\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5604",leadTitle:"A Global Scientific Vision",fullTitle:"A Global Scientific Vision - Prevention, Diagnosis, and Treatment of Lung Cancer",title:"Prevention, Diagnosis, and Treatment of Lung Cancer",subtitle:null,reviewType:"peer-reviewed",abstract:"Lung cancer is the number one cause of cancer deaths around the world. This devastating disease takes strength not only in people who smoke but also in poor people that eat polluted food and use heating sources, and in those exposed naturally to toxic compounds present in indoor and outdoor environments. Lung cancer patients and their families wait actions from the science that give not only answer to their demands but also a light of hope at the moment of receiveing the diagnosis. This book meets the experience of several researchers who dedicate many hours a day to find not only the cure of lung cancer but also the way to convert the pathology of this chronic disease. In 12 chapters, the lectures will give information related to the relationship of lung cancer and smoking habit, the crucial role of the image technology for diagnosis of lung cancer, and a molecular vision of prevention, diagnosis, and treatment of lung cancer. The authors with a clinic and/or lab vision and with a great spirit to collaborate with the science and with each past, present, and future patient and their families have dedicated many hours to write each chapter. Probably, the final answer to find the cure of lung cancer is not in this book. However, the lectures will give scientific information that will contribute in the near future improvement to the life quality of the patients.",isbn:"978-953-51-2966-0",printIsbn:"978-953-51-2965-3",pdfIsbn:"978-953-51-7345-8",doi:"10.5772/63687",price:119,priceEur:129,priceUsd:155,slug:"a-global-scientific-vision-prevention-diagnosis-and-treatment-of-lung-cancer",numberOfPages:230,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"4505dc77580ec45906ab34f7d159cd0b",bookSignature:"Marta Adonis",publishedDate:"March 1st 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5604.jpg",numberOfDownloads:19163,numberOfWosCitations:6,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:13,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:26,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 23rd 2016",dateEndSecondStepPublish:"June 13th 2016",dateEndThirdStepPublish:"September 9th 2016",dateEndFourthStepPublish:"December 8th 2016",dateEndFifthStepPublish:"February 6th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"160392",title:"Dr.",name:"Marta",middleName:null,surname:"Adonis",slug:"marta-adonis",fullName:"Marta Adonis",profilePictureURL:"https://mts.intechopen.com/storage/users/160392/images/system/160392.jpeg",biography:"Dr. Marta Adonis has a wide experience as a director, leading and managing national and international research projects, as well as in human capacity building. At the research level, she has participated in different national and international projects, not only relevant at the scientific level but also with important public impact. Her role in each grant has been related with the formulation, development, human capacity building, and national and international diffusion through different media (scientific journals, newspapers, TV and radio interview, congress, workshops, etc.) Dr. Adonis has several publications not only in journals but also books, related mainly to science, technology, and medicine.",institutionString:"University of Chile",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1047",title:"Pulmonology",slug:"pulmonology"}],chapters:[{id:"53841",title:"The Epidemiology of Tobacco and Lung Cancer: Some Conclusions from a Lifetime of Research",doi:"10.5772/67167",slug:"the-epidemiology-of-tobacco-and-lung-cancer-some-conclusions-from-a-lifetime-of-research",totalDownloads:1648,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This review summarizes evidence on the smoking/lung cancer relationship, based on the author's 50 years’ experience. It starts by illustrating variations in national rates by time and sex. It then demonstrates that the relationship of smoking to overall lung cancer risk is strong, consistently seen and dose‐related with amount smoked, duration, age of start and time of quitting. Relative risks vary markedly by country, but little by sex, age, race, occupation, genetics and other factors. Though precisely estimating the smoking risk is difficult, the relationship is clearly causal, not explained by bias or confounding. The risk from smoking is reduced in lower tar filter cigarettes, and essentially independent of mentholation and type of curing. Lung cancer risk is not increased by smokeless tobacco use. The relative risk is much greater for squamous/small‐cell carcinoma than for adeno/large‐cell carcinoma. The argument that the increasing ratio of squamous to adenocarcinoma results from changes in cigarettes is shown to be weak, the increase also being seen in never smokers, starting before filters were introduced, and associated with diagnostic changes. Most of the weak association of lung cancer with passive smoking is explicable by confounding and by misclassification of some ever smokers as never smokers.",signatures:"Peter N. Lee",downloadPdfUrl:"/chapter/pdf-download/53841",previewPdfUrl:"/chapter/pdf-preview/53841",authors:[{id:"193212",title:"Dr.",name:"Peter",surname:"Lee",slug:"peter-lee",fullName:"Peter Lee"}],corrections:null},{id:"53900",title:"How Effective is Fear of Lung Cancer as a Smoking Cessation Motivator?",doi:"10.5772/67235",slug:"how-effective-is-fear-of-lung-cancer-as-a-smoking-cessation-motivator-",totalDownloads:1487,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"A risk score for lung cancer derived from genetic and clinical data has been shown to motivate smokers to quit. However, smokers with a relatively low (but not insignificant) risk score are more likely to carry on smoking. To understand this observation, the balance between smoking cessation motivators and de‐motivators must be understood. A relatively low risk score can act as a de‐motivator. Other de‐motivators that have been recorded and were observed by researchers involved in this project were: nicotine addiction and fear of withdrawal symptoms, optimism bias, confirmation bias, attentional bias, post‐traumatic stress disorder (PTSD), anxieties about smoking cessation and weight gain, side effects of smoking cessation therapy, fatalism, peer pressure and lack of family cohesion. This long list of de‐motivators serves to emphasize the complexity of the psychological make‐up of the individual smoker. This is illustrated by a set of case histories (anonymised for confidentiality). The future use of a risk score as a smoking cessation motivator is discussed and suggestions are made as to how a risk score could be made more effective including inclusion of scoring for cardiovascular risk.",signatures:"John A.A. Nichols",downloadPdfUrl:"/chapter/pdf-download/53900",previewPdfUrl:"/chapter/pdf-preview/53900",authors:[{id:"94057",title:"Dr.",name:"John",surname:"Nichols",slug:"john-nichols",fullName:"John Nichols"}],corrections:null},{id:"53034",title:"Low-Dose Computed Tomography Screening for Lung Cancer",doi:"10.5772/66358",slug:"low-dose-computed-tomography-screening-for-lung-cancer",totalDownloads:1451,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In the landmark American National Lung Cancer Screening Trial (NLST), low-dose CT (LDCT) screening produced a relative mortality reduction of 20%. These results have not been replicated in any of the European studies, although these are of limited statistical power. Besides doubt about the general applicability of the NLST findings, if LDCT screening is to be successfully implemented, a number of developments are still required, including better characterisation of entry criteria and refinement of screening and nodule management protocols. The high incidence of false-positive findings increases costs and morbidity. Even when histologically malignant tumours are identified, frequently these would not have manifested as disease, i.e. they are “overdiagnosed”. These patients are liable to receive unnecessary treatment. LDCT screening is relatively expensive in comparison with other cancer screening modalities. Whilst cost-effectiveness can be improved by integration with smoking cessation programmes, how this would be done in practice remains unclear. Furthermore, individuals at high-risk of lung cancer are virtually by definition risk prone, raising concerns about how attractive participation in a screening programme would be, especially given the very small reported absolute risk reduction in the NLST.",signatures:"Trevor Keith Rogers",downloadPdfUrl:"/chapter/pdf-download/53034",previewPdfUrl:"/chapter/pdf-preview/53034",authors:[{id:"192376",title:"Dr.",name:"Trevor",surname:"Rogers",slug:"trevor-rogers",fullName:"Trevor Rogers"}],corrections:null},{id:"53815",title:"Transthoracic Ultrasonography: Advantages and Limitations in the Assessment of Lung Cancer",doi:"10.5772/67169",slug:"transthoracic-ultrasonography-advantages-and-limitations-in-the-assessment-of-lung-cancer",totalDownloads:1639,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Lung cancer (LC) represents the leading cause of cancer-related mortality worldwide, with most of the cases being still diagnosed in advanced stages. Recently published data estimates an increase of LC deaths worldwide from 1.6 million in 2012 to 3 million in 2035. In this context, ultrasonography (US) aspires to become the method of choice that can offer essential information concerning subpleural LC. Therefore, it is an urgent need for an objective evaluation of the role of US and US-guided biopsies as an accurate diagnosis method, as until now large studies to assess this have been seldom performed. Our main aim was to perform a review over the use of US and US-guided biopsy in the assessment of LC, and our second aim was to illustrate how US is a valuable tool in the approach of patients with LC. We also compared the advantages and disadvantages of different types of biopsy needles. Other non-invasive applications of US (contrast-enhanced US and elastography) and their usefulness for LC were also evaluated. Though transthoracic US is today underused for lung cancer diagnosis, it offers multiple advantages that seem extremely useful for the efficient management of such tumours.",signatures:"Romeo Ioan Chira, Alexandra Chira and Petru Adrian Mircea",downloadPdfUrl:"/chapter/pdf-download/53815",previewPdfUrl:"/chapter/pdf-preview/53815",authors:[{id:"189838",title:"Dr.",name:"Alexandra",surname:"Chira",slug:"alexandra-chira",fullName:"Alexandra Chira"},{id:"190070",title:"Dr.",name:"Romeo",surname:"Chira",slug:"romeo-chira",fullName:"Romeo Chira"},{id:"193917",title:"Prof.",name:"Petru Adrian",surname:"Mircea",slug:"petru-adrian-mircea",fullName:"Petru Adrian Mircea"}],corrections:null},{id:"53847",title:"Clinical Lung Cancer Mutation Detection",doi:"10.5772/67168",slug:"clinical-lung-cancer-mutation-detection",totalDownloads:1706,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"As the promise of personalized medicine in the treatment of cancer begins to be realized, the diagnostic techniques needed to drive that revolution have continued to evolve. What started as optical imaging of banded chromosomes for karyotyping has progressed to DNA sequencing and now next‐generation sequencing capable of producing billions of reads. There are currently a large number of techniques that are used in the clinical laboratory for assessing the presence of mutations in lung tumors, all with their own strengths and weaknesses. Here, we survey the technology that is available and take a closer look at next‐generation sequencing. We discuss the instruments that are currently on the market and demonstrate the common workflow from patient to data. Additionally, the outside factors that influence the use of these technologies, from government regulation to insurance reimbursement, are presented.",signatures:"Stephan C. Jahn and Petr Starostik",downloadPdfUrl:"/chapter/pdf-download/53847",previewPdfUrl:"/chapter/pdf-preview/53847",authors:[{id:"192350",title:"Associate Prof.",name:"Petr",surname:"Starostik",slug:"petr-starostik",fullName:"Petr Starostik"},{id:"195560",title:"Dr.",name:"Stephan",surname:"Jahn",slug:"stephan-jahn",fullName:"Stephan Jahn"}],corrections:null},{id:"53462",title:"Sphingolipid in Lung Cancer Pathogenesis and Therapy",doi:"10.5772/66359",slug:"sphingolipid-in-lung-cancer-pathogenesis-and-therapy",totalDownloads:1520,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Recent genomic research has ranked sphingolipid metabolism as the top dysregulated pathways in lung cancer, demonstrating that these lipids and their metabolic enzymes