Risk Factors for Osteoporosis
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"5156",leadTitle:null,fullTitle:"Trending Topics in Multiple Sclerosis",title:"Trending Topics in Multiple Sclerosis",subtitle:null,reviewType:"peer-reviewed",abstract:"Multiple sclerosis (MS) is a chronic inflammatory disease characterized by progressive demyelination and neurodegeneration of the central nervous system (CNS), constituting the most common demyelinating disease of the CNS in humans. Although intensive research over many decades has unveiled many pathophysiological mechanisms in the development of MS, the cause is still unknown. Nevertheless, it does seem clear that genetic susceptibility and environmental factors play crucial roles. Trending Topics in Multiple Sclerosis is a book that provides an insight into some of the main problems currently debated in this area of research, focusing on topics that deal with genetic and environmental risk factors, pathophysiological mechanisms, neurocognitive findings, and neuroprotective strategies.",isbn:"978-953-51-2657-7",printIsbn:"978-953-51-2656-0",pdfIsbn:"978-953-51-7310-6",doi:"10.5772/61417",price:139,priceEur:155,priceUsd:179,slug:"trending-topics-in-multiple-sclerosis",numberOfPages:338,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"d45419fbcebc3e77a226b73a87ad441b",bookSignature:"Alina Gonzalez-Quevedo",publishedDate:"September 8th 2016",coverURL:"https://cdn.intechopen.com/books/images_new/5156.jpg",numberOfDownloads:22485,numberOfWosCitations:12,numberOfCrossrefCitations:13,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:46,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:71,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 1st 2015",dateEndSecondStepPublish:"October 22nd 2015",dateEndThirdStepPublish:"January 26th 2016",dateEndFourthStepPublish:"April 25th 2016",dateEndFifthStepPublish:"July 6th 2016",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"112886",title:"Dr.",name:"Alina",middleName:null,surname:"Gonzalez-Quevedo",slug:"alina-gonzalez-quevedo",fullName:"Alina Gonzalez-Quevedo",profilePictureURL:"https://mts.intechopen.com/storage/users/112886/images/3145_n.jpg",biography:"Alina González-Quevedo graduated from medical school at the University of Havana in 1972 with specialization in Clinical Biochemistry. Since 1977, she is a full-time professor of Biochemistry at the Medical University of Havana and senior researcher at the Institute of Neurology and Neurosurgery, where she occupied the positions of Head of the Department of Neurochemistry (1977–2009) and Assistant Director of Research (1995–2010). Her doctoral thesis engaged in the pathophysiological mechanisms of Cuban epidemic optic neuropathy in collaboration with the Venezuelan Institute for Scientific Research (1997–2002). She has also worked in other research areas such as brain barrier systems, demyelinating diseases, blood and CSF biomarkers for brain damage in essential hypertension and stroke and has published more than 100 scientific papers in peer-reviewed journals.",institutionString:null,position:"Investigadora y Profesora Titular",outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1056",title:"Neurology",slug:"neurology"}],chapters:[{id:"50808",title:"Genetic and Biochemical Factors Related to the Risk and Disability Progression in Multiple Sclerosis",doi:"10.5772/63468",slug:"genetic-and-biochemical-factors-related-to-the-risk-and-disability-progression-in-multiple-sclerosis",totalDownloads:1555,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Sclerosis multiplex (multiple sclerosis, MS) is a chronic autoimmune inflammatory disease of the central nervous system. The immune regulatory defects lead to the process of inflammation and neurodegenerationthat results in the deterioration of neurological functions. It is still unclear as to why MS is so devastating and rapidly progressive in one patient and less so in another. It is known that the etiopathogenesis of MS is very complex, and many factors can be involved in the risk and character of the disease and its progression. In this chapter, we discuss the general molecular and cellular mechanisms of action of genetic and biochemical factors that are related to immune system regulation and thus can be connected to the individually varying risk and disability progression of MS. We found that gene variants of the gene polymorphism rs6897932 in interleukin 7 receptor α chain gene rs10735810 in vitamin D receptor gene and HLA-DR and HLA-DQ genes as well as the serum level of vitamin D are associated with MS risk or disability progression in Central European Slovak population.",signatures:"Daniel Čierny, Jozef Michalik, Ema Kantorová, Egon Kurča and Ján\nLehotský",downloadPdfUrl:"/chapter/pdf-download/50808",previewPdfUrl:"/chapter/pdf-preview/50808",authors:[{id:"90214",title:"Prof.",name:"Ján",surname:"Lehotský",slug:"jan-lehotsky",fullName:"Ján Lehotský"},{id:"179418",title:"Dr.",name:"Daniel",surname:"Cierny",slug:"daniel-cierny",fullName:"Daniel Cierny"},{id:"184882",title:"Prof.",name:"Egon",surname:"Kurča",slug:"egon-kurca",fullName:"Egon Kurča"},{id:"184883",title:"Dr.",name:"Jozef",surname:"Michalik",slug:"jozef-michalik",fullName:"Jozef Michalik"}],corrections:null},{id:"50444",title:"The Gateway Reflex, a Novel Neuro‐immune Interaction, is Critical for the Development of Mouse Multiple Sclerosis (MS) Models",doi:"10.5772/62938",slug:"the-gateway-reflex-a-novel-neuro-immune-interaction-is-critical-for-the-development-of-mouse-multipl",totalDownloads:1507,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The central nervous system (CNS) is an immune‐privileged tissue protected by the brain–blood barrier (BBB), which limits the absorption of substances and cells from blood flow. In the case of inflammatory diseases in the CNS, such as multiple sclerosis (MS), however, autoreactive T cells that attack brain autoantigens, including myelin proteins, circumvent the BBB. Despite the wide distribution of brain autoantigens, demyelination often occurs as discrete foci. This fact suggests that there might be a certain cue that guides autoreactive T cells to particular site(s) in the CNS. In other words, there exists a mechanism that facilitates a site‐specific accumulation of autoreactive T cells in the CNS. Using a murine model of MS, experimental autoimmune encephalomyelitis (EAE), we identified dorsal vessels of the fifth lumbar (L5) spinal cord as the initial entry site of immune cells. The formation of a gateway for immune cells is defined by local neural stimulations. For example, neural stimulation by gravity creates this gateway by increasing the expression of chemokines that attract autoreactive T cells. Regional neural activation by the other stimuli, such as electric pulses or pain sensation, also induces gateway formation, but at different blood vessels via chemokine expression. These neuro‐immune interactions are examples of the gateway reflex and are extensively reviewed in this chapter.",signatures:"Daisuke Kamimura, Yasunobu Arima, Andrea Stofkova, Naoki\nNishikawa, Kotaro Higuchi, Takuto Ohki and Masaaki Murakami",downloadPdfUrl:"/chapter/pdf-download/50444",previewPdfUrl:"/chapter/pdf-preview/50444",authors:[{id:"178981",title:"Prof.",name:"Masaaki",surname:"Murakami",slug:"masaaki-murakami",fullName:"Masaaki Murakami"},{id:"179235",title:"Dr.",name:"Daisuke",surname:"Kamimura",slug:"daisuke-kamimura",fullName:"Daisuke Kamimura"},{id:"179236",title:"Dr.",name:"Yasunobu",surname:"Arima",slug:"yasunobu-arima",fullName:"Yasunobu Arima"},{id:"179237",title:"Dr.",name:"Andrea",surname:"Stofkova",slug:"andrea-stofkova",fullName:"Andrea Stofkova"},{id:"179239",title:"Dr.",name:"Naoki",surname:"Nishikawa",slug:"naoki-nishikawa",fullName:"Naoki Nishikawa"},{id:"179240",title:"Mr.",name:"Kotaro",surname:"Higuchi",slug:"kotaro-higuchi",fullName:"Kotaro Higuchi"},{id:"179241",title:"Mr.",name:"Takuto",surname:"Ohki",slug:"takuto-ohki",fullName:"Takuto Ohki"}],corrections:null},{id:"50603",title:"Intrathecal Immunoglobulin Synthesis in MS—A Complete Reappraisal",doi:"10.5772/63201",slug:"intrathecal-immunoglobulin-synthesis-in-ms-a-complete-reappraisal",totalDownloads:3011,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Multiple sclerosis (MS) is characterized by the intrathecal synthesis (ITS) of immunoglobulins (Igs), which, although nonspecific, is the strongest biological marker. Since no specific target has been elucidated, this synthesis is considered to be disease‐irrelevant. We demonstrate that this synthesis provides pertinent information about the pathophysiological processes involved.\nQuantification of ITS is based on an approximation intrinsically underestimating its level and it remains constant in MS, albeit sometimes at a low level. B‐cell maturation seems to be initiated within the cervical lymph nodes and B‐cells traffic on both sides of the blood‐brain barrier by rounds of bidirectional traffic. During this process, they undergo somatic hypermutation, which is the hallmark of antigen‐driven antibody maturation, suggesting that most of the ITS is probably directed against as yet unknown targets. Alternatively, examining”non‐disease‐relevant” ITS in the light of meningeal tertiary lymphoid organs provides new insights into the pathophysiology of MS. Although no specific target has yet been identified in MS, recent developments in the search for targeted antigens point to non‐conventional antigens (posttranslationally modified proteins or oxidized products) of which a few are promising for future research.",signatures:"Mickael Bonnan",downloadPdfUrl:"/chapter/pdf-download/50603",previewPdfUrl:"/chapter/pdf-preview/50603",authors:[{id:"110897",title:"Dr",name:"Mickael",surname:"Bonnan",slug:"mickael-bonnan",fullName:"Mickael Bonnan"}],corrections:null},{id:"51342",title:"Autoimmune Processes in Multiple Sclerosis: Production of Harmful Catalytic Antibodies Associated with Significant Changes in the Hematopoietic Stem Cell Differentiation and Proliferation",doi:"10.5772/63824",slug:"autoimmune-processes-in-multiple-sclerosis-production-of-harmful-catalytic-antibodies-associated-wit",totalDownloads:1377,totalCrossrefCites:6,totalDimensionsCites:32,hasAltmetrics:0,abstract:"Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. MS pathogenesis is not clear. Destruction of myelin by inflammation caused by autoimmune reactions has been proposed. Interestingly, healthy humans usually do not develop abzymes (Abzs). It was shown that DNase and MBP-hydrolyzing Abzs are easily detectable at the beginning of autoimmune