2012 International Chapel Hill Consensus Conference Nomenclature of Vasculitides [3].
\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"Milestone",originalUrl:"/media/original/124"}},components:[{type:"htmlEditorComponent",content:'
Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
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\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:"5780",leadTitle:null,fullTitle:"Serotonin - A Chemical Messenger Between All Types of Living Cells",title:"Serotonin",subtitle:"A Chemical Messenger Between All Types of Living Cells",reviewType:"peer-reviewed",abstract:"Serotonin - A Chemical Messenger Between All Types of Living Cells is a very interesting book on the most ancient neurotransmitter, hormone and trophic factor serotonin or 5-hydroxytryptamine (5-HT). This unique chemical is present in all living cells including plants and animals. This book will take us through a serene journey of the evolutionary history of serotonin and its role from man to mollusk. There are many interesting chapters incorporated in this book, including novel approaches for detecting minor metabolites of serotonin in human plasma, production and function of serotonin in cardiac cells, immuno-thrombotic effects of serotonin in platelets to the identification and localization of serotonin in the nervous system and gonad of bivalve mollusks.",isbn:"978-953-51-3362-9",printIsbn:"978-953-51-3361-2",pdfIsbn:"978-953-51-4720-6",doi:"10.5772/65233",price:139,priceEur:155,priceUsd:179,slug:"serotonin-a-chemical-messenger-between-all-types-of-living-cells",numberOfPages:316,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"5fe2c461c95b4ee2d886e30b89d71723",bookSignature:"Kaneez Fatima Shad",publishedDate:"July 26th 2017",coverURL:"https://cdn.intechopen.com/books/images_new/5780.jpg",numberOfDownloads:21005,numberOfWosCitations:27,numberOfCrossrefCitations:26,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:61,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:114,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 23rd 2016",dateEndSecondStepPublish:"November 14th 2016",dateEndThirdStepPublish:"February 6th 2017",dateEndFourthStepPublish:"April 3rd 2017",dateEndFifthStepPublish:"June 6th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"31988",title:"Prof.",name:"Kaneez",middleName:null,surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRhwqQAC/Profile_Picture_1643703122186",biography:"Professor Kaneez Fatima Shad, an Australian neuroscientist with a medical background, obtained a Ph.D. from the Faculty of Medicine, University of New South Wales (UNSW), Australia, in 1994, followed by a postdoc at the Allegheny University of Health Sciences, Philadelphia, USA. She taught medical and biological sciences at various universities in Australia, the United States, United Arab Emirates, Bahrain, Pakistan, and Brunei. During this period, she was also engaged in research by obtaining local and international grants (a total of more than $3 million USD) and developing products such as a rapid diagnostic test for stroke and other vascular disorders (i.e., schizophrenia). She has published more than sixty-eight articles in refereed journals, edited nine books, authored ten book chapters, presented at more than ninety international conferences, and mentored thirty-four postgraduate students. She is an international mentor and a protocol development specialist.",institutionString:"University of Technology Sydney",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"7",institution:{name:"University of Technology Sydney",institutionURL:null,country:{name:"Australia"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1174",title:"Neurochemistry",slug:"neurochemistry"}],chapters:[{id:"56300",title:"Introductory Chapter: Serotonin - The Most Ancient Neurotransmitter, Hormone and Trophic Factor",doi:"10.5772/intechopen.70146",slug:"introductory-chapter-serotonin-the-most-ancient-neurotransmitter-hormone-and-trophic-factor",totalDownloads:1866,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:1,abstract:null,signatures:"Kaneez Fatima Shad",downloadPdfUrl:"/chapter/pdf-download/56300",previewPdfUrl:"/chapter/pdf-preview/56300",authors:[{id:"31988",title:"Prof.",name:"Kaneez",surname:"Fatima Shad",slug:"kaneez-fatima-shad",fullName:"Kaneez Fatima Shad"}],corrections:null},{id:"55923",title:"Pharmacology and Molecular Identity of Serotonin Receptor in Bivalve Mollusks",doi:"10.5772/intechopen.69680",slug:"pharmacology-and-molecular-identity-of-serotonin-receptor-in-bivalve-mollusks",totalDownloads:1480,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"It is now known that 5-HT regulates several neurobehavioral systems such as mood, appetite, sleep, learning, and memory. It also plays critical roles in the physiological functions of peripheral organs involved in stress, growth, and reproduction in the animal kingdom. 5-HT content has seen to be higher in the nervous system of bivalves than those of other examined invertebrates and vertebrates. Thus, bivalves have been considered as an excellent model to investigate 5-HT functions in neurological and peripheral systems. The present study reviews knowledge on 5-HT signaling mediated through 5-HT receptor and its physiological contribution to regulate reproduction in bivalves. Two G-protein-coupled 5-HT1-like receptors have been cloned in bivalve species. However, binding affinities of the 5-HT agonists and antagonists to the isolated plasma membrane proteins and their effects on spawning in bivalves suggest the presence of a single or mixed 5-HT1-, 5-HT2-, and 5-HT3-like receptors. It has suggested that the 5-HT-like receptors in bivalves are distinct from those of mammalian 5-HT receptors due to pharmacological properties. The present review pays a special attention to future research perspectives to better understand 5-HT regulation of reproduction in bivalves, which can provide us with satisfactory knowledge to elucidate reproductive disorders associated with dysfunctions of the neurotransmitter system.",signatures:"Sayyed Mohammad Hadi Alavi, Kazue Nagasawa, Keisuke G.\nTakahashi and Makoto Osada",downloadPdfUrl:"/chapter/pdf-download/55923",previewPdfUrl:"/chapter/pdf-preview/55923",authors:[{id:"198996",title:"Prof.",name:"Makoto",surname:"Osada",slug:"makoto-osada",fullName:"Makoto Osada"}],corrections:null},{id:"55803",title:"Structure-Function of Serotonin in Bivalve Molluscs",doi:"10.5772/intechopen.69165",slug:"structure-function-of-serotonin-in-bivalve-molluscs",totalDownloads:1690,totalCrossrefCites:5,totalDimensionsCites:7,hasAltmetrics:1,abstract:"It has been observed that 5-HT excites the heart nerves in hard clam and regulates contraction and relaxation of the anterior byssus retractor muscle in the blue mussel. It is now known that 5-HT regulates several neurobehavioral systems such as mood, appetite, sleep, learning, and memory. It also plays critical roles in the physiological functions of peripheral organs involved in stress, growth, and reproduction in the animal kingdom. The present study reviews conserved 5-HT biosynthesis and its localization in the nervous system, and its physiological contribution to regulate reproduction in bivalves. In the cytosol of neurons, tryptophan hydroxylase catalyzes hydroxylation of l-tryptophan to 5-hydroxytryptophan, which is converted to 5-HT by aromatic l-amino acid decarboxylase. A 5-HT transporter and a monoamine oxidase reuptakes and metabolizes 5-HT to control the amount of released 5-HT in the nervous system and peripheral organs. Perikarya and fibers of 5-HT neurons are mostly located in the cortices and neuropil of ganglia, respectively, and innervate the gonad. However, distribution and 5-HT content differ among species and sexes and undergo seasonal variations associated with gonadal development. The present review pays a special attention to future research perspectives to better understand 5-HT regulation of reproduction in bivalves.",signatures:"Sayyed Mohammad Hadi Alavi, Kazue Nagasawa, Keisuke G.\nTakahashi and Makoto Osada",downloadPdfUrl:"/chapter/pdf-download/55803",previewPdfUrl:"/chapter/pdf-preview/55803",authors:[{id:"198996",title:"Prof.",name:"Makoto",surname:"Osada",slug:"makoto-osada",fullName:"Makoto Osada"},{id:"198998",title:"Dr.",name:"Sayyed Mohammd",surname:"Hadi Alavi",slug:"sayyed-mohammd-hadi-alavi",fullName:"Sayyed Mohammd Hadi Alavi"},{id:"205318",title:"Dr.",name:"Kazue",surname:"Nagasawa",slug:"kazue-nagasawa",fullName:"Kazue Nagasawa"},{id:"205319",title:"Dr.",name:"Keisuke",surname:"Takahashi",slug:"keisuke-takahashi",fullName:"Keisuke Takahashi"}],corrections:null},{id:"55964",title:"4WD to Travel Inside the 5-HT1A Receptor World",doi:"10.5772/intechopen.69348",slug:"4wd-to-travel-inside-the-5-ht1a-receptor-world",totalDownloads:1365,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"5-HT1A receptor is one of the most important members of the numerous families of serotoninergic receptors. Though it was the first 5-HT receptor to be identified and cloned, the knowledge of its activation/transduction mechanisms, mediated effects, and connection with other systems is still uncompleted. For this reason, relevant is the study of the four Ws of the title: first of all “who” this receptor is, then “why” it continues to be a so attractive target after several years after its identification, then “where” is 5-HT1A receptor expressed within the body, and, finally, “what” effects this receptor can elicit under physiological and pathological conditions. Obviously, more and more potent, safe, and selective “drugs” might be discovered once the responses to these questions are given.",signatures:"Wilma Quaglia, Carlo Cifani, Fabio Del Bello, Mario Giannella,\nGianfabio Giorgioni, Maria Vittoria Micioni Di Bonaventura and\nAlessandro Piergentili",downloadPdfUrl:"/chapter/pdf-download/55964",previewPdfUrl:"/chapter/pdf-preview/55964",authors:[{id:"198136",title:"Prof.",name:"Wilma",surname:"Quaglia",slug:"wilma-quaglia",fullName:"Wilma Quaglia"},{id:"198141",title:"Prof.",name:"Carlo",surname:"Cifani",slug:"carlo-cifani",fullName:"Carlo Cifani"},{id:"198142",title:"Dr.",name:"Fabio",surname:"Del Bello",slug:"fabio-del-bello",fullName:"Fabio Del Bello"},{id:"198143",title:"Prof.",name:"Mario",surname:"Giannella",slug:"mario-giannella",fullName:"Mario Giannella"},{id:"198144",title:"Dr.",name:"Gianfabio",surname:"Giorgioni",slug:"gianfabio-giorgioni",fullName:"Gianfabio Giorgioni"},{id:"198145",title:"Dr.",name:"Maria Vittoria",surname:"Micioni Di Bonaventura",slug:"maria-vittoria-micioni-di-bonaventura",fullName:"Maria Vittoria Micioni Di Bonaventura"},{id:"198146",title:"Prof.",name:"Alessandro",surname:"Piergentili",slug:"alessandro-piergentili",fullName:"Alessandro Piergentili"}],corrections:null},{id:"55466",title:"Sculpting Cerebral Cortex with Serotonin in Rodent and Primate",doi:"10.5772/intechopen.69000",slug:"sculpting-cerebral-cortex-with-serotonin-in-rodent-and-primate",totalDownloads:1638,totalCrossrefCites:2,totalDimensionsCites:8,hasAltmetrics:0,abstract:"The mammalian cerebral cortex is critical for sensory and motor integrations and, for higher-order cognitive functions. The construction of mammalian cortical circuits involves the coordinated interplay between cellular processes such as proliferation, migration and differentiation of neural and glial cell subtypes followed by accurate connectivity evolving in complexity in primates. Alteration in cortical development may induce the emergence of various pathological traits and behaviours. Among the large array of factors that regulate the assembly of cortical circuits, serotonin (5-HT) plays important role as a developmental signal that impacts on a broad diversity of cellular processes. 5-HT plays distinct roles during specific sensitive periods and is produced from various sources depending on the perinatal stage. Its roles are mediated by more than fourteen 5-HT receptors that are all G-protein coupled receptors except the ionotropic 5-HT type 3A receptor (5-HT3A) mediating rapid neuronal activation. Importantly, 5-HT metabolism and signalling are influenced by numerous epigenetic and genetic factors, including nutrition and gut microbiota, perinatal stress, infection and inflammation. In this review, we will recapitulate some evidences showing that dysregulation of 5-HT homeostasis and 5-HT3A signalling impairs distinct steps of cortical circuit formation leading to the predisposition of the onset of various psychiatric diseases.",signatures:"Tania Vitalis and Catherine Verney",downloadPdfUrl:"/chapter/pdf-download/55466",previewPdfUrl:"/chapter/pdf-preview/55466",authors:[{id:"197392",title:"Dr.",name:"Tania",surname:"Vitalis",slug:"tania-vitalis",fullName:"Tania Vitalis"},{id:"201322",title:"Dr.",name:"Catherine",surname:"Verney",slug:"catherine-verney",fullName:"Catherine Verney"}],corrections:null},{id:"55574",title:"Association of 5-HT1A Receptors with Affective Disorders",doi:"10.5772/intechopen.68975",slug:"association-of-5-ht1a-receptors-with-affective-disorders",totalDownloads:1673,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Serotonin or 5-hydroxytryptamine (5-HT) is synthesized in both the brain and peripheral system, which exert their actions at a wide family of receptors classified as 5-HT1 to 5-HT7. Pharmacological, behavioral, and clinical studies involve particularly to the 5-HT1A receptors (5-HT1A-R) - auto-receptors (presynaptic) and heteroreceptors (postsynaptic) - in the control of motivated behavior, and consequently in the physiopathology of affective disorders and in the action mechanism of antidepressant drugs. In this way, some research support that 5-HT1A-R participates in the delayed effect of different types of antidepressants, including selective serotonin reuptake inhibitors (SSRIs), and tricyclic drugs, principally. The therapeutic effect of serotonergic drugs as the SSRIs, starting with the binding to auto-receptors, which produces increases of 5-HT in the synaptic cleft as consequence of blockade of serotonin reuptake. While these molecular events occur initially, in the long-term are produced plastic changes at neuronal level, as well as down-regulation of the 5-HT1A-R, which is associated with the therapeutic effects of antidepressant drugs. The purpose of this chapter is to analyze and discuss the current information about of 5-HT1A-R-mediated signaling cascades, the intracellular signaling of 5-HT1A-R, in addition to their expression and pharmacology that are important to treatment of affective disorders symptoms.",signatures:"Cesar Soria-Fregozo, Maria Isabel Perez-Vega, Juan Francisco\nRodríguez-Landa, León Jesús Germán-Ponciano, Rosa Isela García-\nRíos and Armando Mora-Perez",downloadPdfUrl:"/chapter/pdf-download/55574",previewPdfUrl:"/chapter/pdf-preview/55574",authors:[{id:"45702",title:"Dr.",name:"Juan Francisco",surname:"Rodríguez-Landa",slug:"juan-francisco-rodriguez-landa",fullName:"Juan Francisco Rodríguez-Landa"},{id:"174652",title:"MSc.",name:"León Jesús",surname:"Germán-Ponciano",slug:"leon-jesus-german-ponciano",fullName:"León Jesús Germán-Ponciano"},{id:"174653",title:"Dr.",name:"Rosa Isela",surname:"García-Ríos",slug:"rosa-isela-garcia-rios",fullName:"Rosa Isela García-Ríos"},{id:"174654",title:"Dr.",name:"Cesar",surname:"Soria-Fregozo",slug:"cesar-soria-fregozo",fullName:"Cesar Soria-Fregozo"},{id:"198324",title:"Dr.",name:"Maria Isabel",surname:"Perez-Vega",slug:"maria-isabel-perez-vega",fullName:"Maria Isabel Perez-Vega"},{id:"198327",title:"Dr.",name:"Armando",surname:"Mora-Perez",slug:"armando-mora-perez",fullName:"Armando Mora-Perez"}],corrections:null},{id:"55421",title:"Application of 5-HT-SO4 in Biomarker Research",doi:"10.5772/intechopen.69042",slug:"application-of-5-ht-so4-in-biomarker-research",totalDownloads:1069,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"A serotonin catabolite, serotonin O‐sulphate (5‐HT‐SO4), is hypothesised to accentuate the intensity of serotonin metabolism in the central nervous system (CNS). We hypothesised that serotonin O‐sulphate