Atherogenicity of small dense LDL
\\n\\n
IntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\\n\\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\\n\\nLaunching 2021
\\n\\nArtificial Intelligence, ISSN 2633-1403
\\n\\nVeterinary Medicine and Science, ISSN 2632-0517
\\n\\nBiochemistry, ISSN 2632-0983
\\n\\nBiomedical Engineering, ISSN 2631-5343
\\n\\nInfectious Diseases, ISSN 2631-6188
\\n\\nPhysiology (Coming Soon)
\\n\\nDentistry (Coming Soon)
\\n\\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\\n\\nNote: Edited in October 2021
\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/132"}},components:[{type:"htmlEditorComponent",content:'With the desire to make book publishing more relevant for the digital age and offer innovative Open Access publishing options, we are thrilled to announce the launch of our new publishing format: IntechOpen Book Series.
\n\nDesigned to cover fast-moving research fields in rapidly expanding areas, our Book Series feature a Topic structure allowing us to present the most relevant sub-disciplines. Book Series are headed by Series Editors, and a team of Topic Editors supported by international Editorial Board members. Topics are always open for submissions, with an Annual Volume published each calendar year.
\n\nAfter a robust peer-review process, accepted works are published quickly, thanks to Online First, ensuring research is made available to the scientific community without delay.
\n\nOur innovative Book Series format brings you:
\n\nIntechOpen Book Series will also publish a program of research-driven Thematic Edited Volumes that focus on specific areas and allow for a more in-depth overview of a particular subject.
\n\nIntechOpen Book Series will be launching regularly to offer our authors and editors exciting opportunities to publish their research Open Access. We will begin by relaunching some of our existing Book Series in this innovative book format, and will expand in 2022 into rapidly growing research fields that are driving and advancing society.
\n\nLaunching 2021
\n\nArtificial Intelligence, ISSN 2633-1403
\n\nVeterinary Medicine and Science, ISSN 2632-0517
\n\nBiochemistry, ISSN 2632-0983
\n\nBiomedical Engineering, ISSN 2631-5343
\n\nInfectious Diseases, ISSN 2631-6188
\n\nPhysiology (Coming Soon)
\n\nDentistry (Coming Soon)
\n\nWe invite you to explore our IntechOpen Book Series, find the right publishing program for you and reach your desired audience in record time.
\n\nNote: Edited in October 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"8837",leadTitle:null,fullTitle:"Human Teeth - Key Skills and Clinical Illustrations",title:"Human Teeth",subtitle:"Key Skills and Clinical Illustrations",reviewType:"peer-reviewed",abstract:"This book provides information on nomenclature, tooth numbering systems, tooth morphology, and anatomy and stages of tooth formation. It continues with root canal morphology and anatomy of incisors, canines, premolars, and molars. External and internal anatomies of mandibular permanent incisors and maxillary permanent first molars are presented according to a literature review. Orofacial structures affecting tooth morphology are discussed in detail. The book ends with the evolution of dental implant shapes and today�s custom root analog implants.",isbn:"978-1-78923-840-2",printIsbn:"978-1-78923-839-6",pdfIsbn:"978-1-78984-522-8",doi:"10.5772/intechopen.81278",price:119,priceEur:129,priceUsd:155,slug:"human-teeth-key-skills-and-clinical-illustrations",numberOfPages:258,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"ac055c5801032970123e0a196c2e1d32",bookSignature:"Zühre Akarslan and Farid Bourzgui",publishedDate:"January 22nd 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8837.jpg",numberOfDownloads:16369,numberOfWosCitations:4,numberOfCrossrefCitations:10,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:15,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:29,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 3rd 2018",dateEndSecondStepPublish:"September 24th 2018",dateEndThirdStepPublish:"November 23rd 2018",dateEndFourthStepPublish:"February 11th 2019",dateEndFifthStepPublish:"April 12th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:{id:"52177",title:"Prof.",name:"Farid",middleName:null,surname:"Bourzgui",slug:"farid-bourzgui",fullName:"Farid Bourzgui",profilePictureURL:"https://mts.intechopen.com/storage/users/52177/images/system/52177.png",biography:"Prof. Farid Bourzgui obtained his DMD and his DNSO option in Orthodontics at the School of Dental Medicine, Casablanca Hassan II University, Morocco, in 1995 and 2000, respectively. Currently, he is a professor of Orthodontics. He holds a Certificate of Advanced Study type A in Technology of Biomaterials used in Dentistry (1995); Certificate of Advanced Study type B in Dento-Facial Orthopaedics (1997) from the Faculty of Dental Surgery, University Denis Diderot-Paris VII, France; Diploma of Advanced Study (DESA) in Biocompatibility of Biomaterials from the Faculty of Medicine and Pharmacy of Casablanca (2002); Certificate of Clinical Occlusodontics from the Faculty of Dentistry of Casablanca (2004); University Diploma of Biostatistics and Perceptual Health Measurement from the Faculty of Medicine and Pharmacy of Casablanca (2011); and a University Diploma of Pedagogy of Odontological Sciences from the Faculty of Dentistry of Casablanca (2013). He is the author of several scientific articles, book chapters, and books.",institutionString:"University of Hassan II Casablanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Hassan II Casablanca",institutionURL:null,country:{name:"Morocco"}}},equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"174",title:"Dentistry",slug:"dentistry"}],chapters:[{id:"68734",title:"Can Orofacial Structures Affect Tooth Morphology?",doi:"10.5772/intechopen.88807",slug:"can-orofacial-structures-affect-tooth-morphology-",totalDownloads:879,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"This chapter presents how orofacial muscles can affect teeth positioning, occlusion, and also the size/shape of teeth. Pressures exerted on teeth will be discussed in specific cases such as mouth breathing, chronic mastication disorders, oral habits, like thumb sucking or tongue thrust, and also when there is hyperfunction of masticatory muscles during sleep or wakefulness. In these situations, the imbalance of muscle forces brings undesirable consequences to the dentition. Each condition will be explained, showing which muscle is affected, how it changes, and what consequences to the teeth it brings. It is a chapter that shows how close the relationship is between dentistry and speech language pathology (orofacial myology).",signatures:"Amanda Valentim, Renata Furlan, Mariana Amaral and Fernanda Martins",downloadPdfUrl:"/chapter/pdf-download/68734",previewPdfUrl:"/chapter/pdf-preview/68734",authors:[{id:"106418",title:"BSc.",name:"Amanda",surname:"Valentim",slug:"amanda-valentim",fullName:"Amanda Valentim"},{id:"113857",title:"MSc.",name:"Renata",surname:"Furlan",slug:"renata-furlan",fullName:"Renata Furlan"},{id:"274941",title:"MSc.",name:"Mariana",surname:"Amaral",slug:"mariana-amaral",fullName:"Mariana Amaral"},{id:"274942",title:"BSc.",name:"Fernanda",surname:"Guimarães",slug:"fernanda-guimaraes",fullName:"Fernanda Guimarães"}],corrections:null},{id:"66644",title:"Embryological Development of Human Molars",doi:"10.5772/intechopen.85703",slug:"embryological-development-of-human-molars",totalDownloads:1089,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Dental development is a complex process by which teeth from embryonic cells grow and erupt into the mouth. It is governed by epithelio-mesenchymal interactions. The biological mechanism is the same for all teeth; however, epithelial signaling and homeogenous combinatorics are different from one type of tooth to another. The primary dental blade splits into the vestibular and primary dental blades opposite to the mesenchymal condensation. During dental development, three successive stages are described: bud, cup, and bell. The secondary dental blade responsible for the formation of germs in permanent teeth is formed from the primary dental blade in the bell stage. For the central incisor, lateral incisor, canine, first temporary molar, and second temporary molar, each primary dental blade gives rise to a single secondary dental blade for the corresponding permanent tooth. On the other hand, the primary dental blade of the second temporary molar will cause the formation of four secondary dental blades that will cause the formation of permanent germs of the second premolar, the first permanent molar, the second permanent molar, and the third permanent molar. The objective of this chapter is to focus on the cellular and molecular mechanisms explaining the normal development of molars by presenting the different current data and theories of science illustrating the human molar embryological development.",signatures:"Fatiha Rhrich and Hakima Aghoutan",downloadPdfUrl:"/chapter/pdf-download/66644",previewPdfUrl:"/chapter/pdf-preview/66644",authors:[{id:"172240",title:"Prof.",name:"Hakima",surname:"Aghoutan",slug:"hakima-aghoutan",fullName:"Hakima Aghoutan"},{id:"288550",title:"Prof.",name:"Fatiha",surname:"Rhrich",slug:"fatiha-rhrich",fullName:"Fatiha Rhrich"}],corrections:null},{id:"68957",title:"Prologue: Tooth Anatomy and Morphology",doi:"10.5772/intechopen.89148",slug:"prologue-tooth-anatomy-and-morphology",totalDownloads:933,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Zühre Akarslan",downloadPdfUrl:"/chapter/pdf-download/68957",previewPdfUrl:"/chapter/pdf-preview/68957",authors:[{id:"171887",title:"Prof.",name:"Zühre",surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan"}],corrections:null},{id:"65806",title:"External and Internal Anatomy of Mandibular Permanent Incisors",doi:"10.5772/intechopen.84636",slug:"external-and-internal-anatomy-of-mandibular-permanent-incisors",totalDownloads:1206,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A clear understanding of dental root anatomy, external and internal, is an essential prerequisite to all dental procedures. In periodontology, the external root morphology has been proven to have a clinical significance in the predisposing factors of periodontal diseases. Orthodontic literature shows the importance of radicular anatomy in orthodontic mechanics through the concept of anchorage. The significance of internal root anatomy has been emphasized by studies demonstrating that variations in canal geometry before cleaning, shaping, and obturation procedures had a greater effect on the outcome than the techniques themselves. The mandibular central incisor is the smallest tooth in the mouth, but the buccolingual dimension of its root is very large. This tooth is usually single-rooted; however, the root canal system of this group is unpredictable. The incidence of two canals has been reported as low as 0.3% and as high as 45.3%. The wide range of variation reported in literature regarding the prevalence of a second canal has been related to methodological and racial differences. This chapter will summarize the morphological aspects of the root canal anatomy published in the literature of the anterior mandibular teeth. This will provide precious knowledge regarding root canal morphology and its variation among populations.",signatures:"Mohammed A. Aldawla, Abdulbaset A. Mufadhal and Ahmed A. Madfa",downloadPdfUrl:"/chapter/pdf-download/65806",previewPdfUrl:"/chapter/pdf-preview/65806",authors:[{id:"204110",title:"Dr.",name:"Ahmed A.",surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa"},{id:"281125",title:"Dr.",name:"Mohammed A.",surname:"Aldawla",slug:"mohammed-a.-aldawla",fullName:"Mohammed A. Aldawla"},{id:"281126",title:"Dr.",name:"Abdulbaset A.",surname:"Mufadhal",slug:"abdulbaset-a.-mufadhal",fullName:"Abdulbaset A. Mufadhal"}],corrections:null},{id:"67975",title:"Tooth Morphology Overview",doi:"10.5772/intechopen.87153",slug:"tooth-morphology-overview",totalDownloads:1740,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"This chapter provides an overview of tooth morphology, including a review of tooth anatomy, tooth development, and associated nomenclature and numbering systems. First, basic tooth morphology nomenclature is presented. Next, various tooth numbering systems are described and discussed, and the Federation Dentaire Internationale (FDI) system is detailed. Third, tooth surfaces and ridges are explained along with terminology, followed by an explanation of tooth crown and root anatomy. Fourth, the stages of tooth formation are described, starting with the bud stage, and followed by the cap stage, bell stage, and maturation. Annotated diagrams are presented for clarity. Finally, two currently accepted hypotheses explaining tooth formation are presented.",signatures:"Abeer ALShami, Shatha ALHarthi, Munerah Binshabaib and Monika Wahi",downloadPdfUrl:"/chapter/pdf-download/67975",previewPdfUrl:"/chapter/pdf-preview/67975",authors:[{id:"190958",title:"Ms.",name:"Monika M.",surname:"Wahi",slug:"monika-m.-wahi",fullName:"Monika M. Wahi"},{id:"280663",title:"Dr.",name:"Shatha",surname:"ALHarthi",slug:"shatha-alharthi",fullName:"Shatha ALHarthi"},{id:"280665",title:"Dr.",name:"Abeer",surname:"Alshami",slug:"abeer-alshami",fullName:"Abeer Alshami"},{id:"280666",title:"Dr.",name:"Munirah",surname:"Binshabaib",slug:"munirah-binshabaib",fullName:"Munirah Binshabaib"}],corrections:null},{id:"65711",title:"External and Internal Anatomy of Maxillary Permanent First Molars",doi:"10.5772/intechopen.84518",slug:"external-and-internal-anatomy-of-maxillary-permanent-first-molars",totalDownloads:1370,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Adequate knowledge of the tooth morphology is of paramount importance for clinicians worked in the different branches of dentistry in order to maintain good oral health. Unfortunately, tooth morphology shows a high level of complexity and variability. These anatomical variations have been reported to be related to many factors including age, gender and ethnicity. The permanent first molars are the largest teeth in the maxilla which play an important role in mastication. Because of their early eruption, they are more vulnerable to caries and subsequent pulp and periapical pathoses. This chapter will summarize the internal and external morphologic features of these teeth with the reported variations in relation to age, gender and population in order to provide clinicians with the morphological knowledge necessary for performing successful dental treatments.",signatures:"Abdulbaset A. Mufadhal, Mohammed A. Aldawla and Ahmed A. Madfa",downloadPdfUrl:"/chapter/pdf-download/65711",previewPdfUrl:"/chapter/pdf-preview/65711",authors:[{id:"204110",title:"Dr.",name:"Ahmed A.",surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa"},{id:"281125",title:"Dr.",name:"Mohammed A.",surname:"Aldawla",slug:"mohammed-a.-aldawla",fullName:"Mohammed A. Aldawla"},{id:"281126",title:"Dr.",name:"Abdulbaset A.",surname:"Mufadhal",slug:"abdulbaset-a.