diseases (ADs) including MS, when concentrations of antibodies to autoantigens are not yet significantly increased and correspond to levels in healthy donors. In addition, the relative enzymatic activity of antibodies from cerebrospinal fluid (CSF) is ~50-fold higher than that from the sera of the same MS patients. Experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, a model mimicking relevant aspects of human MS was used. During development of spontaneous and MOG35-55-induced EAE in C57BL/6 mice, a specific reorganization of the immune system of mice was observed. It leads to a condition which was associated with the generation of catalytically active IgGs-hydrolyzing DNA, myelin basic protein (MBP), and MOG. Production of Abzs was associated with increased proteinuria, leading changes in differentiation of mice bone marrow hematopoietic stem cells (HSCs) and an increase in proliferation of lymphocytes in bone marrow, spleen, and thymus as well as a significant suppression of cell apoptosis in these organs. Treatment of control non-autoimmune CBA mice with MOG led to the different differentiation and proliferation of HSCs comparing with EAE C57BL/6 mice. The treatment of EAE mice with cuprizone inducing demyelination lead to a significant decrease in the size of the brain corpus callosum, but do not significantly change the differentiation profile of HSCs differentiation when compared with untreated mice. It indicates that cuprizone treatment is associated with demyelination, but not autoimmune reactivity. The possible differences in immune system reorganizations during preclinical phases of the disease, acute and late EAE, leading to production of different autoantibodies and Abzs as well other changes are discussed.",signatures:"Georgy A. Nevinsky",downloadPdfUrl:"/chapter/pdf-download/51342",previewPdfUrl:"/chapter/pdf-preview/51342",authors:[{id:"47119",title:"Dr.",name:"Georgy",surname:"Nevinsky",slug:"georgy-nevinsky",fullName:"Georgy Nevinsky"}],corrections:null},{id:"51950",title:"Multiple Sclerosis and Its Relationship with Oxidative Stress, Glutathione Redox System, ATPase System, and Membrane Fluidity",doi:"10.5772/64737",slug:"multiple-sclerosis-and-its-relationship-with-oxidative-stress-glutathione-redox-system-atpase-system",totalDownloads:1860,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) with a focus on inflammation, demyelination, and damage to axons leading to neurological deficits. MS pathology is associated with excessive reactive oxygen species (ROS) and generation of reactive nitrogen species (RNS), causing oxidative/nitrosative stress. Deregulation of glutathione homeostasis and alterations in glutathione‐dependent enzymes are implicated in MS. Reactive oxygen species enhance both monocyte adhesion and migration across brain endothelial cells. In addition, ROS can activate the expression of the nuclear transcription factor‐kappa, which upregulates the expression of many genes involved in MS, such as tumor necrosis factor‐α and nitric oxide synthase, among others, leading to mitochondrial dysfunction and energy deficits that result in mitochondrial and cellular calcium overload. Loss of mitochondrial membrane potential can increase the release of cytochrome c, one pathway that leads to neuronal apoptosis. Clinical studies suggest that omega‐3 long‐chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have anti‐inflammatory, antioxidant, and neuroprotective effects in MS and animal models of MS. Here, we review the relationship of oxidative stress, the glutathione redox system, the ATPase system, and membrane fluidity with the development of MS. In addition, we describe the main findings of a clinical trial conducted with relapsing‐remitting MS patients who received a diet supplemented with 4 g/day of fish oil or olive oil. The effects of PUFAs supplementation on the parameters indicated above are analyzed in this work.",signatures:"Genaro G. Ortiz, Fermín P. Pacheco‐Moisés, Erandis D. Torres‐\nSánchez, Tanya E. Sorto‐Gómez, Mario Mireles‐Ramírez, Alfredo\nLeón‐Gil, Héctor González‐Usigli, Luis J. Flores‐Alvarado, Erika D.\nGonzález‐Renovato, Angelica L. Sánchez‐López, Margarita Cid‐\nHernández and Irma E. Velázquez‐Brizuela",downloadPdfUrl:"/chapter/pdf-download/51950",previewPdfUrl:"/chapter/pdf-preview/51950",authors:[{id:"26109",title:"Dr.",name:"Genaro",surname:"Ortiz",slug:"genaro-ortiz",fullName:"Genaro Ortiz"},{id:"166323",title:"Dr.",name:"Fermín",surname:"Pacheco-Moisés",slug:"fermin-pacheco-moises",fullName:"Fermín Pacheco-Moisés"},{id:"166328",title:"Dr.",name:"Erandis D",surname:"Tórres-Sánchez",slug:"erandis-d-torres-sanchez",fullName:"Erandis D Tórres-Sánchez"},{id:"173290",title:"MSc.",name:"Erica Daniela",surname:"González-Renovato",slug:"erica-daniela-gonzalez-renovato",fullName:"Erica Daniela González-Renovato"},{id:"173292",title:"Ph.D.",name:"Angélica L.",surname:"Sánchez López.",slug:"angelica-l.-sanchez-lopez.",fullName:"Angélica L. Sánchez López."},{id:"173295",title:"Dr.",name:"Mario",surname:"Mireles-Ramírez",slug:"mario-mireles-ramirez",fullName:"Mario Mireles-Ramírez"},{id:"173377",title:"Dr.",name:"J Luis",surname:"Flores-Alvarado",slug:"j-luis-flores-alvarado",fullName:"J Luis Flores-Alvarado"},{id:"178191",title:"Dr.",name:"Héctor",surname:"González-Usigli",slug:"hector-gonzalez-usigli",fullName:"Héctor González-Usigli"},{id:"179800",title:"Dr.",name:"Alfredo",surname:"León-Gil",slug:"alfredo-leon-gil",fullName:"Alfredo León-Gil"},{id:"179801",title:"Dr.",name:"Tania E",surname:"Gómez-Sorto",slug:"tania-e-gomez-sorto",fullName:"Tania E Gómez-Sorto"},{id:"179802",title:"MSc.",name:"Margarita",surname:"Cid-Hernández",slug:"margarita-cid-hernandez",fullName:"Margarita Cid-Hernández"}],corrections:null},{id:"51025",title:"Pediatric Multiple Sclerosis",doi:"10.5772/63919",slug:"pediatric-multiple-sclerosis",totalDownloads:1558,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disorder of the central nervous system. Although pediatric and adult-onset MS have similar neurologic symptoms, there are some differences from adults in radiologic findings, cognitive features, clinical course, and diagnostic criteria of pediatric MS. Diagnostic criteria and radiologic features of pediatric MS have been defined in recent years. There are no large, randomized, controlled therapeutic trials in pediatric MS. In this chapter, clinical characteristics, diagnostic criteria, laboratory findings, differential diagnosis, and treatment of pediatric MS are summarized.",signatures:"Ozgul Ekmekci",downloadPdfUrl:"/chapter/pdf-download/51025",previewPdfUrl:"/chapter/pdf-preview/51025",authors:[{id:"179039",title:"Prof.",name:"Ozgul",surname:"Ekmekci",slug:"ozgul-ekmekci",fullName:"Ozgul Ekmekci"}],corrections:null},{id:"51151",title:"Association Between Multiple Sclerosis Risk and Human Immunodeficiency Virus Infection: Insights and Challenges",doi:"10.5772/63828",slug:"association-between-multiple-sclerosis-risk-and-human-immunodeficiency-virus-infection-insights-and-",totalDownloads:1976,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Multiple sclerosis (MS) is a convoluted autoimmune and inflammatory disease of the central nervous system (CNS) in which the protective myelin sheath is eroded and the underlying nerve fibers are damaged. There is no conclusive knowledge on the role played by different etiological factors in its development, and studies have shown that it primarily results due to complex interactions between the genetic, geographic and infectious components. Among the risk factors reported to have a possible role in MS development, retroviruses also appear to influence it. Studies suggest human immunodeficiency virus (HIV) infection to be inversely related to MS risk, but to date, the association between the two remains enigmatic. This protective inverse association has become an area of active research and the most plausible explanations for this may be immune suppression and/or antiretroviral medications. The purpose of writing this chapter is to provide background information on the unfathomable relationship between HIV infection and the risk of developing MS while at the same time providing description of the insights garnered from recent studies. While highlighting the application of ART (antiretroviral therapy) as budding future alternative for MS management, this chapter provides momentum for further studies.",signatures:"Ehtishamul Haq, Insha Zahoor and Mushfiquddin Khan",downloadPdfUrl:"/chapter/pdf-download/51151",previewPdfUrl:"/chapter/pdf-preview/51151",authors:[{id:"181077",title:"Dr.",name:"Ehtishamul",surname:"Haq",slug:"ehtishamul-haq",fullName:"Ehtishamul Haq"},{id:"185233",title:"Dr.",name:"Insha",surname:"Zahoor",slug:"insha-zahoor",fullName:"Insha Zahoor"},{id:"185234",title:"Dr.",name:"Mushfiquddin",surname:"Khan",slug:"mushfiquddin-khan",fullName:"Mushfiquddin Khan"}],corrections:null},{id:"51341",title:"The Role of Over-Nutrition and Obesity in Multiple Sclerosis",doi:"10.5772/63992",slug:"the-role-of-over-nutrition-and-obesity-in-multiple-sclerosis",totalDownloads:1436,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In countries with high standard of living, lowered risk of infectious diseases is parallel to increased incidence of autoimmune diseases. One of the autoimmune disorders, multiple sclerosis, affects genetically susceptible individuals. Genetic susceptibility is supposed to interact with lifestyle and environmental factors in developing autoimmunity in MS. From this point of view, epigenetics provides the bridge between the external environment and the internal genetic system. In MS, environmental burden can modulate gene expression by epigenetic modification of chromatin components, microRNAs or by subtle changes in DNA methylation. Our paper focuses on describing the epigenetic mechanisms linking environmental factors with pathogenesis of multiple sclerosis. We summarise current knowledge about the role of over-nutrition and obesity as epigenetic factors in multiple sclerosis.",signatures:"Ema Kantorová, Egon Kurča, Daniel Čierny, Dušan Dobrota and\nŠtefan Sivák",downloadPdfUrl:"/chapter/pdf-download/51341",previewPdfUrl:"/chapter/pdf-preview/51341",authors:[{id:"179418",title:"Dr.",name:"Daniel",surname:"Cierny",slug:"daniel-cierny",fullName:"Daniel Cierny"},{id:"178642",title:"Dr.",name:"Ema",surname:"Kantorova",slug:"ema-kantorova",fullName:"Ema Kantorova"},{id:"184896",title:"Prof.",name:"Egon",surname:"Kurča",slug:"egon-kurca",fullName:"Egon Kurča"},{id:"184897",title:"Prof.",name:"Dušan",surname:"Dobrota",slug:"dusan-dobrota",fullName:"Dušan