The common effects of ketamine in snorted doses.
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Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"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:"8087",leadTitle:null,fullTitle:"Neuroprotection - New Approaches and Prospects",title:"Neuroprotection",subtitle:"New Approaches and Prospects",reviewType:"peer-reviewed",abstract:"Neurological disease affects nearly 25%–30% of the world’s population, exerting enormous financial strain on the healthcare system. Estimated current costs are around $800 annual billion, and this number is expected to increase exponentially as the global population ages. As such, new and alternative neuroprotective strategies are urgently needed. This book examines some of the most promising approaches in neuroprotection as well as discusses current goals and prospects. Organized into three sections, chapters cover such topics as the use of cannabinoids, medicinal plants, and essential oils in Alzheimer’s and Parkinson’s; protein misfolding and the neuroprotective potential of vitamin E in cerebral ischemia; and potential new neurological treatments and their mechanisms of action.",isbn:"978-1-83880-440-4",printIsbn:"978-1-83880-439-8",pdfIsbn:"978-1-83969-261-1",doi:"10.5772/intechopen.77918",price:139,priceEur:155,priceUsd:179,slug:"neuroprotection-new-approaches-and-prospects",numberOfPages:348,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"10acd587ca2c942616bfc09c4b79df39",bookSignature:"Matilde Otero-Losada, Francisco Capani and Santiago Perez Lloret",publishedDate:"November 26th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8087.jpg",numberOfDownloads:11077,numberOfWosCitations:5,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:10,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:21,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 27th 2019",dateEndSecondStepPublish:"October 1st 2019",dateEndThirdStepPublish:"November 30th 2019",dateEndFourthStepPublish:"February 18th 2020",dateEndFifthStepPublish:"April 18th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"193560",title:null,name:"Matilde",middleName:null,surname:"Otero-Losada",slug:"matilde-otero-losada",fullName:"Matilde Otero-Losada",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSC0wQAG/Profile_Picture_2022-08-08T10:20:33.jpg",biography:"Dr. Matilde Otero-Losada graduated from the School of Pharmacy and Biochemistry, University of Buenos Aires (UBA), Argentina. She obtained a SciD in Neuropharmacology from the same univeristy and completed a PhD in Psychiatry at Wolverhampton University, England. Her following studies in psychometrics and statistical methods, radioisotopes and radiochemistry, and signal processing and microcomputers, took her to the University of California San Diego (UCSD) for training in human psychophysics. Back to Argentina, she carried on studying smell, taste, and trigeminal perception at the Hospital de Clínicas, UBA. She is devoted to the diagnosis, counseling, support, and treatment of people with olfactory and neurocognitive disorders. Focused on the study of metabolic syndrome, soft drinks, and cardiovascular-renal morbidity for the last ten years, in the last two years she is back to her roots in neuroscience. Dr. Otero-Losada has published more than ninety 90 papers in prestigious, indexed journals and authored several book chapters. She is a senior researcher at the National Research Council (Argentina) and a reviewer and praised editor of books and scientific journals, acknowledged for her stylish writing and editing skills.",institutionString:"National Scientific and Technical Research Council. CONICET",position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"1",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"120703",title:"Dr.",name:"Francisco",middleName:null,surname:"Capani",slug:"francisco-capani",fullName:"Francisco Capani",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS7QPQA0/Profile_Picture_2022-07-13T14:54:22.PNG",biography:"Dr. Francisco Capani graduated from the School of Medicine, University of Buenos Aires (UBA), Argentina, and completed his doctoral studies in Neuroscience at the Institute of Cell Biology and Neuroscience 'Prof. E. De Robertis,” School of Medicine (UBA), Argentina. He completed his postdoctoral studies abroad at the University of California San Diego (UCSD-NCMIR) and the Karolinska Institute, Department of Neuroscience. Over an eight-year period, his research focused on synaptic organization, combining electron tomography, 3D reconstruction, and correlative light and electron microscopy techniques. Upon his return to Argentina in 2006, he devoted his study to the mechanisms involved in the pathophysiology of the perinatal asphyxia supported by his broad experience in electron microscopy. Dr. Capani has published 115 papers in recognized journals and has been an invited speaker at several international conferences.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Buenos Aires",institutionURL:null,country:{name:"Argentina"}}},coeditorTwo:{id:"168475",title:"Dr.",name:"Santiago Perez",middleName:null,surname:"Lloret",slug:"santiago-perez-lloret",fullName:"Santiago Perez Lloret",profilePictureURL:"https://mts.intechopen.com/storage/users/168475/images/system/168475.jpeg",biography:"Santiago Perez-Lloret is a leading expert in neurophysiology and neuropharmacology with more 100 papers published in international medical journals (H-index = 34). He has recently edited the book Clinical Trials in Parkinson’s Disease. After obtaining his MD and PhD, he pursued master courses in pharmacoepidemiology, clinical pharmacology, and biostatistics at the Universities of Bordeaux and Paris. Dr. Perez-Lloret is Assistant Professor of Neurophysiology at the University of Buenos Aires, and a senior researcher at the National Research Council. He is also an associate editor for Frontiers in Pharmacology. He is a member of the Education Committee of the International Parkinson’s Disease and Movement Disorder Society (MDS).",institutionString:"University of Buenos Aires",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of Buenos Aires",institutionURL:null,country:{name:"Argentina"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1056",title:"Neurology",slug:"neurology"}],chapters:[{id:"70726",title:"Neuroprotective Properties of Cannabinoids in Cellular and Animal Models: Hypotheses and Facts",doi:"10.5772/intechopen.90761",slug:"neuroprotective-properties-of-cannabinoids-in-cellular-and-animal-models-hypotheses-and-facts",totalDownloads:474,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Progressive neuronal loss is a typical characteristic of neurodegenerative diseases. In Parkinson’s disease, the loss of dopaminergic neurons in the basal ganglia results in impaired mobility and flawed muscle control. The loss of cholinergic neurons largely in the basal forebrain contributes to memory and attention deficits and the overall cognitive impairment in Alzheimer’s disease. This being said, neuroprotective drugs should be expected to preserve and/or restore the functions affected by neuronal loss, and substantially prevent cell death. The endocannabinoid system, comprising lipid mediators able to bind to and activate cannabinoid receptors, has emerged as a therapeutic target of potential interest in a variety of central nervous system diseases. Palmitoylethanolamide (PEA) is one of the most important endocannabinoids, which has a key role in modulating oxidative stress and inflammatory response with neuroprotective potential in neurological disorders. Neurodegenerative diseases undergo varied, progressive stages. The current therapeutical approaches are beginning to fall short when it comes to meet the expected results, urging to either develop or identify or develop new effective treatments. This chapter discusses the neuroprotective potential of new drugs, aiming to shed some light on their proposed mechanism of action and their effect in cellular and animal models of neurodegeneration.",signatures:"Lucas D. Udovin, Andrea Aguilar, Tamara Kobiec, María I. Herrera, Santiago Perez Lloret, Nicolás Toro Urrego and Rodolfo A. Kölliker Frers",downloadPdfUrl:"/chapter/pdf-download/70726",previewPdfUrl:"/chapter/pdf-preview/70726",authors:[{id:"205589",title:"Dr.",name:"Rodolfo Alberto",surname:"Kölliker Frers",slug:"rodolfo-alberto-kolliker-frers",fullName:"Rodolfo Alberto Kölliker Frers"},{id:"306021",title:"Dr.",name:"Lucas",surname:"Udovin",slug:"lucas-udovin",fullName:"Lucas Udovin"},{id:"308462",title:"Dr.",name:"Tamara",surname:"Kobiec",slug:"tamara-kobiec",fullName:"Tamara Kobiec"},{id:"308463",title:"Dr.",name:"María Inés",surname:"Herrera",slug:"maria-ines-herrera",fullName:"María Inés Herrera"},{id:"308464",title:"Dr.",name:"Santiago",surname:"Perez Lloret",slug:"santiago-perez-lloret",fullName:"Santiago Perez Lloret"},{id:"308465",title:"Dr.",name:"Nicolás",surname:"Toro Urrego",slug:"nicolas-toro-urrego",fullName:"Nicolás Toro Urrego"},{id:"308466",title:"Dr.",name:"Andrea",surname:"Aguilar",slug:"andrea-aguilar",fullName:"Andrea Aguilar"}],corrections:null},{id:"71014",title:"An Alternate View of Neuroprotection with Peptides in Alzheimer’s Disease",doi:"10.5772/intechopen.91065",slug:"an-alternate-view-of-neuroprotection-with-peptides-in-alzheimer-s-disease",totalDownloads:683,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Neuroprotection plays a crucial role in everyday life, maintaining a clean environment in the central nervous system to allow for normal functioning. In Alzheimer’s disease and other neurodegenerative disorders, neuroprotection may have two roles. Under standard circumstances, the immune system protects the CNS, but sometimes it can exacerbate the pathophysiology of some diseases through neuroinflammation leading to further degeneration. Alzheimer’s disease is fast getting out of control, with no new approvals in therapeutics since 2003, and of those approved, all target symptomatic treatment. Initiated by a microglial response to Aβ plaques, therapeutic development should focus on the amyloid cascade as a neuroprotective measure for Alzheimer’s disease. This chapter will examine the status of the types of therapeutics in clinical trials for Alzheimer’s disease, offering insights into peptides as an area of opportunity for neuroprotection and detailing considerations for the use of peptides in Alzheimer’s disease.",signatures:"Samuel King and Cenk Suphioglu",downloadPdfUrl:"/chapter/pdf-download/71014",previewPdfUrl:"/chapter/pdf-preview/71014",authors:[{id:"72841",title:"Prof.",name:"Cenk",surname:"Suphioglu",slug:"cenk-suphioglu",fullName:"Cenk Suphioglu"},{id:"307928",title:"Ph.D. Student",name:"Samuel",surname:"King",slug:"samuel-king",fullName:"Samuel King"}],corrections:null},{id:"69463",title:"Polyphenols as Potential Therapeutic Drugs in Neurodegeneration",doi:"10.5772/intechopen.89575",slug:"polyphenols-as-potential-therapeutic-drugs-in-neurodegeneration",totalDownloads:920,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Several therapeutic approaches have been suggested so far for the treatment of neurodegenerative diseases, but to date, there are no approved therapies. The available ones are only symptomatic; they are employed to mitigate the disease manifestations and to improve the patient life quality. These diseases are characterized by the accumulation and aggregation of misfolded proteins in the nervous system, with different specific hallmarks. The onset mechanisms are not completely elucidated. Some promising approaches are focused on the inhibition of the amyloid aggregation of the proteins involved in the etiopathology of the disease, such as Aβ peptide, Tau, and α-synuclein, or on the increase of their clearance in order to avoid their aberrant accumulation. Here, we summarize traditional and new therapeutic approaches proposed for Alzheimer’s and Parkinson’s diseases and the recent technologies for brain delivery.",signatures:"Patrizia Polverino de Laureto, Luana Palazzi and Laura Acquasaliente",downloadPdfUrl:"/chapter/pdf-download/69463",previewPdfUrl:"/chapter/pdf-preview/69463",authors:[{id:"304488",title:"Associate Prof.",name:"Patrizia",surname:"Polverino De Laureto",slug:"patrizia-polverino-de-laureto",fullName:"Patrizia Polverino De Laureto"},{id:"304490",title:"Dr.",name:"Luana",surname:"Palazzi",slug:"luana-palazzi",fullName:"Luana Palazzi"},{id:"309335",title:"Dr.",name:"Laura",surname:"Acquasaliente",slug:"laura-acquasaliente",fullName:"Laura Acquasaliente"}],corrections:null},{id:"70907",title:"Extracts and Essential Oils from Medicinal Plants and Their Neuroprotective Effect",doi:"10.5772/intechopen.90903",slug:"extracts-and-essential-oils-from-medicinal-plants-and-their-neuroprotective-effect",totalDownloads:850,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Current therapies for neurodegenerative diseases offer only limited benefits to their clinical symptoms and do not prevent the degeneration of neuronal cells. Neurological diseases affect millions of people around the world, and the economic impact of treatment is high, given that health care resources are scarce. Thus, many therapeutic strategies to delay or prevent neurodegeneration have been the subject of research for treatment. One strategy for this is the use of herbal and essential oils of different species of medicinal plants because they have several bioactive compounds and phytochemicals with neuroprotective capacity. In addition, they respond positively to neurological disorders, such as dementia, oxidative stress, anxiety, cerebral ischemia, and oxidative toxicity, suggesting their use as complementary treatment agents in the treatment of neurological disorders.",signatures:"Ianara Mendonça da Costa, Elaine Cristina Gurgel Andrade Pedrosa, Ana Paula de Carvalho Bezerra, Luciana Cristina Borges Fernandes, José Rodolfo Lopes de Paiva Cavalcanti, Marco Aurélio Moura Freire, Dayane Pessoa de Araújo, Amália Cinthia Meneses do Rego, Irami Araujo Filho, Francisco Irochima Pinheiro and Fausto Pierdoná Guzen",downloadPdfUrl:"/chapter/pdf-download/70907",previewPdfUrl:"/chapter/pdf-preview/70907",authors:[{id:"269470",title:"Ms.",name:"Ianara",surname:"Costa",slug:"ianara-costa",fullName:"Ianara Costa"},{id:"308905",title:"Prof.",name:"Fausto",surname:"Guzen",slug:"fausto-guzen",fullName:"Fausto Guzen"},{id:"311004",title:"Ms.",name:"Ana Paula",surname:"Bezerra",slug:"ana-paula-bezerra",fullName:"Ana Paula Bezerra"},{id:"311005",title:"Ms.",name:"Luciana",surname:"Fernandes",slug:"luciana-fernandes",fullName:"Luciana Fernandes"},{id:"311006",title:"Dr.",name:"José Rodolfo",surname:"Cavalcanti",slug:"jose-rodolfo-cavalcanti",fullName:"José Rodolfo Cavalcanti"},{id:"311010",title:"MSc.",name:"Elaine",surname:"Pedrosa",slug:"elaine-pedrosa",fullName:"Elaine Pedrosa"},{id:"311011",title:"Dr.",name:"Marco",surname:"Freire",slug:"marco-freire",fullName:"Marco Freire"},{id:"311014",title:"Dr.",name:"Dayane",surname:"Araújo",slug:"dayane-araujo",fullName:"Dayane Araújo"},{id:"311017",title:"Dr.",name:"Amália",surname:"Rego",slug:"amalia-rego",fullName:"Amália Rego"},{id:"311018",title:"Dr.",name:"Irami",surname:"Araújo Filho",slug:"irami-araujo-filho",fullName:"Irami Araújo Filho"},{id:"311019",title:"Dr.",name:"Francisco Irochima",surname:"Pinheiro",slug:"francisco-irochima-pinheiro",fullName:"Francisco Irochima Pinheiro"}],corrections:null},{id:"68971",title:"Glycodendrimers as Potential Multitalented Therapeutics in Alzheimer’s Disease",doi:"10.5772/intechopen.88974",slug:"glycodendrimers-as-potential-multitalented-therapeutics-in-alzheimer-s-disease",totalDownloads:809,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Finding successful therapies for the treatment of Alzheimer’s disease (AD) is one of the most challenging tasks existing for human health. Several drugs have been found and validated in preclinical studies with some success, but not with the desired breakthroughs in the following clinical development phases. AD causes multiple brain dysfunctions that can be described as a brain organ failure, resulting in significant cognitive decline. Aggregation of amyloid proteins and neuronal loss are the hallmarks of AD. Thus, one of the strategies to treat AD is to find a multifunctional drug that may combine both anti-aggregation and neuroprotective properties. Such a candidate could be chemically modified dendrimers. Dendrimers are branched, nonlinear molecules with multiple reactive groups located on their surface. Chemical modification of reactive surface groups defines the property of the dendrimers. In this chapter, I will discuss poly(propylene imine) dendrimers with the surface functionalized with histidine and maltose as an example of a multifunctional therapeutic drug candidate able to protect the memory of AD transgenic model mice.",signatures:"Oxana Klementieva",downloadPdfUrl:"/chapter/pdf-download/68971",previewPdfUrl:"/chapter/pdf-preview/68971",authors:[{id:"303288",title:"Prof.",name:"Oxana",surname:"Klementieva",slug:"oxana-klementieva",fullName:"Oxana Klementieva"}],corrections:null},{id:"71578",title:"Alzheimer’s Disease Neuroprotection: Associated Receptors",doi:"10.5772/intechopen.91918",slug:"alzheimer-s-disease-neuroprotection-associated-receptors",totalDownloads:643,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Research with humans and animals has been developed over the past few years to identify receptors involved in Alzheimer’s disease, aiming at a better understanding of the mechanisms and pathophysiological aspects associated with the disease. Such receptors, whether or not directly associated with current AD therapy, are relevant since their blockage or activation might result in improving or worsening the clinical scenario of the disease. In other words, such receptors might be involved in the AD prognosis. This chapter discusses some relevant points about the receptors involved with AD.",signatures:"Alice Barros Câmara",downloadPdfUrl:"/chapter/pdf-download/71578",previewPdfUrl:"/chapter/pdf-preview/71578",authors:[{id:"315734",title:"Dr.",name:"Alice",surname:"Câmara",slug:"alice-camara",fullName:"Alice Câmara"}],corrections:null},{id:"72902",title:"In Vivo Studies of Protein Misfolding and Neurodegeneration Induced by Metabolic Syndrome Relative to Chronic Cerebral Hypoperfusion: A Critical Review",doi:"10.5772/intechopen.92603",slug:"-em-in-vivo-em-studies-of-protein-misfolding-and-neurodegeneration-induced-by-metabolic-syndrome-rel",totalDownloads:347,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Metabolic syndrome (MetS) leads to microvascular dysfunction and chronic cerebral hypoperfusion (CCH) in an insidious way. Clinical evidence and several rodent models have contributed to determining the neurodegenerative effect of a sustained decrease in cerebral blood flow (CBF). Protein misfolding and aggregation derived from CCH might account for the establishment of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD). However, the complex and multifactorial etiology of cerebrovascular disease demands the combination of experimental models in scientific research. In this sense, the present work aims at summarizing the differential available rodent paradigms for studying the establishment of cognitive decline resulting from protein misfolding induced by MetS in association with CCH. Revising experimental findings in the field will help further basic research on the pathophysiology of cerebrovascular disease and the future testing of protein-remodeling factors as neuroprotective agents for the prevention of cognitive impairment.",signatures:"María I. Herrera, Juan P. Luaces, Lucas D. Udovin, Nicolás Toro-Urrego, Matilde Otero-Losada and Francisco Capani",downloadPdfUrl:"/chapter/pdf-download/72902",previewPdfUrl:"/chapter/pdf-preview/72902",authors:[{id:"193560",title:null,name:"Matilde",surname:"Otero-Losada",slug:"matilde-otero-losada",fullName:"Matilde Otero-Losada"},{id:"120703",title:"Dr.",name:"Francisco",surname:"Capani",slug:"francisco-capani",fullName:"Francisco Capani"},{id:"306021",title:"Dr.",name:"Lucas",surname:"Udovin",slug:"lucas-udovin",fullName:"Lucas Udovin"},{id:"308465",title:"Dr.",name:"Nicolás",surname:"Toro Urrego",slug:"nicolas-toro-urrego",fullName:"Nicolás Toro Urrego"},{id:"306022",title:"Dr.",name:"María Inés",surname:"Herrera",slug:"maria-ines-herrera",fullName:"María Inés Herrera"},{id:"308469",title:"Dr.",name:"Juan P.",surname:"Luaces",slug:"juan-p.