-mufadhal",fullName:"Abdulbaset A. Mufadhal"}],corrections:null},{id:"67177",title:"External and Internal Root Canal Anatomy of the First and Second Permanent Maxillary Molars",doi:"10.5772/intechopen.85746",slug:"external-and-internal-root-canal-anatomy-of-the-first-and-second-permanent-maxillary-molars",totalDownloads:1296,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"A successful endodontic treatment depends on a comprehensive knowledge of the morphology of canal and its variations, an appropriate access cavity, cleaning and shaping, and adequate root canal filling. Lack of knowledge in this regard and missing a root canal are among the most common causes of failure of root canal treatments. Most previous studies on maxillary molars have reported that they usually have three roots and four canals since an extra canal is often found in the mesiobuccal root. Other anatomical variations, such as an extra C-shaped canal, have also been reported in distobuccal and palatal roots. Thus, because of having a more complex anatomy compared to other teeth, maxillary molars have the highest rate of endodontic failure. Several studies have assessed the morphology of root canal anatomy in different populations using different techniques such as sectioning, root canal clearing, association of a dental operating microscope and ultrasonic tips, periapical radiography, and computed tomography scanning. Recently, CBCT was suggested to three-dimensionally explore the root canal details before an endodontic treatment. The purpose of this chapter was to highlight the importance of having a thorough knowledge about the root canal morphology of the permanent first and second maxillary molar.",signatures:"Said Dhaimy, Lamyae Bedida, Hafsa El Merini and Imane Benkiran",downloadPdfUrl:"/chapter/pdf-download/67177",previewPdfUrl:"/chapter/pdf-preview/67177",authors:[{id:"289623",title:"Prof.",name:"Said",surname:"Dhaimy",slug:"said-dhaimy",fullName:"Said Dhaimy"},{id:"297310",title:"Dr.",name:"Lamyae",surname:"Bedida",slug:"lamyae-bedida",fullName:"Lamyae Bedida"},{id:"297367",title:"Dr.",name:"Imane",surname:"Benkiran",slug:"imane-benkiran",fullName:"Imane Benkiran"},{id:"298239",title:"Dr.",name:"Hafsa",surname:"El Merini",slug:"hafsa-el-merini",fullName:"Hafsa El Merini"}],corrections:null},{id:"65451",title:"Morphology of Root Canal System of Maxillary and Mandibular Molars",doi:"10.5772/intechopen.84151",slug:"morphology-of-root-canal-system-of-maxillary-and-mandibular-molars",totalDownloads:1147,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The root canal system is complicated and has many anatomical variations among different populations. It is so important to understand the morphology of root canal system before any endodontic procedure, since the lack of knowledge of root canal system could lead to missing the additional root canals which causes failure of endodontic treatment. The study of root canal anatomy was carried out by many researchers and among different populations using various techniques. The presence of additional root canals was most commonly observed in molars. The aim of this chapter is to provide an overview of the morphology of root canal system of maxillary and mandibular molars and its variation among populations.",signatures:"Svetlana Razumova, Anzhela Brago, Haydar Barakat and Ammar Howijieh",downloadPdfUrl:"/chapter/pdf-download/65451",previewPdfUrl:"/chapter/pdf-preview/65451",authors:[{id:"282099",title:"Ph.D.",name:"Haydar",surname:"Barakat",slug:"haydar-barakat",fullName:"Haydar Barakat"},{id:"282405",title:"Dr.",name:"Ammar",surname:"Howijieh",slug:"ammar-howijieh",fullName:"Ammar Howijieh"},{id:"283571",title:"Prof.",name:"Svetlana",surname:"Razumova",slug:"svetlana-razumova",fullName:"Svetlana Razumova"},{id:"283572",title:"Prof.",name:"Anzhela",surname:"Brago",slug:"anzhela-brago",fullName:"Anzhela Brago"}],corrections:null},{id:"67419",title:"Root Canal Morphology and Anatomy",doi:"10.5772/intechopen.86096",slug:"root-canal-morphology-and-anatomy",totalDownloads:1115,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Success in root canal treatment depends on the proper application of all procedures of root canal treatment. This wholistic approach includes leakproof crown restoration, following ideal instrumentation, irrigation and hermetic obturation. Therefore, the first step of root canal treatment begins with understanding the tooth morphology in detail. The teeth vary according to their localization at the jaws and the gender and race of people. Detection of the extra canals, canal curvatures, isthmuses and lateral and accessory canals plays an important role in the success of root canal treatment. With all this, the academic knowledge and proficiency of the dentist and/or endodontist enable tooth morphology to be more clearly understandable.",signatures:"Esra Pamukcu Guven",downloadPdfUrl:"/chapter/pdf-download/67419",previewPdfUrl:"/chapter/pdf-preview/67419",authors:[{id:"277522",title:"Associate Prof.",name:"Esra",surname:"Pamukcu Guven",slug:"esra-pamukcu-guven",fullName:"Esra Pamukcu Guven"}],corrections:null},{id:"68918",title:"The C-Shaped Root Canal",doi:"10.5772/intechopen.89121",slug:"the-c-shaped-root-canal",totalDownloads:796,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"A thorough understanding of root canal anatomy is of paramount importance in the field of dentistry. The C-shaped root canal is an anatomical variation occurring mostly in mandibular second molars. In a transverse section, the shape of this canal is observed as the letter C. The presence of a fin or web connecting the individual root canals is another anatomic feature. Due to its complex anatomy, different classifications have been proposed through the years for a better comprehension. In endodontic literature, the C-shaped root canal has been of high interest and its prevalence is reported in different regions of the world. Additionally, its endodontic management has been widely described and analyzed.",signatures:"Jesús Alejandro Quiñones Pedraza",downloadPdfUrl:"/chapter/pdf-download/68918",previewPdfUrl:"/chapter/pdf-preview/68918",authors:[{id:"284538",title:"Dr.",name:"Jesús Alejandro",surname:"Quiñones Pedraza",slug:"jesus-alejandro-quinones-pedraza",fullName:"Jesús Alejandro Quiñones Pedraza"}],corrections:null},{id:"69760",title:"Pathology and Abnormality of the First Permanent Molar among Children",doi:"10.5772/intechopen.89725",slug:"pathology-and-abnormality-of-the-first-permanent-molar-among-children",totalDownloads:1283,totalCrossrefCites:4,totalDimensionsCites:4,hasAltmetrics:0,abstract:"The first permanent molar (FPM) plays an essential role in the masticatory function by contributing to the implementation and the maintenance of the occlusion. However, it is considered as the most frequently affected and the earliest affected tooth by caries; 27.4% of the 6–8 years old children have developed at least one cavity on one of the four first permanent molars, according to a study conducted among 3276 school children in Casablanca .Therefore, the FPM should benefit from special vigilance on the part of the practitioner to ensure that any early carious lesion is intercepted. In addition, the FPM, due to its period of mineralization coinciding with early childhood diseases, can erupt with a structural abnormality. Molar incisor hypomineralization (MIH) is considered to be the most common defects observed on first permanent molars among children. A study conducted among 1077 children aged 7–10 years enrolled in schools in Casablanca showed that 7.9% of children were affected with MIH. About 84.7% of the children had the four molars affected. Children with HIM had a significantly higher prevalence of caries: 78.8 versus 33.5%.These structural abnormalities of the enamel must be carried out earlier to ensure that the coronary anatomy is the least compromised.",signatures:"Mouna Hamza, Amal Chlyah, Bouchra Bousfiha, Bouchra Badre, Maria Mtalsi, Hasna Saih and Samira El Arabi",downloadPdfUrl:"/chapter/pdf-download/69760",previewPdfUrl:"/chapter/pdf-preview/69760",authors:[{id:"52178",title:"Ms.",name:"Mouna",surname:"Hamza",slug:"mouna-hamza",fullName:"Mouna Hamza"},{id:"288350",title:"Prof.",name:"Samira",surname:"El Arabi",slug:"samira-el-arabi",fullName:"Samira El Arabi"},{id:"288775",title:"Prof.",name:"Bouchra",surname:"Bousfiha",slug:"bouchra-bousfiha",fullName:"Bouchra Bousfiha"},{id:"288776",title:"Prof.",name:"Amal",surname:"Chlyah",slug:"amal-chlyah",fullName:"Amal Chlyah"},{id:"288778",title:"Prof.",name:"Bouchra",surname:"Badre",slug:"bouchra-badre",fullName:"Bouchra Badre"},{id:"311623",title:"Prof.",name:"Maria",surname:"Mtalsi",slug:"maria-mtalsi",fullName:"Maria Mtalsi"},{id:"311624",title:"Dr.",name:"Hasna",surname:"Saih",slug:"hasna-saih",fullName:"Hasna Saih"}],corrections:null},{id:"66877",title:"Orthodontic Management of Residual Spaces of Missing Molars: Decision Factors",doi:"10.5772/intechopen.85944",slug:"orthodontic-management-of-residual-spaces-of-missing-molars-decision-factors",totalDownloads:1421,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"In the daily practice, the orthodontist may be confronted with particular clinical situations with one or more missing teeth. This can complicate the therapeutic plan and influence the choice of possible extractions imposed by treatment requirements. In case of permanent molar absence, making decision becomes even more delicate. The practitioner must use his/her critical sense and clinical common sense to make the right choice between closing and redeveloping the residual spaces. Its choice must meet the patient’s expectations and correct the clinical problem without risking overtreatment, or extending duration care. Several factors guide the therapeutic decision, ranging from the patient’s age to economic factors, not to mention the technical complexity, therapeutic predictability, and patient comfort, which determine proper compliance and therefore success. In this chapter, we will focus on these decision-making factors by determining the scientific evidence level in terms of success, survival, and patient-centered outcomes (quality of life and functional efficiency).",signatures:"Hakima Aghoutan, Sanaa Alami, Amal El Aouame and Farid El Quars",downloadPdfUrl:"/chapter/pdf-download/66877",previewPdfUrl:"/chapter/pdf-preview/66877",authors:[{id:"172240",title:"Prof.",name:"Hakima",surname:"Aghoutan",slug:"hakima-aghoutan",fullName:"Hakima Aghoutan"},{id:"172553",title:"Prof.",name:"Sanaa",surname:"Alami",slug:"sanaa-alami",fullName:"Sanaa Alami"},{id:"290814",title:"Dr.",name:"Amal",surname:"El Aouame",slug:"amal-el-aouame",fullName:"Amal El Aouame"},{id:"290815",title:"Prof.",name:"Farid",surname:"El Quars",slug:"farid-el-quars",fullName:"Farid El Quars"}],corrections:null},{id:"69931",title:"Impacted First and Second Permanent Molars: Overview",doi:"10.5772/intechopen.86671",slug:"impacted-first-and-second-permanent-molars-overview",totalDownloads:1362,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Impaction of a permanent tooth is a relatively common clinical occurrence in the human dentition. First mandibular molars and maxillary second molars are rarely impacted with a reported prevalence of 0–2.3% for second molars, 0.02% for the maxillary first molar, and of less than 0.01% for the mandibular first molar. The failures in their eruption mechanism may occur due to an obstacle such as the presence of a supernumerary tooth or an odontoma, lack of adequate space in the arch, an abnormal eruption path, or with idiopathic etiology. It is an asymptomatic pathology which is usually a casual discovery. Early diagnosis and treatment of permanent molars eruption disturbances contributes to optimal outcomes and favorable long-term prognosis by reduction of complication. The purpose of this is chapter is (1) to define prevalence and etiopathogeny of impacted first and second permanent molars, (2) to pinpoint the needs of earlier diagnosis, and finally (3) to highlight the treatment options.",signatures:"Sanaa Alami, Hakima Aghoutan, Meriem Bellamine and Farid El Quars",downloadPdfUrl:"/chapter/pdf-download/69931",previewPdfUrl:"/chapter/pdf-preview/69931",authors:[{id:"172241",title:"Dr.",name:"Sana",surname:"Alami",slug:"sana-alami",fullName:"Sana Alami"},{id:"285209",title:"Prof.",name:"Hakima",surname:"Aghoutan",slug:"hakima-aghoutan",fullName:"Hakima Aghoutan"}],corrections:null},{id:"65527",title:"Evolution of Dental Implant Shapes and Today’s Custom Root Analogue Implants",doi:"10.5772/intechopen.83746",slug:"evolution-of-dental-implant-shapes-and-today-s-custom-root-analogue-implants",totalDownloads:735,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Native tooth has a unique design to serve perfect stomatognathic function and esthetics which could never be replaced with another material or apparatus if it is lost. Over the past few decades, screw-type endosseous implants have been considered to be as the gold standard for the rehabilitation of edentulism owing to the similarity with the anatomical root shape and location inside the alveolar bone. They have been widely investigated so as to find out the ideal characteristics. Further researches have focused on the cervical region of the dental implant because the maximum stress is pronounced around the implant neck. The ideal characteristics indicate that a wide implant neck for better stress distribution, and a large surface area with a minimal thread geometry for a better long term crestal bone stability. Along with the growing clinical knowledge and digital technology, an innovative and noteworthy approach for implant dentistry, custom root analogue implant (RAI), has evolved. With the computer aided design and manufacturing (CAD/CAM) methods, original and optimized characteristics could be transferred to the custom dental implants just as performing an original root replacement.",signatures:"Ayse Sumeyye Akay",downloadPdfUrl:"/chapter/pdf-download/65527",previewPdfUrl:"/chapter/pdf-preview/65527",authors:[{id:"217236",title:"Dr.",name:"Ayşe",surname:"Sümeyye Akay",slug:"ayse-sumeyye-akay",fullName:"Ayşe Sümeyye Akay"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"1",series:{id:"3",title:"Dentistry",issn:"2631-6218",editor:{id:"419588",title:"Ph.D.",name:"Sergio",middleName:"Alexandre",surname:"Gehrke",slug:"sergio-gehrke",fullName:"Sergio Gehrke",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038WgMKQA0/Profile_Picture_2022-06-02T11:44:20.jpg",biography:"Dr. Sergio Alexandre Gehrke is a doctorate holder in two fields. The first is a Ph.D. in Cellular and Molecular Biology from the Pontificia Catholic University, Porto Alegre, Brazil, in 2010 and the other is an International Ph.D. in Bioengineering from the Universidad Miguel Hernandez, Elche/Alicante, Spain, obtained in 2020. In 2018, he completed a postdoctoral fellowship in Materials Engineering in the NUCLEMAT of the Pontificia Catholic University, Porto Alegre, Brazil. He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}}}},tags:null},relatedBooks:[{type:"book",id:"6668",title:"Dental Caries",subtitle:"Diagnosis, Prevention and Management",isOpenForSubmission:!1,hash:"b0f7667770a391f772726c3013c1b9ba",slug:"dental-caries-diagnosis-prevention-and-management",bookSignature:"Zühre Akarslan",coverURL:"https://cdn.intechopen.com/books/images_new/6668.jpg",editedByType:"Edited by",editors:[{id:"171887",title:"Prof.",name:"Zühre",surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited 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Thus α-thalassemia is characterized by deficient synthesis of α globin, and β-thalassemia is characterized by reduced or absent production of β globin. The resulting syndromes range from asymptomatic to severe microcytic anemias. Recognition of these disorders is important for the obstetrician to provide appropriate care for patients with thalassemia syndrome. Genetic counseling, prenatal diagnosis, and newborn screening are all issues of importance in these inherited disorders. This book intends to provide the reader with a comprehensive overview of thalassemia syndromes regarding types, methods for diagnosis, and early detection and screening for different types of thalassemia syndromes for better management and satisfactory outcome. We hope that the reader will get more knowledge and experience about this very important topic of thalassemia syndromes.