play key roles in lung cancer pathogenesis. Hence, sphingolipid metabolism has become a forefront in lung cancer research. However, the function of the diverse sphingolipids and their metabolic enzymes and the underlying mechanism in lung cancer are still unclear. In this chapter, we will focus on ceramide and sphingosine-1-phosphate (S1P), the best characterized sphingolipids so far, to summarize the most recent studies and highlight the essential role of sphingolipids in lung cancer pathology, diagnosis, and treatment.",signatures:"Erhard Bieberich and Guanghu Wang",downloadPdfUrl:"/chapter/pdf-download/53462",previewPdfUrl:"/chapter/pdf-preview/53462",authors:[{id:"193090",title:"Dr.",name:"Guanghu",surname:"Wang",slug:"guanghu-wang",fullName:"Guanghu Wang"}],corrections:null},{id:"53985",title:"Prognostic and Predictive Value of PD-L1 in Patients with Lung Cancer",doi:"10.5772/66757",slug:"prognostic-and-predictive-value-of-pd-l1-in-patients-with-lung-cancer",totalDownloads:1536,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Improved understanding of the molecular mechanisms has led to identification of checkpoint signalling and development of checkpoint inhibitors in the treatment of many cancers, including lung cancer. To be able to select the patients who benefit most from checkpoint inhibitors, predictive biomarkers are needed. Currently, the only predictive biomarker that has been approved in clinical use is PD-L1, the ligand of the inhibitory T-cell checkpoint PD-1. The use of PD-L1 as a predictive biomarker is confounded by multiple unresolved issues, from testing issues (e.g., cut-off values for positivity) to clinical use (e.g., the response to anti–PD-1 and anti–PD-L1 antibodies in patients without any expression of PD-L1). Even more open questions exist in the evaluation of PD-L1 as a prognostic biomarker. In the future, we expect that an improved understanding of immune system, tumor microenvironment, mechanism of action of immunotherapeutic drugs, and PD-L1 testing methods will elucidate the value of PD-L1 as a prognostic and predictive biomarker in detail.",signatures:"Mirjana Rajer",downloadPdfUrl:"/chapter/pdf-download/53985",previewPdfUrl:"/chapter/pdf-preview/53985",authors:[{id:"194329",title:"Ph.D.",name:"Mirjana",surname:"Rajer",slug:"mirjana-rajer",fullName:"Mirjana Rajer"}],corrections:null},{id:"53826",title:"Checkpoint Inhibitors in Nonsmall Cell Lung Cancer",doi:"10.5772/66841",slug:"checkpoint-inhibitors-in-nonsmall-cell-lung-cancer",totalDownloads:1533,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Lung cancer remains the leading cause of cancer‐related deaths worldwide. The majority of NSCLC patients present with advanced stage disease. Lung cancer was once thought of as a low antigenicity cancer unlikely to benefit from immunotherapy, but has recently been found to have a high level of antigenicity. Moreover, a large body of research now exists to support both the safety and efficacy of immunotherapy in advanced stage NSCLC. The checkpoint inhibitors nivolumab, pembrolizumab, and atezolizumab are now approved by the U.S. Federal Drug Administration for second‐line treatment in advanced stage NSCLC. In addition to being efficacious, checkpoint inhibitors have a superior safety profile compared to previous standard of care, chemotherapy. Further trials are needed to investigate the checkpoint inhibitors’ role in combination treatment, first‐line treatment, and early stage disease.",signatures:"Karen G. Zeman, Joseph E. Zeman, Christina E. Brzezniak and Corey\nA. Carter",downloadPdfUrl:"/chapter/pdf-download/53826",previewPdfUrl:"/chapter/pdf-preview/53826",authors:[{id:"193530",title:"Dr.",name:"Karen",surname:"Zeman",slug:"karen-zeman",fullName:"Karen Zeman"},{id:"193566",title:"Dr.",name:"Corey",surname:"Carter",slug:"corey-carter",fullName:"Corey Carter"},{id:"193567",title:"Dr.",name:"Christina",surname:"Brzezniak",slug:"christina-brzezniak",fullName:"Christina Brzezniak"}],corrections:null},{id:"54070",title:"Repurposing Metformin for Lung Cancer Management",doi:"10.5772/67160",slug:"repurposing-metformin-for-lung-cancer-management",totalDownloads:1424,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:1,abstract:"In this article, we introduced the background knowledge of lung cancer management and considered repurposing old drugs to overcome therapy bottleneck. We chose metformin to prove both its antihyperglycemia and antitumor formation effects. Based on the metformin-related AMPK-dependent pathway, we tried to explore the AMPK-independent pathway in inhibition of lung tumorigenesis by metformin. Using preclinical data mining from clinical settings with a literature review, we attempted to clarify the role of metformin in lung cancer management. Additional objective and strong evidence are needed using randomized control studies to verify the benefit of metformin in clinical practice. Furthermore, we proposed two lung cancer animal models and showed the establishment processes thoroughly. We hope that these two lung cancer animal models provide a useful platform for furthering old drug repurposing as well as new drug investigations in the future.",signatures:"Chuan-Mu Chen, Jiun-Long Wang, Yi-Ting Tsai, Jie-Hau Jiang and\nHsiao-Ling Chen",downloadPdfUrl:"/chapter/pdf-download/54070",previewPdfUrl:"/chapter/pdf-preview/54070",authors:[{id:"36984",title:"Prof.",name:"Chuan-Mu",surname:"Chen",slug:"chuan-mu-chen",fullName:"Chuan-Mu Chen"}],corrections:null},{id:"54036",title:"The Bioenergetic Role of Mitochondria in Lung Cancer",doi:"10.5772/67238",slug:"the-bioenergetic-role-of-mitochondria-in-lung-cancer",totalDownloads:1779,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In 1920s, Otto Warburg made the observation that cancer cells utilize significantly more glucose than normal, healthy cells, which led him to believe that cancer cells relied on glycolysis more than healthy cells. However, many subsequent studies have shown that glucose is not only necessary for glycolysis but also for oxidative phosphorylation and production of building blocks for the synthesis of other molecules. There are many challenges associated with studying and treating lung cancer, and there is a diverse set of metabolic factors influencing the tumorigenesis and metastasis of lung cancer. Lung cancer cells rely heavily on mitochondrial respiration, and several studies have shown that inhibiting mitochondrial function is an effective method to combat lung cancer. Several agents have been used to inhibit mitochondrial function, including cyclopamine and metformin. Further, more research has noted increased levels of heme flux and function as critical to intensified oxygen consumption and accompanying amplified pathogenesis and progression of lung cancer. The upregulation of mitochondrial DNA and biogenesis genes are also correlated with lung cancer. In this chapter, we will cover these recent and emerging topics in lung cancer bioenergetics research.",signatures:"Keely Erin FitzGerald, Purna Chaitanya Konduri, Chantal Vidal,\nHyuntae Yoo and Li Zhang",downloadPdfUrl:"/chapter/pdf-download/54036",previewPdfUrl:"/chapter/pdf-preview/54036",authors:[{id:"174952",title:"Ms.",name:"Purna Chaitanya",surname:"Konduri",slug:"purna-chaitanya-konduri",fullName:"Purna Chaitanya Konduri"},{id:"193479",title:"Ms.",name:"Keely",surname:"FitzGerald",slug:"keely-fitzgerald",fullName:"Keely FitzGerald"},{id:"193480",title:"Ms.",name:"Chantal",surname:"Vidal",slug:"chantal-vidal",fullName:"Chantal Vidal"},{id:"193481",title:"Dr.",name:"Li",surname:"Zhang",slug:"li-zhang",fullName:"Li Zhang"},{id:"195648",title:"Dr.",name:"Hyuntae",surname:"Yoo",slug:"hyuntae-yoo",fullName:"Hyuntae Yoo"}],corrections:null},{id:"53191",title:"Long Non-Coding RNA in Non-Small Cell Lung Cancers",doi:"10.5772/66487",slug:"long-non-coding-rna-in-non-small-cell-lung-cancers",totalDownloads:1416,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Non-small cell lung cancer (NSCLC) accounts for nearly 80% of diagnosed lung cancers. Due to the predominantly late diagnosis of NSCLC and drug resistance in the targeted therapy approaches, the 5-year overall survival rate is still less than 19%. Thus, novel diagnosis and treatment approaches are needed. Many efforts have been made to achieve great progress in understanding the genomic landscape of NSCLC and the molecular mechanisms involved in tumorigenesis. Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides with little or no protein-coding potential. They are encoded across the genome and are involved in a wide range of cellular and biological processes. Dysregulation of lncRNAs is associated with a number of cancer-related processes, including epigenetic regulation, microRNA silencing, and DNA damage. Furthermore, lncRNAs have been reported to have the potential as biomarker for diagnosis and prognosis, as well as the therapy targets. Here in this chapter, we review some well-characterized lncRNAs associated with NSCLCs and the potential of lncRNAs as biomarkers in the diagnosis and prognosis of NSCLCs.",signatures:"Zule Cheng and Hongju Mao",downloadPdfUrl:"/chapter/pdf-download/53191",previewPdfUrl:"/chapter/pdf-preview/53191",authors:[{id:"193201",title:"Ph.D. Student",name:"Cheng",surname:"Zule",slug:"cheng-zule",fullName:"Cheng Zule"},{id:"195593",title:"Prof.",name:"Hongju",surname:"Mao",slug:"hongju-mao",fullName:"Hongju Mao"}],corrections:null},{id:"54039",title:"Antitumor Effect of Natural Product Molecules against Lung Cancer",doi:"10.5772/67241",slug:"antitumor-effect-of-natural-product-molecules-against-lung-cancer",totalDownloads:2028,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:1,abstract:"Lung cancer treatment remains difficult because of multidrug resistance and adverse effects, and natural product molecules show powerful activity in lung cancer with few side effects. The molecular targets and efficacy of natural product molecules remain unclear. We described the molecular regulation of natural product molecules with antitumor activities, the antilung cancer activities and the clinical trials for lung cancer treatment of natural product molecules. The results support the updated systemic information on the use of natural product molecules to prevent cancer progression and their constituents for lung cancer treatment.",signatures:"Wei-long Zhong, Yuan Qin, Shuang Chen and Tao Sun",downloadPdfUrl:"/chapter/pdf-download/54039",previewPdfUrl:"/chapter/pdf-preview/54039",authors:[{id:"184913",title:"Associate Prof.",name:"Tao",surname:"Sun",slug:"tao-sun",fullName:"Tao Sun"},{id:"184922",title:"Dr.",name:"Yuan",surname:"Qin",slug:"yuan-qin",fullName:"Yuan Qin"},{id:"184923",title:"Dr.",name:"Wei-Long",surname:"Zhong",slug:"wei-long-zhong",fullName:"Wei-Long Zhong"},{id:"196046",title:"Mr.",name:"Shuang",surname:"Chen",slug:"shuang-chen",fullName:"Shuang Chen"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"956",title:"Cystic Fibrosis",subtitle:"Renewed Hopes Through Research",isOpenForSubmission:!1,hash:"703f0969078948d82535b7b0c08ab613",slug:"cystic-fibrosis-renewed-hopes-through-research",bookSignature:"Dinesh Sriramulu",coverURL:"https://cdn.intechopen.com/books/images_new/956.jpg",editedByType:"Edited by",editors:[{id:"91317",title:"Dr.",name:"Dinesh",surname:"Sriramulu",slug:"dinesh-sriramulu",fullName:"Dinesh Sriramulu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"969",title:"Lung Diseases",subtitle:"Selected State of the Art Reviews",isOpenForSubmission:!1,hash:"b4344208b8b993d83e0131d23db46343",slug:"lung-diseases-selected-state-of-the-art-reviews",bookSignature:"Elvis Malcolm Irusen",coverURL:"https://cdn.intechopen.com/books/images_new/969.jpg",editedByType:"Edited by",editors:[{id:"87213",title:"Prof.",name:"Elvis",surname:"Irusen",slug:"elvis-irusen",fullName:"Elvis Irusen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"648",title:"Chronic Obstructive Pulmonary Disease",subtitle:"Current Concepts and Practice",isOpenForSubmission:!1,hash:"d52ddc19c473a70b91e5a64f41760a04",slug:"chronic-obstructive-pulmonary-disease-current-concepts-and-practice",bookSignature:"Kian-Chung Ong",coverURL:"https://cdn.intechopen.com/books/images_new/648.jpg",editedByType:"Edited by",editors:[{id:"103585",title:"Dr.",name:"Kian Chung",surname:"Ong",slug:"kian-chung-ong",fullName:"Kian Chung Ong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3843",title:"Lung Inflammation",subtitle:null,isOpenForSubmission:!1,hash:"92938e8752fa3444849d88b776cd7892",slug:"lung-inflammation",bookSignature:"Kian Chung Ong",coverURL:"https://cdn.intechopen.com/books/images_new/3843.jpg",editedByType:"Edited by",editors:[{id:"103585",title:"Dr.",name:"Kian Chung",surname:"Ong",slug:"kian-chung-ong",fullName:"Kian Chung Ong"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5444",title:"Hypoxia and Human Diseases",subtitle:null,isOpenForSubmission:!1,hash:"331b1aa8d399bc404988a8bc5e431582",slug:"hypoxia-and-human-diseases",bookSignature:"Jing Zheng and Chi Zhou",coverURL:"https://cdn.intechopen.com/books/images_new/5444.jpg",editedByType:"Edited by",editors:[{id:"89898",title:"Dr.",name:"Jing",surname:"Zheng",slug:"jing-zheng",fullName:"Jing Zheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3309",title:"Respiratory Disease and Infection",subtitle:"A New Insight",isOpenForSubmission:!1,hash:"2e85d47bf0576f1c2ccf642156ccbda2",slug:"respiratory-disease-and-infection-a-new-insight",bookSignature:"Bassam H. 