IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
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By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
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"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
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"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
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In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
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Feel free to share this news on social media and help us mark this memorable moment!
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\n
By listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
All three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n
"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n
"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\n
In conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n
“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\n
We invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\n
Feel free to share this news on social media and help us mark this memorable moment!
\n\n
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"8331",leadTitle:null,fullTitle:"Pharmaceutical Formulation Design - Recent Practices",title:"Pharmaceutical Formulation Design",subtitle:"Recent Practices",reviewType:"peer-reviewed",abstract:"Pharmaceutical formulations have evolved from simple and traditional systems to more modern and complex novel dosage forms. Formulation development is a tedious process and requires an enormous amount of effort from many different people. Developing a stable novel dosage form and further targeting it to the desired site inside the body has always been a challenge. The purpose of this book is to bring together scholarly articles that highlight recent developments and trends in pharmaceutical formulation science. Each article has been written by authors specializing in the subject area and hailing from top institutions around the world. The book has been written in a systematic and lucid style explaining all basic concepts and fundamentals in a very simple way. This book aims to serve the need of all individuals involved at any level in the pharmaceutical dosage form development. I sincerely hope that the book will be liked by inquisitive students and learned colleagues.",isbn:"978-1-78985-839-6",printIsbn:"978-1-78985-662-0",pdfIsbn:"978-1-78985-840-2",doi:"10.5772/intechopen.78460",price:119,priceEur:129,priceUsd:155,slug:"pharmaceutical-formulation-design-recent-practices",numberOfPages:164,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"e7b436a5e31db5f48ba1b6220a11848f",bookSignature:"Usama Ahmad and Juber Akhtar",publishedDate:"February 5th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/8331.jpg",numberOfDownloads:19285,numberOfWosCitations:11,numberOfCrossrefCitations:25,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:60,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:96,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"July 9th 2018",dateEndSecondStepPublish:"September 6th 2018",dateEndThirdStepPublish:"November 5th 2018",dateEndFourthStepPublish:"January 24th 2019",dateEndFifthStepPublish:"March 25th 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"255360",title:"Dr.",name:"Usama",middleName:null,surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/255360/images/system/255360.png",biography:"Dr. Usama Ahmad holds a specialization in Pharmaceutics from Amity University, Lucknow, India. He received his Ph.D. from Integral University, Lucknow, India, with his work titled ‘Development and evaluation of silymarin nanoformulation for hepatic carcinoma’. Currently, he is an Assistant Professor of Pharmaceutics, at the Faculty of Pharmacy, Integral University. He has been teaching PharmD, BPharm, and MPharm students and conducting research in the novel drug delivery domain. From 2013 to 2014 he worked on a research project funded by SERB-DST, Government of India. He has a rich publication record with more than twenty-four original journal articles, two edited books, four book chapters, and several scientific articles to his credit. He is a member of the American Association for Cancer Research, the International Association for the Study of Lung Cancer, and the British Society for Nanomedicine. Dr. Ahmad’s research focus is on the development of nanoformulations to facilitate the delivery of drugs.",institutionString:"Integral University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Integral University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"252107",title:"Dr.",name:"Juber",middleName:null,surname:"Akhtar",slug:"juber-akhtar",fullName:"Juber Akhtar",profilePictureURL:"https://mts.intechopen.com/storage/users/252107/images/system/252107.jpg",biography:"Dr. Juber Akhtar obtained a BPharm from Jamia Hamdard University, New Delhi, in 2005, MPharm from Manipal University, Karnataka, in 2007, and Ph.D. from Integral University, Lucknow, in 2014. He is currently an associate professor at Integral University. From 2014 to 2016, Dr. Akhtar was head of the Faculty of Pharmacy, Integral University. He also served as chairman cum biological scientist for Institutional Animal Ethics Committee (IAEC) from October 2015 to May 2017. He has experience teaching abroad and was previously a professor at Buraydah College of Pharmacy and Dentistry, Kingdom of Saudi Arabia (KSA). Dr. Akhtar has more than eighty publications in reputed journals and is an editorial board member for many esteemed journals. He has supervised a dozen Ph.D. and MPharm students in research projects. Dr. Akhtar’s areas of research interest include the development of nanoparticulate drug delivery systems.",institutionString:"Integral University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Integral University",institutionURL:null,country:{name:"India"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1188",title:"Pharmacokinetics",slug:"drug-discovery-pharmacokinetics"}],chapters:[{id:"67588",title:"Preformulation Studies: An Integral Part of Formulation Design",doi:"10.5772/intechopen.82868",slug:"preformulation-studies-an-integral-part-of-formulation-design",totalDownloads:4122,totalCrossrefCites:2,totalDimensionsCites:5,hasAltmetrics:0,abstract:"When a promising new chemical entity is synthesized, it needs transformation to appropriate formulation in order to show a better and desirable action at appropriate site. Preformulation study is a phase which is initiated once the new molecule