-luaces",fullName:"Juan P. Luaces"}],corrections:null},{id:"71298",title:"Neuroprotective and Neurorestorative Properties of Copolymer-1: Its Immunomodulating Effects on Ischemic Stroke",doi:"10.5772/intechopen.91343",slug:"neuroprotective-and-neurorestorative-properties-of-copolymer-1-its-immunomodulating-effects-on-ische",totalDownloads:718,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Stroke is a pathology of great relevance worldwide as it currently occupies the second motif of death and the third reason of disability. Although exits some therapies that are used successfully in the clinic, a very high percentage of patients do not have the opportunity to benefit from them; therefore, it is imperative to propose other alternatives that may favor more patients. In this chapter, we briefly review the inflammatory response induced by stroke and also its deleterious and protective effects. We will describe the characteristics of copolymer-1 and the effects that this compound has shown in models of cerebral ischemia.",signatures:"María Yolanda Cruz Martínez, Melanie Tessa Saavedra Navarrete and José Juan Antonio Ibarra Arias",downloadPdfUrl:"/chapter/pdf-download/71298",previewPdfUrl:"/chapter/pdf-preview/71298",authors:[{id:"72488",title:"Dr.",name:"José Juan Antonio",surname:"Ibarra Arias",slug:"jose-juan-antonio-ibarra-arias",fullName:"José Juan Antonio Ibarra Arias"},{id:"312349",title:"Ms.",name:"Melanie Tessa",surname:"Saavedra Navarrete",slug:"melanie-tessa-saavedra-navarrete",fullName:"Melanie Tessa Saavedra Navarrete"},{id:"312580",title:"Dr.",name:"Maria Yolanda",surname:"Cruz Martinez",slug:"maria-yolanda-cruz-martinez",fullName:"Maria Yolanda Cruz Martinez"}],corrections:null},{id:"69376",title:"Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art",doi:"10.5772/intechopen.89539",slug:"trends-in-neuroprotective-strategies-after-spinal-cord-injury-state-of-the-art",totalDownloads:750,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Spinal cord injury (SCI) is an important pathology leading to possibly fatal consequences. The most common repercussions are those affecting motor and sensitivity skills. SCI-damage occurs in its first phase—as a result of the lesion mechanism (contusion, compression, transection, and primary lesion). After this primary damage, there is a second phase with further deleterious effects on neural degeneration and tissue restoration. At the moment, several investigation groups are working on developing therapeutic strategies to induce neuroprotection. This chapter pretends to introduce the reader to a wide range of these therapies, particularly those with promising results and tested in preclinical and clinical studies. In the first section, physiopathology of SCI will be addressed. Afterwards, the chapter will review neuroprotective strategies such as cyclooxygenase, calpain, and apoptosis inhibitors. Finally, the effect of immunophilin ligands, neural-derived peptides, antioxidants, hypoglycemic agent, gonadal hormones, Na channel blockers, and transplant of cultured cells will also be reviewed.",signatures:"Roxana Rodríguez-Barrera, Marcela Garibay-López and Antonio Ibarra",downloadPdfUrl:"/chapter/pdf-download/69376",previewPdfUrl:"/chapter/pdf-preview/69376",authors:[{id:"72488",title:"Dr.",name:"José Juan Antonio",surname:"Ibarra Arias",slug:"jose-juan-antonio-ibarra-arias",fullName:"José Juan Antonio Ibarra Arias"},{id:"280102",title:"Dr.",name:"Roxana",surname:"Rodríguez-Barrera",slug:"roxana-rodriguez-barrera",fullName:"Roxana Rodríguez-Barrera"},{id:"303311",title:"BSc.",name:"Marcela",surname:"Garibay Lopéz",slug:"marcela-garibay-lopez",fullName:"Marcela Garibay Lopéz"}],corrections:null},{id:"70943",title:"Neuroprotective Potentials of Natural Vitamin E for Cerebral Small Vessel Disease",doi:"10.5772/intechopen.91028",slug:"neuroprotective-potentials-of-natural-vitamin-e-for-cerebral-small-vessel-disease",totalDownloads:925,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cerebral small vessel disease (CSVD) refers to a spectrum of clinical and neuroimaging findings resulting from pathological processes of various etiologies affecting cerebral arterioles, perforating arteries, capillaries, and venules. It is the commonest neurological problem that results in significant disability, but awareness of it remains poor. It affects over half of people over 65 years old and inflicts up to third of acute strokes, over 40% of dementia, and a significant decline in physical ability in otherwise asymptomatic, aging individuals. Moreover, the unifying theory for the pathomechanism of the disease remains elusive and hence the apparent ineffective therapeutic approaches. Given the growing literature for natural vitamin E (tocopherols and tocotrienols) as a potent antioxidant, this chapter attempts to consolidate the contemporary evidence to shed plausible insights on the neuroprotective potentials of natural vitamin E in addressing the heterogenous CSVD spectrum, in health and in disease.",signatures:"Muzaimi Mustapha, Che Mohd Nasril Che Mohd Nassir, Yuen Kah Hay, Fung Wai Yee and Hafizah Abdul Hamid",downloadPdfUrl:"/chapter/pdf-download/70943",previewPdfUrl:"/chapter/pdf-preview/70943",authors:[{id:"180412",title:"Dr.",name:"Mustapha",surname:"Muzaimi",slug:"mustapha-muzaimi",fullName:"Mustapha Muzaimi"},{id:"313133",title:"Dr.",name:"Che Mohd Nasril",surname:"Che Mohd Nassir",slug:"che-mohd-nasril-che-mohd-nassir",fullName:"Che Mohd Nasril Che Mohd Nassir"},{id:"316151",title:"Prof.",name:"Kah Hay",surname:"Yuen",slug:"kah-hay-yuen",fullName:"Kah Hay Yuen"},{id:"316152",title:"Dr.",name:"Wai Yee",surname:"Fung",slug:"wai-yee-fung",fullName:"Wai Yee Fung"},{id:"316153",title:"Dr.",name:"Hafizah",surname:"Abdul Hamid",slug:"hafizah-abdul-hamid",fullName:"Hafizah Abdul Hamid"}],corrections:null},{id:"73869",title:"Neuroactive Steroids in Hypoxic–Ischemic Brain Injury: Overview and Future Directions",doi:"10.5772/intechopen.93956",slug:"neuroactive-steroids-in-hypoxic-ischemic-brain-injury-overview-and-future-directions",totalDownloads:564,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Hypoxic–ischemic brain injury is a number one cause of long-term neurologic disability and death worldwide. This public health burden is mainly characterized by a decrease in oxygen concentration and blood flow to the tissues, which lead to an inefficient supply of nutrients to the brain. This condition induces cell death by energy depletion and increases free radical generation and inflammation. Hypoxic–ischemic brain injury may occur in ischemic-stroke and over perinatal asphyxia, being both leading causes of morbidity in adults and children, respectively. Currently, there are no effective pharmaceutical strategies to prevent the triggering of secondary injury cascades, including oxidative stress and metabolic dysfunction. Neuroactive steroids like selective estrogen receptor modulators, SERMs, and selective tissue estrogenic activity regulators, STEARs, exert several neuroprotective effects. These encompass mitochondrial survival, a decrease in reactive oxygen species, and maintenance of cell viability, among others. In this context, these neurosteroids constitute promising molecules, which could modify brain response to injury. Here we show an updated overview of the underlying mechanisms of hypoxic–ischemic brain injury. We also highlight the neuroprotective effects of neurosteroids and their future directions.",signatures:"Nicolas Toro-Urrego, Marco Avila-Rodriguez, María Inés Herrera, Andrea Aguilar, Lucas Udovin and Juan P. Luaces",downloadPdfUrl:"/chapter/pdf-download/73869",previewPdfUrl:"/chapter/pdf-preview/73869",authors:[{id:"306021",title:"Dr.",name:"Lucas",surname:"Udovin",slug:"lucas-udovin",fullName:"Lucas Udovin"},{id:"308465",title:"Dr.",name:"Nicolás",surname:"Toro Urrego",slug:"nicolas-toro-urrego",fullName:"Nicolás Toro Urrego"},{id:"306022",title:"Dr.",name:"María Inés",surname:"Herrera",slug:"maria-ines-herrera",fullName:"María Inés Herrera"},{id:"308469",title:"Dr.",name:"Juan P.",surname:"Luaces",slug:"juan-p.-luaces",fullName:"Juan P. Luaces"},{id:"311483",title:"Dr.",name:"Marco Fidel",surname:"Avila-Rodriguez",slug:"marco-fidel-avila-rodriguez",fullName:"Marco Fidel Avila-Rodriguez"},{id:"332900",title:"Dr.",name:"Andrea",surname:"Aguilar",slug:"andrea-aguilar",fullName:"Andrea Aguilar"}],corrections:null},{id:"71098",title:"Glyproline Pro-Ampakine with Neuroprotective Activity",doi:"10.5772/intechopen.91192",slug:"glyproline-pro-ampakine-with-neuroprotective-activity",totalDownloads:666,totalCrossrefCites:5,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Previously it was shown that neuropeptide cyclo-L-prolylglycine (CPG) is a positive modulator of AMPA receptors, which increases BDNF level in neuronal cell cultures. The spectrum of CPG’s pharmacological effects corresponds to that of BDNF. Dipeptide N-phenylacetyl-glycyl-L-proline ethyl ester (GZK-111) was designed and synthesized as a linear analog of CPG. The aim of the present work was to reveal the pharmacological profile of GZK-111. Dipeptide GZK-111 was shown to metabolize into CPG in vitro and increased cell survival by 28% at concentrations of 10-7–10-6 M in a Parkinson’s disease cell model. In a model of cerebral ischemia, GZK-111, at a dose of 0.5 mg/kg, i.p., was found to have neuroprotective effects, reducing the cerebral infarct volume by 1.6 times. Similar to CPG, GZK-111, at the range 0.1–1.0 mg/kg, i.p., possessed a stereospecific antiamnesic activity. A significant anxiolytic effect was observed at a dose of 1.5 mg/kg. GZK-111, at the range 0.5–4.0 mg/kg, i.p., demonstrated analgesic activity. GZK-111, at a dose of 10 mg/kg/7 days, i.p., possessed antidepressant-like activity. So, the neuroprotective, nootropic, antihypoxic, anxiolytic, antidepressant-like, and analgesic effects of GZK-111 were revealed. Thus, GZK-111 can be considered as a pharmacologically active pro-ampakine with a BDNF-ergic mechanism of action.",signatures:"Ksenia N. Koliasnikova, Polina Yu. Povarnina, Anna V. Tallerova, Yulia N. Firsova, Sergei V. Nikolaev, Tatiana A. Antipova, Anna V. Nadorova, Larisa G. Kolik, Tatiana A. Gudasheva and Sergei B. Seredenin",downloadPdfUrl:"/chapter/pdf-download/71098",previewPdfUrl:"/chapter/pdf-preview/71098",authors:[{id:"273501",title:"Prof.",name:"Tatiana",surname:"Gudasheva",slug:"tatiana-gudasheva",fullName:"Tatiana Gudasheva"},{id:"273505",title:"Dr.",name:"Polina",surname:"Povarnina",slug:"polina-povarnina",fullName:"Polina Povarnina"},{id:"273506",title:"Prof.",name:"Sergey",surname:"Seredenin",slug:"sergey-seredenin",fullName:"Sergey Seredenin"},{id:"312384",title:"Dr.",name:"Ksenia",surname:"Koliasnikova",slug:"ksenia-koliasnikova",fullName:"Ksenia Koliasnikova"},{id:"312385",title:"Dr.",name:"Anna",surname:"Tallerova",slug:"anna-tallerova",fullName:"Anna Tallerova"},{id:"312386",title:"Prof.",name:"Larisa",surname:"Kolik",slug:"larisa-kolik",fullName:"Larisa Kolik"},{id:"316364",title:"Dr.",name:"Yulia",surname:"Firsova",slug:"yulia-firsova",fullName:"Yulia Firsova"},{id:"316365",title:"Dr.",name:"Sergey",surname:"Nikolaev",slug:"sergey-nikolaev",fullName:"Sergey Nikolaev"},{id:"316366",title:"Mrs.",name:"Anna",surname:"Nadorova",slug:"anna-nadorova",fullName:"Anna Nadorova"},{id:"316367",title:"Dr.",name:"Tatiana",surname:"Antipova",slug:"tatiana-antipova",fullName:"Tatiana Antipova"}],corrections:null},{id:"70228",title:"Aptamers and Possible Effects on Neurodegeneration",doi:"10.5772/intechopen.89621",slug:"aptamers-and-possible-effects-on-neurodegeneration",totalDownloads:737,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Aptamers are a new class of recognizing agents which are defined as short biomolecules like oligonucleotides and peptides that are used in diagnostics and therapeutics. They can bind to specific targets with extremely high affinity based on their structural conformations. It is believed that in the near future, aptamers could replace monoclonal antibody. The biggest advantage of using aptamers is that the process is in vitro in nature and does not require the use of animals and they also have unique properties, such as thermal stability, low cost, and unlimited applications. Aptamers have been studied as a biomaterial in numerous investigations concerning their use as a diagnostic and therapeutic tool and biosensing probe. DNA aptamers were also used for the diagnosis and treatment of neurodegeneration and neurodegenerative diseases. For example, functional nucleic acid aptamers have been developed to detect Aβ fragments in Alzheimer’s brain hippocampus tissue samples. Aptamers are promising materials for diverse areas, not just as alternatives to antibodies but as the core components of medical equipment. Although they are in the preliminary stages of development, results are quite encouraging, and it seems that aptamer research has a very bright future in neuroscience.",signatures:"Fatma Söylemez and Çağatay Han Türkseven",downloadPdfUrl:"/chapter/pdf-download/70228",previewPdfUrl:"/chapter/pdf-preview/70228",authors:[{id:"173956",title:"Associate Prof.",name:"Fatma",surname:"Söylemez",slug:"fatma-soylemez",fullName:"Fatma Söylemez"},{id:"240771",title:"Dr.",name:"Cagatay Han",surname:"Turkseven",slug:"cagatay-han-turkseven",fullName:"Cagatay Han Turkseven"}],corrections:null},{id:"69122",title:"Lifestyle Factors, Mitochondrial Dynamics, and Neuroprotection",doi:"10.5772/intechopen.89416",slug:"lifestyle-factors-mitochondrial-dynamics-and-neuroprotection",totalDownloads:841,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The brain requires vast amounts of energy to carry out neurotransmission; indeed, it is responsible for approximately one-fifth of the body’s energy consumption. Therefore, in order to understand functions of brain cells under both normal and pathological conditions, it is critical to elucidate dynamics of intracellular energy. The mitochondrion is the key intercellular organelle that controls neuronal energy and survival. Numerous studies have reported a correlation between altered mitochondrial function and brain-associated diseases; thus mitochondria may serve as a promising target for treating these conditions. In this chapter, we will discuss the mechanisms of mitochondrial production, movement, and degradation in order to understand accessibility of energy during physiological and pathological conditions of the brain. While research targeting molecular dynamics is promising, translation into clinical relevance based on bench research is challenging. For these reasons, we will also summarize lifestyle factors, including interventions and chronic comorbidities that disrupt mitochondrial dynamics. By determining lifestyle factors that are readily accessible, we can propose a new viewpoint for a synergistic and translational approach for neuroprotection.",signatures:"Katheryn Broman, Abigail U. Davis, Jordan May and Han-A Park",downloadPdfUrl:"/chapter/pdf-download/69122",previewPdfUrl:"/chapter/pdf-preview/69122",authors:[{id:"304239",title:"Dr.",name:"Han-A",surname:"Park",slug:"han-a-park",fullName:"Han-A Park"},{id:"309383",title:"MSc.",name:"Katheryn",surname:"Broman",slug:"katheryn-broman",fullName:"Katheryn Broman"},{id:"309385",title:"BSc.",name:"Abigail",surname:"Davis",slug:"abigail-davis",fullName:"Abigail Davis"},{id:"309386",title:"Mr.",name:"Jordan",surname:"May",slug:"jordan-may",fullName:"Jordan May"}],corrections:null},{id:"70624",title:"Hydrogen Sulfide as a Factor of Neuroprotection during the Constitutive and Reparative Neurogenesis in Fish Brain",doi:"10.5772/intechopen.90547",slug:"hydrogen-sulfide-as-a-factor-of-neuroprotection-during-the-constitutive-and-reparative-neurogenesis-",totalDownloads:545,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The H2S-producing systems were studied in trout telencephalon, tectum, and cerebellum at 1 week after eye injury. The results of ELISA analysis have shown a 1.7-fold increase in the CBS expression at 1 week post-injury, as compared to the intact trout. In the ventricular and subventricular regions of trout telencephalon, CBS+ cells, as well as neuroepithelial and glial types, were detected. As a result of injury, the number of CBS+ neuroepithelial cells in the pallial and subpallial periventricular regions of the telencephalon increases. In the tectum, a traumatic damage leads to an increase in the CBS expression in radial glia with a simultaneous decrease in the number of CBS immunopositive neuroepithelial cells detected in intact animals. In the cerebellum, we revealed neuroglial interrelations, in which H2S is probably released from the astrocyte-like cells with subsequent activation of the neuronal NMDA receptors. The organization of the H2S-producing cell complexes suggests that the amount of glutamate produced in the trout cerebellum and its reuptake is controlled with the involvement of astrocyte-like cells, reducing its excitotoxicity. We believe that the increase in the number of H2S-producing cells constitutes a response to oxidative stress, and the overproduction of H2S neutralizes the reactive oxygen species.",signatures:"Evgeniya V. Pushchina, Anatoly A. Varaksin and Dmitry K. Obukhov",downloadPdfUrl:"/chapter/pdf-download/70624",previewPdfUrl:"/chapter/pdf-preview/70624",authors:[{id:"169621",title:"Dr.",name:"Evgeniya",surname:"Pushchina",slug:"evgeniya-pushchina",fullName:"Evgeniya