Dobrota"}],corrections:null},{id:"51048",title:"Cognitive Deficits and Neuropsychological Assessment in Multiple Sclerosis",doi:"10.5772/63968",slug:"cognitive-deficits-and-neuropsychological-assessment-in-multiple-sclerosis",totalDownloads:1891,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The aim of this chapter was to introduce the contents of neuropsychological assessment in multiple sclerosis, which should include the functional evaluation of cognitive domains, the psychopathology of personality, levels of depression, and the assessment of psychosocial aspects and quality of life with multiple sclerosis. Further, the most commonly used neuropsychological diagnostics are described. The chapter hopes to draw attention to the importance of neuropsychological assessment which should be a part of neurological diagnostics and therapy, including rehabilitation and psychotherapy.",signatures:"Alena Javůrková, Denisa Zimová, Katarína Tomašovičová and\nJaroslava Raudenská",downloadPdfUrl:"/chapter/pdf-download/51048",previewPdfUrl:"/chapter/pdf-preview/51048",authors:[{id:"180038",title:"Dr.",name:"Alena",surname:"Javůrková",slug:"alena-javurkova",fullName:"Alena Javůrková"},{id:"185899",title:"Dr.",name:"Jaroslava",surname:"Raudenská",slug:"jaroslava-raudenska",fullName:"Jaroslava Raudenská"},{id:"185900",title:"Dr.",name:"Denisa",surname:"Zimová",slug:"denisa-zimova",fullName:"Denisa Zimová"},{id:"185902",title:"BSc.",name:"Katarína",surname:"Tomašovičová",slug:"katarina-tomasovicova",fullName:"Katarína Tomašovičová"}],corrections:null},{id:"50652",title:"Social Cognition Impairments in Patients with Multiple Sclerosis and Comparison with Imaging Studies, Disease Duration and Grade of Disability",doi:"10.5772/63465",slug:"social-cognition-impairments-in-patients-with-multiple-sclerosis-and-comparison-with-imaging-studies",totalDownloads:1350,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Cognitive impairments in multiple sclerosis (MS) are heterogeneous and their rate varies between 43% and 70%. A less studied aspect of cognition is social cognition, which is not a uniform theoretical construct. It includes emotion perception, prosody, empathy, theory of mind (ToM) and assessment of mood. In addition to progressive physical disability, social cognitive impairments are a reason for job loss in 24–80% of patients with MS, increased divorce rate, dissolution of partnerships and social communication difficulties.",signatures:"Valentina Ignatova, Lyudmila Todorova and Jivko Surchev",downloadPdfUrl:"/chapter/pdf-download/50652",previewPdfUrl:"/chapter/pdf-preview/50652",authors:[{id:"178891",title:"Dr.",name:"Valentina",surname:"Ignatova",slug:"valentina-ignatova",fullName:"Valentina Ignatova"},{id:"179772",title:"Prof.",name:"Lyudmila",surname:"Todorova",slug:"lyudmila-todorova",fullName:"Lyudmila Todorova"},{id:"179773",title:"Dr.",name:"Jivko",surname:"Surchev",slug:"jivko-surchev",fullName:"Jivko Surchev"}],corrections:null},{id:"50653",title:"Sex Hormones and Multiple Sclerosis",doi:"10.5772/63630",slug:"sex-hormones-and-multiple-sclerosis",totalDownloads:1569,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Experimental and clinical data about the influence of sex hormones on the course of multiple sclerosis (MS) grow rapidly during the past two decades. Estrogens, progesterone, and androgens have been shown to ameliorate experimental autoimmune encephalomyelitis (EAE) in animals, and pregnancy in women is associated with a dramatic reduction in disease activity. Immunomodulatory and neuroprotective properties of sex hormones are the most probable underlying mechanisms, creating a background for testing similar hormonal treatments in humans. Several pilot studies in this field present promising results, but larger trials are necessary to identify the adverse events and to estimate precisely the place of sex steroids in multiple sclerosis therapeutic strategies.",signatures:"Anastasiya G. Trenova",downloadPdfUrl:"/chapter/pdf-download/50653",previewPdfUrl:"/chapter/pdf-preview/50653",authors:[{id:"179041",title:"Dr.",name:"Anastasiya",surname:"Trenova",slug:"anastasiya-trenova",fullName:"Anastasiya Trenova"}],corrections:null},{id:"51080",title:"Neuroprotection and Recovery in Multiple Sclerosis",doi:"10.5772/63829",slug:"neuroprotection-and-recovery-in-multiple-sclerosis",totalDownloads:1583,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Multiple sclerosis is a complex and heterogeneous immune-mediated disease that results in the progressive accumulation of mental and physical symptoms. Currently approved disease-modifying drugs (DMDs) are immunomodulatory or immunosuppressive, but these drugs have little effect on disease progression. In addition to studies that have directly targeted inflammation and immune responses, a large number of studies, most of them experimental, have investigated neuroprotective therapies and remyelination strategies. However, to date, attempts to provide neuroprotection have failed not just in multiple sclerosis but in neurological disorders in general; this situation has emphasized the need to revise the old paradigm of a “magic bullet” with a single mechanism of action. Remyelination strategies involve either promoting endogenous remyelination or replacing lost myelinating cells through exogenous sources. However, several puzzle pieces regarding the physiology of remyelination remain unknown, including feasible treatment monitoring methods, the selection of patients, and the optimal time of treatment initiation. This chapter will describe the direct and indirect neuroprotective effects of DMDs, as suggested by basic research studies and confirmed by clinical studies in some cases. Current knowledge of potential neuroprotective therapies and remyelination strategies is also reviewed.",signatures:"Dafin F. Muresanu, Maria Balea, Olivia Rosu, Anca Buzoianu and\nDana Slavoaca",downloadPdfUrl:"/chapter/pdf-download/51080",previewPdfUrl:"/chapter/pdf-preview/51080",authors:[{id:"64889",title:"Prof.",name:"Dafin F.",surname:"Muresanu",slug:"dafin-f.-muresanu",fullName:"Dafin F. Muresanu"}],corrections:null},{id:"50910",title:"Neuroprotection: A New Therapeutic Approach of Relapsing Remitting Multiple Sclerosis",doi:"10.5772/63730",slug:"neuroprotection-a-new-therapeutic-approach-of-relapsing-remitting-multiple-sclerosis",totalDownloads:1813,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Neurodegenerative changes occurring early from primary acute immune-mediated inflammation support the hypothesis that multiple sclerosis (MS) is a complex disease. Axonal loss progresses with the disease course and represents the principal driver of disability. In this context, the pursuit of neuroprotective therapies in multiple sclerosis provides new valid alternatives that could significantly impact on disease progression and neurodegenerative changes, including the promotion of restoration of myelin sheaths through the remyelination process. This chapter reviews promising drugs with proposed neuroprotective or neuroregenerative effects that are currently approved or in clinical trials for the treatment of multiple sclerosis. 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Osteoporosis is a systemic disease that is characterized by low bone mass and deterioration of the microarchitecture of bone, resulting in an increased risk of fracture in postmenopausal women and men over 50 years old. Several factors have been identified that contribute to the risk of osteoporosis, and oxidative stress has now emerged as one of the most important life style risk factor associated with loss of bone mass. Phytochemicals as antioxidants have been shown to counteract the deleterious effects of oxidative stress in the risk of osteoporosis. This review will include an overview on osteoporosis, the deleterious effects of oxidative stress and the beneficial effects of phytochemical antioxidants, with emphasis on the results of our clinical studies on the phytochemical lycopene and polyphenols present in nutritional supplements.
Osteoporosis is a metabolic bone disease known as “the silent thief” because the gradual loss of bone associated with this disease usually occurs over the years, and there are usually no noticeable symptoms until the bones are so fragile that a fracture occurs [1]. Osteoporosis is “a major public health threat” that is projected to results to 8.1 million fractures (78 % women, 22 % men) during the period between 2010 and 2050 [2]. Approximately 1 in 2 women and 1 in 5 men older than 50 years will eventually experience osteoporotic fractures [3]. The condition costs our healthcare system $18 billion per year [4]. Newer findings on all aspects of osteoporosis have increased exponentially. The more importantly ones are discovering an ever increasing number of risk factors including oxidative stress, opening up new knowledge on the involvement of the bone forming cells osteoblasts and the bone resorbing cells osteoclasts in the development of osteoporosis, the introduction and improvement of more sensitive diagnostic instruments, and finding new drugs and the nutritional alternatives for the prevention and treatment of osteoporosis. Advances in the knowledge on osteoporosis is not without pitfalls. Hormone Replacement Therapy (HRT), once a first line of treatment for osteoporosis has been discontinued due to side effects [5]. It is becoming more evident that the drugs known as bisphosphonates, although effective in stopping the resoption of bone and preventing osteoporosis in women, are associated with a number of side effects [6, 7]. Because of this, a number of women are now resorting to other modes of treatment, including that from natural food components. Our laboratory has carried out studies on the use of phytochemical antioxidants such as lycopene and polyphenols present in nutritional supplements as possible alternatives and/or complementary to drugs in the treatment and prevention of osteoporosis. This chapter will include an overview on osteoporosis, oxidative stress as a risk factor in the development of osteoporosis and a review of studies on the use of antioxidants in counteracting oxidative stress in the prevention of osteoporosis. These topics should put our research in perspective and offer a rationale to our study approaches. Finally we will highlight our pioneering clinical studies on the lipid-soluble phytochemical antioxidant lycopene and the water-soluble antioxidant polyphenols present in a nutritional supplement in the prevention of risk for osteoporosis in postmenopausal women.