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",isbn:"978-1-80356-438-8",printIsbn:"978-1-80356-437-1",pdfIsbn:"978-1-80356-439-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"9843dc1d810407088ed9eef10768a64b",bookSignature:"Prof. Joceli Mayer",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11922.jpg",keywords:"Audio Watermarking, Video Watermarking, Text Watermarking, Speech Watermarking, Watermark Transparency, Watermarking Robustness, Print-Scan Channel, Multiple Copies Resilience, Intelectual Property Protection, Watermarking Copy Control, Watermarking Tamper Detection, Watermarking Authentication",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 1st 2022",dateEndSecondStepPublish:"May 3rd 2022",dateEndThirdStepPublish:"July 2nd 2022",dateEndFourthStepPublish:"September 20th 2022",dateEndFifthStepPublish:"November 19th 2022",remainingDaysToSecondStep:"20 days",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Jocely Mayer received the Master's degree in computer engineering from the University of California at Santa Cruz and the Dr. Phil. degree in 1999 from UCSC. He has published over 100 articles, authored two books and one book chapter, has developed and supervised projects on super-resolution, speech compression, VOIP systems, image processing, digital watermarking, and others. His research has been supported by the industry and government agencies such as FINEP, CNPq, Hewlett Packard, and Intelbras.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"110638",title:"Prof.",name:"Joceli",middleName:null,surname:"Mayer",slug:"joceli-mayer",fullName:"Joceli Mayer",profilePictureURL:"https://mts.intechopen.com/storage/users/110638/images/system/110638.png",biography:"Joceli Mayer graduated in electrical engineering from the Universidade Federal de Santa Catarina (UFSC), Brazil, in 1998, received the Master's degree in electrical engineering from UFSC in 1991, the Master's degree in computer engineering from the University of California at Santa Cruz (UCSC) in 1998, and the Dr. Phil. degree in 1999 from UCSC. Received the Best Student Paper Award by the IEEE International Conference on Image Processing and IBM, in 2006, and become an IEEE Senior Member in 2012. Currently he has been a Full Professor of Electrical Engineering at UFSC. He has published over 100 articles in conferences and periodicals, authored two books and one book chapter, advised undergraduate and graduate students on research projects. He has developed and supervised projects on super-resolution, speech compression, VOIP systems, image processing, digital watermarking, hardcopy document authentication, assistive technology applications for hearing, speech and mobility disabled people with internet of things and speech recognition technologies. His research has been supported by the industry and government agencies including the FINEP, CNPq, Hewlett Packard, Intelbras, among others.",institutionString:"Universidade Federal de Santa Catarina",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Universidade Federal de Santa Catarina",institutionURL:null,country:{name:"Brazil"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"9",title:"Computer and Information Science",slug:"computer-and-information-science"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"453623",firstName:"Silvia",lastName:"Sabo",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/453623/images/20396_n.jpg",email:"silvia@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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This practical technique is most effective when the focal mechanism of a small event is similar to that of a targeted event. When the focal mechanisms differ more significantly, the empirical Green’s tensor spatial derivative (EGTD) method, proposed by Plicka and Zahradnik [3], is more appropriate. This can predict the ground motion for events with diverse focal mechanisms. Using single-station inversion of waveform data of several small events whose focal mechanisms and source time functions are well determined, the EGTD elements can be estimated, with the expectation of stable and accurate ground motion prediction. However, discussion in the literature of EGTD applications has been limited [4, 5, 6, 7, 8, 9, 10, 11].
In recent studies [9, 10], the authors sought to simulate strong broadband motions, beyond the corner frequencies, for the same events as in previous studies [6, 8]. This chapter extends these recent studies and applies the results to other stations. The scaling law based on the ω−2 model [12] was used to correct differences between the corner frequencies of events, assuming spectral amplitude decay at higher frequencies. The 0.2–10 Hz band-pass-filtered waveforms of 11 aftershock events were used to estimate the EGTD and then to simulate the strong motion records for main and aftershocks. The EGTD elements were multiplied by the moment tensor elements followed by summation. The spectral amplitude was adjusted by taking the corner frequency of each event into account. Agreement between the simulated waveforms, at the closest epicentral distance, and observation were acceptable.
Figure 1 shows epicenter locations, determined by the Japan Meteorological Agency (JMA), of the mainshock (MJ5.4) and 25 aftershocks (MJ3.1–4.7) of the 2001 Hyogo-ken Hokubu earthquake at the target station, HYG004, one of the K-NET stations operated by the National Research Institute for Earth Science and Disaster Prevention (NIED). The fault zone is roughly 4 km east-west and 6 km north-south. HYG004 is on a nearby rock site (6–10 km from the fault zone). Acceleration data for the mainshock and 15 of the aftershocks (MJ3.5–4.7) came from the K-NET. Two other stations, HYG001 and HYG007, are shown in the inset of Figure 1; they were also tested to verify the applicability of the EGTD method.
Map showing the epicenter locations of the mainshock and aftershocks of the 2001 Hyogo-ken Hokubu earthquake. The mainshock and 15 aftershocks analyzed are indicated by a solid circle and solid triangles, respectively. The 10 aftershocks not used in the present study are represented by open diamonds. The target station HYG004 is shown by an inverted solid triangle. The inset at the top right shows the surrounding region with the target area (solid rectangle) and the other stations, HYG001 and HYG007. (After Ohori and Hisada [8] with slight modification).
The EGTD method is most accurate if the focal mechanism and source time functions are known as accurately as possible. The source model described below, and illustrated in Figure 2, has been reevaluated from previous work [6]. Strike, dip, and rake of a double-couple point source, and source depth, were estimated using the grid search technique [13]. The observed acceleration records at HYG004 for the mainshock and 15 aftershocks were integrated into velocity waveform data with a band-pass filter of 0.2–1.0 Hz. A total of 5 s of data, which included the P-wave arrival and S-wave main portions, was inverted. The theoretical Green’s function for the layered underground structure [14] was calculated assuming a smoothed ramp function with a rise time of 0.32 s. The searching ranges of the strike, dip, and rake angles were set within 20° of the solutions determined by the F-net of the NIED. The source depth was estimated as 8–12 km. Seismic moments, released by five sequential slips with intervals of 0.16 s, and a source time function were then determined by the least-squares method with nonnegative constraints [15]. Events 3, 17, 19, and 26 were excluded from the EGTD inversion because of a relatively large discrepancy in waveform matching between the observation data and synthesis.
Map showing focal mechanisms and source time functions of 16 events (the mainshock and 15 aftershocks) from the work of Ohori and Hisada (2006). Single-station inversion for each event was performed using strong motion records recorded at the K-NET station HYG004. (After Ohori and Hisada [8]).
The EGTD estimation method has been fully explained by Ohori and Hisada [6, 8]. It is applicable to simulation of strong motion in a frequency range below the corner frequency. The process is summarized below. Methods for compensating the spectral amplitude decay, beyond the corner frequencies, and simulating the broadband ground motion follow.
Ground motion displacement
Hereafter,
Considering symmetrical conditions (
where
In the moment tensor inversion undertaken for a particular event using data of all possible components at all possible stations simultaneously,
To compensate for differences in the locations of the main and aftershocks, the focal mechanisms are horizontally and vertically rotated, as described in the literature [4, 5], such that each event can be treated as a point source at the same location. Through the horizontal rotation, shown in Figure 3(a), the station azimuths of the mainshock and aftershocks are set to 90°, as measured from north [6]. Thus, the number of Green’s tensor spatial derivative elements is reduced to three (
Schematic diagram explaining how the focal mechanisms are rotated to reduce the number of unknowns in the empirical Green’s tensor spatial derivative (EGTD) and to compensate for the different locations of the mainshock and aftershocks. In the horizontal rotation (a), the station azimuths for the mainshock and aftershocks are set to 90°, measured from north, so that the number of EGTD elements is reduced to three for the radial and vertical components and two for the transverse component. In the vertical rotation (b), following horizontal rotation, the discrepancies in the take-off angles between the mainshock and aftershocks are corrected. In the top right panel, take-off angles for the mainshock and aftershocks are denoted
Time shifts were estimated from the 0.2–1.0 Hz band-pass-filtered velocity waveforms and then applied to the observation data of aftershocks to fit their S-wave arrival time with that of the mainshock. In addition, the observation data was deconvolved to remove discrepancy in the source time function. The observed waveforms, used in the estimation of the EGTDs, were corrected such that the source time function has a constant seismic moment (1.0 × 1015 Nm, nearly equal to
Assuming the source spectrum obeys the ω−2 model [12], the corner frequency of the mainshock was about 1.0 Hz, while those of 11 aftershocks were between 1.2 and 3.0 Hz, as shown in Figure 4. To simulate the broadband ground motion beyond the corner frequency, the effect of the differences among corner frequencies must be removed. Again, assuming a ω−2 scaling law, and compensating for spectral amplitude decay beyond the corner frequency, each event could then be treated as having the same corner frequency as that of the mainshock.
Relationship between the corner frequency and the seismic moment. The numeral next to solid circle represents the sequential event number in the present study. According to the scaling law, the seismic moment is inversely proportional to the cube of the corner frequency when the stress drop is constant.
Using the focal mechanisms of aftershocks, rotated and time corrected, as described above, simultaneous linear equations for each component were solved for each of the sampling data sets. No smoothing or minimization for unknown parameters was included in the EGTD estimation. Figure 5 illustrates the transverse component elements of an EGTD for HYG004. Each element is scaled, the same as the mainshock, for an event with a seismic moment of 1.0 × 1015 Nm and a corner frequency of 1.0 Hz. As the Green’s tensor spatial derivative elements are determined by the local underground structure, the EGTD elements could be useful for future structural studies.
An example of the EGTD transverse component elements with normalized peak amplitude.
Figure 6 compares the observed radial, transverse, and vertical component velocity waveforms for HYG004, normalized for time, seismic moment, and corner frequency, with a 0.2–10 Hz band-pass filtering and corresponding synthesis calculated from the EGTD. The top trace for the mainshock (Event 1) is not included in the EGTD inversion. Considering the complexity of the high-frequency components, the broadband synthesis, using EGTD, acceptably reproduced the observed waveforms.