Pushchina"}],corrections:null},{id:"70722",title:"Neuroprotection: The Way of Anti-Inflammatory Agents",doi:"10.5772/intechopen.90509",slug:"neuroprotection-the-way-of-anti-inflammatory-agents",totalDownloads:605,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Neurons are basic structural and functional units of the nervous system with major function being that of integration and interpretation of neuronal input or information. The lifespan of a nerve cell generally last throughout the individual lifetime. However, some physiologic or pathologic processes may affect the neuron causing premature death of this cell or tissue. This premature neurological death caused by pathologic circumstances is what we call neurotoxicity. The biochemical mechanisms put forward to explain neurotoxicity are not fully known. Nonetheless, whatever the mechanism involved, the outcome usually results in apoptosis, pyropoptosis, or necrosis. Examples of these mechanisms include excitotoxicity, oxidative stress, glial cell destruction, vascular interruptions, and inflammation. The idea about possibly protecting neurons against insults using pharmacologic means leads to the birth of the neuroprotection concept. This new concept has emerged based on ongoing research, suggesting it is possible through physical and pharmacological means to prevent or avoid neurotoxicity by the abovementioned mechanisms but with the exception of vascular interruption mechanisms. We will present in this chapter a synoptic view of the inflammatory mechanisms implicated in neurotoxicity and bring out the possible implications in neuroprotection.",signatures:"Patrice Mendel Nzogang and Martial Boris Donkeng",downloadPdfUrl:"/chapter/pdf-download/70722",previewPdfUrl:"/chapter/pdf-preview/70722",authors:[{id:"303070",title:"Dr.",name:"Patrice Mendel",surname:"Nzogang",slug:"patrice-mendel-nzogang",fullName:"Patrice Mendel Nzogang"},{id:"308442",title:"Dr.",name:"Martial Boris",surname:"Donkeng",slug:"martial-boris-donkeng",fullName:"Martial Boris Donkeng"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"745",title:"Neurodegenerative Diseases",subtitle:"Processes, Prevention, Protection and Monitoring",isOpenForSubmission:!1,hash:"3d5795dad33257368f0b7848c22d5dd4",slug:"neurodegenerative-diseases-processes-prevention-protection-and-monitoring",bookSignature:"Raymond Chuen-Chung Chang",coverURL:"https://cdn.intechopen.com/books/images_new/745.jpg",editedByType:"Edited by",editors:[{id:"33396",title:"Dr.",name:"Raymond Chuen-Chung",surname:"Chang",slug:"raymond-chuen-chung-chang",fullName:"Raymond Chuen-Chung Chang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3278",title:"Neurodegenerative Diseases",subtitle:null,isOpenForSubmission:!1,hash:"aa717c2801cf98db641d48414cef8ced",slug:"neurodegenerative-diseases",bookSignature:"Uday Kishore",coverURL:"https://cdn.intechopen.com/books/images_new/3278.jpg",editedByType:"Edited by",editors:[{id:"155691",title:"Dr.",name:"Uday",surname:"Kishore",slug:"uday-kishore",fullName:"Uday Kishore"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"434",title:"Alzheimer's Disease Pathogenesis",subtitle:"Core Concepts, Shifting Paradigms and Therapeutic Targets",isOpenForSubmission:!1,hash:"49f4c7dbf69e8a9eaf780e37f4aae1ab",slug:"alzheimer-s-disease-pathogenesis-core-concepts-shifting-paradigms-and-therapeutic-targets",bookSignature:"Suzanne De La Monte",coverURL:"https://cdn.intechopen.com/books/images_new/434.jpg",editedByType:"Edited by",editors:[{id:"29111",title:"Dr.",name:"Suzanne",surname:"De La Monte",slug:"suzanne-de-la-monte",fullName:"Suzanne De La Monte"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3296",title:"Understanding Alzheimer's 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Rosales",coverURL:"https://cdn.intechopen.com/books/images_new/1062.jpg",editedByType:"Edited by",editors:[{id:"70147",title:"Prof.",name:"Raymond",surname:"Rosales",slug:"raymond-rosales",fullName:"Raymond Rosales"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1360",title:"Mechanisms in Parkinson's Disease",subtitle:"Models and Treatments",isOpenForSubmission:!1,hash:"823c4dc5acbf952ba3723cae01f7f67a",slug:"mechanisms-in-parkinson-s-disease-models-and-treatments",bookSignature:"Juliana Dushanova",coverURL:"https://cdn.intechopen.com/books/images_new/1360.jpg",editedByType:"Edited by",editors:[{id:"36845",title:"Dr.",name:"Juliana",surname:"Dushanova",slug:"juliana-dushanova",fullName:"Juliana Dushanova"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6207",title:"Traumatic Brain Injury",subtitle:"Pathobiology, Advanced Diagnostics and Acute Management",isOpenForSubmission:!1,hash:"b39555959a8969f3d06634703afd3231",slug:"traumatic-brain-injury-pathobiology-advanced-diagnostics-and-acute-management",bookSignature:"Nikolai V. Gorbunov and Joseph B. 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Use theory and possible practical application to drive the knowledge from human involvement in workplace activities to any possible risk of health and safety hazards of the job.
",isbn:"978-1-80356-651-1",printIsbn:"978-1-80356-650-4",pdfIsbn:"978-1-80356-652-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"769f942393275479acca64e4f4fea958",bookSignature:"Dr. Bankole Kolawole Fasanya and Dr. Sridhar Krishnamurti",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11518.jpg",keywords:"Frequency, Sound Power, Absorption, Noise, Soundproof, Reflection, Inverse Square, Perception, Signal, Background Noise, Building, Noise Barrier",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 18th 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:"Dr. Fasanya is an Assistant Professor at Purdue University, USA. Prior to his current position, he has worked in different capacities with different institutions: Senior research associate (Auditory Protection and Prevention - US Army Aeromedical Research Laboratory, Adjunct Assistant Professor-NCAT, Facilities Engineer MVA, etc). Dr. Fasanya holds a Ph.D. in Industrial and systems engineering with a specialization in ergonomics and human factors.",coeditorOneBiosketch:"Dr. Sridhar Krishnamurti is a Professor and Program Director of Audiology at Auburn University. Sridhar has\r\nauthored a book, journal articles, and book chapters in Audiology and Hearing Conservation. He\r\nis a recipient of several Research grant awards, including the 1999 New Investigator Research\r\nAward from the American Academy of Audiology and the 2011 Auburn University Alumni\r\nUndergraduate Teaching Excellence and 2012 Auburn University Faculty Research Awards.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"214494",title:"Dr.",name:"Bankole",middleName:"Kolawole",surname:"Fasanya",slug:"bankole-fasanya",fullName:"Bankole Fasanya",profilePictureURL:"https://mts.intechopen.com/storage/users/214494/images/system/214494.jpg",biography:"Bankole K. Fasanya received a BSc in Mechanical Engineering in 1999 from The Polytechnic Ibadan, Nigeria, his Master’s degree in Industrial and Systems Engineering from Morgan State University, Maryland, USA and his doctorate degree in Industrial and Systems Engineering specialized in ergonomics and human factors from North Carolina Agricultural and Technical State University, USA. His research focuses on human and environmental safety, ergonomics and human factors, auditory prevention and protection and noise assessment and control at workplaces. Dr. Fasanya is currently an assistant professor at Purdue University Northwest in Indiana, USA. He currently serves as one of the executive members of the American Hearing Conservative Association (NHCA). He is an OSHA-Authorized general industry safety train the trainer and a certified occupational hearing conservationist (COHC).",institutionString:"Purdue University Northwest",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Purdue University Northwest",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:{id:"466252",title:"Dr.",name:"Sridhar",middleName:null,surname:"Krishnamurti",slug:"sridhar-krishnamurti",fullName:"Sridhar Krishnamurti",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003RKaOOQA1/Profile_Picture_2022-04-08T11:15:28.jpg",biography:"Dr. Sridhar Krishnamurti is a Professor and Program Director of Audiology at Auburn University.\r\nHe has served on the research grants review panel for several agencies and journals including\r\nAlzheimer’s Association, DOD Hearing Restoration Research, Ear and Hearing, American\r\nJournal of Public Health, and Journal of the American Academy of Audiology. Sridhar\r\nKrishnamurti has served as the past-continuing education administrator for Audiology Special\r\nInterest Divisions 6-9 and a Fellow of the American Academy of Audiology. Sridhar has\r\nauthored a book, journal articles, and book chapters in Audiology and Hearing Conservation. He\r\nis a recipient of several Research grant awards, including the 1999 New Investigator Research\r\nAward from the American Academy of Audiology and the 2011 Auburn University Alumni\r\nUndergraduate Teaching Excellence and 2012 Auburn University Faculty Research Awards.\r\nSridhar is currently President of the Council of Au.D Programs and an Executive Council member\r\nfor the National Hearing Conservation Association. His research has been funded by Oak Ridge\r\nAssociated Universities (ORISE) program and CDC-NIOSH.",institutionString:"Auburn University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Auburn University",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429342",firstName:"Zrinka",lastName:"Tomicic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429342/images/20008_n.jpg",email:"zrinka@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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It is well-known that vascular disease – irrespectively of its manifestation – is a generalized disorder, the majority of patients with vascular disease smoke and have chronic pulmonary disease, also suffers from diabetes and hypertension.
Hypertension and diabetes are often associated with coronary artery disease which determines the short and long-term survival of vascular procedures. Coronary artery disease is one of the most frequent cause of the perioperative mortality and morbidity (1-5%). Goldman et al. drew the attention to the frequency of cardiac complication of vascular operations as far back as 1977 and aimed to establish a multi-factorial score index. Based on detailed surveys which covered a large patient population the perioperative incidence of myocardial infarction among patient undergoing vascular surgical procedures is 2,1 – 8,0 %, whilst the mortality is 0,6 – 5,4 %. These examinations did not consider the type of operations – open or endovascular. Beside Goldman’s classic risk index numerous task forces have established their own score system for the assessment of perioperative cardiac risk. All of these highlight the significance of the fact that after being aware of the clinical risk, consultation and mutual decision making of cardiologists, anesthetists and vascular surgeons in evaluation the long-term efficiency and risk ratio is essential. The most important weak point of all score system is the utilization of data derived from patients underwent elective operations. Kertai et al. developed a simplified risk index, which is suitable for the assessment of perioperative mortality of either acute or elective patients undergoing vascular surgical operations. The American College of Cardiologist and the American Heart Association has developed a guideline for the assessment of cardiovascular risk among patients with different diseases who are undergoing non-cardiac surgery. This guideline includes the risk assessment for the patient undergoing vascular surgery. Three categories of cardiac risk have been classified in the guideline, high, intermediate and low. High cardiac risk involves the history of acute coronary syndrome, congestive heart failure, significant arrhythmias and severe heart valve diseases. Among non-cardiac surgeries associated with higher cardiac risk, the acute operations, surgery on extremely old patient, operations of the aorta, prolonged operations, operations with excessive fluid or blood loss are considered to be high-risk while carotid endarterectomy should be considered within the intermediate-risk category. The most simple clinical determining factors of cardiac risk are the age, body weight, known diabetes, congestive heart failure, angina pectoris, history of myocardial infarction and previous coronary revascularization.
Preoperative examination should include the assessment of patient’s functional capacity.
In the presence of lower extremity peripheral vascular disease performing exercise stress test may be difficult, thus pharmacological stress test or specific upper body exercise test should be carried out. Severely impaired functional capacity further increases the cardiac risk. Diseases of the aorta are frequently associated with severe coronary artery disease/ The incidence and severity of coronary artery disease are remarkably higher at the diseases of the aorta.
Preoperative examination should include the following:
Assessment of cardiac risk using different noninvasive examinations.Noninvasive stress testing are the following: dipyridamole myocardial perfusion scintigraphy, radionuclide ventriculography, Holter ECG monitoring, dobutamine stress echocardiography. Several authors ( Eagle and collegues, Lee and coworkers) have examined the sensitivity and specificity of these methods, and have found the dobutamine stress echocardiography to be the most appropriate test to assess this group of patients. This examination not only assesses the left ventricular dysfunction but also provides other valuable information on the ground of echocardiography. However, choosing the most appropriate type of test is undoubtedly influenced by local availabilities and cost effectiveness, as well. After assessing the cardiac risk, what therapeutic options are available to decrease it? Beta-blocker therapy at high-risk vascular patient has been proven to improve not only the perioperative but also the long-term survival. Manago et al. carried out a study, which covered a large number of patients on the effect of bisoprolol and atenolol on mortality and cardiovascular morbidity after non-cardiac surgery. Treatment of hypertension: blood pressure fluctuation at high-risk vascular patients further increases the cardiac risk. Previous anti-hypertensive therapy should be broadened by administration of beta-blockers and the directly acting, alpha-2 agonist, clonidine. Perioperative ACE-inhibitors therapy may cause intraoperative hypotension, thus administration of them are not recommended.
What further medical therapy is available to decrease the perioperative risk?
Poldermans and colleagues evaluated the effectiveness of statin therapy, and they found that the perioperative statin therapy is associated with lower postoperative mortality.
Among the evaluated drug therapies, only the perioperative beta-blocker therapy has been found to significantly decrease the mortality. Increased risk of urgent surgery, especially in elderly patients, a longer surgery, excessive blood loss due to classify interventions in high-risk group.
Of smoking among patients with vascular risk factors are also important, so increased the perioperative complications between the role of pulmonary complications. Chronic obstructive pulmonary disease and chronic bronchitis, which often encounter. The kidney complications should be considered. First, the generalized vessel disease associated with hypertension, the renin-angiotensin system leads to damage, and the second associated with diabetes to nephropathy.
Growing the progressive aortic aneurysm rupture in the final output. In ruptured cases, the deaths of over 50% indicate a value and this value has not changed significantly over the past 40 years, developments in technology and the introduction of the endovascular technique does not like routine. If known and expanding aortic aneurysm is detected, and reconstruction is the surgical mortality rate is between 0.4 to 2.3%.
The technique of anesthesia during general anesthesia supplemented with epidural anesthesia benefits. We must work towards the introduction of anesthesia, the hemodynamic stability, to eliminate changes caused by intubation. Cross-clamping of the aorta, causes a sudden increse in the afterload. This growth, provoke arrhythmias and myocardial ischemia and left ventricular failure.
Aortic aneurysm rupture due to a significant amount of blood in the abdomen, in any event be deemed hypovolemic. The abdominal muscle tone affects the capacity for intra-abdominal blood vessels, this relaxation is terminated and the formation of the blood pressure to fall, then a further decrease in blood pressure by opening the abdominal cavity should be expected. So close to the team\'s work comes to the fore the importance of continued vigilance isolation inhalating 100% oxygen, and then rapidly after induction opening the stomach, fast and high aortic cross clamp immediately save the patient\'s life. This type of surgery with surgical mortality of 50% is over, and over the past 4 decades has not changed.
The anesthesia and surgical technique despite the development of the aorta during surgery thoraco-abdomial section of the complications and mortality has not changed significantly over the past 20 years. High-traffic, high number of sick institutions in 5-14% mortality rates reported.The paraplegia, paraparetikus complication rate of 50-40% of the shares are known. The percentage of complications depends on which section of the aorta, the exclusion should be carried out. The neurological complications after pulmonary complications to be expected. The monitoring of the thoracic aneurysm surgery should be extended. Close cooperation is required between the vascular surgeon and anesthesiologist, the surgical plan must be designed carefully crafted after, the every aspect of the monitoring and the distal aortic perfusion technique. Important aspects of the arteries of the spinal cord and the renal arteries perfusion ensure and the adequate oxygenation.
If the exclusion (cross clamping) is happening, a retrograde perfusion provides security for patients. In surgery for thoracic aortic aneurysm general anesthesia of suitable technology. The most important is protection of the spinal cord, 20-30 minute cross clamping time is safe for the patient. The hypothermia is one of the most suitable
method for neuroprotection.
The patient who has been diagnosed with significant coronary artery disease during preoperative examination and is a candidate for high-risk vascular surgery is the most challenging. In case of acute operation beta-blockers remains the only therapeutic option, while in elective patients coronary revascularization should be carried out.
