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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{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"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"8018",leadTitle:null,fullTitle:"Extracellular Matrix - Developments and Therapeutics",title:"Extracellular Matrix",subtitle:"Developments and Therapeutics",reviewType:"peer-reviewed",abstract:"Understanding extracellular matrix (ECM) structure and function is important for developing biomedical applications that are as close to ‘native’ as possible. Written by pioneering scientists from all over the world, this book reports research and new developments in the field of collagen structure, function, and biomechanics and discusses the relevance of hyaluronic acid and its therapeutic uses. It gives readers a glimpse of what is current in this area and we hope it piques their interest in learning more about ECM biology.",isbn:"978-1-83968-236-0",printIsbn:"978-1-83968-235-3",pdfIsbn:"978-1-83968-237-7",doi:"10.5772/intechopen.77848",price:119,priceEur:129,priceUsd:155,slug:"extracellular-matrix-developments-and-therapeutics",numberOfPages:170,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"c85e82851e80b40282ff9be99ddf2046",bookSignature:"Rama Sashank Madhurapantula, Joseph Orgel P.R.O. and Zvi Loewy",publishedDate:"October 27th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/8018.jpg",numberOfDownloads:1745,numberOfWosCitations:1,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:13,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 3rd 2020",dateEndSecondStepPublish:"July 24th 2020",dateEndThirdStepPublish:"September 22nd 2020",dateEndFourthStepPublish:"December 11th 2020",dateEndFifthStepPublish:"February 9th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"212416",title:"Dr.",name:"Rama Sashank",middleName:null,surname:"Madhurapantula",slug:"rama-sashank-madhurapantula",fullName:"Rama Sashank Madhurapantula",profilePictureURL:"https://mts.intechopen.com/storage/users/212416/images/system/212416.jpg",biography:"Rama Sashank Madhurapantula is a research assistant professor in the Biology Department, Illinois Institute of Technology, Chicago. His current research involves developing microscopy techniques to establish macroscopic stress vs strain relations in body tissues that present mixed-tissue compositions, in conjunction with X-ray diffraction scanning techniques to establish tissue composition.\t\nHis doctoral work was in understanding molecular changes to collagens with diseases and changes in fibrous structures such as myelin. In recognition of scientific endeavors and achievements, Dr. Madhurapantula was elected as chair to the Fiber Diffraction Special Interest Group of the American Crystallographic Association in 2020 and awarded the Margaret C. Etter Student Lecturer award in 2014.",institutionString:"Illinois Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"212413",title:"Prof.",name:"Joseph",middleName:null,surname:"Orgel P.R.O.",slug:"joseph-orgel-p.r.o.",fullName:"Joseph Orgel P.R.O.",profilePictureURL:"https://mts.intechopen.com/storage/users/212413/images/system/212413.jpg",biography:"Professor Joseph Orgel is a British American scientist based at the Illinois Institute of Technology (Illinois Tech), Chicago, with appointments in biology and biomedical engineering. His research explores fundamental structural biochemistry underlying disease and possible treatments. Using novel techniques, Dr. Orgel and his group have been able to visualize the molecular organization of connective and neurological tissues at nanometer (or better) resolution. He leads investigations of diseases such as Alzheimer’s, traumatic brain injury, heart disease, and arthritis in collaboration with the US Army. An awardee of the NSF CAREER award, he has been Biochemistry Section Editor of PLOS ONE since 2008. In early 2021, he was named Vice Provost for Academic Affairs at Illinois Tech.",institutionString:"Illinois Institute of Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Illinois Institute of Technology",institutionURL:null,country:{name:"United States of America"}}},coeditorTwo:{id:"235950",title:"Ph.D.",name:"Zvi",middleName:null,surname:"Loewy",slug:"zvi-loewy",fullName:"Zvi Loewy",profilePictureURL:"https://mts.intechopen.com/storage/users/235950/images/system/235950.png",biography:"Dr. Zvi Loewy is a senior academic leader and an experienced global pharmaceutical–biotechnology executive. He leverages a diversified background in big-pharma senior management, biotech startup creation, and academia. Dr. Loewy has served as a board member of the New Jersey Bioscience Center Incubator since 2010. From 2005 to 2020 he was a board member of the Jerusalem College of Technology. His international experience has included leading international research teams; championing the penetration and commercial launch of healthcare products worldwide; and leading open innovation in the Mideast. Dr. Loewy received his BA from Yeshiva University, New York, his MS from Rensselaer Polytechnic Institute, New York, and his Ph.D. in Molecular Biology from the Albert Einstein College of Medicine, New York. He has more than twenty-five issued patents to his credit.",institutionString:"New York Medical College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"New York Medical College",institutionURL:null,country:{name:"United States of America"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"919",title:"Tissue Engineering",slug:"biomaterials-tissue-engineering"}],chapters:[{id:"74538",title:"The Cellular Stress Response Interactome and Extracellular Matrix Cross-Talk during Fibrosis: A Stressed Extra-Matrix Affair",doi:"10.5772/intechopen.95066",slug:"the-cellular-stress-response-interactome-and-extracellular-matrix-cross-talk-during-fibrosis-a-stres",totalDownloads:342,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Diverse internal and external pathologic stimuli can trigger cellular stress response pathways (CSRPs) that are usually counteracted by intrinsic homeostatic machinery, which responds to stress by initiating complex signaling mechanisms to eliminate either the stressor or the damaged cells. There is growing evidence that CSRPs can have context-dependent homeostatic or pathologic functions that may result in tissue fibrosis under persistence of stress. CSRPs can drive intercellular communications through exosomes (trafficking and secretory pathway determinants) secreted in response to stress-induced proteostasis rebalancing. The injured tissue environment upon sensing the stress turns on a precisely orchestrated network of immune responses by regulating cytokine-chemokine production, recruitment of immune cells, and modulating fibrogenic niche and extracellular matrix (ECM) cross-talk during fibrotic pathologies like cardiac fibrosis, liver fibrosis, laryngotracheal stenosis, systemic scleroderma, interstitial lung disease and inflammatory bowel disease. Immunostimulatory RNAs (like double stranded RNAs) generated through deregulated RNA processing pathways along with RNA binding proteins (RBPs) of RNA helicase (RNA sensors) family are emerging as important components of immune response pathways during sterile inflammation. The paradigm-shift in RNA metabolism associated interactome has begun to offer new therapeutic windows by unravelling the novel RBPs and splicing factors in context of developmental and fibrotic pathways. We would like to review emerging regulatory nodes and their interaction with CSRPs, and tissue remodeling with major focus on cardiac fibrosis, and inflammatory responses underlying upper airway fibrosis.",signatures:"Maryada Sharma, Kavita Kaushal, Sanjay Singh Rawat, Manjul Muraleedharan, Seema Chhabra, Nipun Verma, Anupam Mittal, Ajay Bahl, Madhu Khullar, Anurag Ramavat and Naresh K. Panda",downloadPdfUrl:"/chapter/pdf-download/74538",previewPdfUrl:"/chapter/pdf-preview/74538",authors:[{id:"30568",title:"Prof.",name:"Madhu",surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar"},{id:"41185",title:"Dr.",name:"Ajay",surname:"Bahl",slug:"ajay-bahl",fullName:"Ajay Bahl"},{id:"121502",title:"Prof.",name:"Naresh",surname:"Panda",slug:"naresh-panda",fullName:"Naresh Panda"},{id:"327124",title:"Dr.",name:"Maryada",surname:"Sharma",slug:"maryada-sharma",fullName:"Maryada Sharma"},{id:"336274",title:"MSc.",name:"Kavita",surname:"Kaushal",slug:"kavita-kaushal",fullName:"Kavita Kaushal"},{id:"336275",title:"M.Sc.",name:"Sanjay",surname:"Rawat",slug:"sanjay-rawat",fullName:"Sanjay Rawat"},{id:"336276",title:"Dr.",name:"Manjul",surname:"Muraleedharan",slug:"manjul-muraleedharan",fullName:"Manjul Muraleedharan"},{id:"336277",title:"Dr.",name:"Seema",surname:"Chhabra",slug:"seema-chhabra",fullName:"Seema Chhabra"},{id:"336279",title:"Dr.",name:"Nipun",surname:"Verma",slug:"nipun-verma",fullName:"Nipun Verma"},{id:"336280",title:"Dr.",name:"Anupam",surname:"Mittal",slug:"anupam-mittal",fullName:"Anupam Mittal"},{id:"336281",title:"Dr.",name:"Anuarg",surname:"Ramavat",slug:"anuarg-ramavat",fullName:"Anuarg Ramavat"}],corrections:null},{id:"75606",title:"Extracellular Matrix in Cardiac Tissue Mechanics and Physiology: Role of Collagen Accumulation",doi:"10.5772/intechopen.96585",slug:"extracellular-matrix-in-cardiac-tissue-mechanics-and-physiology-role-of-collagen-accumulation",totalDownloads:297,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The extracellular matrix (ECM) forms a mesh surrounding tissue, made up of fibrous and non-fibrous proteins that contribute to the cellular function, mechanical properties of the tissue and physiological function of the organ. The cardiac ECM remodels in response to mechanical alterations (e.g., pressure overload, volume overload) or injuries (e.g., myocardial infarction, bacterial infection), which further leads to mechanical and functional changes of the heart. Collagen, the most prevalent ECM protein in the body, contributes significantly to the mechanical behavior of myocardium during disease progression. Alterations in collagen fiber morphology and alignment, isoform, and cross-linking occur during the