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In the last few decades, lipoprotein research has focused on the phenomenon of atherogenic and non-atherogenic lipoproteins, specifically, atherogenic and non-atherogenic lipoprotein profiles phenotype A and phenotype B [7, 18, 60] after it was reported that more than 75% of patients with an acute coronary syndrome or myocardial infarction had normal plasma values of cholesterol, Low Density Lipoprotein cholesterol (LDL cholesterol) and High Density Lipoprotein cholesterol (HDL cholesterol) [15 - 17].
Thus, it was necessary to look for other risks factors in plasma, the presence of which in relevant quantities could cause damage to endothelial cells and resultant endothelial dysfunction [59]. This called into question whether an increased total cholesterol level, or increased LDL-cholesterol, as a criterion for the degree of atherogenic risk, provided a universal explanation for the origin of atherogenesis. A reasonable explanation was found in atherogenic lipoprotein subpopulations, the presence of which in plasma, even in very low concentrations, could impair the integrity of the vessel wall and lead to endothelial dysfunction with its fatal consequences [Table 1]: formation of atherothrombotic plaques, acute myocardial infarction, ischemic stroke, or sudden death [39, 59, 64].
The predominance of atherogenic lipoproteins in plasma is characteristic for the atherogenic lipoprotein spectrum, phenotype B. When present in plasma in high concentrations, these lipoproteins contribute to ischemic vascular impairment [6, 8, 57, 60]. The process of degenerative changes in vessels results in the formation of atheromatous vascular plaques. These later play an important role in the formation of stable or unstable angina (pectoris), and critical ischemia of peripheral and/or cerebral arteries as well [39,56]. When atherogenic lipoproteins in plasma are present in small quantities, we obtain a picture of a non-atherogenic lipoprotein profile, phenotype A.
Various methods have been developed (gradient gel electrophoresis, ultracentrifugation, magnetic resonance spectroscopy, endothelial models for testing lipoprotein cytotoxicity) to identify atherogenic lipoproteins [2, 26, 45, 48], but because of technical and financial issues, long-term analyses and high operating costs, the previously mentioned methods were used primarily in basic research. Simple analytical procedures for routine distribution were lacking and the possibility of their implementation in every day laboratory practice remained limited.
An electrophoretic method by which to separate lipoproteins on polyacrylamide gel (PAG) with the use of Lipoprint LDL System [29, 41] has become a milestone in routine laboratory analysis and in diagnosing metabolism disorders of lipoproteins. It enables the analysis of 12 lipoprotein subfractions: VLDL, IDL 1-3, LDL 1-7, and HDL.
The Lipoprint LDL system identifies and quantifies
Atherogenic lipoproteins (VLDL, IDL1, IDL2, and LDL3-7, so-called small dense LDL)
Non-atherogenic lipoprotein entities (IDL3, HDL)
Lipoproteins with uncertain atherogenicity (LDL1, LDL2)
And determines
The atherogenic vs. non-atherogenic lipoprotein spectrum, phenotype B vs. phenotype A
Atherogenic lipoprotein spectrums are characterized according to the predominance of atherogenic lipoproteins: very low density (VLDL); intermediate density IDL1 and IDL2; and by the presence of small dense-low density lipoproteins (sd-LDL). The last represented small dense LDL are highly atherogenic LDL subfractions that form fractions LDL3-7. As the name implies, they are smaller than the other types of LDL with a diameter < 26.5 nm (265 Angströms) and they float within the density range of 1.048–1.065 g/ml, that is, higher than LDL1 and LDL2. On the separating polyacrylamide gel (PAG) sd-LDL are detected as subtle bands on the anodic end of the gel, right behind HDL, that migrate to the head of separated lipoproteins.
\n\t\t\t\t\t | \n\t\t\t|
* Low recognition by LDL-receptors (configuration alterations Apo B ) | \n\t\t\t | \n
* Enhanced aptitude for oxidation and acetylation | \n\t | \n
* Oxide-LDL | \n\t|
* Oxide-LDL | \n\t|
* Oxide-LDL | \n\t|
* Easier penetration into the subendothelial space and formation of cholesterol deposits | \n
Atherogenicity of small dense LDL
In our studies were analyzed serum lipoprotein spectrums in patients with newly recognized a) arterial hypertension, b) coronary heart disease, c) lower extremity arterial disease, and d) in patients who survived a stroke. As mentioned earlier, an analytical method for a quantitative evaluation of lipoprotein fractions was used, and the incidence of an atherogenic lipoprotein spectrum phenotype B (vs. phenotype A) in these four representatives of cardiovascular diseases was identified. At the same time, a lipoprotein spectrum of a control group of healthy individuals was examined and tested for the incidence of phenotype B.
Arterial hypertension (AH) (Fig. 3) is one of the most serious cardiovascular diseases. More than 20% of the adult population suffers from this disease. AH is one of the risk factors for atherosclerosis development of coronary, brain, and peripheral arteries, together with the main cardinal risk factors, that is, dyslipoproteinemia and tobacco smoking [14,20,38]. Atherogenic LDL subfractions also play a role in the development of the arterial hypertension [32, 43].
AH is a permanent, long-lasting increase in blood pressure of more than 140/90 mmHg in people of middle age. In people older than 70 years of age, values higher than 160/95 mmHg are considered increased. For more extensive guidelines see the Statement of WHO/ISH (International Society of Hypertension) on the management of hypertension [61].
Dyslipoproteinemia, which frequently accompanies AH and multiplies the risk of atherosclerosis development, can also be considered one of the multiple sources that give rise to AH [35, 64].
Atherogenic lipoproteins in plasma cause endothelial dysfunction, increase vessel tone, and support the development of AH, which terminates in organ ischemia [8,50,51,55,57,59].
In our study 107 patients with newly diagnosed arterial hypertension were examined. Repeated blood pressure (BP) examination confirmed an increased blood pressure more than 150 mmHg for systolic and more than 90 mmHg for diastolic blood pressure in all hypertensive patients. Average systolic blood pressure was 172 ±19 mmHg and average diastolic blood pressure was 102 ±10 mmHg. The group of hypertensive patients comprised 66 men and 41 women. The average age of the men was 50 ± 17.6 years and the average age of the women was 51.0 ± 13.4 years.
The control group consisted of 150 healthy normotensive and normolipemic volunteers, all non-smokers, without signs of cardiovascular disease and without biochemical signs of lipid metabolism disorders. The average age of the subjects was 21 years, and the control group involved 50 males and 100 females. Volunteers were recruited from medical students at the Medical Faculty, who gave written, informed consent, and the study was approved by the local ethics committee.
A blood sample from an antecubital vein was obtained in the morning after a 12-hour fasting period. Total cholesterol and triglycerides in serum were analyzed from lipid parameters, using the enzymatic CHOD-PAP method, Roche Diagnostics Germany. To determine the non-atherogenic lipoprotein phenotype A and the atherogenic lipoprotein phenotype B, the Lipoprint LDL System Quantimetrix CA, USA, was used.
The Score of the Anti-Atherogenic Risk (SAAR) was calculated as the ratio between non-atherogenic and atherogenic lipoproteins in serum [42]. SAAR values over 10.8 represented a non-atherogenic lipoprotein profile, whereas values under 9.8 represented an atherogenic lipoprotein profile. The cut off values for a non-atherogenic lipoprotein profile and an atherogenic lipoprotein profile were calculated from the results of 940 Lipoprint LDL analyses. Using the Quantimetrix Lipoprint LDL system interpretation, all 940 individuals were examined (general group of subjects) and tested for the occurrence of atherogenic vs. non-atherogenic lipoprotein profile and were divided into the two subgroups of subjects with an LDL profile:
Indicative of Type A, that is, a non-atherogenic lipoprotein profile phenotype A
Not indicative of Type A, that is, an atherogenic lipoprotein profile, phenotype B [29]
Statistical evaluation of obtained values was performed with an unpaired student’s t-test. The level of significance was accepted at p < 0.05.
In the control group shown in Table 2, along with the individuals with non-atherogenic normolipidemia, that is, an ideal lipoprotein profile (Fig. 1), a subgroup of normolipidemic individuals with an atherogenic lipoprotein profile was also identified. This group represented people with an atherogenic normolipidemia (Fig. 2). These people are clinically healthy, without clinical or laboratory signs of cardiovascular diseases, but with a positive familial history for cardiovascular diseases (myocardial infarction) in the parents’ or grandparents’ generation. The triglycerides and LDL3-7 concentrations in the control group with the atherogenic profile, compared to the individuals with a non-atherogenic lipoprotein profile, were increased (p < 0.05, respectively, p < 0.0001). The Score of the Anti-Atherogenic Risk (SAAR) for a non-atherogenic lipoprotein profile is a sensitive indicator by which to differentiate between an atherogenic and non-atherogenic plasma lipoprotein constellation (non-atherogenic vs. atherogenic: p < 0.0001).
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|||
\n\t\t\t | (mmol/l±SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |||
\n\t\t\t | \n\t\t4.28 | \n\t\t1.15 | \n\t\t0.60 | \n\t\t1.29 | \n\t\t0.03 | \n\t\t2.31 | \n\t\t1.35 | \n\t\t37.8 | \n\t|||
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.38 | \n\t\t±0.003 | \n\t\t±0.53 | \n\t\t±0.32 | \n\t\t±19.7 | \n\t|||
(non atherogenic profile n =140) | \n\t|||||||||||
\n\t\t\t | \n\t\t4.25 | \n\t\t1.44 | \n\t\t0.68 | \n\t\t1.16 | \n\t\t0.22 | \n\t\t2.24 | \n\t\t1.32 | \n\t\t6.0 | \n\t|||
\n\t\t | ±0.54 | \n\t\t±0.40 | \n\t\t±0.14 | \n\t\t±0.24 | \n\t\t±0.08 | \n\t\t±0.36 | \n\t\t±0.31 | \n\t\t±2.0 | \n\t|||
(atherogenic profile n = 10) | \n\t|||||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|||
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.37 | \n\t\t±0.004 | \n\t\t±0.52 | \n\t\t±0.32 | \n\t\t±18.5 | \n\t|||
\n\t\t\t | \n\t|||||||||||
Non-atherogenic vs. atherogenic | \n\t|||||||||||
\n\t\t | \n\t\t | \n\t\t\t | \n\t\t\n\t\t | \n\t\t | \n\t\t\t | \n\t\t\n\t\t | \n\t\t | \n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in the control group
Non-atherogenic profile, 93.4 % vs. atherogenic profile, 6.6 %, in control group
Non-atherogenic normolipidemia – Control group, SAAR score: 62.5
Atherogenic normolipidemia – atherogenic subgroup of control group atherogenic small dense LDL are present in LDL 3,4 subfractions SAAR score: 2.7
A non-atherogenic lipoprotein profile in the control group was confirmed in 93.4% healthy normolipidemic individuals, and an atherogenic lipoprotein profile was found in 6.6%.
Table 3 shows high statistical significance for the analyzed lipid and lipoprotein parameters between the control group and the group of subjects with arterial hypertension (p < 0.0001, and for HDL, p <0.03).
In Table 4, 78.5% of patients with arterial hypertension have an atherogenic lipoprotein profile. There is a highly significantly increased concentration of small dense LDL (subfractions LDL3-7) in a subgroup of AH-patients, who have an atherogenic profile, compared to the concentration of small dense LDL in the subgroup of AH-patients with a non-atherogenic profile, which confirms the predominance of atherogenic lipoproteins in AH-patients and the creation of atherogenic lipoprotein profile, phenotype B, as well. SAAR in patients with AH is low, that is, 9.2 (cut off is 10.8), and confirms also the predominance of atherogenic lipoproteins in serum.
Arterial hypertension with a borderline hypertriglyceridemia, small dense LDL are present in LDL3, 4 subfractions, SAAR score: 0.9
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t | (mmol/l SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.37 | \n\t\t±0.004 | \n\t\t±0.52 | \n\t\t±0.32 | \n\t\t±18.5 | \n\t|
(total number n=150) | \n\t|||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±1.10 | \n\t\t±1.07 | \n\t\t±0.34 | \n\t\t±0.55 | \n\t\t±0.25 | \n\t\t±0.91 | \n\t\t±0.34 | \n\t\t± 4.5 | \n\t|
(total number n= 107) | \n\t|||||||||
\n\t\t\t | \n\t|||||||||
\n\t\t | \n\t\t | \n\t\t | \n\t\t | \n\t\t\t | \n\t\t\n\t\t | \n\t\t | \n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in AH patients vs.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t | (mmol/l SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t |
AH | \n\t\t5.32 | \n\t\t1.56 | \n\t\t0.84 | \n\t\t1.78 | \n\t\t0.08 | \n\t\t3.02 | \n\t\t1.49 | \n\t\t24.2 | \n\t
\n\t\t | ±0.98 | \n\t\t±0.55 | \n\t\t±0.31 | \n\t\t±0.44 | \n\t\t±0.04 | \n\t\t±0.71 | \n\t\t±0.34 | \n\t\t±13.6 | \n\t
(non-atherogenic profile n= 23) | \n\t||||||||
AH | \n\t\t5.15 | \n\t\t2.48 | \n\t\t1.01 | \n\t\t1.47 | \n\t\t0.42 | \n\t\t2.99 | \n\t\t1.18 | \n\t\t5.1 | \n\t
\n\t\t | ±1.14 | \n\t\t±1.34 | \n\t\t±0.35 | \n\t\t±0.58 | \n\t\t±0.31 | \n\t\t±0.96 | \n\t\t±0.34 | \n\t\t± 2.0 | \n\t
(atherogenic profile n= 84) | \n\t||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
\n\t\t | ±1.10 | \n\t\t±1.07 | \n\t\t±0.34 | \n\t\t±0.55 | \n\t\t±0.25 | \n\t\t±0.91 | \n\t\t±0.34 | \n\t\t± 4.5 | \n\t
\n\t\t\t | \n\t||||||||
Non-atherogenic vs. atherogenic | \n\t\t\n\t | |||||||
\n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in patients with arterial hypertension
Atherogenic 78.5% vs. non-atherogenic 21.5% – arterial hypertension
Coronary heart disease (CHD) (Fig. 4) is a common manifestation of cardiovascular diseases and is frequently associated with lipid and lipoprotein metabolism disorders. Hypercholesterolemia and hypertriglyceridemia, as well as combined hyperlipoproteinemia are regular features that accompany CHD [22,50,51]. Pathophysiologically, the cause of myocardial ischemia is a disproportion, or imbalance, between myocardial oxygen supply and oxygen demand. Ischemia in stable angina is generally due to fixed atheromatous stenosis of one or more coronary arteries as a consequence of impaired lipoprotein metabolism and the formation of lipid atheromas in the coronary arteries [5, 33, 34,49].