If the vascular procedure is not urgent, CABG operation is preferable over PCI. Elective non-cardiac surgery is not recommended within 6 weeks of coronary revascularization with PCI and stent implantation. In these cases careful risk assessment and effectiveness evaluation is necessary. Among patients with vascular disease tobacco smoking is a significant risk factor, thus perioperative pulmonary complications are frequent. Chronic obstructive pulmonary disease and chronic bronchitis are the most common ones. Perioperative blood gas analysis can be useful in assessing the risk. If the arterial carbon-dioxide partial pressure is higher than 45 mmHg, the risk for postoperative pulmonary complication is increased. If a tobacco smoking patient is presented at the preoperative evaluation meeting 2-4 weeks prior to the operation, it is reasonable to try to persuade the patient to cease the cigarette smoking, although, cessation will increase the amount of bronchial discharge. Smoking cessation 2-3 days prior to the surgery only results in decrease of the blood carboxi-hemoglobin level. In case of history of COPD and asthma preoperative glucocorticoid therapy (40 mg of prednisolon for two days) can decrease the risk of pulmonary complications. Treating the bronchial spasm, mobilizing the bronchial discharge and performing chest physiotheraphy would improve the patients’ condition. One to two days prior to surgery preoperative pulmonary function test should be performed. Decreased FEV1/FVC ratio suggests obstructive pulmonary disease. Performing regional anesthesia can lower the operative risk by eliminating the administration of the respiratory depressive opiates. On the other hand intraoperative blood CO2 pressure monitoring is important, since the probability of developing hypercapnia is high, as well as the postoperative CO2 level follow up, since the pain can lead to hypoventilation. Thus adequate pain management is strongly advisable.
Renal complications should also be taken into consideration, because of the pre-existing hypertension which is usually accompanied to generalized vascular disease and which can lead to impairment of the renin-angiotensin system. Preexisting diabetic nephropathy can also influence the development of postoperative renal complications.
The final outcome of aneurysms that present progressive growth is the rupture. In case of aneurysm rupture the mortality reaches the 50 %, this ratio has not changed over the last 40 years, despite the technical development and the introduction and routine application of endovascular techniques. Postoperative mortality rate of reconstruction of previously known and growing aortic aneurysm varies from 0,4 to 2,3 percents.
Preparation for the operation includes setting up the following:
two 14 G peripheral venous line
central venous line
arterial line
ECG monitoring from 5 different points
pulsoxymetry
urinary catheter
gastric tube
body temperature monitoring
noninvasive blood pressure measurement (from the opposite side than the direct arterial pressure line)
In case of impaired ejection fraction (less than 30 %) or suprarenal aortic cross-clamping, routine monitoring should be completed by the use of PICCO or Swan-Ganz catheter. In case of patients with significant diastolic dysfunction continuous intraoprative TEE (trans-esophageal echocardiography) monitoring can help to evaluate the need of fluid or catecholamine therapy.
The anticoagulation maintained with use of heparin 100 unit/kg, additional heparin necessary if the clamping time prolonged. Heparin can be reversed by protamine ( 4mg/kg over 15 minutes ) it may lead to anaphylaxis, pulmonary hypertension and myocardial depression.
At aortic operations it is recommended to prepare 4 - 6 units of red blood cell transfusion, if possible, autologous transfusion should be performed. The use of cell saver (intraoperative cell salvage machine) improves the efficacy of transfusion therapy, if it is not available normovolaemic hemodilution is required. Hemodilution does not increase the oxygen deficit of the myocardium. During fluid therapy close monitoring the 24-hour diuresis and warming the fluid infusions increases patients’ safety. (Myers G)
During anesthesia, general anesthesia can be completed by the benefits of application epidural anesthesia. The thoracic epidurals decrease the stress response to surgical procedure. During induction of anesthesia care must be taken to maintain the patient’s hemodynamic stability and to eliminate the hyperdynamic response caused by the intubation. In case of aortic operation close attention must be paid to physiologic changes during aortic cross-clamping. In case of abdominal aortic operation the level of cross-clamping is infrarenal, i.e. aorta is fully cross-clamped under the origin of renal arteries. Changes in patient’s condition appear rapidly, thus taking prompt actions are necessary. Aortic cross-clamping causes sudden increase in systemic vascular resistance, i.e. in afterload. This increase can provoke myocardial ischemia, arrhythmia and left ventricular failure. The more proximal the cross-clamping is, the more severe the myocardial adverse consequences are. Administration of vasodilators and activation the epidural anesthesia before the cross-clamping can stabilize the patient’s condition and have beneficial effect. During aortic cross-clamping the lower extremities and certain parts of large intestines receive minimal blood flow through collateral circulation, but the renal circulation are also impaired. As a result of these circulatory changes inflammatory mediators are released by leukocytes, platelets and endothelial cells.
Cessation of aortic cross-clamping causes sudden decrease in afterload, which is on the one side caused by the discontinuation of mechanical obstruction but the accumulated vasodilator mediators by getting back into the systemic circulation plays also an important role in this. Beside vasodilation, metabolic acidosis and increased capillary permeability aggravates the condition. Providing adequate circulatory volume and maintaining stable blood pressure is necessary before releasing the aortic cross-clamp. Administering mannitol and pressor drugs can be helpful to fulfill this. Every efforts must be made in order to reach as short hypoperfusion time as possible.
In the postoperative period the close monitoring should be continued and care must be taken of the adequate pain management. If the infrarenal cross-clamp time exceeds 60 minutes, the subsequent pressure rise in the renal arteries may cause systemic hypertension in the early postoperative period, which is usually transient.
Patients require monitoring after abdominal aortic aneurysm operation. The postoperative pain management is important, the early extubation, and the enteral nutrition. Appropriate thrombotic profilaxis and postoperative gastrointestinal ulcus profilaxis, the use of antacids.
In case of acute operation of ruptured aortic aneurysm, the patient should be considered hypovolaemic under all circumstances due to the excessive amount of extravascular blood found in the abdominal cavity. Increased abdominal muscle tone has a pressor effect on the intraabdominal capacity vessels, which is ceased if muscle relaxants are administered during the anesthesia and this causes subsequent blood pressure drop. Hypotension is further aggravated by the opening of abdominal cavity. This fact underlines the importance of team work. Isolation and draping of the operative field is carried out while the patient is awake, under simultaneous 100 % of oxygen inhalation, followed by rapid induction, quick opening the abdominal cavity and immediate high aortic cross-clamp which actions can only save the patient’s life. Heparinization is not required until the aorta is not cross clamped. After the aorta is cross clamped the fluid resuscitation can be instituted with colloids and blood. The dilutional coagulopathy is precnse, FFP and platelets ordered for the patient, and heparin is omissioned. Mortality rate of these operations exceeds the 50 percents and has not changed over the past four decades. The predictors of the survival are the patients age, the total blood loss, and the time of hypotension.
Preparation for the operation includes setting up the following:
two 14 G peripheral venous line
blood count, electrolytes coagulation screen
arterial line
ECG monitoring from 5 different points
pulsoxymetry
urinary catheter
gastric tube
body temperature monitoring
noninvasive blood pressure measurement (from the opposite side than the direct arterial pressure line)
Drugs and fluids:
6-10 units of cross matched blood, fresh frozen plasma and platelets
Crystalloids and colloids
Inotropes (ephedrine 3 mg/ml, adrenaline 1:100 000) and vasopressor agents ( phenylephrine 100 mcg/ml, metaraminol 0.5 mg/ ml )
Operative complications and mortality rate of thoracoabdominal aneurysm surgeries has remained remarkably high despite the development of anesthetic and surgical techniques. High, 5-14 % of mortality rates have been reported by even specialized aneurysm centers which are dealing with a large number of patients. Paraplegia and paraparesis, as postoperative complications develop at 5 - 40 % of all cases. The incidence of complications is influenced by the site of the cross-clamp. The most commonly occurring neurological complications are followed by the pulmonary ones. At thoracic aneurysm operations more vital signs is required to be monitored. It also demands closer collaboration between the vascular surgeon and the anesthetist, because every step of the monitoring has to be set up after developing the operative plan. Particular attention must be paid to the perfusion technique of the distal aorta. Providing adequate perfusion of vertebral and renal arteries and application of satisfactory ventilation are also very important.
Preparation for the operation includes setting up the following:
High flow venous catheter, 2 peripheral venous line and 3-lumen central venous line
Radial arterial cannula, inserted in the right side if the cross-clamp is placed proximally to the left subclavian artery.
Femoral arterial cannula, if the bypass is used to maintain the distal aortic flow.
Radial + femoral, more information can be obtained about the circulation of the lower part of the body
Transesophageal echocardiography – intraoperative information: LVEDP, the myocardial function and the valves status
Preparation for unilateral ventilation
Positioning the double-lumen tube can be helped by bronchofiberoscopic intubation.
Ten units of red blood cell transfusion, FFP and platelet transfusion.
Monitoring of SSEPs (somatosensory evoked potentials)
Body temperature monitoring: core and peripheral temperature.
The aneurysm of the ascending aorta is destroyed, need an urgent surgical procedure.
If cross-clamping is applied, significant pressure elevation proximally to the cross-clamping is common. Administration of nitrates and vasodilators is recommended, in case of patient with preserved myocardial systolic function administration of isofluran and desfluran is also suggested. Nitrates can optimize the preload and are able to decrease the left ventricular wall tension. If the operation is performed under the protection of cardiopulmonary bypass (CPB), patient safety is improved if retrograde aortic perfusion is used. In order to ensure appropriate therapy, direct arterial pressure monitoring is registered from two separate regions, above and under the cross-clamping.
In case of thoracic aortic aneurysm surgery balanced anesthesia is the appropriate technique of choice. Protection of the vertebral spine is the most important task, from 20 to 30 minutes of cross-clamping time is considered to be safety. Spinal blood pressure is equal to the difference of mean distal aortic pressure and the cerebrospinal fluid pressure. Cerebrospinal fluid pressure is approximately equal to the central venous pressure. The spinal perfusion autoregulation is similar to the cerebral, appropriate blood flow is maintained between 60-120 mmHg of perfusion pressure.
Applying hypothermia is one of the best solution to ensure adequate neuroprotection, 32 – 34 degrees of Celsius of body temperature is recommended during the operation.
Impairment of renal circulation can also lead to severe complications, administration of mannitol and loop-diuretics and applying hypothermia can prevent these adverse outcomes.
During anesthesia strict attention must be paid to maintain the patient’s body fluid and electrolyte balance. If the procedure is done with the patient in the left lateral thoracotomy the CPB is constructed through the femoral artery with venous drainage through right atrial, bicaval, or femoral venous cannulation. Systemic hypothermia is used, with a circulatory arrest. Surface cooling is used along with core cooling and rewarming through the CPB heat exchanger. The cooling of the head with ice during core cooling and kept cold until the period of arrest is important. The core temperature is monitored in the esophagus or tympanic membrane. (Kumar N)
Drugs and fluids:
6-10 units of cross matched blood, fresh frozen plasma and platelets
Crystalloids and colloids
Inotropes (ephedrine 3 mg/ml, adrenaline 1:100 000) and vasopressor agents ( phenylephrine 100 mcg/ml, metaraminol 0.5 mg/ ml ).
It is very important during induction is to minimize the hypertensive response to laryngoscopy and intubation, which may lead to further spreading of the tear and result in rupture of an aneurysm or propagation of a dissection. Dispite the factthat we could make a long surgery, a large doses of pancuronium are generally avoided. This drug has a vagolytic and norepinephrine releasing effects, which produce hypertension and tachycardia. In patients with significant reduced myocardial function etomidate 0.2 to 0.3 mg/kg may provide the hemodynamic stability during induction. Anesthesia is maintained with inhalation agents, opiates and non-depolarizing muscle relaxants.
Airway management : lesions of the ascending and transverse aortic arch are managed with a single-lumen endotracheal tube. If the aortic lesions may cause tracheal or bronchial compression better to use a left-sided double-lumen tube (DLT). The tube should be placed with using fiberoptic bronchoscopy.
Bleeding and hematologic dysfunction: A thoracic aortic surgery involves using large amounts of blood. The amount of blood used for depends on the bypass time. The time of deep hypothermia has an effect on the clotting system.
Aneurysms of the descending thoracic and thoracoabdominal aorta
Aneurysm of descending thoracic aorta involves diffenert parts of the thoracic aorta and may extend to the abdominal aorta too. Several techniques can be used to control upper- and lower-body blood flow during the operation.
- Aortic cross-clamping, This is the method for resection in a short period of time. The problems are the organ ischemia because of arterial hypertension, and metabolic acidosis. The cross clamp duration and severity of complications is directly proportional. A cross-clamping time longer than 30 minutes increases the risk of spinal cord injury- Passive shunts, the most commonly used shunt is the 9-mm heparin-coated conduit (Gott shunt), which does not require systemic anticoagulation.- Centrifugal pump bypass flow, the left atriofemoral centrifugal pump bypass may be useful in patients with decreased left ventricular function, coronary artery disease, renal failere.. and anticipated longer then 30 minutes aortic cross-clamping time.- Partial Cardiopulmonary Bypass, it is used from the femoral vein to the femoral artery, or from the right atria to the femoral artery. This techique adds the use of oxigenator. - Deep Hypothermic Circulatory Arrest has been used to protect vital organs and the spinal cord. Despite the detailed research work has not found the perfect way to protect the spinal cord. Containing a high number of patients in studies based on the present position is that hypothermic protection with CPB and DHCA may be the useful methods.
Endovascular stent graft implantation is one of the most suitable alternatives to open aortic aneurysm surgery today. Aortic operations have remarkably changed since the introduction of endovascular techniques. Extremities of implantation technique have been reported in the scientific literature, from the stent-grafts implanted in the X-ray lab percutaneously toward the open stent-graft implantation procedures. Stent-graft implantation is less invasive, more tolerable for the patients, the length of surgery is shorter, less transfusion is required and the shorter ICU and hospital stay are also the advantages of this technique. Based on our experience stent-graft implantation is considered at those patients, who are referred to be high-risk due to the large number of severe accompanying diseases. In our institute we intend to perform epidural anesthesia at abdominal aortic aneurysm stent-graft repair operations and balanced anesthesia at thoracic cases. Standards of the monitoring technique are the same as that is described at the open procedures. Monitoring improves patient’s safety.
Preparation for the procedure includes setting up the following:
two 14 G peripheral venous line
laboratory exams : blood count, electrolytes, coagulation screen
arterial line
ECG monitoring from 5 different points
pulseoxymetry
urinary catheter
body temperature monitoring - prolonged operations
noninvasive blood pressure measurement (from the opposite side than the direct arterial pressure line)
At the endovascular procedures hemodynamic changes caused by the cross-clamping are not presented. The postoperative period is better tolerated, the pain is milder and the cardiovascular status is more stable. Endovascular stent-graft repair of aortic aneurysms. At present, aortic stent-grafts are most frequently used to repair infrarenal aortic aneurysms. The hemodynamic consequences of infrarenal endovascular balloon inflation are minimal compared with those of suprarenal, supraceliac, or thoracic aortic occlusion. More significant hemodynamic changes are likely to be encountered during stent-graft repair of the descending thoracic aorta.
The high-risk patients undergoing endovascular stent-graft aortic repair appear to have greater hemodynamic stability compared with for the traditional open technique was. Despite this, hypotension and hemodynamic instability could detected, especially during manipulation with expended balloon. Causes of hypotension include hemorrhage and loss of blood into the aneurysm sac after graft implantation, release of endothelial vasoactive substances, and/or an autonomic reflex in response to endovascular balloon inflation.Along the course of the operation, theres is a significant advamtage with the change int he opersation technique, and that the clamping of the aorta is left out or restricted to only a few minutes. During the positioning of the graft, the measured systemic vascular resistence increases but the value (9,2 ±3%)compared to total aortic clamping (32,8 ± 7,6 %) is significantly lower. At this point, following clamping of the abdominal aorta, we experienced a decrease in stroke volume and cardiac output which reached 38% in the cross clamping patients. In patients with stent graft technique this value remained under 9%. The decrease in venous backflow is much lower and therefore the decrease in end diastolic pressure is also lower which influences the left ventricular filling pressure. In a series of 12 patients undergoing infrarenal aortic repair with an EVT endovascular graft under neuroaxial blockade (epidural or continuous spinal), 25% of patients had sudden severe bradycardia and hypotension necessitating immediate therapy. Accordingly, blood must be immediately available, and large-bore intravenous access must be obtained before the procedure. Because of the high incidence of CAD, careful monitoring and aggressive treatment of myocardial ischemia is essential. Conversion to open repair may be required in 2% to 20% of patients (average, 9%) due to technical difficulty with graft deployment or acute surgical complications such as aneurysm rupture or arterial injury With increasing experience, the need for emergency conversion to open repair is decreasing to approximately 2% to 5% of cases but is still associated with increased morbidity and mortality in these high-risk surgical patients (Kumar N)
In patients with significant coexisting atherosclerotic vascular disease of major organs (heart, brain, kidneys), induced hypertension should be avoided altogether or its duration minimized. A stent-graft that does not require hemodynamic manipulations for its deployment would be more desirable in such patients. The anesthetic technique may consist of general anesthesia, regional anesthesia (epidural, spinal, or continuous spinal), or local anesthesia plus sedation. The choice of technique is influenced by multiple factors, including local customs and the experience of the surgical and anesthetic teams. Consideration should be given to the potential for intraoperative hemodynamic instability and the possible need to react rapidly to surgical complications. The anesthetic goals include analgesia, sedation, anxiolysis, patient immobility, and maintenance of hemodynamic stability. General anesthesia was the most commonly used method during the initial experience with endovascular infrarenal aortic repairs because it provided the ability to rapidly convert to open surgical repair. With evolving experience, regional anesthesia (epidural or spinal) and even local anesthesia with sedation and monitoring are being increasingly used for endovascular aortic repairs A variety of drugs have been used successfully for general anesthesia, including etomidate,, propofol, potent synthetic opioids, volatile anesthetics, and muscle relaxants In patients with severely impaired left ventricular function, etomidate together with a potent opioid such as fentanyl or sufentanil provides adequate hemodynamic stability. Advantages of regional anesthesia include minimization of systemic drug use, continuation of pain relief into the postoperative period, and the improved ability to detect symptoms of myocardial ischemia in patients who can report the occurrence of chest pain. Central neuroaxial blockade was shown to reduce the postoperative hypercoagulable state, which may result in a decreased incidence of deep vein thrombosis and vascular graft occlusion.