progression of various cardiac diseases. Acute or compensatory remodeling of cardiac ECM maintains normal cardiac function. However, chronic or decompensatory remodeling eventually results in heart failure, and the exact mechanism of transition into maladaptation remains unclear. This review aims to summarize the primary role of collagen accumulation (fibrosis) in heart failure progression, with a focus on its effects on myocardial tissue mechanical properties and cellular and organ functions.",signatures:"Kristen LeBar and Zhijie Wang",downloadPdfUrl:"/chapter/pdf-download/75606",previewPdfUrl:"/chapter/pdf-preview/75606",authors:[{id:"328709",title:"Assistant Prof.",name:"Zhijie",surname:"Wang",slug:"zhijie-wang",fullName:"Zhijie Wang"},{id:"344999",title:"BSc.",name:"Kristen",surname:"LeBar",slug:"kristen-lebar",fullName:"Kristen LeBar"}],corrections:null},{id:"75952",title:"The Extracellular Matrix of the Human and Whale Cornea and Sclera: Implications in Glaucoma and Other Pathologies",doi:"10.5772/intechopen.97023",slug:"the-extracellular-matrix-of-the-human-and-whale-cornea-and-sclera-implications-in-glaucoma-and-other",totalDownloads:148,totalCrossrefCites:3,totalDimensionsCites:3,hasAltmetrics:0,abstract:"The cornea is the transparent part of the eye that allows light to enter into the eye and reach the retina, thereby activating the neurons that will send messages to the brain. The sclera is the hard-white part of the eye, and its main function is to provide structure and form to the eye, and to support the retina. Indeed, while the cornea best performs its main functions when transparent and it is capable of adapting its curvature to allow the eye to focus, the sclera must be opaque and hard to function correctly. Both structures are mainly composed of collagen, some elastic fibres and ground substance, all components of the Extracellular Matrix. The disposition of the collagen fibres and the amount of ground substance around the fibres is responsible for the differences in the aspect of both these structures. In this chapter, for the first time we have compared the structure and ultrastructure of the cornea and sclera in humans and the whale adult (18mts) Balaenoptera physalus, the second largest animal on the planet. We will discuss how the differences in their structure may be related to the maintenance of intraocular pressure in their distinct environments, which is of particular clinical interest as increased intraocular pressure is one of the main causes underlying the development of open angle glaucoma.",signatures:"Elena Vecino, Noelia Ruzafa, Xandra Pereiro, Ane Zulueta, Alfredo Sarmiento and Alejandro Díez",downloadPdfUrl:"/chapter/pdf-download/75952",previewPdfUrl:"/chapter/pdf-preview/75952",authors:[{id:"31685",title:"Prof.",name:"Elena",surname:"Vecino",slug:"elena-vecino",fullName:"Elena Vecino"},{id:"345872",title:"Dr.",name:"Xandra",surname:"Pereiro",slug:"xandra-pereiro",fullName:"Xandra Pereiro"},{id:"345873",title:"Dr.",name:"Noelia",surname:"Ruzafa",slug:"noelia-ruzafa",fullName:"Noelia Ruzafa"},{id:"346752",title:"MSc.",name:"Ane",surname:"Zulueta",slug:"ane-zulueta",fullName:"Ane Zulueta"},{id:"346754",title:"Dr.",name:"Alfredo",surname:"Sarmiento",slug:"alfredo-sarmiento",fullName:"Alfredo Sarmiento"},{id:"346756",title:"Dr.",name:"Alejandro",surname:"Diez",slug:"alejandro-diez",fullName:"Alejandro Diez"}],corrections:null},{id:"74739",title:"The Evolutionary Origin of Elastin: Is Fibrillin the Lost Ancestor?",doi:"10.5772/intechopen.95411",slug:"the-evolutionary-origin-of-elastin-is-fibrillin-the-lost-ancestor-",totalDownloads:222,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Elastin is the extracellular matrix protein providing large arteries, lung parenchyma and skin with the properties of extensibility and elastic recoil. Within these tissues, elastin is found as a polymer formed by tropoelastin monomers assembled and cross-linked. In addition to specific protein regions supporting the covalent cross-links, tropoelastin is featured by the presence of highly repetitive sequences rich in proline and glycine making up the so-called hydrophobic domains. These protein segments promote structural flexibility and disordered protein properties, a fundamental aspect to explain its elastomeric behavior. Unlike other matrix proteins such as collagens or laminins, elastin emerged relatively late in evolution, appearing at the divergence of jawed and jawless fishes, therefore present in all species from sharks to humans, but absent in lampreys and other lower chordates and invertebrates. In spite of an intense interrogation of the key aspects in the evolution of elastin, its origin remains still elusive and an ancestral protein that could give rise to a primordial elastin is not known. In this chapter, I review the main molecular features of tropoelastin and the available knowledge on its evolutionary history as well as establish hypotheses for its origin. Considering the remarkable similarities between the hydrophobic domains of the first recognizable elastin gene from the elasmobranch Callorhinchus milii with certain fibrillin regions from related fish species, I raise the possibility that fibrillins might have provided protein domains to an ancestral elastin that thereafter underwent significant evolutionary changes to give the elastin forms found today.",signatures:"Fernando Rodriguez-Pascual",downloadPdfUrl:"/chapter/pdf-download/74739",previewPdfUrl:"/chapter/pdf-preview/74739",authors:[{id:"327242",title:"Ph.D.",name:"Fernando",surname:"Rodriguez-Pascual",slug:"fernando-rodriguez-pascual",fullName:"Fernando Rodriguez-Pascual"}],corrections:null},{id:"75828",title:"The Interplay of ECM-Based Graft Materials and Mechanisms of Tissue Remodeling",doi:"10.5772/intechopen.96954",slug:"the-interplay-of-ecm-based-graft-materials-and-mechanisms-of-tissue-remodeling",totalDownloads:205,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Wound healing is a complex natural process that involves the recruitment of cells, the renewal of tissue composition, and the reinforcement of structural tissue architecture. Following ischemic injury or chronic disease, wound healing is delayed, and can often result in chronic inflammation or permanent morbidity. Tissue engineering strategies to harness the wound healing process include the use of naturally derived extracellular matrix (ECM) scaffolds with inherent bioactivity to both passively facilitate and actively direct healing toward a successful resolution. As the body heals, the properly designed ECM scaffold is gradually remodeled and integrated into the body, leaving behind organized tissue that provides long-term strength. Herein we explain the interplay of the ECM (i.e., its complex composition and bioactivity) with the cells of the body throughout the process of tissue remodeling, thus explaining how even a tissue-engineered xenograft material can direct the body to restore itself.",signatures:"Jason P. Hodde and Michael C. Hiles",downloadPdfUrl:"/chapter/pdf-download/75828",previewPdfUrl:"/chapter/pdf-preview/75828",authors:[{id:"328075",title:"M.Sc.",name:"Jason P.",surname:"Hodde",slug:"jason-p.-hodde",fullName:"Jason P. Hodde"},{id:"332682",title:"Dr.",name:"Michael C.",surname:"Hiles",slug:"michael-c.-hiles",fullName:"Michael C. Hiles"}],corrections:null},{id:"76149",title:"Hyaluronic Acid Fillers: Where We Have Been and Where We Are Going",doi:"10.5772/intechopen.97264",slug:"hyaluronic-acid-fillers-where-we-have-been-and-where-we-are-going",totalDownloads:103,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Since the approval of the United States’ first hyaluronic acid (HA) filler in December 2003, HA fillers have become mainstays of soft tissue augmentation due to their favorable safety profile and minimally invasive treatment nature. The past two decades have not only brought an expansion in the popularity of HA fillers, but also in the number of available HA filler products and indications for cosmetic enhancement. Accordingly, HA filler injection has become one of the most commonly performed cosmetic procedures worldwide. The progression of HA filler products is a study in both biomedical engineering advancements, as well as evolving concepts of beauty and cosmesis. In this chapter, we review the history of these products, including their composition and indications for use. We then explore the prospect of HA fillers for the future of esthetic medicine, as they remain a vital component of nonsurgical soft tissue augmentation.",signatures:"Alexander Daoud and Robert Weiss",downloadPdfUrl:"/chapter/pdf-download/76149",previewPdfUrl:"/chapter/pdf-preview/76149",authors:[{id:"328230",title:"Associate Prof.",name:"Robert",surname:"Weiss",slug:"robert-weiss",fullName:"Robert Weiss"},{id:"329813",title:"Dr.",name:"Alexander",surname:"Daoud",slug:"alexander-daoud",fullName:"Alexander Daoud"}],corrections:null},{id:"76651",title:"Hyaluronic Acid Derivatives for Targeted Cancer Therapy",doi:"10.5772/intechopen.97224",slug:"hyaluronic-acid-derivatives-for-targeted-cancer-therapy",totalDownloads:202,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Targeted therapeutics are considered next generation cancer therapy because they overcome many limitations of traditional chemotherapy. Cancerous cells may be targeted by various hyaluronic acid modified nanovehicles that kill these cells. Particularly, hyaluronic acid and its derivatives bind with high affinity to cell surface protein, CD44 enriched tumor cells. Moreover, these molecules have the added advantage of being biocompatible and biodegradable, and may be conjugated with a variety of drugs and drug carriers for developing various formulations as anti-cancer therapies such as nanogels, self-assembled and metallic nanoparticulates. In this chapter, we have covered various aspects of hyaluronic acid-modified delivery systems including strategies for synthesis, characterization, and biocompatibility. Next, the use of hyaluronic acid-modified systems as anti-cancer therapies is discussed. Finally, the delivery of small molecules, and other pharmaceutical