Coronary heart disease combined with an atherogenic hypercholesterolemia. High concentration of atherogenic small dense LDL in LDL 3,4 subfractions SAAR score: 5.1
However, clinically, stable angina is not the only form of manifestation of coronary heart disease. Stable angina, as an ischemia due to fixed atheromatous stenosis, can turn into a myocardial ischemia due to plaque rupture with thrombosis and spasm of the artery (instable angina). In addition, myocardial necrosis (myocardial infarction), caused by acute occlusion of a coronary artery (due to plaque rupture and thrombosis), can have fatal consequences for disabled persons. It can be supposed that the modified forms of lipoproteins can play an important role in any form of clinical manifestation of coronary heart disease. Recently, clinical studies reported that the atherogenic lipoprotein populations (lipoprotein subfractions), presented in the plasma lipoprotein spectrum in high concentrations, play an important role in the development of atherosclerotic changes in the arterial wall [14, 38, 39].
We distinguish facultative atherogenic very low density lipoproteins, VLDL, and their remnants, intermediate density lipoproteins, IDL, low density lipoproteins, LDL (considered a lipoprotein family with high atherogenicity), and high density lipoproteins, HDL. Modified lipoprotein entities in all these lipoprotein families can play a role in the formation of atherogenic lipoproteins, which accelerate the atherogenesis in the artery walls, including in the coronary arteries.
In our study, we focused on the determination of the incidence of an atherogenic lipoprotein phenotype in patients with coronary heart disease – in stable angina patients.
In our study, 104 patients with newly diagnosed coronary heart disease were examined. The diagnosis of CHD (stable angina pectoris grade I or II) was confirmed by medical examination, laboratory results, resting ECG, results of echocardiography, and duplex ultrasound of the carotid arteries.
See methods published in the section “Arterial hypertension (AH).”
The results of lipid parameters presented in Table 5 confirm a highly significant increased concentration of analyzed lipid and lipoprotein parameters (p<0.0001) in CHD-patients, compared to control values and a low value of the SAAR. These low values (< 10.8) are regularly found in atherogenic lipoprotein phenotype B.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t | (mmol/l SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.37 | \n\t\t±0.004 | \n\t\t±0.52 | \n\t\t±0.32 | \n\t\t±18.5 | \n\t|
(total number n=150) | \n\t|||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
(total number n= 104) | \n\t|||||||||
Control vs. CHD | \n\t|||||||||
\n\t\t | \n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in CHD patients vs. control group
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t | (mmol/l±SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t |
CHD | \n\t\t5.26 | \n\t\t1.44 | \n\t\t0.82 | \n\t\t1.73 | \n\t\t0.13 | \n\t\t3.11 | \n\t\t1.29 | \n\t\t12.7 | \n\t
\n\t\t | ±0.99 | \n\t\t±0.50 | \n\t\t±0.27 | \n\t\t±0.49 | \n\t\t±0.06 | \n\t\t±0.80 | \n\t\t±0.31 | \n\t\t±5.1 | \n\t
(non-atherogenic profile = 19) | \n\t||||||||
CHD | \n\t\t5.25 | \n\t\t2.63 | \n\t\t1.02 | \n\t\t1.47 | \n\t\t0.48 | \n\t\t3.05 | \n\t\t1.16 | \n\t\t4.0 | \n\t
\n\t\t | ±1.19 | \n\t\t±2.03 | \n\t\t±0.47 | \n\t\t±0.46 | \n\t\t±0.35 | \n\t\t±0.86 | \n\t\t±0.28 | \n\t\t±3.5 | \n\t
(atherogenic profile n= 85) | \n\t||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
\n\t\t | ±1.15 | \n\t\t±1.72 | \n\t\t±0.43 | \n\t\t±0.47 | \n\t\t±0.29 | \n\t\t±0.85 | \n\t\t±0.29 | \n\t\t±3.8 | \n\t
\n\t\t\t | \n\t||||||||
Non-atherogenic vs. atherogenic profile | \n\t||||||||
\n\t\t | \n\t\t | \n\t\t\t | \n\t\t\n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t | \n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in coronary heart disease
Note: In the column without published p values, the differences in the evaluated parameter were not significant (n.s.)
Atherogenic 81.7% vs. non-atherogenic 18.3%, in coronary heart disease
In Table 6, an atherogenic lipoprotein phenotype B is present in 81.7% of patients with CHD. An increased concentration of small dense LDL (LDL3-7) in the CHD-patient subgroup with an atherogenic lipoprotein profile, compared to the results of the CHD-patient subgroup with a non-atherogenic lipoprotein profile (p<0.0001), confirms a predominance of atherogenic lipoproteins in the serum of patients with CHD.
Lower extremity arterial disease (LEAD) (Fig. 5) is a common atherogenic disease of the cardiovascular system. Patients with LEAD exhibit normal to high atherogenic dyslipoproteinemia [8, 31, 50 -52, 62].
Lower extremity arterial disease with combined atherogenic hyperlipoproteinemia with high concentration of atherogenic small dense LDL (LDL3,4 subfractions) SAAR score: 1.5
Almost all lower extremity arterial disease is due to atherosclerotic changes in artery vessels, and the pathology of LEAD is also similar to coronary heart disease. The most important risk factor for the development and progression of atherosclerotic LEAD are tobacco smoking, arterial hypertension, and hyperlipidemia. Other risk factors include diabetes mellitus, low physical activity, and a diet rich in lipids and carbohydrates. However, dyslipidemia plays an important role. Increased lipid levels of cholesterol and triglycerides are generally accepted as important risk factors for the development of atherosclerosis [14,25, 47].
In the last few decades, there has been much discussion about which atherogenic lipoproteins participate in the formation of the atherogenic lipoprotein profile, phenotype B. Atherogenic lipoproteins in relevant concentration in the blood serum are responsible for the acceleration of the development of atherogenic cardiovascular diseases, including the development of LEAD. The LDL subpopulations of small dense LDL are considered to be strongly atherogenic lipoprotein entities in the plasma/serum lipoprotein spectrum [38,59] with consequent acceleration of endothelial dysfunction and formation of the atheromatous subendothelial plaques in the arteries [21]. In the present study, we have focused on determining the incidence of an atherogenic lipoprotein phenotype, along with determining the role of atherogenic serum lipoproteins, in patients with lower extremity arterial disease.
In the clinical study, 100 patients with newly diagnosed lower extremity arterial disease were examined. The study included 55 males and 45 females: the average age of males was 56.0 years ±11 years and the average age of females 52.5 years ± 14 years. The patients had C2a degree, according to the Claudication classification: [proximal type (AP), the first degree (P1) with dyslipidemia]. Patients were ex-smokers.
LEAD was diagnosed according to the history of disease, intermittent claudication, the medical examination, including physical examination (Ratschow’s test in the modification according to Linhart, see the Angiological Section of Slovak Medical Chamber) [23, 24, 27, 28] and examination of the ankle-brachial (pressure) index (ABPI) [40, 55, 57].
See methods published earlier in the section “Arterial hypertension (AH).”
Results of lipid parameters presented in Table 7 confirm the highly significant increased concentration of analyzed lipid and lipoprotein parameters in LEAD-patients (p<0.0001), compared to control values. The low values of the SAAR, which is generally low (< 10.8) in the atherogenic lipoprotein phenotype, also confirms the atherogenic lipoprotein constellation in the serum of LEAD-patients.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t | (mmol/l SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.37 | \n\t\t±0.004 | \n\t\t±0.52 | \n\t\t±0.32 | \n\t\t±18.5 | \n\t|
(total number n=150) | \n\t|||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
(total number n= 100) | \n\t|||||||||
Control vs. LEAD | \n\t|||||||||
\n\t\t | \n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in LEAD-patients vs. control group
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t | (mmol/l±SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t |
LEAD | \n\t\t5.37 | \n\t\t1.81 | \n\t\t0.86 | \n\t\t1.82 | \n\t\t0.10 | \n\t\t3.18 | \n\t\t1.33 | \n\t\t17.4 | \n\t
\n\t\t | ±0.95 | \n\t\t±0.51 | \n\t\t±0.26 | \n\t\t±0.54 | \n\t\t±0.03 | \n\t\t±0.82 | \n\t\t±0.29 | \n\t\t± 6.5 | \n\t
(non-atherogenic profile n= 20) | \n\t||||||||
LEAD | \n\t\t5.28 | \n\t\t2.31 | \n\t\t0.98 | \n\t\t1.52 | \n\t\t0.46 | \n\t\t3.09 | \n\t\t1.18 | \n\t\t4.6 | \n\t
\n\t\t | ±1.28 | \n\t\t±1.18 | \n\t\t±0.39 | \n\t\t±0.50 | \n\t\t±0.34 | \n\t\t±0.99 | \n\t\t±0.32 | \n\t\t± 4.0 | \n\t
(atherogenic profile n= 80) | \n\t||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
\n\t\t | ±1.21 | \n\t\t±1.05 | \n\t\t±0.37 | \n\t\t±0.51 | \n\t\t±0.28 | \n\t\t±0.96 | \n\t\t±0.31 | \n\t\t± 4.5 | \n\t
(total number n=100) | \n\t||||||||
Non-atherogenic vs. atherogenic | \n\t||||||||
\n\t\t | p<0.01 | \n\t\tp<0.001 | \n\t\t\n\t\t | p<0.05 | \n\t\tp< 0.0001 | \n\t\t\n\t\t | \n\t\t | p< 0.0001 | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in lower extremity arterial disease
Atherogenic 80% vs. non-atherogenic 20% in lower extremity arterial disease
In 80% of patients (Table 8), LEAD was associated with an atherogenic lipoprotein phenotype. An increased concentration of small dense LDL (LDL3-7 subgroups) in the LEAD-patients with an atherogenic lipoprotein profile, compared to the results from the LEAD-patients with a non-atherogenic lipoprotein profile (p<0.0001), confirms the predominance of atherogenic lipoproteins in serum in the subgroup of patients with an atherogenic lipoprotein profile.
Stroke (Fig. 6) is the leading cause of mortality and of long-term morbidity in the populations of developed industrialized countries in the world. The atherogenic serum lipoproteins in high concentrations create an atherogenic lipoprotein profile, which plays a key role in the acute onset of cardiovascular and cerebrovascular events, that is, stroke [54,55]. Cerebral stroke attack remains a frequent medical problem and is the third most frequent cause of mortality all over the world. It represents a heterogeneous group of diseases with more than 150 known causes. In 25–39% of strokes, the cause leading to the acute cerebrovascular event cannot usually be definitively explained [4].
Patient survived an ischemic stroke with combined atherogenic hyperlipoproteinemia high concentration of VLDL, VLDL remnants and atherogenic small dense LDL, i.e. LDL 3, 4 subfractions. SAAR score: 2.4
*Reference ranges derived from 125 serum samples that met the NCEP ATPIII guidelines for desirable lipid status
**LDL-C comprised of the sum of cholesterol in Md bands C through A as well as all the subfractions
Dyslipidemia represents a risk factor for the development of cardiovascular disease, and thus dyslipidemia has been classified as an atherogenic phenomenon. The goal of the treatment of hyperlipoproteinemia, that is, of dyslipidemia, is to reduce the lipid concentration in serum to established target values of lipids (cholesterol and triglycerides), but the primary goal is to reduce the atherogenic potential of serum lipids [9, 21, 53]. Dyslipoproteinemia is also the key phenomenon in the pathogenesis of the onset of atherosclerotic alterations in brain vessels [64]. Accompanied by high cholesterol levels – a classic risk factor for the development of cardiovascular diseases – an increased concentration of triglycerides in the blood serum can also play an important role in atherogenesis [3,58].
There are several studies that have provided evidence for the relation between carotid artery stenosis and an ischemic cerebral event [55]. However, the causal inter-relation between dyslipidemia and stroke has not been explained sufficiently [3, 4, 63]. Relapsing ischemic strokes account for one-fourth of all strokes in a year and are a strong evidence for a failure of secondary prevention [10]. This hard reality leads rightly so to the idea of optimal stroke prevention through the selection of individuals, who are at risk of stroke [13]. The aim of this pilot study was to identify the atherogenic lipoproteins and determine the lipoprotein profile in subjects who had suffered an ischemic cerebrovascular event, that is, stroke.
The study included 55 patients, 23 men, with an average age of 64 years ± 13 years, and 32 women, average age 74 years ± 13 years, who survived an ischemic cerebrovascular event, that is, a large-artery atherosclerosis subtype of stroke. To determine the subtype of ischemic stroke, the original TOAST (Trial of ORG 10172 in Acute Stroke Treatment) [1] criteria were used. The diagnosis of subtype was based on the risk factor profiles, clinical features, and results of diagnostic tests, including CT scan/MRI, vascular imaging (carotid duplex, transcranial Doppler), EEG – electroencephalography, echocardiography (transesophageal/ transthoracic), assessment of prothrombotic syndromes [1,30], activated partial thromboplastin time (aPTT), and international normalized ratio (INR).
See methods published in the section “Arterial hypertension (AH).”
A blood sample from the antecubital vein was obtained throughout the 24 hours after the onset of cerebrovascular event.
The results of lipid parameters presented in Table 9 confirm a highly significantly increased concentration of analyzed lipid and lipoprotein parameters (p<0.0001) in people who survive a stroke, compared to control values, and also a low value on the SAAR, which is generally low (< 10.8) in an atherogenic lipoprotein phenotype.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t|
\n\t\t\t | (mmol/l SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t | |
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±0.60 | \n\t\t±0.39 | \n\t\t±0.16 | \n\t\t±0.37 | \n\t\t±0.004 | \n\t\t±0.52 | \n\t\t±0.32 | \n\t\t±18.5 | \n\t|
(total number n=150) | \n\t|||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t|
\n\t\t | ±1.10 | \n\t\t±0.91 | \n\t\t±0.34 | \n\t\t±0.57 | \n\t\t±0.24 | \n\t\t±0.82 | \n\t\t±0.32 | \n\t\t±4.22 | \n\t|
(total number n= 55 | \n\t|||||||||
Control vs. stroke | \n\t|||||||||
\n\t\t | \n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in stroke patients vs. control group.