Some of the risk factors for osteoporosis [8, 9] are presented in Table 1 [10]. The risk factors that are of interest in our studies are the oxidative stress-generating factors, including nutrition deficiency, low antioxidant status, smoking, alcohol intake, excessive sports activity and caffeine intake.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t||
Race Sex Age Genetics Body size Family History Previous Fractures | \n\t\t\tChronic inactivity | \n\t\t||
\n\t\t\t | Low body weight Low lifetime calcium intake Medication used Oxidative stress-related Factors: | \n\t\t||
\n\t\t\t | \n\t\t\t | Smoking High Alcohol intake Low antioxidant status Nutrition deficiency Excessive sports activity Excessive caffeine intake | \n\t\t
Risk Factors for Osteoporosis
Until 10 years ago, the first line of treatment for women who have gone through menopause and were diagnosed with osteoporosis was hormone replacement therapy (HRT). However, results of the Women’s Health Initiative (WHI) revealed that women taking HRT had higher risks for breast cancer, cardiovascular events, blood clots, cognitive decline, and more [5]. This treatment for osteoporosis has since been discontinued and is prescribed only for a short period of time to alleviate hot flashes in menopausal women [11]. The current treatments which inhibit bone resorption that are approved by the Food and Drug Administration (FDA) include a number of bisphosphonates under specific trademarks [12]. Some are taken daily while others are formulated for weekly, monthly or intermittent oral use [13, 14]. The newer bisphophonates are injectables such as Zoledronate and Ibandronate [14]. Other drugs available include calcitonin; Raloxifene (Evista), the Selective Estrogen Receptor Modulator (SERM) and strontium renalate [15]. Parathyroid hormone, PTH1-34 or teriparatide (Forteo), is the only anabolic agent currently approved for use by the FDA [16, 17]. The new class of osteoporosis drug now approved for use is a human monoclonal antibody (Denosumab) which bind to RANKL, imitating the effects of OPG and acting as an inhibitor of RANKL [18]. Other drugs are still being tested clinically for osteoporotic treatment and prevention [16].
None of the drugs are without side effects. Side effects that emerged in clinical trials include acute phase response with iv treatment or high-dose oral therapy and esophageal irritation with oral administration. Osteonecrosis of the jaw, musculoskeletal complaints, and atypical fractures are some uncommon side effects that have been noted with wide clinical use of bisphosphonate. The number of these events are small, and a clear cause-and-effect relationship between events and bisphosphonate treatment has not been established. Accumulation of Bisphosphonates in the bone create a reservoir leading to continued release from bone for months or years and provide some residual anti-fracture reduction long after treatment is stopped [19]. As a result, there is a recommendation for a drug holiday after 5 –10 yr of treatment with bisphosphonate [7, 19]. The length of the holiday is based on previous duration of treatment, BMD status and fracture risk. Studies with alendronate and risedronate showed that if treatment is stopped after 3–5 yr, there is at least 1–2 yr persisting anti-fracture efficacy. The consensus from expert panels [7] for those who are not on holiday is not to stop the use of drug since the side effects are often rare, and that the benefits outweigh the side effects. In the balance, most individuals who have osteoporosis are much better taking an osteoporosis medication [6].
Diet is now recognized as an important life-style factor in the management of bone health [20]. Given that many nutrients have been identified as being beneficial to bone health [21, 22], there is strong scientific support for the potential benefits of incorporating therapeutic nutritional interventions with contemporary pharmaceutical treatments [23]. As a result of the possible adverse side effects of HRT [5] and the ever increasing reports on the side effects of bisphosphonates that are prescribed for the management of postmenopausal osteoporosis [19], complementary and alternative medicine (CAM) is in demand as an alternative for the prevention and treatment of osteoporosis [24]. CAM is the term for medical practices, services and products that are not a part of standard care. Some of the approaches include exercise, acupuncture, diet, herbs rich in polyphenols and nutritional supplements including calcium, zinc, magnesium boron and other vitamins and minerals [24]. Recent dietary guidelines for the prevention of chronic diseases have recommended an increase in the consumption of fruits and vegetables worldwide [25] that are good sources of dietary antioxidants [26]. The beneficial effects of antioxidants in bone health and osteoporosis are demonstrated epidemiologically and through clinical intervention. As will be reviewed in this chapter, our clinical studies on lycopene treatment and nutritional supplements containing polyphenols and other nutritional components showed positive results on bone health.
Oxidative stress is caused by reactive oxygen species (ROS) which are the main by-products formed in the cells of aerobic organisms that can initiate autocatalytic reactions in such a way that the target molecules get converted into free radicals causing a chain of damage [27]. There is ample evidence to show that oxidative stress induces an increase in the rate of bone loss and is therefore a risk factor for osteoporosis. Epidemiological evidence in humans and studies in animals indicate that aging and the associated increase in reactive oxygen species (ROS) are responsible for bone loss [28]. Oxidative stress is associated with the activity and function of both the osteoblasts and osteoclasts cells, the two major bone cells involved in the pathogenesis of osteoporosis [29, 30].
Under normal physiological conditions, the cells can fight free radical attack or oxidative stress by promoting antioxidant defenses. A number of endogenous defense mechanisms are present in the body, including the metal chelating proteins and the endogenous antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) [31]. Exogenous antioxidants come from dietary sources present in fruits and vegetables containing several phytonutrient antioxidants two of which are the potent antioxidant lipid-soluble lycopene and the water-soluble antioxidant polyphenols [32]. In cases where the exogenous antioxidants or antioxidants from diet fail to prevent oxidative damage, the repair antioxidants come into play which include DNA repair enzymes, protease, lipase, and transferase [33]. When antioxidants loses its fight with oxidative stress, diseases associated with oxidative stress develop, which include cardiovascular disease, cancer, diabetes, neurological diseases and osteoporosis [26].
The role of lycopene in the prevention of human diseases is supported by a number of evidence and previously reviewed [34, 35]. Since then, there have been several epidemiological as well as clinical intervention studies showing the relationship between lycopene intake and the prevention of cancers at other sites, as well as coronary heart disease, diabetes, hypertension, macular degenerative disease, neurodegenerative disease and male infertility [26]. The role of lycopene in bone health has so far been based on its potent antioxidant properties, the well-known role of oxidative stress in bone health, the limited studies on the effects of lycopene in bone cells in culture [34, 35] and the results of epidemiological studies [36, 37]. To date our clinical intervention studies at St. Michael’s Hospital on the role of lycopene and elucidation of its mechanism in lowering the risk for osteoporosis in postmenopausal women (aged 50 to 60 years) are so far the only clinical studies reported in the literature.
Polyphenols are a class of water-soluble molecules naturally found in plants [38]. It is estimated that there are 10,000 different phytonutrients (phyto, meaning from plants). The health benefits associated with fruits, vegetables, tea, red wine, and Mediterranean diets are probably linked to the polyphenol antioxidants [21, 39, 40]. The polyphenols of interest in our study are a mixture of flavonoids such as quercetin, apigenin, kaempferol and luteolin present in the supplement greens+TM [41]. greens+TM in combination with another supplement, bone builderTM, were used in our study on osteoblasts cells and in clinical intervention studies on the prevention of risk of osteoporosis in postmenopausal women as will be reviewed below.
The direct role of lycopene in osteoblasts and osteoclasts, the cells involved in the pathogenesis of osteoporosis, is now being unraveled. This involvement is further supported by both epidemiological and clinical intervention with lycopene in postmenopausal women who are at risk of osteoporosis [29, 30].
An epidemiological study to determine the beneficial role of lycopene in the prevention of risk for osteoporosis was carried out by Rao et al [36]. In a cross-sectional study, 33 postmenopausal women aged 50–60 years participants were recruited and asked to provide seven-day dietary records and blood samples for analyses of total antioxidant capacity; oxidative stress parameters including lipid peroxidation and protein oxidation; and bone turnover markers including bone resorption marker NTX and bone formation marker. Their results showed that the estimated dietary lycopene had a significant and direct correlation with serum lycopene, suggesting that lycopene from the diet is bioavailable. Their conclusion that the higher serum lycopene was associated with a low NTx (
The overall conclusions that can be derived from the cross-sectional study is that lycopene has a role in the prevention of risk for osteoporosis. Further clinical studies described below support this conclusion.
Mackinnon et al [42] studied whether the elevated dose obtained through lycopene supplementation compared to intakes typically obtained from the usual daily diet was more beneficial in reducing bone turnover markers. Serum lycopene, bone turnover markers and oxidative stress parameter data were compared between postmenopausal women who were supplemented with lycopene and those who obtained both a low and high intake lycopene from daily food diet. Results showed that women who consumed lycopene supplement had significantly lower TBARS values than participants who obtained a low intake or high intake lycopene through their usual daily diets. These differences in TBARS value may be attributed to a significantly higher concentration of serum 5-
Another study was carried out to determine the effects of a lycopene-restricted diet on oxidative stress parameters and bone turnover markers in postmenopausal women [43]. Results showed that restricting the participants from consuming lycopene-containing products resulted in significant decreases in serum lycopene, α-/β-carotene and lutein/zeaxanthin, with the overall change in the serum carotenoids being lower than that seen for lycopene. All configurations of lycopene (all trans, 5-cis- and other cis lycopene) were found to be decreased and the antioxidant enzymes SOD and CAT were also significantly depressed after lycopene restriction. These changes were accompanied by a significant increase in the bone resorption marker NTx. The important conclusion from this study is the possibility that the significant increase in the bone resorption marker NTx could lead to a long-term decrease in BMD and increased fracture risk as was observed by Brown et al. [44]; longer restriction period may be detrimental to a group of postmenopausal women who were already at high risk for osteoporosis. Therefore, shorter wash-out periods of no lycopene consumption is all that is needed in clinical trials examining the effects of lycopene on bone health [43].
A clinical fully randomized controlled intervention study was next carried out by Mackinnon et al [45] to investigate directly the effects of lycopene supplementation on decreasing the risk for osteoporosis. Lycopene supplements include lycopene capsules, tomato juice with normal amount of lycopene, tomato juice with high amount of lycopene. They have shown that after the 4-month duration, the LYCOPENE-supplemented group had a significant increase in total antioxidant capacity, decrease in oxidative stress parameters protein oxidation as shown by increase in thiol values and lipid peroxidation as shown by TBARS which correlated to a decrease in NTx; all changes were significantly different from the PLACEBO group. These findings suggest that lycopene obtained in the form of tomato juice or capsule exerted equivalent antioxidant potency in reducing the risk of osteoporosis in postmenopausal women [45].
Mackinnon et al studied whether polymorphism plays a role in the development of osteoporosis [46]. To do this, Mackinnon et al. studied the role of 172T→A or 584A→G polymorphisms of the paraoxonase 1 (PON 1) in modulating the effects of serum lycopene on antioxidant capacity, oxidative stress parameters and bone turnover markers, and in women between the ages of 25-70 years). Their results showed that the PON1 polymorphism modified the association between lycopene and NTx and BAP, an interaction that may also moderate the risk of osteoporosis [46].