could be quantified in human plasma using modern liquid chromatography‐mass spectrometry. To test our hypothesis, we performed a critical literature review and a three‐stage trial. First, a suitable liquid chromatography‐mass spectrometry (LC‐MS/MS) method for detection of 5‐HT‐SO4 in human plasma samples was developed. Second, a pilot phase involving four healthy volunteers was executed. Finally, nine healthy volunteers were selected for the main study, where a basal plasma level of 5‐HT‐SO4 was measured before and after serotonergic stimulation of the central nervous system. One h after stimulation, six study subjects showed a decrease in 5‐HT‐SO4 levels, while three subjects showed an increase. This was the first study in which naturally occurring 5‐HT‐SO4 was detected by liquid chromatography–mass spectrometry (LC‐MS/MS) in the samples of human plasma obtained from healthy volunteers. The method developed was specific to the measurement of 5‐HT‐SO4 and opens up new possibilities to evaluate minor pathways or serotonin metabolism by minimally invasive methods.",signatures:"Raimond Lozda",downloadPdfUrl:"/chapter/pdf-download/55421",previewPdfUrl:"/chapter/pdf-preview/55421",authors:[{id:"200035",title:"M.D.",name:"Raimond",surname:"Lozda",slug:"raimond-lozda",fullName:"Raimond Lozda"}],corrections:null},{id:"55260",title:"Energy Homeostasis by the Peripheral Serotonergic System",doi:"10.5772/intechopen.68831",slug:"energy-homeostasis-by-the-peripheral-serotonergic-system",totalDownloads:1528,totalCrossrefCites:1,totalDimensionsCites:6,hasAltmetrics:0,abstract:"Energy homeostasis is maintained by balancing energy intake and energy expenditure. In addition to the central nervous system, several hormones play a key role in energy homeostasis in the whole body. In particular, serotonin is regarded as one of the key regulators of energy homeostasis. Serotonin is unique in that it is able to act in both the brain as a neurotransmitter and the peripheral tissue as a gastrointestinal hormone. In the brain, serotonin is thought of as a pharmacological target for anti-obesity treatments because it greatly inhibits meal size and body weight gain. In contrast, serotonin in the periphery has not been targeted as a strategy for anti-obesity treatment, even though almost all of the serotonin produced in the body is produced in the peripheral tissue. Recently, the peripheral serotonergic signal has been shown to regulate glucose and lipid metabolism through autocrine and paracrine signals in energy homeostasis-related tissues, including the pancreatic β cell, liver, white adipose tissue, brown adipose tissue, and skeletal muscle. Thus, it is possible that the serotonergic system in the peripheral tissue is a new therapeutic target for metabolic disease, including obesity and diabetes. Here, we summarize the role of peripheral serotonin in the regulation of energy homeostasis.",signatures:"Hitoshi Watanabe, Michael Rose, Yoshinori Kanayama, Hitoshi\nShirakawa and Hisashi Aso",downloadPdfUrl:"/chapter/pdf-download/55260",previewPdfUrl:"/chapter/pdf-preview/55260",authors:[{id:"128157",title:"Dr.",name:"Michael",surname:"Rose",slug:"michael-rose",fullName:"Michael Rose"},{id:"180389",title:"Dr.",name:"Hitoshi",surname:"Shirakawa",slug:"hitoshi-shirakawa",fullName:"Hitoshi Shirakawa"},{id:"198097",title:"Prof.",name:"Hisashi",surname:"Aso",slug:"hisashi-aso",fullName:"Hisashi Aso"},{id:"198154",title:"Dr.",name:"Hitoshi",surname:"Watanabe",slug:"hitoshi-watanabe",fullName:"Hitoshi Watanabe"}],corrections:null},{id:"54443",title:"Serotonin Effects on Expression of the LDL Receptor Family Member LR11 and 7-Ketocholesterol–Induced Apoptosis in Human Vascular Smooth Muscle Cells",doi:"10.5772/67679",slug:"serotonin-effects-on-expression-of-the-ldl-receptor-family-member-lr11-and-7-ketocholesterol-induced",totalDownloads:1239,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"We previously confirmed the effect of sarpogrelate hydrochloride (sarpogrelate), 5-hydroxytryptamine (5-HT) 2A receptor antagonist on cardio-ankle vascular index (CAVI) as a marker of systemic arterial stiffness. After 6 months of treatment with sarpogrelate for 35 type 2 diabetic patients, decreased CAVI, indicating the ameliorated arterial stiffness, was observed. Therefore, via 5-HT2A receptor blockade, sarpogrelate might effect as a vasoactive agent, as well as an inhibitor of platelet aggregation. 5-HT is a known mitogen for vascular smooth muscle cells (VSMCs). In addition, the pathogenic change of VSMCs such as dedifferentiation and proliferation/apoptosis represents one of the atherosclerotic changes. On the other hand, LR11, a mosaic LDL receptor family member, may involve in the invasion of VSMCs into neointimal thickening. We therefore investigated an in vitro study to clarify whether 5-HT was concerned to LR11 expression and apoptosis of human VSMCs induced by 7-ketocholesterol (7KCHO), a major oxidation product of cholesterol involved in plaque destabilization. Resultantly, 5-HT accelerated the proliferation of VSMCs, and this effect was suppressed by simultaneous addition of sarpogrelate. Sarpogrelate also attenuated the 5-HT–induced LR11 mRNA expression in VSMCs. Additionally, 5-HT attenuated the 7KCHO-induced apoptosis of VSMCs through caspase-dependent pathway. These results suggest new knowledge on the modification of human VSMCs induced by 5-HT.",signatures:"Daiji Nagayama and Ichiro Tatsuno",downloadPdfUrl:"/chapter/pdf-download/54443",previewPdfUrl:"/chapter/pdf-preview/54443",authors:[{id:"198108",title:"Ph.D.",name:"Daiji",surname:"Nagayama",slug:"daiji-nagayama",fullName:"Daiji Nagayama"},{id:"204711",title:"Prof.",name:"Ichiro",surname:"Tatsuno",slug:"ichiro-tatsuno",fullName:"Ichiro Tatsuno"}],corrections:null},{id:"55438",title:"Serotonin in Neurological Diseases",doi:"10.5772/intechopen.69035",slug:"serotonin-in-neurological-diseases",totalDownloads:2006,totalCrossrefCites:5,totalDimensionsCites:9,hasAltmetrics:1,abstract:"Serotonin (5-HT) is responsible for anxiety, aggression, and stress. Alterations in a serotonergic system play a significant role in pathogenesis of neurological diseases and neuropsychiatric disorders. A wide range of disturbances associated with serotonergic neurotransmission results from different functions of 5-HT in a nervous system. It is believed that 5-HT may be involved in the pathogenesis of migraine, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), attention-deficit hyperactivity disorder (ADHD), and autism spectrum disorder (ASD). In these diseases, disturbances of 5-HT and its metabolites, such as 5-hydroxyindoleacetic acid (5-HIAA), were observed in the plasma, blood platelets, and cerebrospinal fluid (CSF). Changes in the level of this biogenic amine (5-HT) may be associated with malfunction of 5-HT receptors, reuptake transporter for 5-HT (5-HTT, SERT), the enzymes responsible for the synthesis and metabolism of 5-HT, and genetic variants for serotonergic system. It seems that 5-HT and its metabolites may be used as a diagnostic and prognostic marker for neurological diseases or a target for more efficient therapy in neurology in the future.",signatures:"Jolanta Dorszewska, Jolanta Florczak-Wyspianska, Marta Kowalska,\nMarcin Stanski, Alicja Kowalewska and Wojciech Kozubski",downloadPdfUrl:"/chapter/pdf-download/55438",previewPdfUrl:"/chapter/pdf-preview/55438",authors:[{id:"31962",title:"Dr.",name:"Jolanta",surname:"Dorszewska",slug:"jolanta-dorszewska",fullName:"Jolanta Dorszewska"},{id:"83372",title:"Prof.",name:"Wojciech",surname:"Kozubski",slug:"wojciech-kozubski",fullName:"Wojciech Kozubski"},{id:"183236",title:"Dr.",name:"Jolanta",surname:"Florczak-Wyspianska",slug:"jolanta-florczak-wyspianska",fullName:"Jolanta Florczak-Wyspianska"},{id:"186528",title:"MSc.",name:"Marta",surname:"Kowalska",slug:"marta-kowalska",fullName:"Marta Kowalska"},{id:"197937",title:"Mr.",name:"Marcin",surname:"Stanski",slug:"marcin-stanski",fullName:"Marcin Stanski"},{id:"197995",title:"Mrs.",name:"Alicja",surname:"Kowalewska",slug:"alicja-kowalewska",fullName:"Alicja Kowalewska"}],corrections:null},{id:"55400",title:"The Role of Serotonin in Aggression and Impulsiveness",doi:"10.5772/intechopen.68918",slug:"the-role-of-serotonin-in-aggression-and-impulsiveness",totalDownloads:2048,totalCrossrefCites:5,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Serotonin is a neuromodulator that has a critical role on the regulation of essential events in neuronal and glial development, such as cell proliferation, differentiation, migration, apoptosis, and synaptogenesis, and acts as a developmental signal. It has been known that a serotonergic system is associated with many psychiatric disorders. The serotonergic system also predominates on the etiopathogenesis of two important endophenotypes: impulsivity and aggression. Impulsiveness is defined as personality trait and an implusive temperament is associated with clinical conditions such as pathological gambling, eating disorders, and borderline personality disorder as well as being a risk factor for self‐harm, suicide, and emotional liability. Aggression is not a personality trait like impulsivity, but it is the behavior of harm or injury to others. Besides being a natural human behavior toward survival, aggression can be harmful to the individual and the community when it is constant and excessive. In this chapter, we aimed to review the role of the serotonergic system on impulsivity and aggression, which are two important endophenotypes that identified in many psychiatric disorders.",signatures:"Fatih Hilmi Çetin, Yasemin Taş Torun and Esra Güney",downloadPdfUrl:"/chapter/pdf-download/55400",previewPdfUrl:"/chapter/pdf-preview/55400",authors:[{id:"44984",title:"M.D.",name:"Esra",surname:"Guney",slug:"esra-guney",fullName:"Esra Guney"},{id:"171467",title:"Dr.",name:"Yasemin",surname:"Tas Torun",slug:"yasemin-tas-torun",fullName:"Yasemin Tas Torun"},{id:"205773",title:"Dr.",name:"Fatih Hilmi",surname:"Çetin",slug:"fatih-hilmi-cetin",fullName:"Fatih Hilmi Çetin"}],corrections:null},{id:"55699",title:"Immuno-Thrombotic Effects of Platelet Serotonin",doi:"10.5772/intechopen.69349",slug:"immuno-thrombotic-effects-of-platelet-serotonin",totalDownloads:1821,totalCrossrefCites:3,totalDimensionsCites:6,hasAltmetrics:1,abstract:"Platelets transport and store serotonin at a high concentration in dense granules and release it upon activation. Abnormal serotonin concentrations in the blood plasma or increased platelet serotonin release promote the development of thrombosis, sepsis, allergic asthma, myocardial infarction, and stroke. Consequently, experimental data suggest possible benefits of serotonin receptor blockade or inhibition of platelet serotonin uptake in the indicated human diseases. Here, we highlight the current state of basic biological research regarding the role of platelet serotonin in normal and pathophysiological conditions focusing on thrombotic and inflammatory diseases. We also describe the possible clinical applicability of targeting thrombo-immune-modulatory effects of platelet serotonin to treat common health problems.",signatures:"Elmina Mammadova-Bach, Maximilian Mauler, Attila Braun and\nDaniel Duerschmied",downloadPdfUrl:"/chapter/pdf-download/55699",previewPdfUrl:"/chapter/pdf-preview/55699",authors:[{id:"198138",title:"Dr.",name:"Daniel",surname:"Duerschmied",slug:"daniel-duerschmied",fullName:"Daniel Duerschmied"},{id:"205547",title:"Dr.",name:"Elmina",surname:"Mammadova-Bach",slug:"elmina-mammadova-bach",fullName:"Elmina Mammadova-Bach"},{id:"205548",title:"Dr.",name:"Maximilian",surname:"Mauler",slug:"maximilian-mauler",fullName:"Maximilian Mauler"},{id:"205549",title:"Dr.",name:"Attila",surname:"Braun",slug:"attila-braun",fullName:"Attila Braun"}],corrections:null},{id:"55884",title:"Production and Function of Serotonin in Cardiac Cells",doi:"10.5772/intechopen.69111",slug:"production-and-function-of-serotonin-in-cardiac-cells",totalDownloads:1584,totalCrossrefCites:4,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Serotonin [5-hydroxy-tryptamine (5-HT)] exerts a number of effects in the mammalian heart: increase in heart rate, increase in force of contraction, fibrosis of cardiac valves, coronary constriction, arrhythmias and thrombosis. These effects are, in part, mediated by 5-HT-receptors, in part, directly by 5-HT action on intracellular proteins. In the beginning, 5-HT was thought to be only produced in the gut and then transported into the heart via platelets, because platelets can take up 5-HT in the gut and enter the capillaries and thus the mammalian heart. 5-HT is to a large extent metabolized in the liver and excreted via the urine. Here, we will also overview data that argue for additional pathways, namely production and degradation of 5-HT in the cells of the heart itself.",signatures:"Joachim Neumann, Britt Hofmann and Ulrich Gergs",downloadPdfUrl:"/chapter/pdf-download/55884",previewPdfUrl:"/chapter/pdf-preview/55884",authors:[{id:"198376",title:"Prof.",name:"Joachim",surname:"Neumann",slug:"joachim-neumann",fullName:"Joachim Neumann"},{id:"205353",title:"Dr.",name:"Britt",surname:"Hofmann",slug:"britt-hofmann",fullName:"Britt Hofmann"},{id:"205354",title:"Dr.",name:"Ulrich",surname:"Gergs",slug:"ulrich-gergs",fullName:"Ulrich Gergs"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"1624",title:"Patch Clamp Technique",subtitle:null,isOpenForSubmission:!1,hash:"24164a2299d5f9b1a2ef1c2169689465",slug:"patch-clamp-technique",bookSignature:"Fatima Shad 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\r\n\tGeodesy is one of the scientific disciplines that has benefited the most from advances in satellite technology since the first artificial satellite was launched into orbit. Higher-resolution mapping of the earth, higher accuracy geodetic position computations based on global geodetic reference systems, and a better understanding of dynamic processes have all been achieved as a result of data obtained from satellites and satellite systems. As satellites and satellite systems continue to advance, observations obtained provide more detailed and long-term data on the earth's dynamic processes, and predictions and models based on these data enable effective risk management and the improvement of future living conditions on the Earth. In this regard, the chapters on data processing and modeling methodologies, accompanied by significant case study examples, in this book in preparation aim to highlight the use and importance of satellite and satellite system observations in geodetic applications and Earth observation studies. The following are the major categories of themes that are intended to be discussed in the book's content: low-Earth-orbiting satellites; observation techniques, data processing, and achievements in the branch of Earth gravity field studies obtained with the contribution of these satellite missions data (CHAMP, GOCE, GRACE/GRACE-Follow On, and future concepts in satellite gravimetry), ii-) satellite altimetry; recent progress in the techniques and applications including marine gravity and sea-level change determination, coastal altimetry and inland water studies, iii-) global navigation satellite systems; geodetic positioning, GNSS meteorology, and GNSS reflectometry studies including new data processing strategies (multi-GNSS, PPP, RT-PPP) and case study examples in various application fields, iv-) remote sensing satellites in Earth observation, monitoring, and mapping surface deformations and natural disasters, environmental changes because of global warming and its consequences in vulnerable areas, and v-) global, regional and national geodetic reference frames, which are necessary for efficient utilization of the satellite-based techniques in geodetic applications and monitoring Earth dynamic processes. Within the scope of outlined content, this book is intended to be a useful reference for all researchers and practitioners from engineering and geoscience disciplines who conduct research and applications using satellite and satellite system data.