The infrarenal cross clamping acts on kidney function only bedside refle and hemodinamic changes. In our stent graft patients we did not experienced a decrease in the renal functions. The infrarenal aortic clamping convincingly increases renin release from the kidney. The increase in plasma renin and angiotensin levels causes a postoperative increase in blood pressure, compared to preoperative values. Because of the variable and unpredictable duration of these procedures, epidural anesthesia is the most commonly used technique because it has the flexibility of providing anesthesia of indefinite duration. Careful titration of the dermatomal level helps minimize the sympathectomy-related hypotension.
Continuation of epidural blockade beyond the operating room is an excellent method of providing postoperative analgesia. A normal coagulation profile must be assured before catheter placement and removal. Continuous spinal anesthesia using an intrathecally placed epidural catheter provides a more rapid onset of a more dense neuroaxial block than does epidural anesthesia. The stent graft technique not only makes the task of the surgeon easier but eases the work of the anesthesiologists. It is important to note that considering the high risk patients we cannot lax th tight monitoring end technical equipment which encure the patient’s safety and well being.
The decision of using endograft configuration in the RAAA depends of several factors. For the anesthesia the most important is the hypotension. We are in the position to use intra-aortic occlusion balloons in hemodinamically unstable patients, after the unsuccesfull volumen resuscitaion. It seems to be the hemodinamical instability is the most important factor of the survival in the patients with RAAA undergoing endovascular aortic aneurysm repair.
Hybrid solutions are called for vascular interventions, which are the traditional methods of open vascular surgery and insertion of the endograft are combined in order to reduce the risk of interference. The anesthesiologist must be always ready for a planned change in surgical technique, and the situation has changed to provide the surgeon and the patient to the optimal situation.
After revascularization of an acute arterial occlusion the development of a serious ischaemic-reperfusion injury is a menacing challenge and a hard task in vascular surgery. A whale of evidences point to oxidative stress, as an important trigger, in the complex chain of events leading to reperfusion injury.
Arató et al. made examinations, after reperfusion in the 2nd and 24th hours, and on 7th day. Superoxide-dismutase activity, reduced glutathion concentration and leukocytes free radical production were measured. The degree of lipidperoxidation was marked with the quantity of malondialdehyde. The expressions of adhesion molecules were measured with flowcytometry. The speed and rate of free radical production significantly increased in the early reperfusion (
Revascularization procedures performed on acutely ischaemized extremities are accompanied by metabolic and functional derangements which may be life threatening. Determination of selected biochemical, oxidative and inflammatory parameters which belong to the most objective criteria will alert physicians reducing the reperfusion injury cascade. Malondyaldehide plasma level has shown significant elevation after the operation and during reperfusion, it remained almost constant during first post operative week, this determines lipidperoxidation and membrane impairment (Fig. 1).
(∗∗
Fig. 1. The malondialdehyde plasma concentration elevated significantly in all of the operated groups
During early reperfusion period GSH level dramatically diminished (
(##p < 0.01 vs. ischaemia).,
Fig. 2. The plasma concentration of reduced glutathion (GSH) decreased significantly in the early, acute phase of reperfusion
Plasma concentration of –SH groups decreased significantly in the early reperfusion, then showed a slight elevation till the end of the week (##p < 0.01 vs. ischaemia, ∗p < 0.05 and ∗∗p < 0.01 vs. control).
Regarding SOD activation a notable difference has been noticed between the two groups (control: 894
Total superoxide dismutase activity was significantly lower during ischaemia versus control group, and decreased further in the 24th hour of reperfusion. Even, after a week could not reach the control value (∗∗p < 0.01 vs. control; ##p < 0.01 vs.ischaemia).
Plasma myeloperoxidase (MPO) level elevated significantly after revascularization, shows a slight decrease in 24 hours,than increase further in the late reperfusion period (∗∗p < 0.01; ∗∗∗p < 0.001 vs. control)..
The results show that the reperfusion induced, prompt oxidative stress does not disappear after the early period, but persist until the examined one week postoperative period. The basic pathology in the early reperfusion injury is the oxidative burst with the generation of a mass of oxygen free radicals.
The postischaemic, immediately oxidative turnover induces a massive inflammatory response with the activation of the leukocytes after 24 hours and in the late period these tissue inflammatory responses will maintain the oxidative imbalance.
Maximal free radical production of leukocytes was significantly higher during ischaemia (versus control), and continuously increased until the seventh day (
The “lag time” (taking from induction until the superoxide production) decreased significantly during the reperfusion This showed the significant activation of the leukocytes (#
The long time monitoring of the oxidative and inflammatory changes in reperfusion helps to understand the pathology and to develop a more effective therapy.
During exclusion of blood from the circulation ischemia and acidosis appear in the surrounding tissues of the occluded vessels, which try to adapt to the absence of oxygen by switching their metabolism from aerobic to anaerobic, but finally these strategy will lead to tissue damage and loss. In the chronic or acute occlusive diseases the tissue injuries depend on the duration of hypoxia, the mass of tissues involved and the blood pressure of the patients. Reconstruction of the occluded vessels is not without risk, because it can cause volume, pressure and metabolic load, with further tissue damage resulting in the so-called reperfusion injury. Peripheral arterial diseases are a seriously under-diagnosed disorder affecting up to 20 % of the adult population worldwide. Atherosclerotic involvements frequently are in the background, thrombosis or embolization can occur within the narrowed or calcified vessels, or within the aneurismal sites, resulting in serious tissue ischemia.
It is very difficult to monitor the cellular processes, which influence the outcome of the surgical manoeuvres or serve as a marker of the following events. A huge amount of data emerged for the characterization of ischemia reperfusion injury, but function of thrombocytes has been hardly investigated by Kürthy M et al. In their study showed that the duration of hypoxia basicaIly influenced the degree of reperfusion injury in revascularization surgery, resulting in a different outcome in ADP and collagen induced platelet aggregation in whole blood even one week after surgery. Platelet aggregation highly and significantly elevated, in spite of the intensive antiplatelet and antiaggregation therapy. Sinay et al. measured in an
Simplified presentation of the mechanism of ischaemic–reperfusion injury. Emphasizing, that the engine of reperfusion injury is the ROI–cytokine–leukocyte positive feedback circle (ROI: reactive oxygen intermediers; ATP: adenosine triphosphate; DNA: deoxyribonucleic acid).
The management of patients undergoing vascular surgery is one of the most challanging and contraversial area of anesthesiology. The high incidence of coexisting disease, the metabolic stress associated with cross-clamping and unclamping, the ischemic insults in the brain, the heart, the kidneys and the spinal cord resulting a relative high perioperative morbidity in these patients. While these pathways are well known in vascular surgery, there is no real effective tool in the hand of the operating team to treat or to prevent them. As we know how to limit ischemic damage (mostly by reducing the ischemia time via an early reperfusion, and improving O2 demand/supply balance), postconditioning might be the way to prevent or reduce reperfusion damage.
Postconditioning has the advantage of being a way to influence and modify ischaemia–reperfusion injury after it has occurred. This may open a therapeutic alternative in situations of unexpected and uncontrolled ischaemic injury, for instance in the situation where complications occur during surgery, making a simple procedure into a complicated one, and making aortic cross-clamping longer than anticipated.
Ketamine has long been known as a potent anesthetic drug with analgesic properties, however, it quickly evolved into a recreational drug in the early 1980s [1]. The first use of ketamine as a drug was recorded in 1965 [2]. Widespread, nonmedical uses of ketamine expanded through that time due to sub-cultures began experimented with the drug for mind exploration the inner psyche, and New Age spiritualism.
Ketamine is also known as the ‘club drug’ and since the mid-1980s, it has been linked to a variety of dance cultures, because of its trance-like state potency. That also explained why teenagers and young adults (16 to 25 years) are the people who are most susceptible to ketamine abuse. Ketamine is known by various names, by clubbers usually called “K”, “vitamin K”, “super K”, or “special K” [3, 4]. In the United States of America as well as in the United Kingdom ketamine was used as an adulterant in methylenedioxy-methamphetamine (MDMA) under the name of “horse pill” [5].
The typical ketamine users are regular visitors of the electronic dance music scene [6]; psychonauts; injecting heroin users, and the ‘gay’ club/party scene [7]. In addition, according to the data from the Crime Survey for England and Wales (CSEW) for 2012/2013, it is usually single male, aged 20–24, unemployed or studying, and from Chinese or mixed-race ethnic roots [8].
The most important reasons for ketamine’s recreational use are as follows: short time to effect; duration of action (up to 3 h), as well as low cost. Ketamine was gained popularity as a party drug due to the appearance of powerful psychoactive effects even at low, subanesthetic (0.1–0.5 mg/kg) doses [9]. As a dissociative anesthetic, ketamine and other drugs such as phencyclidine (PCP) or dextromethorphan (DXM), distort the user’s perception of sight and sound, while producing illusions of detachment from the environment or body, known as a „falling into a K-hole” (near-death experience). This state is also associated with the lack of the ability to speak and move around easily, not accompanied by actual loss of consciousness [10]. It is considered that; ketamine had the highest degree of out-of-body experiences among any other drugs, like a bad LSD trip. While not all ketamine users had out-of-body experiences, less than 10% of subjects experience this phenomenon regularly [11]. Of note, these symptoms can be prolonged and even create psychosis associated with schizophrenic and other psychotic disorders. In fact, ketamine has been used experimentally to develop a ‘ketamine model’ of psychosis [12, 13].
Additionally, hallucinations, emotional withdrawal, and “melting into the surrounding” may occur. It is also very likely for users (at very high doses of ketamine or those combining ketamine with alcohol or other drugs) to experience numbness, amnesia, more intense dissociations, and delirium [14].
Ketamine’s ability to induce confusion, amnesia and alter some of the perceptual effects make this drug a so-called “date rape drug”. For this reason, ketamine was included in the Drug-Induced Rape Prevention Act of 1966 [15]. Unfortunately, some of the symptoms and side-effects are long-lasting (i.e., impairment to episodic and possibly attentional functioning). Although semantic memory impairments are thought to be reversible as a consequence of ketamine cessation or substantial reduction of its use [9, 16].
The recreational use of ketamine has climbed over decades in the UK [17, 18], Australia [7], Southeast Asian countries such as Taiwan, Malaysia, and China, particularly such phenomenon was reported among the youth and adolescents [19, 20, 21, 22]. It could be, in part, due to ketamine’s lower status in regulatory systems and lower price, compared to still expensive “ecstasy” or methamphetamine. In Hong Kong, where ketamine was classified as a Schedule I drug since 2000, ketamine became the most commonly misused drug in the early 2000s [21].
The abuse of ketamine has been declining over the past years but is still relatively common. According to the national survey-based ‘Monitoring the Future Study’ in the United States ketamine ingestion decreased between 2002 and 2012 from 2.5% to 1.5%, and from 1.3% to 0.4%, among 12th graders and college students, respectively [23].
The decreasing ketamine popularity was also noticed in the United Kingdom (UK), where it has been classified on the list as a Class C drug since 2006 [21], and then was reclassified as a Class B drug from 10 June 2014 [24]. The World Health Organization fact file has demonstrated the ketamine usage in the UK decreased from 0.6% to 0.4% and from 1.8% to 0.8%, respectively, between 2011 and 2013 [23]. Similarly, in another study the level was continued to fall in 2013 to 50.6% and 31.5%, but these were still higher than for US respondents (26.3% and 15.4%, respectively) [25].
Before the COVID-19 pandemic global last year use rates of ketamine were 6.72% in 2016, 8.6% in 2017 and 6.5% in 2018; lifetime rates for 2017 and 2018 were 11.7% and 10.4%, respectively [26, 27]. During the COVID-19 pandemic state, a reduction in ‘party drugs’-like ketamine consumption was expected. As the limited access to pubs, clubs, and festivals cancelation were the primary reasons for decreases in the recreational use of illicit drugs which are typically linked to the nightlife and party scenes. In fact, in Australia, the use of ecstasy/MDMA and related drugs (e.g., cocaine, ketamine) had fallen compared to the pre-pandemic level [28, 29]. The less interest in club drugs like ketamine was also noticed by Neutravel, an Italian non-governmental organization (NGO) [30].
Surprisingly, in the U.S. according to the national survey-based ‘Monitoring the Future Study’, it has been demonstrated the ketamine use raised between 2019 and 2020 from 0.7 to 1.3% respectively among 12th graders [31]. Some individuals paradoxically start to use ketamine due to anxiety caused by the pandemic time, while others increased its consumption during lockdown spent at home. [32].
In 1999, ketamine including its salts, isomers, become a Schedule II non-narcotic substance under the Federal Controlled Substances Act in the U.S. This means that the drug does have lower misuse potential but is still approved for use in hospitals and other medical settings as an anesthetic. Because of this, it is illegal to possess ketamine without a medical reason, prescription, or as a part of the research. Thus, the illicit use of ketamine appears to be from illegal diversion from legal prescription, but analogs which usually contain a range of undeclared psychoactive substances (i.e., amphetamine, benzocaine, cocaine, MDMA, methoxetamine, paracetamol, piperazines, and synthetic cathinones) may also be found on the streets [33].
Nowadays, in the U.S., ketamine is classified as a schedule III drug under the DEA Controlled Substances Act. Medications in this category are often used for pain control, or anesthesia, or appetite suppression. It means that ketamine has less potential for abuse than Schedule I (heroin) or Schedule II (cocaine) drug, and it is not as tightly regulated as most opioids. However, abuse of Schedule III substances may lead to moderate or low physical dependence but more commonly leads to high psychological dependence. This means that for users outside the approved limits, its adverse mental and physical health effects can be hazardous [34].
Ketamine has been revived a couple of times in 2003, 2006, and 2012 by The Expert Committee on Drug Dependence of the World Health Organization (WHO), and finally, it has remained on the list as an essential medicine. The experts considered that the international control is not appropriate in this case, as new facts about ketamine were not sufficient to warrant scheduling. In the recent World Drug Report by United Nations Office on Drugs Control 2019 (UNOD 2019) [35], ketamine is classified under new psychoactive substances (NPSs), which are not under the control of international drug conventions, but which may pose a threat to public health. Since 2000, in the European Union, ketamine is not under the control, however further monitoring of drug use is recommended by the European Commission. Despite the increasing trends of abuse, dependence, and dying from ketamine recreational use, its status did not change significantly over time. It seems to be still relatively low, especially when compared with other Novel Psychoactive Substances (i.e., synthetic cannabinoids and cathinones or ‘designer benzos’). This raises important concerns about the underestimation of ketamine.
The route of ketamine administration is crucial for the type and the intensity of the experience the effect. Ketamine has a dose–response curve with variable effects (Table 1). However, unlike other psychedelic drugs like LSD, ketamine triggers a short trip, lasting no more than 1.5 hours. The illicit product mostly involves evaporating the liquid from the diverted injectable solution to produce a dry powder that is formed into tablets or sold as a powder. The most common method of ketamine abuse is “snorting” and 96% of ketamine users choose such a way for its usefulness and rapid action noticed in roughly 5 to 10 minutes [33]. In comparison, oral consumption requires between 15 and 20 minutes (Table 2) [25]. For nonmedical use, a typical intranasal dose is 50 mg and the oral dose is 100 mg [38, 39], but the usual recreational dose range between 60 and 250 mg of ketamine [40]. Ketamine abusers will often self-administer several sequential doses of the drug to maintain psychotropic effects over time. However, an injection results in the most rapid effect (within seconds to minutes), though such a way of administration is quite difficult especially in clubs. Interestingly, a recent animal study has revealed that a high IV ketamine dose caused the complete cessation of cortical EEG activity for several minutes, similarly to the ‘K-hole’ in humans [41]. Recently, online user fora, as well as research findings, also support vaping as a possible route of ketamine administration [42, 43].
Dose range [mg] | Related effects |
---|---|
Low: 10–75 | mild euphoria, feeling of well-being, feelings of calmness and relaxation, empathy, smell, and tastes muted, visual hallucinations, enhanced color vision, sense of touch deterioration |
Medium: 60–125 | slow motion, auditory hallucinations (ringing in the ears), detached feeling from the body, loss of coordination, diminished reflexes |
High: 100–250 | felling light, timelessness, body dysmorphia, ‘K-hole’ out-of-body experiences |
The common effects of ketamine in snorted doses.
Single dose [mg]* | Route | Onset of action [min] | Duration of action [min] |
---|---|---|---|
75–125 | i.m. | 1–5 | 30–45 |
60–250 | i.n. | 5–10 | 45–60 |
50–100 | i.v. | seconds | 30–45 |
200–300 | p.o. | 15–20 | 60–120 |
Ketamine recreational dose ranges, the routes of administration, onset and duration of action ([36] with some modifications).
Typical recreational dose is 10–25% of the effective general anesthetic dose [37].
Abbreviations: intramuscular (i.m.); insufflation, intranasal or “snorting” (i.n.); intravenously (i.v.), per os, orally “by mouth” (p.o).
There are no medical uses in which ketamine is provided chronically. The majority of reported long-term effects of ketamine are those which have developed in chronic recreational users or animals during preclinical studies. Although controlled human studies of repeated doses of ketamine are prohibited because it would be unethical to give an anesthetic with pronounced adverse effects more often. In clinical settings, ketamine is rather well tolerated. Although the pattern of adverse effects of non-medical ketamine use may differ from that expected from prescribed medical use. In individuals who misuse ketamine, serious sequelae, including prolonged neuro-, urological-, and gastro-toxicity may occur. The residual effects which may persist beyond acute ketamine dosing and its long-term consequences have been compiled and presented in the following subsections below.
Evidence of the psychotogenic potency of ketamine initially emerged from general anesthetic use where clinicians noted drug- related post-anesthetic reactions (i.e., confusion, vivid dreams, and hallucinations) leading to a reduction in the clinical drug utility [9, 44, 45].
There are some evidences that infrequent and frequent ketamine users exhibited higher levels of schizophrenia-like, dissociative, and depressive symptoms [13]. Hansen et al. [46] described the most common subjective effects of ketamine in recreational users including the sensation of light through the body; novel experiences concerning “body consistency” (e.g., being made of wood, rubber, or plastic); unreal shape or size of body parts; a sensation of floating or hovering in a weightless condition; timeless; sudden insight into the self; the experience of being at one with the universe; an experience of leaving the body; visions and hallucinations).
