\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"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:"8300",leadTitle:null,fullTitle:"Vascular Biology - Selection of Mechanisms and Clinical Applications",title:"Vascular Biology",subtitle:"Selection of Mechanisms and Clinical Applications",reviewType:"peer-reviewed",abstract:"The two main causes of death in the world are directly related to cardiovascular system disorders, ischemic heart disease, and stroke. These pathological conditions are caused by complex molecular mechanisms related to endothelial dysfunction and, finally, structural and functional alterations of blood vessels. Clinical evidence demonstrates the relevance of knowledge about vascular biology, from molecular mechanisms to clinical applications, especially for students of medical sciences or basic sciences. This book is an international effort of collaboration, with the purpose to create an academic tool for students or people interested in learning about vascular biology. I invite the readers to check the chapters and explore the topics developed by experts in the field.",isbn:"978-1-83969-036-5",printIsbn:"978-1-83969-035-8",pdfIsbn:"978-1-83969-037-2",doi:"10.5772/intechopen.78429",price:119,priceEur:129,priceUsd:155,slug:"vascular-biology-selection-of-mechanisms-and-clinical-applications",numberOfPages:228,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"478078d1af7d5e3c606698a33dc2550b",bookSignature:"Marcelo",publishedDate:"November 11th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8300.jpg",numberOfDownloads:10225,numberOfWosCitations:2,numberOfCrossrefCitations:7,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:14,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:23,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 18th 2018",dateEndSecondStepPublish:"September 4th 2018",dateEndThirdStepPublish:"November 3rd 2018",dateEndFourthStepPublish:"January 22nd 2019",dateEndFifthStepPublish:"March 23rd 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"202594",title:"Dr.",name:"Marcelo",middleName:null,surname:"González",slug:"marcelo-gonzalez",fullName:"Marcelo González",profilePictureURL:"https://mts.intechopen.com/storage/users/202594/images/system/202594.jpeg",biography:"Dr. Marcelo González studied Biochemistry at the Universidad de Concepción, Chile, and has a Doctoral degree in Physiological Sciences from the Universidad Católica de Chile. From 2009 he has been working at the Universidad de Concepción, first in the Department of Physiology and now in the Department of Obstetrics and Gynecology. \nHis research interest include the description of placental vascular regulation mechanisms, both in physiological conditions and in pregnancy diseases such as gestational diabetes and preeclampsia. In his laboratory, scientists use different methods of cellular biology, molecular biology, biochemistry, and vascular reactivity to elucidate the mechanisms of vascular regulation from the molecular interactions to organ function. \nRecently, his work has focused on the study of potassium channel regulation and its interaction with nitric oxide signaling in the human placenta, to determine the potential alterations of these mechanisms in gestational diabetes. \nHe has published 32 articles in WOS journals and 4 book chapters.",institutionString:"University of Concepción",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of Concepción",institutionURL:null,country:{name:"Chile"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"170",title:"Cardiology and Cardiovascular Medicine",slug:"cardiology-and-cardiovascular-medicine"}],chapters:[{id:"65637",title:"Nitric Oxide and Oxidative Stress-Mediated Cardiovascular Functionality: From Molecular Mechanism to Cardiovascular Disease",doi:"10.5772/intechopen.82556",slug:"nitric-oxide-and-oxidative-stress-mediated-cardiovascular-functionality-from-molecular-mechanism-to-",totalDownloads:1273,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:0,abstract:"The underlying pathology of most cardiovascular diseases (CVDs) such as coronary artery disease, high blood pressure, and stroke involves decreased cardiovascular contractility and anatomic alterations in cardiovascular structures. Nitric oxide (NO) regulates vascular tone and contractile function of myocardium and maintains blood vessel homeostasis. Interestingly, the effect of NO is like a double-edged sword in the body. Insufficient NO causes hypertension and atherosclerosis, while an overproduction of NO may foster inflammation and cause heart infarction and shock. In addition, growing evidences have shown that oxidative stress plays pivotal roles in the initiation and progression of CVDs. This chapter will discuss in detail the roles NO plays in the cardiovascular system under both physiological and pathological conditions. We will focus on: (1) the molecular mechanism of cardiovascular contraction, (2) NO/Ca2+-induced muscle relaxation, (3) NO-related structural change in blood vessels, and (4) redox balance in the cardiovascular system. The relationships between these molecular mechanisms and the characteristics of CVDs will be highlighted.",signatures:"Weilue He, Maria Paula Kwesiga, Eyerusalem Gebreyesus and Sijia Liu",downloadPdfUrl:"/chapter/pdf-download/65637",previewPdfUrl:"/chapter/pdf-preview/65637",authors:[null],corrections:null},{id:"64765",title:"Potassium Channels in the Vascular Diseases",doi:"10.5772/intechopen.82474",slug:"potassium-channels-in-the-vascular-diseases",totalDownloads:852,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The vessel wall is an intricate structure composed of three layers: the intima (consisting of endothelial cells), media (consisting of smooth muscle cells and elastic fibers), and externa (consisting of the extracellular matrix scaffold). The homeostasis of the vasculature depends on the consistent function of each layer. In the vascular system, potassium channels are well known to regulate vascular function. The interactions between vascular conditions and membrane potential are complicated. In this chapter, we will focus on the functional regulation of KCa channel, KATP channel, and KV channel in the vascular system. Researchers may continuously obtain insights into the functions of these channels and identify new therapeutic targets for vascular diseases.",signatures:"Yan-Rong Zhu, Xiao-Xin Jiang, Peng Ye, Shao-liang Chen and Dai-Min Zhang",downloadPdfUrl:"/chapter/pdf-download/64765",previewPdfUrl:"/chapter/pdf-preview/64765",authors:[null],corrections:null},{id:"73096",title:"L-Arginine/Nitric Oxide Pathway and KCa Channels in Endothelial Cells: A Mini-Review",doi:"10.5772/intechopen.93400",slug:"l-arginine-nitric-oxide-pathway-and-kca-channels-in-endothelial-cells-a-mini-review",totalDownloads:628,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"The endothelium is an organ with a key role in the maintenance of cardiovascular health through the regulation of vascular tone, vascular resistance, blood flow, and arterial pressure. These functions are related with the synthesis and release of vasoactive molecules, mainly vasodilators like nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Both factors are released and diffused from endothelial cells to the smooth muscle cells, where there is a subsequent activation of signaling pathways that finally decrease the intracellular calcium to induce the vascular relaxation. The study of the molecular mechanisms that underlie the endothelial function still is in development, but from the evidence obtained from the endothelial cells in vitro studies are possible to partially describe the pathways to regulate the physiological endothelial function and the disturbances in pathological conditions. In this mini-review, we describe the main mechanisms for NO synthesis and the role of potassium channels related with EDHF. We include schemes and graphical summaries for better understanding of the molecular regulation of vascular tone in the human cardiovascular system.",signatures:"Marcelo González and José Carlos Rivas",downloadPdfUrl:"/chapter/pdf-download/73096",previewPdfUrl:"/chapter/pdf-preview/73096",authors:[{id:"202594",title:"Dr.",name:"Marcelo",surname:"González",slug:"marcelo-gonzalez",fullName:"Marcelo González"}],corrections:null},{id:"69145",title:"The Role of Physical Activity on Insulin Resistance-Associated Endothelial Dysfunction",doi:"10.5772/intechopen.89314",slug:"the-role-of-physical-activity-on-insulin-resistance-associated-endothelial-dysfunction",totalDownloads:708,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Enhanced physical activity and cardiorespiratory fitness significantly impact morbidity and mortality across the spectrum of noncommunicative chronic illnesses experienced by modern lifestyles. Physical activity itself prompts an intricate interplay of physiological responses across vital organ systems including microvascular adaptations to optimize nutrient, oxygen, and hormone delivery, some of which involves insulin-mediated regulation. Insulin has been known to act on the vasculature in multiple ways by its effects on endothelium and skeletal muscle blood flow. This is important to understand as it has implications for conditions associated with insulin resistance (IR) such as obesity, metabolic syndrome, prediabetes, diabetes, and polycystic ovarian syndrome among others. These conditions are associated with increased morbidity and mortality contributed by endothelial dysfunction via increased atherosclerosis, hypertension, and increased free fatty acid levels. In this chapter, we will discuss the effects of insulin on the vasculature, IR on the endothelium, and lastly, what impact physical activity may have on such processes.",signatures:"Shruti M. Gandhi, Eric S. Nylen and Sabyasachi Sen",downloadPdfUrl:"/chapter/pdf-download/69145",previewPdfUrl:"/chapter/pdf-preview/69145",authors:[null],corrections:null},{id:"65781",title:"Therapeutic Applications and Mechanisms of YC-1: A Soluble Guanylate Cyclase Stimulator",doi:"10.5772/intechopen.84572",slug:"therapeutic-applications-and-mechanisms-of-yc-1-a-soluble-guanylate-cyclase-stimulator",totalDownloads:764,totalCrossrefCites:2,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Nitric oxide (NO) is an essential endogenous vasodilator to maintain vascular homeostasis, whose effects are mainly mediated by NO-dependent soluble guanylate cyclase (sGC) which catalyzes the synthesis of cyclic guanosine monophosphate (cGMP), a critical mediator of vascular relaxation. YC-1, a novel NO-independent sGC stimulator, was first introduced as an inhibitor of platelet aggregation and thrombosis. Accumulating studies revealed that YC-1 has multiple medication potentials to use for a broad spectrum of diseases ranging from cardiovascular diseases to cancers. In contrast to NO donors, YC-1 has a more favorable safety profile and low medication tolerance. In this chapter, we introduce canonical and pathological roles of NO, review activations, and regulatory mechanisms of YC-1 on NO-independent sGC/cGMP pathway and present the potential pharmacological applications and molecular mechanisms of YC-1.",signatures:"Chieh-Hsi Wu, Chun-Hsu Pan and Ming-Jyh Sheu",downloadPdfUrl:"/chapter/pdf-download/65781",previewPdfUrl:"/chapter/pdf-preview/65781",authors:[null],corrections:null},{id:"70933",title:"Giant Cell Arteritis: Current Advances in Pathogenesis and Treatment",doi:"10.5772/intechopen.91018",slug:"giant-cell-arteritis-current-advances-in-pathogenesis-and-treatment",totalDownloads:686,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Giant cell arteritis (GCA) is the most common vasculitis in adults, with the incidence increasing with the advancing age. The aorta and its branches, especially the carotid extracranial branches, are the classic targets of inflammation in GCA. Visual loss, upper limb ischemia, and stroke are complications described. Suspicion of GCA is a medical emergency, and patients need to be quickly diagnosed/treated to prevent irreversible damage. Headache is the most common symptom, and a new-onset headache in older adults should always raise the suspicion of GCA. Patients may also present with scalp tenderness or tongue/jaw pain. GCA is often found to be the cause of an obscure-origin fever in older patients. A positive temporal artery biopsy is considered the gold standard for the diagnosis, but imaging techniques enable the assessment of cranial and extracranial arteries and the aorta. Ultrasound of temporal arteries is recommended and noncompressible “halo” sign is the typical finding. PET, MRI, or CT may be useful for the detection of the disease in the aorta and other vessels. The treatment must be started promptly with prednisone 1 mg/kg/day. When visual symptoms/unilateral visual loss is present, methylprednisolone pulse is recommended. Methotrexate, leflunomide and tocilizumab may be effective and well-tolerated glucocorticoid-sparing agents in GCA. Cardiovascular diseases are the leading causes of death in patients.",signatures:"Marília A. Dagostin and Rosa M.R. Pereira",downloadPdfUrl:"/chapter/pdf-download/70933",previewPdfUrl:"/chapter/pdf-preview/70933",authors:[null],corrections:null},{id:"61983",title:"Anomalous Origin of Coronary Arteries",doi:"10.5772/intechopen.76912",slug:"anomalous-origin-of-coronary-arteries",totalDownloads:989,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Coronary arteries supply the heart muscle with blood maintaining myocardial hemostasis and function. Coronary artery anomalies may persist after birth affecting cardiovascular system through haemodynamic impairment caused from shunting, ischaemia, especially in young children or adolescents and young adults. In patients undergoing coronary angiography the incidence of anomalous origination of the left coronary artery from right sinus is 0.15% and the right coronary artery from the left sinus is 0.92%. A recent classification of the coronary anomalies is based on anatomical considerations, recognizing three categories: anomalies of the origin and course, anomalies of the intrinsic coronary artery anatomy, and anomalies of the termination. In the setting of anomalous coronary artery from the opposite sinus, the proximal anomalous CA may run anterior to the pulmonary trunk (prepulmonic), posterior to the aorta (retroaortic), septal (subpulmonic), or between the pulmonary artery and the aorta itself (interarterial). Among them, only those with an interarterial aorta-pulmonary course are regarded as hidden conditions at risk of ischaemia and even sudden death. We presented two cases with anomalous origin of coronary arteries from opposite sinus, and two other cases with anomalous origin of left circumflex artery. The atherosclerotic coronary artery disease leads to the