agents are also elaborated in this chapter.",signatures:"Nilkamal Pramanik and Sameer Kumar Jagirdar",downloadPdfUrl:"/chapter/pdf-download/76651",previewPdfUrl:"/chapter/pdf-preview/76651",authors:[{id:"327038",title:"Dr.",name:"Nilkamal",surname:"Pramanik",slug:"nilkamal-pramanik",fullName:"Nilkamal Pramanik"},{id:"334285",title:"Ph.D. Student",name:"Sameer",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar"}],corrections:null},{id:"77440",title:"Plant Natural Products: A Promising Source of Hyaluronidase Enzyme Inhibitors",doi:"10.5772/intechopen.98814",slug:"plant-natural-products-a-promising-source-of-hyaluronidase-enzyme-inhibitors",totalDownloads:226,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Hyaluronidase enzyme degrades hyaluronan, the primary component of the extracellular matrix found in connective tissues animals and on the surface of certain pathogenic bacteria. The degradation of hyaluronan is linked to a wide range of physiological and pathological process. Inhibiting the hyaluronidase enzyme is thus significant as an approach to treat a variety of diseases and health conditions such as anti-fertility, anti-tumor, antimicrobial, and anti-venom/toxin agents. HAase inhibitors of different chemical types have been identified include both synthetic compounds and constituents obtained from naturally sources. Plant natural products as HAase inhibitors are unique due to their structural features and diversity. Medicinal plants have historically been used as contraceptives, antidote for snakebites and to promote wound healing. In recent years, small molecules, particularly plant natural products (alkaloids, flavonoids, polyphenol and flavonoids, triterpenes and steroids) possessing potent HAase have been discovered. A number of plant species from various families, which have folk medicinal claims for these ailments (related to hyaluronan disturbances) were scientifically proven for their potential to block HAase enzymes.",signatures:"Muhammad Zeeshan Bhatti and Aman Karim",downloadPdfUrl:"/chapter/pdf-download/77440",previewPdfUrl:"/chapter/pdf-preview/77440",authors:[{id:"328295",title:"Dr.",name:"Aman",surname:"Karim",slug:"aman-karim",fullName:"Aman Karim"},{id:"345782",title:"Dr.",name:"Muhammad Zeeshan",surname:"Bhatti",slug:"muhammad-zeeshan-bhatti",fullName:"Muhammad Zeeshan Bhatti"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:{id:"14",series:{id:"11",title:"Biochemistry",issn:"2632-0983",editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"6",institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}}}},tags:null},relatedBooks:[{type:"book",id:"3420",title:"Advances in Biomaterials Science and Biomedical Applications",subtitle:null,isOpenForSubmission:!1,hash:"381d506a331ddc9ae4d423dea265e0a2",slug:"advances-in-biomaterials-science-and-biomedical-applications",bookSignature:"Rosario Pignatello",coverURL:"https://cdn.intechopen.com/books/images_new/3420.jpg",editedByType:"Edited by",editors:[{id:"64447",title:"Prof.",name:"Rosario",surname:"Pignatello",slug:"rosario-pignatello",fullName:"Rosario 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\r\n\tMalaria is an acute febrile illness caused by Plasmodium parasites, which are spread to people through the bites of infected female Anopheles mosquitoes. It’s the second commonest infectious disease worldwide (following hepatitis B). Despite being potentially preventable and curable, in 2020 there were an estimated 241 million cases; the estimated number of deaths being 627,000. Nearly half of the world's population is at risk of malaria. However, some population groups are at considerably higher risk of contracting malaria and developing the severe disease: children, pregnant women, and patients with low immunity. Noteworthy, 95% of malaria cases and 96% of malaria deaths occur in African Countries, with 80% of all deaths being in children under 5. Recent advancements include more accurate vectors control, chemotherapies, and possibly vaccine development. In this book, the current and most advanced knowledge about malaria is discussed, by focusing on pathobiology, diagnosis, clinical features, and management.
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For instance, it is widely developed in macro‐ or microscopy for measuring in the flow the location or size of particles [2, 3] or for measuring the temperature or the thermal exchanges in the flames [4, 5]. Other authors have developed digital colour holographic interferometry by using three different wavelengths (one red, one green and one blue) as a luminous source. Qualitative results have been obtained for visualizing convective flows induced by the thermal dissipation in a tank filled with oil [6]. Quantitatively, the feasibility of three‐wavelength digital holographic interferometry has been demonstrated for analysing the variations in the refractive index induced by a candle flame [7] and the technique has been applied in wind tunnel on two‐dimensional unsteady flows where the time evolution of the gas density field has been determined on the subsonic near wake flow downstream a circular cylinder [8]. But, when the flow regime reaches the transonic or supersonic domain, problems appear because refractive index gradients become very strong and a shadow effect is generated by the shock waves, for instance, superimposes to the micro‐fringes of interferences. Phase shifts appear and limit the interferogram analysis. In order to solve these different problems, the authors propose to study three different cases of flows presenting high‐density gradients using specific optical techniques based on digital holography. The first one concerns a small supersonic jet analysed by Michelson colour digital interferometry, colour holographic interferometry using Wollaston prisms and monochromatic digital holography without reference wave. The second case is to compare Michelson and Mach‐Zehnder interferometers for analysing the unsteady wake flow around a circular cylinder at transonic Mach number. And finally, digital and image holographic methods are presented to visualize and measure the refractive index variations, convection currents or thermal gradients occurring inside a transparent and strongly refracting object. In the case of image holographic interferometry, a comparison with transmission and reflection holograms is provided.
\nDigital holography has been widely developed for analysing diffusive objects since the digitally reconstructing of the optical wavefront was shown by Goodman and Lawrence [9]. But, in fluid mechanics, the objects under analysis are very often transparent because it is the field of refractive index of the flow which is measured. There are two ways to measure variations in the refractive index by digital holography. The first one, presented in Figure 1, is comparable to the technique used for measuring diffusive objects in structural mechanics.
\nFresnel holography for measuring transparent objects.
For example, if three different wavelengths are considered, ∑MR for the red line, ∑MG for the green line and ∑MB for the blue line, the wavefronts of measurement which cross the transparent object in the test section can be sent on a ground plate and each point of the plate diffracts and interferes on the sensor with the three reference waves, ∑RR, ∑RG and ∑RB. In this case, the sensor can be a Bayer mosaic, a stack of photodiodes or a 3CDD. The recorded image is a speckle image which can be processed using Fresnel transform and the field
Fourier holography for measuring transparent objects.
All details and basic fundamentals of these two techniques can be found in the study of Picart et al. [10].
\nIn this part, the supersonic flow of a small vertical jet has been analysed using three different techniques based on digital holography. The first one is based on Michelson digital holographic interferometer using three wavelengths as a luminous source [8], the second one uses the same source (three wavelengths) and Wollaston prisms to separate the reference waves and the measurement waves [11] and the last one is a little bit particular because a specific diffraction grating is manufactured to obtain several different diffractions of measurement waves and to avoid having the reference wave [12].
\nThe optical set‐up presented in Figure 3 is very simple and looks like a conventional Michelson interferometer in which a beam splitter cube (7) is inserted between the spatial filter (6) and the aerodynamic phenomenon under analysis (11). The light source consists of three diode‐pumped solid‐state lasers, one red (R), one green (G) and one blue (B), emitting respectively at 660, 532 and 457 nm. A half wave plate (1) is used to rotate by 90° the polarization of the blue line (S to P) and a flat mirror (2) and two dichroic plates (3) allow the superimposing of the three wavelengths. An acousto‐optical cell (4) deflects the parasitic wavelengths in a mask (5) and diffracts the three wavelengths RGB using three characteristic frequencies injected into the crystal. The spatial filter (6), composed of microscope objective (60×) and a small hole of 25 μm, is placed at the focal length of the achromatic lens (9) in order to illuminate the phenomenon with a parallel beam. On‐going, 50% of the light is returned towards the concave mirror (8) to form the three reference beams and 50% of the light passes through the test section (between (9) and (12) to form the measuring waves. The flat mirror (12) placed behind the test section (11) returns the beams in the beam splitter cube (7). 25% of the light focused on the diaphragm which is placed in front of the achromatic lens (13). It is the same for the 25% of the reference beam which is focused on the same diaphragm by the concave mirror (8).
\nMichelson digital holographic interferometer.
Michelson digital holographic interferometer has been implemented around the ONERA wind tunnel and two optical tables isolate the optical set‐up from external vibrations. Figure 4 shows the generation of micro‐fringes used as spatial carrier frequencies.
\nMicro‐fringes formation by the transparent object.