is seeded. In a broader way, it deals with studies of physical, chemical, analytical, and pharmaceutical properties related to molecule and provides idea about suitable modification in molecule to show a better performance. Study of these parameters and suitable molecular modification can be linked to generation of effective, safer, stable, and reliable pharmaceutical formulation. Therefore, preformulation study is an approach for generation of pharmaceutical formulation which utilizes knowledge and area application of toxicology, biochemistry, medicinal chemistry, and analytical chemistry. The highlighted chapter is framed with a vision to provide an in-depth knowledge about pharmaceutical formulation development.",signatures:"Pinak Patel",downloadPdfUrl:"/chapter/pdf-download/67588",previewPdfUrl:"/chapter/pdf-preview/67588",authors:[null],corrections:null},{id:"68656",title:"Drug Analysis",doi:"10.5772/intechopen.88739",slug:"drug-analysis",totalDownloads:1752,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Instrumental methods are widely used for the analysis and stability studies of compounds in bulk and pharmaceutical forms. They vary in their sensitivity, techniques and reagents involved. This chapter will overview those different techniques and the application of the analytical methods. It will also describe how to design and develop simple, sensitive and accurate method for routine quality control of specified compound depending on its molecular structure. Quality control and assurance of the analytical process will be discussed. Furthermore, the chapter will describe a number of factors affecting the chemical and physical stability of Pharmaceutical formulations and how to develop stability-indicating methods to qualify and quantify the drug degradation.",signatures:"Shaza W. Shantier",downloadPdfUrl:"/chapter/pdf-download/68656",previewPdfUrl:"/chapter/pdf-preview/68656",authors:[null],corrections:null},{id:"68199",title:"Microcrystalline Cellulose as Pharmaceutical Excipient",doi:"10.5772/intechopen.88092",slug:"microcrystalline-cellulose-as-pharmaceutical-excipient",totalDownloads:3718,totalCrossrefCites:3,totalDimensionsCites:19,hasAltmetrics:1,abstract:"Microcrystalline cellulose (MCC) is a pure partially depolymerized cellulose synthesized from α-cellulose precursor (type Iβ), obtained as a pulp from fibrous plant material, with mineral acids using hydrochloric acid to reduce the degree of polymerization. The MCC can be synthesized by different processes such as reactive extrusion, enzyme mediated, steam explosion, and acid hydrolysis. It is commonly manufactured by spray-drying the neutralized aqueous slurry of hydrolyzed cellulose. The MCC is a valuable additive in pharmaceutical, food, cosmetic, and other industries. MMC obtained from different sources will differ considerably in chemical composition, structural organization, and physicochemical properties (crystallinity, moisture content, surface area and porous structure, molecular weight, etc.). The high demand of microcrystalline cellulose used in pharmaceutical industries has led to the utilization of locally and naturally occurring materials in the production of microcrystalline cellulose. Many studies on the physicochemical properties of locally produced MCC derived from natural sources have been extensively evaluated in the development of a new natural source for MCC as a substitution of wood, the most abundant one.",signatures:"Anis Yohana Chaerunisaa, Sriwidodo Sriwidodo and Marline Abdassah",downloadPdfUrl:"/chapter/pdf-download/68199",previewPdfUrl:"/chapter/pdf-preview/68199",authors:[null],corrections:null},{id:"66222",title:"Bioavailability and Bioequivalence Studies",doi:"10.5772/intechopen.85145",slug:"bioavailability-and-bioequivalence-studies",totalDownloads:3436,totalCrossrefCites:3,totalDimensionsCites:5,hasAltmetrics:1,abstract:"In vivo bioavailability studies are performed for new drug to establish essential pharmacokinetic parameters including rate of absorption, extent of absorption, rates of excretion and metabolism and elimination half-life after a single and multiple dose administration. These essential pharmacokinetic parameters are useful in establishing dosage regimens. Bioequivalence used to assess the expected in vivo biological equivalence of two proprietary preparations of drug products. If two drugs are bioequivalent, it means that they are expected to be same for all intents and purposes. In determining bioequivalence between two drugs such as a reference drug or brand and potential to be test drug or marketed generic drug. Pharmacokinetic studies are conducted whereby each of the drugs is administered in a cross over study to healthy volunteer’s subjects. Plasma is obtained at regular intervals and assayed for parent drug or metabolite concentration to compare the two drugs. For comparison purpose of two formulations, the plasma concentration data are used to assess key pharmacokinetic parameters. If 90% confidence interval for the ratio of the geometric least square means of peak plasma concentration, area under curve of test and reference drugs are within 80–125%, then bioequivalence will be established.",signatures:"Divvela Hema Nagadurga",downloadPdfUrl:"/chapter/pdf-download/66222",previewPdfUrl:"/chapter/pdf-preview/66222",authors:[null],corrections:null},{id:"65701",title:"pH-Responsive Microgels: Promising Carriers for Controlled Drug Delivery",doi:"10.5772/intechopen.82972",slug:"ph-responsive-microgels-promising-carriers-for-controlled-drug-delivery",totalDownloads:1313,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The development of a new drug entity is a time-consuming and an expensive process; therefore, the design of new drug delivery systems for an existing drug molecule can significantly improve the safety and efficacy of the drug with improved patient compliance. In recent years, polymeric carriers have been widely investigated and are playing an important role in controlled drug delivery, biomedical applications, and tissue engineering. Microgels are microscopic hydrogels and have attracted much attention as vehicle for drug delivery. Stimuli-responsive MGs are smart drug delivery carriers and have the capability to incorporate and release their host molecules in response to stimuli (pH, ionic strength, and temperature), for targeted drug delivery. Of the many stimuli, alteration in pH is markedly fascinating because of the availability of pH gradients admissible for drug targeting. For example, pH gradients between normal tissues and some pathological sites between the