In another study, they showed that there was a significant interaction between PON1 genotype and change in TBARS (p<0.05) suggesting that supplementation with lycopene resulted in decreased lipid peroxidation, which interacted with the PON1 genotype to decrease bone resorption markers in postmenopausal women. These results provided a mechanistic evidence of how intervention with lycopene may act to decrease lipid peroxidation and thus the risk of osteoporosis in postmenopausal women [45, 47].
In conclusion, the demand for the use of other natural food components in the management of postmenopausal osteoporosis has increased due to reports on the adverse side effects of the conventional therapy (eg, HRT and bisphosphonates). The studies reviewed above revealed evidence that antioxidants such as lycopene can counteract the damaging effects of oxidative stress brought about by ROS that lead to the development of osteoporosis. The results of studies reviewed here indicate that lycopene maybe useful either as a dietary alternative to drug therapy or as a complement to the drugs presently approved for used by women at risk of osteoporosis.
It is well known that polyphenols have a role in the prevention of chronic diseases such as cancers, diabetes, cardiovascular diseases, neurodegenerative diseases, and osteoporosis. Interest on polyphenols and bone health has increased in the last 10 years [48-51]. The anabolic role of phytonutrients and especially polyphenols in bone was reviewed by Horcajada [49], the mechanisms of action of polyphenol in osteoblast function and its interaction with osteoclasts was reviewed by Trzeciakiewicz [50] and the beneficial effects of green tea polyphenols has been reviewed [52, 53].
Currently, most of the research on polyphenols and their effects have emerged from
Combinations of polyphenols have also been studied. One such source is the nutritional supplement greens+TM, a blend of several herbal and botanical products containing a substantial amount of polyphenols including quercetin, apigenin and luteolin [41] which act as antioxidants and therefore should be able to counteract oxidative stress. Thus, Rao et al [55] have shown that greens+
Two additional nutritional supplements have since been formulated which may prove to be good for bone health. These are the bone builderTM and the greens+bone builderTM ; the latter is the original greens+TM product that has been supplemented with the bone builderTM formula which contains several compounds including vitamins, minerals, and antioxidants. These various components have been separately shown to have some beneficial effect on bone [57]. Using the human osteoblast SaOS-2 cells, Rao et al showed that similarly to the greens+TM, the water-soluble bone-builderTM extract had a significant dose-dependent stimulatory effect on bone nodules formation [58]. It was additionally shown that similarly to the greens+TM, the watersoluble bone-builderTM extract had a significant dose-dependent stimulatory effect on bone nodules formation [58]. In a later study, they have shown that when the two supplements, greens+
A clinical study was then carried out to evaluate the effect of the nutritional supplement greens+ bone builder
In summary, studies reported in the literature on the role of polyphenols in bone health have exploded in the last 10 years, but most of the reports involved in vitro studies in osteoclasts and osteoblasts, animal studies and epidemiologicai studies. There is little doubt from the excellent studies reported that oxidative stress is one of the primary culprits responsible for the pathogenesis of osteoporosis via its role in osteoclastic resoption and the detrimental effects on the bone-forming osteoblasts. To date, only four clinical intervention studies have been reported, including ours. It is easy to see why it is very difficult to evaluate the role of polyphenols since, as we learned from this review, there are at least 8,000 different polyphenols identified to date, and each one probably having different effects on humans. Additionally, polyphenols are present in food with other constituents that may also be beneficial to bone health. In our clinical study, we combined the effects of a combination of polyphenols present in the nutritional supplement from greens+TM with the nutritional components present in bone builderTM such as minerals, vitamins and other nutrients. It is possible that the effects of greens+bone builderTM in increasing total antioxidant capacity, decreasing the oxidative stress markers protein oxidation and lipid peroxidation which correlated to the decrease in bone turnover marker for bone resorption is a result of the combined effects of the different polyphenols it contained with those of the other nutritional components present in the bone builderTM. It remained for future studies to zero in on specific component that is responsible for its beneficial effect.
In conclusion, we showed that oxidative stress due to ROS that are shown to cause the development of osteoporosis may be prevented by supplementation with the antioxidants lycopene and polyphenols. Results of in vitro studies in osteoblasts and osteoclasts, animal intervention studies, epidemiological studies and clinical intervention studies on lycopene and polyphenols are evidence for their potential use as alternative or complementary agent with other established drugs approved for the prevention or treatment of osteoporosis in postmenopausal women.
Funding for this research into Oxidative Stress, Antioxidants and Bone Health is shared by H.J. Heinz Co (Canada), Kagome Co. (Japan), LycoRed Natural Product Industries, Ltd. (Israel), Genuine Health Ltd (Canada), Millenium Biologix Inc. (Canada), and matched by the Canadian Institutes of Health Research (CIHR). We sincerely thanked the valuable contributions to this research by the following students/graduate students and staff at the Calcium Research Laboratory, Department of Medicine at St Michael’s Hospital and the University of Toronto and Department of Nutritional Sciences, University of Toronto: Dr. Bala Balachandran, Jaclyn Beca, Dawn Snyder, Loren Chan, Honglei Shen, Salva Sadeghi, Ayesha Quireshi, Dr. Erin Mackinnon and Nancy Kang. Their contributions were based on their experimental data, written reports published/in press manuscripts/theses. We would also like to thank to Dr. R.G. Josse for providing us with his medical expertise as well as allowing us access to his list of patients we were able to recruit. Special thanks to Dr. H. Vandenberghe for carrying out the CTX assay and for her valuable suggestions.
Hysterectomy is one of the most commonly performed surgeries in the United States. In fact, Merrill et al. reported a 45% lifetime risk of hysterectomy [1] with an overall rate of 5.4 per 1000 women per year. The majority of hysterectomies are performed for benign gynecologic conditions—that is, the presence of fibroids. Other indications include abnormal uterine bleeding, uterovaginal prolapse, and pelvic pain. Hysterectomy can be performed via multiple routes—abdominally, laparoscopically (including robotic approach), or vaginally. Vaginal and laparoscopic procedures are considered minimally invasive surgical approaches based on the ability to avoid a large abdominal incision. These routes of hysterectomy are associated with shortened hospitalization and postoperative recovery when compared to the abdominal approach. As a result, analysis of U.S. surgical data demonstrates evolving practice patterns with an increase in minimally invasive hysterectomies and a decrease in abdominal hysterectomies [2, 3].
The Centers for Disease Control and Prevention defines surgical site infection (SSI) as an infection that occurs after surgery near the surgical site within 30 days following surgery or 90 days where an implant is involved. They can range from superficial infections involving skin, or more serious infections involving tissues underneath the skin, organs, or implanted materials. As such, SSI is classified as superficial, deep, or organ/space. The CDC monitors SSI via the National Healthcare Safety Network with reported SSI rates of 1.7% and 0.9% after abdominal and vaginal hysterectomy respectively [4].
In a retrospective cohort study of 23,366 patients undergoing laparoscopic and abdominal hysterectomy between the years 2005 and 2011, 783 (3%) developed a surgical site infection. The majority of these were wound infections with approximately ¼ of cases being infections of the organ space which represents 0.7% of the entire cohort [5]. A more recent large cohort study examining patients between the years 2012 and 2015 demonstrated a 2% incidence of postoperative infection after hysterectomy [6]. When stratified between abdominal versus minimally invasive approaches, the incidence of SSI in the abdominal hysterectomy group exceeded 1%, while the incidences in the other groups were 0.2–0.3% [7, 8, 9].
It is well known that postoperative infections are associated with increased patient morbidity and mortality, and may result in additional costs, extended hospital stays, and prolonged antibiotic use. On average, patients who had an SSI following hysterectomy incur twice the cost of care of their counterparts who did not have an SSI. In a study examining the clinical and economic burden of surgical site infection following hysterectomy, the highest cost owing to SSI ($19,203; 95% CI 17,260–21,365) was for abdominal hysterectomy. In addition, those who had SSI had a mean length of stay (LOS) that was between three and fivefold the LOS of those who did not have an SSI irrespective of surgical approach [10]. SSI following index surgery is also associated with a significantly greater percentage of hospital readmissions. Surgical site infections after hysterectomy have serious implications on patient care and healthcare as a whole. This chapter will review the current literature on surgical site infection (SSI) after hysterectomy for benign indications and address various methods of prevention and treatment.
There are a variety of factors that influence the route of hysterectomy including informed patient preference, accessibility of the uterus, extent of extrauterine disease, size and shape of the vagina and uterus, concurrent procedures, available hospital technology and support, the nature of the case
Evidence supports that the vaginal approach is associated with better outcomes when compared with other approaches to hysterectomy. A Cochrane review analyzing 47 randomized control trials with a total of 5,102 women determined that vaginal hysterectomy resulted in quicker return to normal activity when compared to abdominal hysterectomy. There was no difference in satisfaction, quality of life, and surgical complications. Similarly, laparoscopic hysterectomy also resulted in more rapid recovery, fewer febrile episodes, and lower incidence of SSI when compared to the abdominal approach [12]. In this systematic review, there were no advantages of laparoscopic over vaginal hysterectomy. In addition, the laparoscopic approach was associated with longer operating times and increased rates of urinary tract injuries [13]. As a result, a vaginal approach continues to be the preferred route of hysterectomy.
When it is not feasible to perform a vaginal hysterectomy, a surgeon must choose between a laparoscopic or an open abdominal approach. A Cochrane review demonstrated faster return to normal activity, shorter hospital stay, fewer infections, and improved quality of life in patients undergoing laparoscopic versus abdominal hysterectomy. However, operating times were longer with higher rates of lower urinary tract (bladder and ureter) injuries in the laparoscopy group [13].
When stratified by the type of hysterectomy
When stratified into various forms of laparoscopic hysterectomy including robotic hysterectomy, laparoscopic-assisted vaginal hysterectomy, and single-port hysterectomy, the authors concluded that more research was needed to determine if there is in fact, a benefit over conventional laparoscopic approaches. The largest study available on single port laparoscopy in gynecology was a retrospective study from Cleveland Clinic reviewing a total of 908 cases. The authors concluded that single port access was safe and feasible in gynecologic surgery inclusive of both malignant and premalignant conditions with a low rate of adverse outcomes. Perhaps the most prevalent adverse outcome is an increased risk of incisional hernia with a rate of 5.5% [15, 16]. Well-designed studies that compare outcomes of alternative hysterectomy routes (robotic, laparoscopic assisted vaginal, and single-port) are needed to determine if patients may benefit from these other approaches.