need of coronarography which can find out the presence of coronary artery anomalies. Anomalous origin of coronary artery that is present with atherosclerotic changes continues to exist as a challenge during treatment in interventional cardiology.",signatures:"Xhevdet Krasniqi and Hajdin Çitaku",downloadPdfUrl:"/chapter/pdf-download/61983",previewPdfUrl:"/chapter/pdf-preview/61983",authors:[null],corrections:null},{id:"71306",title:"Systemic Sclerosis",doi:"10.5772/intechopen.91318",slug:"systemic-sclerosis",totalDownloads:656,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Systemic sclerosis (SSc) is a chronic, autoimmune disease which can affect the blood vessels, the visceral organs, and the skin. SSc, most commonly, develops between the ages of 30 and 50, but it can be seen at any age. In terms of skin involvement, SSc can be classified as limited or diffuse. Its etiopathogenesis is still unclear. Microvascular dysfunction is thought to be followed by immunological activation, collagen and extracellular matrix deposition, and finally fibrosis. Diagnosis is based on clinical presentation. Sclerosis of the metacarpophalangeal and/or metatarsophalangeal joints is the major diagnostic criterion, whereas sclerodactylia, digital ulcers (DU), and pulmonary fibrosis are the minor criteria. SSc is diagnosed with one major criterion or two minor criteria. Detection of autoantibodies can help the diagnosis. Antinuclear antibody (ANA), anti-centromere antibody, anti-scl 70, RNA polymerase 1 and 3, and anti-fibrillin antibody can be found positive in SSc. SSc must be differentiated from all sclerosing diseases and the diseases with Raynaud’s phenomenon. Visceral diseases, such as primary pulmonary hypertension, primary biliary cirrhosis, and infiltrative cardiomyopathy, should also be considered in its differential diagnosis. The main treatment goal is to target visceral involvement.",signatures:"Murat Borlu and Eda Öksüm Solak",downloadPdfUrl:"/chapter/pdf-download/71306",previewPdfUrl:"/chapter/pdf-preview/71306",authors:[null],corrections:null},{id:"72511",title:"Vasculitis and Vasculopathies",doi:"10.5772/intechopen.92778",slug:"vasculitis-and-vasculopathies",totalDownloads:657,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Our organism, as complex as it is, needs a giant vascular network to deliver nutrients to all cells, so vasculopathies and vasculitis are diseases present in all medical specialties. The skin and subcutaneous cellular tissue are irrigated by a vast vascular network, with cutaneous involvement related to these frequent pathologies. These can be restricted to the integumentary system or be part of systemic diseases with cutaneous manifestations, which make them of great interest to dermatologists. They can affect any caliber of vessels and present with several dermatological manifestations such as erythema, livedo reticularis, palpable purpura, nodules, ulcers, urticaria, hemorrhagic blisters, gangrene and other manifestations that can be isolated or associated with systemic signs and symptoms. However, there is no worldwide consensus regarding the classification of vasculitis, and the classification proposed in this chapter is based on the International Chapel Hill Conference Nomenclature of Vasculitides 2012, which is based on the size of the vessels. The purpose of this chapter is to compile a review of the most current treatments for these conditions.",signatures:"Ana Paula Urzedo, Mariane Martins Manso and Thaisa Macarini de Faria",downloadPdfUrl:"/chapter/pdf-download/72511",previewPdfUrl:"/chapter/pdf-preview/72511",authors:[null],corrections:null},{id:"72404",title:"Treatment of Vasculitis: Beyond the Basics",doi:"10.5772/intechopen.92729",slug:"treatment-of-vasculitis-beyond-the-basics",totalDownloads:546,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Vasculitis is the inflammation of blood vessels in the human body. It causes changes and remodeling in the walls of the vessels that include thickening, narrowing and scarring. As a result, the blood flow to the organs and tissues gets restricted leading to organ damage. The cause of primary vasculitis is not known; however, most cases are thought to be autoimmune. In the present era, it is getting difficult to treat vasculitis with conventional therapies, which includes cyclophosphamide, methotrexate, azathioprine and mycophenolate mofetil, with increasing rates of relapses. Since ever, corticosteroids and cytotoxic agents or immunosuppressants have been the mainstay for treating systemic vasculitis. However, the introduction of newer biological agents have bring about a revolution in the treatment of relapses and in cases where there is failure to induce and sustain remission.",signatures:"Muhammad Ishaq Ghauri and Muhammad Shariq Mukarram",downloadPdfUrl:"/chapter/pdf-download/72404",previewPdfUrl:"/chapter/pdf-preview/72404",authors:[null],corrections:null},{id:"70549",title:"The Impact of Nailfold Capillaroscopy in the Approach of Microcirculation",doi:"10.5772/intechopen.90525",slug:"the-impact-of-nailfold-capillaroscopy-in-the-approach-of-microcirculation",totalDownloads:786,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Nailfold capillaroscopy (NFC) is a simple, validated, and noninvasive method to assess the microcirculation, through direct visualization of the capillaries. Main patterns are classified, according to Cutolo et al., as scleroderma, further divided into early, active, or late patterns, or nonscleroderma. NFC findings include dilated loops, tortuosities, meandering or bushy capillaries, hemorrhage, or architectural distortion. NFC use has been indicated for the evaluation of Raynaud’s phenomenon (RP), once it permits the distinction between primary and secondary RP. NFC results accounts for diagnostic criteria of systemic sclerosis, but they can also be useful in staging other connective tissue autoimmune diseases, like systemic lupus erythematosus, inflammatory myositis, or vasculitis. The CSURI index uses NFC for prediction of digital ulcer relapse. Recent evidence revealed NFC can also be applied in systemic disorders with vascular involvement.",signatures:"Vera Bernardino, Ana Rodrigues, Ana Lladó, Melissa Fernandes and António Panarra",downloadPdfUrl:"/chapter/pdf-download/70549",previewPdfUrl:"/chapter/pdf-preview/70549",authors:[null],corrections:null},{id:"72602",title:"Nailfold Capillaroscopy in Rheumatic Diseases",doi:"10.5772/intechopen.92786",slug:"nailfold-capillaroscopy-in-rheumatic-diseases",totalDownloads:690,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Nailfold capillaroscopy (NFC) has developed into an indispensable tool for rheumatologists in the evaluation of rheumatic diseases. It offers various advantages in being rapid, noninvasive, and inexpensive. With NFC we are able to visualize the microcirculatory changes in the nail beds. These changes are key to the pathogenesis of connective tissue diseases such as systemic sclerosis. Hence NFC helps in early diagnosis of various connective tissue diseases. There is a lack of standardization in the techniques used and various capillary parameters studied, which could lead to variation in the reporting of the parameters studied. In this chapter we shall try to highlight the most common parameters studied in capillaroscopy and its utility in various connective tissue diseases.",signatures:"Abhishek Patil and Isha Sood",downloadPdfUrl:"/chapter/pdf-download/72602",previewPdfUrl:"/chapter/pdf-preview/72602",authors:[null],corrections:null},{id:"71675",title:"Basic Principles in Microvascular Anastomosis and Free Tissue Transfer",doi:"10.5772/intechopen.91917",slug:"basic-principles-in-microvascular-anastomosis-and-free-tissue-transfer",totalDownloads:994,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Free tissue transfer pursues the best functional and aesthetic results in reconstructive surgery. As these techniques completely maximise the donor tissues’ disposability, these treatments have become a first-line option in many situations. When the donor site is taken form the same patient, these surgeries are often referred to as autotransplants. Free tissue transfer sustains in microvascular anastomosis, which are defined by a vessel lumen diameter inferior to 3 mm. Particular attention to some details is important in these techniques, as, for example, to preclude any damage to the vessel walls or any leakage in the microvascular anastomosis. But the success of these techniques does not only depend on an adequate vascular suture, but also on a constellation of details that must be taken into account. These go from the availability of a trained team, to the ergonomics of the surgeon, through the scrupulous cleanliness of the surgical field.",signatures:"Ignacio Vila, Iván Couto-González and Beatriz Brea-García",downloadPdfUrl:"/chapter/pdf-download/71675",previewPdfUrl:"/chapter/pdf-preview/71675",authors:[null],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"6209",title:"Endothelial Dysfunction",subtitle:"Old Concepts and New Challenges",isOpenForSubmission:!1,hash:"f6e76bbf7858977527679a6e6ad6a173",slug:"endothelial-dysfunction-old-concepts-and-new-challenges",bookSignature:"Helena Lenasi",coverURL:"https://cdn.intechopen.com/books/images_new/6209.jpg",editedByType:"Edited by",editors:[{id:"68746",title:"Dr.",name:"Helena",surname:"Lenasi",slug:"helena-lenasi",fullName:"Helena Lenasi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6373",title:"Myocardial Infarction",subtitle:null,isOpenForSubmission:!1,hash:"10bca0bf18d68ec3c1641dbc3a1ae899",slug:"myocardial-infarction",bookSignature:"Burak Pamukçu",coverURL:"https://cdn.intechopen.com/books/images_new/6373.jpg",editedByType:"Edited by",editors:[{id:"70686",title:"Dr.",name:"Burak",surname:"Pamukçu",slug:"burak-pamukcu",fullName:"Burak Pamukçu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7556",title:"Dyslipidemia",subtitle:null,isOpenForSubmission:!1,hash:"dfd1faefe925f0f8335c42cdb36256c1",slug:"dyslipidemia",bookSignature:"Samy I. McFarlane",coverURL:"https://cdn.intechopen.com/books/images_new/7556.jpg",editedByType:"Edited by",editors:[{id:"53477",title:null,name:"Samy I.",surname:"McFarlane",slug:"samy-i.-mcfarlane",fullName:"Samy I. McFarlane"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6777",title:"Advances in Extra-corporeal Perfusion Therapies",subtitle:null,isOpenForSubmission:!1,hash:"1e52fb6e834ada962495c512111f684e",slug:"advances-in-extra-corporeal-perfusion-therapies",bookSignature:"Michael S. Firstenberg",coverURL:"https://cdn.intechopen.com/books/images_new/6777.jpg",editedByType:"Edited by",editors:[{id:"64343",title:"Dr.",name:"Michael S.",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. 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\r\n\tThis publication will focus on heating, cooling, ventilation, air conditioning systems, and the energy systems they require in buildings disconnected from the thermal and electrical networks. But we will not refer here only to buildings in inhospitable or difficult to access places: society is demanding that the new and refurbished buildings of the future not only be nZEB but also that they produce even more energy than they need.
\r\n\tThis publication will aim to collect those projects and research that seek to make buildings, including urban environments, self-sufficient in terms of energy, focusing here on the solutions for HVAC and the energy systems they require and doing so from a double point of view:
\r\n\t- Complexity. As is the case with the automobile and aeronautics industries, buildings have become human-inhabited spaces with an ever-increasing technological load, which will presumably also be used in other ways, as the pandemic associated with COVID-19 has shown. In these scenarios, will HVAC systems be considered as before, or will new solutions have to be considered for new challenges?
\r\n\t- Disruptive technologies. In the coming years, the implementation of technologies such as hydrogen fuel cells, polygeneration of energy, the use of second-use electric batteries in buildings to accumulate energy from renewable energies, or the resolution of constructive solutions with 3D printing will become widespread in buildings. In this scenario, what will be the answers given by those responsible for HVAC systems?
\r\n\tIn addition, concepts such as artificial intelligence, technology transfer, biomimicry, or stigmergy will undoubtedly provide high-value solutions to new and refurbished buildings that society demands.
Emphysema, enlarged airspaces due to destruction of alveolar walls, respiratory bronchioles, and alveolar ducts, is a well-defined disease. However, in the medical practice, it is mainly encountered as an essential component of the chronic obstructive pulmonary disease syndrome. Other components are chronic bronchitis, small airway disease, small airway hyperactivity, and inflammation. Chronic obstructive pulmonary disease presents with cough, sputum production, and exertional dyspnea. In advanced cases, patients are breathless while doing even simple daily activities and may develop resting hypoxemia (blue cyanotic lips and finger nails) that requires continuous application of supplemental oxygen. Chronic obstructive pulmonary disease during its course is complicated by viral, bacterial, and fungal infections, and pneumonias and chronic obstructive pulmonary disease are the fourth leading cause of death in the USA. Urban air pollution and industrial air pollution are contributory factors in the genesis of chronic obstructive pulmonary disease, and with increase in cigarette smoking in developing countries, an estimate is that the chronic obstructive pulmonary disease will rise from the sixth to the third most common cause of death worldwide by the year 2020 [1].
\nA normal lung consists of airways and alveoli. Airways are tubes (pipes) that conduct air to alveoli where gas exchange occurs. Oxygen (O2) through alveolar wall enters into red blood cells in the alveolar capillaries and binds to hemoglobin, while carbon dioxide (CO2) goes in opposite direction being released from hemoglobin, enters alveoli, and is being exhaled.
\nThe trachea beyond the carina undergoes to about 23 generations of dichotomous branching. Airway tubes with diameter of more than 1 mm are called bronchi. With each division the diameter of the bronchus becomes smaller, but the sum of the two diameters exceeds diameter of the parent bronchus meaning that with divisions resistance to air flow becomes smaller. The bronchus consists of the lumen, mucosa, submucosa, muscularis, cartilage, and adventitia that is composed of connective tissue and contains lymphatics (Figure 1).
\nPortion of the wall of the bronchus with respiratory epithelium with cilia, smooth muscle layer, and cartilage.