Comparison of 0.2–10 Hz band-pass-filtered observed velocity waveforms for HYG004 (red lines) and corresponding syntheses calculated using the EGTD (black lines). For each trace, the source time function, seismic moment, and corner frequency of each event are taken into account. Absolute peak amplitudes are given at the end of each trace: Upper numerals are observed amplitudes and lower are synthesized. Note that the top trace for the mainshock (Event 1) is not included in the EGTD inversion. (a) Radial-comp; (b) Transverse-comp; (c) Vertical-comp.
Three frequency ranges of the band-pass filter are compared in Figure 7: 0.2–1.0, 1.0–10, and 0.2–10 Hz. From this figure, it is evident that simulation results for HYG004 from EGTD are most accurate in a frequency range of 0.2–1.0 Hz, except that the radial components of Event 14 are somewhat overestimated. The results for a frequency range of 1.0–10 Hz are acceptable and very similar to those for a frequency range of 0.2–10 Hz. For most of the events, the maximum amplitude ratio between the synthesized velocity waveforms and observed data is between 0.5 and 1.5. On the whole, the simulation of broadband ground motion, using the EGTD method, successfully reproduced the observed waveforms.
Comparison of the maximum amplitude ratio between the synthesis and observed data for HYG004. The frequency ranges of the band-pass filters are 0.2–1.0 Hz (upper), 1.0–10 Hz (middle), and 0.2–10 Hz (lower).
Finally, Figure 8 shows the results for the other two stations. In this figure, because of data quality issues, only transverse components are shown. Generally, the waveform matching between synthesis and observatory data is inferior to that for HYG004 (see Figure 6(b)). For HYG002, the synthesis underestimated motion for Events 2, 5, 6, and 25. For HYG007, synthesis also underestimated motion for Event 6. On the other hand, for the mainshock (Event 1), the agreement between synthesized and observed waveforms was satisfactory.
Comparison of 0.2–10 Hz band-pass-filtered observed velocity waveforms (red lines) and corresponding syntheses calculated from the EGTD (black lines) for transverse components of data from HYG001 (a) and HYG007 (b). Other conditions are the same as in
A previous study [8] examined the accuracy of simulation results using the EGTD method by comparing them with those obtained using the alternative empirical approach—the EGF method [1, 2]. In that study, velocity waveform data with a 0.2–1.0 Hz band-pass filtering was used. This study compared the two methods over a broader frequency range. The EGF method used was almost the same as in the previous study [8], except the differences in the corner frequencies between the mainshock and each aftershock were corrected using the scaling law of the ω−2 model [12]. In the EGF approach, each aftershock was used in the simulation of the mainshock. To compensate for differences in radiation pattern coefficients, for each aftershock, the data were multiplied by the ratio of radiation pattern coefficients between the mainshock and the aftershock. The radiation pattern coefficients of the SV-waves were used for simulation of the radial components, while SH-waves were used for the transverse components. The source time function of the mainshock was then convolved.
Figure 9 compares the synthesized waveforms of the mainshock for HYG004 (Event 1) obtained using the EGF method, with the observation data and the synthesis obtained using the EGTD method. The EGF method is applied for each of the 11 aftershocks. The amplitude levels of the synthesized waveforms, obtained using the two methods, were mostly in agreement with the observed waveform over the full duration of the analysis. In the low-frequency range examined in the previous study [8], the EGTD method provided a better match with the data than the EGF method. In the broadband frequency range, in this present study, the EGTD method seems to give stable results but not the best match with the data. It is noteworthy that the EGF method, in the case of Events 9 and 16, acceptably reproduced the amplitude for the radial components but twice, and almost a third time, overestimated the amplitude for the transverse components. For simulation using the EGF methods in a low-frequency range, a water-level of 0.20 has best suppressed extraordinary overestimation [8]. A water-level of 0.20, as the minimum absolute value of radiation coefficient, was tested with the current data but could not suppress this overestimation. This may arise from the complexity of high-frequency source processes. The synthesized waveforms using the EGF method look different from event to event. It therefore seems that the EGTD method, by removing the dependency of the EGF method on aftershock selection, provides more stable results.
Comparisons of the synthesized waveforms of the mainshock for HYG004 (Event 1) obtained using the EGF method and each aftershock with the observed data and the synthesis obtained using the EGTD method. The numeral after ‘EGF’ represents the sequential event number of the specific aftershock used in the simulation for the mainshock. (a) Radial-comp; (b) Transverse-comp.
The applicability of the EGTD method to simulating near-field strong motion seismic records has been demonstrated. Previous studies [6, 8] in EGTD estimation used the low-corner frequency of 1.0 Hz for the mainshock of the 2001 Hyogo-ken Hokubu earthquake (
The strong motion data used in this study were recorded at the K-NET stations, provided by the National Research Institute for Earth Science and Disaster Prevention (NIED) on their website (http://www.kyoshin.bosai.go.jp/kyoshin/, last accessed February 2018). The Japan Meteorological Agency (JMA) unified hypocenter catalogue, and the F-net source parameters were also provided by the NIED on their website (http://www.fnet.bosai.go.jp/top.php, last accessed Feburary 2018). This study was partially supported by Grants in Aid for Scientific Research (C) (16 K01316).
Every surgical procedure presents pain and edema in a variable degree, and many pharmacological and alternative methods have been used in an attempt to control and reduce them.
Maxillofacial surgery acts on the patient’s face. The maxillofacial surgical procedures include outpatient surgeries using local anesthesia and also more extensive and invasive procedures under general anesthesia. The most used procedures are exodontia, biopsies, surgical cysts and tumors treatment, bone grafts, rehabilitations with osseous integrable implants, orthognathic surgery, face trauma treatment, and infections treatments.
An inflammatory response is expected after any injury or surgical procedure, in an attempt to defend and repair damage tissues. Inflammatory mediators (prostaglandins, leukotrienes, bradykinin, and others) are released, and consequently, there is an increase in vascular dilatation and permeability, resulting in an edema. However, when it comes to facial edema, the major concerns are related to airway permeability, making the care with this edema a fundamental step for the treatment. It is known that in outpatient surgeries, the extent and the consequence related to edema are smaller and more predictable than in hospital surgeries, but not less important, as we will discuss further on the topic of complications.
Many studies discuss the importance of edema for such surgeries, especially outpatient procedures, which not always presents significant amounts of edema. Besides that, the discussions about the treatment are not conclusive.
Edema is characterized by the excess of plasma proteins in the interstitial space. Its formation occurs when the lymphatic flow exceeds the transport capacity of the lymphatic system or when this system becomes inefficient in absorbing and transporting these proteins [1]. Although the primary edema is a condition usually developed by vascular and/or congenital diseases, the secondary edema occurs due to a lymphatic system injury, whether by infection, cancer, or surgery [2, 3].
Despite the fact that the edema is part of the inflammatory process, and therefore, a consequence of the surgical process, the severity and localization of it can be related to some factors, intrinsic to the patient or related to the surgery.
The increase in the surgical procedure difficulty due to one or more of these factors directly influences on the severity and extension of the postoperative morbidities [4].
Any condition that affects postsurgical inflammatory response directly interferes with the postoperative quality, recovery, and also with the edema formation. Therefore, all efforts are made to maintain airway permeability and prevent its obstruction.
An worrying condition is the angioedema, which results from changes in the immunoglobulins involved in the inflammatory response. Due to the fact that is a severe, acute, and rapidly evolving edema that mainly affects the larynx, pharynx, and face, there is a great risk of airways obstruction, and therefore, it is associated with reintubation and risk of death [5, 6, 7, 8].
Unfortunately, the occurrence of angioedema is a difficult prediction factor, mainly if the patient never presented its manifestation. For this reason, a rapid and accurate diagnosis is essential, as well as the establishment of artificial airways and adequate drug treatment [6, 7, 8].
The BMI consists in the division of ratio of body weight per height of the individual. Despite there is no consensus in the literature, some studies have related BMI with the severity of postoperative edema [4, 9, 10, 11].
Although is expected that individuals with higher BMI (overweight) develop greater edema, this correlation is not always found. Therefore, on those studies, other variables such as age and gender were considered more influential than BMI in the postoperative edema formation [4, 9].
The relation between BMI and the facial edema occurs because adipose tissue is responsible for most of the pro-inflammatory cytokines. So people with a higher BMI have more adipose tissue, more inflammatory biomarkers and, consequently, greater inflammation and greater edema [11, 12].
In the literature, a positive correlation between BMI values and developed edema is observed. Thus, individuals with higher BMI develop greater edema, but their rate of reduction is faster in the first postoperative days [10, 11]. However, individuals with lower BMI develop smaller edema, and although the rate of reduction in the first postoperative days is slower, the total resolution of edema occurs before than in people with a high BMI [10].
The duration of surgery is appointed as one of the predictive factors for a greater or smaller postoperative edema. This is because a longer surgery requires a greater manipulation of the tissues, and consequently, a greater inflammatory process [4, 13, 14, 15, 16].
The increasing of the surgical time can occur due to factors related to the surgery and intrinsic to the patient, such as age and anatomical variations. In addition of it, the surgeon’s experience is related to the increasing or decreasing of the operative time [13, 15, 17].
The operative time is predictive not only for the amount of edema, but also to the intensity of pain and trismus. This is due to a bigger trauma or intraoperative complications, which is directly related to the increase in surgical time [4, 14, 16]. Thus, although studies indicate that there is a correlation between high surgical time and greater postoperative edema, factors that caused an increasing of the surgical time must be considered.
The type of surgery performed interferes directly in postoperative edema. Thus, large surgery (such as orthognathic surgery) is expected to cause a greater inflammatory process and, therefore, larger and more diffuse edema than minor surgery (third molar extraction, for example) [14, 18].
However, when it comes to the same type of surgery, variations can occur depending on the surgical difficulty level. It is expected that a major difficulty surgery occurs in a longer surgical time and causes a more intense and extensive surgical trauma. Therefore, the inflammatory process will be bigger, as well as the postoperative edema [4, 11, 14, 16, 19].
Some factors can contribute to the increasing of the surgery difficulty level, such as denser bones, teeth with roots formed and consolidated in the bone by masticatory stimuli, quantity of procedures, and unfavorable dental position [9, 11, 14].
The position of the third lower molar closer to the lingual wall appears to result in more severe postoperative edema, due to a more extensive surgical trauma in consequence of the bone amount removed [11]. In addition, the distal and horizontal position of the teeth is related to the greater postoperative edema, as the need to perform osteotomy and odontosection, which results in a greater surgical trauma [14].
In large surgeries such as orthognathic surgery, factors like the duration of the surgery, combined procedures (maxillary and mandibular osteotomy and mentoplasty) and bone density are related to the amount of postoperative edema. Thus, surgeries in only one of the jaws present less surgical trauma than the bimaxillaries, and therefore, develop smaller edema. When it comes to bone density, thicker and denser bones cause more difficulty in the osteotomies, increasing surgical trauma and inflammatory process [18, 20].
Surgeries involving maxilla, such as Le Fort I osteotomy, result in greater internal edema to the cavities, increasing the risk of airways obstruction [18].
It is very difficult to evaluate the experience of one surgeon, since there are no preestablished protocols to separate experienced surgeons from inexperienced. Some papers use the classification based on the training phase in which the surgeon is, others how long the surgeon is graduated, or even the amount of surgeries already performed by the professional [14, 17, 21, 22].
Surgeon’s experience indirectly interferes with postoperative edema. This is because it does not directly affect the factors that converge to the edema formation, but rather those that are related to the severity of the postoperative edema [14, 17, 21, 22].