\n\t\t\t | \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
\n\t\t\t | (mmol/l±SD) | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t |
Stroke | \n\t\t5.54 | \n\t\t1.70 | \n\t\t0.93 | \n\t\t2.19 | \n\t\t0.14 | \n\t\t3.30 | \n\t\t1.31 | \n\t\t13.74 | \n\t\t1.22 | \n\t\t0.92 | \n\t
\n\t\t | ±1.30 | \n\t\t±0.44 | \n\t\t±0.14 | \n\t\t±0.86 | \n\t\t±0.07 | \n\t\t±1.01 | \n\t\t±0.35 | \n\t\t±1.36 | \n\t\t±0.45 | \n\t\t±0.44 | \n\t
(non-atherogenic profile n= 8) | \n\t||||||||||
Stroke | \n\t\t5.14 | \n\t\t2.29 | \n\t\t1.11 | \n\t\t1.48 | \n\t\t0.31 | \n\t\t2.86 | \n\t\t1.06 | \n\t\t5.33 | \n\t\t0.72 | \n\t\t0.76 | \n\t
\n\t\t | ±1.11 | \n\t\t±0.94 | \n\t\t±0.37 | \n\t\t±0.41 | \n\t\t±0.23 | \n\t\t±0.72 | \n\t\t±0.29 | \n\t\t±3.32 | \n\t\t±0.26 | \n\t\t±0.26 | \n\t
(atherogenic profile n = 47) | \n\t||||||||||
\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
\n\t\t | ±1.06 | \n\t\t±0.91 | \n\t\t±0.35 | \n\t\t±0.53 | \n\t\t±0.23 | \n\t\t±0.77 | \n\t\t±0.31 | \n\t\t± 4.22 | \n\t\t±0.33 | \n\t\t±0.28 | \n\t
(total number n= 55) | \n\t||||||||||
Non-atherogenic vs. atherogenic | \n\t||||||||||
\n\t\t | \n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t\t\n\t\t\t | \n\t
Serum concentration of lipids, lipoproteins, and SAAR-score in patients with stroke.
Atherogenic 85.5 % vs. non-atherogenic 14.5 % in stroke patients.
In Table 10, an atherogenic lipoprotein phenotype was identified in 85.5 % of the patients who survive a cerebral ischemic stroke. The increased concentration of small dense LDL (LDL3-7 subgroups) in the atherogenic lipoprotein profile of patients with stroke, compared to the results in a non-atherogenic lipoprotein profile, is mild, but significant (p<0.05). The difference in the SAAR between the two subgroups was highly significant (p<0.0001), which also confirmed the overwhelming atherogenic lipoprotein constellation in patients who survived a stroke. The concentration of LDL1 was significantly higher in the subgroup of stroke-patients with a non-atherogenic lipoprotein profile (p<0.0001), however, the difference in the LDL2 lipoprotein subfraction was not significant.
In the last few decades, lipoprotein research has focused on the phenomenon of atherogenic and non-atherogenic lipoproteins, and on the phenotype A vs. phenotype B characterization, as a consequence of the published evidence that the majority of the patients with an acute coronary syndrome or patients who survive a myocardial infarction had normal plasma values of cholesterol, LDL-cholesterol, and HDL-cholesterol [15-17]. A reasonable explanation for this fact was to posit a new, active atherogenic substance in plasma, an atherogenic lipoprotein subfraction, the presence of which in plasma, even in very low concentrations, could impair the integrity of the vessel wall and lead to endothelial dysfunction with its fatal consequences. Several clinical studies reported observations that in the plasma of patients with coronary heart disease there are subfractions of lipoproteins, which could play a crucial role in atherodegenerative processes and form the atherothrombotic plaques [5, 33, 34, 37, 39,49]. The Quebec Cardiovascular Study, a prospective study of 2,103 men [33,34] concluded that “ a significant proportion of the risk for heart disease associated with small, dense LDL particles may be independent of variations in plasma lipid concentrations. Small LDL particles and elevated apo B levels were found to be the most predictive indications for ischemic heart disease ”.
For this reason, patients who were suffering from cardiovascular diseases were examined in order to quantify the atherogenic lipoproteins in serum and to determine the incidence of an atherogenic lipoprotein profile in patients who had a diagnosis of cardiovascular diseases.
The clinical studies included 366 patients with a diagnosis of arterial hypertension (n=107), coronary heart disease (n= 104), lower extremity arterial disease (n= 100), and ischemic stroke (n= 55). Patients were tested with the diagnostic method Lipoprint LDL System, which quantifies atherogenic lipoproteins and identifies an atherogenic and a non-atherogenic lipoprotein profile [29]. This was a fundamental methodological contribution of this new analytical and diagnostic method.
Our study confirmed that more than 80% of tested patents with cardiovascular diseases have an atherogenic lipoprotein profile, with a high level of strongly atherogenic small dense LDL. The atherogenic lipoprotein profile was found to be the overwhelming lipoprotein profile in tested cardiovascular diseases. Such a profile was found in arterial hypertension in 78.5%, in coronary heart disease in 81.7%, in lower extremity arterial disease in 80%, and in patients who survived an ischemic stroke in 85%. The average atherogenic lipoprotein profile in all these tested diagnoses in the study was found to be of 81.3%.
This study also highlights the observation that, in the atherogenic lipoprotein profiles, in all diagnoses, compared to the non-atherogenic profiles, the concentration of total cholesterol is lower (n.s.) and the concentration of triglycerides is higher (even statistically significant; in AH, CHD, LEAD, as well as in the control group, up to p<0.002). Hypertriglyceridemia accompanied the hypercholesterolemia in all tested diagnoses, that is, in AH, CHD, LEAD, and stroke). The concentration of triglycerides, compared to the control group, was significantly increased (p<0.0001) and proportionally even higher than cholesterol. From this result, it can be assumed that triglycerides/hypertriglyceridemia can play a much more important role than was generally accepted, as until now the most important role in the pathogenesis of vascular degenerative atherosclerotic injury was attributed to cholesterol and hypercholesterolemia. Our present results are in agreement with other authors, who have called attention to hypertriglyceridemia as a risk factor for cardiovascular diseases [8,12,19, 36,58], as triglyceride-rich lipoproteins can generate small dense LDL in high quantities [46].
The strong atherogenic lipoproteins – small dense LDL – have been found in the lipoprotein profile of all diagnostic groups [25,52,55,56]. Their presence is decisive for an atherogenic profile declaration. This is a rule that is valid not only for a hyperlipidemia, but also for a normolipidemia.
In the case of normolipidemia (see the atherogenic lipoprotein profile in the control group), a new phenomenon could be established – atherogenic normolipidemia [44] – as a risk factor for the development of cardiovascular disease. A special form of normolipidemia can also be atherogenic. This is new knowledge, and this new knowledge could help in the prevention and treatment of cardiovascular disease.
This study was supported by an EU structural research fund Interreg III AT-SR, project code: 1414-02-000-28 in years 2006-2008.
We would like to acknowledge the excellent technical assistance of MTA Barbara Reif, MTA Judith Trettler, and MTA Karin Waitz, Krankenanstalten Dr. Dostal, Vienna, Austria, and also to acknowledge the excellent technical assistance of MTA Olga Reinoldova, 2nd Department of Internal Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic.
Age-related macular degeneration (AMD) is a complex, degenerative, progressive, multifactorial disease with multiple genetic and environmental factors contributing to its onset and progression [1].
Age-related macular degeneration (AMD) represents damage of the retinal macula and thus the central visual field and is the leading cause of blindness and visual impairment in people over 60 years of age [2, 3]. Prevalence of an early AMD (the presence of medium-sized drusen or drusen with degeneration or hyperpigmentation of the retinal pigment epithelium (RPE)) is 18% in the elderly population between 65 and 74 years of age and as much as 30% in the population older than 74 years [4].
The initial site of damage, according to most researchers, is the retinal pigment epithelium, although some authors find primary damage in the choriocapillary or extracellular matrix of the sensory retina. Regardless of the location and mechanism of initial damage, there is an opinion that oxidative stress plays an increasingly important role in the genesis of age-related macular degeneration.
The eye is a unique organ, because it is constantly exposed to radiation, atmospheric oxygen, chemicals from the environment, but also to the physical damages [5]. Therefore, oxidative stress is one of the most important mechanisms of the onset of many eye diseases such as cataract, glaucoma, uveitis, retrolental fibroplasia, age-related macular degeneration, as well as various forms of retinopathy [6]. Most free radicals are formed as bioproducts of normal cellular physiology. The most common damage to the eye by free radicals is caused by hydroxyl radical (OH
The objective of this review was to describe the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.
Based on the Beckman AMD classification system, the disease is classified into early-stage AMD, intermediate-stage AMD and late-stage AMD [8]. Early-stage AMD encompasses the presence of medium-sized drusen (63–125 μm) without any impairment of visual function. Intermediate-stage AMD is defined by the presence of large drusen (>125 μm) or/and abnormalities in the RPE. Late-stage AMD (advanced AMD) is classified into two clinical entities: central geographic atrophy (GA, dry or nonexudative AMD) and neovascular AMD (wet or exudative AMD) [9]. Irreversible loss of vision occurs in geographic atrophy when there is an irreversible loss of RPE and photoreceptor cells, usually in the perifoveal region of the macula. In the neovascular form of AMD, there is an invasion of new choroidal blood vessels (choroidal neovascularization-CNV), followed by retinal detachment and RPE and vision loss [9].
Oxidative processes participate in almost all pathological processes in the eye. The presence of oxidative stress has also been registered in uveitis, diabetic retinopathy, various forms of glaucoma, cataractogenesis and other degenerative processes [10]. As highly reactive intermediates, free radicals can lead to oxidative tissue damage through a number of mechanisms such as peroxidation of unsaturated fatty acids leading to disturbances in the permeability and fluidity of biological membranes, which is accompanied by increased membrane permeability. Oxidation of thiol groups of enzymes leads to a decrease in their activity and even inactivation of enzymes. Fragmentation of fatty acid chains leads to loss of membrane integrity, while disruption of lysosomal membrane continuity leads to release of hydrolytic enzymes and cell damage [11].
The oxidation of polyunsaturated fatty acids in the phospholipids of the cell membranes could damage the cell integrity and function. In addition to negative and destructive effects, this process may have important physiological functions such as: the lipid metabolism regulation, and changes in their physicochemical properties and permeability. Under controlled conditions, ROS enables the control of synthesis of biologically active prostaglandins and leukotrienes, proliferation and initiation of cell death.
Proteins are also targeted by free radicals’ action that could change their primary, secondary and even tertiary structure. Oxidative modifications of the primary structure of proteins resulting from the modification or loss of some amino acids or aggregation and fragmentation of proteins, which are reflected in changes in solubility and charge, are described [12]. These processes affect the integrity of the cell and its function and lead to oxidative tissue damage.
Oxidation of nucleic acids leads to changes in DNA structure, gene mutations, synthesis of inadequate genes or lack of synthesis of other genes. As a result of such processes, malignant cell transformations occur. Mitochondrial DNA is particularly sensitive to such transformations.
The degree of biomolecule damage depends on their vulnerability and intensity of oxidative stress. The repair of primarily damaged molecules results in structural changes that remain at the molecular, i.e. at the cellular level. At one point, the damage becomes so great that it exceeds the critical mass. At that moment, the symptoms of illness appear [13].
Eye damages caused by these changes as well as the mechanisms of antioxidant protection show certain specifics, not only in the eye as a special organ but also in its highly differentiated and specialised structures. Oxidative stress in epithelial cells occurs mainly as a consequence of a photodynamic process or as a by-product of oxidative phosphorylation in mitochondria.
The retina is very complex in its structure, and it is one of the highest oxygen-consuming tissues that continuously transforms light into vision, generating reactive oxygen species (ROS), such as the superoxide (O2•−), the hydroxyl radical (•OH), hydrogen peroxide (H2O2) and singlet oxygen (1O2) as normal metabolic by-products [14]. Generally, ROS are produced during oxidative metabolism under physiological conditions and participate in normal cellular metabolism [15]. Retinal photoreceptor membranes are rich in polyunsaturated fatty acids.
Photooxidative retinal damage is in the function of duration of intensity and wavelength of light. Changes that occur in the pigment layer of the retina are considered to be initial in the process of genesis of age-related macular degeneration. During ageing, functions of all senses gradually weaken. Degenerative processes in the eye and especially in the lens are the first signs of ageing that are noticed [10].
It is well established that light exposure has the potential to cause detrimental effects in RPE and retina as well as in many other organs and tissues, such as the skin, cornea, conjunctiva and lens [16].
Large quantities of ROS are produced by exposure to ultraviolet light (λ = 100–400 nm) and to blue light (λ = 400–500 nm) [17]. The photoreceptors in the macula absorb parts of the light spectrum through rhodopsin, a photoreceptor molecule in rods [18].
Roehlecke and Schumann [19] suggested that the synthesis of ROS occurred directly in outer segments of photoreceptors in the reaction catalysed by the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NOX) as well as by the mitochondrial activity of the outer segments after absorption of visible blue light (λ = 405 nm) with an output power of 1 mW/cm2 [19]. The authors found that the generation of ROS is highly increased in the photoreceptors of retinal explants after 0.5–1 h of blue light absorption, due to increased NOX activity (especially NOX2 and NOX4). Under these conditions (light exposure of 1 mW/cm2), it is possible to do the following extrapolation to the superoxide anion [20]: 1) One granule of lipofuscin can synthesise 8 x 10−19 mol of superoxide anion/min; 2) since 1 mol contains 6.02 x 1023 molecules, then 1 granule is capable of producing 4.8 x 105 molecules of superoxide/min; and 3) if we take into account that the average cell volume is 2000 μm3 and if up to 19% of that volume is occupied by lipofuscin granules 1 μm in diameter, then each RPE cell has a synthesis capacity of 3.5 x 108 superoxide anions/per cell per minute [21].