extracellular environment and some cellular compartments, and along the gastrointestinal (GI) tract, are well characterized. Microgels can be fabricated through different methods.",signatures:"Zermina Rashid",downloadPdfUrl:"/chapter/pdf-download/65701",previewPdfUrl:"/chapter/pdf-preview/65701",authors:[null],corrections:null},{id:"67848",title:"Using Microbubbles as Targeted Drug Delivery to Improve AIDS",doi:"10.5772/intechopen.87157",slug:"using-microbubbles-as-targeted-drug-delivery-to-improve-aids",totalDownloads:1330,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,abstract:"No preventive vaccines are available for the treatment of AIDS. To improve therapy, combinational antiretroviral drugs are given; however some patients develop resistance to particular combinational drug. Microbubble-mediated drug delivery technology solves the problem by reducing systemic dose and toxicity. Microbubbles are bubbles smaller than one millimeter in diameter but larger than one micrometer. The general composition of microbubble is gas core. The mechanism of microbubbles through which its delivery increases is sonoporation, the formation of openings in the vasculature, induced by ultrasound-triggered oscillations and destruction of microbubbles. Rapid isolation strategy of CD4+ cells is mixing blood and glass microbubbles which then bind with the specific target cells to the microbubble carrying specific antibodies on their surface. The target cells will spontaneously float to the top of the blood vial and can be quickly separated. The microbubbles are particularly used in the diagnosis of AIDS because of their cell isolation techniques which is rapid and inexpensive and their small size to pass through capillary for perfusion in tissue This review demonstrates the problems with the current treatment of the disease and shed light on the remarkable potential of microbubbles to provide more effective treatment and prevention for HIV/AIDS by advancing antiretroviral therapy, gene therapy, immunotherapy, vaccinology, and microbicides.",signatures:"Harsha Virsingh Sonaye, Rafik Yakub Shaikh and Chandrashekhar A. Doifode",downloadPdfUrl:"/chapter/pdf-download/67848",previewPdfUrl:"/chapter/pdf-preview/67848",authors:[null],corrections:null},{id:"67502",title:"Nanopharmaceuticals: A Boon to the Brain-Targeted Drug Delivery",doi:"10.5772/intechopen.83040",slug:"nanopharmaceuticals-a-boon-to-the-brain-targeted-drug-delivery",totalDownloads:1654,totalCrossrefCites:5,totalDimensionsCites:12,hasAltmetrics:0,abstract:"Brain is well known for its multifarious nature and complicated diseases. Brain consists of natural barriers that pose difficulty for the therapeutic agents to reach the brain tissues. Blood-brain barrier is the major barrier while blood-brain tumor barrier, blood-cerebrospinal (CSF) barrier and efflux pump impart additional hindrance. Therapeutic goal is to achieve a considerable drug concentration in the brain tissues in order to obtain desired therapeutic outcomes. To overcome the barriers, nanotechnology was employed in the field of drug delivery and brain targeting. Nanopharmaceuticals are rapidly emerging sub-branch that deals with the drug-loaded nanocarriers or nanomaterials that have unique physicochemical properties and minute size range for penetrating the CNS. Additionally, nanopharmaceuticals can be tailored with functional modalities to achieve active targeting to the brain tissues. The magic behind their therapeutic success is the reduced amount of dose and lesser toxicity, whereby localizing the therapeutic agent to the specific site. Different types of nanopharmaceuticals like polymeric, lipidic and amphiphilic nanocarriers were administered into the living organisms by exploiting different routes for improved targeted therapy. Therefore, it is essential to throw light on the properties, mechanism and delivery route of the major nanopharmaceuticals that are employed for the brain-specific drug delivery.",signatures:"Mahira Zeeshan, Mahwash Mukhtar, Qurat Ul Ain, Salman Khan and Hussain Ali",downloadPdfUrl:"/chapter/pdf-download/67502",previewPdfUrl:"/chapter/pdf-preview/67502",authors:[null],corrections:null},{id:"70715",title:"3D Printing in Pharmaceutical Sector: An Overview",doi:"10.5772/intechopen.90738",slug:"3d-printing-in-pharmaceutical-sector-an-overview",totalDownloads:1960,totalCrossrefCites:11,totalDimensionsCites:16,hasAltmetrics:1,abstract:"The pharmaceutical industry is moving ahead at a rapid pace. Modern technology has enabled the development of novel dosage forms for targeted therapy. However, the fabrication of novel dosage forms at industrial scale is limited and the industry still runs on conventional drug delivery systems, especially modified tablets. The introduction of 3D printing technology in the pharmaceutical industry has opened new horizons in the research and development of printed materials and devices. The main benefits of 3D printing technology lie in the production of small batches of medicines, each with tailored dosages, shapes, sizes, and release characteristics. The manufacture of medicines in this way may finally lead to the concept of personalized medicines becoming a reality. This chapter provides an overview of how 3D printed technology has extended from initial unit operations to developed final products.",signatures:"Asad Ali, Usama Ahmad and Juber Akhtar",downloadPdfUrl:"/chapter/pdf-download/70715",previewPdfUrl:"/chapter/pdf-preview/70715",authors:[{id:"255360",title:"Dr.",name:"Usama",surname:"Ahmad",slug:"usama-ahmad",fullName:"Usama Ahmad"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"10882",title:"Smart Drug Delivery",subtitle:null,isOpenForSubmission:!1,hash:"70c3ce4256324b3c58db970d446ddac4",slug:"smart-drug-delivery",bookSignature:"Usama Ahmad, Md. 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\n
1. Introduction
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Wearable technologies are becoming increasingly popular as personal health system, enabling continuous real-time monitoring of human health on a daily basis and outside clinical environments [1, 2, 3]. The wearable device market is currently having a worldwide profit of around $34 billion and is expected to reach above $50 billion by 2022 owing to wearables’ ease of use, flexibility, and convenience [4]. Real-time monitoring, operational efficiency, and fitness tracking are reported as main factors supporting the market growth of health wearable devices such as smart watches, smart glasses, and other wellness gadgets, with expected $12.1 billion world market by 2021 [5].