Although minimally invasive routes to hysterectomy remain the preferred approach, open abdominal hysterectomy is still an important surgical option for some patients. Open abdominal hysterectomy may become necessary in a variety of clinical scenarios including failure of to maintain a minimally invasive approach.
Preoperative medical optimization is critically important in risk reduction for SSI prior to hysterectomy. Eliminating particular risk factors for SSI contributes vastly to perioperative care. This includes taking an in-depth medical history, performing a comprehensive physical exam, and addressing the patient’s medical comorbidities. Patients should be counseled on modifiable and nonmodifiable risk factors such as smoking status, diabetes stabilization, anatomic anomalies, renal comorbidities, hydrosalpinx, endometrioma, prior laparotomy, and untreated pelvic inflammatory disease (PID) or bacterial vaginosis [17, 18, 19, 20]. Optimal diabetes control is critical in preventing postoperative SSI with both spot glucose levels ≤200 mg/dl and hemoglobin A1C levels below 8.5–9.0% [21, 22].
Preoperative screening for genital tract infections is generally not necessary; however, certain types of infections are clinically important prior to hysterectomy. It has been well established that bacterial vaginosis (BV) is associated with an increased risk of postoperative cuff cellulitis and subsequent pelvic abscess formation after hysterectomy [23]. Treatment of BV prior to scheduled hysterectomy will decrease this risk.
Practicing safe, high-quality, evidence-based operating room care begins first with accurate identification of the patient, surgical site, and procedure.
In an AAGL white paper, “Enhanced Recovery and Surgical Optimization Protocol for Minimally Invasive Gynecologic Surgery”, infection prophylaxis can be achieved via the implementation of SSI prevention bundles [24]. Quality or safety bundles provide a framework for the implementation of evidence-based practices. They have been validated across multiple disciplines to actually decrease SSI [25, 26, 27, 28]. The ACOG Council on Patient Safety in Women’s Health Care has published a consensus bundle on prevention of SSI prior to gynecologic surgery. This provides a framework for hospitals to develop, implement, and practice evidence-based prevention of SSIs [29].
An example of a hysterectomy bundle is as follows:
The degree of contamination at the time of surgery is classified using the National Healthcare Safety Network (NHSN) wound class. Hysterectomy is a clean-contaminated procedure and as a result, is unavoidably associated with a relatively higher risk of infection as the procedure breaches the genital tract. Common sites of infection after hysterectomy include the abdominal wall, the vaginal cuff, bladder, and pelvic floor. Related complications include pelvic abscess or infected hematoma and sepsis. A patient’s individual susceptibility to infection depends on a variety of factors including bacterial virulence, extent of surgery-related tissue trauma and fluid collection, the effectiveness of the patient’s immune system, age, nutritional status, presence of diabetes, smoking, coexistent infection or colonization with microorganisms. Perhaps the most important factors in SSI prevention in hysterectomy are timely administration of appropriate preoperative antibiotics and meticulous surgical technique. Use of β-lactam alternatives in patients who do not report an anaphylactic reaction can lead to increased antimicrobial resistance. In fact, a retrospective cohort study involving over 21,000 women undergoing hysterectomy demonstrated that the use of standard β-lactam antibiotics had a lower risk of SSI compared to those who received an alternative regimen [23]. Thus, we advise judicious use of β-lactam alternatives for patients with a history of IgE-mediated penicillin hypersensitivity. The most common organisms isolated from vaginal cuff infections are anaerobes. In a large retrospective cohort study with over 18,000 patients undergoing hysterectomy of any type, those receiving cefazolin or a second-generation cephalosporin have more than double the SSI risk compared with those receiving combined treatment with cefazolin and metronidazole [25]. This is likely related to enhanced anaerobic coverage with the addition of metronidazole. We recommend that all patients undergoing hysterectomy receive metronidazole in addition to the standard intraoperative antibiotics.
The CDC also advises that the entire body be cleansed with either soap or antiseptic the night prior to the procedure. Intraoperatively, alcohol-based chlorhexidine is more effective for skin preparation when compared to iodine solutions [30, 31]. With regards to vaginal preparation, either povidone-iodine or chlorhexidine gluconate (4%) with a low concentration of isopropyl alcohol is acceptable, as both significantly reduce rates of postoperative infectious morbidity [32].
In general, our practice will have patients return for short-term postoperative evaluation within 2 weeks following their hysterectomy. Patients are counseled to maintain pelvic rest for a minimum of 8 weeks. Postoperative blood and other secretions from the vaginal cuff may raise the vaginal pH and as a result, increase the risk of bacterial vaginosis. Many patients with vaginal cuff infections present more than 2 weeks following hysterectomy, which suggests a late ascending spread of vaginal microorganisms. As a result, our patients return for a second postoperative appointment and vaginal cuff check approximately 4–6 weeks after their hysterectomy.
Gynecological surgical site infections are polymicrobial with a mix of both anaerobic and aerobic infections. Common pathogens contain gram-negative bacilli, enterococci, streptococci, and anaerobes
Wound exploration and debridement are pillars in the management of superficial and deep-incisional SSIs. This includes not only opening the wound, debridement of necrotic and devitalized tissue, but also involves the culture of the wound to allow for speciation of potential pathogens to assist in antibiotic therapy.
The mortality and morbidity of organ/space SSI tend to be higher than superficial or deep SSI. The primary objective in management is to achieve source control. Computed tomography and ultrasound are employed to guide placement of closed suction percutaneous drains into abscess collections when feasible. The initial approach in treatment of post-hysterectomy pelvic abscess depends on three factors: (1) hemodynamic stability, (2) abscess size, and (3) abscess location. Hemodynamically unstable patients require prompt surgical intervention and intensive care monitoring.
Patients who are hemodynamically stable with a post-hysterectomy pelvic abscess should be treated empirically with parenteral broad-spectrum antibiotics. Initial antimicrobial regimens can be tailored to subsequent culture and sensitivity results. If the patient does not respond within 48–72 hours, percutaneous drainage or infectious disease consultation may be warranted. An argument can be made for earlier percutaneous drainage. In fact, a systematic review comparing the success rates of 3 modalities of minimally invasive management of tubo-ovarian abscesses—laparoscopy, ultrasound-guided drainage and computed tomography-guided drainage
Treatment failure is defined as persistent fever, leukocytosis, pain or lack of abscess resolution. Risk factors include residual fluid collection after drainage and increasing patient age. Surgical management is recommended at this time.
The most common reason for unplanned readmission after surgery is surgical site infection. SSIs are associated with increased morbidity, mortality, transfer to an intensive care setting, prolonged hospitalization, hospital readmission, and increased healthcare costs. In addition, the development of SSI negatively impacts patient experience.
The majority of postoperative issues can be anticipated and prevented preoperatively. Systematically addressing these issues at the preoperative evaluation may result in greater patient satisfaction and fewer complications. Thus, prevention of SSI after hysterectomy begins with a calculation of perioperative risk followed by addressing those risk factors prior to the procedure. Intraoperative measures aimed at SSI prevention include the implementation of evidence-based SSI prevention bundles, proper administration of intraoperative antibiotic prophylaxis, and proper skin/vaginal preparation. Postoperatively, hysterectomy patients should be followed closely.