This high level of free radical synthesis may explain why RPE cells contain a high concentration of various antioxidants [22]. The spectral dependence of lipofuscin explains the so-called ‘blue light hazard’ on retina. Light with a wavelength of 550 nm or less can cause ‘actin’ or photochemical damage, but is too low to cause thermal effects [23]. These photochemical lesions are expressed at the level of RPE, where the action spectrum of ‘blue light’ is similar to the bandwidth of the absorption spectrum of melanin [24] and lipofuscin [22, 25]. Photoreactivity analysis of blue light in freshly isolated RPE cells shows a high level of oxygen uptake with increasing age of the donor and that this ‘photo-uptake’ is predominantly related to lipofuscin [26]. These observations suggest a different function of lipofuscin in cells that may explain the association between high levels of lipofuscin and AMD. RPE cells are rich in antioxidants which may be enough to detoxify any reactive oxygen species [27]. Conversely, antioxidants may be insufficient to detoxify all radicals throughout life so that oxidative damage can manifest at some point in life (for example, in old age).
It has also been observed that lipofuscin photosensitivity reactions lead to increased intragranular lipid peroxidation, measured through the accumulation of lipid peroxides and malondialdehyde in pigment granules [26, 28]. Moreover, lipofuscin can perform extracellular lipid peroxidation and enzyme inactivation. Freshly isolated lipofuscin granules incubated with visible light induced up to a 30% increase in lipid peroxidation, compared with the control. Granules incubation with catalase (antioxidant) and lysosomal enzymes (acid phosphatase), in the presence of light, causes as much as 30–50% reduction in enzyme activity. Lipid peroxidation and loss of enzyme activity can be prevented by antioxidants which indicate that lipofuscin photodamage is a product of action of free reactive oxygen species. It is generally accepted that RPE cell dysfunction is an early, crucial moment in the pathogenesis of AMD [29, 30].
RPE cells have a variety of functions from metabolic to supportive, and they are vital for photoreceptors including maintenance of the blood-retinal barrier, participation in the visual cycle (uptake, transport and release of vitamin A and its metabolites) as well as in degradation and uptake of apical phagocited parts of the photoreceptor outer segments [31]. One of the leading factors of RPE cell dysfunction is age-related phagocytic and metabolic insufficiency of postmitotic RPE cells, leading to progressive accumulation of lipofuscin granules which are mainly composed of lipids (~50%) and protein (~44%) of phagosomal, lysosomal and photoreceptor origin (including the retinoid transporter-cellular retinaldehyde binding protein/CRALBP). These substances from the lipofuscin composition can be oxidatively modified either as a result of exposure to UV light or high doses of oxygen in the eye [29, 30].
The well-known cytotoxic constituent of lipofuscin is fluorophore bisretinoid which consists of two retinoid chains derived from the pyridinium ring (A2E) which together with other photoreactive molecules is a powerful photoinducible ROS generator with a strong effect on oxidative damage of lipids, proteins and DNA [31]. N-retinyl-N-retinyldiene-ethanolamine 2-(2,6-dimethyl-8-(2,6,6- trimethyl-1-cyclohexene-1-yl) -1E, 3E, 5E, 7E-octyltetraenyl]-1-(2-hydroxyethyl)-4-[4- methyl-6-(2,6,6-trimethyl] or A2E increases the RPE sensitivity to blue light and exhibits several toxic effects on RPE cells [32, 33]. By the action of light of wavelength, λ = 430 nm, A2E is converted to A2E-epoxide by binding to oxygen. The resulting epoxide can destabilise the membranes of mitochondria and lysosomes [34] and can also inhibit cytochrome oxidase, leading to disruption of electron flow in the respiratory chain [35]. This process, in addition to producing more ROS (reactive oxygen species), reduces the efficiency of energy metabolism. An alternative A2E toxic pathway has been described by Finnemann [36], who in a study with A2E-laden RPE cells demonstrated the presence of destabilised lysosomes, resulting in incomplete digestion of phagocited photoreceptors of the outer segments during 24 h. Since phagocytosis is a circadian regulated process, this will constantly increase the non-degraded phospholipids that are a source of ROS. Mitochondrial destabilisation and incomplete digestion of lipids and proteins caused by lysosome destabilisation lead to increased free radical accumulation. In a closed circle, this mechanism destabilises RPE cells, leading to their loss and this process conditions the initiation of drusen formation [37].
Although lipid peroxidation products are considered to be the main substrates for the genesis of lipofuscin and its cytotoxic constituents, other identified lipofuscin proteins also play a significant role in cytotoxicity [30, 31].
The study of King et al. conducted on the human adult RPE cell line-19 (ARPE-19) revealed that the mitochondrial electron transport chain was an important source of ROS which played a critical role in the death of cells exposed to short-wavelength blue light (425 ± 20 nm) [38].
Except lipofuscin, several other retinal pigments, such as rhodopsin and melanin, were shown to be involved in the oxidative stress process [39]. Grimm et al. reported rhodopsin-mediated blue-light-induced damage in the retina, which occurred after short time exposure to the blue light [40].
In the RPE, lipofuscin is derived primarily from phagocytosis of shed photoreceptor outer segments and is considered a heterogeneous waste material that accumulates with age in active postmitotic cells, such as those of the RPE [41]. The RPE cells are able to phagocyte the photoreceptors of outer segments (POSs) that contain a high amounts of unsaturated fatty acids [42]. During phagocytosis, a high quantity of oxygen is consumed and a significant production of ROS occurs (generated by NOX or peroxidase) via the oxidation of fatty acids in the POSs [43]. Mitter et al. in their study have shown that autophagy plays a significant role in protection of the RPE from oxidative stress [44]. Recent evidence showed that dysfunctional autophagy/mitophagy in the RPE may lead to mitochondrial disintegration by affecting the mitochondrial fission/fusion ratio, resulting in excessive amounts of ROS [45].
Excessive synthesis of free radicals in the eye is associated with the production of oxidatively modified compounds and cytotoxic damage of ocular structures. The cell types with relatively high levels of polyunsaturated fatty acids (PUFAs), such as retinal cells, are highly sensitive to lipid peroxidation. Polyunsaturated fatty acids in phospholipids and glycolipids are the basic substrate of oxidative damage to lipids caused by free radicals.
Lipid peroxidation, a complex process involving the interaction of oxygen-derived free radicals with polyunsaturated fatty acids, finally results in a variety of primary compounds: highly reactive compounds (alkyl radicals, conjugated dienes, peroxy and alkoxy/oxyl radicals and lipid hydroperoxide). During further decomposition of primary compounds, a series of secondary products are produced such as: short-chain evaporable hydrocarbons, aldehydes and end products of lipid peroxidation (i.e. isoprostanes, MDA, 4-hydroxy-2,3, trans nonenal and 4,5-dihydroxydecenal) [46, 47].
MDA is a secondary product of peroxidation of unsaturated fatty acids, (particularly arachidonic acid) and is a physiological ketoaldehyde [48]. In a higher concentration, it reacts with free amino groups of proteins (especially with lysine cysteine or histidine residue). Such modified protein structures have immunogenic features. Some studies have shown that an increased titre of these autoantibodies directly correlates with the extent of oxidative damage and may predict the progression of some diseases. It was suggested that reduced ability to protein proteolysis after their oxidative modification with MDA and 4-HNE represents one of the main factors of lipofuscin synthesis during the development of AMD [49].
Lipid peroxidation highly reactive end products, such as 4-hydroxylnonenal (4-HNE), malondialdehyde (MDA), oxidised nucleotides and carboxyethyl pyrrole (CEP), have been demonstrated to be associated with drusen formation and RPE atrophic modifications in both human and animal eye [50].
Recently, Kim et al. [51] found that the injection of hydroperoxy-octadecadienoic acid (HpODE), (a peroxidized lipid) into the subretinal space of a murine AMD model, could initiate an early increase in the expression of markers of oxidative stress and lipid peroxidation, especially high levels of 4-HNE and MDA [51]. Zor et al. [52] documented a significantly increased MDA values (~15%) in patients with neovascular AMD compared with the controls [53].
F2-isoprostane (F2-IsoPs) is another marker of lipid peroxidation which is considered to be an important ‘in vivo’ marker of oxidative damage in AMD [54, 55]. Sabanayagam et al. [56] demonstrated that the presence of F2-IsoPs in urine was positively associated with AMD.
Oxidative DNA damage of both nuclear and mitochondrial genomes can result in strand breaks, base modifications and DNA-protein cross linkages which are all strongly implicated in ageing and age-related diseases [57, 58]. Over 20 base modifications related to ROS attack of DNA are identified, with the following oxidative DNA damage products: 8-oxo-7,8-dihydroadenine, 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 5,6-dihydroxy-5,6-dihydrothymine as well as the ring-opened lesions of 4,6-diamino-5-formamido-pyrimidine and 2,6-diamino-4-hydroxy-5-formamido-pyrimidine [59]. The 8-oxodG, which is formed through the oxidation of guanine at the C8 position in the guanine base, serves as a reliable biomarker of oxidative stress and oxidative modification of DNA, and it is associated with ageing and ageing-related diseases [58].
Age-related increases in lipofuscin, 8-oxoguanine, CEP, 4-HNE and MDA expression have been observed in the ageing retina [60, 61, 62] which have been reported to cause inflammatory responses and AMD features [63].
Age-related macular degeneration is characterised by degenerative changes involving the outer portion of the retina, RPE, Bruch’s membrane and choriocapillaris. Drusen are considered as a hallmark of AMD and as an amorphous deposit that accumulates extracellularly in the zone between the RPE and the inner collagen zone of the Bruch’s membrane [64]. Clinically, they are divided into two main phenotypes: ‘soft and hard’, depending on their relative size and shape. A few smaller hard drusen (<65 μm) can be found in at least 95% of the elderly population, but do not represent AMD. Only the presence of larger drusen (>125 μm), especially soft drusen (> 125–250 μm) in the macula, is considered as a major risk factor for the development of advanced forms of AMD, i.e. exudative-neovascular forms, especially if they are combined with pigmentation disorders [65].
In the later stage of AMD, neovascularization, exudative changes or disciform scars can occur. In the atrophic form of AMD, there is a loss of pigment epithelium or ‘attenuation’ of the choriocapillaris but without neovascularization [66]. Early pathological changes include basal deposits in the Bruch’s membrane which occur exclusively in pathological samples and have two types: a) basal laminar deposits consisting of basement membrane proteins and long collagen filaments located between RPE and basement membrane and b) basal linear deposits that are more specific for early AMD changes and consist mainly of membrane material located in the Bruch membrane, externally from the RPE basement membrane. The combination of these deposits with secondary changes in RPE results in the formation of drusen [67].
Many different molecules have been identified in drusen, including glycoconjugates and other compounds also found in atherosclerotic plaque (hence the link between atherosclerosis and AMD formation by some authors), including vitronectin, apoprotein B and E, α-crystalline, HtrA1 and lipids [68, 69, 70]. Macrophages found in drusen regression suggest a possible hypothesis that macrophages are involved in the process of degradation of deposits within the Bruch membrane [71]. Activated microglias have also been found in AMD degenerative lesions [72]. Discrete nodules or hard drusen deposits consisting of hyaline-like material were found between the RPE and the Bruch membrane. Soft drusen are usually large and occur with detachment of RPE cells and diffuse changes of the Bruch membrane. They can occur in deeper damages of the RPE and choroids and lead to choroidal neovascularization or cell death in the RPE as well as geographical atrophy. Autofluorescent pigments, such as lipofuscin, which are accumulated in RPE cells, reach a size that often leads to decreased cellular function, retinal ageing and degeneration, mostly in the form of geographic atrophy [73].
Lipofuscin in RPE is the most common cause of fundus autofluorescence. These are spherical particles of micrometre size with characteristic yellow fluorescence when exposed to blue light. The main component of lipofuscin is N-retinylidine-N-retinyletanol-amine (A2E), a quaternary amine and retinoid bioproduct of visual cycle [74]. Lipofuscin synthesis is a pathogenic reaction in which the resulting A2E interferes with the function of RPE cells and leads to their apoptosis. Choroidal neovascularization can occur in the macular, peripapillary and peripheral regions. Early choroidal neovascularization occurs below the RPE cells to later break through the RPE layer and develop an exudative, haemorrhagic or disciform form of AMD. In the neovascular form of AMD, lipid accumulation occurs below the RPE or neuroretin. In the haemorrhagic form of AMD, blood penetrates through the RPE into the subretinal space and sometimes through the retina to the vitreous. In the disciform form of AMD, fibrous tissue with neovascularization and changes in RPE cells proliferates and may partially or totally replace neuroretin [75]. Additional pathological lesions include serous exudation, haemorrhage, gliosis and calcification. Macrophages have been proven both morphologically and functionally in the neovascular form of AMD [76]. Activated macrophages and microglias can secrete chemokines and cytokines, causing further cell damage, degradation of the Bruch’s membrane and angiogenesis [77].
Among AMD cases, approximately 10–15% have neovascular AMD characterised by abnormal vascular morphology and growth [8]. Vascular endothelial growth factor (VEGF) upregulation plays a crucial role in the development of neovascular AMD. Yi and assoc. [78] documented an increased VEGF expression in a study using laser to induce choroidal neovascularization (CNV) in rats. This author suggests that the macrophages could be probably the most important source of VEGF in the early phase of AMD [78]. VEGF expression in subfoveal fibrovascular membranes was concentrated in cells resembling fibroblasts, implicating a significant role of fibroblasts in the progression of CNV [79]. The results showed that even temporary overexpression of VEGF in RPE cells was sufficient to induce CNV in the rat eye [80]. Wang et al. reported that IQ protein motif-containing GTPase activating protein 1 (IQGAP1), scaffold protein with a Rac1-binding domain, regulated VEGF activation by binding to Rac1GTP in choroidal endothelial cells, activating their migration [81]. IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein that is involved in multiple cellular functions such as cell survival and trafficking [82].
The vascular endothelial dysfunction is considered as a crucial event in development and progression of choroidal vascular dysfunction [82]. Nitric oxide and nitric oxide synthase enzymes have been shown to be involved in the upregulation of VEGF. Nitric oxide synthases (NOSs) are a family of enzymes that catalyse the conversion of L-arginine into nitric oxide (NO). They are classified into three isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) [83]. The eNOS maintains the physiological function of the vascular endothelium [84]. It was demonstrated that eNOS mediated endothelium-dependent vasodilation in retinal arterioles and ophthalmic arteries [85]. NO is considered not only a mediator of vasodilation, but also a regulator of various vascular functions. For example, physiologically, NO can dilate a blood vessel, inducing relaxation of vascular smooth muscle cells (VSMCs), inhibiting cell proliferation and regulating angiogenesis and vascular permeability [86]. Bhutto et al. [87] reported that eNOS and nNOS expression was significantly decreased in the eyes of AMD patients. This author suggested that the decreased expression of eNOS and nNOS might reduce the NO production that could induce hemodynamic changes in CNV [87].