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In the past decade, the recent progress in developing wearable devices was more focused on monitoring physical parameters, such as motion, respiration rate, etc. [3, 6, 7]. Today, there is a great interest in evolving wearable sensors capable of detecting chemical markers relevant to the status of health. Different approaches have been applied by researchers to design and fabricate wearable biosensors for remote monitoring of metabolites and electrolytes in body fluids including tear, sweat, and saliva [3, 8, 9, 10]. A great example would be the development of small and reliable sensors that would allow continuous glucose monitoring in diabetic patients [11, 12]. Diabetes is a chronic disease that can significantly impact on quality of life and reduce life expectancy. However, diabetics can stay one step ahead of the disease by monitoring their blood glucose level to minimize the complication of the disease by proper administration of insulin. Currently, blood analysis is the gold standard method for measuring the level of glucose in patient’s blood. However, this technique cannot be applied without penetrating the skin, which can be painful and inconvenient, and requires user obedience. Therefore, current research focuses on the development of portable and wearable devices capable of continuous glucose sensing through noninvasive detection techniques.
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2. Tear analysis
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A majority of the recent studies in this field have targeted the area of personalized medicine, endeavoring to develop miniaturized wearable devices featuring real-time glucose monitoring in diabetic patients [12, 13, 14, 15]. One great example is contact lens which is an ideal wearable device that can be worn for hours without any pain or discomfort [16]. Integration of glucose biosensors into contact lenses has recently been demonstrated by several research groups [9, 17, 18]. However, the level of glucose in tear fluid is very low (0.1–0.6 mM), requiring a high sensitivity of the sensor for picking up the signal from expected chemical reaction [3, 19]. Yao et al. [16] have fabricated a contact lens with integrated sensor for continuous tear glucose monitoring with wireless communication system over a distance of several centimeters. The sensor demonstrated a fast response of 20 s with a minimum detection of less than 0.01 mM glucose, which is 10–60 times lower than glucose level in human tear [16].
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In addition to glucose, lactate is an important metabolite in the human body, which gets converted into l-lactate under hypoxic condition [20]. l-Lactate levels in tear fluid is about 1–5 mmol L−1, which might increase significantly due to some heath conditions including ischemia, inadequate tissue oxygenation, stroke, and different types of cancer [21]. Thomas et al. [22] demonstrated an invasive detection of lactate in human tear by integrating an amperometric lactate sensor with Pt working (WE) and reference (RE) electrodes as well as a counter electrode (CE) as current drain, on a polymer-based contact lens, measuring lactate in situ in human tears without any need for physical sampling [22].
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Very recently, Park et al. [17] reported a novel approach for fabricating fully transparent and stretchable smart contact lens capable of wirelessly monitoring the level of glucose in the tears of diabetic patients. Figure 1 shows the layout of fabricated devices made of glucose sensors, wireless circuit, and display pixel on soft and transparent contact lens substrate (Figure 1a and b). The circuit diagram of the device is illustrated in Figure 1a, with radio frequency antenna receiving signals from a transmitter and a rectifier converting the signals to DC (Figure 1a and c). A continuous network of ultralong Ag nanofibers was used as stretchable electrodes for the antenna and interconnects (Figure 1d). In the case of any change in the concentration of glucose in tear, the sensor resistance changes resulting in the light-emitting diode (LED) pixel turning on or off. The device was tested in vitro using a live rabbit, providing substantial finding for smart contact lenses as one of the promising wearable devices in healthcare system [17].
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Figure 1.
(a) (i) Schematic illustration and (ii) operation of the soft, smart contact lens and (iii) the circuit diagram of the smart contact lens system. The soft, smart contact lens is composed of (b) a hybrid substrate; (c) functional devices including rectifier, LED, and glucose sensor; and (d) a transparent, stretchable conductor for antenna and interconnects [17].
\n
\n
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3. Sweat analysis
\n
In addition to tear, sweat electrolyte concentrations and blood serum are related [2, 8]. As one of the most readily accessible human biofluids, a great deal of information about the human body and its physical performance could be obtained via monitoring sweat electrolyte concentrations [23, 24]. Several groups have reported the key biomarkers in human sweat (e.g., sodium level, pH change, lactate concentration) relevant to human health and well-being, for monitoring athletic performance during sporting activities [25]. Jia et al. fabricated a skin-worn tattoo-based sensor for real-time monitoring of lactate in human sweat, offering substantial benefits for biomedical as well as sport applications [25]. In another approach, Curto et al. [26] fabricated a wearable and flexible microfluidic platform capable of monitoring changes in the sweat pH in real time. Anastasova et al. [27] developed a flexible microfluidic device for real-time monitoring of metabolite such as lactate as well as electrolytes such as pH and sodium in human sweat. Recently, Gao et al. [28] developed a flexible and wearable device (Figure 2) made of arrays of sensors for real-time monitoring of heavy metals, such as Zn, Cu, and Hg in human sweat. The device fabrication method is presented in Figure 2a, showing the deposition and stripping steps on microelectrodes. The sensing mechanism was based on an electrochemical detection of targeted heavy metals through four microelectrodes, including Au and Bi working electrodes, Ag reference electrode, and an Au counter electrode (Figure 2b and c). The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application, via monitoring the level of some heavy metals in human sweat [28]. A balanced level of Zn is necessary in the human body as a low and high Zn concentration can lead to pneumonia and liver damages, respectively [29, 30]. High level of Cu in the human body can lead to several diseases including Wilson’s disease and heart, kidney, and liver failures as well as brain diseases [31, 32]. The fabricated device demonstrated high stability and selectivity toward heavy metals, providing a great platform to advancing the field of wearable biosensors for healthcare application [28].
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Figure 2.