When the focal points of the reference and object waves are superimposed in the diaphragm which is placed in front of the lens (13), see Figure 3, a uniform background colour is observed on the screen for each colour. The combination of three background colour (R, G and B) produces a white colour on 3CCD camera. If the focusing point of the three reference waves is moved in the plane of the diaphragm, straight interference fringes are introduced into the field of visualization. This is achieved very simply by rotating the concave mirror (8). Without flow, these micro‐fringes are recorded on the 3CCD to calculate the three reference phase maps. Then, the wind tunnel is running and the three object waves are distorted by the aerodynamic phenomenon. Micro‐fringe interferences are again recorded to enable calculation of the phase maps related to the object. For maps of phase difference, the reference phase is subtracted from the phase object. This optical technique was tested for analysing the supersonic flow of a small vertical jet, 5.56 mm in inner diameter at different pressures of injection. The location of the vertical jet in the middle of the test section is shown in Figure 3. The exposure time (10 ms) is given by the acousto‐optical cell noted (4) in Figure 3. The fringe space introduced in the field is much narrowed, about four or five pixels between two successive fringes, in order to generate three high spatial carrier frequencies. With this configuration, the sensitivity is increased. Each interferogram is processed with 2D fast Fourier transform and Figure 5 shows the spectra computed for the reference and measurement for each colour plane. One can see that the generated spatial frequencies are respectively equal to 40.5, 30.9 and 28.4 lines per millimetre for the blue, green and red lines. Then, a filtering window is selected to cover the useful signal of the +1 order localized in the spectrum and an inverse 2D FFT is applied to reconstruct the amplitude and the phase of the signal.
\n2D spectra computed from the reference and the measurement interferograms.
First, the phase maps are calculated from the three reference and three measurement spectra so that the modulo 2
Maps of RGB phase difference (modulo 2
Finally, the maps of light intensity and optical thickness difference are calculated from the phase difference maps. They are presented in Figure 7 for pressures ranging from 2 to 5 bar. Concerning the maps of the luminous intensity, they are corresponding to figures which will be obtained if a technique of image holographic interferometry using panchromatic plates has been used. Knowing the wavelength and the phase, the maps of optical thickness can be deduced. They are also presented in Figure 7 from 2 to 5 bar. At 2 bar and in the middle of shock structures, the optical thickness varies up to 0.2 μm and at 5 bar, it varies up to 1μm.
\nEvolution of the luminous intensity and the optical thickness with the pressure.
This part proposes an optical set‐up based on digital holographic interferometry using two widely shifting Wollaston prisms and a single crossing of the phenomenon. Each Wollaston prism is located at the focal point of ‘Z’ astigmatic optical set‐up. The second Wollaston is located in front of the camera and between the two sagittal and transverse focal lines so that a rotation around the optical axis generates interference micro‐fringes which are used as spatial carrier frequency.
\nDifferential interferometry using Wollaston prism visualizes the light deviation of the refractive index in a direction perpendicular to the direction of the interference fringes. Indeed, in the case of quartz prism having a very weak pasting angle, the gradient of the refractive index is measured because the birefringence angle is very weak and the distance between the two interfering beams is of the order of a few tenths of a millimetre or a few millimetres in the test section. Data integration is necessary to obtain the absolute refractive index. To avoid this integration, it was decided to manufacture two Wollaston prisms having a very high birefringence angle so that the distance between the two interfering beams is greater than the dimension of the measuring field (jet size). The interference measurement will be made between a beam which does not pass through the phenomenon (reference beam) and one which crosses the phenomenon under analysis. If
If a very high birefringence angle is sought, the pasting angle and the crystal birefringence have to be as high as possible. To remember, the
If
Thus, for a spherical mirror of 400 mm in diameter and 4 m in the radius of curvature,
Calcite Wollaston prisms with 8° pasting angle have been manufactured.
\nFigure 8 shows the principle of Z optical set‐up using Wollaston prisms. Here also, three different DPSS lasers (red, green and blue) constitute the luminous light source and the optical set‐up uses two spherical mirrors, 250 mm in diameter and 2.5 m in radius of curvature.
\nDigital holographic interferometer using very large Wollaston prisms in ‘Z’ set‐up.
Astigmatism represented by sectional views and Wollaston prism in the front of the camera.
As all optical pieces are not exactly on the optical axis of spherical mirrors, we can observe astigmatism in the optical arrangement. The first prism located at the focal length of the first spherical mirror produces two optical rays which are returned by parallel light beams onto the second spherical mirror. This one refocuses the light beam into the second Wollaston prism which is mounted ‘tumble’ with the first one. An analyser located behind the second prism allows visualizing the interference fringes in colour. The image of the object under analysis is formed by a field lens placed in front of the 3CCD sensor. Here, the advantage of astigmatic set‐up is used because the focusing point in the front of the camera is not unique. Figure 9 shows this particularity: the optical beams are focused on the two focal images successively separated by a few millimetres. The first one gives the tangential image encountered when the beam focuses in the horizontal plane, and the second one, called the sagittal image, is obtained when the beam focuses in the vertical plane.
\nFigure 10 shows, on the reception side, the different figures of interference observed when the second Wollaston prism is moved along the optical axis from the tangential image (TI) towards the sagittal image (SI). The interference fringes which were horizontal and much narrowed, spread. When the interference fringes spread again, we can observe a rotation of 90° by them to give a quasi‐uniform vertical background colour, at half distance between the tangential and sagittal images. Then, they continue to rotate by 90° up to the sagittal image and they narrow to become horizontal. Interference fringes stay horizontal above the sagittal image and narrow more and more. Knowing this property, we can adjust the spatial carrier frequency by the axial displacement of the prism for its amplitude and by rotating the prism for its orientation. In our tests, the Wollaston prism is located at half distance between the tangential and sagittal images, so that the interference fringes are generated in the same direction as the direction of the two interfering beams (vertical shift and vertical fringes). Gontier et al. [13] has widely described this feature. If the number of fringes in the visualized field has to be increased, the Wollaston prism has to be turned on itself in the plane perpendicular to the optical axis. Figure 10 shows two positions of rotation of the Wollaston prism (20 and 45°) with a maximum number of fringes obtained for the rotation of 45°.
\nEvolution of interference fringes when the second Wollaston is moved from the sagittal image to the tangential image.
First, Figure 11 shows the interferograms for the reference and the measurement with an enlarged view near the injection. For a pressure of 4 bar, for instance, one can see the horizontal interference fringes disturbed by the flow. The interferograms of Figure 10 also show that the field is reduced on the right and left sides: this is the result of the rotation of the Wollaston prism at return which has a limited size (15 mm2). The polarization fields which were completely separated on the way interfere with each other as the prism placed in front of the camera is rotated. It is also noteworthy that the polarizer is rotated exactly to the same amount as the Wollaston prism. The tightening of the fringes is maximal when the prism is rotated by 45°.
\nInterference micro‐fringes recorded for the reference and the measurement,
Then, 2D fast Fourier transform is applied to filter the zero and -1 orders on the three channels for the reference and the measurement interferograms. In Figure 12, one sees that the different window filtering size can be taken on the three channels and that the reduced frequencies are equal to 0.12, 0.10 and 0.9 mm-1 for the blue, green and red channels that correspond to resolution of 18.6 lines/mm, 15.5 lines/mm and 13.9 lines/mm. The spatial resolution used is lower than that used in the technique of Michelson interferometry.
\n2D spectra computed on the three channels for the reference interferogram,
Figure 13 shows the spectrum of the measurement for P = 3 bar, the modulo 2
Analysis of the case for red channel
Digital holography without reference wave allows quantitative phase imaging by using a high‐resolution holographic grating for generating a four‐wave shearing interferogram. The high‐resolution holographic grating is designed in a ‘kite’ configuration so as to avoid parasitic mixing of diffraction orders. The selection of six diffraction orders in the Fourier spectrum of the interferogram allows reconstructing phase gradients along specific directions. The spectral analysis yields the useful parameters of the reconstruction process. The derivative axes are exactly determined whatever the experimental configurations of the holographic grating. The integration of the derivative yields the phase and the optical thickness [12].
\nFigure 14 shows the principle of the hologram recording of pure phase modulation where an incident plane crosses the phenomenon under analysis. This wave, disturbed by the phenomenon, is simultaneously diffracted in several directions by a diffraction grating operating in reflection. The different images diffracted by the grating interfere with each other at a
Principle of self‐referenced digital holography by reflection.
The sensor therefore records a digital hologram produced by the coherent superimposition of all the diffraction orders. Let
In Eq. (4),
In Eq. (5), the first term is related to the zero order, and the last one is related to coherent cross‐mixing between the P diffracted orders. The last term includes the useful data related to the phase at the object plane. Noting
Eq. (6) can be simplified by considering spatial derivatives of the object phase according to:\n
In Eq. (7),
First, a holographic grating is recorded with the optical set‐up shown in Figure 15. The holographic plates are single‐layer silver‐halide holographic plates from Gentet (http://www.ultimate‐holography.com/). The spatial resolution reaches 7000 lines per mm and the holographic plate has been preferred to the photopolymer which has lower spatial resolution (1000–2000 lines per mm).
\nOptical set‐up defined for recording of reflection holographic grating.
A first beam splitter cube (80/20) forms a reference beam (blue beam) with 20% of the incident light and 80% of the light is used to form the four‐object beams. Plane waves are obtained with two lenses and two spatial filters. Object waves are generated by three‐beam splitter cubes (50/50) so that the luminous intensities of each beam (reference and object) are all equal to 20% of the initial laser power. After several reflections on flat mirrors (MP), four small mirrors located around a square (configuration no. 1) and around a kite (configuration no. 2) returns each object beams towards the holographic plate. As the reference wave and the four object waves are incoming on each side of the hologram, the hologram is recorded by reflection and the angle
Digital holographic interferometer without reference.