The greater the experience of the surgeon, the lower is the occurrence of postoperative complications. In addition, the more experienced surgeon is capable to solve more quickly and efficiently intraoperative complications, as well as perform the surgical procedure accurately. And more, the surgeon’s experience is closely related to possible planning errors (such as implant and orthognathic surgeries) and execution. Less experienced surgeons are more likely to make these mistakes, culminating in the prolongation in the surgery duration and even possible the need for surgical reintervention [17, 21, 22].
Therefore, the surgeon’s experience interferes in the surgical time, trauma extension, and blood loss, which are decisive factors for the inflammatory process and, consequently, for postoperative edema [14, 21].
Although there are no studies relating the amount of transoperative bleeding to edema, it is known that there is a relation between blood loss and postoperative quality.
Lymphedema is characterized by the increasing volume of a body segment. However, this swelling is not always present only by edema, especially in the postoperative cases. Hematomas and clots also cause enlargement of the region volume. That way, trans- and postoperative bleeding contributes to swelling, as there is an increase in the body segment volume but, unfortunately, it is not possible to clearly distinguish whether it is edema, hematomas, or the combination of them [23].
Besides that, the amount of blood lost during surgery influences the inflammatory process. The greater the bleeding, the more intense and lasting is the inflammatory process, and the greater is the postoperative edema [18, 20].
Due the fact that these surgeries are performed in oral cavity, there is a possibility of swallowing blood during the surgical procedure. Besides the malaise caused by blood loss, postoperative vomiting increases the pressure in the newly operated region and causes an increasing of the edema. In addition, due to the bleeding caused by the pressure increasing, there may be formation and/or increasing of hematomas [24, 25, 26].
Therefore, strategies are necessary in order to reduce the amount of bleeding and, consequently, not only to improve postoperative quality, but also to help control facial edema and reduce the period of hospitalization after oral and maxillofacial surgeries.
The mean arterial pressure interferes directly in the bleeding and, thus in surgical time. Lower mean blood pressure reduces transoperative bleeding, reducing as well the amount of blood lost, improving the visualization of the surgical field, reducing surgical time, and the formation of hematomas and swelling [27, 28, 29, 30].
The hypotension induced during surgery is a strategy to improve the surgical field through the reduction of bleeding and consequently reducing surgical time and postoperative inflammatory process [24, 27, 28, 31]. Induced hypotension, or controlled hypotension, is defined by the reduction of systolic blood pressure to 80–90 mmHg with a reduction in mean arterial pressure (MAP) to 50–65 mmHg or a 30% reduction in MAP [30, 32]. It is obtained through medicament during anesthesia. Despite being considered safe and presenting proven benefits, induced hypotension requires preparation and good skill of the anesthesiologist and should not be maintained for long time due to hypoperfusion risks of the organs such as the central nervous system (CNS), heart, liver, and kidneys [29, 32].
Although in the current literature have not yet been found studies that have investigated the correlation between hypotension induced in face surgeries and postoperative edema, hypotension is capable to improve several factors involved with the development and amount of edema.
The age at which the patient is operated has been pointed out as one of the predictive factors for the development of bigger or smaller edema. Despite studies attempt to find this relation, there is still no consensus on the relation between age and severity of developed edema [4, 14, 15, 33, 34].
On the one hand, some authors argue that face surgery in younger individuals results in less difficulty in the procedure and consequently less surgical trauma and less edema [11]. On the other hand, there are authors who affirm that the reduction of the inflammatory response and diminution of the lymphatic system elasticity occur with the increase in the age. Thus, older individuals develop less edema and have less efficacy of the lymphatic system [4, 14, 15, 16, 33, 34, 35]. Besides that, older patients have a prolonged inflammatory process and, therefore, slower reduction of edema [15].
Another factor pointed as an influencer in the formation of edema and its quantity is gender. Although is expected that women develop greater swelling due to hormonal variations, use of oral contraceptives, and bigger risk for dry socket, the male gender is pointed out in studies as being more predisposed to a greater amount of postoperative edema [11, 13, 34].
Factors such as increased bone density and thickness and stronger muscles can do postoperative edema to be more severe in men than in women. This is because they are factors that directly interfere in the level of difficulty and quantity of surgical trauma, injuring more lymphatic structures and increasing the inflammatory response, generating more edema [11, 34].
However, the smaller thickness of the female mandible increases the chances of fracture of the mandibular ramus during third molar extraction, increasing surgical trauma [4, 13].
Anyway, this significant difference in the amount of developed edema is observed on the first postoperative day, but it is irrelevant on the seventh day [11, 34].
Thus, even in studies in which the amount of postoperative edema does not present a significant difference between the genders, the extent of surgical trauma and the occurrence of intraoperative complications are indicated as the main influential factors for the severity of postoperative edema [10, 19]. However, the occurrence and intensity of these factors are difficult to predict, so that is the reason to consider the gender and its risk factors and predict the level of the surgery difficulty.
The presence of nausea followed or not by vomiting is a factor that can be observed in clinical practice. Increased patient effort during vomiting increases facial edema and also stimulates postoperative bleeding. However, although the relation between nausea and vomiting with edema is not mentioned in the literature, it is a fact that can be verified in clinical practice, especially in the postoperative period of orthognathic surgery.
Another important factor related to the control or prevention of edema formation consists on the postoperative rest and positioning of the patient. It is known that the dorsal decubitus tilted by approximately 30° decreases the pressure in the face blood vessels and helps to control the bleeding and edema.
After surgery, the periosteum is detached in the operated region. Thus, the mobilization of this periosteum, by movement or compression of this region, stimulates the inflammatory response potentiating the edema.
Although these factors are not in specific scientific studies, clinical observation makes it possible to affirm the importance of both bedside and resting care in the postoperative period of face surgeries.
In maxillofacial surgery, the observation, control, and reduction of edema are important postoperative factors, due to the possibility of airway compromise. In this way, surgeries with potential formation of exacerbated edema should present evaluation and control of this condition, in order to assist the decision related to the maintenance or replacement of the edema treatment protocol.
Between the techniques described for evaluating edema, the most used ones clinically are subjective, and are totally dependent on the professional’s experience and on the patient’s report. Although there are more objective methods of clinical evaluation with good reproducibility, these are limited to the upper and lower limbs, making it impossible to apply to regions such as head and neck [35, 36].
In the head and neck regions, most of the methods reported in the literature measure the edema by the distance between two points, based on anatomical points, such as mandibular angle, lateral, and medial epicanto of the eyes and middle of the chin.
Other measurement devices that provide more accurate data about the changes related to edema values include imaging exams. However, due to the fact that it involves high cost and exposes the patient to ionizing radiation, these techniques need specific indication [37]. Ultrasonography (US), magnetic resonance imaging, and computed tomography are examples of usable exams [38]. The US presents changes in the echogenicity of its images, which are not specific for volume changes caused by increasing of subcutaneous fluids [39]. In addition, to the face part, the echographic measurement does not always point the more swollen site due to the reproduction of the distances from the skin to the bone, which leads to imprecise and disproportionate results [40].
Bioelectrical impedance is another method described in the literature for the measurement of edema. This technique measures the amount of peripheral and total fluid in the body. However, low-cost and easily applicable devices for measuring body edemas as well as limbs are still scarce [36].
The evaluation methods developed for use in researches have evolved greatly. The first studies used subjective methods and difficult reproducibility, which made them less reliable in relation to the real magnitudes and behavior of edema. Van Gool et al. and Album et al. demonstrated the lack of correlation between subjective evaluations and objective measures of edema [41, 42, 43]
The measurement methods should be capable of being used in clinical and patient tolerable trials. Thus, portable devices were studied with the objective that they could be easily used with precision and transported to the place where the patient is, making possible to obtain early measures and follow-up of the edema [42, 44].
Therefore, objective measurement methods represent a more appropriate approach to the problem. However, these measurements should be evaluated and validated by doing repeated measurements on untreated individuals to verify its accuracy.
The methods already tested and used in studies were [45, 46]:
facial bow method;
ultrasound method;
stereophotographic method;
method of cuboid element;
measurements with tape measure;
sonographic evaluation;
photo evaluation;
face scanning; and
evaluation with 3D mold.
The early stage of inflammation presents accumulation of fibrin and polymorphonuclear neutrophils in the extracellular space of injured tissues. The processes that occur in this phase are vessel diameter change, increased vascular permeability, exudate formation and migration of neutrophil cellular exudates into the extravascular space. The chemical mediators of acute inflammation include histamine, prostaglandins, leukotrienes, serotonin, and various cytokines. It is known that prostaglandin associated to bradykinin has the most potent pain-activating effect [14, 47, 48].
The control of inflammation and, therefore, swelling aims to reduce pain and improve life quality in the postoperative period. The processes of the inflammatory mediator may last up to 96 hours.
Trismus occurs as a result of muscle spasm caused by the inflammatory process. In this process, there is compression of the nervous structures by the edema, leading to the limitation of movement accompanied by a painful sensation, which can be from discomfort to severe pain [14, 47, 49].
Although it is subjective and dependent on several factors, the evaluation of postoperative pain in maxillofacial surgeries is essential, since this is one of the main complaints of operated patients and is directly related to edema. Therefore, pain, edema and trismus are consequences of the formation and release of prostaglandins, bradykinins, and other mediators of inflammatory response [14, 47].
Patients with moderate and severe edema may be unable to discern pain from discomfort caused by stretching of the skin by increased facial volume. In addition, the pain is related to the patient’s emotional state, being influenced directly by their mood, level of satisfaction, and well-being [18, 20, 50].
Therefore, edema can also cause psychological and emotional problems due to the esthetic alteration of the affected body segment [50]. The maxillofacial surgeries carry great esthetic and functional expectations. However, patients, although relieved to have undergone surgery, may present mood swings due to the difficulty of self-care, pain, and edema. Changes in body image are one of the major complaints related to edema [20].
Edema can also influence self-care. This is because it makes feeding and oral hygiene difficult because it prevents proper visualization of the oral cavity and limits the range of mandibular movement. In addition, patients submitted to orthognathic surgery have shown greater difficulty in removing and placing intermaxillary locking elastics according to the degree of edema they develop [20].
Internal edema to the cavities is a major concern in the postoperative period. This is because breathing may be affected by pressure and possible obstruction of upper airway structures, causing respiratory distress and discomfort, and even leading to the need for re-intubation or performing a tracheostomy in the most serious, life-threatening cases [6, 8].
Severe postoperative edema is an important complication that can affect upper airway permeability and may lead to obstruction in more severe cases. The procedure that presents the greatest risk of airway obstruction due to edema is the Le Fort I type osteotomy, performed in the maxilla and covering the floor of the nasal fossa [18]. Thus, severe edema can cause respiratory and functional problems, which increases hospitalization time and the need for ICU admission.
Peripheral nerve damage is the result of direct or indirect trauma to a nerve. The direct relationship between edema and paresthesia is known and can be explained by the spatial relationship of the nerve vessels with adjacent structures, such as muscles and bones.
Following the same mechanism of acute compressive neuropathies, facial edema caused by surgical trauma, infections, fractures, or injuries can compress the sensory and motor nerves of the face (trigeminal nerve and facial nerve). This compression, or even stretching of these nerve bundles, impairs the conduction of the nerve impulse, resulting in paresthesia and even temporary paralysis.
Studies on nerve conduction measured the magnitude of the conduction blockade of nerve action potentials and the focal slowing of conduction. Direct correlation between degree of changes and duration of compression was demonstrated. Another observation is related to local ischemia, which, in combination with direct pressure effects, contributes to the development of compressive neuropathies. In severe cases of acute compression, with direct relation to extensive and prolonged edema, remyelination of nerve fibers can take weeks or months after resolution of compression.
Another aspect in relation to the neurosensorial disorders is related to the inflammatory mediators that are released when a trauma to the tissue occurs. These are located in the edema region and act temporarily as chemical irritants to the nerves.