",isbn:"978-1-83969-741-8",printIsbn:"978-1-83969-740-1",pdfIsbn:"978-1-83969-742-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"7c21d1a8ed9ad6be081d2e74d977d2bc",bookSignature:"Dr. Bihter Erol",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11489.jpg",keywords:"Satellite Gravimetry, Earth Gravity Field, Coastal Altimetry, Inland Altimetry, Geodetic Positioning, Measurement Errors, GNSS, ITRF, Geodetic Reference System, Polar Research, InSAR, Surface Deformations",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 28th 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"A scientist in Geodesy has publications on Physical Geodesy, height systems, deformation monitoring, and positioning. She has research projects in her research fields and teaches in undergraduate and graduate programs. Member of International Association of Geodesy.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"75478",title:"Dr.",name:"Bihter",middleName:null,surname:"Erol",slug:"bihter-erol",fullName:"Bihter Erol",profilePictureURL:"https://mts.intechopen.com/storage/users/75478/images/system/75478.png",biography:"Dr. Bihter Erol earned a Ph.D. in geodesy from Istanbul Technical University (ITU) in 2007, and she is still a full-time associate professor at the ITU Geomatics Department. Her research interests in physical geodesy include the static and temporal determination of the Earth's gravity field, regional geoid modeling using terrestrial and airborne gravimetry, height systems, and structural deformation analyses. Dr. Bihter Erol has research experience in her field at various departments and institutes in Canada, Germany, and the Netherlands. She has numerous scientific journal articles, book chapters, and proceedings to her credit, as well as contributions as an editor and reviewer in geodetic journals, books, and proceedings. She participates in a number of international symposia organizations and scientific committees. She is a member of the ITU Gravity Research Group, supervises thesis studies in the ITU Graduate School's Geomatics and Geographical Information Technologies programs, and conducts research projects in her research fields.",institutionString:"Istanbul Technical University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Istanbul Technical University",institutionURL:null,country:{name:"Turkey"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"10",title:"Earth and Planetary Sciences",slug:"earth-and-planetary-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466997",firstName:"Patricia",lastName:"Kerep",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/466997/images/21565_n.jpg",email:"patricia@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3828",title:"Application of Nanotechnology in Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"51a27e7adbfafcfedb6e9683f209cba4",slug:"application-of-nanotechnology-in-drug-delivery",bookSignature:"Ali Demir Sezer",coverURL:"https://cdn.intechopen.com/books/images_new/3828.jpg",editedByType:"Edited by",editors:[{id:"62389",title:"PhD.",name:"Ali Demir",surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"72511",title:"Vasculitis and Vasculopathies",doi:"10.5772/intechopen.92778",slug:"vasculitis-and-vasculopathies",body:'\nVasculitis and vasculopathies are a group of diseases that course with an inflammatory process, which attacks vascular endothelium of vessels of different calibers. Usually, they course with dermatology lesions, the diagnosis is difficult, and they have a few treatment options. Despite that, an early diagnosis can contribute to a better quality of patient’s life and prevent further complications (Figure 1) [1].
\nPurpuric macules and papules coalescing into patches (A) in small vessel vasculitis and fixed livedo reticularis and subcutaneous nodules (B) in medium vessel vasculitis (polyarteritis nodosa) [
The authors performed a bibliographic review from cutaneous vasculitis and vasculopathies from literature, including online academics platforms such as PubMed and Google Scholar and dermatology books as Rivitti and Fitispack. The keywords used from this chapter were cutaneous vasculitis, Takayasu arteritis, Giant Cell Arteritis, Polyarteritis Nodosa, Kawasaki Disease, Microscopic polyangiitis, Granulomatosis with Polyangiitis (Wegener’s), Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss), Cryoglobulinemic Vasculitis, Urticaria Vasculitis, Henoch-Schönlein, Behçet’s syndrome, Cutaneous leukocytoclastic angiitis, cutaneous vasculopathies, Phospholipid Antibody Syndrome, Blue Finger Syndrome, Acrocyanosis and others. The final objective was summing up the dermatology vasculitis and vasculopathies and helping physicians in early diagnosis and treatment.
\nCutaneous vasculitis may affect vessels of different calibers, especially small and medium in the skin and the subcutaneous tissue, resulting in just a small cutaneous lesion until serious systemic commitment. Nevertheless, the classification is not a consensus. In general, they are classified using clinical criteria, size of the vessels, histopathological exams, laboratorial findings and etiologic agents [3, 4]. In 2012, the
It is a large vessel vasculitis whose etiologic agent is unknown. It is more frequently found in young Asiatic women, in the proportion from 5 to 12 W:1 M, and usually affects the aorta and its main branches. It is not a rare disease but is not as usual as arteritis of giant cells. The diagnosis is usually late because these patients develop many collateral arteries, they have nonspecific symptoms and the development of these affections is very slow. Pregnancy in patients affected by Takayasu arteritis is a troubling problem because it affects women of childbearing age, and it will cause risks to the mother and the child. The arteritis could be associated with Crohn’s and rectocolitis disease [6].
\nThe more effective treatments are oral corticosteroids, but there are many relapses when corticosteroids taper. High doses of corticosteroids (40–60 mg/day of prednisone or equivalent) should be initiated immediately after the diagnosis to induce remission. During disease remission, it is necessary sparing the drug until 15-20mg/day for two or three months, and after a year decrease the doses to 10mg/day or less. The immunosuppressive agents are used as corticoid sparing agents such as methotrexate, azathioprine, leflunomide, mycophenolate mofetil and cyclophosphamide [6]. There are evidences that biological agents such as anti-TNF-alpha, tocilizumab and rituximab could be effective in refractory cases, but more trials are necessary to evaluate the effectiveness of these drugs [8]. In addition, patients with ischemic problems need endovascular interventions. The mortality range is between 3 and 21% [6].
\nIt is a systemic vasculitis of large vessels, with tropism to the aorta and its branches, mainly external carotid. It is a most common vasculitis in above 50-year-olds and affects more women than men (3 W:2 M). The corticosteroids are the most common therapeutic used in these cases. In the beginning, we need high doses of corticosteroids to control the inflammation, and then it could be used sparingly until controlled in the patient. These strategies are valid for simple and complicated forms of the disease [7].
\nSimple form is defined by cephalic isolated symptoms with visual disturbance or changes in central nervous system. Nowadays, the gold standard treatment is oral prednisone or equivalent 40–60 mg/day, and methylprednisolone is not used anymore. The initial dose recommended is 0.7 mg/kg day of prednisone and the maximum dose is 80 mg/day [7].
\nThe complicated form is defined when there is an ophthalmologic or a central nervous or extracephalic complication, mainly aorta and its branches. In these cases, methylprednisolone in pulses of 500 mg−1 g a day shall be used for 1 to 5 consecutive days. During maintenance, some authors believe in doses less than 5 mg/day. The American Society of Ophthalmology recommends pulses of intravenous methylprednisolone, when patients have ophthalmologic symptoms, but the Rheumatology Society prefers oral corticosteroid [7].
\nIt is strategic to introduce corticosteroid-sparing drugs when the disease course is lasting long. Methotrexate is the most used treatment and with more evidence levels. There are four trials with methotrexate as a sparing drug, but the doses and the management are variable from 7.5–15 mg/week [7].
\nCyclophosphamide has demonstrated effectiveness in patients dependent on corticosteroids or resistant to treatment. It is necessary to give more than 20 mg/day for 6 months or 10 mg/day for 1 year or more. The dose from 500 mg/m2 or 500 mg/injection in 6 courses is standard from 5 months on average. It is highly important to warn patients of several side effects such as bone marrow suppression [7].
\nAzathioprine therapy has less controlled studies. Some studies showed a modest improvement. Hydroxychloroquine, an antimalarial synthetic drug, was tested also. One French study divided patients into two groups: one took prednisone 0.7 mg/kg/day in the beginning associated with hydroxychloroquine (400 mg/day) and the control group just received prednisone and placebo. The group that had hydroxychloroquine and corticoid had usually stopped later the prednisone and they had more relapses [7].
\nNowadays, one option is biologics medicines. Anti-TNF-alpha does not have enough studies that showed control of the disease with this class of medication [7]. Tocilizumab, a humanized antibody that blocked membranous and soluble receptors of IL-6 (IL-6R), is a current option since IL-Il-6 is implicated in the etiopathogenesis of this affection. Three main studies evaluated the efficacy of the drug, although the therapeutics was different between these studies [7, 8].
\nA randomized control trial with 30 patients had tested 20 patients receiving corticoids and tocilizumab (8 mg/kg every 4 week during a year), and 10 received corticoids and placebo. The survival without relapses during a year was highest in patients treated with tocilizumab. However, there are no data available after the medication was stopped [7, 8].
\nAnother promising biotherapy is abatacept. This medication with corticoids could decrease the risk of relapses, although more data is necessary to corroborate this hypothesis.
\nUstekinumab, a subunit against anti-p40 IL-12/23 targeting Th1 and Th17 responses, has been showing similar side effects as corticoids. Some patients, who had refractory disease, have been treated with anakinra and they achieved success. Anakinra is a biopharmaceutical drug that blocks IL-1. All patients who had taken the drug had shown improvement in inflammation biomarkers and/or in their symptoms, with the disappearance of arterial inflammation in PET/CT. More studies are necessary though [7].
\nOther pharmacological drugs can be used as adjuvant treatments such as antiplatelets and anticoagulants, but there is no official recommendation about these drugs in the treatment of GAC. The statins do not influence the evolution of the disease, but they are used to prevent cardiovascular risk. Furthermore, these drugs could have an anti-inflammatory role via the inhibition of TH17 pathway [7].
\nIt is a rare necrotizing systemic vasculitis that affects small- and medium-sized vessels and is not usually associated with ANCA [8, 9], although there are reports in the literature of patients with PAN and positive ANCA. Several treatments are suggested for this condition, and the control is still a challenge [9].
\nCutaneous involvement and peripheral nerves are the favorite sites of the disease, cutaneous and gastrointestinal vasculitis have specific histopathological characteristics, and until now, it has no development glomerulonephritis described. Gastrointestinal tract involvement is common and is one of the predictors of disease morbidity and mortality. There is cutaneous PAN without systemic involvement, and it very rarely progresses to the systemic form of the disease. According to the new classification, PAN is subdivided into idiopathic PAN and hepatitis B-associated PAN [9].
\nTreatment of PAN is usually based on the combination of systemic corticosteroids and immunosuppressants. The most commonly used medications are cyclophosphamide, azathioprine, methotrexate or mycophenolate mofetil [9].
\nThe use of biological medications is reserved for cases of refractory PAN without association with hepatitis B. The use of rituximab, an anti-CD20 monoclonal antibody, has not been formally indicated for patients with PAN, but its use is supported in patients with ANCA-associated vasculitis. There are case reports using anti-TNF-alpha, such as etanercept and infliximab, and tocilizumab, but only in refractory cases [8].
\nIt is a systemic vasculitis, common in male child, with fever, rash, non-exudative bilateral conjunctivitis, oral and pharyngeal mucosal erythema, cervical lymphadenopathy, and it can affect the extremity. They may have fewer common symptoms such as pyuria, meningitis, shock and retropharyngeal or parapharyngeal abscess [10].
\nThe etiology of Kawasaki disease is unknown. The diagnosis of Kawasaki disease is based on the presence of fever for ≥5 days, along with the presence of at least 4 of the 5 main clinical features [10] (Table 2).
\n\n\n | Classification | \nDiseases | \n
---|---|---|
1 | \nLarge vessel vasculitis | \nTakayasu arteritis Giant cell arteritis | \n
2 | \nMedium vessel | \nPolyarteritis nodosa Kawasaki disease | \n
3 | \nSmall vessel vasculitis ANCA-associated vasculitis | \nMicroscopic polyangiitis Granulomatosis with polyangiitis (Wegener’s) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) | \n
4 | \nSmall vessel vasculitis Immune complex | \nAntiglomerular basement membrane disease Cryoglobulinemic vasculitis (CV) Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis) IgA vasculitis (Henoch-Schönlein) | \n
5 | \nVariable vessel vasculitis | \nBehçet’s syndrome Cogan’s syndrome | \n
6 | \nSingle-organ vasculitis | \nCutaneous leukocytoclastic angiitis Cutaneous arteritis Primary central nervous system vasculitis | \n
7 | \nVasculitis associated with systemic disease | \nLupus vasculitis Rheumatoid vasculitis Sarcoid vasculitis Others | \n
8 | \nVasculitis associated with probable cause | \nHepatitis C virus-associated CV Hepatitis B virus-associated vasculitis Syphilis-associated aortitis Drug-associated immune complex vasculitis Drug-associated ANCA-associated vasculitis Cancer-associated vasculitis Others | \n
2012 International Chapel Hill Consensus Conference Nomenclature of Vasculitides [3].
\n | Clinical features | \n
---|---|
1 | \nErythema and cracking of the lips, strawberry tongue and/or pharyngeal and oral mucosa erythema | \n
2 | \nBilateral bulbar conjunctival injection without exudate | \n
3 | \nRash | \n
4 | \nErythema and edema of the hands and feet in the acute phase and/or periungual scaling in the subacute phase | \n
5 | \nCervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral | \n
Clinical features in Kawasaki disease [10].
Patients who have met the diagnostic criteria are considered to have complete Kawasaki disease (also referred to as typical or classic Kawasaki disease). Patients who do not have enough major clinical findings can be diagnosed with incomplete Kawasaki disease [10].
\nIntravenous immunoglobulin (IVIG) is the basis for treatment. Usually, it is initiated before 10 days of fever and significantly reduces coronary artery aneurysms (CAAs) that decrease from 25% to less than 5%. Around 10–30% of patients are resistant to IVIG treatment [10].
\nUnfortunately, in some cases, IVIG is discontinued or administered at a reduced dose due to cost. Evidence for therapies beyond IVIG is limited, with no evidence-based recommendations for the management of patients with resistance to initial IVIG treatment.
\nIn the initial treatment, if the patient is in the acute phase treatment, aspirin (30–50 to 80–100 mg/kg/day) and IVIG (2 g/kg) are recommended. The treatment of patients with resistance (persistent or recurrent fever after the end of IVIG after 24 hours) is to initiate IVIG 2 g/kg, associated to corticosteroids and/or infliximab [10, 11].
\nThe use of corticosteroids is controversial due to the cardiovascular risk in prolonged use.
\nAnti-TNF-alpha is also recommended for patients with coronary artery aneurysms, and in the minority of cases, it can be used in patients without aneurysms. Other therapies possible are anti-interleukin 1, canakinumab and cyclosporine [11].
\nMicroscopic polyangiitis is an ANCA-associated vasculitis with significant morbidity and mortality. Treatment follows the same protocol as granulomatosis with polyangiitis [12].
\nIt is another necrotizing systemic vasculitis that affects small and medium vessels and is often associated with ANCA. It occurs in patients between 45 and 60 years old from both genders and is rarely observed in Negroids. The main features are the involvement of the upper and lower respiratory tract and the kidneys. Ears, nose and throat may develop with sinusitis and crusted rhinorrhea that are usually severe. Pulmonary nodules and renal involvement with crescent glomerulonephritis can be seen [13, 14].
\nIt is a serious disease, and if left untreated, it almost always progresses to death. With the advent of new therapies, 90% of patients evolve to remission and the survival rate is 80% in 10 years. The first phase, known as the induction phase, aims to put the patient into remission, and it lasts between 3 and 6 months according to the clinical response. The second phase is known as the maintenance phase trying to consolidate the first phase and prevent relapses. It lasts from 12–24 months [13] (Figure 2).
\nNecrotic vascular purpura (black arrows) of the upper limbs in granulomatosis with polyangiitis-Wegener’s [
In induction, prednisone 1 mg/kg is recommended. For severe forms, methylprednisolone pulse is indicated at doses of 7.5–15 mg/kg/day for 1–3 consecutive days. After 3–4 weeks of treatment, the corticosteroid dose is gradually decreased, but without reaching doses of less than 15 mg/day until 4th month. The combination of two immunosuppressants in the induction phase is essential for severe or refractory patients such as cyclophosphamide or rituximab.