An interferogram without flow and another with flow are directly recorded on the sensor (2000 × 1500 pixels, 365 mm2), then analysed in delayed time by 2D fast Fourier transform in order to localize the different interference orders. For configuration no. 1, Figure 17 shows the location of four mirrors used at the recording (square). Order 1 results of interaction of the beams incoming from M1 and M2 mirrors and the order 1′ between M3 and M4. Similarly, order 2 is generated by the interference between the waves incoming from M1 and M3 mirrors and order 2′ those issuing from M2 and M4. Order 3 is only produced by the interference between M1 and M4 and order 4 between M2 and M3. For configuration no. 1, order 1 or 2 has been enlarged in order to show that order 1 and 1′ or 2 and 2′ are not quite superimposed.
\nPosition of four mirrors (square and kite) at the recording, localization of different diffraction orders in 2D FFT plane and zoom of +1 order.
In fact, one obtains two spectral signatures slightly shifted. It is not possible to separate them by filtering and to reconstruct the phase derivative map induced by only order 1. For this reason, the four mirrors have been set at the four tops of a kite configuration (no. 2). The problem encountered with configuration no. 1 does not exist and 2D FFT shows that it is very easy to localize all the different diffraction orders (on right in Figure 17). There is no spectral overlap and all orders useful for the reconstruction are well separated. Each order of interference is then selected successively and separately with a circular mask (0.05 mm−1 radius). Then, the phase gradient of reference image is calculated for each order of interference (Figure 18). Subtracting the reference image to the measurement image gives a modulo 2
Recorded interferogram and gradient phase maps obtained for the six interference orders.
Figure 19 shows results obtained with digital holographic interferometry without reference and two other results obtained with digital holographic interferometry using a reference wave. The comparison is made by taking into account the difference of optical thickness.
\nThe scale level is basically the same for the three results (from 0 up to 1.2 μm), and Figure 19 shows at 5 bar that they are in good agreement because spatial locations of the structures of compression and expansion waves are similarly positioned in the three measurements. From a point of view of easiness and accuracy of results, the optical set‐up without reference is complicated to implement and must achieve a kite‐type reference hologram. It is also difficult to obtain a hologram with high diffraction efficiency. In addition, the data obtained must be integrated, which cause a certain imprecision in the measurement. For the optical set‐up using Wollaston prisms, it is very bulky and costly because the Wollaston prisms of ‘large field’ type are expensive and difficult to manufacture. On the other hand, the measured values are absolute values as those obtained with Michelson interferometer that seems the least restrictive optical arrangement of the three set‐ups tested.
\nComparison of experimental results obtained for three different interferometric techniques for a pressure at P=5 bar. (a) Without reference set‐up, (b) Michelson set‐up, (c) Wollaston set‐up.
The unsteady wake flows generated in wind tunnel present a large scale of variations in refractive index from subsonic to supersonic domain. The feasibility of three‐wavelength digital holographic interferometry has been shown on two‐dimensional unsteady flows and the time evolution of the gas density field has been determined on the subsonic near wake flow downstream a circular cylinder [8]. But, when the flow regime reaches the transonic or supersonic domain, problems appear because refractive index gradients become very strong and a shadow effect superimposes to the micro‐fringes of interferences. Moreover, the displacement of vortices is very high compared to the exposure time (300 ns given by the acousto‐optical cell, Figure 3) what leads to blurred zones in interferograms and limits the interferograms analysis (Figure 20).
\nHighlighting of blurred areas and shadow effect—Mach 0.73.
At first, an ORCA Flash 2.8 camera from Hamamatsu with a matrix of 1920 × 1440 pixels, 3.65 μm2, has been bought to increase the spatial resolution and, for the temporal resolution, the continuous laser light source of the interferometer has been replaced by a Quanta‐Ray pulsed laser, Model Lab 170‐10 Hz from Spectra‐Physics. This laser is injected through a 1064 nm laser diode and outputs a wavelength at 1064 nm having 3 m in coherence length (TEM00 mode). Here, the first harmonic is used (532 nm) and delivers about 400 mJ in 8 ns. The beam diameter is about 8–9 mm. Figure 21 shows how the laser was installed in Michelson interferometer presented in Figure 3. The output beam is equipped with two sets ‘
Digital Michelson holographic interferometer using a pulsed laser.
If
Figure 22 shows an interferogram of unsteady wake flow around a circular cylinder at Mach 0.73 with Michelson interferometer, the 2D FFT spectrum with the +1 order used to reconstruct the map of the modulo 2
Interferogram analysis at Mach 0.73—residual phase shifts.
In Mach‐Zehnder interferometer, shown in Figure 23, the measuring beam crosses only once the test section and the reference beam passes outside the test section so that the sensitivity is decreased by a factor 2.
\nDigital Mach‐Zehnder holographic interferometer using a pulsed laser.
In this optical set‐up, the reference beam is reflected successively by several little flat mirrors. That produces a polarization rotation of the reference wave which must be corrected by inserting a
Interferograms analysis at Mach 0.73.
Then, an unwrapping has to be applied to obtain the phase difference map
Instantaneous and averaged gas density fields (
where
The instantaneous interferogram of Figure 25 shows that shock waves emitted by the vortices of the vortex shading are very well analysed (no phase shift) and the averaged gas density field exhibits a strong decreasing of the gas density just behind the cylinder up to 90% of
High‐density gradients can also exist inside strongly refracting objects and the visualization and the measurement of these phenomena remain an open problem. For example, objects as a glass ball, a light bulb, a glass container, a glass flask, etc. are not opaque but they are strongly refracting light and measuring inside is not straightforward. It follows that observing phenomena, such as refractive index variations, convection currents, or thermal gradients, occurring inside the object requires specific methods. Different experimental methods are usually used to investigate fluids and to visualize/measure dynamic flows [7, 8, 17]. Nevertheless, these approaches are appropriated when the envelope including the flow is relatively smooth and transparent (i.e. not strongly refracting). A suitable experimental method should be able to exhibit the phase changes inside the object without suffering from any image distortion. The experimental approach described here is based on stochastic digital holography to investigate flows inside a strongly refracting envelope [18]. It leads to the measurement of the phase change inside the object, so as to get a quantitative measurement. Experimental results are provided in the case of the visualization of refractive index variations inside a light bulb and a comparison with image transmission and reflection holography is also provided.
\nThe approach adapted to visualize inside a strongly refracting object is described in Figure 26. The sensor includes
Stochastic digital holographic set‐up.
In particular, the focal length of the lens has to be judiciously chosen. Especially, the criterion is the observation angle
where α is the accepted tolerance in the superposition of the useful +1 order and the 0 order. Here, the diffuser (considered here as a ‘stochastic screen’) is sized 10 cm × 20 cm and a superposition tolerance of
The proposed method has been applied to the visualization and analysis of light bulb during its lighting. This bulb was submitted to a current to produce light and holograms were recorded at different instants after its lighting. Figure 27 shows the recorded hologram when the bulb is off (a) and when the bulb is lighting (b). The speckle nature of the hologram is clearly observed. Figure 27c shows the amplitude image obtained with the discrete Fresnel transform. The stochastic screen and the ampoule can be clearly seen so that the strand of the bulb. Figure 27d and e shows respectively the modulo 2
Quantitative measurement inside the bulb, (a) virtual phase extracted from numerical reconstruction (bulb off), (b) bulb lighting, (c) image amplitude of the strand, (d) modulo 2
In order to check for the quality of the results obtained with the proposed method, the results obtained were compared with analogue image‐holography [23]. The two possible set‐ups are described in Figure 28 and can be either transmission or reflection holographic interferometry. Figure 28a shows the transmission holography mode and Figure 28b that for reflection holography. Note that the set‐ups require the use of photographic plates and that the diffuser is also used to get a stochastic screen to illuminate the object. The process is as follows: record a transmission or reflection hologram, apply the chemical treatment to the plate to develop and bleach, dry the plate, put the holographic plate in the set‐up anew (exactly at the same location), at this step the holographic image of the ampoule is observable, adjust the camera lens to produce a focused image, then record real‐time interferences between the initial bulb and that currently submitted to the current. Note that only the luminous intensity of interference fringes can be obtained, and not the phase image as it is the case for the digital holographic approach.
\nImage transmission holography (a) and image reflection holography (b).
Figure 29 shows a comparison between results obtained with digital holography and those obtained with image holography. Figure 29a shows the image obtained with the amplitude and phase change measured by digital holography, after calculating the intensity
Comparison between intensity of fringes (a) fringes calculated with digital holography, (b) fringes obtained with transmission holography and (c) fringes obtained with reflection holography.
This chapter has shown several possibilities of digital holographic interferometry for analysing high‐density gradients encountered in transonic and supersonic flows. Concerning the analysis of a small supersonic jet, a comparison is given between three different techniques, two techniques use reference waves: Michelson holographic interferometry and digital holography using Wollaston prisms; the last one uses a specific diffraction grating to obtain several different diffractions of measurement waves and to avoid having the reference wave.