Thus, studies attempt to relate the use of corticosteroids with the improvement of neurosensory symptoms after tissue trauma with considerable edema. However, due to the lack of standardization of the applied tests and classification, only the presence or absence of the disorder was considered [51]. More controlled clinical trials need to be performed to obtain data on neurosensory disorders.
Some local factors (directly related to the wound) and systemic (linked to the individual) can interfere in the cicatricial process, facilitating complications and sequels and causing esthetic and functional damages to the tissue.
Local factors: dimension and depth of the lesion; level of contamination; presence of net collections (bruises, ecchymosis, edema); tissue necrosis and local infection; poor vascular supply; surgical technique used, material and technique of suture, types of bandages; and traction or mechanical pressure on the scar [52, 53, 54].
Systemic factors: age group, ethnic origin, nutritional status, presence of chronic diseases, and use of medicines.
Angiogenesis is essential to healing wounds as it provides restoration of blood flow and transport of nutrients to cells as well as transporting the components of the immune system. Edema makes this stage difficult, because the excessive distension of the tissues leads to compression of the newly formed vessels, altering the blood flow. In this way, the body’s capability to carry defense cells and administered antibiotics is impaired, making healing more difficult.
Hypoxia in the area of the lesion stimulates angiogenesis responsively, aiming formation and remodeling of the extracellular matrix for tissue repair. However, this process is limited to the first 48 hours of the beginning of the repair process, being detrimental to vascular neoformation and regulation of healing factors.
Fibroblasts are involved in deposition of the extracellular matrix and also in approaching the edges of the wound. Thus, the tissue distension caused by edema compromises this narrowing and tissue reepithelialization, making it difficult to form the fibrin network and providing a disordered growth of collagen, which leads to the formation of hypertrophic scars [53].
With excessive edema, a lesion that could have first-intention healing with contact between the edges becomes second intention, due to tissue tension, causing dehiscences of suture and separation of the wound edges. In addition, local edema obstructs the lymphatic vessels, facilitating the accumulation of catabolites and producing a greater level of inflammation.
Inflammation is the local physiological response to tissue injury. Although some amount of inflammation is needed for proper wound healing, the excess of inflammation leads to severe edema and pain that causes discomfort to the patient.
The use of corticosteroids during orthognathic surgery is a fairly common practice for faster resolution of facial edema [55]. However, there is no consensus on its uses, its benefits, and adverse effects. The comparison of drugs in published studies is difficult due to the variety of parameters and methods used. Corticosteroids help reduce facial edema by acting as immunosuppressants that block the early and late stages of inflammation, decreasing the dilation and permeability of blood vessels. From this, there is a reduction of the amounts of liquid, proteins, macrophages, and other inflammatory cells present in the areas of tissue injury. In this terms, corticoids have a beneficial effect on the inflammation control, and consequently, on edema [51].
The use of steroids in patients can be by mouth, intramuscular injection, or intravenous methods. A recent study compared the effects of different routes of methylprednisolone uses on edema and trismus after extraction of third molars [56]. It was concluded that the systemic application of a steroid is more effective for improving the range of motion. However, direct injection of the steroid into the musculature had the best effect in reducing postoperative swelling.
Another study by Ehsan et al. [57] analyzed the effect of preoperative submucosal uses of dexamethasone on swelling and trismus on third molar extraction. They found out that this injection was very effective in reducing these postoperative conditions. In another study, it was found that the uses of corticosteroids in the preoperative period through the parenteral route have a greater impact in the reduction of postoperative swelling and trismus [58]. In addition, patients with zygomatic bone fractures usually present swelling, pain, and trismus before surgery, requiring prolonged treatment than removal of the third molars. Therefore, in order to benefit from steroid medication, patients with facial fractures should receive higher doses than patients undergoing minor surgeries [45].
The use of intravenous systemic corticosteroids before orthognathic surgery helps to reduce facial edema, but adverse effects are not well described in literature [59]. The use of corticosteroids before, during, and after orthognathic surgery, independently of the dosages, promotes reduction in facial edema, mainly until the third postoperative day. The most commonly used corticosteroids are dexamethasone, methylprednisolone, and betamethasone [51, 60]. Betamethasone is considered a potent steroid because it has high anti-inflammatory activity and does not cause fluid retention [60]. Dexamethasone is a highly selective and long-acting synthetic corticosteroid that has potent anti-inflammatory action [61].
In oral surgery, of all pharmacological agents tested, steroids seem to be the most successful for inflammation control. Corticosteroids, such as dexamethasone, may inhibit the early stage of the inflammatory process and have been widely used in different regimens and pathways to decrease inflammatory process after third molar surgery [62].
Although steroids seem to be the most successful in relieving edema after extraction of the third molar, the immunosuppressive effects of cortisol and its synthetic analogues are well known [63]. Previous studies about dexamethasone in third molar surgeries have concluded the need of accurate clinical research for better evaluation protocols for corticosteroid use [64].
The use of analgesics and nonsteroidal anti-inflammatory drugs alone or in combination with corticosteroids or opioids is common after third molar surgeries to reduce facial edema and pain [65]. When nonsteroidal anti-inflammatory drugs are given prior to surgery, they significantly reduce postoperative edema [66]. One study compared the use of diclofenac potassium, etodolac, and naproxen sodium given in preoperative of third molar surgery and concluded that diclofenac potassium showed better edema reduction [67]. Another study compared the use of diclofenac potassium alone or in combination with dexamethasone and concluded that combined therapy was more effective in reducing pain, trismus, and edema after third molar surgery [68]. There is no consensus in literature about which analgesics to use, for how long, and what is the best dosage with the least adverse effects.
A new drug trend that has been used to control edema development is hyaluronic acid (HA). Nowadays, few studies are found in literature and their actual efficacy as well as their use is not well established yet. HA is a high molecular weight glycosaminoglycan, a major component of the extracellular matrix [69]. It can be found in several tissues, and one of its properties is formation induction of early granulation tissue, which helps the healing and improves inflammatory process [70]. HA turned out to be effective in reducing edema when used as spray after third molar extraction [70, 71]. The use of HA associated with platelet-rich fibrin was capable to decrease edema after third molar extraction surgery, compared to the isolated use of platelet fibrin [72]. Further studies using HA in larger groups and in other types of surgeries are necessary to establish a protocol use, consensus on its effects, and investigation of possible adverse effects.
The adverse effects of corticosteroids are rare but important to evaluate. Complications are well known and include immune system suppression, hypertension, hyperglycemia, suppression of adrenal corticosteroid activity, allergic reactions, skin steroid acne, glaucoma, and psychiatric disorders. In addition, the use over 7 days may lead to development of Cushing’s syndrome [54, 73].
Thus, it is noted that complications are related to prolonged use. In maxillofacial surgeries, it is generally used for a short time, at most 24–48 hours, so side effects are rare.
Also, it is known that anti-inflammatory drugs for edema control may increase bleeding by directly interfering in coagulation cascade. Thus, its benefit regarding edema control is compromised.
Cryotherapy is the therapeutic use of cold applied for reducing skin and subcutaneous tissues temperature. It is indicated for inflammation control, pain, and edema after surgery or injury [65, 74]. Thus, physiological cooling exerts autonomic-mediated effect that induces vasoconstriction, favoring minimization and control of edema [75].
It is a treatment modality widely used because it is simple, inexpensive, and can be applied many times. Its therapeutic effects are due to alterations in blood flow, consequent vasoconstriction, and reduction of metabolism, also providing restriction of bacterial growth.
However, information concerning cryotherapy effects on edema is controversial [74]. Few studies report the effects of cryotherapy in maxillofacial surgeries, although its use is consecrated by the great majority of surgeons and in several types of surgeries.
Considering that during the first 10 minutes of ice application, most of the local temperature reduction occurs, most studies recommend the application for 10–20 minutes, having a rest period of the same time or twice as long [74]. The use of cryotherapy for 30 minutes every 1½ hours, for 48 hours after third molar extraction was quite effective in facial edema control [76].
Cryotherapy is contraindicated for patients with peripheral vascular disease, hypersensitivity or cold intolerance, as in Raynaud’s phenomenon and in areas with impaired circulation. A disadvantage of cryotherapy is that its use normally starts at 0° and rapidly reaches room temperature [75].
The cryotherapy protocols use differ greatly from each other, especially regarding duration and application form [74]. Its efficacy has been questioned because despite its common and daily use in clinical practice after maxillofacial surgeries, there is no consensus or protocols on its use, so new studies are needed.
Hilotherapy began to be used recently in postoperative of maxillofacial surgeries for control and reduction of facial edema. It is a preformed polyurethane face mask, in which cold and sterile water stream passes through, promoting cryotherapy at regulated and maintained temperatures [77].
A recent systematic review showed that hilotherapy is used immediately after surgery, with temperatures of 14–15°C. However, in third molar extraction, single application was used for 45 minutes, and after orthognathic surgeries, the application was for continuous period from 48 to 72 hours. Both protocols had positive effect in reducing facial edema [78]. Therefore, it can be concluded that extensive surgeries require longer application.
Hilotherapy, when compared to facial cryotherapy performed using ice blocks, was more efficient in facial edema control and reduction after maxillofacial surgeries [77, 78, 79, 80].
A recent study has shown that the use of facial hilotherapy performed at home after third molar extraction surgery is safe, easy to apply, brings benefits in reducing facial edema and also improves quality of life [75].
One of the difficulties in using hilotherapy is the cost of the device, which can reach high values. However, once this is resolved, its use will probably replace conventional cryotherapy in a few years as studies have shown beneficial effects in reducing edema and postoperative pain with greater patient comfort.
Low-power laser is a relatively recent method and has been used as an alternative to edema control because it is capable of promoting modulation of the inflammatory response, reducing pain, edema and trismus, in addition to accelerate tissue repair [71, 81]. It is considered easy to apply and does not cause adverse effects [65].
Laser acts in reduction of edema by controlling and decreasing inflammatory response. So, it promotes faster recovery of injured lymphatic vessels and potentiates the action of lymph nodes [82].
Despite this, there is still no consensus about which is the best protocol for use in maxillofacial surgeries, so that its effects can be better utilized. However, different protocols can be found in literature, especially regarding to which postoperative moment laser should be applied and how many sessions are necessary. In laboratory tests, low-power laser was able to improve pain by regulating inflammatory factors at doses around 7.5 J/cm2. In addition, application in an area using more than one point promotes better results than the concentrated application in a single point.
The need to control inflammation in preoperative period is known. However, using laser before third molar extraction surgery seems to have only analgesic response [83].
The laser can be applied in minor surgeries, such as dental extractions and also larger, such as orthognathic surgery. Although the application of intraoral and extraoral laser at the end of the surgery does not show benefits in the immediate reduction of edema, when evaluated in the following days, the patients present a reduction in facial edema [82, 83, 84]. That occurs due to the latency period in which there is the biomodulation caused by the laser on the inflammatory response, with prolonged and residual effect [83], not requiring more than one application [84].
Therefore, the use of laser is questioned in small and controlled inflammatory processes, since benefits to patient do not justify treatment costs [85, 86]. Still, in some cases, laser seems to have analgesic effect only, not helping to reduce facial edema [87].
Thus, although low-power laser has potential to control inflammatory process and reduce complications, results depend on an indication that justifies its use and, mainly, the protocol used.
Manual lymphatic drainage is a resource that, if applied correctly and by a trained professional, helps in the resolution of edema. By means of slow movements and gentle pressure (30–40 mmHg) following the lymph pathway, the MLD proposes to potentiate the function of the lymphatic system [88, 89]. Thus, it is a nondrug option in the treatment of edema.