\nCyclophosphamide is preferred if rapid renal failure occurs at a dose of 600 mg/m2 (maximum 1.2 g/bolus) every 2 weeks for 1 month (day+1, day+15, day+30) and then 700 mg/m2 every 3 weeks until remission (average of 6–9 cycles in total).The dose can be adjusted for age and renal function (500 mg/m2 in the presence of renal failure and 500 mg fixed dose every 3 weeks—maximum 6 bolus) [13, 14].
\nRituximab is the choice for pregnant women or patients who have failed cyclophosphamide or have relapsed. It is used at a dose of 375 mg/m2 per week for 4 weeks. Plasmapheresis may be used in severe forms of the disease with severe renal involvement (Cr > 500 μmol/L) or alveolar hemorrhage. Also, corticosteroid therapy can be associated with immunosuppressants [13, 14].
\nFor localized or not very severe cases, methotrexate (20–25 mg per week) is an option. The AGATA study demonstrated efficacy of abatacept (1 mg/kg IV on day+1, day+29 and then once per month) combined with prednisone and an immunosuppressant (azathioprine, methotrexate or mycophenolate mofetil) for recurrent and limited forms.
\nMaintenance lasts between 18 and 24 months after remission has been achieved. Corticosteroids may be combined with azathioprine (2 mg/kg/day) or methotrexate (20–25 mg/week) [13].
\nTreatment with sulfamethoxazole/trimethoprim (400/800 mg) is given to prevent relapse from
Eosinophilic granulomatosis polyangiitis (EGPA), also known as Churg-Strauss disease, is characterized by patients with asthma, eosinophilia and necrotizing vasculitis with extravascular eosinophilic granulomas that affect small and large vessels. It is a vasculitis associated with ANCA (neutrophilic cytoplasmic antibodies) and the rarest vasculitis within the group of ANCA-associated vasculitis, and that is why there are no highly recommended treatments based on the literature [15].
\nCorticosteroids are usually used to induce remission of the disease as well as immunosuppressants, for example cyclophosphamide in more severe cases. Long-term maintenance of immunosuppressants is used to prevent disease recurrence, but their long-term efficacy is discussed. Azathioprine has been recommended as maintenance therapy. The efficacy of mepolizumab, an anti-IL5 monoclonal antibody, has been recommended for these patients alone or in combination with corticotherapy. Others monoclonal anti-IL5, reslizumab and benralizumab drugs are still being studied. Studies suggest that rituximab may be effective in EGPA. Other drugs such as IFN-α appear to be effective in remission induction and maintenance; however, the safety profile restricts their use. Drugs such as anti-IgE (omalizumab) are used to control asthma, but their effects are unknown in the treatment of vasculitis. High doses of immunoglobulin have also been used to induce disease remission with good results. Intravenous immunoglobulin may be effective in treating residual peripheral neuropathy [15].
\nCryoglobulins are cold precipitated immunoglobulins that can cause vasculitis and vasculopathy. Type I cryoglobulins are responsible for 10–15% of symptomatic vasculitis cases and are related to malignant hematological disorders such as myeloma, B-cell lymphoma or undetermined monoclonal gammopathy (MGUS). Mixed cryoglobulins correspond to 80–85% of cases and are associated with infectious diseases, especially chronic hepatitis C, B-cell malignancies and autoimmune diseases such as Sjögren’s syndrome and lupus. Vasculitis is most associated with mixed cryoglobulins. Women are affected more than men 2:1 [12].
\nIn symptomatic patients with cryoglobulinemia type I, it is indicated to treat the hematologic basis diseases. Lymphomas require a combination of chemotherapy and myeloma treatment with drugs such as bortezomib, thalidomide, lenalidomide and other alkylating agents. Bone marrow transplantation can be performed in patients with cryoglobulinemia-associated myeloma. MGUS can be treated with the same myeloma drugs; however, rituximab has been the drug of choice. Plasmapheresis may be used for patients with severe renal involvement or extensive lower limb necrosis. Avoiding exposure to cold is essential [12].
\nMixed cryoglobulins, usually hepatitis C-associated cryoglobulinemic vasculitis, are well-treated as suppression of hepatitis C replication occurs. Studies reported between 2011 and 2013 associated with pegylated interferon (PegIFN) and ribavirin for 12 months achieved a 50–60% control response to hepatitis C. The introduction of antiviral agents dramatically changed cryoglobulinemia-associated vasculitis. They promote shorter treatment without the need for interferon and with responses greater than 95% associated with few adverse effects. The drugs used are sofosbuvir, simeprevir, ledipasvir and daclatasvir, that can be associated with ribavirin. In some cases of more severe vasculitis, low doses of rituximab and other immunosuppressants may be used in selected cases. Rituximab targets B-cell populations that produce cryoglobulins and treats severe vasculitis [12] (Figure 3).
\nClinical manifestations of cryoglobulinemic vasculitis; (a) severe skin ulcer; (b) nerve biopsy specimen showing vasculitis with a perivascular inflammatory infiltrate; (c) distribution of the peripheral neurological involvement indicating length dependency; (d) renal biopsy showing membranoproliferative glomerulonephritis; (e) magnetic resonance imaging of the brain showing vasculitis [
The term urticaria vasculitis is used for plaques of urticaria that present leukocytoclasia on histopathological examination. It is a clinical pathological diagnosis, characterized by a skin inflammation of the dermis capillaries and postcapillary venules, with a range of clinical signs from hives picture to a well-established vasculitis. Like any vasculitis, it can affect the skin and other organs, including skeletal, pulmonary, renal, gastrointestinal, cardiac and ophthalmic systems. The disease is spectral, ranging from mild to severe [16, 17].
\nRelated etiological factors are infections, medications, autoimmune reactions, malignancies or idiopathic reasons. It can be classified as normocomplementemic or NUV that presents normal levels of complement, usually not with systemic involvement, and hypocomplementemic or HUV that has low complement levels and may have systemic involvement [17].
\nThe treatment of vasculitis urticaria is a challenge, and there are no guidelines for the management of this disease. There are reports in the literature of the use of hydroxychloroquine and colchicine, which are as effective as systemic corticosteroids [16, 18].
\nImmunosuppressive drugs are used such as azathioprine, mycophenolate mofetil or cyclophosphamide. Rituximab with the usual doses also seems to have a good response. To manage the symptoms, sedative and nonsedating antihistamines may be used if urticaria is prominent. However, it is not usually effective. Nonsteroidal anti-inflammatory drugs are very useful in these cases such as naproxen, indomethacin and ibuprofen [13, 16].
\nAnother alternative therapy is to combine corticosteroids up to 1 mg/kg and another immunosuppressant (methotrexate, mycophenolate mofetil, azathioprine, cyclosporine and very rarely cyclophosphamide). Recent reports include rituximab, anakinra, canakinumab and omalizumab as therapeutic arsenal [17].
\nIt is the most common small vessel vasculitis of childhood, with a predominance of IgA deposits. Typically, it involves the skin, intestines and glomeruli and may be associated with arthralgia and/or arthritis. In most patients, only supportive treatment is required and analgesia [19, 20]. The disease regresses spontaneously most often within 4 weeks, but in some cases, it may last for more than 6 weeks [19]. In these cases, the therapeutic options may be dapsone (on average 1–2 mg/kg) or colchicine, but there are still no randomized controlled trials with the optimal dose and duration of treatment [18, 21]. Some patients require treatment with systemic corticosteroids, such as nephritis, orchitis, cerebral vasculitis, pulmonary hemorrhage and severe gastrointestinal involvement [19].
\nOther therapies used are the addition of cytotoxic immunosuppressants, intravenous immunoglobulins and plasmapheresis [20]. In case of severe rectal pain or abdominal pain, the use of systemic corticosteroids is recommended [19, 20].
\nThe recommended doses for prednisolone are 1–2 mg/kg/day for 1–2 weeks followed by weaning. In severe cases, it is possible also to use methylprednisolone pulses 10–30 mg/kg maximum 1 g/day for 3 consecutive days. Corticosteroid prophylaxis to decrease the chance of developing nephritis is not indicated. There is evidence showing that the use of angiotensin-converting enzyme inhibitors (ACE inhibitors) may have beneficial effects in patients with proteinuria. In patients with proteinuria longer than 3 months, regardless of whether they are receiving prednisone or another immunosuppressive drug, the use of ACE inhibitors or angiotensin receptor blockers is recommended to prevent and/or limit secondary glomerular injury. The first choice for mild nephritis treatment is prednisolone. If proteinuria persists, azathioprine, mycophenolate mofetil, cyclosporine or other corticosteroid-sparing treatment can be started. Also, IV methylprednisolone pulses can be considered.
\nIn the treatment for moderate nephritis, the first line is oral, or IV prednisolone, or IV methylprednisolone. Azathioprine, mycophenolate mofetil IV or cyclosporine may be used according to renal histopathological findings [19].
\nThe treatment for severe nephritis however is high doses of corticosteroids and IV cyclosporine to induce remission, and low doses of corticosteroids associated with azathioprine or mycophenolate mofetil as maintenance treatment [19].
\nBehçet’s syndrome has been known since ancient times and was described by Hippocrates, but it was reported as a separate disease by Huluci Behçet in 1937. It is currently classified as a vasculitis belonging to the subgroup of variable vessel vasculitis. It was initially reported in countries bordering the silk route, but nowadays, it is found all over the world. The most common manifestation is oral apotheosis and is seen in over 90% of cases [22].
\nIt is characterized by progressing multiple attacks and remissions. The duration of remission may vary from one attack to another and from one system to another. The attack, in most cases, is followed by a complete recovery called Restitutio ad Integrum of the tissue. A good example is oral aphthosis, and it is exceptional to see a scar. In case of oral aphthosis, it is uncommon to have a scar. In other organs such as the eyes, central nervous system and vascular system, we usually observe sequelae, which may even progress to death. In these cases, aggressive treatment is mandatory [22].
\nTreatment will vary depending on systemic involvement. Mucocutaneous manifestations do not require aggressive treatment, only topical treatment. Arthritis goes on with outbreaks and remissions, which can last from weeks to months, but usually respond well to nonsteroidal anti-inflammatory drugs (NSAIDs). Usually, the remission in these cases is long and the patient may discontinue the medication. There is usually no progression to destruction and deformities [22, 23].
\nTreatment of the gastrointestinal tract depends on the severity. For other manifestations, aggressive treatments are often required, starting with cytotoxic/immunomodulatory drugs associated with corticotherapy. Eventually, biological drugs are used such as apremilast [23].
\nWhen the patient suffers from eye involvement, infliximab or adalimumab anti-TNF drugs may be considered as first- or second-line therapies, or in the exacerbation of pre-existing disease. The European League first recommends corticosteroid-associated azathioprine therapy in all patients with subsequent involvement and the addition of cyclosporine or infliximab, or switching to interferon alfa with or without corticosteroids in patients with severe involvement as more than two drop lines in visual acuity on a 10/10 scale and/or retinal disease (retinal vasculitis or macular involvement) [23]. Other biological drugs are being studied such as IL-1 and IL-6 blockers [8].
\nIntravitreal use of fluocinolone acetonide also has been suggested in refractory cases. In these cases, the increased intraocular pressure and infections should be monitored. With the higher cause of morbidity and mortality, it is vascular involvement. It can affect arteries and veins of any caliber, and with various presentations such as thrombosis, occlusions and aneurysms. Immunosuppressive therapy is one of choices in these cases and there is no consensus regarding anticoagulants [23].
\nA retrospective multicenter study demonstrated a decrease in relapse in immunosuppressant versus untreated patients. Behçet-associated Budd-Chiari syndrome has a high mortality rate, and monthly cyclophosphamide pulses associated with corticosteroid therapy are the treatment of choice. Anti-TNF-alpha was used in 5 patients with refractory disease. Two of these patients already had terminal liver disease during infliximab administration and died due to liver failure. Two patients were successfully treated with infliximab and the fifth patient was stable with etanercept but had dural sinus thrombosis during follow-up [23].
\nCutaneous leukocytoclastic angiitis is an inflammation of small vessels, characterized by an inflammatory infiltrate associated with leukocytoclasia by neutrophil fragmentation and fibrinoid necrosis in small vessel postcapillary venules. It is the most common histological type of cutaneous vasculitis and usually is idiopathic, although antibiotics are also linked [24]. It is often clinically manifested by a palpable purpura, which is found anywhere on the body, but usually affects more lower limbs and can cause arthralgia [24, 25].
\nSeveral symptomatic treatments may be proposed to patients: analgesics, nonsteroidal anti-inflammatory drugs and antihistamines. For chronic or persistent vasculitis, dapsone and/or colchicine may be effective. The use of colchicine in the treatment is beneficial through its effect on reducing neutrophil chemotaxis, blocking leukocyte adhesion and stabilizing lysosomal membranes. Colchicine at a dose of 0.6–1.8 mg/day induces resolution within 1–2 weeks, according to several authors [18].
\nThe best indication for colchicine is in moderate severity vasculitis. It is an effective and inexpensive treatment that can be used alone or in combination. However, its prescription is sometimes limited because of its gastrointestinal side effects [18].
\nIn cases of severe skin necrosis and/or systemic manifestations, systemic corticotherapy (prednisolone or prednisone 20–60 mg/d) with progressive weaning may control the situation in some cases. For patients with systemic manifestations, initial therapy should include high doses of corticosteroids and/or cyclophosphamide. Intravenous immunoglobulins may be useful in the treatment of severe and refractory disease in patients who have a contraindication to traditional immunosuppressive therapy [26].
\nOther drug-associated vasculitis, autoimmune diseases or even infectious diseases require treatment of the underlying disease. In some cases, systemic corticosteroid therapy is necessary, and corticosteroid-sparing immunosuppressive drugs and even intravenous immunoglobulin may be required [26].
\nVasculopathies are diseases that present a hyperactivity of blood vessels in the skin with systemic repercussions, but of unknown etiology. They are usually classified as diseases with circulatory disorders such as acrocyanosis, livedo reticularis, Raynaud’s phenomenon, erythromelalgia, vessel occlusion leading to necrosis such as atherosclerosis obliterans, Buerger’s disease, lymphocyte-mediated inflammatory changes such as livedoid vasculitis, malignant atrophic papulosis and neutrophil-mediated inflammatory changes such as pyoderma gangrenosum. Below, the most common representatives will be discussed [27].
\nAntiphospholipid antibodies syndrome or Hughes syndrome is a systemic, autoimmune disease in which there are repeat thrombotic events, repeated fetal losses and positive autoantibodies such as anticardiolipin and lupus anticoagulant. As skin manifestations, ulcerations and livedo reticularis are the most common signs [27, 28]. Some authors relate Sneddon’s syndrome, which is a disease with strokes and livedo reticularis, as a spectrum of APS [29]. Libman-Sacks endocarditis in systemic lupus erythematosus patients also has an accumulation of antiphospholipid antibodies in the subendothelial layer of the heart valves. However, the correlation with APS is not well established [30].
\nFor patients with a diagnosis of APS, treatment as well as prophylaxis is required. However, there are patients who have met the diagnostic criteria but with no thrombotic events. In these patients, behavioral changes such as smoking and alcohol cessation, lipid control, diabetes management and nonuse of exogenous estrogens are the most important measures [27].
\nAvoiding prolonged immobilizations and other behaviors that predispose to thrombotic events is also recommended. Some authors advocate the use of aspirin without scientific consensus [28].
\nPrimary prophylaxis with low-dose aspirin prophylaxis is usually prescribed to prevent thrombosis in women with recurrent miscarriages, but it does not prevent deep vein thrombosis in men with APS. In systemic lupus and secondary APS, hydroxychloroquine has been proven to have a protective effect against thrombosis, as well as a reduction in cholesterol and glycemia. Patients who undergo surgery and require prolonged immobilization require prophylactic heparinization, and in APS, sometimes doses should be higher than usual due to resistance to anticoagulant effects. For treatment, as initial therapy, unfractionated heparin or low molecular weight heparin is used. Warfarin may also be used [28].