(a) A schematic showing the concept of deposition and stripping on microelectrodes. (b) A schematic showing the composition of the microsensor array. (c) Optical image of a flexible sensor array interfacing with a flexible printed circuit connector [28].
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4. Saliva analysis
\n
Saliva, as a great diagnostic fluid, can be used in personal health devices for real-time monitoring of chemical markers including salivary lactate analysis [33]. Chai et al. developed a saliva nanosensor with a radio-frequency identification tag, integrated into dental implants for detecting cardiac biomarkers in saliva and predicting close heart attack in patients suffering from cardiovascular diseases [34]. In another approach, an instrumented mouthguard was designed and fabricated by Kim et al. [35] for measuring salivary uric acid levels which could be a biomarker for several diseases including hyperuricemia, gout, physical stress, and renal syndrome. The fabricated device showed high selectivity and sensitivity to low level of uric acid as well as great stability during a 4-h operation period [35]. Mannoor et al. [36] developed a hybrid biosensor made of graphene layers printed onto water-soluble silk, for noninvasive detection of bacteria through body fluids including sweat and saliva. This graphene/silk hybrid device illustrated an extremely high sensitivity to bacteria in body fluid with detection limits down to a single bacterium [36]. In addition, the fabricated device provided the potential users with battery-free operation and wireless communication system via radio frequency [36]. Arakawa et al. [37] designed and fabricated a salivary sensor equipped with a wireless measurement system, embedded onto a mouthguard support, featuring a high sensitivity toward detection of glucose over a range of 5–1000 μmol L−1. The device demonstrated a great stability during a 5-h real-time glucose monitoring period in an artificial saliva with a phantom jaw [37]. In a similar approach, de Castro et al. [38] developed a microfluidic paper-based device integrated into a mouthguard, for continues monitoring of glucose and nitrite in human saliva. The saliva samples were collected from periodontitis and/or diabetes patients as well as healthy individuals. The fabricated device featured a low detection limit of 27 and 7 μmol L−1 for glucose and nitrite, respectively [38].
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\n
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5. Summary
\n
In summary, there is a great potential for micro- and nanosensors’ integration into healthcare monitoring devices, developing new technologies for noninvasive detection of diseases in the human body. Flexible wearable devices offer promising capabilities in real-time monitoring of body fluids including tear, sweat, and saliva. However, more research is required to expand the use of wearable platforms in continuous analysis of body fluids, providing reliable real-time detection of targeting ions and proteins, among other complex analytes.
\n
\n\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/69186.pdf",chapterXML:"https://mts.intechopen.com/source/xml/69186.xml",downloadPdfUrl:"/chapter/pdf-download/69186",previewPdfUrl:"/chapter/pdf-preview/69186",totalDownloads:827,totalViews:0,totalCrossrefCites:2,totalDimensionsCites:2,totalAltmetricsMentions:0,introChapter:null,impactScore:1,impactScorePercentile:57,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"March 21st 2019",dateReviewed:"August 22nd 2019",datePrePublished:null,datePublished:"December 4th 2019",dateFinished:"September 21st 2019",readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/69186",risUrl:"/chapter/ris/69186",book:{id:"7654",slug:"wearable-devices-the-big-wave-of-innovation"},signatures:"Noushin Nasiri",authors:[{id:"234150",title:"Dr.",name:"Noushin",middleName:null,surname:"Nasiri",fullName:"Noushin Nasiri",slug:"noushin-nasiri",email:"noushin.nasiri@mq.edu.au",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/234150/images/system/234150.jpg",institution:{name:"Macquarie University",institutionURL:null,country:{name:"Australia"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Tear analysis",level:"1"},{id:"sec_3",title:"3. Sweat analysis",level:"1"},{id:"sec_4",title:"4. Saliva analysis",level:"1"},{id:"sec_5",title:"5. Summary",level:"1"}],chapterReferences:[{id:"B1",body:'Trung TQ , Lee NE. Flexible and stretchable physical sensor integrated platforms for wearable human-activity monitoring and personal healthcare. Advanced Materials. 2016;28(22):4338-4372\n'},{id:"B2",body:'Nakata S, Arie T, Akita S, Takei K. Wearable, flexible, and multifunctional healthcare device with an ISFET chemical sensor for simultaneous sweat pH and skin temperature monitoring. ACS Sensors. 2017;2(3):443-448\n'},{id:"B3",body:'Tricoli A, Nasiri N, De S. Wearable and miniaturized sensor technologies for personalized and preventive medicine. Advanced Functional Materials. 2017;27(15):1605271\n'},{id:"B4",body:'Arnold JF, Sade RM. Wearable technologies in collegiate sports: The ethics of collecting biometric data from student-athletes. 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Nature Communications. 2017;8:14997\n'},{id:"B10",body:'Malon RS, Sadir S, Balakrishnan M, Córcoles EP. Saliva-based biosensors: Noninvasive monitoring tool for clinical diagnostics. BioMed Research International. 2014;2014:962903\n'},{id:"B11",body:'Cappon G, Acciaroli G, Vettoretti M, Facchinetti A, Sparacino G. Wearable continuous glucose monitoring sensors: A revolution in diabetes treatment. Electronics. 