.45) |
0 | 0 | 1 | 0.30 (0.20–0.46) | 0.29 (0.18–0.43) | 0.41 (0.27–0.56) |
0 | 0 | 0 | 0.51 (0.35–0.69) | 0.31 (0.17–0.48) | 0.18 (0.09–0.33) |
Probabilities (95%‐CI) for NC, PR and CR calculated by polytomous logistic regression in dependence of the risk factors age, spur length, and duration of symptoms before LD‐EBRT according to Hermann et al. in a collective of 285 heels treated with 6 × 1/6 × 0.5 Gy (taken from [38]).
In modern radiotherapeutic departments, X‐ray sources are less and less available. This is why nowadays most patients are treated with linear accelerators, which were initially developed for the treatment of oncological diseases. However, these machines can be used in the treatment of benign diseases without any modifications or problems. Due to the high efforts in physical, technical, and organizational quality assurances for the operation of an accelerator or an X-ray source, the concentration on accelerators and their use for all indications is recommended.
For irradiation of the heel, the patient has to be placed on the treatment couch with the feet toward the gantry of the accelerator (so‐called “feet first”). Two different patient positions are widely used. He can be placed in supine position, with the irradiated leg is stretched out, while the other leg is angled. Another option is to place the patient in a lateral decubitus position on the side of the involved heel. Again, the symptomatic leg is stretched, while the contralateral leg is bent, with a cushion placed beneath the knee. Using X‐rays, the ipsilateral knee is bent by 90% and the foot is positioned on the treatment table. One anterior‐posterior (AP) beam is usually applied in this technique.
For the treatment itself, there are also two different options. Irradiation may be given as a single stationary field (SSD 100cm by convention). Alternatively, parallel opposing fields from 0° and 180° gantry position (in decubitus position) or lateral opposing fields (90° and 270° in supine position) are also applicable but take a little bit longer in daily clinical practice. The hypothetical advantage of using two opposing fields is a uniform dose distribution in the entire beam path in the calcaneus (Figure 1). However, there has never been a clinical proof, whether this theoretical assumption translates into any clinical advantage for the patient. When applying opposing fields, the dose is specified according to the ICRU 50 report, normally in the center of the calcaneus.
Dose distribution of two different treatment techniques generated in a treatment planning system (XIO®). In A and B just one single 6 MV photon field (8 × 8 cm) is applied, while C and D shows the dose distribution with two opposing fields from 0 and 180°. In the upper row, the so‐called “beams eye views” are given, while in the lower row the respective dose distributions on an axial CT scan directly at the calcaneal insertion are shown. Note the more uniform dose distribution with opposing fields. The 95% isodose is given as a green line (2.85 Gy). This dose encompasses larger parts of the calcaneal bone in D (opposing fields) than in B (single field). More information is given in Section 2.4.
A third option is the so‐called “plantar field” with the patient lying in prone position. A single field is positioned directly over the plantar insertion/calcaneus, potentially with rotations of the patient table and the gantry to compensate for inclinations of the patients surface in the irradiated field. However, this technique is regarded problematic when using linear accelerators due to the dose build‐up effect in the critical tissue depth. This problem is illustrated in Figure 2: photons with 6 MV reach just the half of the prescribed dose at the skin level, 100% is reached at 1.5 cm tissue depth. This would result in an insufficient dose in the critical structures (plantar fascia and heel spur). To overcome this problem, a silicone flap of about 1 cm diameter must be positioned on the skin before radiation.
Depth curves of different megavoltage energies. Blue 6 MV photons, red 15 MV photons. At the surface of the body/skin (depth 0 mm), only half (or even less with 15 MV) of the prescribed dose is applied. By physical interactions between photons and the tissue/water, there is a steep increase in dose. A 100% is reached at 1.5 cm depth with 6 MV and at about 3 cm depth with 15 MV. KV‐radiation reaches the maximum dose directly under the surface/skin (not shown). More information is given in Section 2.4.
Patients are often sent to the radiotherapist after a long unsuccessful history of diverse conservative treatments. The reason for this is a widespread fear among general practitioners that LD‐EBRT might be associated with severe side effects and risks. These fears are not substantiated, as reactions of the nerves or vessels require much higher doses than used for LD‐EBRT. For example, a dose of 45 Gy in normofractionated oncological therapy is considered to be safe for the spinal cord and therefore daily clinical practice [44]. Peripheral nerves are even more radioresistant. Acute or chronic side‐effects have never been reported in all contemporary studies on LD‐EBRT.