It was documented that excessive amounts of NO can have detrimental effects on cells and tissues, implicated that the production of NO is not always beneficial. In that case, NO can be an important stimulator of CNV. Ando et al. suggested that blockade of nNOS and iNOS could reduce CNV formation [88]. Excessive amounts of nitric oxide can react with the superoxide anion to form peroxynitrite, a very toxic and reactive radical which compromises vascular endothelial function [89].
There is some evidence that ROS and vascular dysfunction may together contribute to the pathology of neovascular AMD. It was demonstrated that NOX was the connection between VEGF and ROS in human choroidal endothelial cells [90]. The family of NOX consists of seven isoforms such as: NOX1, NOX2, NOX3, NOX4, NOX5, dual oxidase (Duox) 1 and Duox2) which are differentially expressed in tissues and cells [91]. NOX1, NOX2 and NOX4 are expressed in choroidal vascular endothelial cells [92]. ROS generated by NOX function as signalling molecule promoting endothelial cell proliferation, migration and tube formation [92]. Some studies documented that ROS generated from NOX2 could activate the transcription factors NF-κB and activator protein 1 (AP-1) and increase the expression of intracellular adhesion molecule (ICAM)-1 and VEGF leading to vascular hyperpermeability and retinal neovascularization [93]. Moreover, NOX4-derived ROS generation is essential for the expression of hypoxia-inducible factor 1-alpha (HIF-1α) which was linked to cell proliferation and migration of vascular smooth muscle cells [94].
One of the risk factors for AMD may be increased collagen synthesis in the choriocapillaris which is then incorporated into the Bruch’s membrane, creating thickenings that precede the appearance of linear deposits [95]. Chromatographic analysis of the drusen showed that they contained more than a hundred different proteins originated from retinal pigment epithelial cells, neuronal retinas and choriocapillaris. However, their composition differs depending on the existence i.e. absence of AMD. It is thought that certain ingredients can promote angiogenesis. The integrity of the RPE cellular structures in a culture that is chronically exposed to oxidative stress is impaired by the action of hydrogen peroxide due to the interruption of intercellular compounds. This is one of the possible mechanisms of breaking the blood-brain barrier in the pathogenesis of AMD [96].
Programmed cell death (apoptosis) is an essential protective mechanism of the organism against the accumulation and spread of damaged or unnecessary cells. An increased degree of apoptosis is observed in most ageing cell populations. A similar thing happens in RPE cells. There is an opinion that mitochondria play a key role in the regulation of apoptosis. Reactive oxygen metabolites that are formed in RPE cells exposed to the blue part of the spectrum originate in mitochondrial processes [97]. Oxidative stress can reduce the sensitivity of senescent cells to apoptosis through defective oxidative phosphorylation. The process of drusen formation is very similar to apoptotic process in the retina and predisposes the development of neovascularization during the progression of AMD [98].
In postmitotic tissues, during ageing, the oxidatively modified and damaged mitochondrial DNA are accumulated in mitochondria. It is believed that their genetic material is the main substrate of oxidative damage in the retinal pigment epithelium. With inefficient damage repair, redox potential of mitochondria in the human RPE retinal cells is compromised over time in photoreceptors as well [99].
It was suggested that other types of regulated cell death (e.g. pyroptosis, necroptosis and autophagy) may contribute to development of AMD [100]. Ferroptosis is a newly discovered, iron-dependent, regulated cell death pathway that is initiated by lipid peroxidation. It is implicated in neurodegeneration, ischemia–reperfusion injury and myocardial infarction [101]. It is characterised by iron-dependent accumulation [102, 103]. In contrast to apoptosis, ferroptosis is a pro-inflammatory condition that arises due to the release of intracellular content after the rupture of plasma membrane [104]. Under normal conditions, ferroptosis is a mechanism that protects cellular integrity, but leads to cell death when cellular integrity is compromised, while apoptosis represents a suicide mechanism that eliminates certain types of cells from the whole organism at specific time points [105].
It was documented that angiotensin II (Ang II) was implicated in the pathology of AMD. It was shown that Ang II can mediate various pathological processes in ocular blood vessels such as proliferation and migration of smooth muscle cells and pericytes, increase of VEGF expression and potentiation of VEGF-dependent angiogenic activity [106, 107]. Receptors for AngII have been identified in retinal and optic nerve blood vessels. Some studies have shown that blocking the renin-angiotensin system may delay the breakdown of the blood-retinal barrier and prevent retinal neovascularization and the development of AMD [108].
In this review, we tried to highlight the pathways of oxidative stress and their implication in the pathogenesis of AMD. Considering the unique structure and function of the retina in the eye, as well as the environment in which it is located, it indicates a significant synthesis of free radicals during normal physiological processes as well as during light absorption. The presence of free fatty acids and their exposure to free radicals make lipid peroxidation processes a daily occurrence in the eye. This was confirmed by many studies that found high concentrations of MDA, 4-HNE and other lipid peroxidation products in the eyes (and blood) of AMD patients. Oxidative damage of mitochondria and nuclear DNA was also observed in AMD patients, as well as increased products of oxidative damage of proteins. An impairment of autophagy and other types of cell death such as pyroptosis, necroptosis and ferroptosis were also described in AMD patients. The upregulation of VEGF and isoforms of NOX with impairment of NO synthesis have significant implications in the development of new blood vessels and the onset of choroidal neovascularization (CNV) in the pathogenesis of advanced-wet AMD. In view of all the above, further research is certainly needed in order to find adequate methods for disease prevention as well as adequate drugs for the treatment of various forms of AMD.
These Terms and Conditions outline the rules and regulations pertaining to the use of IntechOpen’s website www.intechopen.com and all the subdomains owned by IntechOpen located at 5 Princes Gate Court, London, SW7 2QJ, United Kingdom.
',metaTitle:"Terms and Conditions",metaDescription:"These terms and conditions outline the rules and regulations for the use of IntechOpen Website at https://intechopen.com and all its subdomains owned by Intech Limited located at 7th floor, 10 Lower Thames Street, London, EC3R 6AF, UK.",metaKeywords:null,canonicalURL:"/page/terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"By accessing the website at www.intechopen.com you are agreeing to be bound by these Terms of Service, all applicable laws and regulations, and agree that you are responsible for compliance with any applicable local laws. Use and/or access to this site is based on full agreement and compliance of these Terms. All materials contained on this website are protected by applicable copyright and trademark laws.
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\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Challenges of water treatment in rural and urban areas will be outlined.",book:{id:"6682",slug:"the-relevance-of-hygiene-to-health-in-developing-countries",title:"The Relevance of Hygiene to Health in Developing Countries",fullTitle:"The Relevance of Hygiene to Health in Developing Countries"},signatures:"Josephine Treacy",authors:[{id:"238173",title:"Dr.",name:"Josephine",middleName:null,surname:"Treacy",slug:"josephine-treacy",fullName:"Josephine Treacy"}]},{id:"44219",doi:"10.5772/54973",title:"Disaster Management Discourse in Bangladesh: A Shift from Post-Event Response to the Preparedness and Mitigation Approach Through Institutional Partnerships",slug:"disaster-management-discourse-in-bangladesh-a-shift-from-post-event-response-to-the-preparedness-and",totalDownloads:4124,totalCrossrefCites:4,totalDimensionsCites:28,abstract:null,book:{id:"3054",slug:"approaches-to-disaster-management-examining-the-implications-of-hazards-emergencies-and-disasters",title:"Approaches to Disaster Management",fullTitle:"Approaches to Disaster Management - Examining the Implications of Hazards, Emergencies and Disasters"},signatures:"C. Emdad Haque and M. Salim Uddin",authors:[{id:"163390",title:"Dr.",name:"C. Emdad",middleName:null,surname:"Haque",slug:"c.-emdad-haque",fullName:"C. Emdad Haque"},{id:"168399",title:"Mr.",name:"Mohammed S",middleName:null,surname:"Uddin",slug:"mohammed-s-uddin",fullName:"Mohammed S Uddin"}]},{id:"59705",doi:"10.5772/intechopen.74943",title:"Augmented Reality Trends in Education between 2016 and 2017 Years",slug:"augmented-reality-trends-in-education-between-2016-and-2017-years",totalDownloads:2513,totalCrossrefCites:19,totalDimensionsCites:27,abstract:"The aim of this chapter is to review literature regarding using augmented reality (AR) in education articles published in between 2016 and 2017 years. The literature source was Web of Science and SSCI, SCI-EXPANDED, A&HCI, CPCI-S, CPCI-SSH, and ESCI indexes. Fifty-two articles were reviewed; however, 14 of them were not been included in the study. As a result, 38 articles were examined. Level of education, field of education, and material types of AR used in education and reported educational advantages of AR have been investigated. All articles are categorized according to target groups, which are early childhood education, primary education, secondary education, high school education, graduate education, and others. AR technology has been mostly carried out in primary and graduate education. “Science education” is the most explored field of education. Mobile applications and marker-based materials on paper have been mostly preferred. The major advantages indicated in the articles are “Learning/Academic Achievement,” “Motivation,” and “Attitude”.",book:{id:"6543",slug:"state-of-the-art-virtual-reality-and-augmented-reality-knowhow",title:"State of the Art Virtual Reality and Augmented Reality Knowhow",fullTitle:"State of the Art Virtual Reality and Augmented Reality Knowhow"},signatures:"Rabia M. Yilmaz",authors:[{id:"225838",title:"Dr.",name:"Rabia",middleName:null,surname:"Yilmaz",slug:"rabia-yilmaz",fullName:"Rabia Yilmaz"}]},{id:"45760",doi:"10.5772/56967",title:"Parenting and Culture – Evidence from Some African Communities",slug:"parenting-and-culture-evidence-from-some-african-communities",totalDownloads:9634,totalCrossrefCites:10,totalDimensionsCites:27,abstract:null,book:{id:"3440",slug:"parenting-in-south-american-and-african-contexts",title:"Parenting in South American and African Contexts",fullTitle:"Parenting in South American and African Contexts"},signatures:"Patricia Mawusi Amos",authors:[{id:"162496",title:"Mrs.",name:"Patricia",middleName:"Mawusi",surname:"Mawusi Amos",slug:"patricia-mawusi-amos",fullName:"Patricia Mawusi Amos"}]}],mostDownloadedChaptersLast30Days:[{id:"58890",title:"Philosophy and Paradigm of Scientific Research",slug:"philosophy-and-paradigm-of-scientific-research",totalDownloads:14074,totalCrossrefCites:9,totalDimensionsCites:17,abstract:"Before carrying out the empirical analysis of the role of management culture in corporate social responsibility, identification of the philosophical approach and the paradigm on which the research carried out is based is necessary. Therefore, this chapter deals with the philosophical systems and paradigms of scientific research, the epistemology, evaluating understanding and application of various theories and practices used in the scientific research. The key components of the scientific research paradigm are highlighted. Theories on the basis of which this research was focused on identification of the level of development of the management culture in order to implement corporate social responsibility are identified, and the stages of its implementation are described.",book:{id:"5791",slug:"management-culture-and-corporate-social-responsibility",title:"Management Culture and Corporate Social Responsibility",fullTitle:"Management Culture and Corporate Social Responsibility"},signatures:"Pranas Žukauskas, Jolita Vveinhardt and Regina Andriukaitienė",authors:[{id:"179629",title:"Prof.",name:"Jolita",middleName:null,surname:"Vveinhardt",slug:"jolita-vveinhardt",fullName:"Jolita Vveinhardt"}]},{id:"74550",title:"School Conflicts: Causes and Management Strategies in Classroom Relationships",slug:"school-conflicts-causes-and-management-strategies-in-classroom-relationships",totalDownloads:2328,totalCrossrefCites:1,totalDimensionsCites:10,abstract:"Conflicts cannot cease to exist, as they are intrinsic to human beings, forming an integral part of their moral and emotional growth. Likewise, they exist in all schools. The school is inserted in a space where the conflict manifests itself daily and assumes relevance, being the result of the multiple interpersonal relationships that occur in the school context. Thus, conflict is part of school life, which implies that teachers must have the skills to manage conflict constructively. Recognizing the diversity of school conflicts, this chapter aimed to present its causes, highlighting the main ones in the classroom, in the teacher-student relationship. It is important to conflict face and resolve it with skills to manage it properly and constructively, establishing cooperative relationships, and producing integrative solutions. Harmony and appreciation should coexist in a classroom environment and conflict should not interfere, negatively, in the teaching and learning process. This bibliography review underscore the need for during the teachers’ initial training the conflict management skills development.",book:{id:"7827",slug:"interpersonal-relationships",title:"Interpersonal Relationships",fullTitle:"Interpersonal Relationships"},signatures:"Sabina Valente, Abílio Afonso Lourenço and Zsolt Németh",authors:[{id:"324514",title:"Ph.D.",name:"Sabina",middleName:"N.",surname:"Valente",slug:"sabina-valente",fullName:"Sabina Valente"},{id:"326375",title:"Ph.D.",name:"Abílio",middleName:"Afonso",surname:"Lourenço",slug:"abilio-lourenco",fullName:"Abílio Lourenço"},{id:"329177",title:"Dr.",name:"Zsolt",middleName:null,surname:"Németh",slug:"zsolt-nemeth",fullName:"Zsolt Németh"}]},{id:"52475",title:"Teenage Pregnancies: A Worldwide Social and Medical Problem",slug:"teenage-pregnancies-a-worldwide-social-and-medical-problem",totalDownloads:8293,totalCrossrefCites:6,totalDimensionsCites:8,abstract:"Teenage pregnancies and teenage motherhood are a cause for concern worldwide. From a historical point of view, teenage pregnancies are nothing new. For much of human history, it was absolutely common that girls married during their late adolescence and experienced first birth during their second decade of life. This kind of reproductive behavior was socially desired and considered as normal. Nowadays, however, the prevention of teenage pregnancies and teenage motherhood is a priority for public health in nearly all developed and increasingly in developing countries. For a long time, teenage pregnancies were associated with severe medical problems; however, most of data supporting this viewpoint have been collected some decades ago and reflect mainly the situation of per se socially disadvantaged teenage mothers. According to more recent studies, teenage pregnancies are not per se risky ones. A clear risk group are extremely young teenage mothers (younger than 15 years) who are confronted with various medical risks, such as preeclampsia, preterm labor, and small for gestational age newborns but also marked social disadvantage, such as poverty, unemployment, low educational level, and single parenting. In the present study, the prevalence and outcome of teenage pregnancies in Austria are focused on.",book:{id:"5392",slug:"an-analysis-of-contemporary-social-welfare-issues",title:"An Analysis of Contemporary Social Welfare Issues",fullTitle:"An Analysis of Contemporary Social Welfare Issues"},signatures:"Sylvia Kirchengast",authors:[{id:"188289",title:"Prof.",name:"Sylvia",middleName:null,surname:"Kirchengast",slug:"sylvia-kirchengast",fullName:"Sylvia Kirchengast"}]},{id:"58060",title:"Pedagogy of the Twenty-First Century: Innovative Teaching Methods",slug:"pedagogy-of-the-twenty-first-century-innovative-teaching-methods",totalDownloads:8832,totalCrossrefCites:17,totalDimensionsCites:22,abstract:"In