\nBecause patients with APS and thrombosis are at high risk for recurrent thromboembolism episodes, prolonged oral anticoagulant therapy is the best option for attempting to prevent further episodes. The most used oral anticoagulant is warfarin with a therapeutic goal of maintaining INR greater than or equal to 3 [31].
\nIn cases of APS secondary to the underlying systemic disease, it should not open the treatment with systemic oral corticoid. Other agents that can be used are plasmapheresis, immunoglobulin and dapsone, among others [27].
\nIn refractory and catastrophic cases that there is multiple organ infarction, anticoagulation combinations, steroids, plasmapheresis, intravenous immunoglobulin and fish oil derivatives can be used. Fibrinolytic agents have no proven benefit [28].
\nIn case of pregnancy, the best alternative during this period is heparin associated with low doses of aspirin. Combined treatment is more effective to prevent miscarriages than just aspirin alone. Unfractionated heparin, low molecular weight heparin (enoxaparin 40 mg/day) and dalteparin 5000 UI/day can be used during this period. Warfarin should not be used in pregnant women. Accidental discovery of antiphospholipid antibodies during pregnancy, with no clinical history of problems such as thromboembolic events or systemic lupus erythematosus, does not require treatment [28].
\nIt is a sudden cutaneous manifestation in which the fingers, especially the toe, develop cyanotic and painful character. The priority etiology is embolic, but there may be other causes such as rheumatologic and neoplastic, among others. Treatment for this condition depends on the treatment of the underlying disease. However, general and local care such as limb warm-up, physical protection, treatment of secondary infections are essential [32].
\nAcrocyanosis is a disease resulting from chronic vasospasm that causes reflex vasodilation in the affected extremities, usually by medication or central nervous system disorders. It may be painful, cold, discolored, hyperhidrosis, paresthesia and even tingling. Like for blue finger syndrome, treatment is only supportive [27].
\nErythromelalgia is characterized by vasodilation of the extremities, especially in male children, and is usually associated with limb warm-up, pain and burning. It is believed that there is some change in calcium channels, so therapy is directed toward this focus.
\nIn the case of primary erythromelalgia, anesthetics, antiarrhythmics, anticonvulsants and even oral magnesium may be used. In the case of secondary erythromelalgia, besides the treatment already discussed, the underlying disease needs to be controlled [27].
\nIts treatment includes topical drugs like 5% lidocaine and 0.075% capsaicin. For oral medications, we have amitriptyline 10 mg/day, gabapentin 900–1800 mg/day, pregabalin 75 mg/day, flecainide 200 mg/day and buflomedil 200–330 mg/day. Tricyclic antidepressants, selective serotonin reuptake inhibitors and, in selected cases, acetylsalicylic acid, beta blockers and calcium channel antagonists may be excellent associations. In refractory cases, we may use epidural infusions of opioids, bupivacaine and, in the latter case, sympathectomy. However, responses are quite variable and complete remission of symptoms is rarely observed [27, 33].
\nReticular livedo is a common dermatological manifestation in which the limb in question suffers a vasospasm and has a cyanotic, erythematous and erythematous-violet coloration. When the blood plot does not have a confluent pattern, it is called a racemose livedo. In clinical practice, it may be isolated by cold or trauma or may be associated with some systemic diseases such as lupus erythematosus, scleroderma and HIV. Although it is more common in the limbs, it can also affect the trunk and there may be ulcerations. Cold stimulates vasospasm, when the cause is removed, however, over time, vessels may become permanently dilated and become permanently telangiectatic [27, 34].
\nThe treatment of livedo, primarily, is protection against the cold. Vasodilators may be an alternative and corticosteroids should be avoided as much as possible. If there are ulcerations or a racemose livedo associated with antiphospholipid antibody syndrome, anticoagulation is recommended. When livedo is associated with some underlying disease, the management of the disease usually improves its manifestation. Other medications may be tried such as danazol, tissue plasminogen activator (tPA), pentoxifylline and antiplatelets. Immunosuppressants such as azathioprine and sympathectomy are reserved for refractory cases [27, 34, 35].
\nIt is a paroxysmal vasospastic disorder characterized by the simultaneous alternation of pallor (vasoconstriction), cyanosis (blood stasis) and redness (compensatory vasodilation).
\nWe consider Raynaud’s disease (20% of the cases) when it occurs primarily and not associated with other acne. And we consider Raynaud’s phenomenon (80%) when it occurs secondary to another disease [27].
\nTreatment consists of treating the basic disease and quitting smoking. Protection against the cold is necessary to avoid triggering the frame. In idiopathic forms, the use of nifedipine 30–120 mg/day can be used. Other treatment modalities may also be employed such as topical nitroglycerin, iloprost, losartan, serotonin receptor inhibitors, phosphodiesterase inhibitors, n-acetylcysteine, botulinum toxin, bosentan, platelet inhibitors and fibrinolytics. In refractory cases, sympathectomy may be performed [27].
\nPerniosis is a rare panniculitis that develops with painful erythematous-violaceous nodules in young people more susceptible to cold. There is also a certain uncertain relationship with tobacco. Treatment, like other cold-related conditions, requires protection from the cold such as appropriate clothing, gloves, socks, boots and smoking cessation. Behavior changes and topical corticoid creams can help to heal the lesions. Some vasodilators may also be applied as nicotinic acid, nifedipine and pentoxifylline. In refractory cases, sympathectomy and UVB phototherapy may also be considered [36].
\nLivedoid vasculitis is one of the most common vasculopathies, described in 1929, and can affect up to about 5% of the healthy population, reaching 70% in patients with venous ulcers. Some authors differentiate livedoid vasculitis from Millian’s white atrophy in relation to etiology. Livedoid vasculitis is persistent livedoid reticularis associated with an ulcer [37]. White atrophy is a white atrophy scar with a stellar pattern most common in the lower limbs of women aged 30–60 years that may or may not be associated with collagenases and neoplasia; however, the best-established link is with chronic venous insufficiency [35].
\nThe treatment for this disease is divided into some of the following groups:
Drugs stimulating endogenous fibrinolytic activity such as danazol, the activating factor of recombinant tissue plasminogen, rt-PA, low dose alteplase, associated or not with heparin and aspirin [27, 35].
Drugs such as dipyridamole, cilostazol, the thienopyridine group (clopidogrel, ticlopidine hydrochloride, whether associated with aspirin) and sarpogrelate.
Hemorheological drugs that decrease blood viscosity, increase red blood cell flexibility and improve circulation. From this group, the example is pentoxifylline and buflomedil hydrochloride [27, 35].
Modulating lymphocyte response therapy as systemic PUVA phototherapy [27].
Other drugs such oral corticosteroids, intravenous immunoglobulin, cyclosporine, hyperbaric oxygen therapy and intravenous iloprost [27].
For patients with any associated thrombophilia, warfarin, unfractionated heparin, low molecular weight heparin and even heparin minidoses may also be used [27].
\nIt is a chronic disease associated with diabetes that gradually occludes the vessel light. It affects the feet more than the hands in patients over 50 years. There is no specific treatment, but oral corticosteroids may be employed associated with diabetes with strict disease control. Behavioral change with diabetes mellitus improvement and antibiotic therapy, if secondary injuries, is the therapy of choice. Vasodilators do not have their proven efficiency. In severe cases, sympathectomy and vascular surgery may be used [38].
\nThe priority treatment is smoking cessation and rest. Iloprost IV may be an alternative to retard evolution. In many cases, amputation is required, with excision of the gangrenous fingers, sympathectomy and surgeries such as arterialization of the venous arch of the foot. The vascular surgeon is extremely important for follow-up [27, 39].
\nMalignant atrophic papulosis (MAP) is an obliterating endovasculitis of small- and medium-sized arteries that produces tissue infarction as its main feature. It is considered an uncommon disease of unknown cause and can affect the skin, gastrointestinal tract and central nervous system, and the involvement of these last two systems can be fatal [40].
\nThere is no fully effective treatment for the disease. Some authors use acetylsalicylic acid (300 mg daily) and/or dipyridamole (75 mg twice daily) as the first therapeutic modality, which facilitates blood perfusion. Other therapeutic options such as aspirin, heparin and warfarin can be used, however, aspirin is more associated with resurgence of lesions when discontinuing the drug [41].
\nMore recently, studies have been conducted using eculizumab that have shown initial efficacy in skin and intestinal lesions, but the drug has not been able to prevent the development or progression of systemic manifestations. Subcutaneous treprostinil has been successfully tested in some cases with dramatic and sustained improvement in clinical status, although the response was not immediate. The mechanism of action of treprostinil in this scenario is not yet well understood [42, 43].
\nThe use of corticosteroids, chloroquine or other immunosuppressants has proved unsatisfactory and has great potential to worsen the disease by unknown mechanism; therefore, they are not indicated [43].
\nThese are vascular inflammations with thrombus formation and consequent occlusion or may occur due to slow flow within a varicose vein. If thrombophlebitis is found in apparently normal superficial veins, attention should be paid to the possibility of underlying malignancy, thrombosing coagulopathy and silent deep vein thrombosis [44].
\nFor therapeutic management, in cases of limited superficial thrombophlebitis below the knee, without evidence of deep vein thrombosis, compression by specific stockings and the use of nonsteroidal anti-inflammatory drugs are enough, providing symptomatic relief. However, if there is deep venous thrombosis or extension to the saphenofemoral or saphenopopliteal junctions, prophylactic use of low molecular weight heparin may be necessary [44].
\nVasculitis and vasculopathies are a challenge physicians face on a daily basis. Due to rarity of the diseases all over the globe, the scientific community is not able to perform studies with a great number of patients and biological medications seem to be the promise to a cure or the disease control. These groups of drugs are relatively new and still expensive in most countries. Furthermore, more studies need to be developed and long follow-ups should be performed before they are considered gold-standard treatment. In the medical reality nowadays, despite any consideration, an early diagnosis can change the whole disease course and prevent inabilities, and even without cure, it is indispensable to control symptoms and provide a better quality of life to patients.
\nVasculitis and vasculopathies are a group of diseases that course with an inflammatory process, which attacks vascular endothelium of vessels of different calibers. Usually, they course with dermatology lesions, the diagnosis is difficult, and they have a few treatment options. Despite that, an early diagnosis can contribute to a better quality of patient’s life and prevent further complications (Figure 1) [1].
\nPurpuric macules and papules coalescing into patches (A) in small vessel vasculitis and fixed livedo reticularis and subcutaneous nodules (B) in medium vessel vasculitis (polyarteritis nodosa) [
The authors performed a bibliographic review from cutaneous vasculitis and vasculopathies from literature, including online academics platforms such as PubMed and Google Scholar and dermatology books as Rivitti and Fitispack. The keywords used from this chapter were cutaneous vasculitis, Takayasu arteritis, Giant Cell Arteritis, Polyarteritis Nodosa, Kawasaki Disease, Microscopic polyangiitis, Granulomatosis with Polyangiitis (Wegener’s), Eosinophilic Granulomatosis with Polyangiitis (Churg-Strauss), Cryoglobulinemic Vasculitis, Urticaria Vasculitis, Henoch-Schönlein, Behçet’s syndrome, Cutaneous leukocytoclastic angiitis, cutaneous vasculopathies, Phospholipid Antibody Syndrome, Blue Finger Syndrome, Acrocyanosis and others. The final objective was summing up the dermatology vasculitis and vasculopathies and helping physicians in early diagnosis and treatment.
\nCutaneous vasculitis may affect vessels of different calibers, especially small and medium in the skin and the subcutaneous tissue, resulting in just a small cutaneous lesion until serious systemic commitment. Nevertheless, the classification is not a consensus. In general, they are classified using clinical criteria, size of the vessels, histopathological exams, laboratorial findings and etiologic agents [3, 4]. In 2012, the
It is a large vessel vasculitis whose etiologic agent is unknown. It is more frequently found in young Asiatic women, in the proportion from 5 to 12 W:1 M, and usually affects the aorta and its main branches. It is not a rare disease but is not as usual as arteritis of giant cells. The diagnosis is usually late because these patients develop many collateral arteries, they have nonspecific symptoms and the development of these affections is very slow. Pregnancy in patients affected by Takayasu arteritis is a troubling problem because it affects women of childbearing age, and it will cause risks to the mother and the child. The arteritis could be associated with Crohn’s and rectocolitis disease [6].
\nThe more effective treatments are oral corticosteroids, but there are many relapses when corticosteroids taper. High doses of corticosteroids (40–60 mg/day of prednisone or equivalent) should be initiated immediately after the diagnosis to induce remission. During disease remission, it is necessary sparing the drug until 15-20mg/day for two or three months, and after a year decrease the doses to 10mg/day or less. The immunosuppressive agents are used as corticoid sparing agents such as methotrexate, azathioprine, leflunomide, mycophenolate mofetil and cyclophosphamide [6]. There are evidences that biological agents such as anti-TNF-alpha, tocilizumab and rituximab could be effective in refractory cases, but more trials are necessary to evaluate the effectiveness of these drugs [8]. In addition, patients with ischemic problems need endovascular interventions. The mortality range is between 3 and 21% [6].
\nIt is a systemic vasculitis of large vessels, with tropism to the aorta and its branches, mainly external carotid. It is a most common vasculitis in above 50-year-olds and affects more women than men (3 W:2 M). The corticosteroids are the most common therapeutic used in these cases. In the beginning, we need high doses of corticosteroids to control the inflammation, and then it could be used sparingly until controlled in the patient. These strategies are valid for simple and complicated forms of the disease [7].
\nSimple form is defined by cephalic isolated symptoms with visual disturbance or changes in central nervous system. Nowadays, the gold standard treatment is oral prednisone or equivalent 40–60 mg/day, and methylprednisolone is not used anymore. The initial dose recommended is 0.7 mg/kg day of prednisone and the maximum dose is 80 mg/day [7].
\nThe complicated form is defined when there is an ophthalmologic or a central nervous or extracephalic complication, mainly aorta and its branches. In these cases, methylprednisolone in pulses of 500 mg−1 g a day shall be used for 1 to 5 consecutive days. During maintenance, some authors believe in doses less than 5 mg/day. The American Society of Ophthalmology recommends pulses of intravenous methylprednisolone, when patients have ophthalmologic symptoms, but the Rheumatology Society prefers oral corticosteroid [7].
\nIt is strategic to introduce corticosteroid-sparing drugs when the disease course is lasting long. Methotrexate is the most used treatment and with more evidence levels. There are four trials with methotrexate as a sparing drug, but the doses and the management are variable from 7.5–15 mg/week [7].
\nCyclophosphamide has demonstrated effectiveness in patients dependent on corticosteroids or resistant to treatment. It is necessary to give more than 20 mg/day for 6 months or 10 mg/day for 1 year or more. The dose from 500 mg/m2 or 500 mg/injection in 6 courses is standard from 5 months on average. It is highly important to warn patients of several side effects such as bone marrow suppression [7].
\nAzathioprine therapy has less controlled studies. Some studies showed a modest improvement. Hydroxychloroquine, an antimalarial synthetic drug, was tested also. One French study divided patients into two groups: one took prednisone 0.7 mg/kg/day in the beginning associated with hydroxychloroquine (400 mg/day) and the control group just received prednisone and placebo. The group that had hydroxychloroquine and corticoid had usually stopped later the prednisone and they had more relapses [7].
\nNowadays, one option is biologics medicines. Anti-TNF-alpha does not have enough studies that showed control of the disease with this class of medication [7]. Tocilizumab, a humanized antibody that blocked membranous and soluble receptors of IL-6 (IL-6R), is a current option since IL-Il-6 is implicated in the etiopathogenesis of this affection. Three main studies evaluated the efficacy of the drug, although the therapeutics was different between these studies [7, 8].
\nA randomized control trial with 30 patients had tested 20 patients receiving corticoids and tocilizumab (8 mg/kg every 4 week during a year), and 10 received corticoids and placebo. The survival without relapses during a year was highest in patients treated with tocilizumab. However, there are no data available after the medication was stopped [7, 8].
\nAnother promising biotherapy is abatacept. This medication with corticoids could decrease the risk of relapses, although more data is necessary to corroborate this hypothesis.