Subanesthetic doses of ketamine in healthy volunteers also trigger positive and negative schizophrenic-like symptoms as well as perceptual alterations similar to dissociative states with altered body perception, depersonalization, derealization, and distorted sensory perception. Of note, ketamine had the highest degree of out-of-body experiences compared to the other drugs as was mentioned in the previous section. While it is given to chronic, stable schizophrenics, ketamine has been shown to cause a re-emergence of the acute phase of the illness [47].
Ketamine exerts its unique behavioral effects mostly by blocking the NMDA receptors [48, 49]. Although phencyclidine (PCP; “angel dust”) has a 10-fold greater affinity for the NMDA receptor and is more excitotoxic than ketamine. Over the past several decades many animal models have been developed using drug mimics endogenous deficits in NMDA receptor function to study the mechanism of schizophrenia [48]. The cumulative effect of repeatedly using ketamine and/or a residual effect has occurred 3 days after abusers took this drug [50]. More importantly, even strong schizophrenic-type symptoms and perceptual distortions may persist after cessation of ketamine use [17, 36].
One of the explanations of such effect is NMDA receptor dysfunction even several days after acute use. Second, a residual effect may also be psychological in that ketamine produces an intensely subjective experience that could affect users’ perceptions of the world for several days after it is taken [13, 50].
There is increasing evidence that regular and long-lasting ketamine use can induce central nervous system depression and impair cognition, in particular visual and verbal memory as well as executive function [50, 51, 52]. The frequent ketamine users with increasing drug doses were more likely to have cognitive deficits, especially with short- and long-term spatial working memory and pattern recognition memory tasks [53]. Short-term memory and visual memory deficits occur usually in users who abused the drug at least 4 days per week. Similarly, according to findings from animal studies, ketamine seems to deteriorate memory at relatively high doses. Short-term memory and spatial memory were impaired in rats administered 30 mg/kg i.p. and were revealed by the delayed spatial alternation task and finding to the hidden platform in the Morris water maze test [54, 55].
Interestingly, ketamine appears to have greater potency to reduce cognition than other drugs of abuse [13]. These cognitive deficits may affect functioning in the abuser’s daily life due to difficulty in remembering conversations and other people’s names [13]. It has been also found that men to be more affected by these effects than women [56]. In addition, cognitive deficits are also related to the impairment of the psychomotor performance, such as coordination, balance, and hand-eye movements. This lack of coordination may cause the inability to drive or operate machinery, thereby increasing accidental injury or even mortality from motor vehicle collisions. Data from an epidemiological study involving drug-related motor vehicle collision fatalities found 9% related to ketamine use, representing a disproportionate number of fatalities compared to alcohol and opioid misuse [57].
In 2007, according to data from a single trauma centre in Hong Kong roughly 4.5% of drivers involved in non-fatal crashes tested positive for ketamine [58].
In addition, ketamine may gradually change the brain’s chemical system affecting opioids, dopamine (it activates dopamine systems), serotonin, noradrenaline, nitric oxide, sigma, GABA (gamma amino-butyric acid), and acetylcholine, among others [59, 60].
Ketamine has been also induced electrophysiological dissociation between the thalamo-neocortical and limbic systems and potentiated the synaptic inhibition of GABA [36, 61, 62]. However, the key pharmacological mechanisms underlying ketamine-related cognitive deficits are mediated via an NMDA glutamate receptors hypofunction [4]. There have been also shown that NMDA antagonists’ potency induced degeneration in a subset of limbic structures like those which are altered in patients with psychoses [63]. Animal studies revealed that direct apoptotic neurodegeneration was induced by NMDA-R antagonists, including ketamine, in the developing rodent brain. However, this ketamine effect was more evident in older rats [64]. According to other findings from animal studies the racemic ketamine (with its preservative benzethonium chloride) and S-ketamine have been associated with neuronal apoptosis and sensorineural consequence following high dose and/or long-term i.v. administration [65, 66, 67, 68]. However, translatability to humans is questioned and the impact of lower subanesthetic doses is uncertain.
In this way, ketamine abuse may display structural damage in multiple brain areas, such as the frontal, occipital, parietal, limbic, and corpus striatum [69, 70].
There have been shown that such detrimental effect is related to time and the dose of ketamine abuse [69]. Data have also revealed that the brain atrophies may occur within 1 year of ketamine intensive use with expected further progression in the following years [70]. In fact, ketamine dose reduction may restore cognition, but we cannot rule out irreversible and residual effects [17, 50].
As data have demonstrated NMDA receptors must be blocked for at least 24 hours to produce irreversible effect or death in the cells, but ketamine has a short half-life (about 20 minutes in rats) thus many injections are needed, over a prolonged period, to produce persistent change [71].
Although we have still limited data regarding cognitive ability from the ketamine ex-user population to provide straightforward conclusions for these findings. To date, there is no specific pharmacotherapy to avoid cognitive deficits in long-term ketamine use. The management of these problems is largely supportive and symptomatic. The cognitive enhancers are taken into consideration, such as modafinil, commonly used in stimulant addiction, as well as cholinesterase inhibitors (i.e., rivastigmine, donepezil, galantamine) usually recommended in other disorders with cognitive impairments (i.e., Alzheimer’s disease, Parkinson’s disease, traumatic brain injury, and schizophrenia), among others [51, 72].
Compared to growing evidence available for the anti-depressant effect of ketamine, there is still less for its pro-depressant potency [73]. Ironically, an intranasal ketamine formulation was recently approved in the USA, and Europe to treat intractable depression and acute suicidal ideation [74]. The depressive potency of ketamine seems to be dose and time-related. Insights from the animal study indicate that the antidepressant action at a dose of 10 mg/kg was not observed in rats receiving a higher dose of ketamine (80 mg/kg) [75]. Likewise, the anti-depressive effects linked to the subanesthetic ketamine dose (0.5 mg/kg) might not correspond to the same effect at the dosages range, preferred by recreational users. It was suggested that an opposite pro-depressant effect may be linked to certain neuroadaptation changes [76]. In fact, some studies demonstrated that chronic use of ketamine causes more lasting depressive effects [4, 36, 53]. There have been shown that ketamine abusers reported depressive symptoms quite common, roughly 72.5%–77.5% of them were diagnosed with moderate to severe depression based on the Beck Depression Inventory scores [77, 78].
According to the results from various studies, the prevalence of major depressive disorder (MDD) in outpatient settings fluctuating between 7.8–18.5%, in comparison to inpatient populations with nearly one-fourth (23.3%) ketamine-dependent MDD comorbidity [79, 80, 81]. Though, according to certain authors, the mood measures revealed little and clinically insignificant difference between groups with slightly higher scores in the ketamine users [50].
Interestingly, increased depression scores have been found in both daily users and ex-users in a longitudinal study, although not more infrequent users [53]. The mechanism of the acute antidepressant and chronic depressant effects may be linked, but it is unclear exactly how this opposite effect is mediated. Why abstinent ketamine users were more depressed is also less clear but may be linked with a change in their lifestyle. In fact, the frequent ketamine users had experienced more negative life events over the 12 months, due probably to their chaotic lifestyles, which may also trigger depressive symptoms [82].
In addition, previous evidence indicates that the depressive symptoms in ketamine users may persist even for 1 year after abstinence [53]. Furthermore, increased depression in frequent users could also reflect their increased dependency on ketamine, as depression is also commonly comorbid in opiate- and alcohol-dependent populations [83, 84]. Recent data imply that depression might be associated with craving (stronger propensity to administer more ketamine). There have been shown that patients with higher craving intensity demonstrated a greater severity of depression, longer history of ketamine administration, and greater use frequency than those with lower craving intensity [81].
Ketamine-induced tolerance may be considered in many aspects, although it is exceptionally mentioned in psychopharmacological clinical studies.
Firstly, ketamine is known as an effective anesthetic drug widely used in the clinic, however, as with many drugs, this effectiveness is often compromised due to tolerance to ketamine’s anesthetic effects, which might be of great importance especially when the patient has a history of drug abuse. Similarly, there are several papers indicating tolerance to the antidepressive effects of ketamine during repeated administrations [85]. Nonetheless, tolerance to ketamine can develop rapidly in all species, including after one large dose [86, 87], or even in patients with major depressive disorder. A great example derived from the case study of Bonnet [85] provided evidence that a continuous antidepressant response to daily ketamine injections can be followed by a swift return of a major depressive episode after cessation of ketamine. Other papers demonstrate animals chronically given ketamine that required increased doses of ketamine to reach the target anesthetic plane. Moreover, animals had a shorter duration of anesthesia [86, 88]. Surprisingly, rats pretreated with intraperitoneal morphine at a dose of 5.6 mg/kg demonstrated cross-tolerance to ketamine’s anesthetic effects [88].
Ketamine, being a drug easily abused, may induce several uncomfortable adverse reactions as a consequence of its cessation. There is increasing evidence that ketamine causes psychological but not physical dependence. Withdrawal symptoms are usually like withdrawal from cocaine with very strong cravings. Symptoms of acute withdrawal may be short-lived and not identified as such [89]. However, the withdrawal from ketamine may paradoxically cause depression [90]. Other withdrawal symptoms after ketamine discontinuation include dysphoria, shaking, sweating, palpitations, tiredness, low appetite, low mood, chills, autonomic arousal, lacrimation, restlessness, anxiety, nightmares, paranoia, delusions, and hallucinations [81, 91, 92]. Noteworthy, these withdrawal symptoms typically begin within 24 h of discontinuation and last approximately 3 days, although in some cases, they may persist for 2 weeks and thereafter stabilize [93].
Apart from the abovementioned, there several reports are indicating that due to ketamine discontinuing mild forms of schizophrenic-like symptoms occur [17].
Recreational abuse of ketamine has been associated with bladder pain syndrome; ulcerative cystitis also known as ‘ketamine bladder’. Up to a quarter of ketamine, abusers may experience such problems. According to the European Medicines Agency (EMA) and the UK Yellow Card Scheme pharmacovigilance database about 23% and 17% of ketamine-related adverse drug reactions (ADR) respectively referred to renal/urinary disorders. Interestingly, such issues being more common among women than men [94]. In general, urological problems occur within 1 month-1 year time frame following the start of ketamine use, but recent pharmacovigilance data revealed that even an acute ketamine administration may be associated with urological risks, as in some cases the risk was noticed within 48 hours of treatment [94].
Initially, ketamine associate bladder disturbance may mimic common conditions such as urine infections and it may be difficult to diagnose, but further urinary symptoms may substantially disturb the quality of the abuser’s life thus extreme individuals have difficulty with passing urine. There are reports of needing to pass urine up to 20 times an hour, leading to hydronephrosis and finally kidney failure [4].
Damage to the urinary barrier initiates bladder pain and, in ketamine-induced cystitis, loss of urothelium from large areas of the bladder wall was reported [95]. Ketamine abuse also induces small bladder volume, bladder wall thickening, and mucosal enhancement. The most common ketamine bladder symptoms reported in the 2018 Global Drug Survey were as follows: urine frequency 38%; pain in the abdomen 25%; burning when urinating 18%; incontinence 7%; and blood 3% [96].
The first report of the urological syndrome was published in 2007 by Shahani and colleagues [97]. The cause of urinary toxicity appears to be multifactorial and not fully explained. It is postulated that the direct toxic effect of ketamine or its active metabolite (norketamine) on the urinary tract may play a crucial role [98]. It is also pointed out, that the urinary toxicity seems to be unrelated to ketamine interaction with NMDA receptors (NMDAR). Thus, in vitro studies revealed that normally human urothelial cells were unresponsive to NMDAR agonists or antagonists, and no expression of NMDAR transcript was detected [95].
A recent study offers new evidence for a mechanism of direct toxicity of ketamine to the urothelial by activating the intrinsic apoptotic pathway. In fact, exposure to ketamine in noncytotoxic concentrations initiates the transient release of calcium Ca(2+) from the endoplasmic reticulum into the cytosol. However, ketamine concentrations >1 mmol/L become cytotoxic and provokes a larger-amplitude increase in cytosolic Ca(2+) concentration. Consequently, sustained elevation in Ca(2+) leads to pathological mitochondrial oxygen consumption and ATP deficiency, and it initiates damage to the urinary barrier [95].
The chronic immune response of the bladder interstitial cells may be another possible underlying mechanism of toxicity [99, 100]. Biopsies have also revealed epithelial denudation, eosinophilic, as well as mast cell infiltration [97, 101]. Ketamine may also trigger interstitial fibrosis by damaging the papillary medullary interstitial cells [98]. There are also reports of metaplasia in the intestine related to ketamine abuse [102]. Furthermore, ketamine through its central action may disturb the contractile response of smooth muscle from appropriate stimuli [103].
In addition, ketamine may induce highly destructive microvascular changes causing epithelial-to-mesenchymal transition, which finally contributes to bladder or kidney fibrogenesis [100, 104].
Compared to the urinary tract, renal damage and bilateral hydronephrosis are less frequent but may also occur. Chronic kidney failure may develop as the final consequence of a long-term sequel [105].
Of note, there a no specific and casual pharmacotherapy for ketamine-related urinary tract disorder. The symptomatic treatment with antibiotics, anti-inflammatory agents, steroids, and anticholinergics in most cases has failed [106]. In such a scenario, the second line of alternative treatment with intravesical agents such as hyaluronic acid, and injections of Botulinum toxin-A should be considered. Preclinical studies have also suggested a future therapy with combined intravesical liposomal onabotulinum toxin-A instillation and mesenchymal stem cells placed directly into the bladder submucosal layer [107]. However, the urinary problems may improve and became reversible if ketamine use is reduced/withdrawn, thus ketamine abstinence should be the first step in ketamine-induced uropathy treatment. The abstinence greater than 3 months is related to some improvement and less severe symptoms. Of note, in some cases, urological issues may persist for up to 1 year after ketamine abstinence [108]. More invasive methods, such as a catheter (tube into the bladder), urinary diversion, and nephrectomy may be required in the prolonged ketamine abuse and irreversible renal damage which may produce a burden to healthcare resources [100, 102, 103].
Regular and long-term ketamine use is associated with gastric pathology of unknown etiology, colloquially termed ‘KCramps’ [37, 98].
In line with the 2010
In a retrospective study of GI symptoms followed by inhalational ketamine use, 28/37 of the subjects experienced upper GI symptoms. The mean time of ketamine use was 4 years before admission. Exclusion criteria included potential risk factors and a history of GI disorder. The most common finding was epigastric pain only, which occurred in 23 (62.2%) users. Four users had epigastric pain with vomiting. In sporadic cases, gastroduodenitis, and intestinal metaplasia have occurred. More importantly, all symptoms relief with abstinence from ketamine use [110]. Of note, pains symptomatology related to GI in ketamine users may resemble irritable bowel syndrome as in some parts tend to be triggered by psychological changes [37, 114].
There has been shown that gastric pathology among ketamine users correlated with the duration of drug use [111, 115]. The exact mechanism by which ketamine produces cholestasis and biliary dilation is unclear but is a possible direct link to NMDA receptor blockade in smooth muscle. In addition, ketamine may also act through the dorsal motor nucleus of the vagus, projecting to the gall bladder [116].
Effective treatment of GI toxicity includes discontinuation of ketamine use which can lead to the relief of symptoms, otherwise, treatment options are nonspecific [110].
Of note, there are certain cases of evidence of causal risk between chronic ketamine use and GI toxicity as dilated common bile duct regressed with abstinence but recurred following a return to ketamine use [111].
The phenomenon of interaction is used in clinical practice as multi-drug therapy. Its aim is to increase the pharmacological potency and obtain desired therapeutic effect while reducing doses of individual drugs. Such steps reduce the likelihood of side effects and are beneficial for the patient. However, the problem arises when unwanted drug interactions occur, and this includes i) pharmaceutical interactions, i.e. incompatibilities arising outside the patient’s body; ii) pharmacokinetic interactions related to the fate of the drug in the body at the stage of its absorption, distribution, metabolism and excretion; and finally iii) pharmacodynamic interactions, where one drug modifies the action of another drug.
All these benefits as well as undesired interactions are true for ketamine and other substances. Use with multiple drugs has been fatal.
Firstly, ketamine (both its R(−)- and S(+)-enantiomers) undergoes hepatic biotransformation through the cytochrome P450 (CYP450), particularly with the involvement of CYP2B6 and CYP3A4, to form norketamine. Therefore, an alteration of CYP450 metabolism results in clinically significant drug–drug interactions that can further cause unanticipated adverse reactions and/or therapeutic failures. For instance, drugs that induce both these cytochrome isoforms may reduce exposure to ketamine. In contrast, substances inhibiting CYP enzymes can lead to an increase the exposure to the drug. As a great example is the treatment with diazepam, being a substrate of CYP3A4, which increases ketamine plasma half-life, thus its sedative effects [117, 118]. On the other hand, ketamine can also influence diazepam metabolism as its decreases CYP3A4 enzyme activity [119].
Apart from the involvement of CYP 450 isoforms in the metabolism of ketamine, also another hepatic phase II enzymes may be taken under consideration. Indeed, ketamine has been shown to inhibit UGT2B7 and thus the metabolism of morphine both in vitro and in vivo [120, 121], therefore increases the liver concentration of the opioid. Intriguingly, also the brain concentration of morphine is found to increased (three- to five-fold 90 min after administration). However, such drug concentration changes in the brain are not because of changes at the blood–brain barrier as it was compared with oxycodone mainly metabolized by cytochrome P450 (CYP) enzymes [122]. Also, when considered oppositely, morphine, but not oxycodone, pretreatment increased the brain and serum concentrations of ketamine [123].
CYP3A4 enzyme is known to be affected by compounds derived from grapefruit juice or whole fruit (i.e., furanocoumarins and, to a lesser extent, flavonoids) [124]. Therefore, in the case of ketamine given orally, a significant increase in plasma concentration can be found in healthy volunteers [125].
Unfortunately, drug metabolism via CYP450 enzymes exhibits also genetic variability (polymorphism), thus in this case also some variations in the exposure to ketamine are obvious. Poor metabolizers of enzymes metabolizing ketamine are extremely rare. However, the paper of Rao et al. [126] provided with information that CYP2B6*6 polymorphism variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in healthy human volunteers, though diminished ketamine metabolism in vitro.