Acute side effects are negligible, as very low doses of ionizing radiation (in comparison with oncological treatments) are applied to a distal extremity. The total dose of LD‐EBRT with 3 or 6 Gy is far too low to cause any acute or late reactions on the skin overlaying the calcaneus. During normofractionated EBRT (single doses of 1.8–2 Gy, treatment on 5 days a week) erythema and mild edema develop at about 30 Gy [45]. Hyperpigmentation occurs at about 45 Gy, moist epitheliolyses at about 50 Gy. A 50–60 Gy might cause telangiectasias years after the therapy. This is why there is no report on acute treatment side effects in LD‐EBRT until now to the best of our knowledge.
About one‐third of the patients might experience a slight increase in pain during LD‐EBRT. In the randomized trial by Heydt et al. this phenomenon was seen in 26% (during 6 × 0.5 Gy) vs. 29% (6 × 1 Gy) [30]. It does not seem to be correlated with treatment outcome; further detailed information is given in Section 2.3.4.
The dose scattered to the male gonads is somewhat higher than to the ovaries. Jansen et al. calculated for 6 × 0.5 Gy about 1.5 mSv received by the testes and 0.75 mSv to the ovaries [46]. Comparable results have repeatedly been measured in the past [47, 48].
Taken together, the dose received by the gonads is insignificant. As the distal extremity is irradiated, scattered dose to the gonads is comparable to normal diagnostic radiological imaging [49]. The hereditary effects of these doses are very small and very likely negligible [46].
Although spermatogonial cells are very radiosensitive, a single dose of at least 100 mSv is needed to induce a temporary failure of spermatogenesis [50]. A single dose of 1000 mSv (equivalent to 1 Gy photon irradiation) results in an azoospermia for 9–18 months [51]. Interestingly, fractionated doses harm these cells even more. A temporary oligospermia is reported after receiving several fractions up to a cumulative dose of 160 mSv [52]. An azoospermia lasting for 14–22 months has been reported for fractionated doses of 620–860 mSv [53]. The actually during LD‐EBRT received testicular dose is about 100 times smaller than the lowest dose causing temporary changes in testicular tissues.
The dose to the testicles can be further reduced by utilizing a special testicular shielding. However, clinically meaningful dose reductions have been only measured in MV treatment of subdiaphragmatic/pelvine lymphatic regions or tumors [54, 55].
The mean lethal dose for human oocytes has been estimated at 2 Gy (2000 mSv) [56]. Permanent ovarian failure after radiotherapy is age dependent: in perimenopausal women, a dose of 6 Gy is sufficient [57], while in younger women up to 20 Gy are tolerated. The dose scattered to the ovaries during LD‐EBRT for calcaneodynia cannot cause such sequelae (0.75 mSv).
Naturally, pregnancy has to be excluded in all premenopausal women before beginning with LD‐EBRT, to avoid any risk to the fetus.
So far, no studies with long‐term observation periods have been published, describing a case of malignancy induced by LD‐EBRT for calcaneodynia. However, induction of malignancies is a stochastic effect of ionizing radiation. This means that there is no threshold dose—in contrast for example to the above‐mentioned reactions of the skin. A photon can accidentally trigger a mutation, which in turn leads to tumor formation many years later. The higher the radiation dose, the higher the probability of such an event occurring.
The best available data on tumor induction of full dose EBRT in oncology has been collected in patients treated with breast cancer. Almost 11,000 patients have been followed for over 20 years. The risk of a radiation‐induced tumor was approx. 1% per decade after radiotherapy [58].
To estimate the risk associated with much lower doses of LD‐EBRT, mathematical models on the basis of epidemiological long‐term observations of atomic bomb victims have been developed by the ICRP [59].
Jansen et al. applied the ICRP model on LD‐EBRT of a painful heel spur [46]. Assumed was a single field entering at the foot sole with a size of 8 × 10 cm, 200 kV photons, SSD 40 cm. For an LD‐EBRT series with 6 × 1 Gy the average attributable lifetime risk for induction of a fatal tumor was calculated to be about 0.5 in a thousand patients. An important risk factor for radiogenic‐induced cancer is the patient\'s age by the time the radiation exposure occurs. The risk is already reduced in the 3rd decade of the patient\'s life, it starts to decrease steadily from the age of 40 [60]. Applying these calculations, the estimated lifetime risk per one thousand patients for a fatal tumor accounts for the age of 25 0.6 (male)/0.8 (female), for the age of 50 0.2/0.3, for the age of 75 0.07/0.1 [46].