Bronchi are accompanied by branches of the pulmonary artery that have a diameter of similar size to the diameter of the bronchus they follow. The mucosa is mainly lined by columnar respiratory epithelium with cilia. All columnar cells lie on a basement membrane, but since columnar cells differ in their length, nuclei differ in their position regarding basal membrane, and respiratory epithelium appears stratified, but in fact it is pseudostratified. The mucosa also contains small number of mucinous cells that contain apical mucin, small number of basal cells, and rare neuroendocrine cells. Basal cells are precursors of ciliated cells and of mucinous goblet cells. Cilia arise from the apices of the respiratory cells and serve as escalator pushing mucin upstream to the throat and nose. Neuroendocrine cells are scattered singly and form small groups, neuroepithelial bodies near the airway bifurcations. The functional significance of the neuroendocrine cells is largely unknown. Beneath the pseudostratified ciliated mucosa is the submucosa that consists of loose connective tissue harboring bronchial mucous (seromucinous) glands, lymphoid tissue aggregates, and plasma cells. Mucinous glands secrete mucus composed of glycoprotein, proteoglycans, lipids, IgA (secretory) immunoglobulins, lysozyme peroxidase, and other substances to inactivate invading microorganisms, and trap air pollution particles. Cartilage plate and muscle bundles lie beneath the submucosa. The cartilage prevents collapse of the bronchial lumen. There are about 9–12 generations of bronchi. The smallest bronchi are 1 mm in diameter. Bronchi branch into the bronchiole. Bronchioles are less than 1 mm in diameter and they lack cartilage and exocrine mucinous glands in their walls. The larger bronchioles are called terminal bronchioles and measure on average 0.5–1 mm. Since terminal bronchioles do not contain cartilage, they are also called membranous bronchioles (Figure 2).
\nTerminal bronchiolus, lined by respiratory epithelium, with no cartilage and no exocrine glands.
Terminal bronchioles consist of respiratory mucosa composed of one layer of cuboidal ciliated respiratory cells and occasional Clara cells. Clara cells are non-ciliated columnar epithelial cells with protuberant apical cytoplasm that contains granules of surfactant and protease inhibitors. Clara cells are also precursors of bronchiolar epithelial cells. Goblet cells are generally not present or rare in the mucosa of the terminal bronchioles. Beneath the mucosa of the terminal bronchiolus is a layer of smooth muscle and connective tissue adventitia. Terminal bronchioles branch into the respiratory bronchioles. One side of the airway wall of the respiratory bronchiolus is lined by simple columnar to cuboidal bronchiolar epithelium without cilia. The opposite wall is lined by alveoli, that is, the wall consists of openings of the alveolar sacs. The average diameter of respiratory bronchioles is 0.15–0.2 mm. The respiratory bronchioles branch into about two more generations of respiratory bronchioles. Respiratory bronchioles branch into alveolar ducts, straight tubular spaces bounded entirely by alveoli (Figure 3).
\nAlveolar duct and alveoli (original magnification × 100) and alveolar septa with alveoli (original magnification × 400). Courtesy of Dr. Nadia N. Naumova.
In fact all alveoli (alveolar sacs) open into the alveolar ducts. Thus alveoli have incomplete wall and alveolar sacs are outpockets of alveolar ducts. Alveoli that appear lined with alveolar walls on all sides are in fact artifact of cut section. Alveolar ducts are not accompanied by the artery. The acinus is a functional unit of the lungs that consists of terminal bronchiolus with its respiratory bronchioles, alveolar ducts, and alveoli forming tridimensional spherical space with average diameter of 7.5 mm. There are about three generations of respiratory bronchioles inside the acinus and approximately 25,000 acini in normal adult male lungs with a volume of 5.25 liters [2]. Cluster of three to five terminal bronchioles, that is, acini, form pulmonary lobule. The pulmonary lobule is an anatomic unit, polygonal in shape, and bound by complete or incomplete connective tissue interlobular septa and measures about 1.5–3 cm.
\nGas exchange starts in respiratory bronchioles and mainly occurs in alveoli. The alveolar wall (also called alveolar septum) is very thin in order to permit efficient gas exchange (Figure 3). It consists only of one layer of epithelial cells called pneumocytes. Pneumocytes type 1 are very thin, flat, large epithelial cells that cover 90% of the alveolar surface and are not capable of mitosis. Pneumocytes type 2 are cuboidal cell with large basal nucleus and prominent nucleolus. Pneumocytes type 2 secrete surfactant, are able to divide and participate in repair, and may become hyperplastic in response to alveolar damage. Pneumocytes type 2 are also precursors of pneumocytes type 1. Pneumocytes lie on the basal membrane that is fused with the basal membrane of the capillary endothelial cell. Thus the alveolar wall (septum) consists only of capillary sandwiched between the two layers of pneumocytes from two adjacent alveoli (Figure 3). An occasional myofibroblast may be present in the alveolar wall as well as rare scattered small lymphocytes, rare mesenchymal cells, and rare macrophages. Hematoxylin and eosin-stained sections of the normal lung on high magnification show delicate alveolar walls (septa) containing inconspicuous capillaries, occasional cuboidal cells of pneumocytes type 2, and nuclei of pneumocytes type 1, endothelial cell nuclei, and nuclei of rare scattered lymphocytes, mesenchymal cells, and macrophages. The cytoplasm of pneumocytes type 1 is too thin to be visible without special immunoperoxidase stains. Alveolar macrophages egress from capillaries, are increased in number in chronic inflammatory settings, and are involved in phagocytosis of foreign material as well in the inflammatory and immune responses.
\nThe interstitium provides the connective tissue framework of the lungs and is composed of collagen fibers, elastic fibers, mesenchymal cells, and few inflammatory cells. In normal lungs the interstitium is generally inconspicuous and can be recognized only along bronchovascular bundles, around veins, and where it forms interlobular septa. In the children up to 4 years of age, the interstitium is more apparent and presents as thickening of the alveolar walls [3]. The term “small airways” includes airways with diameter of 2 mm and smaller and thus includes small bronchi, terminal bronchioles, and respiratory bronchioles.
\nEmphysema is permanent enlargement of airspaces distal to the terminal bronchiole (acinus) due to the destruction of the walls of the alveoli, alveolar ducts, and the respiratory bronchioles. Grossly, the lung is hyperinflated and spongy.
\nAccording to the location of the hyperinflated alveoli inside the acinus, there are four types of emphysema: centriacinar (centrilobular, proximal), panacinar (panlobular), distal acinar (paraseptal), and irregular (associated with scar). Each of the emphysema type has characteristic microscopic morphology and characteristic etiology.
\nThe most frequent is centriacinar emphysema which comprises more than 95% of all emphysemas.
Centriacinar emphysema caused by coal mine dust. Some alveoli are normal, some emphysematous. Hematoxylin and eosin stain, original magnification 20×.
Inhaled cigarette smoke or mineral dust, most frequently coal mine dust, reach respiratory bronchioles. There are no cilia in the respiratory bronchioles; cigarette smoke particles and coal dust particles (silica particles in the coal dust are the most toxic ones) stick there and initiate processes of inflammation and destruction. The first damaged structure is thus respiratory bronchiolus with its dilatation or disappearance. In the beginning, alveolar ducts and alveoli are spared. Soon their destruction and coalescence into the larger air space follows. In the acinus, which contains several (about 14) respiratory bronchioles, some bronchioles and alveoli are damaged, enlarged, and emphysematous, and some are not damaged and are normal in size. Thus characteristic microscopic feature with low power magnification of centroacinar emphysema is that some alveoli are normal and some emphysematous (Figures 4 and 5).
\nCentriacinar emphysema and interstitial fibrosis caused by birefringent silica/silicate particles from coal mine dust. This is the same area as in
Cigarette smoke produces similar damage, and in fact the most frequent cause of centriacinar emphysema is cigarette smoking. Centriacinar emphysema predominantly involves the upper and posterior portions of the lungs and upper parts of the individual lobes. In severe emphysema, emphysematous spaces may coalesce and form bullae which may reach several centimeters in diameters. By definition bulla is at least 1 cm in diameter. Bullae are usually located in the lung apices and subpleurally but can occur anywhere in the emphysematous lungs.
\nPanacinar emphysema (left) and normal lung (right). In panacinar emphysema, all alveoli are enlarged. Figure 6, is reproduced with permission from the American Registry of Pathology from the Atlas of Nontumor Pathology Series; Non-Neoplastic Disorders of the Lower Respiratory Tract by William D. Travis et al published by the American Registry of Pathology and the Armed Forces Institute of Pathology Washington DC, USA, Copyright© 2002.
Panacinar emphysema is associated with alpha-1-antitrypsin deficiency, an autosomal codominant genetic disorder. Since defect is present in the gene (chromosome 14, segment q32.1), every cell, in which this gene is active and its product anti-protease alpha-1 antitrypsin enzyme pertinent, is affected. Thus all respiratory bronchioles, alveolar ducts, and alveoli are affected and about equally damaged and equally hyperinflated. The lungs are diffusely affected by panacinar emphysema, and histologically there is diffuse enlargement of the alveoli affecting the entire acinus. Normal level of alpha-1 antitrypsin in the serum is 20–48 \n
Panacinar emphysema caused by drug abuse. Mild interstitial fibrosis is present as well as birefringent deposits of talc in the interstitium. Figure 7 is reproduced with permission from the American Registry of Pathology from the Atlas of Nontumor Pathology Series; Non-Neoplastic Disorders of the Lower Respiratory Tract by William D. Travis et al published by the American Registry of Pathology and the Armed Forces Institute of Pathology Washington DC, USA, Copyright© 2002.
The pathogenesis of centriacinar and panacinar emphysema is conceptually similar and based on proteinase-antiproteinase imbalance, that is, inequity between enzymes that degrade the extracellular matrix and proteins that oppose this proteolytic activity [6]. The first clue appeared in 1963 when Laurell and Eriksson identified patients with alpha-1 antitrypsin (more appropriate name is alpha-1 antiproteinase) deficiency on serum electrophoresis who had severe emphysema of early onset and in 1964 when Gross and coworkers demonstrated that proteolytic enzyme papain can produce emphysema in rats [7, 8]. Alpha-1 antitrypsin is a proteinase inhibitor that inhibits proteolytic enzymes, primarily neutrophil elastase. Elastase is an enzyme that destroys elastin fibers, and if it is not adequately inhibited by alpha-1 antitrypsin, destruction of acinar tissue follows leading to emphysema. Imbalance between other proteolytic enzymes (metalloproteinases including interstitial collagenase-1, interstitial collagenase-3, metalloelastase, matrilysin, gelatinase A and gelatinase B, cathepsins) and their inhibitors (tissue inhibitors of matrix metalloproteinases, elafin, epithelium-derived secretory leukoprotease inhibitor) also contributes to emphysema and chronic obstructive pulmonary disease [3, 6].
\nCigarette smoking is the most frequent cause of emphysema and accounts to 80–90% of chronic obstructive pulmonary disease cases in the USA [9]. Cigarette smoke and coal mine dust cause emphysema by a similar pathophysiologic pathway. Inhaled cigarette smoke as well as coal mining dust particles travel by airflow to respiratory bronchioles and alveoli where they interfere with epithelial cells, alveolar macrophages, and neutrophils. Cigarette smoke contains per puff an estimated 10\n15\n–1017 oxidants/free radicals and about 4700 different chemical compounds, including reactive aldehydes and quinones [10, 11]. Toxic oxidant compounds in cigarette smoke induce DNA damage and peroxidation of lipids, harm proteins, fold proteins, and cause them to aggregate in the cytoplasm of the respiratory cells and alveolar cells [12]. Alveolar epithelial cells and macrophages damaged by cigarette smoke release cytokines which invite inside alveoli inflammatory cells mainly macrophages but also T cells (T8 more than T4) and small number of neutrophils. Characteristic histologic findings in cigarette smokers are tobacco-associated respiratory bronchiolitis with the presence of macrophages containing smoker granules (yellow-brown) inside alveoli (Figure 8). Macrophages and neutrophils activated by cigarette smoke or silica (quartz) [13] particles in coal mine dust release abovementioned proteolytic enzymes that destroy collagen and elastic alveolar tissue causing connective tissue breakdown and alveolar tissue destruction, that is, emphysema [14]. Oxidative radicals in the cigarette smoke as well as quartz-generated hydrogen peroxide not only damage intracellular proteins but also inactivate alpha-1 antitrypsin by oxidizing the SH group of methionine to methionine sulfoxide [14]. Other proteins, for example, proteasome with caspase-like activity, are also impaired by this oxidation. The final effect of cigarette smoke and inhalation of coal mine dust is unopposed (or insufficiently inhibited) action of proteolytic enzymes that destroy lung parenchyma and cause emphysema.
\nTobacco-associated respiratory bronchiolitis. Macrophages with smoker granules inside alveoli. Hematoxylin and eosin stain, original magnification 400×.
Macrophages also produce transforming growth factor-beta, platelet-derived growth factor, and tumor necrosis-alpha, which all stimulate fibroblast growth, collagen production and repair with associated fibrosis [15]. Repair may not be perfect and interstitial fibrosis may occur. Bronchioles and small bronchi can be involved by fibrosis and contribute to the chronic obstructive pulmonary disease. Tobacco-caused respiratory bronchiolitis-associated interstitial lung disease with fibrosis (Figure 9) is now a plausible and established term [16, 17].
\nTobacco-associated respiratory bronchiolitis with interstitial fibrosis. Hematoxylin and eosin stain, original magnification 200×. Right, same picture under polarized light to demonstrate collagen (silvery shine) fibers in thickened fibrotic alveolar septa.
It is obvious that tobacco-associated emphysema and tobacco-associated interstitial fibrosis are related and that the first step in their genesis is accumulation of macrophages with smoker granules in the alveoli. The similar process can be elicited by silica and silicates from coal mine dust. The first sign of exposure to coal mine dust is accumulation of silica/silicate particles and anthracotic pigment in the alveolar macrophages (Figure 10) [18].
\nInitial event in development of emphysema and interstitial fibrosis in coal miners is appearance of macrophages laden with silica and silicate particles and anthracotic pigment inside alveoli. Hematoxylin and eosin stain, original magnification 400×. Right side, same picture under polarized light to demonstrate birefringent silica and silicate particles in the cytoplasm of macrophages. Very small and faint white dots are silica particles, and small bright dots are silicate particles.