2017;6(3):65\n'},{id:"B12",body:'Kim J, Campbell AS, Wang J. Wearable non-invasive epidermal glucose sensors: A review. Talanta. 2018;177:163-170\n'},{id:"B13",body:'Arakawa T, Kuroki Y, Nitta H, Toma K, Mitsubayashi K, Takeuchi S, et al. Mouth guard type biosensor “cavitous sensor” for monitoring of saliva glucose with telemetry system. In: 2015 9th International Conference on Sensing Technology (ICST), 2015. New Zealand: IEEE; 2015. pp. 46-49\n'},{id:"B14",body:'Blaikie TP, Edge JA, Hancock G, Lunn D, Megson C, Peverall R, et al. 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Sensors & Actuators, B: Chemical. 2016;227:35-42\n'},{id:"B24",body:'Pribil MM, Laptev GU, Karyakina EE, Karyakin AA. Noninvasive hypoxia monitor based on gene-free engineering of lactate oxidase for analysis of undiluted sweat. Analytical Chemistry. 2014;86(11):5215-5219\n'},{id:"B25",body:'Jia W, Bandodkar AJ, Valdés-Ramírez G, Windmiller JR, Yang Z, Ramírez J, et al. Electrochemical tattoo biosensors for real-time noninvasive lactate monitoring in human perspiration. Analytical Chemistry. 2013;85(14):6553-6560\n'},{id:"B26",body:'Curto VF, Fay C, Coyle S, Byrne R, O’Toole C, Barry C, et al. Real-time sweat pH monitoring based on a wearable chemical barcode micro-fluidic platform incorporating ionic liquids. Sensors & Actuators, B: Chemical. 2012;171-172:1327-1334\n'},{id:"B27",body:'Anastasova S, Crewther B, Bembnowicz P, Curto V, Ip HM, Rosa B, et al. A wearable multisensing patch for continuous sweat monitoring. Biosensors & Bioelectronics. 2017;93:139-145\n'},{id:"B28",body:'Gao W, Nyein HY, Shahpar Z, Fahad HM, Chen K, Emaminejad S, et al. Wearable microsensor array for multiplexed heavy metal monitoring of body fluids. ACS Sensors. 2016;1(7):866-874\n'},{id:"B29",body:'Lassi ZS, Moin A, Bhutta ZA. Zinc supplementation for the prevention of pneumonia in children aged 2 months to 59 months. Cochrane Database of Systematic Reviews. 2016;12:CD005978\n'},{id:"B30",body:'Mohammad MK, Zhou Z, Cave M, Barve A, McClain CJ. Zinc and liver disease. Nutrition in Clinical Practice. 2012;27(1):8-20\n'},{id:"B31",body:'Crisponi G, Nurchi VM, Fanni D, Gerosa C, Nemolato S, Faa G. Copper-related diseases: From chemistry to molecular pathology. Coordination Chemistry Reviews. 2010;254(7-8):876-889\n'},{id:"B32",body:'Huster D. Wilson disease. Best Practice & Research. Clinical Gastroenterology. 2010;24(5):531-539\n'},{id:"B33",body:'Lee J, Garon E, Wong D. Salivary diagnostics. Orthodontics & Craniofacial Research. 2009;12(3):206-211\n'},{id:"B34",body:'Chai PR, Castillo-Mancilla J, Buffkin E, Darling C, Rosen RK, Horvath KJ, et al. Utilizing an ingestible biosensor to assess real-time medication adherence. Journal of Medical Toxicology. 2015;11(4):439-444\n'},{id:"B35",body:'Kim J, Imani S, de Araujo WR, Warchall J, Valdés-Ramírez G, Paixão TRLC, et al. Wearable salivary uric acid mouthguard biosensor with integrated wireless electronics. Biosensors & Bioelectronics. 2015;74:1061-1068\n'},{id:"B36",body:'Mannoor MS, Tao H, Clayton JD, Sengupta A, Kaplan DL, Naik RR, et al. Graphene-based wireless bacteria detection on tooth enamel. Nature Communications. 2012;3:763\n'},{id:"B37",body:'Arakawa T, Kuroki Y, Nitta H, Chouhan P, Toma K, Sawada S-I, et al. Mouthguard biosensor with telemetry system for monitoring of saliva glucose: A novel cavitas sensor. Biosensors and Bioelectronics. 2016;84:106-111\n'},{id:"B38",body:'de Castro LF, de Freitas SV, Duarte LC, de Souza JAC, Paixão TR, Coltro WK. Salivary diagnostics on paper microfluidic devices and their use as wearable sensors for glucose monitoring. Analytical and Bioanalytical Chemistry. 2019:1-10\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Noushin Nasiri",address:"noushin.nasiri@mq.edu.au",affiliation:'
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1. Introduction
Canine parvovirus (CPV-2) is a member of the Parvoviridae family, Parvovirinae subfamily, and Protoparvovirus genus. It causes severe, acute hemorrhagic gastroenteritis and myocarditis infection in dogs [1]. It is the most important enteric virus affecting domestic and wild carnivores throughout the globe [2]. CPV-2 is a non-enveloped virus with a single-stranded negative-sense DNA genome [3]. The genetic diversity of CPV-2 resulted in the emergence of 5 distinct antigenic variants such as CPV-2a, CPV-2b, new CPV-2a, new CPV-2b, and CPV-2c with amino acid differences mainly restricted to the capsid VP2 protein [4]. CPV-2 are ubiquitous and sturdy viruses that remain viable for more than one year in the favorable environment [5, 6] and are transmitted usually by the faeco-oral route [7, 8].
CPV-2 causes 100 percent morbidity and mortality rate of 10 percent and 91 percent in adult and young dogs respectively [9]. However, a mortality of 91 percent was reported in experimentally infected dogs that were not treated [10]. CPV-2 affects predominately the younger dogs between 6 weeks and 6 months [8] with an increased susceptibility to puppies less than 6 months. In dogs over the age of 6 months, sexually intact males are more likely (twice) to develop canine parvovirus enteritis (CPVE) in comparison to intact females [11]. The CPV-2 antibody titer transmitted to the newborn via absorbed colostral antibody is 50–60% of the mother’s titer. The half-life of paroviral maternal antibodies is around 10 days [12]. Therefore, puppies are highly susceptible to the CPV-2 infection as the maternal antibody titres start declining. CPVE affects dogs of all ages, although it is more severe in puppies. Puppies can succumb to shock and die within two days after being sick. The most striking symptom of CPV-2 myocarditis is the abrupt mortality in young puppies, generally around the age of 4 weeks [13].