\nFor analysing transonic flows in wind tunnel, two types of interferometer have been developed. The first one is very simple to implement because it is a Michelson interferometer with double crossing of the test section for increasing the sensitivity and the second one is a Mach‐Zehnder interferometer, more difficult to adjust, with a single crossing of the test section. These two interferometers are equipped with a pulsed laser and interferograms obtained have a very good quality and, basically, no phase shift.
\nFinally, a digital holographic method is proposed to visualize and measure refractive index variations, convection currents, or thermal gradients, occurring inside transparent but a strongly refracting object. The principle of this technique is provided through the visualization of refractive index variation inside a lighting ampoule. Comparisons with image transmission and reflection holographic interferometry demonstrate the high image and phase quality that can be extracted from the stochastic digital holographic set‐up.
\nCurrently, digital holographic interferometry is developed by ONERA for studying 3D flows from multi directional tomographic interferograms recorded in several directions. The aim is first to compare this method with other techniques yielding the gas density field as differential interferometry, back‐oriented schlieren (BOS) and colour BOS; and secondly, to find the best compromise between the number of sight of view, the computation time and the results accuracy.
\nThe authors thank the French National Agency for Research (ANR) for funding this work under grant agreement no. ANR‐14‐ASTR‐0005‐01.
Lead is one of the most dangerous toxic metals. This metal has no known beneficial function in the human body. In contrast, lead can impair every system of the human body and specially the renal, hematopoietic, neurological, and reproductive systems. Exposure to lead has been associated with a broad range of physiological, biochemical, and behavioral and harmful effects. There is evidence of several reproductive damages in humans exposed to lead. In women, lead exposure has been associated with spontaneous abortion [1], low birth weight [2], preterm delivery [3], fetal growth restriction [4], premature rupture of membranes [5], pregnancy hypertension [6], preeclampsia [7], and gestational diabetes [8]. Maternal blood lead has also been associated with a decrease in length of gestation [9].
With respect to men, exposure to inorganic lead has been linked to a decrease in some parameters of semen quality. Lead exposure has been considered to adversely affect spermatogenesis [10] and reduced fertility [10]. High lead concentrations in seminal plasma can reduce the sperm count [10]. Sperm motility and sperm morphology also can be affected by lead [11].
The present chapter focuses on the harmful effects of lead on reproductive health of both men and women, due to the importance to established preventive measures to protect the health of parents and children exposed to this toxic metal.
Exposure to lead has been associated to several reproductive dysfunctions in men, such as decreased libido, impairment of spermatogenesis, and chromosomal damage, among others. However, studies about the relationship between lead exposure and male reproductive damage have shown inconsistent results. Most of the studies have analyzed the relationship between blood lead and semen quality due to the correlation observed between semen lead and blood lead [12]. Some studies have reported reduction in sperm count, morphology, and motility in men exposed to lead [13].
The effects of lead on sperm quality have been frequently studied in occupationally exposed individuals. National Institute for Occupational Safety and Health (OSHA) recommends that blood lead levels (BLL) above 40 μg/dL require health intervention. Nevertheless, studies in men without occupational exposure also showed evidence of the effects of lead on fertility. In a prospective, double-blind study carried out to evaluate the impact of seminal plasma lead levels on fertility, seminal plasma lead below this threshold value was associated with adverse effects on in vitro fertilization rates. In this survey, semen donors who participated in an artificial insemination program were included. Sperm lead concentrations were also negatively correlated with mannose receptors and mannose-induced acrosome reactions, the two biomarkers of sperm function [14]. These results show that increased lead concentrations in semen can harm male fertility.
Although most studies on the relationship between lead and infertility have been carried out in occupationally exposed workers, alterations in semen concentration of lead have been also observed in men without occupational exposure, probably due to other sources of exposure such as environment and foods. In a prospective and randomized clinical study carried out in men from infertile couples without occupational exposure to lead, a negative correlation between semen lead concentration and sperm count was observed in semen samples collected after 3–5 days of abstinence [10]. These results provide evidence that lead from environment and diet can also affect semen quality and, therefore, male fertility.
Several studies have evaluated the effect of lead exposure on the endocrine system. In lead smelting workers without clinical symptoms of lead poisoning, a decrease in serum testosterone (T) and an increase in steroid-binding globulin (SGG) levels were observed [15, 16, 17, 18]. It is considered that lead impairs the majority of the endocrine glands. The analysis of the effect of long-term exposure to lead on thyroid function in exposed workers showed a negative association with T4 and FT4, and the depressed thyroid function was especially observed when the exposure was the most intensive [18]. In a group of workers occupationally exposed to lead from three battery factories, concentrations of FSH and LH were higher in comparison with a control group of non-exposed men, which constitutes an indicator that lead exposure alters testicular function [19]. From the biochemical point of view, it is considered that lead first causes testicular damage, and long-term exposure alters the hypothalamic-pituitary axis [17, 18, 20].
However, the results on this topic cannot be considered conclusive. In a study of the relationship between lead exposure and sex hormone levels in 133 men who had worked, at least for 6 months, in a battery manufacturing plant, BLL was measured, and endocrine system function was assessed by measuring testosterone, free testosterone, follicle stimulated hormone (FSH), and luteinizing hormone (LH). Workers were classified into two groups based on OSHA BLL standard: with BLL lower than 40 μg/dl and those with BLL equal or higher than 40 μg/dL. Statistical analysis showed no significant association between blood lead concentrations (BLC) and the sex hormone values. The authors concluded that lead exposure is not related to changes in male hormone levels [21]. In contrast, the evaluation of sperm count, sperm morphology, and hormonal levels (LH and FSH) of individuals attended in an infertility clinic in Iran showed negative significant correlations with BLL, while no correlation between BLC and sperm morphology was found [22].
Despite some contradictory results, there is a growing concern about the harmful effects of lead on male fertility, semen quality, and hormonal levels [15, 22]. Experiments in animal models have demonstrated that lead contributes to decreased male reproductive function [23]. In humans, lead exposure has been also associated with male endocrine dysfunction [24]. It is considered that oxidative stress plays an important role on male infertility. Lower total antioxidant capacity (TAC) and vitamin E concentrations were observed in seminal plasma of infertile men in comparison with fertile subjects [25]. In addition, there were significant differences between compared groups in accumulation of malondialdehyde. Moreover, concentration of malondialdehyde negatively correlated with sperm motility and morphology. On the basis of these results, it is suggested that seminal antioxidants and blood antioxidants can be used as biomarkers of sperm quality.
The effect of lead on reproductive health may vary due to the length of exposure. Taking into account the above-mentioned points, in a cross-sectional study of male workers, the effects of current and long-term occupational lead exposures on several biomarkers of male reproductive health were evaluated [11]. Semen and blood samples from male employees of a lead smelter were obtained, and concentrations of testosterone, follicle stimulated hormone, luteinizing hormone, and blood lead were determined. A decreasing trend in total sperm count was observed in relation to the increase in BLL. In addition, total motile sperm count, sperm concentration, and total sperm count showed an inverse relationship with long-term lead exposure. Nevertheless, lead exposure was not associated to sperm motility, sperm morphology, or serum concentrations of reproductive hormones.
The effects of lead exposure on male reproductive function have also been studied in animals. Experiments in mouse have shown that lead can interfere with the binding of androgens [26], suppress follicle stimulating hormone production [27], affect the function of Sertoli cell, and increase the lactate production, which constitute an essential substrate for spermatogenesis [28]. Lead exposure has been also associated with decreases in the activity of testicular oxidizing enzymes [29] and in the synthesis of testicular RNA in rats [28]. A study conducted in rats showed a positive correlation between blood lead and levels of lead in epididymal sperm and demonstrated that lead can cause generation of reactive oxygen species in sperm, which led to oxidative stress and, therefore, impairment of sperm function [30].
Epidemiological data indicate that exposure to lead can cause prostate diseases in adult males. In a study, blood lead in patients suffering from prostate cancer (PCA), patients with benign prostate hyperplasia (BPH), and a control group of men living in similar socioeconomic conditions was examined [31]. Results indicated significant higher concentrations of lead in blood in PCA and BPH males in comparison with controls. In addition, patients with PCA and BPH had significantly lower blood levels of zinc and copper than the comparative group. It is well known that Zn has an essential role in the regulation of prostate epithelium homeostasis and in ejaculation [32]. Zinc is a cofactor for many enzymes and an essential metal for the integrity of cellular membrane [33]. Lead can displace zinc ions at the proteins, provoking the inhibition of the enzymes. The displacement of zinc by lead in seminal fluid could determine the effects of prostate function, leading to decreased fertility [32].
Some authors consider that the main effect of lead on the male reproductive system is the alteration of the reproductive hormonal axis and the hormonal control of spermatogenesis, instead of the direct effect on the seminiferous tubules of the testes [23, 34]. Moreover, there is evidence that the blood-testis barrier acts as a protection for the testis cells against the harmful effects of lead [35, 36]. On the other hand, some researchers pay more attention to the impairment of sperm parameters, such as volume of ejaculation, sperm density, abnormal morphology, sperm count, and motility, by the toxic effect of lead [10, 14, 22, 37].
Although the mechanisms by which lead affects male reproductive health are still unclear, there is no doubt that this toxic metal can jeopardize fertility in men due to alterations in semen quality, in the function of reproductive hormones, or both (see Figure 1). Despite conflicting reported results, there is growing evidence that lead exposure, even at low levels, can impair male reproductive health. Future research should deepen the analysis concerning these issues.