In coal miners with complicated coal worker’s pneumoconiosis, the role of smoking in causing fibrosis is insignificant in comparison with that of silica/silicate particles from coal mine dust [18]. Since smoking and coal mine dust simultaneously may cause pulmonary fibrosis and emphysema by destruction of lung tissue and healing by fibrosis, it is plausible that in some patients emphysema is dominant, in others interstitial fibrosis, and in some others combined pulmonary fibrosis and emphysema syndrome (Figure 11) may occur [18, 19].
\nTobacco caused emphysema and tobacco caused respiratory bronchiolitis-associated interstitial lung disease with fibrosis, called combined pulmonary fibrosis and emphysema syndrome. Courtesy of Dr. Nadia N. Naumova.
Alpha-1 antitrypsin deficiency is not the only one known genetic cause of emphysema. Telomere length is also associated with emphysema [20]. Both tips (ends) of the chromosomes are capped (protected) by telomeres composed of tandemly repeated DNA sequences. Telomeres are highly conserved and practically identical from protozoa to vertebrates. In humans, the TTAGGG repeat region is 10–15 kilobytes long. With each mitosis terminal nucleotides at the tail of telomeres are lost, and telomeres become shorter with each cell division. When telomere becomes critically short, the cell cannot divide anymore and thus becomes an old cell that will finally end up in apoptosis. Telomerase is an enzyme that synthesizes telomeres. Mutations in telomerase gene and telomere genes cause short telomere length for cell age and disease spectrum called short telomere syndrome/accelerated aging syndrome. The main presentation (90%) of short telomere syndromes are idiopathic pulmonary (interstitial) fibrosis and emphysema. They may be associated with other features of premature aging including early graying, osteoporosis, liver disease, predisposition to bone marrow failure, infertility, as well as myelodysplastic syndrome and acute myeloid leukemia [21]. Reduced telomere length may be identified in 25% of patients with sporadic idiopathic pulmonary fibrosis and half of those cases with family aggregation [22]. Telomerase deficiency and telomere shortening are responsible for only 1% of all emphysemas but are conceptually important as a link between interstitial fibrosis, emphysema, combined emphysema and interstitial fibrosis, and effect of environment on phenotypic presentation of genetic defect [21]. Pathogenic mechanism is premature senescence of alveolar epithelial stem cells, their apoptosis, disappearance of alveoli (emphysema), and abnormal repair with excessive interstitial fibrosis. The same genetic change, germline deletion in the Box H domain of the RNA telomerase, can cause in the father idiopathic pulmonary fibrosis, in one daughter emphysema, and in the other daughter combined pulmonary fibrosis and emphysema syndrome [20]. Interaction between the gene and environment determines lung disease. Never-smokers develop pulmonary interstitial fibrosis, while smokers develop an early onset emphysema alone or combined emphysema and pulmonary interstitial fibrosis [20, 21]. Cigarette smoke causes additive DNA damage to telomere function, and genetic defect in this setting expresses as emphysema [20].
\nIn short, the main causes of emphysema and interstitial fibrosis are cigarette smoking and in coal miners silica and silicate particles from coal dust. Hereditary emphysemas caused by alpha-1 antitrypsin deficiency and short telomere length are epidemiologically insignificant but can help to elucidate pathogenesis of emphysema and interstitial fibrosis. Not all smokers develop emphysema and chronic obstructive pulmonary disease. Only 10–20% of the smokers develop chronic obstructive pulmonary disease pointing at an additional risk factor such as genetic susceptibility reflected in polymorphisms in genes coding for various antiproteases, a disintegrin, and metalloproteinase 33 or antioxidant superoxide dismutase and proinflammatory mediators including tumor necrosis factor-alpha [10] and possibly genes associated with telomeres. Combined pulmonary fibrosis and emphysema are also in the vast majority of cases caused by cigarette smoking or in coal miners by coal dust, and the above mentioned genetic factors might contribute to a now unknown degree of susceptibility.
\nPatients with emphysema only are extremely rare, and in practice emphysema is component of the chronic obstructive pulmonary disease which affects about 24 million people in the USA. Chronic bronchitis is chronic mucous hypersecretion syndrome and is clinically defined as productive cough for at least 3 months in 2 successive years. Its pathohistological features (Figure 12) include enlargement of the mucus-secreting glands in the bronchial wall, goblet cell metaplasia of the respiratory epithelium, infiltration of the bronchial mucosa with lymphocytes, squamous metaplasia and dysplasia in the bronchial epithelium, increased bronchial smooth muscle, as well as mucous plugging, inflammation, and fibrosis of the bronchioles.
\nChronic bronchitis presenting with mucus in the lumen of the bronchus, partial goblet cell metaplasia of the respiratory epithelium, predominance of the mucinous cells in the bronchial exocrine gland, infiltration the bronchial wall by small lymphocytes and plasma cells, hypertrophy of the muscle layer, and peribronchial fibrosis.
Chronic bronchitis becomes chronic obstructive bronchitis when airflow obstruction occurs. It can be detected by spirometry or expiratory wheezing can be heard by auscultation. Bronchial airways are being compressed during expiration, and expiration is in chronic obstructive bronchitis difficult and prolonged. Auscultation reveals diminished breath sounds, prolonged expiratory phase, and expiratory wheezing. The main airflow obstruction occurs in small airways, with diameter less than 2 mm. Obstruction is caused by mucosal thickening, due to lymphocytic infiltration, fibrosis, edema, mucous plugging, and smooth muscle hypertrophy. Figure 13 demonstrates thickening of the wall of the terminal bronchiolus by fibrous tissue and smooth muscle hypertrophy caused by birefringent silica/silicate particles from coal mine dust.
\nThe wall of the terminal bronchiolus is thickened by fibrosis and smooth muscle hypertrophy and this is one of the essential pathologic bases for obstructive pulmonary disease. Birefringent silica and silicate particles are etiological factor. Hematoxylin and eosin stain, original magnification 200×, polarized light.
Clara cells that secrete surfactant are replaced by goblet cells, and decrease of surfactant increases surface tension at the air-tissue interface, and small bronchi and bronchiole are prone to collapse. Emphysema also contributes to airflow obstruction. Destruction and disappearance of respiratory bronchiole and alveolar ducts decrease total airway diameter. Destruction of acinar tissue with disappearance of elastic fibers decreases lung recoil and decreases expiratory air force. The net effect of chronic obstructive pulmonary disease is difficulty in breathing, prolonged expiration with expiratory wheezing, air trapping in the lungs with hyperinflation of lungs, increased residual volume, decreased vital capacity, and dyspnea.
\nThree cardinal features of chronic obstructive pulmonary disease are cough, sputum production, and exertional dyspnea. Dyspnea during physical activity may start insidiously, and patients complain of difficult breathing, gasping and air hunger, heaviness in chest in the beginning only during rather heavy physical work and later during light daily physical activity. Patients with chronic obstructive pulmonary disease poorly tolerate physical activity with arms but tolerate better physical work like pushing shopping cart when arms are fixed and enable the use of accessory respiratory muscles [1]. Acute exacerbations of chronic obstructive pulmonary disease are prominent feature of its natural history and are characterized by cough, increase in amount and character (color) of sputum, and dyspnea and may or may not be accompanied with fever, myalgia, and sore throat. The health-related quality of life of patients with chronic obstructive pulmonary disease better correlates (inverse correlation) with frequency of acute exacerbations than with the degree of airflow obstruction (Reilly-Harrison). Patients with advanced emphysema due to hyperinflation of lungs have barrel chest with poor diaphragmatic excursion as assessed by percussion and dramatic decrease in breath sounds and are sitting in the characteristic tripod position with stretched fixed arms to enable the use of accessory respiratory muscles including sternocleidomastoid, scalene, and intercostal ones [1]. Patients with predominant emphysema are called “pink puffers” because they breathe through pursed lips with the help of accessory respiratory muscles. When small airway obstruction ensues, patients become hypoxic and cyanotic in the lips and nail beds, and when fluid retains due to right heart decompensation, they become “blue bloaters.” However the majority of chronic obstructive pulmonary disease patients have some signs of both, “pink puffers” and “blue bloaters.” Advanced chronic obstructive lung disease is accompanied by systemic wasting due to high energy expenditure for increased work of breathing muscles including accessory breathing muscles and elevated levels of inflammatory cytokines including tumor necrosis factor-alpha. Such patients have a significant weight loss and diffuse loss of subcutaneous fatty tissue. Some patients with advanced chronic obstructive pulmonary disease have paradoxical inward movement of the lower rib cage (Hoover sign) due to diaphragmatic contraction in a setting of permanently hyperinflated lungs [1]. Advanced chronic obstructive pulmonary disease, especially during acute exacerbation, can be accompanied by right heart failure. Signs include right ventricular heave, third heart sound, distended jugular veins, congested liver, ascites, and edema of legs.
\nCardinal features of emphysema, hyperinflation of the lungs, and lung tissue destruction can be visualized by radiologic means. On the chest roentgenogram hyperinflation presents with increased lucency, increased retrosternal air space, depression and flattening of the diaphragm. Lung destruction presents in focal lucencies and areas of decreased vascularity. Mild emphysema is usually missed by standard chest X-rays.
\nHigh-resolution computerized tomography is superior to the chest X-ray in detecting emphysema. High-resolution computerized tomography can visualize focal areas of decreased attenuation sharply circumscribed without visible walls and with small centrilobular vessel in the areas of emphysema [3]. Several studies showed good correlation between the degree of pathologic findings and high-resolution computerized tomography findings [23]. However, mild focal areas might not be detected, and high-resolution computerized tomography cannot be used to rule out emphysema [24].
\nSpirometry and pulse oximetry are basic simple pulmonary function tests that can be performed in the ambulatory settings. The patient exhales in the spirometry instrument as completely as possible, then forcibly inhales as much as possible, and then forcibly exhales as much as possible. Forced vital capacity is the maximum amount of air forcibly expired after maximum inspiration. Residual volume is amount of air retained in the lungs after maximal and forceful exhalation, and it can be calculated after using gas dilution technique or body-box plethysmography. In the emphysema due to the destruction of respiratory bronchioles, spirometry will demonstrate obstructive pattern. Forced expiratory volume in 1 second will be decreased. Alveolar destruction in emphysema decreases amount of lung parenchyma, and thus forced vital capacity will decrease. Essentially emphysema is a mixed lung disorder, both obstructive and restrictive.
\nTranscutaneous pulse oximetry estimates oxygen (O2) saturation of capillary blood using instrument in shape of clip positioned on a finger. Estimation is accurate and correlates to 5% of measured atrial O2 saturation obtained by invasive procedure.
\nCentriacinar emphysema is a progressive disabling disease for which there are no good therapeutic options. Large bullae that compress functional lung tissue can be surgically removed. Patients with severe, predominantly upper lung emphysema, and low baseline exercise capacity may benefit from lung volume reduction by resection, including bronchoscopic lung volume reduction, of non-functioning emphysematous areas. Dyspnea decreases because of reduced hyperinflation and residual volume and because forced expiration volume in the first second is increased [25]. Exercise tolerance and 2-year mortality rate are improved supposedly to decreased residual lung volume, enhanced lung recoil, and improved diaphragmatic function. Long-term effects of the lung volume reduction surgery are unknown. Improvement after lung transplantation is better than after the lung volume reduction surgery. Candidates for lung transplantation are younger than 60 years, with an FEV1 less than 25% predicted or pulmonary artery hypertension. The 5-year survival after transplantation for emphysema is 45–60%. Lifelong immunosuppression brings risk of opportunistic infections.
\nNone declared.
\nEmphysema, enlarged airspaces due to destruction of alveolar walls, respiratory bronchioles, and alveolar ducts, is a well-defined disease. However, in the medical practice, it is mainly encountered as an essential component of the chronic obstructive pulmonary disease syndrome. Other components are chronic bronchitis, small airway disease, small airway hyperactivity, and inflammation. Chronic obstructive pulmonary disease presents with cough, sputum production, and exertional dyspnea. In advanced cases, patients are breathless while doing even simple daily activities and may develop resting hypoxemia (blue cyanotic lips and finger nails) that requires continuous application of supplemental oxygen. Chronic obstructive pulmonary disease during its course is complicated by viral, bacterial, and fungal infections, and pneumonias and chronic obstructive pulmonary disease are the fourth leading cause of death in the USA. Urban air pollution and industrial air pollution are contributory factors in the genesis of chronic obstructive pulmonary disease, and with increase in cigarette smoking in developing countries, an estimate is that the chronic obstructive pulmonary disease will rise from the sixth to the third most common cause of death worldwide by the year 2020 [1].
\nA normal lung consists of airways and alveoli. Airways are tubes (pipes) that conduct air to alveoli where gas exchange occurs. Oxygen (O2) through alveolar wall enters into red blood cells in the alveolar capillaries and binds to hemoglobin, while carbon dioxide (CO2) goes in opposite direction being released from hemoglobin, enters alveoli, and is being exhaled.
\nThe trachea beyond the carina undergoes to about 23 generations of dichotomous branching. Airway tubes with diameter of more than 1 mm are called bronchi. With each division the diameter of the bronchus becomes smaller, but the sum of the two diameters exceeds diameter of the parent bronchus meaning that with divisions resistance to air flow becomes smaller. The bronchus consists of the lumen, mucosa, submucosa, muscularis, cartilage, and adventitia that is composed of connective tissue and contains lymphatics (Figure 1).