The benefit of manual lymphatic drainage is undeniable; however, in maxillofacial surgeries, it is still little used and little known, due to the scarcity of studies that demonstrate its effectiveness in this type of surgery and also prove the safety of its application. In surgeries in other regions of the body, the use of MLD to decrease edema is quite consistent, with well-established protocols and benefits. In maxillofacial surgery, there are still no protocols for beginning and no consensus regarding their benefits due to the amount of work done so far.
The MLD had proven efficacy in the postoperative period of third molar extraction, alveolar bone graft, and orthognathic surgery [90, 91, 92]. In a clinical trial with a split mouth model, third molar extraction was performed by adding MLD on one side only in the postoperative period. Using reproducible facial measures and Visual Analogue Scale (VAS) for pain, it was concluded that MLD is able to significantly reduce postoperative swelling and pain in this surgery [93].
The same effect was observed in the postoperative period of alveolar bone graft with filling of the bone defect by spongy bone of the iliac crest. However, this study compared the MLD performed by a physiotherapist to an adapted drain that was taught and applied by the patient. Both groups showed improvement over the course of the day, but MLD applied by physiotherapist had better results on edema and pain compared to self-drainage [92]. Despite that, attention should be paid to the absence of a control group so that the study would effectively prove the benefits of MLD. However, it is possible to conclude the importance of the physical therapist in the postoperative period of this surgery, since this professional has skills that can contribute to the improvement of the discomfort caused by the edema and the referred pain.
In the orthognathic surgeries, MLD was very effective in reducing postoperative edema when compared to a placebo, both applied by a physiotherapist. In these cases, not only was drainage capable to accelerate the regression process of edema, but also to anticipate its peak. It was also observed that the maximum edema was lower in the patients who received the MLD. Thus, MLD is able to promote the control of edema when applied during its development period and also to accelerate the process of regression of swelling in the postoperative period [91, 94].
However, even in this study, MLD was not effective in relation to pain perception. The authors attribute this to two factors: the application of a placebo, which may have interfered in patients’ perception of pain and the fact that the patients did not develop severe edema, and therefore, the pain or discomfort related to the edema may have been lower, as well as the perception of relief in the group that received the MLD [91].
Although the benefits of MLD in the postoperative period of oral and maxillofacial surgeries have been studied, there is still no agreement as to when the application of MLD should begin. However, it is known that the peak of edema in maxillofacial surgeries occurs between 48 and 72 hours after surgery, and therefore, the beginning of MLD before this period seems to anticipate the peak of edema and regression, causing the amount of edema at the peak being lower [91, 94].
It can be concluded that MLD represents a safe nondrug option in the treatment of postoperative edema, when well indicated and applied by a qualified professional. Despite all the proven benefits, it is necessary to observe the need for MLD in various oral and maxillofacial surgeries. It is known that it is able to accelerate the process of regression of edema and provide relief of pain, but the need should be questioned in cases of small surgeries with the formation of discrete and local edema. In those cases, typical of a small controlled inflammatory process, MLD can be an unnecessary treatment to the patient, increasing the costs of the treatment and not having all its benefits observed.
Elastic bandage, or Kinesio taping, was first used in athletes, to aid in the recovery of muscle injuries, provide more stability to the joints, and provide relief from pain. However, it was realized that due to its way of functioning, it could be beneficial in the treatment of lymphedema.
KT, through the formation of convolutions in the skin, increases the interstitial space. Thus, through this increased space, fluids tend to move from higher pressure areas (congesta) to areas of lower pressure, improving blood and lymphatic flow. This occurs following the placement of the KT, which is positioned according to the path of the lymphatic system. In that way, KT may be able to relieve swelling caused by bruising and edema [23, 45, 95, 96].
In maxillofacial surgeries, its efficacy has already been tested in several surgeries: surgical reduction of mandible fracture, surgery to reduce fractures of the zygomatic-orbital complex, third molar extraction, and orthognathic surgery [97].
In the surgical reduction of mandibular fracture and zygomatic-orbital complex, KT is effective in reducing edema, anticipating the day of peak edema, the amount of edema formed on this day, and accelerating its reduction. However, despite the more rapid resolution of edema, no effects on trismus or pain relief were found [95].
In third molar extraction surgeries, KT anticipates the day of maximum edema and the amount of edema formed on this day. However, the rate of edema reduction is lower when compared to patients who did not use KT. Despite that, patients who use KT postoperatively seem to have resolution of the edema earlier. Furthermore, KT was effective in relieving pain, but not in trismus [96].
Even so, in the exodontia, when compared to the placement of drains for the treatment of lymphedema, KT is not as effective. Drain placement at the surgical site is shown to be much more effective not only at the faster reduction of edema but also in relation to pain, although it is an invasive approach. Despite this, none of the treatments helped reduce trismus in this study. It should also be considered that drainage placement, despite being effective in reducing edema, may lead to other complications, in relation to the possibility of subcutaneous emphysema, infection, and external facial scar [98].
In orthognathic surgeries, the application of KT is beneficial in the treatment of postoperative edema, being capable to anticipate the day of maximum edema, reduce the maximum amount of edema formed, and accelerate the regression process of edema. However, it does not appear to have significant effects with regard to pain or trismus [97].
Thus, KT is a nonmedicated treatment option for the control and treatment of postoperative lymphedema of maxillofacial surgeries. However, its effects on pain and trismus need to be better elucidated. Although one of the goals of KT is to prevent the formation of bruises and/or to treat them, there is still no proof of it. Therefore, it is a function to be explored with great interest, since the increase in volume of a body segment is not only due to edema but also due to hematomas.
Therefore, KT is a relatively inexpensive treatment option, but it requires specific training and professional habilitation, as well as presurgery testing to check for allergy to the components of the bandage.
In this chapter, factors related to edema development in maxillofacial surgeries and alternatives for its control and treatment were presented. It is known that this condition is strictly related to the inflammatory process, and therefore, controlling edema also requires controlling postoperative inflammation.
Several factors contribute to edema severity, and knowing which factors cause these and their influence on inflammatory process, it is possible to predict the quality of the postoperative period. The inflammatory process control, and consequently edema restriction, is fundamental for the quality of healing process and postoperative. Thus, it is necessary to have attention and intervention of surgical team on controllable factors that lead to a most severe or mild formation of edema, such as surgical time and precise surgical planning.
In addition, knowing about the risks for each factor related to the edema development makes individual and personalized treatment possible, which brings great benefits to the patient. Aiming at reducing complications related to edema, better postoperative quality, increased satisfaction and reduction of hospitalization time and treatment costs, and several drug and nondrug methods may be employed. Currently, there is a tendency in reducing medicament use in order to reduce the occurrence and severity of adverse effects. In this way, nondrug methods are increasingly study targets and used in clinical practice.
Therefore, more studies are needed to prove the efficacy and safety of these methods. Also, the formation of a well-trained and integrated multiprofessional team is necessary, aiming for safety, comfort, and faster patient recovery in postoperative period of maxillofacial surgeries.
The authors declare that they have no conflict of interest.
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A Role for Antioxidants"},signatures:"Maria de Lourdes Reis Giada",authors:[{id:"153687",title:"Associate Prof.",name:"Maria De Lourdes",middleName:"Reis",surname:"Giada",slug:"maria-de-lourdes-giada",fullName:"Maria De Lourdes Giada"}]}],mostDownloadedChaptersLast30Days:[{id:"69775",title:"Principles of Chromatography Method Development",slug:"principles-of-chromatography-method-development",totalDownloads:4113,totalCrossrefCites:5,totalDimensionsCites:10,abstract:"This chapter aims to explain the key parameters of analytical method development using the chromatography techniques which are used for the identification, separation, purification, and quantitative estimation of complex mixtures of organic compounds. Mainly, the versatile techniques of ultra−/high-performance liquid chromatography (UPLC/HPLC) are in use for the analysis of assay and organic impurities/related substances/degradation products of a drug substance or drug product or intermediate or raw material of pharmaceuticals. A suitable analytical method is developed only after evaluating the major and critical separation parameters of chromatography (examples for UPLC/HPLC are selection of diluent, wavelength, detector, stationary phase, column temperature, flow rate, solvent system, elution mode, and injection volume, etc.). The analytical method development is a process of proving the developed analytical method is suitable for its intended use for the quantitative estimation of the targeted analyte present in pharmaceutical drugs. And it mostly plays a vital role in the development and manufacture of pharmaceuticals drugs.",book:{id:"8912",slug:"biochemical-analysis-tools-methods-for-bio-molecules-studies",title:"Biochemical Analysis Tools",fullTitle:"Biochemical Analysis Tools - Methods for Bio-Molecules Studies"},signatures:"Narasimha S. Lakka and Chandrasekar Kuppan",authors:[{id:"304950",title:"Prof.",name:"Chandrasekar",middleName:null,surname:"Kuppan",slug:"chandrasekar-kuppan",fullName:"Chandrasekar Kuppan"},{id:"309984",title:"Mr.",name:"Narasimha S",middleName:null,surname:"Lakka",slug:"narasimha-s-lakka",fullName:"Narasimha S Lakka"}]},{id:"33046",title:"Affinity Chromatography: Principles and Applications",slug:"affinity-chromatography-principles-and-applications",totalDownloads:48519,totalCrossrefCites:8,totalDimensionsCites:20,abstract:null,book:{id:"1490",slug:"affinity-chromatography",title:"Affinity Chromatography",fullTitle:"Affinity Chromatography"},signatures:"Sameh Magdeldin and Annette Moser",authors:[{id:"123648",title:"Dr.",name:"Sameh",middleName:null,surname:"Magdeldin",slug:"sameh-magdeldin",fullName:"Sameh Magdeldin"},{id:"136483",title:"Dr.",name:"Annette",middleName:"C.",surname:"Moser",slug:"annette-moser",fullName:"Annette Moser"}]},{id:"50574",title:"Bioinformatics for RNA‐Seq Data Analysis",slug:"bioinformatics-for-rna-seq-data-analysis",totalDownloads:5797,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"While RNA sequencing (RNA‐seq) has become increasingly popular for transcriptome profiling, the analysis of the massive amount of data generated by large‐scale RNA‐seq still remains a challenge. RNA‐seq data analyses typically consist of (1) accurate mapping of millions of short sequencing reads to a reference genome, including the identification of splicing events; (2) quantifying expression levels of genes, transcripts, and exons; (3) differential analysis of gene expression among different biological conditions; and (4) biological interpretation of differentially expressed genes. Despite the fact that multiple algorithms pertinent to basic analyses have been developed, there are still a variety of unresolved questions. In this chapter, we review the main tools and algorithms currently available for RNA‐seq data analyses, and our goal is to help RNA‐seq data analysts to make an informed choice of tools in practical RNA‐seq data analysis. In the meantime, RNA‐seq is evolving rapidly, and newer sequencing technologies are briefly introduced, including stranded RNA‐seq, targeted RNA‐seq, and single‐cell RNA‐seq.",book:{id:"5160",slug:"bioinformatics-updated-features-and-applications",title:"Bioinformatics",fullTitle:"Bioinformatics - Updated Features and Applications"},signatures:"Shanrong Zhao, Baohong Zhang, Ying Zhang, William Gordon,\nSarah Du, Theresa Paradis, Michael Vincent and David von Schack",authors:[{id:"176364",title:"Dr.",name:"Shanrong",middleName:null,surname:"Zhao",slug:"shanrong-zhao",fullName:"Shanrong Zhao"}]},{id:"49873",title:"An Introduction to