Some effects of lead on male reproductive system.
It is well known that lead has harmful effects on female reproductive system. Women at reproductive age are at risk of suffering some health disorders due to the toxic effects of this metal. Occupational exposure to lead is more frequent in men compared to women. However, there are some reports on the harmful effects of lead suffered by women who work in places where lead or some lead compounds are used. In a study conducted to determine the effects of occupational exposure on bone and lead blood levels, women who were former workers at a smelter were compared with a cohort of women with no-known occupational exposure. Higher levels of lead in blood and tibia were found in the exposed group. In addition, the difference in bone lead levels between compared groups was significantly higher than the difference in BLCs [38]. In accord with these findings, a study carried out in Mexico showed that women who work with lead have greater probability to have BLCs above the CDC recommended value of 5 μg/dL compared to non-exposed women [39].
It is necessary to consider that women can be exposed to lead not only at work but also through the clothes, shoes, and work instruments that are taken home by the cohabitants who work in places where lead is used. Higher BLCs in pregnant women who live with someone who is exposed to lead at work in comparison with those who live in houses where nobody works in places that lead is used have been observed [40]. In addition, lead exposure may occur when women use some cosmetics, such as surma or kolh, and other beauty products [41, 42, 43].
Women can also be exposed to lead by pica habit, an eating disorder that consists of the consumption of non-food items without nutritional value. Among the most harmful types of pica is the consumption of soil, paint chips, and pottery. Pregnant women consuming these items put both themselves and the fetus at risk of lead poisoning [44, 45]. In Mexican, women who were recognized that they used to eat soil had significantly higher BLL compared to those who did not have this habit [40]. In one study in New York, pica behavior among lead-poisoned pregnant women (BLL ≥ 20 μg/dL) was 9%. The most common practice among them was eating soil (64.6%). The probability of having BLLs ≥40 μg/dL among women who reported pica was three times higher in comparison with those women who did not report this habit. In addition, pica-reporting women had a mean peak of BLL during pregnancy significantly higher compared to those who did not report pica (29.5 μg/dL vs. 23.8 μg/dL) [45].
In addition to the effects of lead on women’s fertility, a wide range of published reports refers to the damage caused by this heavy metal during pregnancy (see Figure 2). Prenatal exposure to lead can cause several obstetric complications and adverse pregnancy outcomes [46]. Lead absorbed into the body, mainly by ingestion or inhalation, enters the bloodstream and accumulates in soft organs (mostly in brain, liver, and kidney) and bones [47, 48]. It is considered that lead in bone represents approximately 95% of the total body burden in adults [47]. During pregnancy, the demand of calcium rises, and lead stored in bone can replace the calcium and recirculate in the bloodstream, becoming an endogenous source of exposure [16, 48, 49, 50]. Lead from the blood can cross the placenta and impair the development of the fetus [51, 52]. Therefore, lead-exposed women are at risk of suffering various pregnancy complications, such as spontaneous abortion [1, 53], preterm delivery [54, 55], GDM [8, 56], pregnancy hypertension [57, 58, 59], preeclampsia [60, 61, 62, 63, 64], premature rupture of membranes [65, 66], intrauterine growth restriction [67], and low weight birth [68, 69], among others.
Harmful effects of lead on female reproductive health.
Although some researchers have failed to demonstrate the relationship between lead and abortion [70, 71], a study conducted in Mexico showed evidence that, even low-to-moderate lead exposure, below 30 μg/dL of blood lead can increase the risk of spontaneous abortion [1]. In this case, the range of BLLs in pregnant women was 1.4–29 μg/dL. Those lead concentrations can be considered common in general population in many countries, and lower to those observed in occupationally exposed women. It is considered that the mechanism by which lead induces abortion is related to the direct transmission of the metal to the developing fetus due to the demineralization of bones during pregnancy [72, 73].
Several studies have confirmed that pregnant women exposed to lead have more probability of having a preterm delivery compared with non-exposed women. Nevertheless, results are still inconsistent. In a prospective cohort study carried out in China, maternal urinary lead was measured and adjusted by creatinine, and newborns were classified as preterm birth and early term birth. The mean urinary lead levels were significantly higher in preterm births. In addition, among all newborns, an increase in maternal urinary lead was associated with a decrease in gestational age [3].
Lead can displace calcium because they both have similar chemical characteristics and follow analogous metabolic pathways [74]. It has been recognized that when lead crosses from the bloodstream to the placenta, the growth of the fetus can be impaired due to the interference of lead with calcium metabolism [68, 69]. The evaluation of prenatal exposure to lead has shown inverse association between maternal urine lead levels and preterm low birth weight [68]. Other studies analyzed the relationship between the levels of lead in tibia and patella and birth weight, considering that bone lead is a better biomarker to estimate the effect of lead on the fetus compared to blood lead [75, 76].
In a study conducted to evaluate the relationship between lead exposure and birth weight in Mexican women, lead levels were measured in maternal venous blood, umbilical cord, and tibia and patella. The weight of newborns was determined within the first 12 hours of delivery. Although all biomarkers of lead exposure were negatively associated with a decreased size of newborns, this association resulted statistically significant only for tibia lead levels [75]. Similar results were observed in the analysis of the relationship between maternal lead burden and early postnatal growth in a cohort of breastfed newborns [75]. In this study, maternal BLL measured at 1 month postpartum and maternal bone lead levels were significantly associated with infant BLL. Moreover, infant BLL and maternal patella lead level were inversely associated with weight gain. The weight gain from birth to the first month of life was 142 g lower in infants with BLL ≥ 10 compared to those with lower BLCs.
There is growing evidence that lead is a risk factor for gestational diabetes mellitus. Experiments with rats have demonstrated that lead exposure can induce glucose intolerance and hyperglycemia [8]. But epidemiological studies showed contradictory results. In women at 22–28 weeks of gestation, slightly mean BLCs were observed compared to those without GDM, but this difference was not statistically significant. The geometric mean BLCs were 6.13 ng/g in women with GDM and 6.05 ng/g in women without GDM. Based on this result, authors suggested that lead at these low levels of exposure is not associated with the risk of suffering GDM [77]. In contrast, in a French mother-child prospective cohort study, blood lead was associated with IGT, supporting the evidence that maternal exposure to lead is a risk factor for GDM [56]. Further studies have to be performed to confirm the deleterious effect of lead on metabolic processes and, particularly, on the development of GDM.
A large number of investigations provide evidence that exposure to lead is associated with hypertension in adults [78, 79, 80, 81]. For this reason, the question of whether lead is associated with gestational hypertension (GH) and preeclampsia (PE) has gained a great importance in recent years.
In a cohort of pregnant women in Los Angeles, California, blood and bone lead were assessed in the 3rd trimester and post-delivery, and the prevalence of hypertension was measured [82]. The relationship of both biomarkers with GH was analyzed. After adjusting by covariables, no significant association between BLLs in 3rd trimester and hypertension was observed. Nevertheless, calcaneus bone lead was significantly associated with the risk of hypertension.
In a cross-sectional study with Maltese Caucasian women at third trimester of gestation, significantly higher BLCs in hypertensive women compared to normotensive women were observed [83]. Moreover, BLL showed a positive relationship with systolic and diastolic blood pressure.
The relationship between BLL at mid-pregnancy and blood pressure was assessed in a study carried out in pregnant women of two French municipalities [83]. In this study, hypertensive women had significantly higher BLL than normotensive women. Additionally, lowest frequency of hypertension was observed among women in the lowest quartile of BLL. These findings are in accord with those observed in Nigeria, in which the impact of lead on pregnancy outcomes was investigated [84]. Significantly higher frequency of hypertension was observed in women with BLL ≥ 10 μg/dL compared to those who had lower concentrations of lead in blood.
The findings on the association of lead exposure with GH led to investigate if this toxic metal could be considered a risk factor for preeclampsia, a pregnancy disorder characterized by high blood pressure and proteinuria detected after 20 weeks of gestation [85]. In a cross-sectional study that included women between 29 and 43 weeks of gestation, significantly higher concentrations of lead in red blood cells of pregnant women diagnosed with preeclampsia were found compared to those without hypertension. Furthermore, women with severe preeclampsia had also higher blood cell lead concentrations than mild preeclamptic women [61]. In contrast, in a case-control study conducted in women without occupational exposure, BLCs measured within 24 hours of delivery did not differ between women with preeclampsia and normotensive group, but a significant difference between the groups was observed with respect to umbilical cord lead (UCB) concentration [64]. In addition, the ratio of umbilical cord lead to whole blood lead was significantly associated with preeclampsia.
Despite the contradictory results of some studies, the majority of those supported the hypothesis that lead can cause preeclampsia. Some possible mechanisms have been suggested to explain the roll of lead in the development of this pregnancy disorder. It is considered that lead increases the circulating levels of endothelin, a vasoactive substance that causes constriction of the blood vessels, leading to the increase of blood pressure [63]. Lead also interferes in the increase of reactive oxygen species reducing the serum levels of nitric oxide (NO) and other vasodilator substances [86, 87, 88, 89]. From the molecular point of view, lead causes inhibition of membrane adenosine triphosphatases (ATPases), which produces vasoconstriction due to the increase of intracellular calcium ions [63, 90].