\nPortion of the wall of the bronchus with respiratory epithelium with cilia, smooth muscle layer, and cartilage.
Bronchi are accompanied by branches of the pulmonary artery that have a diameter of similar size to the diameter of the bronchus they follow. The mucosa is mainly lined by columnar respiratory epithelium with cilia. All columnar cells lie on a basement membrane, but since columnar cells differ in their length, nuclei differ in their position regarding basal membrane, and respiratory epithelium appears stratified, but in fact it is pseudostratified. The mucosa also contains small number of mucinous cells that contain apical mucin, small number of basal cells, and rare neuroendocrine cells. Basal cells are precursors of ciliated cells and of mucinous goblet cells. Cilia arise from the apices of the respiratory cells and serve as escalator pushing mucin upstream to the throat and nose. Neuroendocrine cells are scattered singly and form small groups, neuroepithelial bodies near the airway bifurcations. The functional significance of the neuroendocrine cells is largely unknown. Beneath the pseudostratified ciliated mucosa is the submucosa that consists of loose connective tissue harboring bronchial mucous (seromucinous) glands, lymphoid tissue aggregates, and plasma cells. Mucinous glands secrete mucus composed of glycoprotein, proteoglycans, lipids, IgA (secretory) immunoglobulins, lysozyme peroxidase, and other substances to inactivate invading microorganisms, and trap air pollution particles. Cartilage plate and muscle bundles lie beneath the submucosa. The cartilage prevents collapse of the bronchial lumen. There are about 9–12 generations of bronchi. The smallest bronchi are 1 mm in diameter. Bronchi branch into the bronchiole. Bronchioles are less than 1 mm in diameter and they lack cartilage and exocrine mucinous glands in their walls. The larger bronchioles are called terminal bronchioles and measure on average 0.5–1 mm. Since terminal bronchioles do not contain cartilage, they are also called membranous bronchioles (Figure 2).
\nTerminal bronchiolus, lined by respiratory epithelium, with no cartilage and no exocrine glands.
Terminal bronchioles consist of respiratory mucosa composed of one layer of cuboidal ciliated respiratory cells and occasional Clara cells. Clara cells are non-ciliated columnar epithelial cells with protuberant apical cytoplasm that contains granules of surfactant and protease inhibitors. Clara cells are also precursors of bronchiolar epithelial cells. Goblet cells are generally not present or rare in the mucosa of the terminal bronchioles. Beneath the mucosa of the terminal bronchiolus is a layer of smooth muscle and connective tissue adventitia. Terminal bronchioles branch into the respiratory bronchioles. One side of the airway wall of the respiratory bronchiolus is lined by simple columnar to cuboidal bronchiolar epithelium without cilia. The opposite wall is lined by alveoli, that is, the wall consists of openings of the alveolar sacs. The average diameter of respiratory bronchioles is 0.15–0.2 mm. The respiratory bronchioles branch into about two more generations of respiratory bronchioles. Respiratory bronchioles branch into alveolar ducts, straight tubular spaces bounded entirely by alveoli (Figure 3).
\nAlveolar duct and alveoli (original magnification × 100) and alveolar septa with alveoli (original magnification × 400). Courtesy of Dr. Nadia N. Naumova.
In fact all alveoli (alveolar sacs) open into the alveolar ducts. Thus alveoli have incomplete wall and alveolar sacs are outpockets of alveolar ducts. Alveoli that appear lined with alveolar walls on all sides are in fact artifact of cut section. Alveolar ducts are not accompanied by the artery. The acinus is a functional unit of the lungs that consists of terminal bronchiolus with its respiratory bronchioles, alveolar ducts, and alveoli forming tridimensional spherical space with average diameter of 7.5 mm. There are about three generations of respiratory bronchioles inside the acinus and approximately 25,000 acini in normal adult male lungs with a volume of 5.25 liters [2]. Cluster of three to five terminal bronchioles, that is, acini, form pulmonary lobule. The pulmonary lobule is an anatomic unit, polygonal in shape, and bound by complete or incomplete connective tissue interlobular septa and measures about 1.5–3 cm.
\nGas exchange starts in respiratory bronchioles and mainly occurs in alveoli. The alveolar wall (also called alveolar septum) is very thin in order to permit efficient gas exchange (Figure 3). It consists only of one layer of epithelial cells called pneumocytes. Pneumocytes type 1 are very thin, flat, large epithelial cells that cover 90% of the alveolar surface and are not capable of mitosis. Pneumocytes type 2 are cuboidal cell with large basal nucleus and prominent nucleolus. Pneumocytes type 2 secrete surfactant, are able to divide and participate in repair, and may become hyperplastic in response to alveolar damage. Pneumocytes type 2 are also precursors of pneumocytes type 1. Pneumocytes lie on the basal membrane that is fused with the basal membrane of the capillary endothelial cell. Thus the alveolar wall (septum) consists only of capillary sandwiched between the two layers of pneumocytes from two adjacent alveoli (Figure 3). An occasional myofibroblast may be present in the alveolar wall as well as rare scattered small lymphocytes, rare mesenchymal cells, and rare macrophages. Hematoxylin and eosin-stained sections of the normal lung on high magnification show delicate alveolar walls (septa) containing inconspicuous capillaries, occasional cuboidal cells of pneumocytes type 2, and nuclei of pneumocytes type 1, endothelial cell nuclei, and nuclei of rare scattered lymphocytes, mesenchymal cells, and macrophages. The cytoplasm of pneumocytes type 1 is too thin to be visible without special immunoperoxidase stains. Alveolar macrophages egress from capillaries, are increased in number in chronic inflammatory settings, and are involved in phagocytosis of foreign material as well in the inflammatory and immune responses.
\nThe interstitium provides the connective tissue framework of the lungs and is composed of collagen fibers, elastic fibers, mesenchymal cells, and few inflammatory cells. In normal lungs the interstitium is generally inconspicuous and can be recognized only along bronchovascular bundles, around veins, and where it forms interlobular septa. In the children up to 4 years of age, the interstitium is more apparent and presents as thickening of the alveolar walls [3]. The term “small airways” includes airways with diameter of 2 mm and smaller and thus includes small bronchi, terminal bronchioles, and respiratory bronchioles.
\nEmphysema is permanent enlargement of airspaces distal to the terminal bronchiole (acinus) due to the destruction of the walls of the alveoli, alveolar ducts, and the respiratory bronchioles. Grossly, the lung is hyperinflated and spongy.
\nAccording to the location of the hyperinflated alveoli inside the acinus, there are four types of emphysema: centriacinar (centrilobular, proximal), panacinar (panlobular), distal acinar (paraseptal), and irregular (associated with scar). Each of the emphysema type has characteristic microscopic morphology and characteristic etiology.
\nThe most frequent is centriacinar emphysema which comprises more than 95% of all emphysemas.
Centriacinar emphysema caused by coal mine dust. Some alveoli are normal, some emphysematous. Hematoxylin and eosin stain, original magnification 20×.
Inhaled cigarette smoke or mineral dust, most frequently coal mine dust, reach respiratory bronchioles. There are no cilia in the respiratory bronchioles; cigarette smoke particles and coal dust particles (silica particles in the coal dust are the most toxic ones) stick there and initiate processes of inflammation and destruction. The first damaged structure is thus respiratory bronchiolus with its dilatation or disappearance. In the beginning, alveolar ducts and alveoli are spared. Soon their destruction and coalescence into the larger air space follows. In the acinus, which contains several (about 14) respiratory bronchioles, some bronchioles and alveoli are damaged, enlarged, and emphysematous, and some are not damaged and are normal in size. Thus characteristic microscopic feature with low power magnification of centroacinar emphysema is that some alveoli are normal and some emphysematous (Figures 4 and 5).
\nCentriacinar emphysema and interstitial fibrosis caused by birefringent silica/silicate particles from coal mine dust. This is the same area as in
Cigarette smoke produces similar damage, and in fact the most frequent cause of centriacinar emphysema is cigarette smoking. Centriacinar emphysema predominantly involves the upper and posterior portions of the lungs and upper parts of the individual lobes. In severe emphysema, emphysematous spaces may coalesce and form bullae which may reach several centimeters in diameters. By definition bulla is at least 1 cm in diameter. Bullae are usually located in the lung apices and subpleurally but can occur anywhere in the emphysematous lungs.
\nPanacinar emphysema (left) and normal lung (right). In panacinar emphysema, all alveoli are enlarged. Figure 6, is reproduced with permission from the American Registry of Pathology from the Atlas of Nontumor Pathology Series; Non-Neoplastic Disorders of the Lower Respiratory Tract by William D. Travis et al published by the American Registry of Pathology and the Armed Forces Institute of Pathology Washington DC, USA, Copyright© 2002.
Panacinar emphysema is associated with alpha-1-antitrypsin deficiency, an autosomal codominant genetic disorder. Since defect is present in the gene (chromosome 14, segment q32.1), every cell, in which this gene is active and its product anti-protease alpha-1 antitrypsin enzyme pertinent, is affected. Thus all respiratory bronchioles, alveolar ducts, and alveoli are affected and about equally damaged and equally hyperinflated. The lungs are diffusely affected by panacinar emphysema, and histologically there is diffuse enlargement of the alveoli affecting the entire acinus. Normal level of alpha-1 antitrypsin in the serum is 20–48 \n
Panacinar emphysema caused by drug abuse. Mild interstitial fibrosis is present as well as birefringent deposits of talc in the interstitium. Figure 7 is reproduced with permission from the American Registry of Pathology from the Atlas of Nontumor Pathology Series; Non-Neoplastic Disorders of the Lower Respiratory Tract by William D. Travis et al published by the American Registry of Pathology and the Armed Forces Institute of Pathology Washington DC, USA, Copyright© 2002.
The pathogenesis of centriacinar and panacinar emphysema is conceptually similar and based on proteinase-antiproteinase imbalance, that is, inequity between enzymes that degrade the extracellular matrix and proteins that oppose this proteolytic activity [6]. The first clue appeared in 1963 when Laurell and Eriksson identified patients with alpha-1 antitrypsin (more appropriate name is alpha-1 antiproteinase) deficiency on serum electrophoresis who had severe emphysema of early onset and in 1964 when Gross and coworkers demonstrated that proteolytic enzyme papain can produce emphysema in rats [7, 8]. Alpha-1 antitrypsin is a proteinase inhibitor that inhibits proteolytic enzymes, primarily neutrophil elastase. Elastase is an enzyme that destroys elastin fibers, and if it is not adequately inhibited by alpha-1 antitrypsin, destruction of acinar tissue follows leading to emphysema. Imbalance between other proteolytic enzymes (metalloproteinases including interstitial collagenase-1, interstitial collagenase-3, metalloelastase, matrilysin, gelatinase A and gelatinase B, cathepsins) and their inhibitors (tissue inhibitors of matrix metalloproteinases, elafin, epithelium-derived secretory leukoprotease inhibitor) also contributes to emphysema and chronic obstructive pulmonary disease [3, 6].
\nCigarette smoking is the most frequent cause of emphysema and accounts to 80–90% of chronic obstructive pulmonary disease cases in the USA [9]. Cigarette smoke and coal mine dust cause emphysema by a similar pathophysiologic pathway. Inhaled cigarette smoke as well as coal mining dust particles travel by airflow to respiratory bronchioles and alveoli where they interfere with epithelial cells, alveolar macrophages, and neutrophils. Cigarette smoke contains per puff an estimated 10\n15\n–1017 oxidants/free radicals and about 4700 different chemical compounds, including reactive aldehydes and quinones [10, 11]. Toxic oxidant compounds in cigarette smoke induce DNA damage and peroxidation of lipids, harm proteins, fold proteins, and cause them to aggregate in the cytoplasm of the respiratory cells and alveolar cells [12]. Alveolar epithelial cells and macrophages damaged by cigarette smoke release cytokines which invite inside alveoli inflammatory cells mainly macrophages but also T cells (T8 more than T4) and small number of neutrophils. Characteristic histologic findings in cigarette smokers are tobacco-associated respiratory bronchiolitis with the presence of macrophages containing smoker granules (yellow-brown) inside alveoli (Figure 8). Macrophages and neutrophils activated by cigarette smoke or silica (quartz) [13] particles in coal mine dust release abovementioned proteolytic enzymes that destroy collagen and elastic alveolar tissue causing connective tissue breakdown and alveolar tissue destruction, that is, emphysema [14]. Oxidative radicals in the cigarette smoke as well as quartz-generated hydrogen peroxide not only damage intracellular proteins but also inactivate alpha-1 antitrypsin by oxidizing the SH group of methionine to methionine sulfoxide [14]. Other proteins, for example, proteasome with caspase-like activity, are also impaired by this oxidation. The final effect of cigarette smoke and inhalation of coal mine dust is unopposed (or insufficiently inhibited) action of proteolytic enzymes that destroy lung parenchyma and cause emphysema.
\nTobacco-associated respiratory bronchiolitis. Macrophages with smoker granules inside alveoli. Hematoxylin and eosin stain, original magnification 400×.
Macrophages also produce transforming growth factor-beta, platelet-derived growth factor, and tumor necrosis-alpha, which all stimulate fibroblast growth, collagen production and repair with associated fibrosis [15]. Repair may not be perfect and interstitial fibrosis may occur. Bronchioles and small bronchi can be involved by fibrosis and contribute to the chronic obstructive pulmonary disease. Tobacco-caused respiratory bronchiolitis-associated interstitial lung disease with fibrosis (Figure 9) is now a plausible and established term [16, 17].
\nTobacco-associated respiratory bronchiolitis with interstitial fibrosis. Hematoxylin and eosin stain, original magnification 200×. Right, same picture under polarized light to demonstrate collagen (silvery shine) fibers in thickened fibrotic alveolar septa.