However, it must be critically noted that this mathematical model was developed for radiation protection and relates to the exposure of complete organ systems with approx. 1 Gy. Therefore, other groups argue that a significantly lower risk of radiogenic cancer induction— approx. ten times less—should be adopted [49, 61]. Furthermore, taken the new standard scheme with 6 × 0.5 Gy into account, these risks are additionally halved.
This risk (max. 1/1000, very likely much lower) must be seen in relation to the tumor risk of the not additionally radiotherapeutical‐treated population. In 2008, the lifetime risk of a man in Germany to suffer from cancer was 50.7% (25.9% to die from malignancy), in women 42.8% and 20.2% respectively [62].
By limiting the application of LD‐EBRT treatment to patients > 30 years of age, an exposure of the juvenile “relatively higher risk” patient population is avoided.
Traditionally target volume definition has been quite large. Field sizes of 12 × 17cm were treated, including the entire dorsal and middle foot, and not just the calcaneus [37, 82] (Figure 3A).
Field definitions in LD‐EBRT of a painful plantar heel spur/fasciitis. (A) traditional field definition including the entire dorsal and middle foot. (B) In randomized trials and large prospective series commonly used field definition encompassing the entire calcaneus, including insertion of the plantar fascia and the Achilles tendon. (C) Proposed small field definition for localized painful plantar fasciitis/plantar spur, encompassing only the painful area with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad).
In the recent randomized trials and prospective observational studies target volume definition was more restricted and confined to the calcaneus (Figure 3B). “The target volume consisted of the calcaneus and the region of the plantar aponeurosis” [26]. “The ventral margin is corresponding to the ventral surface of the calcaneus, the plantar and dorsal margins are surrounding the soft‐tissue border, and the cranial margin is below the ankle” [30]. “Target volume is the calcaneus, normally with a field size of 6 cm × 8 cm” [32]. “The calcaneus and the plantar aponeurosis were included in the target volume” [25].
In a German national survey 2001 on LD‐EBRT of painful heel spurs the target volume definition “large” (dorsal and middle foot) vs. “small” (entire calcaneus) was not correlated with treatment outcome [83]. Consequently, very large field definitions should be regarded as obsolete.
However, as the pathophysiological cause of calcaneodynia is thought to be a localized inflammatory process (see Section 1), it is questionable, whether the entire calcaneus has to be irradiated (as long as there are not a plantar as well as a painful dorsal spurs). There are some clinical data that support a further restriction of target volume definition.
Field sizes have been given in the study by Miszczyk et al. on 327 patients treated with X‐ray beams [39]. Target volume was “… the insertion of the plantar fascia with a calcaneal spur and a reasonable margin. The field size varied from 27 to 150 cm2 (mean 47 cm2).” However, although not explicitly stated, no correlation was found between field size and duration of pain relief after LD‐EBRT. Treatment efficacy in itself was apparently not investigated.
In the above‐mentioned series of 285 heels Hermann et al. analyzed treatment efficacy in dependence of field sizes, too [38]. The mean field size was 74 cm2. No correlation between field size (smaller vs. larger than 74 cm2) with treatment efficacy was found. Further analyses of small fields (< 6 × 6 cm), medium‐sized fields (36–64 cm2) and larger fields revealed no significant differences.
This is why it seems to suffice to encompass the painful region with 2 cm margins extending into the neighboring areas (calcaneus, fascia, fat pad; Figure 3C). However, this recommendation is deducted from pathophysiological considerations and the above‐mentioned case series. A randomized trial is necessary to proof clinical equivalence of a field definition “entire calcaneus” (Figure 3B) vs. “insertion of the plantar fascia” (Figure 3C).
The optimal fractionation schedule has not been elucidated yet. All randomized trial used twice weekly treatments. Only one experimental arm was scheduled three times a week [25]. In a National Survey in Germany with 146 answering institutions, about 45% applied two fractions and 37.5% three fractions weekly [83].
Interestingly, in the landmark study by von Pannewitz a fractionation schedule of only once per week was established [34]. Until now, there is no proof of a higher efficacy applying LD‐EBRT twice or three times per week.
In radiotherapy of another benign disease (endocrine orbitopathy) a 1 Gy per week over 20 weeks schedule was more effective than the standard schedules (10 × 2 Gy or 10 × 1 Gy every working day) [84]. Although other immunological mechanisms cause endocrine orbitopathy in comparison with plantar fasciitis, there is sufficient clinical evidence to test in a randomized trial different fractionation schedules (twice a week vs. once a week, possibly thrice a week).
Other therapies than LD‐EBRT have been applied in painful heel spur. In the following, just a rough overview can be given.