Concerning pharmacodynamic interaction once should be said that the nature of ketamine-drug interactions together with the observable effect is highly dependent on the drug type and thus the molecular target (i.e., opioidergic system, dopaminergic, serotoninergic, etc.) as well as from the dose used. There is a great several papers characterizing possible pharmacodynamics interactions between ketamine and different drugs both natural and synthetic. For instance, estrogen together with progesterone potentiated ketamine-induced antidepressant effect [127], while BNN27, a synthetic derivative of dehydroepiandrosterone reduced ketamine-induced ataxia [128]. Ketamine was found to produce additive effects when combined with gamma-aminobutyric acid (GABA) activity. This was found true for barbiturates such as thiopental at a hypnotic endpoint [129], but not with a benzodiazepine - midazolam [130]. Also, for anesthesia induction, the combination of ketamine and midazolam was found additive rather than synergistic at the endpoint of loss of response to verbal command [130]. When introduced with other benzodiazepines (i.e., clonazepam, alprazolam, lorazepam), specifically for the treatment of long-lasting depression, as well as considering that both types of drugs act on interneurons, ketamine antidepressant efficacy was mute [131, 132]. This finding suggested that benzodiazepines inhibitory activity towards ketamine’s antidepressant effect may be related to attenuation of neuroplastic processes, emerging subsequently after the acute effect and after ketamine and its active metabolites are eliminated from the blood since benzodiazepines occurred ineffective in the first 24 h post-concomitant administration of both drugs [131].
Analyzing other effects mediated by simultaneous ketamine and benzodiazepines, the following can be mentioned: (1) inhibition of ketamine-induced hyperlocomotion by diazepam [133]; (2) ketamine’s emotional stress reduction by a sub-hypnotic lorazepam [134]; (3) lorazepam intensification of ketamine sedative effects [134]; (4) potentiation of ketamine amnestic action by diazepam and lorazepam [134, 135]; (5) antagonism of the cardiovascular effects of ketamine by diazepam [136], or (6) ketamine-induced emergence delirium prevented by midazolam [137]. Whereas concerning antipsychotics such as haloperidol it has been shown that it can reduce ketamine-induced cognitive impairment. In addition, haloperidol was found to attenuate the increase of locomotor activity and stereotyped behavior, reversed the motor incoordination, and blocked the hypermobility induced by acute administration of ketamine in rodents [138].
Yet another possible interaction occurs between ketamine and the opioid system, as ketamine (in particular (S)-ketamine) was characterized as a drug that partially interacts with the opioid system, particularly mu-opioid receptors [139]. Indeed, as already mentioned, ketamine enhances levels of morphine, which may explain the long-lasting morphine-induced antinociception [120]. Importantly, the enhanced level of morphine is strictly associated with ketamine inhibitory activity towards morphine tolerance, which is mainly by N-methyl-d-aspartate (NMDA) receptor antagonism [121, 140]. On the other hand, it has long been suggested that opioids may enhance the antidepressant effect induced by ketamine, as naltrexone attenuated this activity [141]. However, currently, the involvement of the opioid system in this specific action is unclear since partial agonists (i.e., methadone and buprenorphine) did not influence ketamine’s antidepressant effect [142].
Opioids are well known for their great ability to induce respiratory depression, especially when overdosed. Intriguingly, also in this aspect, an interaction between ketamine and opioids exists. In fact, intraperitoneal (i.p.) administration of ketamine has led to significant respiratory depression in mice, but not in mu-opioid receptor knock-out mice [143].
As with other CNS medications, it should be mentioned that ketamine is capable of modifying effects mediated by alcohol consumption and illicit drugs. In the first case, it has been revealed that subjects simultaneously taking alcohol and ketamine are more vulnerable to suffer from the urinary tract and gastrointestinal problems such as pain with urination, increased frequency of urination, or even lower abdominal pain [144]. Of note, individuals with a family history of alcoholism with altered NMDA activity may have a blunted effect on the negative psychological reactions to ketamine. Whereas, as a great example of a drug of abuse, apart from the aforementioned opioids, for which a concomitant use with ketamine may result in unpredictable and extremely dangerous side effects is a so-called “liquid Extasy” [92, 145]. This compound is a gamma-hydroxybutyric acid (GHB), being a naturally occurring analog of gamma-aminobutyric acid (GABA), with esthetic and euphoric properties. Concerning ketamine, it has been shown that this drug together with GHB, in particularly high doses, results in an increased risk of respiratory depression and fatality. In addition, ketamine produced and enhanced GHB-mediated cataleptic effects in mice [146]. Also, can lead to a significant increase in sleep time.
Dangerous interactions were also noted for ketamine and methamphetamine both in vitro and in vivo. In fact, the co-exposure of these two drugs resulted in significant cytotoxicity and synergy on oxidative stress in HepG2 cells [147]. While in mice treated with a low dose of methamphetamine and ketamine, the stress-related depressive and anxiety-related behavioral alterations caused by the psychostimulant were antagonized consistently by both high and low doses of ketamine [148]. Furthermore, a combined repeated administration of both drugs was reported to increase significantly the risk of psychological dependence as shown in a rat conditioned place preference test [149]. In turn, in methamphetamine-dependent humans, a very high prevalence of psychotic disorders was suggested for those who occasionally or continuously use ketamine [150]. Moreover, when used with other stimulant drugs such as ecstasy, high blood pressure may appear [50]. Ketamine may be also toxic when is combined with caffeine. Theoretically, this may be a concern in people who have consumed energy drinks, especially at nightclubs where ketamine may be abused.
Ketamine is also a very popular drug taken together with cocaine. Unfortunately, such a combination occurred to result in a potentiation of cocaine-induced hepatotoxicity associated with sub-massive hepatic necrosis. These observations were indicated for rats pretreated with ketamine for three consecutive days at a dose of 100 mg/kg with a single dose of cocaine (5 mg/kg, i.v.) [151]. This information is especially intriguing when compared with recent data demonstrated that a single ketamine infusion in cocaine abusers, coupled with a mindfulness behavioral modification program, seems to be a promise to achieve both the abstinence and reduction of the risk of relapse [152].
Ketamine is known to be related to several molecular targets, either directly or indirectly. Indeed, due to its interactions with sodium channels (local anesthetic properties), i.e. L-type calcium channels and potassium channels [153], ketamine when administered with grapefruit juice may cause harmful effects ranging from relatively mild hypotension and dizziness. Furthermore, ketamine being an antagonist towards acetylcholinergic receptors produces various effects while interacting with cholinesterase and anticholinesterase agents. One great example is the interaction with atropine which was found to slightly increase the ketamine-induced time of immobility in rats [154]. On the other hand, ketamine blocked the EEG and the behavioral toxic effects of neostigmine and physostigmine. While physostigmine can reverse the central anticholinergic effects and also antagonize ketamine hypnotic effects [155]. However, in the aspect of somnolence reverse, there are contradictory results. In fact, while Balmer [156] found physostigmine effective in reversing ketamine-induced somnolence. Drummond et al. [157] indicated physostigmine as ineffective in producing a rapid patient awaking or even in reducing hallucinatory behavior.
Another possible cellular target of ketamine includes the monoaminergic system, particularly noradrenergic and serotonergic. Alpha2 agonists such as xylazine or medetomidine as well as dexmedetomidine were found safe when combining with ketamine [158]. Both these drugs were shown to reduce the dosage of ketamine and the occurrence of psychomotor symptoms after ketamine. As for compounds actin at serotonergic receptors of various types or being selective serotonin reuptake inhibitors (SSRIs) it can be provided that repeated subanaesthetic doses of ketamine can redeem the time lag for the antidepressant-like effects of citalopram [159]. Also, such a combination given to rats resulted in a decrease in the immobility time and increase in struggle time in the Forced Swim Test (FST) and Tail Suspension Test (TST) as compared to control group [160].
Beneficial effects were also observed for other serotonergic agents. For instance, intravenous ketamine emetic properties were inhibited by ondasteron in children [161]. Moreover, ketamine was reported to potentiate the anxiolytic effects of SSRIs such as fluoxetine [162].
Apart from the above-mentioned, also cannabinoids were indicated to be vulnerable to interact with ketamine. These includes delta 9-tetrahydrocannabinol being the major psychoactive molecule among synthetic cannabinoid ligands that act at cannabinoid 1 receptor (CB1), as well as cannabidiol (CBD) displaying potency as an antagonist of CB1 and CB1 receptor agonist, respetively. Indeed, Frizza et al. [163] reported 9-tetrahydrocannabinol to prolong the anesthesia induced by ketamine in mice. Whereas CBD was found reduced depersonalization when administered with ketamine, as measured by the Clinical Administered Dissociative State Scale in healthy humans [164].
Overall, it can be noted that ketamine, possibly due to the complex mechanism of action, may interact with various molecular targets resulting in both critical and beneficial effects. Therefore, there is no unequivocal opinion as to whether ketamine should be used with caution or not; this depends strictly on the type of the second drug used as well as on other physiological and pathophysiological factors, including age, genetic polymorphism, and occurrence of diseases and disorders.
Non-medical, recreational use of ketamine has increased in certain populations/sub-groups with geographical variations in its use patterns. Ketamine abuse seems to be an important public health challenge due to its association with multiple physical and psychological harms. Noteworthy, the psychedelic effect may have a therapeutic value in some points and be harmful in others. Long term users may develop different neurobiological alterations, psychological dependency, withdrawal, tolerance, schizophrenia-type symptoms, poor psychological well-being, memory difficulties, and finally worse quality of daily life. In the long-term use, there is also evidence of deleterious effects for the peripheral system, associated with serious lower urinary tract symptoms, and gastrointestinal pathology. In addition, polysubstance consumption is inherently risky and can lead to serious adverse consequences, especially when abusers mixing ketamine with eighter depressants or stimulants. Although of concern did not cause any significant changes in ketamine’s legal status over the years. There are numerous studies revealed the effects of a single administration of ketamine, thus the effects following repeated use and long-term consequences are still less known and underestimated. More study is needed to better elucidate the real ketamine safety profile regarding both its long-term recreational use and its clinically use as an antidepressant agent.
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Badria"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11072",title:"Sample Preparation Techniques for Chemical Analysis",subtitle:null,isOpenForSubmission:!1,hash:"38fecf7570774c29c22a0cbca58ba570",slug:"sample-preparation-techniques-for-chemical-analysis",bookSignature:"Massoud Kaykhaii",coverURL:"https://cdn.intechopen.com/books/images_new/11072.jpg",editedByType:"Edited by",editors:[{id:"349151",title:"Prof.",name:"Massoud",middleName:null,surname:"Kaykhaii",slug:"massoud-kaykhaii",fullName:"Massoud Kaykhaii"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:193,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"36171",doi:"10.5772/36942",title:"Research of Calcium Phosphates Using Fourier Transform Infrared Spectroscopy",slug:"research-of-calcium-phosphates-using-fourier-transformation-infrared-spectroscopy",totalDownloads:9264,totalCrossrefCites:132,totalDimensionsCites:379,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"Liga Berzina-Cimdina and Natalija Borodajenko",authors:[{id:"110522",title:"Prof.",name:"Liga",middleName:null,surname:"Berzina-Cimdina",slug:"liga-berzina-cimdina",fullName:"Liga Berzina-Cimdina"},{id:"112181",title:"MSc.",name:"Natalija",middleName:null,surname:"Borodajenko",slug:"natalija-borodajenko",fullName:"Natalija Borodajenko"}]},{id:"36178",doi:"10.5772/36323",title:"Applications of FTIR on Epoxy Resins - Identification, Monitoring the Curing Process, Phase Separation and Water Uptake",slug:"applications-of-ftir-on-epoxy-resins-identification-monitoring-the-curing-process-phase-separatio",totalDownloads:20862,totalCrossrefCites:84,totalDimensionsCites:256,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"María González González, Juan Carlos Cabanelas and Juan Baselga",authors:[{id:"107857",title:"Prof.",name:"Juan",middleName:null,surname:"Baselga",slug:"juan-baselga",fullName:"Juan Baselga"},{id:"138113",title:"Dr.",name:"María",middleName:null,surname:"González",slug:"maria-gonzalez",fullName:"María González"},{id:"138114",title:"Dr.",name:"Juan C.",middleName:null,surname:"Cabanelas",slug:"juan-c.-cabanelas",fullName:"Juan C. Cabanelas"}]},{id:"53973",doi:"10.5772/66927",title:"Phenolic Compounds in Water: Sources, Reactivity, Toxicity and Treatment Methods",slug:"phenolic-compounds-in-water-sources-reactivity-toxicity-and-treatment-methods",totalDownloads:7311,totalCrossrefCites:77,totalDimensionsCites:166,abstract:"Phenolic compounds exist in water bodies due to the discharge of polluted wastewater from industrial, agricultural and domestic activities into water bodies. They also occur as a result of natural phenomena. These compounds are known to be toxic and inflict both severe and long‐lasting effects on both humans and animals. They act as carcinogens and cause damage to the red blood cells and the liver, even at low concentrations. Interaction of these compounds with microorganisms, inorganic and other organic compounds in water can produce substituted compounds or other moieties, which may be as toxic as the original phenolic compounds. This chapter dwells on the sources and reactivity of phenolic compounds in water, their toxic effects on humans, and methods of their removal from water. Specific emphasis is placed on the techniques of their removal from water with attention on both conventional and advanced methods. Among these methods are ozonation, adsorption, extraction, photocatalytic degradation, biological, electro‐Fenton, adsorption and ion exchange and membrane‐based separation.",book:{id:"6029",slug:"phenolic-compounds-natural-sources-importance-and-applications",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Natural Sources, Importance and Applications"},signatures:"William W. Anku, Messai A. Mamo and Penny P. Govender",authors:[{id:"195237",title:"Dr.",name:"Messai",middleName:"A.",surname:"Mamo",slug:"messai-mamo",fullName:"Messai Mamo"},{id:"196465",title:"Dr.",name:"William Wilson",middleName:null,surname:"Anku",slug:"william-wilson-anku",fullName:"William Wilson Anku"},{id:"196466",title:"Dr.",name:"Penny",middleName:null,surname:"Govender",slug:"penny-govender",fullName:"Penny Govender"}]},{id:"36184",doi:"10.5772/36186",title:"Infrared Spectroscopy in the Analysis of Building and Construction Materials",slug:"infrared-spectroscopy-of-cementitious-materials",totalDownloads:7810,totalCrossrefCites:77,totalDimensionsCites:157,abstract:null,book:{id:"1591",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",title:"Infrared Spectroscopy",fullTitle:"Infrared Spectroscopy - Materials Science, Engineering and Technology"},signatures:"Lucia Fernández-Carrasco, D. Torrens-Martín, L.M. Morales and Sagrario Martínez-Ramírez",authors:[{id:"107401",title:"Dr.",name:"Lucia J",middleName:null,surname:"Fernández",slug:"lucia-j-fernandez",fullName:"Lucia J Fernández"}]},{id:"53128",doi:"10.5772/66368",title:"Phenolic Compounds: Functional Properties, Impact of Processing and Bioavailability",slug:"phenolic-compounds-functional-properties-impact-of-processing-and-bioavailability",totalDownloads:9381,totalCrossrefCites:77,totalDimensionsCites:148,abstract:"In this chapter, we discuss the influence of the processing methods on the content of phenolic compounds in fruits and vegetables. The intake of fruits and vegetables based‐foods are associated with delayed aging and a decreased risk of chronic disease development. Fruits and vegetables can be consumed in natura, but the highest amounts are ingested after some processing methods, such as cooking procedures or sanitizing methods. These methods are directly methods are directly related to alteration on the phenolic content. In addition, the postharvest conditions may modify several phytochemical substances. Phenolic compounds are referred to as phytochemicals found in a large number of foods and beverages. The relative high diversity of these molecules produced by plants must be taken into account when methods of preparation are employed to obtain industrial or homemade products. Phenolic compounds comprise one (phenolic acids) or more (polyphenols) aromatic rings with attached hydroxyl groups in their structures. Their antioxidant capacities are related to these hydroxyl groups and phenolic rings. Despite the antioxidant activity, they have many other beneficial effects on human health. However, before attributing health benefits to these compounds, absorption, distribution, and metabolism of each phenolic compound in the body are important points that should be considered.",book:{id:"5609",slug:"phenolic-compounds-biological-activity",title:"Phenolic Compounds",fullTitle:"Phenolic Compounds - Biological Activity"},signatures:"Igor Otavio Minatel, Cristine Vanz Borges, Maria Izabela Ferreira,\nHector Alonzo Gomez Gomez, Chung-Yen Oliver Chen and\nGiuseppina Pace Pereira Lima",authors:[{id:"146379",title:"Dr.",name:"Giuseppina",middleName:null,surname:"Lima",slug:"giuseppina-lima",fullName:"Giuseppina Lima"},{id:"194002",title:"MSc.",name:"Cristine",middleName:null,surname:"Vanz Borges",slug:"cristine-vanz-borges",fullName:"Cristine Vanz Borges"},{id:"194003",title:"Prof.",name:"Igor Otavio",middleName:null,surname:"Minatel",slug:"igor-otavio-minatel",fullName:"Igor Otavio Minatel"},{id:"194004",title:"Dr.",name:"Maria Izabela",middleName:null,surname:"Ferreira",slug:"maria-izabela-ferreira",fullName:"Maria Izabela Ferreira"},{id:"194005",title:"Prof.",name:"Hector",middleName:null,surname:"Gomez-Gomez",slug:"hector-gomez-gomez",fullName:"Hector Gomez-Gomez"},{id:"194006",title:"Prof.",name:"Chung-Yen Oliver",middleName:null,surname:"Chen",slug:"chung-yen-oliver-chen",fullName:"Chung-Yen Oliver Chen"}]}],mostDownloadedChaptersLast30Days:[{id:"55500",title:"Interpretation of Mass Spectra",slug:"interpretation-of-mass-spectra",totalDownloads:12503,totalCrossrefCites:12,totalDimensionsCites:25,abstract:"The chapter includes an introduction to the main ionisation techniques in mass spectrometry and the way the resulting fragments can be analysed. First, the fundamental notions of mass spectrometry are explained, so that the reader can easily cover this chapter (graphs, main pick, molecular ion, illogical pick, nitrogen rule, etc.). Isotopic percentage and nominal mass calculation are also explained along with fragmentation mechanism. A paragraph emphasises the ionisation energy issues, the basics of ionisation voltage, the developing potential and the energy balance. A frame time of the main theoretical milestones in both theory and experimental mass spectrometry is highlighted here. In the second part of the chapter, the molecular fragmentation for alkanes, iso-alkanes, cycloalkanes, halogen, alcohols, phenols, ethers, carbonyl compounds, carboxylic acids and functional derivatives, nitrogen compounds (amines, nitro compounds), sulphur compounds, heterocycles and biomolecules (amino acids, steroids, triglycerides) is explained. Fragmentation schemes are followed by the simplified spectra, which help the understanding of such complex phenomena. At the end of the chapter, acquisition of mass spectrum is discussed. The chapter presented here is an introduction to mass spectrometry, which, we think, helps the understanding of the mechanism of fragmentation corroborating spectral data and molecular structures.",book:{id:"5735",slug:"mass-spectrometry",title:"Mass Spectrometry",fullTitle:"Mass Spectrometry"},signatures:"Teodor Octavian Nicolescu",authors:[{id:"196775",title:"Dr.",name:"Teodor Octavian",middleName:"Octavian",surname:"Nicolescu",slug:"teodor-octavian-nicolescu",fullName:"Teodor Octavian Nicolescu"}]},{id:"57909",title:"Validation of Analytical Methods",slug:"validation-of-analytical-methods",totalDownloads:6989,totalCrossrefCites:13,totalDimensionsCites:21,abstract:"Method validation is a key element in the establishment of reference methods and within the assessment of a laboratory’s competence in generating dependable analytical records. Validation has been placed within the context of the procedure, generating chemical data. Analytical method validation, thinking about the maximum relevant processes for checking the best parameters of analytical methods, using numerous relevant overall performance indicators inclusive of selectivity, specificity, accuracy, precision, linearity, range, limit of detection (LOD), limit of quantification (LOQ), ruggedness, and robustness are severely discussed in an effort to prevent their misguided utilization and ensure scientific correctness and consistency among publications.