In recent years, CPVE outbreaks caused by multiple CPV-2 variants have been recorded in diverse geographical locations throughout the world. Previously, CPV-2, which could not infect cats, has been replaced by CPV-2 variants that can now infect cats, suggesting that CPV-2 may be capable of spreading between species [14]. Since CPV-2 infects a wide range of wild animals in the order Carnivora, subclinical infection appears to be prevalent. As a result, significant CPV-2 reservoirs in wildlife appear to exist, and transmission of virus between domestic dogs and wildlife appears to be common and bidirectional [15]. Despite the availability of a wide range of immunoprophylactic and antiviral agents to control CPV-2 infections in dogs, many outbreaks have been reported throughout the world, and the disease has remained a major veterinary and economic concern due to the presence of unvaccinated dogs, intervention of active immunization by maternally derived antibodies, and the emergence of a different antigenic variants of CPV-2.
2. Virology of CPV-2
Canine parvovirus infection is caused by Carnivore protoparvovirus-1 which is characterized under the genus Protoparvovirus, family Parvoviridae. CPV-2 is a member of the Parvoviridae family, which includes two subfamilies: Parvovirinae (infects vertebrates) and Densovirinae (infects invertebrates) Parvovirus, Erythrovirus, Dependovirus, Amdovirus, Bocavirus, and other unclassified vertebrate parvoviruses are all the genus which comes under Parvovirinae (Figure 1) [16]. CPV-2 genome is a single stranded, negative sense, linear DNA of about 5 kb [17] contained by two ORFs translated into 4 proteins through alternative splicing [18, 19]. One ORF is associated with the non-structural proteins NS1 and NS2, which are mainly related to the viral replication and the second ORF is related with the viral capsid constituents VP1 and VP2. After the cleavage of VP2, VP3 is formed due to the involvement of host proteases. The capsid has 60 protein subunits, 90% of which are VP2 (67 kDa) and 10% are VP1 (83 kDa) [20].
Figure 1.
Schematic representation of Parvovirdae taxonomy.
The virus is nonenveloped having icosahedral symmetry and is 25 nm in diameter. The CPV virus is made up of the sixty protein subunits containing VP1 (5–6 units) and VP2 (54–55 units). The protein structure is made up of antiparallel β-barrel (8-stranded) capsid. The viral replication occurs inside the nucleus of multiplying cells and therefore the intranuclear inclusion bodies are formed during the infection. The viral capsid structure is made up of spike at the three-fold axes of the icosahedral unit, a 15-Å depression around the five-fold axes and two-fold axes is formed. Antigenic determinant regions have been plotted to the three-fold protrusion and the two-fold depression are related to the host cell features [17]. The surface of the capsid is composed of four loops inserted between the strands, resulting in spike-like protrusions around threefold axes of approximately 22 Å. The antigen neutralization site, also known as epitope A, is composed of loops 1 and 2 of one VP2 and loop 4 of a threefold related molecule [21]. The molecular weight (MW) is around 5.5 to 6.2 × 106 Da. There is an equal ratio of protein to nucleic acid.
NS1 is the largest non structural protein in CPV-2, and it is primarily involved in viral replication and pathogenicity [22]. NS1 is a key mediator of cytotoxicity of CPV and can selectively cause tumor cell lysis by inducing an antitumor immune response in different tumor models [23]. A recent study demonstrated the amino acid residues of T598 and T601 in the C-terminal phosphorylation sites of NS1 protein, involved in replication and pathogenicity of CPV-2 [24].
In the 1970s, CPV-2 emerged as a novel pathogen in dogs. Since then, CPVE has been reported across all the continents [25, 26]. Other related viruses such as Feline panleukopenia virus (FPV), Mink enteritis virus (MEV), Raccoon parvovirus (RPV) are closely related to the CPV-2 [27]. Mutations in the canine transferrin receptor (TfR) type-1 lead to adaptation of CPV-2 in different species 2 [28, 29]. There is more than 98% genome homology reported in the CPV and FPV nonetheless infect different species and have typical antigenic capsid and haemagglutination (HA) properties [28, 30]. The mutations in different amino acid positions have led to the effective adaptation in the new hosts [30]. There are over five to six mutations in the VP2 residue of the CPV-2 and FPV and also 375 and 323 amino acid position regulates the pH functionality of HA [31, 32]. CPV-2a (Asn CPV-2a) replaced CPV 2 in 1980s in the USA and various European countries. CPV 2a can infect the cats which was not a feature of CPV 2. CPV 2a has been displaced by the CPV-2b (426Asp) which was first reported in USA in 1982 and CPV-2c (426Glu) variant in Italy [31, 33]. Although two variants, CPV-2a and 2b had been identified much earlier, however, the third variant CPV-2c had been recognized in early 2000 [33]. Thereafter it has been reported frequently from many different countries. In addition, new CPV-2a and new CPV-2b have also been documented due to non-synonymous substitution at 297 residues (Ser to Ala) of VP2 protein [34]. In India, CPV-2a has recently become the most prevailing antigenic type among all variants. Recent emergence of new antigenic variants that differ significantly from the current vaccine strains is a matter of concern for efficacy of vaccine [35].