Different kinds of insoles and foot orthoses have been developed. The goal was to reduce plantar contact pressure and to distribute the pressure uniformly over the whole rearfoot [63]. Magnetic insoles do not seem to provide additional benefit [64]. As a short‐term treatment, low‐Dye taping techniques are often used. However, in a randomized trial only a modest improvement in ‘first‐step’ pain was seen in comparison with sham‐intervention [65].
Manual stretching is often recommended. A systematic review of six studies found only statistically significant differences in comparison with the control in one study combining calf muscle and plantar fascia stretches [66].
Several trials have investigated acupuncture. A systematic review from 2010 showed (limited) evidence for the effectiveness [67]. A randomized trial published in 2014 recruited 84 patients [68]. The authors concluded, that “dry needling provided statistically significant reductions in plantar heel pain, but the magnitude of this effect should be considered against the frequency of minor transitory adverse events.”
Ultrasound therapy has led to questionable results [69], but a randomized trial on cryo‐ultrasound with about 100 patients published in 2014 showed good effectiveness [70].
Low‐level laser light (635 nm), given twice a week for a total of six applications, reduced in a randomized trial VAS scores significantly after 8 weeks in comparison with placebo [71]. However, the study comprised of just 69 patients; other similar studies have not been reported so far.
Extracorporeal shock waves are widely applied. Three metaanalyses comprising at least five randomized trials found significant short‐term pain relief and improved functional outcomes for this therapeutic option [72–74]. Another study compared the analgesic efficacy of ultrasound and shock wave therapy in 47 patients [75]. The results suggested that the shock wave therapy had greater analgesic efficacy.
Another basic approach is the oral administration of nonsteroidal anti‐inflammatory drugs (NSAID) to achieve a symptomatic relief. Injections into the painful area are also recommended. A recent review summarized ten randomized trials on corticosteroid injections into the plantar fascia [76]. A significant effect of the steroids on the pain has been shown. However, it was usually short‐term, lasting 4–12 weeks in duration. No advantage of ultrasound‐guided injection techniques in comparison with palpation guidance was found, and no superiority of one type of corticosteroid over another was seen. A longer lasting pain relief has been suggested by a small randomized trial of botulinum toxin injections [77]. Another option is the injection of autologous platelet‐rich plasma. A recent review identified three randomized trials, all showing promising results [78]. However, a very small trial challenged this method of plasma preparation, as the same clinical effectivity was observed after the injection of whole blood [79].
Different surgical approaches have been developed. Releases of the plantar fascia are done, in some studies combined with a spur resection [80]. Due to a probably faster recovery after surgery with comparable functional results endoscopic procedures are recommended nowadays [81]. Surgery is usually indicated after failure of conservative therapies as the ultimate “salvage‐therapy.”
There is only a limited amount of studies randomizing patients between LD‐EBRT and the above‐mentioned alternative therapies.
Canyilmaz et al. randomized 123 patients between LD‐EBRT (6 × 1 Gy, three times a week) and 1 ml injection of 40 mg methylprednisolone and 0.5 ml 60 mg 1% lidocaine under the guidance of palpation [85]. After 3 and 6 months, VAS values and CS‐scores were compared between both groups. After 3 months, the results in the radiotherapy arm were significantly superior compared with those after injections.
To corroborate these findings, similar studies should be conducted. Furthermore, more studies randomizing LD‐EBRT against other therapies (e.g. extracorporeal shock waves) are needed. A minimum size of 50 patients per treatment arm should be assured to gain more statistically relevant results. Recruiting patients without prior excessive other therapies for these studies would be optimal.
The goal must be an evidence‐based algorithm defining the therapeutic sequence of the different conservative treatment modalities for plantar fasciitis.
LD‐EBRT for painful plantar fasciitis/heel spur is an effective and safe treatment option for patients over 30 years of age and after exclusion of pregnancy. A fractionation of 6 × 0.5 Gy twice weekly up to a total dose of 3 Gy is currently recommended. In the case of an insufficient response a second course can be offered to the patient.
Randomized trials on target volume definition and further optimization of LD‐EBRT fractionation are currently in the process of planning. Further trials to compare the different conservative therapies for plantar fasciitis with each other are necessary to allow the development of an evidence‐based treatment algorithm.
This chapter is dedicated to Professor Gisela Hermann‐Brennecke on the occasion of her 70th birthday.