The influence of sex in the effect of lead on health is a controversial subject. Although sex differences regarding exposure, absorption, and metabolism of lead have been reported by certain researchers [91, 92], the results are not conclusive. In a prospective cohort, the effects of gender differences in the relationship between lead exposure and neurodevelopmental toxicity were analyzed [91]. Lead levels were determined in maternal blood in early and late pregnancy, in cord blood at birth, and in children’s blood at 2, 3, and 5 years old. As a result, significant association between lead concentrations at late pregnancy and the risk of behavioral problems was observed in males, while blood lead measured in 2- and 5-year-old children was associated with an increased risk of behavioral problems in females. According to previous data, early in life, the susceptibility to neurotoxic effect of lead is higher in boys than in girls. On the other hand, experimental data suggest that susceptibility to immunotoxic effects of lead is higher in females [92]. More research is needed to elucidate these inconsistencies.
The biological effects of lead exposure in human also appear to be different according to the gender. In a study carried out in Japan, the authors aimed to determine the effects of gender on porphyrin metabolic disorders induced by lead exposure [93]. Blood lead, plasma delta-aminolevulinic acid (ALA), urinary ALA, and urinary coproporphyrin (CP) were determined in exposed workers. Although no significant differences in blood lead concentrations between male and female workers were observed, women had higher plasma ALA concentrations, as well as higher excretion of urine ALA and CP in comparison with men. The mechanism that could explain this difference is still unclear.
With respect to the reproductive system, health damages in female have been observed even at very low levels of exposure. In a study carried out in Taiwan, the relationship between low-level lead exposure and risk of infertility was evaluated [94]. The average lead concentration in infertile women (3.5 μg/dL) was significantly higher than in a control group (2.78 μg/dL). Furthermore, women with BLL >2.5 μg/dL had a threefold higher risk of infertility than those with BLL ≤ 2.5 μg/dL. In contrast, the harmful effects of lead in male reproductive system have been detected at higher levels of exposure than those in female. The importance of finding explanation of gender effects for lead and other environmental toxic substances was discussed by the Society for Women’s Health Research in a roundtable at the National Institute of Environmental Health Sciences in October 2002 [95].
Despite the above-mentioned results, gender differences in susceptibility to lead poisoning have been considered in few investigations. Some studies have included gender as a confounding factor in the relationship between lead exposure and health impairment [96]. However, in other investigations, differences between male and female in regard to the harmful effects of lead have not been found.
According to the results of the investigations, the following differences between men and women regarding lead exposure can be highlighted:
Generally, in non-exposed individuals, blood lead levels are higher in males than in females.
Damages to female reproductive health can occur at lower levels of exposure than in men.
The risk of suffering behavioral problems in relation to prenatal lead exposure at early childhood is higher in females.
The susceptibility to neurotoxic effects of lead appears to be higher in boys than in girls.
The susceptibility to immunotoxic effects of lead is higher in females.
From the biological point of view, porphyrin metabolic disorders induced by lead exposure affect females more than males.
The impairment in the synthesis and function of hormones has been observed in both genders. But, little is known about the differences between male and female regarding the mechanisms by which lead affects the reproductive system.
In summary, gender difference should be considered an important factor for a better evaluation of the harmful effects of lead on health. Further research is needed to better understand the role of sex as a modifier of the effects of lead exposure.
Lead is considered to be able to affect the development of children’s reproductive system. There is evidence that both paternal and maternal lead exposure can cause a detrimental impact on the structure and function of gametes, which might cause adverse effects on newborn’s health [97]. Embryos and fetus are extremely sensitive to environmental toxicants. Exposure to lead during pregnancy is known to be able to impair fetal development, since lead can cross the placental barrier and reach the fetus [51, 52].
Lead is known to affect testosterone levels in adults, leading to reproductive dysfunction. Low levels of testosterone can reduce semen quality in men and increase genital malformations [98]. In contrast, high levels of testosterone in women are associated with higher frequency of polycystic ovary syndrome (POS) [99] and puberty disorders [100]. In spite of this, there are few studies that have focused on the relationship between lead exposure and androgen hormone levels in children. One of the few longitudinal studies on this issue was carried out in Russia [101]. This study evaluated the impact of organochlorine chemicals and lead in growth and pubertal timing in 516 boys. Children were enrolled in the study at the age of 5–7 years and were followed up until the age of 18–19 years. Lead exposure was negatively associated with growth during puberty. In addition, it was suggested that lead may delay the timing of male puberty.
In a study carried out to evaluate the relationship between blood metal concentrations and testosterone levels in the USA, children and adolescents’ concentrations of lead, cadmium, mercury, and selenium in blood, as well as serum testosterone levels, were determined [102]. Although no significant association between blood lead and total testosterone (TT) was observed, the concentrations of TT were significantly higher for girls in the fourth quartile compared to those in the first quartile. On the other hand, in a prospective study conducted in Mexico City, maternal patella lead and early childhood blood lead were inversely associated with breast growth in girls [103]. Furthermore, an increase in girl’s maternal patella lead was associated with later age of menarche. In addition, blood lead during childhood negatively associated with pubic hair growth in girls. No associations were observed in boys.
The fact that lead exposure is related to a wide range of adverse effects on reproductive health is accepted by most researchers nowadays. The main source of exposure remains occupational. But there is no doubt that, in recent years, the environmental exposure to lead has decreased, especially in developed countries like the United State, Canada, and others [104]. A main role in this reduction is attributed to the elimination of leaded gasoline [105]. Nevertheless, the risk of lead poisoning still remains, mainly in developing countries, due to some sources of exposure, such as lead paint, cosmetics, traditional medicines, electronic waste, and glazed ceramic vessels, among others [106].
It is very difficult to dispense with lead due to its uses in a wide range of industrial lines, such as smelting, manufacturing and recycling of car batteries, and lead crystal glassware. However, in recent years, there has been an increase in the diffusion of the damage that lead can cause and the measures that must be taken to protect people’s health. The identification of risk factors for having high BLLs has contributed to reduce the prevalence and severity of lead poisoning. In a way, the results of research have helped people to become aware of the toxicity of this metal and the danger it poses to their health.
Health interventions in last decades have led to a decrease in lead exposure. In spite of this, it is necessary to increase protection measures, especially for women and children. To date, there is no exposure lead level that can be considered safe. Although the CDC established 5 μg/dL as the reference value for BLLs in children, epidemiological research has demonstrated that even at lower lead concentrations adverse health effects can occur. With respect to females, adverse reproductive outcomes have been observed also at BLLs below 5 μg/dL, decrease in delta-aminolevulinic acid dehydratase (ALAD) activity has been detected in pregnant women at mean blood lead ≥2.2 μg/dL [107], and damages in female reproductive system have been reported at BLLs above 2.5 μg/dL [95]. Some prevention strategies should be considered for protection of the toxic effects of lead. Preventive measures should include at least the following:
Developing public awareness campaigns to identify sources of health exposure
Evaluation of risk factors for all pregnant women in their prenatal care
Education of childbearing age women to avoid sources of lead exposure
Screening of lead exposure for all pregnant women by means of diagnosis tests, such as blood lead, ALAD activity, and urine ALA
Keeping children and pregnant women with BLL ≥ 5 μg/dL out of exposure sources
Requiring employers to take measures to reduce lead levels in workplaces
Requiring exposed workers to use protective means
To carry out a review of regulations to ensure greater protection for the exposed population
Increasing environmental monitoring (lead in air, soil, water, etc.) to detect any deviation from established standards
Searching for new biomarkers, with high sensitivity and specificity, to assess the exposure and effects of lead in the body
There is enough evidence that lead exposure can harm reproductive health of both men and women. The harmful effects of lead have been mostly observed in occupationally exposed people. Nevertheless, in recent decades, research has demonstrated that these damages can occur at levels of lead formerly considered harmless. Most observed effects on male reproductive system are related to the direct impact of lead on semen quality, such as volume of ejaculation, sperm density, abnormal morphology, sperm count, and motility. In addition, lead can alter the concentrations of some male reproductive hormones, such as follicle stimulating hormones, testosterone, and luteinizing hormone.
In women, prenatal exposure to lead, even at very low levels of exposure, has shown to be harmful for both the mother and the fetus. Thus, any level of lead exposure could be associated with adverse reproductive outcomes. Lead has been associated with a wide range of adverse outcomes, including spontaneous abortion, intrauterine growth restriction, premature delivery, stillbirths, pregnancy hypertension, preeclampsia, and low birth weight, among others.
Several recent studies have suggested hypothesis related to the mechanisms by which lead affects male and female reproductive health. However, more research is needed to clarify these mechanisms. In conclusion, lead exposure remains a health problem for both male and female reproductive health. It is important to implement protective measures to avoid the harmful effects of this toxic metal on reproductive health of both men and women.
The authors are grateful to researchers, managers, and technicians, who contributed and collaborated in this research. The authors are grateful to researchers Eloisa Esquivel, Gonzalo García Vargas, Ada Sandoval Carrillo, Edna Mendez Hernandez, and Francisco Castellanos Juárez for the assistance in the preparation of this chapter. The authors would also like to recognize the Council of Science and Technology of the State of Durango (COCYTED) for the support to their investigations.
The authors declare no conflicts of interest.
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In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Infectious Diseases",id:"6"},selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/52907",hash:"",query:{},params:{id:"52907"},fullPath:"/chapters/52907",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()