Thanks to the faculty, residents, fellows, and medical students of the Zucker School of Medicine.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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Abdurakhmonov"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11332",title:"Essential Oils",subtitle:"Advances in Extractions and Biological Applications",isOpenForSubmission:!1,hash:"742e6cae3a35686f975edc8d7f9afa94",slug:"essential-oils-advances-in-extractions-and-biological-applications",bookSignature:"Mozaniel Santana de Oliveira and Eloisa Helena de Aguiar Andrade",coverURL:"https://cdn.intechopen.com/books/images_new/11332.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"195290",title:"Ph.D.",name:"Mozaniel",middleName:null,surname:"Santana De Oliveira",slug:"mozaniel-santana-de-oliveira",fullName:"Mozaniel Santana De Oliveira"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11080",title:"Engineering Principles",subtitle:"Welding and Residual Stresses",isOpenForSubmission:!1,hash:"6c07a13a113bce94174b40096f30fb5e",slug:"engineering-principles-welding-and-residual-stresses",bookSignature:"Kavian Omar Cooke and Ronaldo Câmara Cozza",coverURL:"https://cdn.intechopen.com/books/images_new/11080.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"138778",title:"Dr.",name:"Kavian",middleName:"Omar",surname:"Cooke",slug:"kavian-cooke",fullName:"Kavian Cooke"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10839",title:"Protein Detection",subtitle:null,isOpenForSubmission:!1,hash:"2f1c0e4e0207fc45c936e7d22a5369c4",slug:"protein-detection",bookSignature:"Yusuf Tutar and Lütfi Tutar",coverURL:"https://cdn.intechopen.com/books/images_new/10839.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10858",title:"MOOC (Massive Open Online Courses)",subtitle:null,isOpenForSubmission:!1,hash:"d32f86793bc72dde32532f509b1ec5b0",slug:"mooc-massive-open-online-courses-",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/10858.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11371",title:"Cerebral Circulation",subtitle:"Updates on Models, Diagnostics and Treatments of Related Diseases",isOpenForSubmission:!1,hash:"e2d3335445d2852d0b906bb9750e939f",slug:"cerebral-circulation-updates-on-models-diagnostics-and-treatments-of-related-diseases",bookSignature:"Alba Scerrati, Luca Ricciardi and Flavia Dones",coverURL:"https://cdn.intechopen.com/books/images_new/11371.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"182614",title:"Dr.",name:"Alba",middleName:null,surname:"Scerrati",slug:"alba-scerrati",fullName:"Alba Scerrati"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"11120",title:"Environmental Impact and Remediation of Heavy Metals",subtitle:null,isOpenForSubmission:!1,hash:"9e77514288e7394f1e6cd13481af3509",slug:"environmental-impact-and-remediation-of-heavy-metals",bookSignature:"Hosam M. Saleh and Amal I. Hassan",coverURL:"https://cdn.intechopen.com/books/images_new/11120.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"144691",title:"Prof.",name:"Hosam M.",middleName:null,surname:"Saleh",slug:"hosam-m.-saleh",fullName:"Hosam M. Saleh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10696",title:"Applications of Calorimetry",subtitle:null,isOpenForSubmission:!1,hash:"8c87f7e2199db33b5dd7181f56973a97",slug:"applications-of-calorimetry",bookSignature:"José Luis Rivera Armenta and Cynthia Graciela Flores Hernández",coverURL:"https://cdn.intechopen.com/books/images_new/10696.jpg",editedByType:"Edited by",publishedDate:"June 23rd 2022",editors:[{id:"107855",title:"Dr.",name:"Jose Luis",middleName:null,surname:"Rivera Armenta",slug:"jose-luis-rivera-armenta",fullName:"Jose Luis Rivera Armenta"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"1165",title:"Urologic Oncology",slug:"urologic-oncology",parent:{id:"204",title:"Urology",slug:"urology"},numberOfBooks:4,numberOfSeries:0,numberOfAuthorsAndEditors:93,numberOfWosCitations:10,numberOfCrossrefCitations:3,numberOfDimensionsCitations:8,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"1165",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"10339",title:"Modern Approach to Diagnosis and Treatment of Bladder Cancer",subtitle:null,isOpenForSubmission:!1,hash:"d1fdae263fb8a59eef2795dc748a1155",slug:"modern-approach-to-diagnosis-and-treatment-of-bladder-cancer",bookSignature:"Francesco Ziglioli and Umberto Maestroni",coverURL:"https://cdn.intechopen.com/books/images_new/10339.jpg",editedByType:"Edited by",editors:[{id:"62240",title:"Dr.",name:"Francesco",middleName:null,surname:"Ziglioli",slug:"francesco-ziglioli",fullName:"Francesco Ziglioli"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6424",title:"Evolving Trends in Kidney Cancer",subtitle:null,isOpenForSubmission:!1,hash:"e9305ef1c5e6ad63407fd9262a27cf31",slug:"evolving-trends-in-kidney-cancer",bookSignature:"Sashi S. Kommu and Inderbir S. Gill",coverURL:"https://cdn.intechopen.com/books/images_new/6424.jpg",editedByType:"Edited by",editors:[{id:"9902",title:"Dr.",name:"Sashi S.",middleName:"S",surname:"Kommu",slug:"sashi-s.-kommu",fullName:"Sashi S. Kommu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6423",title:"Prostate Cancer",subtitle:null,isOpenForSubmission:!1,hash:"d072a079624084c12169a118fdbbfa87",slug:"prostate-cancer",bookSignature:"Cem Onal",coverURL:"https://cdn.intechopen.com/books/images_new/6423.jpg",editedByType:"Edited by",editors:[{id:"43940",title:"Dr.",name:"Cem",middleName:null,surname:"Onal",slug:"cem-onal",fullName:"Cem Onal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"5516",title:"Bladder Cancer",subtitle:"Management of NMI and Muscle-Invasive Cancer",isOpenForSubmission:!1,hash:"fa255c022acc85f2bd2c12ce4cd9a67b",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",bookSignature:"M. Hammad Ather",coverURL:"https://cdn.intechopen.com/books/images_new/5516.jpg",editedByType:"Edited by",editors:[{id:"88868",title:"Prof.",name:"M Hammad",middleName:null,surname:"Ather",slug:"m-hammad-ather",fullName:"M Hammad Ather"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:4,seriesByTopicCollection:[],seriesByTopicTotal:0,mostCitedChapters:[{id:"54132",doi:"10.5772/67473",title:"Cross-Polarization OCT for In Vivo Diagnostics and Prediction of Bladder Cancer",slug:"cross-polarization-oct-for-in-vivo-diagnostics-and-prediction-of-bladder-cancer",totalDownloads:1098,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"This chapter contains three parts covering recent efforts to increase the accuracy of optical coherence tomography (OCT) differential diagnostics of bladder pathologies. The first part compares the diagnostic efficacy of traditional OCT and cross-polarization OCT (CP OCT); CP OCT and fluorescence cystoscopy (FC) for detecting flat lesions in the bladder at the early stages of cancer. The second part contains a report on achievements in application of CP OCT for detection of recurrent carcinoma in the scar area that is a hardly distinguishable form of bladder cancer using an optimized CP OCT image analysis. The third part of the chapter reviews the results on CP OCT usage for in vivo diagnosis of the bladder cancer after radiation therapy of cervical cancer.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Elena Kiseleva, Gladkova Natalia, Streltzova Olga, Kirillin Mikhail,\nMaslennikova Anna, Dudenkova Varvara, Yunusova Katerina and\nSergeeva Ekaterina",authors:[{id:"68196",title:"Prof.",name:"Natalia",middleName:null,surname:"Gladkova",slug:"natalia-gladkova",fullName:"Natalia Gladkova"},{id:"191970",title:"Dr.",name:"Elena",middleName:null,surname:"Kiseleva",slug:"elena-kiseleva",fullName:"Elena Kiseleva"},{id:"191990",title:"Dr.",name:"Olga",middleName:null,surname:"Streltzova",slug:"olga-streltzova",fullName:"Olga Streltzova"},{id:"191992",title:"Mrs.",name:"Varvara",middleName:null,surname:"Dudenkova",slug:"varvara-dudenkova",fullName:"Varvara Dudenkova"},{id:"191993",title:"Prof.",name:"Anna",middleName:null,surname:"Maslennikova",slug:"anna-maslennikova",fullName:"Anna Maslennikova"},{id:"191994",title:"Dr.",name:"Katerina",middleName:null,surname:"Yunusova",slug:"katerina-yunusova",fullName:"Katerina Yunusova"},{id:"191995",title:"Dr.",name:"Mikhail",middleName:null,surname:"Kirillin",slug:"mikhail-kirillin",fullName:"Mikhail Kirillin"},{id:"193422",title:"Dr.",name:"Ekaterina",middleName:null,surname:"Sergeeva",slug:"ekaterina-sergeeva",fullName:"Ekaterina Sergeeva"}]},{id:"54019",doi:"10.5772/67309",title:"Bladder Cancer Markers and Recent Innovations",slug:"bladder-cancer-markers-and-recent-innovations",totalDownloads:1684,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Bladder cancer (urothelial carcinoma) is the most common tumor of the urinary tract. It occurs more frequently among men about 65 years old on average. Two forms of the tumor are known: a non–muscle-invasive one and a muscle-invasive one. The latter turns out to be very aggressive with a survival of 5 years average. The non–muscle-invasive form frequently recurs (60–70%) and in 15% of cases, it progresses into the invasive form. The diagnosis is made mainly by cystoscopy and urine cytology. A high number of researches were dedicated in order to find a simple test using voided urine to frequently monitor possible tumor recurrence. During the last 10 years, many tests were proposed concerning either special proteins of which the most common are the bladder tumor antigen (BTA) and the nuclear matrix protein 22 (NMP22) or the presence of genetic mutations [most frequently, fibroblasts growth factor receptor 3 (FGFR3) and TP53], alteration of DNA methylation, chromatin structure and, more recently, the presence of specific micro-RNA. Recently the analysis of lipids present in voided urine showed a difference in fatty acids between healthy individuals and those affected by non-invasive forms. These markers appear to have a high specificity and sensitivity: a deepening of these results could lead to the development of a test that avoids invasive treatment and the cost of cystoscopy.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Mariapia Viola-Magni, Samuela Cataldi and Daniela Marocco",authors:[{id:"192375",title:"Prof.",name:"Mariapia",middleName:null,surname:"Viola-Magni",slug:"mariapia-viola-magni",fullName:"Mariapia Viola-Magni"},{id:"197851",title:"BSc.",name:"Samuela",middleName:null,surname:"Cataldi",slug:"samuela-cataldi",fullName:"Samuela Cataldi"},{id:"197852",title:"Dr.",name:"Daniela",middleName:null,surname:"Marocco",slug:"daniela-marocco",fullName:"Daniela Marocco"}]},{id:"54063",doi:"10.5772/67280",title:"Intravesical Chemohyperthermia for NMIBC: Rationale and Results of This Developing Treatment",slug:"intravesical-chemohyperthermia-for-nmibc-rationale-and-results-of-this-developing-treatment",totalDownloads:1379,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Bladder cancer is the fourth most common cancer in men, and the lifetime risk of getting bladder cancer is 2.4%. Approximately 75% of newly diagnosed cases of bladder cancer are non-muscle-invasive bladder cancer (NMIBC), and half of them will show recurrence and/or progression after transurethral resection. Therefore, after transurethral resection, in high-risk patients, intravesical therapy is mandatory. However, bacillus Calmette-Guérin (BCG) is associated with important side effects such as systemic tuberculosis and bladder retraction. Chemohyperthermia (CHT) has shown a 60% lower recurrence rate than standard mitomycin C (MMC). However, its effectiveness in high-risk patients, especially CIS and BCG refractory patients, is even more important. CHT will probably be an option for patients unsuitable for radical cystectomy or those on whom BCG can’t be used. Two main technologies are currently available for intravesical CHT: microwaves and recirculating heated fluids. Both of them have pros and cons that should be known and evaluated by a urologist. In this chapter, we will speak about rationale, technical options, clinical results, ongoing studies, and future perspective for this interesting treatment option for intermediate and high-risk patients with NMIBC.