It is obvious that tobacco-associated emphysema and tobacco-associated interstitial fibrosis are related and that the first step in their genesis is accumulation of macrophages with smoker granules in the alveoli. The similar process can be elicited by silica and silicates from coal mine dust. The first sign of exposure to coal mine dust is accumulation of silica/silicate particles and anthracotic pigment in the alveolar macrophages (Figure 10) [18].
\nInitial event in development of emphysema and interstitial fibrosis in coal miners is appearance of macrophages laden with silica and silicate particles and anthracotic pigment inside alveoli. Hematoxylin and eosin stain, original magnification 400×. Right side, same picture under polarized light to demonstrate birefringent silica and silicate particles in the cytoplasm of macrophages. Very small and faint white dots are silica particles, and small bright dots are silicate particles.
In coal miners with complicated coal worker’s pneumoconiosis, the role of smoking in causing fibrosis is insignificant in comparison with that of silica/silicate particles from coal mine dust [18]. Since smoking and coal mine dust simultaneously may cause pulmonary fibrosis and emphysema by destruction of lung tissue and healing by fibrosis, it is plausible that in some patients emphysema is dominant, in others interstitial fibrosis, and in some others combined pulmonary fibrosis and emphysema syndrome (Figure 11) may occur [18, 19].
\nTobacco caused emphysema and tobacco caused respiratory bronchiolitis-associated interstitial lung disease with fibrosis, called combined pulmonary fibrosis and emphysema syndrome. Courtesy of Dr. Nadia N. Naumova.
Alpha-1 antitrypsin deficiency is not the only one known genetic cause of emphysema. Telomere length is also associated with emphysema [20]. Both tips (ends) of the chromosomes are capped (protected) by telomeres composed of tandemly repeated DNA sequences. Telomeres are highly conserved and practically identical from protozoa to vertebrates. In humans, the TTAGGG repeat region is 10–15 kilobytes long. With each mitosis terminal nucleotides at the tail of telomeres are lost, and telomeres become shorter with each cell division. When telomere becomes critically short, the cell cannot divide anymore and thus becomes an old cell that will finally end up in apoptosis. Telomerase is an enzyme that synthesizes telomeres. Mutations in telomerase gene and telomere genes cause short telomere length for cell age and disease spectrum called short telomere syndrome/accelerated aging syndrome. The main presentation (90%) of short telomere syndromes are idiopathic pulmonary (interstitial) fibrosis and emphysema. They may be associated with other features of premature aging including early graying, osteoporosis, liver disease, predisposition to bone marrow failure, infertility, as well as myelodysplastic syndrome and acute myeloid leukemia [21]. Reduced telomere length may be identified in 25% of patients with sporadic idiopathic pulmonary fibrosis and half of those cases with family aggregation [22]. Telomerase deficiency and telomere shortening are responsible for only 1% of all emphysemas but are conceptually important as a link between interstitial fibrosis, emphysema, combined emphysema and interstitial fibrosis, and effect of environment on phenotypic presentation of genetic defect [21]. Pathogenic mechanism is premature senescence of alveolar epithelial stem cells, their apoptosis, disappearance of alveoli (emphysema), and abnormal repair with excessive interstitial fibrosis. The same genetic change, germline deletion in the Box H domain of the RNA telomerase, can cause in the father idiopathic pulmonary fibrosis, in one daughter emphysema, and in the other daughter combined pulmonary fibrosis and emphysema syndrome [20]. Interaction between the gene and environment determines lung disease. Never-smokers develop pulmonary interstitial fibrosis, while smokers develop an early onset emphysema alone or combined emphysema and pulmonary interstitial fibrosis [20, 21]. Cigarette smoke causes additive DNA damage to telomere function, and genetic defect in this setting expresses as emphysema [20].
\nIn short, the main causes of emphysema and interstitial fibrosis are cigarette smoking and in coal miners silica and silicate particles from coal dust. Hereditary emphysemas caused by alpha-1 antitrypsin deficiency and short telomere length are epidemiologically insignificant but can help to elucidate pathogenesis of emphysema and interstitial fibrosis. Not all smokers develop emphysema and chronic obstructive pulmonary disease. Only 10–20% of the smokers develop chronic obstructive pulmonary disease pointing at an additional risk factor such as genetic susceptibility reflected in polymorphisms in genes coding for various antiproteases, a disintegrin, and metalloproteinase 33 or antioxidant superoxide dismutase and proinflammatory mediators including tumor necrosis factor-alpha [10] and possibly genes associated with telomeres. Combined pulmonary fibrosis and emphysema are also in the vast majority of cases caused by cigarette smoking or in coal miners by coal dust, and the above mentioned genetic factors might contribute to a now unknown degree of susceptibility.
\nPatients with emphysema only are extremely rare, and in practice emphysema is component of the chronic obstructive pulmonary disease which affects about 24 million people in the USA. Chronic bronchitis is chronic mucous hypersecretion syndrome and is clinically defined as productive cough for at least 3 months in 2 successive years. Its pathohistological features (Figure 12) include enlargement of the mucus-secreting glands in the bronchial wall, goblet cell metaplasia of the respiratory epithelium, infiltration of the bronchial mucosa with lymphocytes, squamous metaplasia and dysplasia in the bronchial epithelium, increased bronchial smooth muscle, as well as mucous plugging, inflammation, and fibrosis of the bronchioles.
\nChronic bronchitis presenting with mucus in the lumen of the bronchus, partial goblet cell metaplasia of the respiratory epithelium, predominance of the mucinous cells in the bronchial exocrine gland, infiltration the bronchial wall by small lymphocytes and plasma cells, hypertrophy of the muscle layer, and peribronchial fibrosis.
Chronic bronchitis becomes chronic obstructive bronchitis when airflow obstruction occurs. It can be detected by spirometry or expiratory wheezing can be heard by auscultation. Bronchial airways are being compressed during expiration, and expiration is in chronic obstructive bronchitis difficult and prolonged. Auscultation reveals diminished breath sounds, prolonged expiratory phase, and expiratory wheezing. The main airflow obstruction occurs in small airways, with diameter less than 2 mm. Obstruction is caused by mucosal thickening, due to lymphocytic infiltration, fibrosis, edema, mucous plugging, and smooth muscle hypertrophy. Figure 13 demonstrates thickening of the wall of the terminal bronchiolus by fibrous tissue and smooth muscle hypertrophy caused by birefringent silica/silicate particles from coal mine dust.
\nThe wall of the terminal bronchiolus is thickened by fibrosis and smooth muscle hypertrophy and this is one of the essential pathologic bases for obstructive pulmonary disease. Birefringent silica and silicate particles are etiological factor. Hematoxylin and eosin stain, original magnification 200×, polarized light.
Clara cells that secrete surfactant are replaced by goblet cells, and decrease of surfactant increases surface tension at the air-tissue interface, and small bronchi and bronchiole are prone to collapse. Emphysema also contributes to airflow obstruction. Destruction and disappearance of respiratory bronchiole and alveolar ducts decrease total airway diameter. Destruction of acinar tissue with disappearance of elastic fibers decreases lung recoil and decreases expiratory air force. The net effect of chronic obstructive pulmonary disease is difficulty in breathing, prolonged expiration with expiratory wheezing, air trapping in the lungs with hyperinflation of lungs, increased residual volume, decreased vital capacity, and dyspnea.
\nThree cardinal features of chronic obstructive pulmonary disease are cough, sputum production, and exertional dyspnea. Dyspnea during physical activity may start insidiously, and patients complain of difficult breathing, gasping and air hunger, heaviness in chest in the beginning only during rather heavy physical work and later during light daily physical activity. Patients with chronic obstructive pulmonary disease poorly tolerate physical activity with arms but tolerate better physical work like pushing shopping cart when arms are fixed and enable the use of accessory respiratory muscles [1]. Acute exacerbations of chronic obstructive pulmonary disease are prominent feature of its natural history and are characterized by cough, increase in amount and character (color) of sputum, and dyspnea and may or may not be accompanied with fever, myalgia, and sore throat. The health-related quality of life of patients with chronic obstructive pulmonary disease better correlates (inverse correlation) with frequency of acute exacerbations than with the degree of airflow obstruction (Reilly-Harrison). Patients with advanced emphysema due to hyperinflation of lungs have barrel chest with poor diaphragmatic excursion as assessed by percussion and dramatic decrease in breath sounds and are sitting in the characteristic tripod position with stretched fixed arms to enable the use of accessory respiratory muscles including sternocleidomastoid, scalene, and intercostal ones [1]. Patients with predominant emphysema are called “pink puffers” because they breathe through pursed lips with the help of accessory respiratory muscles. When small airway obstruction ensues, patients become hypoxic and cyanotic in the lips and nail beds, and when fluid retains due to right heart decompensation, they become “blue bloaters.” However the majority of chronic obstructive pulmonary disease patients have some signs of both, “pink puffers” and “blue bloaters.” Advanced chronic obstructive lung disease is accompanied by systemic wasting due to high energy expenditure for increased work of breathing muscles including accessory breathing muscles and elevated levels of inflammatory cytokines including tumor necrosis factor-alpha. Such patients have a significant weight loss and diffuse loss of subcutaneous fatty tissue. Some patients with advanced chronic obstructive pulmonary disease have paradoxical inward movement of the lower rib cage (Hoover sign) due to diaphragmatic contraction in a setting of permanently hyperinflated lungs [1]. Advanced chronic obstructive pulmonary disease, especially during acute exacerbation, can be accompanied by right heart failure. Signs include right ventricular heave, third heart sound, distended jugular veins, congested liver, ascites, and edema of legs.
\nCardinal features of emphysema, hyperinflation of the lungs, and lung tissue destruction can be visualized by radiologic means. On the chest roentgenogram hyperinflation presents with increased lucency, increased retrosternal air space, depression and flattening of the diaphragm. Lung destruction presents in focal lucencies and areas of decreased vascularity. Mild emphysema is usually missed by standard chest X-rays.
\nHigh-resolution computerized tomography is superior to the chest X-ray in detecting emphysema. High-resolution computerized tomography can visualize focal areas of decreased attenuation sharply circumscribed without visible walls and with small centrilobular vessel in the areas of emphysema [3]. Several studies showed good correlation between the degree of pathologic findings and high-resolution computerized tomography findings [23]. However, mild focal areas might not be detected, and high-resolution computerized tomography cannot be used to rule out emphysema [24].
\nSpirometry and pulse oximetry are basic simple pulmonary function tests that can be performed in the ambulatory settings. The patient exhales in the spirometry instrument as completely as possible, then forcibly inhales as much as possible, and then forcibly exhales as much as possible. Forced vital capacity is the maximum amount of air forcibly expired after maximum inspiration. Residual volume is amount of air retained in the lungs after maximal and forceful exhalation, and it can be calculated after using gas dilution technique or body-box plethysmography. In the emphysema due to the destruction of respiratory bronchioles, spirometry will demonstrate obstructive pattern. Forced expiratory volume in 1 second will be decreased. Alveolar destruction in emphysema decreases amount of lung parenchyma, and thus forced vital capacity will decrease. Essentially emphysema is a mixed lung disorder, both obstructive and restrictive.
\nTranscutaneous pulse oximetry estimates oxygen (O2) saturation of capillary blood using instrument in shape of clip positioned on a finger. Estimation is accurate and correlates to 5% of measured atrial O2 saturation obtained by invasive procedure.
\nCentriacinar emphysema is a progressive disabling disease for which there are no good therapeutic options. Large bullae that compress functional lung tissue can be surgically removed. Patients with severe, predominantly upper lung emphysema, and low baseline exercise capacity may benefit from lung volume reduction by resection, including bronchoscopic lung volume reduction, of non-functioning emphysematous areas. Dyspnea decreases because of reduced hyperinflation and residual volume and because forced expiration volume in the first second is increased [25]. Exercise tolerance and 2-year mortality rate are improved supposedly to decreased residual lung volume, enhanced lung recoil, and improved diaphragmatic function. Long-term effects of the lung volume reduction surgery are unknown. Improvement after lung transplantation is better than after the lung volume reduction surgery. Candidates for lung transplantation are younger than 60 years, with an FEV1 less than 25% predicted or pulmonary artery hypertension. The 5-year survival after transplantation for emphysema is 45–60%. Lifelong immunosuppression brings risk of opportunistic infections.
\nNone declared.