Actinobacteria",slug:"an-introduction-to-actinobacteria",totalDownloads:7968,totalCrossrefCites:27,totalDimensionsCites:96,abstract:"Actinobacteria, which share the characteristics of both bacteria and fungi, are widely distributed in both terrestrial and aquatic ecosystems, mainly in soil, where they play an essential role in recycling refractory biomaterials by decomposing complex mixtures of polymers in dead plants and animals and fungal materials. They are considered as the biotechnologically valuable bacteria that are exploited for its secondary metabolite production. Approximately, 10,000 bioactive metabolites are produced by Actinobacteria, which is 45% of all bioactive microbial metabolites discovered. Especially Streptomyces species produce industrially important microorganisms as they are a rich source of several useful bioactive natural products with potential applications. Though it has various applications, some Actinobacteria have its own negative effect against plants, animals, and humans. On this context, this chapter summarizes the general characteristics of Actinobacteria, its habitat, systematic classification, various biotechnological applications, and negative impact on plants and animals.",book:{id:"5056",slug:"actinobacteria-basics-and-biotechnological-applications",title:"Actinobacteria",fullTitle:"Actinobacteria - Basics and Biotechnological Applications"},signatures:"Ranjani Anandan, Dhanasekaran Dharumadurai and Gopinath\nPonnusamy Manogaran",authors:[{id:"48914",title:"Dr.",name:"Dharumadurai",middleName:null,surname:"Dhanasekaran",slug:"dharumadurai-dhanasekaran",fullName:"Dharumadurai Dhanasekaran"}]},{id:"72074",title:"The Chemistry Behind Plant DNA Isolation Protocols",slug:"the-chemistry-behind-plant-dna-isolation-protocols",totalDownloads:3546,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Various plant species are biochemically heterogeneous in nature, a single deoxyribose nucleic acid (DNA) isolation protocol may not be suitable. There have been continuous modification and standardization in DNA isolation protocols. Most of the plant DNA isolation protocols used today are modified versions of hexadecyltrimethyl-ammonium bromide (CTAB) extraction procedure. Modification is usually performed in the concentration of chemicals used during the extraction procedure according to the plant species and plant part used. Thus, understanding the role of each chemical (viz. CTAB, NaCl, PVP, ethanol, and isopropanol) used during the DNA extraction procedure will benefit to set or modify protocols for more precisions. A review of the chemicals used in the CTAB method of DNA extraction and their probable functions on the highly evolved yet complex to students and researchers has been summarized.",book:{id:"8912",slug:"biochemical-analysis-tools-methods-for-bio-molecules-studies",title:"Biochemical Analysis Tools",fullTitle:"Biochemical Analysis Tools - Methods for Bio-Molecules Studies"},signatures:"Jina Heikrujam, Rajkumar Kishor and Pranab Behari Mazumder",authors:[{id:"74521",title:"Dr.",name:"Rajkumar",middleName:null,surname:"Kishor",slug:"rajkumar-kishor",fullName:"Rajkumar Kishor"},{id:"309357",title:"Prof.",name:"Pranab Behari",middleName:null,surname:"Mazumder",slug:"pranab-behari-mazumder",fullName:"Pranab Behari Mazumder"},{id:"318351",title:"Ph.D. Student",name:"Jina",middleName:null,surname:"Heikrujam",slug:"jina-heikrujam",fullName:"Jina Heikrujam"}]}],onlineFirstChaptersFilter:{topicId:"6",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"80495",title:"Iron in Cell Metabolism and Disease",slug:"iron-in-cell-metabolism-and-disease",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.101908",abstract:"Iron is the trace element. We get the iron from the dietary sources. The enterocytes lining the upper duodenal of the intestine absorb the dietary iron through a divalent metal transporter (DMT1). The absorbed ferrous iron is oxidized to ferric iron in the body. This ferric iron from the blood is carried to different tissues by an iron transporting protein, transferrin. The cells in the tissues take up this ferric form of iron by internalizing the apo transferrin with its receptors on them. The apo transferrin complex in the cells get dissociated resulting in the free iron in cell which is utilized for cellular purposes or stored in the bound form to an iron storage protein, ferritin. The physiological levels of iron are critical for the normal physiology and pathological outcomes, hence the iron I rightly called as double-edged sword. This chapter on iron introduces the readers basic information of iron, cellular uptake, metabolism, and its role cellular physiology and provides the readers with the scope and importance of research on iron that hold the great benefit for health care and personalized medicine or diseases specific treatment strategies, blood transfusions and considerations.",book:{id:"10842",title:"Iron Metabolism - Iron a Double‐Edged Sword",coverURL:"https://cdn.intechopen.com/books/images_new/10842.jpg"},signatures:"Eeka Prabhakar"},{id:"81799",title:"Cross Talk of Purinergic and Immune Signaling: Implication in Inflammatory and Pathogenic Diseases",slug:"cross-talk-of-purinergic-and-immune-signaling-implication-in-inflammatory-and-pathogenic-diseases",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.104978",abstract:"Purine derivatives like adenosine 5′-triphosphate (ATP) is the powerhouse of the cell and is essential to maintain the cellular homeostasis and activity. Besides this they also act as a chemical messenger when released into the extracellular milieu because of stress and cellular insult. The extracellular ATP (eATP) as well as its metabolite adenosine triggers purinergic signaling affecting various cellular processes such as cytokine and chemokine production, immune cell function, differentiation, and maturation, and mediates inflammatory activity. Aberrant purinergic signaling had been implicated in several diseased conditions. This chapter will focus on the dynamics of purinergic signaling and immune signaling in driving under various diseased conditions like autoimmunity and infectious disease.",book:{id:"10801",title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg"},signatures:"Richa Rai"},{id:"81800",title:"Long Non-Coding RNAs: Biogenesis, Mechanism of Action and Role in Different Biological and Pathological Processes",slug:"long-non-coding-rnas-biogenesis-mechanism-of-action-and-role-in-different-biological-and-pathologica",totalDownloads:10,totalDimensionsCites:0,doi:"10.5772/intechopen.104861",abstract:"RNA or ribonucleic acid constitutes of nucleotides, which are ribose sugars coupled to nitrogenous bases and phosphate groups. Nitrogenous bases include adenine, guanine, cytosine and uracil. Messenger RNA, ribosomal RNA and Transfer RNA are three main types of RNA that are involved in protein synthesis. Apart from its primary role in synthesis of protein, RNA comes in variety of forms like snRNA, miRNA, siRNA, antisense RNA, LncRNA etc., that are involved in DNA replication, post-transcriptional modification, and gene regulation etc. LncRNAs regulate gene expression by various ways including at, transcriptional, post-transcriptional, translational, post-translational and epigenetic levels by interacting principally with mRNA, DNA, protein, and miRNA. Among other biological functions, they are involved in chromatin remodelling, transcriptional interference, transcriptional activation, mRNA translation and RNA processing. In this chapter we shall be discussing the origin of lncRNAs, their biogenesis, their mechanism of action and their role in many biological and pathological processes like epigenetics, genome imprinting, several cancers and autoimmune diseases.",book:{id:"11353",title:"Recent Advances in Non-Coding RNAs",coverURL:"https://cdn.intechopen.com/books/images_new/11353.jpg"},signatures:"Ishteyaq Majeed Shah, Mashooq Ahmad Dar, Kaiser Ahmad Bhat, Tashook Ahmad Dar, Fayaz Ahmad and Syed Mudasir Ahmad"},{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.105052",abstract:"Apoptosis is a highly regulated cell death program that can be mediated by death receptors in the plasma membrane, as well as the mitochondria and the endoplasmic reticulum. Apoptosis plays a key role in the pathogenesis of a variety of human diseases. Peroxisomes are membrane-bound organelles occurring in the cytoplasm of eukaryotic cells. Peroxisomes engage in a functional interplay with mitochondria. They cooperate with each other to maintain the balance of reactive oxygen species homeostasis in cells. Given the key role of mitochondria in the regulation of apoptosis, there could also be an important relationship between peroxisomes and the apoptotic process. Peroxisome dysfunction severely affects mitochondrial metabolism, cellular morphological stability, and biosynthesis, and thus contributes directly or indirectly to a number of apoptosis-related diseases. This chapter provides an overview of the concept, characteristics, inducing factors, and molecular mechanisms of apoptosis, as well as evidence for apoptosis in cancer, cardiovascular diseases, and neurodegenerative disorders, and discusses the important role of the peroxisome in the apoptosis-associated diseases.",book:{id:"10837",title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg"},signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao"},{id:"81738",title:"How Do Extraction Methods and Biotechnology Influence Our Understanding and Usages of Ginsenosides?: A Critical View and Perspectives",slug:"how-do-extraction-methods-and-biotechnology-influence-our-understanding-and-usages-of-ginsenosides-a",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.103863",abstract:"Ginseng saponins, aka ginsenosides, are bioactive phytochemicals from Panax species. Panax comes from the Greek word “panakos,” which means “cure-all.” Owing to their involvement in the creation of numerous medications and nutritional supplements, ginseng saponins play an essential part, especially in the pharmaceutical sector. The main ginsenosides (i.e., Rb1, Rb2, Rc, Rd and Rf) are extracted using a variety of extraction methods, although from a limited number of Panax species. However, more than ca 1000 unique ginsenosides and 18 Panax species have been reported so far, thus demonstrating our present challenge in better understanding of the potential medicinal uses of these compounds. Moreover, ginsenoside production and extraction methods are both time-consuming and inefficient, which has stimulated the development of several efficient extraction and biotechnological technologies to speed up these processes. In this chapter, we highlighted the need to expand the cutting-edge research approaches involving these unique ginsenosides to better understand their biological activities and discover new bioactive ginsenosides as well. The main objective of this chapter is to discuss the undiscovered aspects and limitations of the current biotechnological and extraction technologies, eventually to provide a platform for the production of these unique ginsenosides.",book:{id:"10539",title:"Ginseng - Modern Aspects of the Famed Traditional Medicine",coverURL:"https://cdn.intechopen.com/books/images_new/10539.jpg"},signatures:"Christophe Hano, Duangjai Tungmunnithum, Samantha Drouet, Mohamed Addi, Saikat Gantait and Jen-Tsung Chen"},{id:"81764",title:"Involvement of the Purinergic System in Cell Death in Models of Retinopathies",slug:"involvement-of-the-purinergic-system-in-cell-death-in-models-of-retinopathies",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.103935",abstract:"Literature data demonstrate already that the presence of adenine nucleotides in the extracellular environment induces cell death that leads to several retinopathies. As said, the objective is to carry out a systematized review of the last decade, relating purinergic signaling to the outcome of cell death and retinopathies. It is possible to identify different mechanisms that occur through the activation of purinergic receptors. The exacerbated activation of the P2X7 receptor is mainly involved in the apoptotic death pathway, and this response is due to the dysregulation of some components in the intracellular environment, such as the Ca2+ ion, CD40, MiR-187, and influence of mononuclear macrophages. The A2A receptor is involved in increasing levels of cytokines and promoting inflammatory processes. The data presented can be used as a basis to better understand the mechanisms of death in retinopathies, in addition to proposing therapeutic strategies with the potential to be transposed to several other models.",book:{id:"10801",title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg"},signatures:"Douglas Penaforte Cruz, Marinna Garcia Repossi and Lucianne Fragel Madeira"}],onlineFirstChaptersTotal:96},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"25",title:"Environmental Sciences",doi:"10.5772/intechopen.100362",issn:"2754-6713",scope:"\r\n\tScientists have long researched to understand the environment and man’s place in it. The search for this knowledge grows in importance as rapid increases in population and economic development intensify humans’ stresses on ecosystems. Fortunately, rapid increases in multiple scientific areas are advancing our understanding of environmental sciences. Breakthroughs in computing, molecular biology, ecology, and sustainability science are enhancing our ability to utilize environmental sciences to address real-world problems.
\r\n\tThe four topics of this book series - Pollution; Environmental Resilience and Management; Ecosystems and Biodiversity; and Water Science - will address important areas of advancement in the environmental sciences. They will represent an excellent initial grouping of published works on these critical topics.