the twenty-first century, significant changes are occurring related to new scientific discoveries, informatization, globalization, the development of astronautics, robotics, and artificial intelligence. This century is called the age of digital technologies and knowledge. How is the school changing in the new century? How does learning theory change? Currently, you can hear a lot of criticism that the classroom has not changed significantly compared to the last century or even like two centuries ago. Do the teachers succeed in modern changes? The purpose of the chapter is to summarize the current changes in didactics for the use of innovative teaching methods and study the understanding of changes by teachers. In this chapter, we consider four areas: the expansion of the subject of pedagogy, environmental approach to teaching, the digital generation and the changes taking place, and innovation in teaching. The theory of education, figuratively speaking, has two levels. At the macro-level, in the “education-society” relationship, decentralization and diversification, internationalization of education, and the introduction of digital technologies occur. At the micro-level in the “teacher-learner” relationship, there is an active mix of traditional and innovative methods, combination of an activity approach with an energy-informational environment approach, cognition with constructivism and connectivism.",book:{id:"5980",slug:"new-pedagogical-challenges-in-the-21st-century-contributions-of-research-in-education",title:"New Pedagogical Challenges in the 21st Century",fullTitle:"New Pedagogical Challenges in the 21st Century - Contributions of Research in Education"},signatures:"Aigerim Mynbayeva, Zukhra Sadvakassova and Bakhytkul\nAkshalova",authors:[{id:"201997",title:"Dr.",name:"Aigerim",middleName:null,surname:"Mynbayeva",slug:"aigerim-mynbayeva",fullName:"Aigerim Mynbayeva"},{id:"209208",title:"Dr.",name:"Zukhra",middleName:null,surname:"Sadvakassova",slug:"zukhra-sadvakassova",fullName:"Zukhra Sadvakassova"},{id:"209210",title:"Dr.",name:"Bakhytkul",middleName:null,surname:"Akshalova",slug:"bakhytkul-akshalova",fullName:"Bakhytkul Akshalova"}]},{id:"58894",title:"Research Ethics",slug:"research-ethics",totalDownloads:3371,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Research ethics is closely related to the ethical principles of social responsibility. This research covers a wide context of working with people, so the researchers raised a task not only to gain confidence in the respondents’ eyes, to receive reliable data, but also to ensure the transparency of the science. This chapter discusses the theoretical and practical topics of research, after evaluation of which ethical principles of organization and conducting the research are presented. There is a detailed description of how and what ethical principles were followed on the different stages of the research.",book:{id:"5791",slug:"management-culture-and-corporate-social-responsibility",title:"Management Culture and Corporate Social Responsibility",fullTitle:"Management Culture and Corporate Social Responsibility"},signatures:"Pranas Žukauskas, Jolita Vveinhardt and Regina Andriukaitienė",authors:[{id:"179629",title:"Prof.",name:"Jolita",middleName:null,surname:"Vveinhardt",slug:"jolita-vveinhardt",fullName:"Jolita Vveinhardt"}]}],onlineFirstChaptersFilter:{topicId:"23",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83053",title:"Apologies in L2 French in Canadian Context",slug:"apologies-in-l2-french-in-canadian-context",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.106557",abstract:"This article presents the results of an analysis of apology strategies in native and non-native French in Canadian context. The data used were obtained through a Discourse Completion Task questionnaire that was completed by a group of native French speakers (FL1) and a group of learners of French as a second language (FL2). The goal was to identify and compare pragmatic and linguistic choices made by both groups when apologizing in three different situations. Several differences and similarities emerged between the two groups regarding the use of exclamations to introduce apologies, direct apologies, indirect apologies, and supportive acts. For instance, it was found that the FL1 speakers used “expressions of regret”, “offers of apology” 15 and “requests for forgiveness” to apologize directly, while the FL2 speaking informants used 16 only “expressions of regret” and “offers of apology”. While the respondents of both groups 17 mostly chose “offers of repair” to apologize indirectly, they displayed divergent preferences 18 regarding the use of other indirect apology strategies. Differences were also documented 19 with respect to the use of intensification devices in direct apologies and the use of supportive acts. Implications of the findings for L2 French pedagogy were also discussed.",book:{id:"11480",title:"Second Language Acquisition - Learning Theories and Recent Approaches",coverURL:"https://cdn.intechopen.com/books/images_new/11480.jpg"},signatures:"Bernard Mulo Farenkia"},{id:"83049",title:"An Ethnographic Study on Sense of a Community: The “Awramba” Experience",slug:"an-ethnographic-study-on-sense-of-a-community-the-awramba-experience",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105953",abstract:"The study was conducted on “Awramba” Community who are living in “Amhara” region, south “Gondor” Zone, Ethiopia. The general objective of this study was to capture an understanding of sense of community in “Awramba” community. The study tried to answer the following questions: How the community was established? What are the criteria to be part of the community? What are the shared values of social practice that has survived for the test of time? What is the historical background of the “Awramba” Community? The researcher used realist ethnography method to achieve the above objective and to answer the questions. In-depth interview and observational guide techniques were applied to collect reliable data for the study. The observation and in-depth interview data were analyzed qualitatively. The study showed the following themes: Membership criteria of the community are based on adhering to the community norm. They have a strong sense of community based on shared story, cooperative work, marriage and mourning values, religious view, gender equality, commitment to be honest, and solving their problem by themselves. The emotional connection of the “Awramba” community is strengthened by their common celebration of the yearly anniversary of New Year and scheduled meeting.",book:{id:"11429",title:"Sustainability, Ecology, and Religions of the World",coverURL:"https://cdn.intechopen.com/books/images_new/11429.jpg"},signatures:"Nassir-Maru Yesuf"},{id:"83014",title:"Culture: A Pillar of Organizational Sustainability",slug:"culture-a-pillar-of-organizational-sustainability",totalDownloads:3,totalDimensionsCites:0,doi:"10.5772/intechopen.106523",abstract:"Sustainability is a concern that permeates all levels of society and is premised on meeting the needs of the present without compromising the ability of future generations to meet theirs. More recently, policies and research have emerged that guide organizations to align their activities with the broader sustainable development agendas, including cultural issues, not just economic, social, and environmental ones. Culture is the material and immaterial attribute of society. It incorporates social organizations, literature, religion, myths, beliefs, behaviors and entrepreneurial practices of the productive segment, use of technology, and expressive art forms on which future generations depend. Thus, cultural sustainability is a fundamental issue and is configured as the fourth pillar of sustainability, equal to social, economic, and environmental issues, which has to do with the ability to sustain or continue with cultural beliefs and practices, preserve cultural heritage as its entity, and try to answer whether any culture will exist in the future. The importance of cultural sustainability lies in its power to influence people. Their beliefs are in the decisions made by society. Thus, there can be no sustainable development without including culture.",book:{id:"11429",title:"Sustainability, Ecology, and Religions of the World",coverURL:"https://cdn.intechopen.com/books/images_new/11429.jpg"},signatures:"Clea Beatriz Macagnan and Rosane Maria Seibert"},{id:"82949",title:"Corruption and Deterioration of Democracy: The Brazilian Lesson",slug:"corruption-and-deterioration-of-democracy-the-brazilian-lesson",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.106194",abstract:"Although it has emerged, nationally and internationally, as one of the largest investigations against political corruption, Operation Car Wash—at its peak of popular prestige—cleared the path for the political rise of Jair Bolsonaro to the Presidency of the Republic of Brazil. And by doing so, to a certain extent, it paved the way for a set of arbitrary practices that today threaten and weaken the main Brazilian democratic institutions. Brazilian democracy today pays a high price for the Judiciary’s lethargic and condescending response to the unorthodox and illegal practices of Federal Judge Sérgio Moro during the golden years of Operation Car Wash (2014–2018). The lesson that the Brazilian episode brings to the international legal community is that the constant disrespect for the rules of due criminal procedure in large cases of corruption erodes the institutional bases that support the proper confrontation of this type of crime. The pertinent fight against corruption in a democracy can only take place in strict obedience to the law.",book:{id:"11772",title:"Corruption - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11772.jpg"},signatures:"Fabio Roberto D’Avila and Theodoro Balducci de Oliveira"},{id:"82903",title:"Walking Accessibility to Primary Healthcare Services: An Inequity Factor for Olders in the Lisbon Metropolitan Area (Portugal)",slug:"walking-accessibility-to-primary-healthcare-services-an-inequity-factor-for-olders-in-the-lisbon-met",totalDownloads:4,totalDimensionsCites:0,doi:"10.5772/intechopen.106265",abstract:"This chapter discusses the walking accessibility to primary healthcare by the olders in Lisbon Metropolitan Area (LMA), Portugal, and its contribution for age-friendly environments as a factor of inequity. Constrains emerged from the collation of the supply approach, represented by service catchment areas based on walking distance time, and the demand approach, through a survey. The location and density of primary health network are a major factor, as it is related to distinct land use patterns within the LMA. The settlement structure influences the potential walkability to primary healthcare. The discrepancy between the potential walking accessibility and the real options is notorious, as olders` choices are diversified in terms of transportation modes and destinations, but mostly keeping relatively short time distances. This phenomenon is also influenced by factors such as personal preference, difficulty to walk, negative perceptions about the surroundings, and insufficient care support. This debate is already an effective concern of local authorities with spatial planning, social and health competences, insofar as solutions in terms of service flexibility and new travel solutions adapted to the specific needs of the olders are a growing reality in the LMA, promoting more age-friendly, health, and inclusive environments, and hence an equitable metropolis.",book:{id:"11479",title:"Social Aspects of Ageing - Selected Challenges, Analyses, and Solutions",coverURL:"https://cdn.intechopen.com/books/images_new/11479.jpg"},signatures:"Eduarda Marques da Costa, Ana Louro, Nuno Marques da Costa, Mariana Dias and Marcela Barata"},{id:"82834",title:"Perspective Chapter: Social Work Education in University Curricula for Sustainable Development",slug:"perspective-chapter-social-work-education-in-university-curricula-for-sustainable-development",totalDownloads:5,totalDimensionsCites:0,doi:"10.5772/intechopen.106246",abstract:"Universities of both global North and South have been changing from the traditional teaching-learning centers to cater to sustainability issues of those countries. Yet, there is a remarkable difference between the universities in the developed and the developing world. It has been found out that the different disciplines of university curricula can be integrated to address and minimize the adverse effects of unsustainability issues. The graduates of the universities will be the future leaders who have to cater to the needs and cope with the challenges of the next generation. There is a dearth of professional social workers to provide the necessary services as numerous catastrophes occur. The global society needs individuals who are equally sound in the knowledge of theory and the experience of practice. As the contemporary global issues become complex, the world needs competent social workers who can serve in different fields of practice. Social work could be the pivotal discipline in understanding common tragedies of the people to apply problem-solving model with the practitioners who are equipped with twenty-first century skills. Social work has to take a transition from a unidisciplinary to a multi- and trans-disciplinary perspective in achieving this objective.",book:{id:"11095",title:"Social Work - Perspectives on Leadership and Organisation",coverURL:"https://cdn.intechopen.com/books/images_new/11095.jpg"},signatures:"Upul Lekamge"}],onlineFirstChaptersTotal:146},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,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:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{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"}}}},{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"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"July 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:14,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). 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Dr. Khalid\\'s research interests include leadership and negotiations, digital transformations, gamification, eLearning, blockchain, Big Data, and management of information technology. Dr. Bilal Khalid also serves as an academic editor at Education Research International and a reviewer for international journals.",institutionString:"KMITL Business School",institution:{name:"King Mongkut's Institute of Technology Ladkrabang",country:{name:"Thailand"}}},{id:"418514",title:"Dr.",name:"Muhammad",middleName:null,surname:"Mohiuddin",slug:"muhammad-mohiuddin",fullName:"Muhammad Mohiuddin",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038UqSfQAK/Profile_Picture_2022-05-13T10:39:03.jpg",biography:"Dr. Muhammad Mohiuddin is an Associate Professor of International Business at Laval University, Canada. He has taught at Thompson Rivers University, Canada; University of Paris-Est, France; Osnabruck University of Applied Science, Germany; and Shanghai Institute of Technology and Tianjin University of Technology, China. He has published research in Research Policy, Applied Economics, Review of Economic Philosophy, Strategic Change, International Journal of Logistics, Sustainability, Journal of Environmental Management, Journal of Global Information Management, Journal of Cleaner Production, M@N@GEMENT, and more. He is a member of CEDIMES Institut (France), Academy of International Business (AIB), Strategic Management Society (SMS), Academy of Management (AOM), Administrative Science Association of Canada (ASAC), and Canadian council of small business and entrepreneurship (CCSBE). He is currently the director of the Research Group on Contemporary Asia (GERAC) at Laval University. He is also co-managing editor of Transnational Corporations Review and a guest editor for Electronic Commerce Research and Journal of Internet Technology.",institutionString:"Université Laval",institution:{name:"Université Laval",country:{name:"Canada"}}},{id:"189147",title:"Dr.",name:"Hailan",middleName:null,surname:"Salamun",slug:"hailan-salamun",fullName:"Hailan Salamun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/189147/images/19274_n.jpeg",biography:"Hailan Salamun, (Dr.) was born in Selangor, Malaysia and graduated from Tunku Ampuan Jamaah Religious High School at Shah Alam. Obtained a degree from the International Islamic University (UIA), Gombak in the field of Islamic Revealed Knowledge and Heritage. Next, I furthered my studies to the professional level to obtain a Diploma in Education at UIA. After serving for several years in school, I furthered my studies to the Master of Dakwah and Leadership at Universiti Kebangsaan Malaysia (UKM), Bangi. 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