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Tentu Nageswara Rao",authors:[{id:"220824",title:"Dr.",name:"Tentu",middleName:null,surname:"Nageswara Rao",slug:"tentu-nageswara-rao",fullName:"Tentu Nageswara Rao"}]},{id:"55440",title:"Solubility Products and Solubility Concepts",slug:"solubility-products-and-solubility-concepts",totalDownloads:3090,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"The chapter refers to a general concept of solubility product Ksp of sparingly soluble hydroxides and different salts and calculation of solubility of some hydroxides, oxides, and different salts in aqueous media. A (criticized) conventional approach, based on stoichiometry of a reaction notation and the solubility product of a precipitate, is compared with the unconventional/correct approach based on charge and concentration balances and a detailed physicochemical knowledge on the system considered, and calculations realized according to generalized approach to electrolytic systems (GATES) principles. An indisputable advantage of the latter approach is proved in simulation of static or dynamic, two-phase nonredox or redox systems.",book:{id:"5891",slug:"descriptive-inorganic-chemistry-researches-of-metal-compounds",title:"Descriptive Inorganic Chemistry Researches of Metal Compounds",fullTitle:"Descriptive Inorganic Chemistry Researches of Metal Compounds"},signatures:"Anna Maria Michałowska-Kaczmarczyk, Aneta Spórna-Kucab and\nTadeusz Michałowski",authors:[{id:"35273",title:"Prof.",name:"Tadeusz",middleName:null,surname:"Michalowski",slug:"tadeusz-michalowski",fullName:"Tadeusz Michalowski"},{id:"203867",title:"Dr.",name:"Anna Maria",middleName:null,surname:"Michałowska-Kaczmarczyk",slug:"anna-maria-michalowska-kaczmarczyk",fullName:"Anna Maria Michałowska-Kaczmarczyk"},{id:"203868",title:"Dr.",name:"Aneta",middleName:null,surname:"Spórna-Kucab",slug:"aneta-sporna-kucab",fullName:"Aneta Spórna-Kucab"}]},{id:"62736",title:"Radioisotope: Applications, Effects, and Occupational Protection",slug:"radioisotope-applications-effects-and-occupational-protection",totalDownloads:4543,totalCrossrefCites:10,totalDimensionsCites:17,abstract:"This chapter presents a brief introduction to radioisotopes, sources and types of radiation, applications, effects, and occupational protection. The natural and artificial sources of radiations are discussed with special reference to natural radioactive decay series and artificial radioisotopes. Applications have played significant role in improving the quality of human life. The application of radioisotopes in tracing, radiography, food preservation and sterilization, eradication of insects and pests, medical diagnosis and therapy, and new variety of crops in agricultural field is briefly described. Radiation interacts with matter to produce excitation and ionization of an atom or molecule; as a result physical and biological effects are produced. These effects and mechanisms are discussed. The dosimetric quantities used in radiological protection are described. Radiological protections and the control of occupational and medical exposures are briefly described.",book:{id:"5903",slug:"principles-and-applications-in-nuclear-engineering-radiation-effects-thermal-hydraulics-radionuclide-migration-in-the-environment",title:"Principles and Applications in Nuclear Engineering",fullTitle:"Principles and Applications in Nuclear Engineering - Radiation Effects, Thermal Hydraulics, Radionuclide Migration in the Environment"},signatures:"Sannappa Jadiyappa",authors:[{id:"239626",title:"Dr.",name:null,middleName:null,surname:"Sannappa J.",slug:"sannappa-j.",fullName:"Sannappa J."}]},{id:"58596",title:"Linearity of Calibration Curves for Analytical Methods: A Review of Criteria for Assessment of Method Reliability",slug:"linearity-of-calibration-curves-for-analytical-methods-a-review-of-criteria-for-assessment-of-method",totalDownloads:8095,totalCrossrefCites:19,totalDimensionsCites:44,abstract:"Calibration curve is a regression model used to predict the unknown concentrations of analytes of interest based on the response of the instrument to the known standards. Some statistical analyses are required to choose the best model fitting to the experimental data and also evaluate the linearity and homoscedasticity of the calibration curve. Using an internal standard corrects for the loss of analyte during sample preparation and analysis provided that it is selected appropriately. After the best regression model is selected, the analytical method needs to be validated using quality control (QC) samples prepared and stored in the same temperature as intended for the study samples. Most of the international guidelines require that the parameters, including linearity, specificity, selectivity, accuracy, precision, lower limit of quantification (LLOQ), matrix effect and stability, be assessed during validation. Despite the highly regulated area, some challenges still exist regarding the validation of some analytical methods including methods when no analyte-free matrix is available.",book:{id:"6379",slug:"calibration-and-validation-of-analytical-methods-a-sampling-of-current-approaches",title:"Calibration and Validation of Analytical Methods",fullTitle:"Calibration and Validation of Analytical Methods - A Sampling of Current Approaches"},signatures:"Seyed Mojtaba Moosavi and Sussan Ghassabian",authors:[{id:"216099",title:"Dr.",name:"Sussan",middleName:null,surname:"Ghassabian",slug:"sussan-ghassabian",fullName:"Sussan Ghassabian"},{id:"216101",title:"Mr.",name:"Seyed Mojtaba",middleName:null,surname:"Moosavi",slug:"seyed-mojtaba-moosavi",fullName:"Seyed Mojtaba Moosavi"}]}],onlineFirstChaptersFilter:{topicId:"8",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83005",title:"Catalytic Behavior of Extended π-Conjugation in the Kinetics of Sensitizer-Mediator Interaction",slug:"catalytic-behavior-of-extended-conjugation-in-the-kinetics-of-sensitizer-mediator-interaction",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106511",abstract:"This chapter discusses the catalytic effect of extended π-conjugation on the electron transfer process between ferricyphen-ferrocyanide and ferricypyr-ferrocyanide in an aqueous medium. Ferricyphen and ferricypyr may be feasible options for the sensitizer in dye-sensitized solar cells due to their high reduction potential, stability, capability as an outer-sphere oxidant, and photosensitivity. Meanwhile, ferrocyanide could be used as a mediator in DSSCs instead of iodide to avoid iodate production and achieve a similar reduction potential and stability. This chapter compared the ability of competent putative sensitizers to oxidize the likely mediator in water. In contrast to the 2,2′-dipyridyl chelate, the extended π-conjugation in 1,10-phenanthroline accelerated the redox process by increasing the electron affinity of ferricyphen as compared to ferricypyr. The reactions had the same kinetics but different rate constants, indicating that the ferricyphen-ferrocyanide reaction was several times faster than the ferricypyr-ferrocyanide reaction, revealing and confirming the catalytic influence of extended π-conjugation on the redox process.",book:{id:"11217",title:"Recent Advances in Chemical Kinetics",coverURL:"https://cdn.intechopen.com/books/images_new/11217.jpg"},signatures:"Rozina Khattak"},{id:"83004",title:"Pyridine Heterocycles in the Therapy of Oncological Diseases",slug:"pyridine-heterocycles-in-the-therapy-of-oncological-diseases",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106406",abstract:"Oncological diseases pose a major challenge for modern medicine. Heterocyclic compounds play a vital role in modern medical and pharmaceutical science as most medicinal substances incorporate them. Nitrogen-containing heterocycles serve as the basis of numerous drugs and, therefore, are deeply involved in the design and synthesis of promising new therapeutic agents. Pyridine or pyrimidine scaffolds, with a number of substituents attached, comprise a large portion of FDA-approved drugs. They are chemically stable in the human body, manifest an affinity for DNA via hydrogen bonding, and present an opportunity for the development of novel anticancer agents. A large number of pyridine-based molecules are synthesized and tested for anticancer activity each year. The present chapter aims to introduce the most current synthetic approaches, published in scientific literature, and would also elaborate on structure-activity relationships described therein.",book:{id:"11562",title:"Chemistry with Pyridine Derivatives",coverURL:"https://cdn.intechopen.com/books/images_new/11562.jpg"},signatures:"Lozan T. Todorov and Irena P. Kostova"},{id:"82969",title:"Utilizing Photocatalysts in Reducing Moisture Absorption in Composites of Natural Fibers",slug:"utilizing-photocatalysts-in-reducing-moisture-absorption-in-composites-of-natural-fibers",totalDownloads:1,totalDimensionsCites:0,doi:"10.5772/intechopen.106543",abstract:"Due to growing environmental consciousness and the depletion of oil supplies, numerous efforts have been made to replace synthetic fibers in fiber-reinforced composites with natural fibers (NFr). The low cost and abundance of NFr and its biodegradability and low density have encouraged researchers worldwide to study their potential applications in several industrial sectors. However, NFr has several disadvantages: excessive moisture absorption and subsequent swelling and degradation, low chemical and fire resistance, and insufficient interfacial interactions with polymers. Consequently, there is great interest in modifying the surface of NFr using a variety of methods. This chapter presents an overview of the NFr, its characterization, the problems associated with adding NFr to polymer composites. This literature survey suggests an in-depth review of photocatalysis by utilizing photocatalysts nanoparticle (PHNPs) aimed at increasing the hydrophobicity and interfacial bonding between the NFr and the matrix Using a photo-induced oxidation mechanism to disassemble water molecules, pollutants, and bacteria in a wet environment. Additionally, we reviewed the effects of these PHNPs on the moisture absorption, mechanical characteristics, and dimensional stability of NFr composites. As a result, this review article may make a valuable contribution to researchers interested in coating and treating NFr to further enhance their surface characteristics.",book:{id:"11559",title:"Photocatalysts - New Perspectives",coverURL:"https://cdn.intechopen.com/books/images_new/11559.jpg"},signatures:"Mohammed Mohammed and Rozyanty Rahman"},{id:"82853",title:"Revealing Retention Mechanisms in Liquid Chromatography: QSRR Approach",slug:"revealing-retention-mechanisms-in-liquid-chromatography-qsrr-approach",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.106245",abstract:"One-factor-at-a-time experimentation was used for a long time as gold-standard optimization for liquid chromatographic (LC) method development. This approach has two downsides as it requires a needlessly great number of experimental runs and it is unable to identify possible factor interactions. At the end of the last century, however, this problem could be solved with the introduction of new chemometric strategies. This chapter aims at presenting quantitative structure–retention relationship (QSRR) models with structuring possibilities, from the point of feature selection through various machine learning algorithms that can be used in model building, for internal and external validation of the proposed models. The presented strategies of QSRR model can be a good starting point for analysts to use and adopt them as a good practice for their applications. QSRR models can be used in predicting the retention behavior of compounds, to point out the molecular features governing the retention, and consequently to gain insight into the retention mechanisms. In terms of these applications, special attention was drawn to modified chromatographic systems, characterized by mobile or stationary phase modifications. Although chromatographic methods are applied in a wide variety of fields, the greatest attention has been devoted to the analysis of pharmaceuticals.",book:{id:"11557",title:"Chemometrics - Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11557.jpg"},signatures:"Jovana Krmar, Bojana Svrkota, Nevena Đajić, Jevrem Stojanović, Ana Protić and Biljana Otašević"},{id:"82796",title:"A Revisit of the Underlying Fundamentals in the Laser Emission from BODIPYs",slug:"a-revisit-of-the-underlying-fundamentals-in-the-laser-emission-from-bodipys",totalDownloads:13,totalDimensionsCites:0,doi:"10.5772/intechopen.106334",abstract:"This chapter aims to provide a comprehensive assessment of the laser performance of commercially available laser dyes based on the boron-dipyrromethene (BODIPY) chromophore in a liquid state, as well as to remark the main underlying photophysical signatures triggering such photonic behavior. First, we describe their light absorption and fluorescence properties in solution. This spectroscopic study is supplemented with quantum mechanics calculations and electrochemical measurements. Afterward, the dyes are tested as active media of tunable lasers under transversal pumping. The recorded laser efficiencies and photostabilities are correlated with the registered photophysical properties identifying the main structural guidelines and photonic parameters, which rule the laser bands’ position, intensity, and stability. As a result, we provide a comparative dataset of the laser performance, not available hitherto. Besides, the unraveling of the complex molecular structure-photophysics-laser relationship should help in the rational design of new tunable dye lasers with an improved photonic response along the entire visible region and reaching eventually the near infrared.",book:{id:"12081",title:"Dyes and Pigments - Insights and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/12081.jpg"},signatures:"Alaitz Peñafiel, Ainhoa Oliden-Sánchez, Edurne Avellanal-Zaballa, Leire Gartzia-Rivero, Rebeca Sola-Llano and Jorge Bañuelos"},{id:"82706",title:"Applications of Near-Infrared Spectroscopy (NIRS) in Fish Value Chain",slug:"applications-of-near-infrared-spectroscopy-nirs-in-fish-value-chain",totalDownloads:18,totalDimensionsCites:0,doi:"10.5772/intechopen.105736",abstract:"Near-infrared spectroscopy (NIRS) has undergone a significant evolution in the last years due to the numerous scientific studies that revealed its potential for industrial applications, attracting a growing interest in the food sector. Furthermore, new advances have allowed the reduction in size and cost of the NIR devices, making them appropriate for on-site determinations. The complex structure of the fish value chain, combined to its high market value, makes this sector particularly vulnerable to fraud and adulteration practices. Also, the perishable nature of fish and fish products, as well as the lack of traceability, arises the urgent need for a fast, reliable and portable tool capable of precisely characterizing the quality and authenticity of the product while also ensuring its safety. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. 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He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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(Eng.) in Telematics from the Universidad de Colima, Mexico. He obtained both his M.Sc. and Ph.D. from the University of Liverpool, England, in the field of Intelligent Systems. He is a full professor at the Universidad Autonoma de Queretaro, Mexico, and a member of the National System of Researchers (SNI) since 2009. Dr. Aceves Fernandez has published more than 80 research papers as well as a number of book chapters and congress papers. He has contributed in more than 20 funded research projects, both academic and industrial, in the area of artificial intelligence, ranging from environmental, biomedical, automotive, aviation, consumer, and robotics to other applications. He is also a honorary president at the National Association of Embedded Systems (AMESE), a senior member of the IEEE, and a board member of many institutions. His research interests include intelligent and embedded systems.",institutionString:"Universidad Autonoma de Queretaro",institution:{name:"Autonomous University of Queretaro",institutionURL:null,country:{name:"Mexico"}}}]},{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and Applications",editors:[{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",institutionURL:null,country:{name:"Spain"}}}]},{type:"book",id:"7656",title:"Fuzzy Logic",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7656.jpg",slug:"fuzzy-logic",publishedDate:"February 5th 2020",editedByType:"Edited by",bookSignature:"Constantin Volosencu",hash:"54f092d4ffe0abf5e4172a80025019bc",volumeInSeries:3,fullTitle:"Fuzzy Logic",editors:[{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. 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After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. Dr. Satué is a scientific reviewer for various prestigious international journals such as Animals, American Journal of Obstetrics and Gynecology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology, among others. Since 2014 she has been responsible for the Clinical Analysis Laboratory of the CEU-Cardenal Herrera University Veterinary Clinical Hospital.",institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"439435",title:"Dr.",name:"Feda S.",middleName:null,surname:"Aljaser",slug:"feda-s.-aljaser",fullName:"Feda S. Aljaser",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"428600",title:"MSc.",name:"Adriana",middleName:null,surname:"García-Alarcón",slug:"adriana-garcia-alarcon",fullName:"Adriana García-Alarcón",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428599",title:"MSc.",name:"Gabino",middleName:null,surname:"De La Rosa-Cruz",slug:"gabino-de-la-rosa-cruz",fullName:"Gabino De La Rosa-Cruz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"428601",title:"MSc.",name:"Juan Carlos",middleName:null,surname:"Campuzano-Caballero",slug:"juan-carlos-campuzano-caballero",fullName:"Juan Carlos Campuzano-Caballero",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}}]}},subseries:{item:{id:"7",type:"subseries",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11403,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. 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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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