\nUstekinumab, a subunit against anti-p40 IL-12/23 targeting Th1 and Th17 responses, has been showing similar side effects as corticoids. Some patients, who had refractory disease, have been treated with anakinra and they achieved success. Anakinra is a biopharmaceutical drug that blocks IL-1. All patients who had taken the drug had shown improvement in inflammation biomarkers and/or in their symptoms, with the disappearance of arterial inflammation in PET/CT. More studies are necessary though [7].
\nOther pharmacological drugs can be used as adjuvant treatments such as antiplatelets and anticoagulants, but there is no official recommendation about these drugs in the treatment of GAC. The statins do not influence the evolution of the disease, but they are used to prevent cardiovascular risk. Furthermore, these drugs could have an anti-inflammatory role via the inhibition of TH17 pathway [7].
\nIt is a rare necrotizing systemic vasculitis that affects small- and medium-sized vessels and is not usually associated with ANCA [8, 9], although there are reports in the literature of patients with PAN and positive ANCA. Several treatments are suggested for this condition, and the control is still a challenge [9].
\nCutaneous involvement and peripheral nerves are the favorite sites of the disease, cutaneous and gastrointestinal vasculitis have specific histopathological characteristics, and until now, it has no development glomerulonephritis described. Gastrointestinal tract involvement is common and is one of the predictors of disease morbidity and mortality. There is cutaneous PAN without systemic involvement, and it very rarely progresses to the systemic form of the disease. According to the new classification, PAN is subdivided into idiopathic PAN and hepatitis B-associated PAN [9].
\nTreatment of PAN is usually based on the combination of systemic corticosteroids and immunosuppressants. The most commonly used medications are cyclophosphamide, azathioprine, methotrexate or mycophenolate mofetil [9].
\nThe use of biological medications is reserved for cases of refractory PAN without association with hepatitis B. The use of rituximab, an anti-CD20 monoclonal antibody, has not been formally indicated for patients with PAN, but its use is supported in patients with ANCA-associated vasculitis. There are case reports using anti-TNF-alpha, such as etanercept and infliximab, and tocilizumab, but only in refractory cases [8].
\nIt is a systemic vasculitis, common in male child, with fever, rash, non-exudative bilateral conjunctivitis, oral and pharyngeal mucosal erythema, cervical lymphadenopathy, and it can affect the extremity. They may have fewer common symptoms such as pyuria, meningitis, shock and retropharyngeal or parapharyngeal abscess [10].
\nThe etiology of Kawasaki disease is unknown. The diagnosis of Kawasaki disease is based on the presence of fever for ≥5 days, along with the presence of at least 4 of the 5 main clinical features [10] (Table 2).
\n\n\n | Classification | \nDiseases | \n
---|---|---|
1 | \nLarge vessel vasculitis | \nTakayasu arteritis Giant cell arteritis | \n
2 | \nMedium vessel | \nPolyarteritis nodosa Kawasaki disease | \n
3 | \nSmall vessel vasculitis ANCA-associated vasculitis | \nMicroscopic polyangiitis Granulomatosis with polyangiitis (Wegener’s) Eosinophilic granulomatosis with polyangiitis (Churg-Strauss) | \n
4 | \nSmall vessel vasculitis Immune complex | \nAntiglomerular basement membrane disease Cryoglobulinemic vasculitis (CV) Hypocomplementemic urticarial vasculitis (anti-C1q vasculitis) IgA vasculitis (Henoch-Schönlein) | \n
5 | \nVariable vessel vasculitis | \nBehçet’s syndrome Cogan’s syndrome | \n
6 | \nSingle-organ vasculitis | \nCutaneous leukocytoclastic angiitis Cutaneous arteritis Primary central nervous system vasculitis | \n
7 | \nVasculitis associated with systemic disease | \nLupus vasculitis Rheumatoid vasculitis Sarcoid vasculitis Others | \n
8 | \nVasculitis associated with probable cause | \nHepatitis C virus-associated CV Hepatitis B virus-associated vasculitis Syphilis-associated aortitis Drug-associated immune complex vasculitis Drug-associated ANCA-associated vasculitis Cancer-associated vasculitis Others | \n
2012 International Chapel Hill Consensus Conference Nomenclature of Vasculitides [3].
\n | Clinical features | \n
---|---|
1 | \nErythema and cracking of the lips, strawberry tongue and/or pharyngeal and oral mucosa erythema | \n
2 | \nBilateral bulbar conjunctival injection without exudate | \n
3 | \nRash | \n
4 | \nErythema and edema of the hands and feet in the acute phase and/or periungual scaling in the subacute phase | \n
5 | \nCervical lymphadenopathy (≥1.5 cm in diameter), usually unilateral | \n
Clinical features in Kawasaki disease [10].
Patients who have met the diagnostic criteria are considered to have complete Kawasaki disease (also referred to as typical or classic Kawasaki disease). Patients who do not have enough major clinical findings can be diagnosed with incomplete Kawasaki disease [10].
\nIntravenous immunoglobulin (IVIG) is the basis for treatment. Usually, it is initiated before 10 days of fever and significantly reduces coronary artery aneurysms (CAAs) that decrease from 25% to less than 5%. Around 10–30% of patients are resistant to IVIG treatment [10].
\nUnfortunately, in some cases, IVIG is discontinued or administered at a reduced dose due to cost. Evidence for therapies beyond IVIG is limited, with no evidence-based recommendations for the management of patients with resistance to initial IVIG treatment.
\nIn the initial treatment, if the patient is in the acute phase treatment, aspirin (30–50 to 80–100 mg/kg/day) and IVIG (2 g/kg) are recommended. The treatment of patients with resistance (persistent or recurrent fever after the end of IVIG after 24 hours) is to initiate IVIG 2 g/kg, associated to corticosteroids and/or infliximab [10, 11].
\nThe use of corticosteroids is controversial due to the cardiovascular risk in prolonged use.
\nAnti-TNF-alpha is also recommended for patients with coronary artery aneurysms, and in the minority of cases, it can be used in patients without aneurysms. Other therapies possible are anti-interleukin 1, canakinumab and cyclosporine [11].
\nMicroscopic polyangiitis is an ANCA-associated vasculitis with significant morbidity and mortality. Treatment follows the same protocol as granulomatosis with polyangiitis [12].
\nIt is another necrotizing systemic vasculitis that affects small and medium vessels and is often associated with ANCA. It occurs in patients between 45 and 60 years old from both genders and is rarely observed in Negroids. The main features are the involvement of the upper and lower respiratory tract and the kidneys. Ears, nose and throat may develop with sinusitis and crusted rhinorrhea that are usually severe. Pulmonary nodules and renal involvement with crescent glomerulonephritis can be seen [13, 14].
\nIt is a serious disease, and if left untreated, it almost always progresses to death. With the advent of new therapies, 90% of patients evolve to remission and the survival rate is 80% in 10 years. The first phase, known as the induction phase, aims to put the patient into remission, and it lasts between 3 and 6 months according to the clinical response. The second phase is known as the maintenance phase trying to consolidate the first phase and prevent relapses. It lasts from 12–24 months [13] (Figure 2).
\nNecrotic vascular purpura (black arrows) of the upper limbs in granulomatosis with polyangiitis-Wegener’s [
In induction, prednisone 1 mg/kg is recommended. For severe forms, methylprednisolone pulse is indicated at doses of 7.5–15 mg/kg/day for 1–3 consecutive days. After 3–4 weeks of treatment, the corticosteroid dose is gradually decreased, but without reaching doses of less than 15 mg/day until 4th month. The combination of two immunosuppressants in the induction phase is essential for severe or refractory patients such as cyclophosphamide or rituximab.
\nCyclophosphamide is preferred if rapid renal failure occurs at a dose of 600 mg/m2 (maximum 1.2 g/bolus) every 2 weeks for 1 month (day+1, day+15, day+30) and then 700 mg/m2 every 3 weeks until remission (average of 6–9 cycles in total).The dose can be adjusted for age and renal function (500 mg/m2 in the presence of renal failure and 500 mg fixed dose every 3 weeks—maximum 6 bolus) [13, 14].
\nRituximab is the choice for pregnant women or patients who have failed cyclophosphamide or have relapsed. It is used at a dose of 375 mg/m2 per week for 4 weeks. Plasmapheresis may be used in severe forms of the disease with severe renal involvement (Cr > 500 μmol/L) or alveolar hemorrhage. Also, corticosteroid therapy can be associated with immunosuppressants [13, 14].
\nFor localized or not very severe cases, methotrexate (20–25 mg per week) is an option. The AGATA study demonstrated efficacy of abatacept (1 mg/kg IV on day+1, day+29 and then once per month) combined with prednisone and an immunosuppressant (azathioprine, methotrexate or mycophenolate mofetil) for recurrent and limited forms.
\nMaintenance lasts between 18 and 24 months after remission has been achieved. Corticosteroids may be combined with azathioprine (2 mg/kg/day) or methotrexate (20–25 mg/week) [13].
\nTreatment with sulfamethoxazole/trimethoprim (400/800 mg) is given to prevent relapse from
Eosinophilic granulomatosis polyangiitis (EGPA), also known as Churg-Strauss disease, is characterized by patients with asthma, eosinophilia and necrotizing vasculitis with extravascular eosinophilic granulomas that affect small and large vessels. It is a vasculitis associated with ANCA (neutrophilic cytoplasmic antibodies) and the rarest vasculitis within the group of ANCA-associated vasculitis, and that is why there are no highly recommended treatments based on the literature [15].
\nCorticosteroids are usually used to induce remission of the disease as well as immunosuppressants, for example cyclophosphamide in more severe cases. Long-term maintenance of immunosuppressants is used to prevent disease recurrence, but their long-term efficacy is discussed. Azathioprine has been recommended as maintenance therapy. The efficacy of mepolizumab, an anti-IL5 monoclonal antibody, has been recommended for these patients alone or in combination with corticotherapy. Others monoclonal anti-IL5, reslizumab and benralizumab drugs are still being studied. Studies suggest that rituximab may be effective in EGPA. Other drugs such as IFN-α appear to be effective in remission induction and maintenance; however, the safety profile restricts their use. Drugs such as anti-IgE (omalizumab) are used to control asthma, but their effects are unknown in the treatment of vasculitis. High doses of immunoglobulin have also been used to induce disease remission with good results. Intravenous immunoglobulin may be effective in treating residual peripheral neuropathy [15].
\nCryoglobulins are cold precipitated immunoglobulins that can cause vasculitis and vasculopathy. Type I cryoglobulins are responsible for 10–15% of symptomatic vasculitis cases and are related to malignant hematological disorders such as myeloma, B-cell lymphoma or undetermined monoclonal gammopathy (MGUS). Mixed cryoglobulins correspond to 80–85% of cases and are associated with infectious diseases, especially chronic hepatitis C, B-cell malignancies and autoimmune diseases such as Sjögren’s syndrome and lupus. Vasculitis is most associated with mixed cryoglobulins. Women are affected more than men 2:1 [12].
\nIn symptomatic patients with cryoglobulinemia type I, it is indicated to treat the hematologic basis diseases. Lymphomas require a combination of chemotherapy and myeloma treatment with drugs such as bortezomib, thalidomide, lenalidomide and other alkylating agents. Bone marrow transplantation can be performed in patients with cryoglobulinemia-associated myeloma. MGUS can be treated with the same myeloma drugs; however, rituximab has been the drug of choice. Plasmapheresis may be used for patients with severe renal involvement or extensive lower limb necrosis. Avoiding exposure to cold is essential [12].
\nMixed cryoglobulins, usually hepatitis C-associated cryoglobulinemic vasculitis, are well-treated as suppression of hepatitis C replication occurs. Studies reported between 2011 and 2013 associated with pegylated interferon (PegIFN) and ribavirin for 12 months achieved a 50–60% control response to hepatitis C. The introduction of antiviral agents dramatically changed cryoglobulinemia-associated vasculitis. They promote shorter treatment without the need for interferon and with responses greater than 95% associated with few adverse effects. The drugs used are sofosbuvir, simeprevir, ledipasvir and daclatasvir, that can be associated with ribavirin. In some cases of more severe vasculitis, low doses of rituximab and other immunosuppressants may be used in selected cases. Rituximab targets B-cell populations that produce cryoglobulins and treats severe vasculitis [12] (Figure 3).
\nClinical manifestations of cryoglobulinemic vasculitis; (a) severe skin ulcer; (b) nerve biopsy specimen showing vasculitis with a perivascular inflammatory infiltrate; (c) distribution of the peripheral neurological involvement indicating length dependency; (d) renal biopsy showing membranoproliferative glomerulonephritis; (e) magnetic resonance imaging of the brain showing vasculitis [
The term urticaria vasculitis is used for plaques of urticaria that present leukocytoclasia on histopathological examination. It is a clinical pathological diagnosis, characterized by a skin inflammation of the dermis capillaries and postcapillary venules, with a range of clinical signs from hives picture to a well-established vasculitis. Like any vasculitis, it can affect the skin and other organs, including skeletal, pulmonary, renal, gastrointestinal, cardiac and ophthalmic systems. The disease is spectral, ranging from mild to severe [16, 17].
\nRelated etiological factors are infections, medications, autoimmune reactions, malignancies or idiopathic reasons. It can be classified as normocomplementemic or NUV that presents normal levels of complement, usually not with systemic involvement, and hypocomplementemic or HUV that has low complement levels and may have systemic involvement [17].
\nThe treatment of vasculitis urticaria is a challenge, and there are no guidelines for the management of this disease. There are reports in the literature of the use of hydroxychloroquine and colchicine, which are as effective as systemic corticosteroids [16, 18].
\nImmunosuppressive drugs are used such as azathioprine, mycophenolate mofetil or cyclophosphamide. Rituximab with the usual doses also seems to have a good response. To manage the symptoms, sedative and nonsedating antihistamines may be used if urticaria is prominent. However, it is not usually effective. Nonsteroidal anti-inflammatory drugs are very useful in these cases such as naproxen, indomethacin and ibuprofen [13, 16].
\nAnother alternative therapy is to combine corticosteroids up to 1 mg/kg and another immunosuppressant (methotrexate, mycophenolate mofetil, azathioprine, cyclosporine and very rarely cyclophosphamide). Recent reports include rituximab, anakinra, canakinumab and omalizumab as therapeutic arsenal [17].
\nIt is the most common small vessel vasculitis of childhood, with a predominance of IgA deposits. Typically, it involves the skin, intestines and glomeruli and may be associated with arthralgia and/or arthritis. In most patients, only supportive treatment is required and analgesia [19, 20]. The disease regresses spontaneously most often within 4 weeks, but in some cases, it may last for more than 6 weeks [19]. In these cases, the therapeutic options may be dapsone (on average 1–2 mg/kg) or colchicine, but there are still no randomized controlled trials with the optimal dose and duration of treatment [18, 21]. Some patients require treatment with systemic corticosteroids, such as nephritis, orchitis, cerebral vasculitis, pulmonary hemorrhage and severe gastrointestinal involvement [19].
\nOther therapies used are the addition of cytotoxic immunosuppressants, intravenous immunoglobulins and plasmapheresis [20]. In case of severe rectal pain or abdominal pain, the use of systemic corticosteroids is recommended [19, 20].
\nThe recommended doses for prednisolone are 1–2 mg/kg/day for 1–2 weeks followed by weaning. In severe cases, it is possible also to use methylprednisolone pulses 10–30 mg/kg maximum 1 g/day for 3 consecutive days. Corticosteroid prophylaxis to decrease the chance of developing nephritis is not indicated. There is evidence showing that the use of angiotensin-converting enzyme inhibitors (ACE inhibitors) may have beneficial effects in patients with proteinuria. In patients with proteinuria longer than 3 months, regardless of whether they are receiving prednisone or another immunosuppressive drug, the use of ACE inhibitors or angiotensin receptor blockers is recommended to prevent and/or limit secondary glomerular injury. The first choice for mild nephritis treatment is prednisolone. If proteinuria persists, azathioprine, mycophenolate mofetil, cyclosporine or other corticosteroid-sparing treatment can be started. Also, IV methylprednisolone pulses can be considered.