AP | anterior‐posterior |
CI | confidence interval |
CR | complete remission |
CS | Calcaneodynia score |
Cu | chemical element symbol for copper |
EC | endothelial cells |
GCG‐BD | German Cooperative Group on Radiotherapy for Benign Diseases |
Gy | Gray |
ICRP | International Commission on Radiological Protection |
IL | interleukin |
iNOS | inducible nitric oxide synthases |
KV | kilovoltage |
LD‐EBRT | low dose external beam radiotherapy |
mA | milliampere |
mRNA | messenger ribonuclein acid |
mSv | milliSievert |
MV | megavoltage |
NC | no change |
NF‐κB | nuclear factor kappa B |
NO | nitric oxide |
NSAID | non‐steroidal anti‐inflammatory drug |
PBMC | peripheral blood mononuclear cells |
PR | partial remission |
QOL | quality of life |
ROS | reactive oxygen species |
SSD | skin‐to‐source distance |
TGF‐β1 | transforming growth factor β1 |
VAS | visual analogue scale |
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Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. 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Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",country:{name:"Argentina"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",biography:"Francisco Javier Martín-Romero (Javier) is a Professor of Biochemistry and Molecular Biology at the University of Extremadura, Spain. He is also a group leader at the Biomarkers Institute of Molecular Pathology. Javier received his Ph.D. in 1998 in Biochemistry and Biophysics. At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. The interest of Javier's lab is the study of cell signaling with a special focus on Ca2+ signaling, and how Ca2+ transport modulates the cytoskeleton, migration, differentiation, cell death, etc. He is especially interested in the study of Ca2+ channels, and the role of STIM1 in the initiation of pathological events.",institutionString:null,institution:{name:"University of Extremadura",country:{name:"Spain"}}},{id:"217323",title:"Prof.",name:"Guang-Jer",middleName:null,surname:"Wu",slug:"guang-jer-wu",fullName:"Guang-Jer Wu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217323/images/8027_n.jpg",biography:null,institutionString:null,institution:null},{id:"148546",title:"Dr.",name:"Norma Francenia",middleName:null,surname:"Santos-Sánchez",slug:"norma-francenia-santos-sanchez",fullName:"Norma Francenia Santos-Sánchez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/148546/images/4640_n.jpg",biography:null,institutionString:null,institution:null},{id:"272889",title:"Dr.",name:"Narendra",middleName:null,surname:"Maddu",slug:"narendra-maddu",fullName:"Narendra Maddu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272889/images/10758_n.jpg",biography:null,institutionString:null,institution:null},{id:"242491",title:"Prof.",name:"Angelica",middleName:null,surname:"Rueda",slug:"angelica-rueda",fullName:"Angelica Rueda",position:"Investigador Cinvestav 3B",profilePictureURL:"https://mts.intechopen.com/storage/users/242491/images/6765_n.jpg",biography:null,institutionString:null,institution:null},{id:"88631",title:"Dr.",name:"Ivan",middleName:null,surname:"Petyaev",slug:"ivan-petyaev",fullName:"Ivan Petyaev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Lycotec (United Kingdom)",country:{name:"United Kingdom"}}},{id:"423869",title:"Ms.",name:"Smita",middleName:null,surname:"Rai",slug:"smita-rai",fullName:"Smita Rai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424024",title:"Prof.",name:"Swati",middleName:null,surname:"Sharma",slug:"swati-sharma",fullName:"Swati Sharma",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"439112",title:"MSc.",name:"Touseef",middleName:null,surname:"Fatima",slug:"touseef-fatima",fullName:"Touseef Fatima",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Integral University",country:{name:"India"}}},{id:"424836",title:"Dr.",name:"Orsolya",middleName:null,surname:"Borsai",slug:"orsolya-borsai",fullName:"Orsolya Borsai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",country:{name:"Romania"}}},{id:"422262",title:"Ph.D.",name:"Paola Andrea",middleName:null,surname:"Palmeros-Suárez",slug:"paola-andrea-palmeros-suarez",fullName:"Paola Andrea Palmeros-Suárez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Guadalajara",country:{name:"Mexico"}}}]}},subseries:{item:{id:"12",type:"subseries",title:"Human Physiology",keywords:"Anatomy, Cells, Organs, Systems, Homeostasis, Functions",scope:"Human physiology is the scientific exploration of the various functions (physical, biochemical, and mechanical properties) of humans, their organs, and their constituent cells. The endocrine and nervous systems play important roles in maintaining homeostasis in the human body. Integration, which is the biological basis of physiology, is achieved through communication between the many overlapping functions of the human body's systems, which takes place through electrical and chemical means. Much of the basis of our knowledge of human physiology has been provided by animal experiments. Because of the close relationship between structure and function, studies in human physiology and anatomy seek to understand the mechanisms that help the human body function. The series on human physiology deals with the various mechanisms of interaction between the various organs, nerves, and cells in the human body.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11408,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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