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The bamboo industry has attracted new opportunities as a new energy source, particularly renewable energy, and may be considered a lignocellulose substrate for bioethanol production because of its environmental benefits and high annual biomass yield.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Weiyi Liu, Chaomao Hui, Fang Wang, Meng Wang and Guanglu Liu",authors:[{id:"218573",title:"Dr.",name:"Liu",middleName:null,surname:"Weiyi",slug:"liu-weiyi",fullName:"Liu Weiyi"},{id:"218577",title:"Prof.",name:"Hui",middleName:null,surname:"Chaomao",slug:"hui-chaomao",fullName:"Hui Chaomao"},{id:"221875",title:"Dr.",name:"Fang",middleName:null,surname:"Wang",slug:"fang-wang",fullName:"Fang Wang"}]},{id:"61253",doi:"10.5772/intechopen.76359",title:"Bamboo, Its Chemical Modification and Products",slug:"bamboo-its-chemical-modification-and-products",totalDownloads:2714,totalCrossrefCites:6,totalDimensionsCites:20,abstract:"Bamboo, a perennial woody grass belonging to Gramineae family and Bambuseae subfamily, is ubiquitous in many parts of the world. This biomass possesses high potential as a substitute for many lignocellulosic and non-lignocellulosic materials in various capacities of applications owing to its chemical composition as well as its physical properties. Its abundance, chemical composition and numerous applications are reviewed in this work. This chapter also examined some investigated chemical modifications through alkali hydrolysis, acid hydrolysis, coupling to enhance properties of bamboo fibre for specialised applications.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Mayowa Akeem Azeez and Joshua Iseoluwa Orege",authors:[{id:"197473",title:"Dr.",name:"Mayowa Akeem",middleName:null,surname:"Azeez",slug:"mayowa-akeem-azeez",fullName:"Mayowa Akeem Azeez"},{id:"249430",title:"Mr.",name:"Joshua Iseoluwa",middleName:null,surname:"Orege",slug:"joshua-iseoluwa-orege",fullName:"Joshua Iseoluwa Orege"}]},{id:"60430",doi:"10.5772/intechopen.75626",title:"The Use of Bamboo for Erosion Control and Slope Stabilization: Soil Bioengineering Works",slug:"the-use-of-bamboo-for-erosion-control-and-slope-stabilization-soil-bioengineering-works",totalDownloads:3007,totalCrossrefCites:8,totalDimensionsCites:11,abstract:"The potential of bamboo in erosion control and slope stabilization has been proven worldwide. Bamboos are being used as living plants as well as construction material in different soil bioengineering techniques in many countries. The soil and water bioengineering approach is combined with bamboo traits and mechanical properties. The existing accumulated experiences of using bamboo in soil and water bioengineering works, along with the existing standards and design guidelines, make bamboo species an essential and cost-effective material for erosion control and slope stabilization works. In this chapter, all the necessary aspects to be taken into account for an appropriate use of bamboo in soil bioengineering works are addressed, and the design approaches for soil bioengineering works using bamboos are presented.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Guillermo Tardio, Slobodan B. Mickovski, Hans Peter Rauch, Joao\nPaulo Fernandes and Madhu Sudan Acharya",authors:[{id:"221706",title:"Dr.",name:"Guillermo",middleName:null,surname:"Tardio",slug:"guillermo-tardio",fullName:"Guillermo Tardio"},{id:"225058",title:"Dr.",name:"Slobodan B.",middleName:null,surname:"Mickovski",slug:"slobodan-b.-mickovski",fullName:"Slobodan B. Mickovski"},{id:"225059",title:"Dr.",name:"Joao Paulo",middleName:null,surname:"Fenandes",slug:"joao-paulo-fenandes",fullName:"Joao Paulo Fenandes"},{id:"225061",title:"Dr.",name:"Johann Peter",middleName:null,surname:"Rauch",slug:"johann-peter-rauch",fullName:"Johann Peter Rauch"}]},{id:"60797",doi:"10.5772/intechopen.76463",title:"A Review of Bambusicolous Ascomycetes",slug:"a-review-of-bambusicolous-ascomycetes",totalDownloads:1572,totalCrossrefCites:9,totalDimensionsCites:10,abstract:"Bamboo with more than 1500 species is a giant grass and was distributed worldwide. Their culms and leaves are inhabited by abundant microfungi. A documentary investigation points out that more than 1300 fungi including 150 basidiomycetes and 800 ascomycetous species with 240 hyphomycetous taxa and 110 coelomycetous taxa are associated with bamboo. Ascomycetes are the largest group with totally 1150 species. Families Xylariaceae and Hypocreaceae, which are most represented, have 74 species and 63 species in 18 and 14 genera, respectively, known from bamboo. The genus Phyllachora with a maximum number of species (22) occurs on bamboo, followed by Nectria (21) and Hypoxylon (20). The most represented host genera Bambusa, Phyllostachys, and Sasa are associated by 268, 186, and 105 fungal species, respectively. The brief review of major morphology and phylogeny of bambusicolous ascomycetes is provided, as well as research prospects.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Dong-Qin Dai, Li-Zhou Tang and Hai-Bo Wang",authors:[{id:"219411",title:"Dr.",name:"Dong-Qin",middleName:null,surname:"Dai",slug:"dong-qin-dai",fullName:"Dong-Qin Dai"},{id:"228691",title:"Prof.",name:"Li-Zhou",middleName:null,surname:"Tang",slug:"li-zhou-tang",fullName:"Li-Zhou Tang"},{id:"228708",title:"Prof.",name:"Hai-Bo",middleName:null,surname:"Wang",slug:"hai-bo-wang",fullName:"Hai-Bo Wang"}]},{id:"70724",doi:"10.5772/intechopen.90747",title:"Effects of Fire on Grassland Soils and Water: A Review",slug:"effects-of-fire-on-grassland-soils-and-water-a-review",totalDownloads:1099,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Grasslands occur on all of the continents. They collectively constitute the largest ecosystem in the world, making up 40.5% of the terrestrial land area, excluding Greenland and Antarctica. Grasslands are not entirely natural because they have formed and developed under natural and anthropogenic pressures. Their importance now is to the variety of ecosystem services that they provide: livestock grazing areas, water catchments, biodiversity reserves, tourism sites, recreation areas, religious sites, wild food sources, and natural medicine sources. An important function of grasslands is their sequestration and storage of carbon (C). Mollisol soils of grasslands have deep organic matter horizons that make this vegetation type almost as important as forests for C fixation and storage. Fire has been and continues to be an important disturbance in grassland evolution and management. Natural wildfires have been a component of grasslands for over 300 million years and were important in creating and maintaining most of these ecosystems. Humans ignited fires over many millennia to improve habitat for animals and livestock. Prescribed fire practiced by humans is a component of modern grassland management. The incidence of wildfires in grasslands continues to grow as an issue as droughts persist in semi-arid regions. Knowledge of fire effects on grasslands has risen in importance to land managers because fire, as a disturbance process, is an integral part of the concept of ecosystem management and restoration ecology. Fire is an intrusive disturbance in both managed and wildland forests and grasslands. It initiates changes in ecosystems that affect the composition, structure, and patterns of vegetation on the landscape. It also affects the soil and water resources of ecosystems that are critical to overall ecosystem functions and processes.",book:{id:"8088",slug:"grasses-and-grassland-aspects",title:"Grasses and Grassland Aspects",fullTitle:"Grasses and Grassland Aspects"},signatures:"Daniel George Neary and Jackson McMichael Leonard",authors:[{id:"40845",title:"Dr.",name:"Daniel G.",middleName:"George",surname:"Neary",slug:"daniel-g.-neary",fullName:"Daniel G. Neary"},{id:"276254",title:"Dr.",name:"Jackson",middleName:null,surname:"Leonard",slug:"jackson-leonard",fullName:"Jackson Leonard"}]}],mostDownloadedChaptersLast30Days:[{id:"61253",title:"Bamboo, Its Chemical Modification and Products",slug:"bamboo-its-chemical-modification-and-products",totalDownloads:2710,totalCrossrefCites:6,totalDimensionsCites:20,abstract:"Bamboo, a perennial woody grass belonging to Gramineae family and Bambuseae subfamily, is ubiquitous in many parts of the world. This biomass possesses high potential as a substitute for many lignocellulosic and non-lignocellulosic materials in various capacities of applications owing to its chemical composition as well as its physical properties. Its abundance, chemical composition and numerous applications are reviewed in this work. This chapter also examined some investigated chemical modifications through alkali hydrolysis, acid hydrolysis, coupling to enhance properties of bamboo fibre for specialised applications.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Mayowa Akeem Azeez and Joshua Iseoluwa Orege",authors:[{id:"197473",title:"Dr.",name:"Mayowa Akeem",middleName:null,surname:"Azeez",slug:"mayowa-akeem-azeez",fullName:"Mayowa Akeem Azeez"},{id:"249430",title:"Mr.",name:"Joshua Iseoluwa",middleName:null,surname:"Orege",slug:"joshua-iseoluwa-orege",fullName:"Joshua Iseoluwa Orege"}]},{id:"55730",title:"Vetiver Grass: A Tool for Sustainable Agriculture",slug:"vetiver-grass-a-tool-for-sustainable-agriculture",totalDownloads:3101,totalCrossrefCites:3,totalDimensionsCites:7,abstract:"Vetiver grass is a densely tufted bunch grass which can be easily established in both tropics and temperate regions of the world. It plays a vital role in watershed protection by slowing down and spreading runoff harmlessly on the farmland, recharging ground water, reducing siltation of drainage systems and water bodies, reducing agro-chemicals loading into water bodies and for rehabilitation of degraded soils. Vetiver grass could tolerate extremely high levels of heavy metals. It could be used as biological pest control. The use of vetiver grass has been regarded as a low-cost technology for soil and water conservation; on- and off-farm land and water sources stabilization and remediation of polluted soils; and enhancement of water quality for irrigation purposes when compared with other soil conservation technologies. It could be a dynamic tool for mitigating environmental and agricultural problems, thereby enhancing crop yield and supporting all-year round agricultural cultivation. Recently, vetiver grass has been used to raise animals of different kinds. Thus, this chapter in the book explores several applications of vetiver grass, its impacts and resultant benefits as a technology that could enhance sustainable agricultural development.",book:{id:"5889",slug:"grasses-benefits-diversities-and-functional-roles",title:"Grasses",fullTitle:"Grasses - Benefits, Diversities and Functional Roles"},signatures:"Suarau O. Oshunsanya and OrevaOghene Aliku",authors:[{id:"175778",title:"Dr.",name:"Suarau",middleName:null,surname:"Oshunsanya",slug:"suarau-oshunsanya",fullName:"Suarau Oshunsanya"},{id:"176082",title:"Mr.",name:"OrevaOghene",middleName:null,surname:"Aliku",slug:"orevaoghene-aliku",fullName:"OrevaOghene Aliku"}]},{id:"60430",title:"The Use of Bamboo for Erosion Control and Slope Stabilization: Soil Bioengineering Works",slug:"the-use-of-bamboo-for-erosion-control-and-slope-stabilization-soil-bioengineering-works",totalDownloads:2997,totalCrossrefCites:8,totalDimensionsCites:11,abstract:"The potential of bamboo in erosion control and slope stabilization has been proven worldwide. Bamboos are being used as living plants as well as construction material in different soil bioengineering techniques in many countries. The soil and water bioengineering approach is combined with bamboo traits and mechanical properties. The existing accumulated experiences of using bamboo in soil and water bioengineering works, along with the existing standards and design guidelines, make bamboo species an essential and cost-effective material for erosion control and slope stabilization works. In this chapter, all the necessary aspects to be taken into account for an appropriate use of bamboo in soil bioengineering works are addressed, and the design approaches for soil bioengineering works using bamboos are presented.",book:{id:"5812",slug:"bamboo-current-and-future-prospects",title:"Bamboo",fullTitle:"Bamboo - Current and Future Prospects"},signatures:"Guillermo Tardio, Slobodan B. Mickovski, Hans Peter Rauch, Joao\nPaulo Fernandes and Madhu Sudan Acharya",authors:[{id:"221706",title:"Dr.",name:"Guillermo",middleName:null,surname:"Tardio",slug:"guillermo-tardio",fullName:"Guillermo Tardio"},{id:"225058",title:"Dr.",name:"Slobodan B.",middleName:null,surname:"Mickovski",slug:"slobodan-b.-mickovski",fullName:"Slobodan B. Mickovski"},{id:"225059",title:"Dr.",name:"Joao Paulo",middleName:null,surname:"Fenandes",slug:"joao-paulo-fenandes",fullName:"Joao Paulo Fenandes"},{id:"225061",title:"Dr.",name:"Johann Peter",middleName:null,surname:"Rauch",slug:"johann-peter-rauch",fullName:"Johann Peter Rauch"}]},{id:"70724",title:"Effects of Fire on Grassland Soils and Water: A Review",slug:"effects-of-fire-on-grassland-soils-and-water-a-review",totalDownloads:1099,totalCrossrefCites:2,totalDimensionsCites:8,abstract:"Grasslands occur on all of the continents. They collectively constitute the largest ecosystem in the world, making up 40.5% of the terrestrial land area, excluding Greenland and Antarctica. Grasslands are not entirely natural because they have formed and developed under natural and anthropogenic pressures. Their importance now is to the variety of ecosystem services that they provide: livestock grazing areas, water catchments, biodiversity reserves, tourism sites, recreation areas, religious sites, wild food sources, and natural medicine sources. An important function of grasslands is their sequestration and storage of carbon (C). Mollisol soils of grasslands have deep organic matter horizons that make this vegetation type almost as important as forests for C fixation and storage. Fire has been and continues to be an important disturbance in grassland evolution and management. Natural wildfires have been a component of grasslands for over 300 million years and were important in creating and maintaining most of these ecosystems. Humans ignited fires over many millennia to improve habitat for animals and livestock. Prescribed fire practiced by humans is a component of modern grassland management. The incidence of wildfires in grasslands continues to grow as an issue as droughts persist in semi-arid regions. Knowledge of fire effects on grasslands has risen in importance to land managers because fire, as a disturbance process, is an integral part of the concept of ecosystem management and restoration ecology. Fire is an intrusive disturbance in both managed and wildland forests and grasslands. It initiates changes in ecosystems that affect the composition, structure, and patterns of vegetation on the landscape. It also affects the soil and water resources of ecosystems that are critical to overall ecosystem functions and processes.",book:{id:"8088",slug:"grasses-and-grassland-aspects",title:"Grasses and Grassland Aspects",fullTitle:"Grasses and Grassland Aspects"},signatures:"Daniel George Neary and Jackson McMichael Leonard",authors:[{id:"40845",title:"Dr.",name:"Daniel G.",middleName:"George",surname:"Neary",slug:"daniel-g.