\nIn the treatment for moderate nephritis, the first line is oral, or IV prednisolone, or IV methylprednisolone. Azathioprine, mycophenolate mofetil IV or cyclosporine may be used according to renal histopathological findings [19].
\nThe treatment for severe nephritis however is high doses of corticosteroids and IV cyclosporine to induce remission, and low doses of corticosteroids associated with azathioprine or mycophenolate mofetil as maintenance treatment [19].
\nBehçet’s syndrome has been known since ancient times and was described by Hippocrates, but it was reported as a separate disease by Huluci Behçet in 1937. It is currently classified as a vasculitis belonging to the subgroup of variable vessel vasculitis. It was initially reported in countries bordering the silk route, but nowadays, it is found all over the world. The most common manifestation is oral apotheosis and is seen in over 90% of cases [22].
\nIt is characterized by progressing multiple attacks and remissions. The duration of remission may vary from one attack to another and from one system to another. The attack, in most cases, is followed by a complete recovery called Restitutio ad Integrum of the tissue. A good example is oral aphthosis, and it is exceptional to see a scar. In case of oral aphthosis, it is uncommon to have a scar. In other organs such as the eyes, central nervous system and vascular system, we usually observe sequelae, which may even progress to death. In these cases, aggressive treatment is mandatory [22].
\nTreatment will vary depending on systemic involvement. Mucocutaneous manifestations do not require aggressive treatment, only topical treatment. Arthritis goes on with outbreaks and remissions, which can last from weeks to months, but usually respond well to nonsteroidal anti-inflammatory drugs (NSAIDs). Usually, the remission in these cases is long and the patient may discontinue the medication. There is usually no progression to destruction and deformities [22, 23].
\nTreatment of the gastrointestinal tract depends on the severity. For other manifestations, aggressive treatments are often required, starting with cytotoxic/immunomodulatory drugs associated with corticotherapy. Eventually, biological drugs are used such as apremilast [23].
\nWhen the patient suffers from eye involvement, infliximab or adalimumab anti-TNF drugs may be considered as first- or second-line therapies, or in the exacerbation of pre-existing disease. The European League first recommends corticosteroid-associated azathioprine therapy in all patients with subsequent involvement and the addition of cyclosporine or infliximab, or switching to interferon alfa with or without corticosteroids in patients with severe involvement as more than two drop lines in visual acuity on a 10/10 scale and/or retinal disease (retinal vasculitis or macular involvement) [23]. Other biological drugs are being studied such as IL-1 and IL-6 blockers [8].
\nIntravitreal use of fluocinolone acetonide also has been suggested in refractory cases. In these cases, the increased intraocular pressure and infections should be monitored. With the higher cause of morbidity and mortality, it is vascular involvement. It can affect arteries and veins of any caliber, and with various presentations such as thrombosis, occlusions and aneurysms. Immunosuppressive therapy is one of choices in these cases and there is no consensus regarding anticoagulants [23].
\nA retrospective multicenter study demonstrated a decrease in relapse in immunosuppressant versus untreated patients. Behçet-associated Budd-Chiari syndrome has a high mortality rate, and monthly cyclophosphamide pulses associated with corticosteroid therapy are the treatment of choice. Anti-TNF-alpha was used in 5 patients with refractory disease. Two of these patients already had terminal liver disease during infliximab administration and died due to liver failure. Two patients were successfully treated with infliximab and the fifth patient was stable with etanercept but had dural sinus thrombosis during follow-up [23].
\nCutaneous leukocytoclastic angiitis is an inflammation of small vessels, characterized by an inflammatory infiltrate associated with leukocytoclasia by neutrophil fragmentation and fibrinoid necrosis in small vessel postcapillary venules. It is the most common histological type of cutaneous vasculitis and usually is idiopathic, although antibiotics are also linked [24]. It is often clinically manifested by a palpable purpura, which is found anywhere on the body, but usually affects more lower limbs and can cause arthralgia [24, 25].
\nSeveral symptomatic treatments may be proposed to patients: analgesics, nonsteroidal anti-inflammatory drugs and antihistamines. For chronic or persistent vasculitis, dapsone and/or colchicine may be effective. The use of colchicine in the treatment is beneficial through its effect on reducing neutrophil chemotaxis, blocking leukocyte adhesion and stabilizing lysosomal membranes. Colchicine at a dose of 0.6–1.8 mg/day induces resolution within 1–2 weeks, according to several authors [18].
\nThe best indication for colchicine is in moderate severity vasculitis. It is an effective and inexpensive treatment that can be used alone or in combination. However, its prescription is sometimes limited because of its gastrointestinal side effects [18].
\nIn cases of severe skin necrosis and/or systemic manifestations, systemic corticotherapy (prednisolone or prednisone 20–60 mg/d) with progressive weaning may control the situation in some cases. For patients with systemic manifestations, initial therapy should include high doses of corticosteroids and/or cyclophosphamide. Intravenous immunoglobulins may be useful in the treatment of severe and refractory disease in patients who have a contraindication to traditional immunosuppressive therapy [26].
\nOther drug-associated vasculitis, autoimmune diseases or even infectious diseases require treatment of the underlying disease. In some cases, systemic corticosteroid therapy is necessary, and corticosteroid-sparing immunosuppressive drugs and even intravenous immunoglobulin may be required [26].
\nVasculopathies are diseases that present a hyperactivity of blood vessels in the skin with systemic repercussions, but of unknown etiology. They are usually classified as diseases with circulatory disorders such as acrocyanosis, livedo reticularis, Raynaud’s phenomenon, erythromelalgia, vessel occlusion leading to necrosis such as atherosclerosis obliterans, Buerger’s disease, lymphocyte-mediated inflammatory changes such as livedoid vasculitis, malignant atrophic papulosis and neutrophil-mediated inflammatory changes such as pyoderma gangrenosum. Below, the most common representatives will be discussed [27].
\nAntiphospholipid antibodies syndrome or Hughes syndrome is a systemic, autoimmune disease in which there are repeat thrombotic events, repeated fetal losses and positive autoantibodies such as anticardiolipin and lupus anticoagulant. As skin manifestations, ulcerations and livedo reticularis are the most common signs [27, 28]. Some authors relate Sneddon’s syndrome, which is a disease with strokes and livedo reticularis, as a spectrum of APS [29]. Libman-Sacks endocarditis in systemic lupus erythematosus patients also has an accumulation of antiphospholipid antibodies in the subendothelial layer of the heart valves. However, the correlation with APS is not well established [30].
\nFor patients with a diagnosis of APS, treatment as well as prophylaxis is required. However, there are patients who have met the diagnostic criteria but with no thrombotic events. In these patients, behavioral changes such as smoking and alcohol cessation, lipid control, diabetes management and nonuse of exogenous estrogens are the most important measures [27].
\nAvoiding prolonged immobilizations and other behaviors that predispose to thrombotic events is also recommended. Some authors advocate the use of aspirin without scientific consensus [28].
\nPrimary prophylaxis with low-dose aspirin prophylaxis is usually prescribed to prevent thrombosis in women with recurrent miscarriages, but it does not prevent deep vein thrombosis in men with APS. In systemic lupus and secondary APS, hydroxychloroquine has been proven to have a protective effect against thrombosis, as well as a reduction in cholesterol and glycemia. Patients who undergo surgery and require prolonged immobilization require prophylactic heparinization, and in APS, sometimes doses should be higher than usual due to resistance to anticoagulant effects. For treatment, as initial therapy, unfractionated heparin or low molecular weight heparin is used. Warfarin may also be used [28].
\nBecause patients with APS and thrombosis are at high risk for recurrent thromboembolism episodes, prolonged oral anticoagulant therapy is the best option for attempting to prevent further episodes. The most used oral anticoagulant is warfarin with a therapeutic goal of maintaining INR greater than or equal to 3 [31].
\nIn cases of APS secondary to the underlying systemic disease, it should not open the treatment with systemic oral corticoid. Other agents that can be used are plasmapheresis, immunoglobulin and dapsone, among others [27].
\nIn refractory and catastrophic cases that there is multiple organ infarction, anticoagulation combinations, steroids, plasmapheresis, intravenous immunoglobulin and fish oil derivatives can be used. Fibrinolytic agents have no proven benefit [28].
\nIn case of pregnancy, the best alternative during this period is heparin associated with low doses of aspirin. Combined treatment is more effective to prevent miscarriages than just aspirin alone. Unfractionated heparin, low molecular weight heparin (enoxaparin 40 mg/day) and dalteparin 5000 UI/day can be used during this period. Warfarin should not be used in pregnant women. Accidental discovery of antiphospholipid antibodies during pregnancy, with no clinical history of problems such as thromboembolic events or systemic lupus erythematosus, does not require treatment [28].
\nIt is a sudden cutaneous manifestation in which the fingers, especially the toe, develop cyanotic and painful character. The priority etiology is embolic, but there may be other causes such as rheumatologic and neoplastic, among others. Treatment for this condition depends on the treatment of the underlying disease. However, general and local care such as limb warm-up, physical protection, treatment of secondary infections are essential [32].
\nAcrocyanosis is a disease resulting from chronic vasospasm that causes reflex vasodilation in the affected extremities, usually by medication or central nervous system disorders. It may be painful, cold, discolored, hyperhidrosis, paresthesia and even tingling. Like for blue finger syndrome, treatment is only supportive [27].
\nErythromelalgia is characterized by vasodilation of the extremities, especially in male children, and is usually associated with limb warm-up, pain and burning. It is believed that there is some change in calcium channels, so therapy is directed toward this focus.
\nIn the case of primary erythromelalgia, anesthetics, antiarrhythmics, anticonvulsants and even oral magnesium may be used. In the case of secondary erythromelalgia, besides the treatment already discussed, the underlying disease needs to be controlled [27].
\nIts treatment includes topical drugs like 5% lidocaine and 0.075% capsaicin. For oral medications, we have amitriptyline 10 mg/day, gabapentin 900–1800 mg/day, pregabalin 75 mg/day, flecainide 200 mg/day and buflomedil 200–330 mg/day. Tricyclic antidepressants, selective serotonin reuptake inhibitors and, in selected cases, acetylsalicylic acid, beta blockers and calcium channel antagonists may be excellent associations. In refractory cases, we may use epidural infusions of opioids, bupivacaine and, in the latter case, sympathectomy. However, responses are quite variable and complete remission of symptoms is rarely observed [27, 33].
\nReticular livedo is a common dermatological manifestation in which the limb in question suffers a vasospasm and has a cyanotic, erythematous and erythematous-violet coloration. When the blood plot does not have a confluent pattern, it is called a racemose livedo. In clinical practice, it may be isolated by cold or trauma or may be associated with some systemic diseases such as lupus erythematosus, scleroderma and HIV. Although it is more common in the limbs, it can also affect the trunk and there may be ulcerations. Cold stimulates vasospasm, when the cause is removed, however, over time, vessels may become permanently dilated and become permanently telangiectatic [27, 34].
\nThe treatment of livedo, primarily, is protection against the cold. Vasodilators may be an alternative and corticosteroids should be avoided as much as possible. If there are ulcerations or a racemose livedo associated with antiphospholipid antibody syndrome, anticoagulation is recommended. When livedo is associated with some underlying disease, the management of the disease usually improves its manifestation. Other medications may be tried such as danazol, tissue plasminogen activator (tPA), pentoxifylline and antiplatelets. Immunosuppressants such as azathioprine and sympathectomy are reserved for refractory cases [27, 34, 35].
\nIt is a paroxysmal vasospastic disorder characterized by the simultaneous alternation of pallor (vasoconstriction), cyanosis (blood stasis) and redness (compensatory vasodilation).
\nWe consider Raynaud’s disease (20% of the cases) when it occurs primarily and not associated with other acne. And we consider Raynaud’s phenomenon (80%) when it occurs secondary to another disease [27].
\nTreatment consists of treating the basic disease and quitting smoking. Protection against the cold is necessary to avoid triggering the frame. In idiopathic forms, the use of nifedipine 30–120 mg/day can be used. Other treatment modalities may also be employed such as topical nitroglycerin, iloprost, losartan, serotonin receptor inhibitors, phosphodiesterase inhibitors, n-acetylcysteine, botulinum toxin, bosentan, platelet inhibitors and fibrinolytics. In refractory cases, sympathectomy may be performed [27].
\nPerniosis is a rare panniculitis that develops with painful erythematous-violaceous nodules in young people more susceptible to cold. There is also a certain uncertain relationship with tobacco. Treatment, like other cold-related conditions, requires protection from the cold such as appropriate clothing, gloves, socks, boots and smoking cessation. Behavior changes and topical corticoid creams can help to heal the lesions. Some vasodilators may also be applied as nicotinic acid, nifedipine and pentoxifylline. In refractory cases, sympathectomy and UVB phototherapy may also be considered [36].
\nLivedoid vasculitis is one of the most common vasculopathies, described in 1929, and can affect up to about 5% of the healthy population, reaching 70% in patients with venous ulcers. Some authors differentiate livedoid vasculitis from Millian’s white atrophy in relation to etiology. Livedoid vasculitis is persistent livedoid reticularis associated with an ulcer [37]. White atrophy is a white atrophy scar with a stellar pattern most common in the lower limbs of women aged 30–60 years that may or may not be associated with collagenases and neoplasia; however, the best-established link is with chronic venous insufficiency [35].
\nThe treatment for this disease is divided into some of the following groups:
Drugs stimulating endogenous fibrinolytic activity such as danazol, the activating factor of recombinant tissue plasminogen, rt-PA, low dose alteplase, associated or not with heparin and aspirin [27, 35].
Drugs such as dipyridamole, cilostazol, the thienopyridine group (clopidogrel, ticlopidine hydrochloride, whether associated with aspirin) and sarpogrelate.
Hemorheological drugs that decrease blood viscosity, increase red blood cell flexibility and improve circulation. From this group, the example is pentoxifylline and buflomedil hydrochloride [27, 35].
Modulating lymphocyte response therapy as systemic PUVA phototherapy [27].
Other drugs such oral corticosteroids, intravenous immunoglobulin, cyclosporine, hyperbaric oxygen therapy and intravenous iloprost [27].
For patients with any associated thrombophilia, warfarin, unfractionated heparin, low molecular weight heparin and even heparin minidoses may also be used [27].
\nIt is a chronic disease associated with diabetes that gradually occludes the vessel light. It affects the feet more than the hands in patients over 50 years. There is no specific treatment, but oral corticosteroids may be employed associated with diabetes with strict disease control. Behavioral change with diabetes mellitus improvement and antibiotic therapy, if secondary injuries, is the therapy of choice. Vasodilators do not have their proven efficiency. In severe cases, sympathectomy and vascular surgery may be used [38].
\nThe priority treatment is smoking cessation and rest. Iloprost IV may be an alternative to retard evolution. In many cases, amputation is required, with excision of the gangrenous fingers, sympathectomy and surgeries such as arterialization of the venous arch of the foot. The vascular surgeon is extremely important for follow-up [27, 39].
\nMalignant atrophic papulosis (MAP) is an obliterating endovasculitis of small- and medium-sized arteries that produces tissue infarction as its main feature. It is considered an uncommon disease of unknown cause and can affect the skin, gastrointestinal tract and central nervous system, and the involvement of these last two systems can be fatal [40].
\nThere is no fully effective treatment for the disease. Some authors use acetylsalicylic acid (300 mg daily) and/or dipyridamole (75 mg twice daily) as the first therapeutic modality, which facilitates blood perfusion. Other therapeutic options such as aspirin, heparin and warfarin can be used, however, aspirin is more associated with resurgence of lesions when discontinuing the drug [41].
\nMore recently, studies have been conducted using eculizumab that have shown initial efficacy in skin and intestinal lesions, but the drug has not been able to prevent the development or progression of systemic manifestations. Subcutaneous treprostinil has been successfully tested in some cases with dramatic and sustained improvement in clinical status, although the response was not immediate. The mechanism of action of treprostinil in this scenario is not yet well understood [42, 43].