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Sousa-Escandón Manuel Alejandro, Flores Carbajal Javier, Sousa-\nGonzález Daniel and Rodriguez Gómez Silvia",authors:[{id:"191356",title:"Dr.",name:"Alejandro",middleName:null,surname:"Sousa-Escandón",slug:"alejandro-sousa-escandon",fullName:"Alejandro Sousa-Escandón"}]},{id:"54147",doi:"10.5772/67443",title:"Lymphadenectomy in Muscle Invasive Bladder Cancer",slug:"lymphadenectomy-in-muscle-invasive-bladder-cancer",totalDownloads:1248,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Bladder cancer is the second most common genitourinary malignancy with urothelial cancer comprising nearly 90% of primary bladder tumors. Urothelial carcinoma of the urinary bladder is the fifth most common malignancy in the United States, with an estimated 76,960 new cases and 163,900 deaths in 2016. Radical cystectomy with lymph node dissection remains the standard treatment for patients with muscle-invasive urothelial carcinoma of the bladder, and also for nonmuscle-invasive disease, refractory to intravesical therapy. The current approaches to pelvic lymph node dissections are based on the removal of lymph nodes most commonly harboring metastatic disease, notably the external iliac, obturator, and hypogastric lymph nodes. The boundaries for a standard pelvic lymph node dissection generally include the bifurcation of the common iliac vessels superiorly and the genitofemoral nerve laterally. Extended pelvic lymph node includes the removal of lymph nodes between the bifurcation of the common iliac vessels and the level of the aortic bifurcation, sometimes including distal aortic and caval nodes up to the level of the inferior mesenteric artery, as well as presacral nodes. Extended and superextended dissection has been reported to be associated with superior survival outcome.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Mustafa Ozan Horsanali and Kutan Ozer",authors:[{id:"59702",title:"Dr.",name:"Mustafa Ozan",middleName:null,surname:"Horsanali",slug:"mustafa-ozan-horsanali",fullName:"Mustafa Ozan Horsanali"},{id:"192699",title:"Dr.",name:"Kutan",middleName:null,surname:"Ozer",slug:"kutan-ozer",fullName:"Kutan Ozer"}]},{id:"59222",doi:"10.5772/intechopen.73515",title:"Development of Oncolytic Adenoviruses for the Management of Prostate Cancer",slug:"development-of-oncolytic-adenoviruses-for-the-management-of-prostate-cancer",totalDownloads:1099,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Prostate cancer (PCa) is the fifth most common cause of cancer-related deaths in men globally. Androgen receptor (AR) signalling plays a vital role in initiation and progression and antiandrogens are standard of care first-line therapeutics. However, resistance frequently develops resulting in metastatic castration-resistant prostate cancer (mCRPC). Management of CRPC is currently chemotherapy and/or radiotherapy but is mostly palliative due to rapid development of resistance. The need for novel approaches to eliminate mCRPC is compelling; a promising option is replication-selective (oncolytic) adenoviruses with demonstrated efficacy in preclinical models of multidrug-resistant PCa. The safety of various viral mutants has been confirmed in numerous clinical trials with minimal toxicity in patients. Importantly, oncolytic adenoviruses synergise with the current standard of care for mCRPC even in treatment-resistant cells. In early phase I–II clinical trials, promising efficacy in patients with localised PCa was reported after intratumoural administration, and phase III trials are underway. To enable systemic delivery, for targeting of mCRPC, further developments are necessary because of the short half-life of the adenoviral mutants in human blood. Current progress in preventing the high-affinity binding of adenovirus to erythrocytes, hepatocyte uptake, and elimination by hepatic Kupffer cells will be described.",book:{id:"6423",slug:"prostate-cancer",title:"Prostate Cancer",fullTitle:"Prostate Cancer"},signatures:"Ahmed A. Ali and Gunnel Halldén",authors:[{id:"80427",title:"Dr.",name:"Gunnel",middleName:null,surname:"Hallden",slug:"gunnel-hallden",fullName:"Gunnel Hallden"},{id:"232386",title:"MSc.",name:"Ahmed",middleName:null,surname:"Ali",slug:"ahmed-ali",fullName:"Ahmed Ali"}]}],mostDownloadedChaptersLast30Days:[{id:"70881",title:"Robot-Assisted Partial Nephrectomy: Evolving Techniques",slug:"robot-assisted-partial-nephrectomy-evolving-techniques",totalDownloads:481,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Robotic-assisted partial nephrectomy is now embraced in urology as a recommended treatment option for small localised renal tumours. There is an increasing trend towards setting up robotic-assisted services in urological centres across the world. Our aim is to review the available published common robotic-assisted partial nephrectomy techniques. We present our institutions’ established step-by-step technique for performing robotic-assisted partial nephrectomy, in order to guide aspiring urologists interested in performing robotic-assisted partial nephrectomies. The importance of pre-operative review of imaging in a multi-disciplinary approach is critical. We emphasise certain tips inperforming a safer procedure.",book:{id:"6424",slug:"evolving-trends-in-kidney-cancer",title:"Evolving Trends in Kidney Cancer",fullTitle:"Evolving Trends in Kidney Cancer"},signatures:"Mohammed Kamil Quraishi, Edward Ramez Latif, Milan Thomas, Ben Eddy, Elio Mazzone and Alexandre Mottrie",authors:[{id:"277566",title:"Dr.",name:"Mohammed Kamil",middleName:null,surname:"Quraishi",slug:"mohammed-kamil-quraishi",fullName:"Mohammed Kamil Quraishi"},{id:"277570",title:"Dr.",name:"Milan",middleName:null,surname:"Thomas",slug:"milan-thomas",fullName:"Milan Thomas"},{id:"277571",title:"Dr.",name:"Ben",middleName:null,surname:"Eddy",slug:"ben-eddy",fullName:"Ben Eddy"}]},{id:"54132",title:"Cross-Polarization OCT for In Vivo Diagnostics and Prediction of Bladder Cancer",slug:"cross-polarization-oct-for-in-vivo-diagnostics-and-prediction-of-bladder-cancer",totalDownloads:1098,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"This chapter contains three parts covering recent efforts to increase the accuracy of optical coherence tomography (OCT) differential diagnostics of bladder pathologies. The first part compares the diagnostic efficacy of traditional OCT and cross-polarization OCT (CP OCT); CP OCT and fluorescence cystoscopy (FC) for detecting flat lesions in the bladder at the early stages of cancer. The second part contains a report on achievements in application of CP OCT for detection of recurrent carcinoma in the scar area that is a hardly distinguishable form of bladder cancer using an optimized CP OCT image analysis. The third part of the chapter reviews the results on CP OCT usage for in vivo diagnosis of the bladder cancer after radiation therapy of cervical cancer.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Elena Kiseleva, Gladkova Natalia, Streltzova Olga, Kirillin Mikhail,\nMaslennikova Anna, Dudenkova Varvara, Yunusova Katerina and\nSergeeva Ekaterina",authors:[{id:"68196",title:"Prof.",name:"Natalia",middleName:null,surname:"Gladkova",slug:"natalia-gladkova",fullName:"Natalia Gladkova"},{id:"191970",title:"Dr.",name:"Elena",middleName:null,surname:"Kiseleva",slug:"elena-kiseleva",fullName:"Elena Kiseleva"},{id:"191990",title:"Dr.",name:"Olga",middleName:null,surname:"Streltzova",slug:"olga-streltzova",fullName:"Olga Streltzova"},{id:"191992",title:"Mrs.",name:"Varvara",middleName:null,surname:"Dudenkova",slug:"varvara-dudenkova",fullName:"Varvara Dudenkova"},{id:"191993",title:"Prof.",name:"Anna",middleName:null,surname:"Maslennikova",slug:"anna-maslennikova",fullName:"Anna Maslennikova"},{id:"191994",title:"Dr.",name:"Katerina",middleName:null,surname:"Yunusova",slug:"katerina-yunusova",fullName:"Katerina Yunusova"},{id:"191995",title:"Dr.",name:"Mikhail",middleName:null,surname:"Kirillin",slug:"mikhail-kirillin",fullName:"Mikhail Kirillin"},{id:"193422",title:"Dr.",name:"Ekaterina",middleName:null,surname:"Sergeeva",slug:"ekaterina-sergeeva",fullName:"Ekaterina Sergeeva"}]},{id:"61307",title:"Genetics in the Prostate Cancer",slug:"genetics-in-the-prostate-cancer",totalDownloads:1119,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Any disruption in the intracellular functions ranging from DNA transcription to protein ligand binding as well as intercellular communication may cause cellular transformation to malignant cell in the proper microenvironment when it could escape from the immune system. In this chapter, specifically, genetic alterations playing role in the prostate cancer are intended to be reviewed briefly under the subheadings of genomic instability and the hallmarks of cancer which are sustaining proliferative signaling, evading growth suppressors, resisting cell death, enabling the replicative immortality, inducing angiogenesis, activating invasion and progression to metastatic disease, reprogramming of the energy metabolism and evading immune destruction.",book:{id:"6423",slug:"prostate-cancer",title:"Prostate Cancer",fullTitle:"Prostate Cancer"},signatures:"Hikmet Köseoğlu",authors:[{id:"111496",title:"Dr.",name:"Hikmet",middleName:null,surname:"Köseoǧlu",slug:"hikmet-koseolu",fullName:"Hikmet Köseoǧlu"}]},{id:"54587",title:"Genital Organs‐Sparing Radical Cystectomy in Female Patients with Muscle Invasive Urothelial Carcinoma of the Bladder",slug:"genital-organs-sparing-radical-cystectomy-in-female-patients-with-muscle-invasive-urothelial-carcino",totalDownloads:1275,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"There has been considerable interest in urethral‐sparing cystectomy and preservation of the gynecological tract to maintain continence mechanism, sexual function, and reproductive function in young patients who undergo radical cystectomy for muscle‐invasive bladder cancer and this new technique gained acceptance in many centers. The issue of oncological safety of a urethra and anterior vaginal wall‐sparing cystectomy in selected patients has been addressed by several authors. The chapter will discuss the following items: (I) Technique of genital‐sparing radical cystectomy in female patients with muscle invasive transitional cell carcinoma of the bladder. (II) Definition and rationale of genital‐sparing radical cystectomy in female patients. (III) Rational and value of urethral preservation in genital‐sparing cystectomy in female patients with urothelial carcinoma. (IV) Previous reports about genital‐sparing cystectomy in patients with urothelial carcinoma. (V) Value of preservation of the internal genital organs in female patients undergoing radical cystectomy.",book:{id:"5516",slug:"bladder-cancer-management-of-nmi-and-muscle-invasive-cancer",title:"Bladder Cancer",fullTitle:"Bladder Cancer - Management of NMI and Muscle-Invasive Cancer"},signatures:"Hosni Khairy Salem",authors:[{id:"96052",title:"Prof.",name:"Hosni",middleName:"Khairy",surname:"Salem",slug:"hosni-salem",fullName:"Hosni Salem"}]},{id:"67209",title:"Robotic Surgery and Successful Set-Up: A Stepwise Approach",slug:"robotic-surgery-and-successful-set-up-a-stepwise-approach",totalDownloads:662,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Robot purchase, implementation, and sustainability require a number of key challenges to overcome. We provide our experience of managing a potentially daunting task, summarizing the key steps to help deliver such an exciting project. We will take you through team approach options for purchase and safe implementation in the current financial climate.",book:{id:"6424",slug:"evolving-trends-in-kidney-cancer",title:"Evolving Trends in Kidney Cancer",fullTitle:"Evolving Trends in Kidney Cancer"},signatures:"Christopher J. Anderson and Hiten R.H. 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