-neary",fullName:"Daniel G. Neary"},{id:"276254",title:"Dr.",name:"Jackson",middleName:null,surname:"Leonard",slug:"jackson-leonard",fullName:"Jackson Leonard"}]},{id:"55524",title:"Importance of Grass Carp (Ctenopharyngodon idella) for Controlling of Aquatic Vegetation",slug:"importance-of-grass-carp-ctenopharyngodon-idella-for-controlling-of-aquatic-vegetation",totalDownloads:1847,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"Aquatic plants are beneficial and a necessary part of lakes and reservoirs. Also, some kind of plants are the main food source for aquatic animals. Plants are able to stabilize sediments, improve water clarity and add diversity to the shallow areas of lakes. On the other hand, overgrown plants can become a nuisance by hindering human uses of water and threaten the structure and function of diverse native aquatic ecosystems. This chapter aims to make analysis of using of grass carp to control aquatic vegetation. In this concept, origin and distribution, biological features, reproduction, feeding behaviour and effects of grass carp on aquatic plants, water body and sediments are also discussed.",book:{id:"5889",slug:"grasses-benefits-diversities-and-functional-roles",title:"Grasses",fullTitle:"Grasses - Benefits, Diversities and Functional Roles"},signatures:"Yusuf Bozkurt, İlker Yavas, Aziz Gül, Beytullah Ahmet Balcı and\nNurdan Coskun Çetin",authors:[{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt"},{id:"119796",title:"Associate Prof.",name:"İlker",middleName:null,surname:"Yavaş",slug:"ilker-yavas",fullName:"İlker Yavaş"},{id:"207165",title:"Dr.",name:"Aziz",middleName:null,surname:"Gül",slug:"aziz-gul",fullName:"Aziz Gül"},{id:"207166",title:"Dr.",name:"Beytullah Ahmet",middleName:null,surname:"Balcı",slug:"beytullah-ahmet-balci",fullName:"Beytullah Ahmet Balcı"},{id:"207167",title:"MSc.",name:"Nurdan",middleName:null,surname:"Coşkun Çetin",slug:"nurdan-coskun-cetin",fullName:"Nurdan Coşkun Çetin"}]}],onlineFirstChaptersFilter:{topicId:"352",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82027",title:"Underutilized Grasses Production: New Evolving Perspectives",slug:"underutilized-grasses-production-new-evolving-perspectives",totalDownloads:21,totalDimensionsCites:0,doi:"10.5772/intechopen.105375",abstract:"Globally, over-reliance on major food crops (wheat, rice and maize) has led to food basket’s shrinking, while climate change, environmental pollution and deteriorating soil fertility demand the cultivation of less exhaustive but nutritious grasses. Unlike neglected grasses (grass species restricted to their centres of origin and only grown at the subsistence level), many underutilized grasses (grass species whose yield or usability potential remains unrealized) are resistant and resilient to abiotic stresses and have multiple uses including food (Coix lacryma-jobi), feed (Eragrostis amabilis and Cynodon dactylon), esthetic value (Miscanthus sinensis and Imperata cylindrica), renewable energy production (Spartina pectinata and Andropogon gerardii Vitman) and contribution to ecosystem services (Saccharum spontaneum). Lack of agricultural market globalization, urbanization and prevalence of large commercial enterprises that favor major grasses trade, improved communication means that promoted specialization in favor of established crops, scant planting material of underutilized grasses and fewer research on their production technology and products development are the prime challenges posed to underutilized grasses promotion. Integration of agronomic research with novel plant protection measures and plant breeding and molecular genetics approaches for developing biotic and abiotic stresses tolerant cultivars along with the development of commercially attractive food products hold the future key for promoting underutilized grasses for supplanting food security and sustainably multiplying economic outcomes.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Muhammad Aamir Iqbal, Sadaf Khalid, Raees Ahmed, Muhammad Zubair Khan, Nagina Rafique, Raina Ijaz, Saira Ishaq, Muhammad Jamil, Aqeel Ahmad, Amjad Shahzad Gondal, Muhammad Imran, Junaid Rahim and Umar Ayaz Aslam Sheikh"},{id:"81038",title:"Earth’s Energy Budget Impact on Grassland Diseases",slug:"earth-s-energy-budget-impact-on-grassland-diseases",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.99971",abstract:"The change in climate have caused different biotic and abiotic factors to be more prominent when management plan is executed. The increase in temperature have then cause frequent drought that may attract alien species of vectors to spread novel diseases among the native plants. However, the change in climate varies in different countries. Thus, common diseases that threatens food security such as Xanthomonas spp., Pseudomonas spp are in limelight of research. Vectors lifecycle may cause plant diseases to by cyclative. Therefore, to find the break in the vector’s lifecycle will be a method to eradicate harmful population in grassland. Modern days will then call for innovative method and limitations should be considered. Climate change have also impacted pathogens migration and mating pattern. The need for innovative management is constantly on the rise.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Ang Jia Wei Germaine"},{id:"79504",title:"Interaction of Grassland Ecosystem with Livelihood and Wildlife Sustainability: Tanzanian Perspectives",slug:"interaction-of-grassland-ecosystem-with-livelihood-and-wildlife-sustainability-tanzanian-perspective",totalDownloads:153,totalDimensionsCites:0,doi:"10.5772/intechopen.101343",abstract:"In Tanzania, pure grasslands cover is estimated to be 60,381 km2, about 6.8% of the total land area, and is distributed in different parts. These grasslands are diverse in dominant grass species depending on rainfall, soil type, altitude, and management or grazing system. They support livestock and wildlife distributed in different eco-tomes and habitats of the country. The potential of grasslands for the livelihood of rural people is explicit from the fact that local people depend solely on natural production to satisfy their needs for animal products. Analysis of grazing lands indicated that livestock population, production of meat, and milk from grasslands increased. But the wildlife population, when considered in terms of livestock equivalent units (Large Herbivore Units) showed a declining trend. The contribution of grasslands to the total volume of meat produced in the country showed a declining state, while milk production showed a slight increase. This situation entails a need to evaluate the grasslands of Tanzania to ascertain their potential for supporting people’s livestock, wildlife, and livelihood. This study concluded that more research is needed to establish the possibility of grasslands to keep large numbers of grazing herbivores for sustainable livestock and wildlife production.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Pius Yoram Kavana, John Kija Bukombe, Hamza Kija, Stephen Nindi, Ally Nkwabi, Iddi Lipende, Simula Maijo, Baraka Naftali, Victor M. Kakengi, Janemary Ntalwila, Sood Ndimuligo and Robert Fyumagwa"},{id:"79291",title:"Spinless Forage Cactus: The Queen of Forage Crops in Semi Arid Regions",slug:"spinless-forage-cactus-the-queen-of-forage-crops-in-semi-arid-regions",totalDownloads:117,totalDimensionsCites:0,doi:"10.5772/intechopen.100104",abstract:"Forage cactus is a perennial crop, which has been widely exploited for feeding ruminants in the semiarid region of different countries around the world. The main objective of this chapter is to describe the use and importance of spineless cactus as forage, desertification mitigation, source of water for animals and a source of income for producers in semiarid regions. The main species explored in Brazil are Opuntia spp. and Nopalea spp., due to characteristics such as resistance to pests, productivity, water-use efficiency and demand for soil fertility. The productivity of the species in a region will depend on its morphological characteristics, plant spacing, planting systems and its capacity to adapt to climatic and soil conditions. In other parts of the world, cactus species are the most cosmopolitan and destructive among invasive plants. However, the use of spineless forage cactus in areas where it can develop normally and may become the basis for ruminants’ feed would increase the support capacity production systems. Thus, specifically for Brazil’s semiarid region these species can make the difference as forage for animal feeding, cultivated as monoculture or intercropped, for soil conservation and desertification mitigation, source of water for animals, preservation of the Caatinga biome and be a potential source of income for producers if cultivated as vegetable for nutritional properties and medicinal derivative of fruits and cladodes for exports.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Marcelo de Andrade Ferreira, Luciano Patto Novaes, Ana María Herrera Ângulo and Michelle Christina Bernardo de Siqueira"},{id:"78933",title:"Implement and Analysis on Current Ecosystem Classification in Western Utah of the United States & Yukon Territory of Canada",slug:"implement-and-analysis-on-current-ecosystem-classification-in-western-utah-of-the-united-states-yuko",totalDownloads:129,totalDimensionsCites:0,doi:"10.5772/intechopen.100557",abstract:"The study cases in western Utah of the United States and Yukon Territory of Canada have more natural land and conservative ecosystems in North America. The ecosystem classification of land (ECL) in these two ecoregions had been analyzed and validated through implementation. A full ECL case study was accomplished and examined with eight upper levels of ECOMAP plus ecological site and vegetation stand in Western Utah, the US. Theoretically, applying Köppen climate system classification, Bailey’s Domain and Division were applied to the United States, North America, and world continents. However, Canada’s continental upper level ecoregion framework defined the ecological Mozaic on a sub-continental scale, representing an area of the hierarchical ecological units characterized by interactive and adjusting abiotic and biotic factors. Using Bailey’s Domain as the top level of Canada’s territorial ecoregion was recommended. Eight levels of ELCs were established for Yukon Territory, Canada. Thus, the second study case recommends integrating the ecosystem approaches with Bailey’s upper level ECL, broad ecosystem classification, and objectively defined ecological site in different countries, or ecoregions. Our study cases had exemplified the implementations with a full ELCs in Bailey’s 300 Dry Domain and 100 Polar Domain.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"YanQing Zhang and Neil E. West"},{id:"78440",title:"Miscanthus Grass as a Nutritional Fiber Source for Monogastric Animals",slug:"miscanthus-grass-as-a-nutritional-fiber-source-for-monogastric-animals",totalDownloads:150,totalDimensionsCites:1,doi:"10.5772/intechopen.99951",abstract:"While fiber is not an indispensable nutrient for monogastric animals, it has benefits such as promoting gastrointestinal motility and production of short chain fatty acids through fermentation. Miscanthus x giganteus is a hybrid grass used as an ornamental plant, biomass for energy production, construction material, and as a cellulose source for paper production. More recently Miscanthus grass (dried ground Miscanthus x giganteus) was evaluated for its fiber composition and as a fiber source for poultry (broiler chicks) and pets (dogs and cats). As a fiber source, this ingredient is mostly composed of insoluble fiber (78.6%) with an appreciable amount of lignin (13.0%). When added at moderate levels to broiler chick feed (3% inclusion) Miscanthus grass improved dietary energy utilization. However, when fed to dogs at a 10% inclusion Miscanthus grass decreased dry matter, organic matter, and gross energy digestibility, and increased dietary protein digestibility compared to dogs fed diets containing similar concentrations of beet pulp. Comparable results were reported for cats. In addition, when Miscanthus grass was fed to cats to aid in hairball management, it decreased the total hair weight per dry fecal weight. When considering the effects Miscanthus grass has on extruded pet foods, it behaves in a similar manner to cellulose, decreasing radial expansion, and increasing energy to compress the kibbles, likely because of changes in kibble structure. To date, Miscanthus grass has not been evaluated in human foods and supplements though it may have applications similar to those identified for pets.",book:{id:"10895",title:"Grasses and Grassland - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/10895.jpg"},signatures:"Renan Donadelli and Greg Aldrich"}],onlineFirstChaptersTotal:8},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:11,numberOfPublishedChapters:91,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:333,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:11,numberOfPublishedChapters:144,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:124,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:113,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:23,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:12,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. 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Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. 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He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:null,institution:null},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"417317",title:"Mrs.",name:"Chiedza",middleName:null,surname:"Elvina Mashiri",slug:"chiedza-elvina-mashiri",fullName:"Chiedza Elvina Mashiri",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"352140",title:"Dr.",name:"Edina",middleName:null,surname:"Chandiwana",slug:"edina-chandiwana",fullName:"Edina Chandiwana",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"342259",title:"B.Sc.",name:"Leonard",middleName:null,surname:"Mushunje",slug:"leonard-mushunje",fullName:"Leonard Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"347042",title:"Mr.",name:"Maxwell",middleName:null,surname:"Mashasha",slug:"maxwell-mashasha",fullName:"Maxwell Mashasha",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Midlands State University",country:{name:"Zimbabwe"}}},{id:"2941",title:"Dr.",name:"Alberto J.",middleName:"Jorge",surname:"Rosales-Silva",slug:"alberto-j.-rosales-silva",fullName:"Alberto J. Rosales-Silva",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"437913",title:"Dr.",name:"Guillermo",middleName:null,surname:"Urriolagoitia-Sosa",slug:"guillermo-urriolagoitia-sosa",fullName:"Guillermo Urriolagoitia-Sosa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"435126",title:"Prof.",name:"Joaquim",middleName:null,surname:"José de Castro Ferreira",slug:"joaquim-jose-de-castro-ferreira",fullName:"Joaquim José de Castro Ferreira",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Aveiro",country:{name:"Portugal"}}},{id:"437899",title:"MSc.",name:"Miguel Angel",middleName:null,surname:"Ángel Castillo-Martínez",slug:"miguel-angel-angel-castillo-martinez",fullName:"Miguel Angel Ángel Castillo-Martínez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"289955",title:"Dr.",name:"Raja",middleName:null,surname:"Kishor Duggirala",slug:"raja-kishor-duggirala",fullName:"Raja Kishor Duggirala",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Jawaharlal Nehru Technological University, Hyderabad",country:{name:"India"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",slug:"anca-pantea-stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",slug:"attilio-rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of 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