\nThe use of corticosteroids, chloroquine or other immunosuppressants has proved unsatisfactory and has great potential to worsen the disease by unknown mechanism; therefore, they are not indicated [43].
\nThese are vascular inflammations with thrombus formation and consequent occlusion or may occur due to slow flow within a varicose vein. If thrombophlebitis is found in apparently normal superficial veins, attention should be paid to the possibility of underlying malignancy, thrombosing coagulopathy and silent deep vein thrombosis [44].
\nFor therapeutic management, in cases of limited superficial thrombophlebitis below the knee, without evidence of deep vein thrombosis, compression by specific stockings and the use of nonsteroidal anti-inflammatory drugs are enough, providing symptomatic relief. However, if there is deep venous thrombosis or extension to the saphenofemoral or saphenopopliteal junctions, prophylactic use of low molecular weight heparin may be necessary [44].
\nVasculitis and vasculopathies are a challenge physicians face on a daily basis. Due to rarity of the diseases all over the globe, the scientific community is not able to perform studies with a great number of patients and biological medications seem to be the promise to a cure or the disease control. These groups of drugs are relatively new and still expensive in most countries. Furthermore, more studies need to be developed and long follow-ups should be performed before they are considered gold-standard treatment. In the medical reality nowadays, despite any consideration, an early diagnosis can change the whole disease course and prevent inabilities, and even without cure, it is indispensable to control symptoms and provide a better quality of life to patients.
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There is a plethora of research carried out regarding professionalism in policing to meet the needs and challenges of the twenty-first century. Considering the recent developments in police education and training, this chapter mainly discusses three newly introduced routes for recruitment and education of police constables under the Policing Education Qualifications Framework (PEQF), namely Police Constable Degree Apprenticeship (PCDA), Degree Holder Entry Programme (DHEP), and Pre-Join Degree (PJD). Higher education institutions (HEIs), in partnership with the police forces, are providing professional qualifications for policing as a graduate level profession. Though they have made remarkable progress in developing police education programmes, they are facing various challenges in implementing the qualification framework. This chapter also explores pedagogical aspects of police education including the effectiveness and contrast between different forms of teaching and learning. While featuring the challenges and prospects of the new police education programmes, this chapter also outlines different aspects of partnership for delivering these professional qualification programmes.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"M. Mahruf C. Shohel, Gias Uddin, Julian Parker-McLeod and Daniel Silverstone",authors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. 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Two UNESCO World Heritage sites will be discussed briefly: Otrar and the surrounding oasis, a medieval complex of sites along the Great Silk Route, and Tamgaly, a petroglyph and archaeological reserve. These two UNESCO World Heritage archaeological sites or preserves will be contrasted with the Talgar Iron Age sites (400 BC–100 CE) situated in a rapidly changing landscape due to economic development and infrastructure (pipelines, railways, roads, and housing) about 12–15 km east of the major city of Almaty. The goal of this article is to discuss the complexity of the entangled sectors of cultural and historic preservation, economic development, tourism, and global transnational heritage within the framework of sustainability.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Claudia Chang",authors:[{id:"296402",title:"Dr.",name:"Claudia",middleName:null,surname:"Chang",slug:"claudia-chang",fullName:"Claudia Chang"}]},{id:"71206",doi:"10.5772/intechopen.91053",title:"Uprising and Human Rights Abuses in Southern Cameroon-Ambazonia",slug:"uprising-and-human-rights-abuses-in-southern-cameroon-ambazonia",totalDownloads:949,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In 2016, lawyers, teachers and students in the two Anglophone regions initially led demonstrations and strikes, which eventually involved a wider section of the population. This mobilization was against their marginalization by the Francophone-dominated government in which they were chronically under-represented in all aspects of national life: political appointments and professional training and had been treated as second-class citizens since their reunification. They argued that their vibrant economic and political institutions had been completely erased, and their education and judicial systems had been undermined and degraded. Activists spread videos that show security forces abusing human rights (by suppressing peaceful gatherings, beating, harassing, arresting and killing protesters, burning their houses, schools and hospitals) in order to produce a counter-narrative to the ‘official story’ that main-stream media had been producing. We collected and analyzed 30 videos to better appreciate the human rights abuses. The videos provide information that cannot be provided by other types of data. They are used as ‘proofs of facts’ and they contain much more visual information on bodily movement and acoustic data. The videos show appalling images not just of how French-speaking soldiers tortured Anglophones but also their inability to communicate with them adequately although they share the same country.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Nanche Billa Robert",authors:[{id:"285893",title:"Dr.",name:"Nanche Billa",middleName:null,surname:"Robert",slug:"nanche-billa-robert",fullName:"Nanche Billa Robert"}]}],mostDownloadedChaptersLast30Days:[{id:"68136",title:"Globalization of the Cruise Industry: A Tale of Ships Part II - Asia Post 1994",slug:"globalization-of-the-cruise-industry-a-tale-of-ships-part-ii-asia-post-1994",totalDownloads:926,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Cruising has grown over 7% a year since 1980. Sustained rapid expansion in North America, followed by local expansion in Europe and Asia, has made cruising a global industry, with 365 ships and estimated sales of $37.8 US billion (CIN, 2017). This global development has been fueled by innovation and introduction of market changing resident ships appealing to the mass traveler which were quickly matched by competitors, establishment of industry and port marketing organizations, awareness of cruising as a vacation option, and availability of suitable port and berthing facilities. When these four conditions coexisted the industry experienced rapid growth. Since 1966, the cruise industry has developed from a Miami-centered industry to a global industry centered in North America, Europe, Asia, and Australia/New Zealand. Given the high cost of state-of-the-art ships, their deployment is a good indication of industry’s confidence in market growth. This chapter chronicles the development of the Asian cruise industry from 1994 through 2017. Data from Cruise Industry News Annual Reports (CIN) and Berlitz Complete Guide to Cruising and Cruise Ships (Ward) are examined and conclusions are drawn.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Andrew O. Coggins",authors:[{id:"229658",title:"Prof.",name:"Andrew",middleName:null,surname:"Coggins Jr",slug:"andrew-coggins-jr",fullName:"Andrew Coggins Jr"}]},{id:"72435",title:"Police Education in the United Kingdom: Challenges and Future Directions",slug:"police-education-in-the-united-kingdom-challenges-and-future-directions",totalDownloads:1132,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"This chapter outlines the historical development of police education in the United Kingdom, more precisely in England and Wales, and highlights new strategies and planning for the professional development of the police. There is a plethora of research carried out regarding professionalism in policing to meet the needs and challenges of the twenty-first century. Considering the recent developments in police education and training, this chapter mainly discusses three newly introduced routes for recruitment and education of police constables under the Policing Education Qualifications Framework (PEQF), namely Police Constable Degree Apprenticeship (PCDA), Degree Holder Entry Programme (DHEP), and Pre-Join Degree (PJD). Higher education institutions (HEIs), in partnership with the police forces, are providing professional qualifications for policing as a graduate level profession. Though they have made remarkable progress in developing police education programmes, they are facing various challenges in implementing the qualification framework. This chapter also explores pedagogical aspects of police education including the effectiveness and contrast between different forms of teaching and learning. While featuring the challenges and prospects of the new police education programmes, this chapter also outlines different aspects of partnership for delivering these professional qualification programmes.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"M. Mahruf C. Shohel, Gias Uddin, Julian Parker-McLeod and Daniel Silverstone",authors:[{id:"94099",title:"Dr.",name:"M. Mahruf C.",middleName:null,surname:"Shohel",slug:"m.-mahruf-c.-shohel",fullName:"M. Mahruf C. Shohel"},{id:"319810",title:"Mr.",name:"Gias",middleName:null,surname:"Uddin",slug:"gias-uddin",fullName:"Gias Uddin"},{id:"321004",title:"Dr.",name:"Julian",middleName:null,surname:"Parker-McLeod",slug:"julian-parker-mcleod",fullName:"Julian Parker-McLeod"},{id:"321005",title:"Dr.",name:"Daniel",middleName:null,surname:"Silverstone",slug:"daniel-silverstone",fullName:"Daniel Silverstone"}]},{id:"73702",title:"Approaches to Analysis of Interstate Cooperation",slug:"approaches-to-analysis-of-interstate-cooperation",totalDownloads:643,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"At the present day cultural diplomacy plays a rather important role in the development of international relations and world politics. This concept is receiving increasing attention from various countries, international and non-governmental organizations and other actors. This trend exists due to a number of reasons, such as the desire of states to create a positive image of their country, the expansion of international cooperation, changes in the global and domestic political situation, the protection of national interests, the prevention of conflicts between states, etc. Cultural diplomacy, beyond historical precedents, consists of a relatively new practice of a country’s foreign policy, which has traditionally focused on trade and security and defense issues. It is true that in European countries there are institutions of cultural foreign relations since the beginning of the century, but in the last decade the issues, related to the projection of the international image of countries, have become more important.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Alexander Rozanov, Maria Ivanchenko, Alexandra Baranova, Elena N. Antonova, Mikhail Smirnov, Olga Belyaeva, Maria Ilicheva, Ludmila Ilicheva, Maria Krotovskaya, Tatiana Grabovich, Zaru Utekova, Dmitry Medvedev, Natalya Ogneva, Furat Al-Mutairi, Elvira Shishlo, Amina Surpkelova, Irina Kopachevskaya, Irina Sokurova, Yulia Borisova, Fernando Joao, Artyom Pakulskikh, Polina Chernova, Alexandra Khramova, Oksana Gryuk, Jesus Yaniz Gonzalez, Valentina Komleva, Alina Papsheva and Arkadi Bessonov",authors:[{id:"233092",title:"Dr.",name:"Alexander",middleName:null,surname:"Rozanov",slug:"alexander-rozanov",fullName:"Alexander Rozanov"},{id:"312194",title:"Prof.",name:"Valentina",middleName:"Vycheslavovna",surname:"Komleva",slug:"valentina-komleva",fullName:"Valentina Komleva"},{id:"312195",title:"Ms.",name:"Alexandra",middleName:null,surname:"Baranova",slug:"alexandra-baranova",fullName:"Alexandra Baranova"},{id:"312196",title:"Dr.",name:"Furat",middleName:null,surname:"Al Mutairi",slug:"furat-al-mutairi",fullName:"Furat Al Mutairi"},{id:"312197",title:"Ms.",name:"Maria",middleName:null,surname:"Ivanchenko",slug:"maria-ivanchenko",fullName:"Maria Ivanchenko"},{id:"312198",title:"Associate Prof.",name:"Arkadi",middleName:null,surname:"Bessonov",slug:"arkadi-bessonov",fullName:"Arkadi Bessonov"},{id:"312199",title:"Ms.",name:"Alina",middleName:null,surname:"Papsheva",slug:"alina-papsheva",fullName:"Alina Papsheva"},{id:"312200",title:"Prof.",name:"Ludmila",middleName:null,surname:"Ilicheva",slug:"ludmila-ilicheva",fullName:"Ludmila Ilicheva"},{id:"312201",title:"Ph.D. Student",name:"Aleksandra",middleName:null,surname:"Khramova",slug:"aleksandra-khramova",fullName:"Aleksandra Khramova"},{id:"316768",title:"Dr.",name:"Maria",middleName:null,surname:"Ilicheva",slug:"maria-ilicheva",fullName:"Maria Ilicheva"},{id:"317753",title:"Dr.",name:"Oksana",middleName:null,surname:"Gryuk",slug:"oksana-gryuk",fullName:"Oksana Gryuk"}]},{id:"71206",title:"Uprising and Human Rights Abuses in Southern Cameroon-Ambazonia",slug:"uprising-and-human-rights-abuses-in-southern-cameroon-ambazonia",totalDownloads:951,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"In 2016, lawyers, teachers and students in the two Anglophone regions initially led demonstrations and strikes, which eventually involved a wider section of the population. This mobilization was against their marginalization by the Francophone-dominated government in which they were chronically under-represented in all aspects of national life: political appointments and professional training and had been treated as second-class citizens since their reunification. They argued that their vibrant economic and political institutions had been completely erased, and their education and judicial systems had been undermined and degraded. Activists spread videos that show security forces abusing human rights (by suppressing peaceful gatherings, beating, harassing, arresting and killing protesters, burning their houses, schools and hospitals) in order to produce a counter-narrative to the ‘official story’ that main-stream media had been producing. We collected and analyzed 30 videos to better appreciate the human rights abuses. The videos provide information that cannot be provided by other types of data. They are used as ‘proofs of facts’ and they contain much more visual information on bodily movement and acoustic data. The videos show appalling images not just of how French-speaking soldiers tortured Anglophones but also their inability to communicate with them adequately although they share the same country.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Nanche Billa Robert",authors:[{id:"285893",title:"Dr.",name:"Nanche Billa",middleName:null,surname:"Robert",slug:"nanche-billa-robert",fullName:"Nanche Billa Robert"}]},{id:"72097",title:"Towards Global Peace and Sustainability: Role of Education in Peace-Building in the Great Lakes Region of Sub-Saharan Africa",slug:"towards-global-peace-and-sustainability-role-of-education-in-peace-building-in-the-great-lakes-regio",totalDownloads:683,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The Great Lakes Region of sub-Saharan Africa is well known for being volatile and turbulent in terms of peace and stability. For over 60 years, almost all countries in the region have experienced some kind of political and social turmoil such as civil war, coup de tat, and genocides. In 1960, the first democratically elected Congolese prime minister was assassinated. There were unprecedented social and political havoc in a nearby “other Congo” characterized by power struggle between various political and ethnic factions in the post-independence Congo Brazzaville. In Burundi and Rwanda, ethnic tensions between the Tutsi and Hutu engulfed the developmental dreams of nationalist freedom fighters until 2015. Though arguably stable, Tanzania has experienced its own share of socio-political messy including the 1998 Mwembechai and 2001 Pemba massacres. Efforts to build a sense of sustainable peace and development based on mutual understanding and socio-political harmony has brought limited success. In all these countries, the missing link in building sustainable peace and security has been a lack of education. The chapter intends to fill this gap by critically analyzing the potential role of basic education, especially pre-primary and early grades education, in sustainable peace-building in the sub-Saharan context.",book:{id:"6950",slug:"education-human-rights-and-peace-in-sustainable-development",title:"Education, Human Rights and Peace in Sustainable Development",fullTitle:"Education, Human Rights and Peace in Sustainable Development"},signatures:"Laurent Gabriel Ndijuye and Pambas Basil Tandika",authors:[{id:"301740",title:"Dr.",name:"Laurent Gabriel",middleName:null,surname:"Ndijuye",slug:"laurent-gabriel-ndijuye",fullName:"Laurent Gabriel Ndijuye"},{id:"319403",title:"Dr.",name:"Pambas Basilius",middleName:null,surname:"Tandika",slug:"pambas-basilius-tandika",fullName:"Pambas Basilius Tandika"}]}],onlineFirstChaptersFilter:{topicId:"476",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"July 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:14,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:16,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. Udoh, Josephine U. Agogbua, Eberechi R. Keyagha and Itorobong I. 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From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",institutionURL:null,country:{name:"Hungary"}}}]},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",slug:"antioxidants",publishedDate:"November 6th 2019",editedByType:"Edited by",bookSignature:"Emad Shalaby",hash:"76361b4061e830906267933c1c670027",volumeInSeries:5,fullTitle:"Antioxidants",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby",profilePictureURL:"https://mts.intechopen.com/storage/users/63600/images/system/63600.png",biography:"Dr. Emad Shalaby is a professor of biochemistry on the Biochemistry Department Faculty of Agriculture, Cairo University. He\nreceived a short-term scholarship to carry out his post-doctoral\nstudies abroad, from Japan International Cooperation Agency\n(JICA), in coordination with the Egyptian government. Dr.\nShalaby speaks fluent English and his native Arabic. He has 77\ninternationally published research papers, has attended 15 international conferences, and has contributed to 18 international books and chapters.\nDr. Shalaby works as a reviewer on over one hundred international journals and is\non the editorial board of more than twenty-five international journals. 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Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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