3. Canine parvovirus enteritis (CPVE)
The CPV is of two types: CPV-1, commonly known as minute virus of canine and accountable for gastrointestinal and respiratory infection of dogs whereas, CPV-2, most pathogenic type and is responsible for severe gastroenteritis/hemorrhagic gastroenteritis, in young puppies as well as adult dogs.
It is quite difficult to distinguish the clinical diseases caused by CPV-2 variants owing to its overlapping nature of signs and symptoms. These variants are believed to produce similar pathogenicity however; some studies showed that severity of clinical manifestations is influenced by variants of CPV-2 based on clinical, hematological, serological and histopathological examinations [36, 37].
Although puppies under 6 months of age are highly susceptible, adult dogs with insufficient immunity are also considered as high risk to the CPVE. CPV-2 can persist in the environment for more than a year, enabling susceptible dogs to pick up infection from CVP-2 contaminated feces, vomitus, or fomites. Although the feco-oral route is considered as primary path of disease transmission, infection through the oro-nasal route is also common in naive or under-immunized dogs due to ingestion of viruses shed in the vomitus or feces of CPV-2-infected animals [38]. However, direct contact or environmental contamination may also play a role [39]. Breed predisposition and seasonal prevalence of the disease are subject to considerable variations in wide geographical areas [40, 41].
Doberman, Rottweiler, and German shepherd (GS) dogs have been reported to be more susceptible to CPVE than other breeds [42]. Due to inherited immunodeficiency, the exotic breeds, German Sphered and Doberman, are more susceptible than the other breeds [43]. German shepherd has the highest CPV infection rate (70%) followed by the Doberman (55%) [44]. A cytokine bioassay revealed that the magnitude of TNF-α production by peripheral blood monocytes was greatest in dogs with a breed-related risk for CPVE. When compared to mixed breeds, highly susceptible breeds such as Rottweiler and Doberman Pinscher produce more TNF-α in response to LPS stimulation [45]. Increased TNF activity is predictive of mortality in naturally occurring CPVE infection in veterinary medicine [46]. Therefore, it has been hypothesized that dogs with a breed-related risk of developing CPVE, a disease associated with sepsis, would have a greater pro-inflammatory cytokine response to endotoxin [45].
The incubation period of CPV-2 infection ranges from 4 to 14 days. The infected dogs start to shed virus few days prior to the visible clinical signs and shedding of virus gradually declines 3–4 weeks postexposure [47]. Following entry into the body, the CPV-2 rapidly multiply in oropharyngeal lymph node, thymus and mesenteric lymph node, resulting in viremia within one week of exposure. After that, the virus attacks rapidly multiplying cells of crypts of intestine, epithelium of the tongue, oral cavity, bone marrow, and cardiac myocytes, besides lung, spleen, liver, and kidneys [48]. The key pathogenic event in CPV-2 infection is the virus-induced destruction of enterocyte, leading to mucosal barrier disruption, and villous atrophy. This causes profuse vomiting and hemorrhagic diarrhea, nutrient malabsorption, dehydration/hypovolemia, metabolic acidosis and/or alkalosis. The disruption of mucosal barrier allows bacterial translocation from intestinal compartment to systemic circulation, resulting in septicemia, endotoxemia, systemic inflammatory response syndrome as well as hypercoagulability [49]. The CPV-2 infection in the thymus and bone marrow precursor cells results in loss of thymic cortex and profound leucopenia, respectively [48]. Death may occur due to multi-organ failure when the affected dogs remain unattended [40, 49]. Previously, myocarditis was thought to be the acute cause of death in young puppies however, this form nowadays occurs rarely because of widespread CPV vaccination of dogs. The concurrent infections with parasitic, virus, or bacterial intestinal pathogens or stressors may aggravate the disease [50, 51, 52].
The degree of clinical manifestations may vary with age, breed, and immune status, duration of illness and virulence of virus. The clinical signs of dogs with CPV infection are nonspecific in nature and resembles to gastritis and enteritis. The most notable clinical signs of CPVE are lethargy, depression, weakness, lack of appetence, bouts of vomiting, and diarrhea. The diarrhea is characterized by foul-smell and mucoid to purely hemorrhagic because slugging of intestinal mucosa and bleeding. The excessive loss of fluid during vomiting and diarrhea causes marked dehydration that results in development of hypovolemic shock. Occasionally, intussusception occurs due to intestinal dysmotility. Neurologic signs in puppies with CPVE may result from hypoxia secondary to myocarditis, hypoglycemia, or intracranial thrombosis or hemorrhages [52]. The bacterial translocation from intestine to systemic circulation can cause fever, systemic inflammatory response syndrome and septic shock with hypotension and organ failure [40, 48]. Apart from diarrhea, respiratory distress, pulmonary congestion and edema, alveolar and bronchiolar hemorrhage and convulsions are also occasionally manifested due to hypovolemia, endotoxic and septicemic shock [8, 53]. The malabsorbtion of nutrients and inadequate storage of glycogen in muscle and liver result in hypoglycemic encephalopathy which leads to seizures. On hospital admission, the prognosis is poor in CPVE dogs with intussusception, systemic inflammatory response syndrome and severe leucopenia.
4. Diagnostic approaches
4.1 Virus isolation
Virus isolation is considered as a gold standard for any viral disease diagnosis. In case of CPV-2 different cell lines like CRFK (Crandell Rees feline kidney), MDCK (Madin-Darby canine kidney) and A-72 are used for the isolation and propagation of the virus. The adapted virus causes distinct cytopathic effect in infected cell lines as cell rounding, aggregation, and necrosis of the affected cells. This requires the presence of special laboratory and is laborious [54].
4.2 Electron microscopy
It is an expensive technique for the detection of the virions by negative staining in the stool samples or culture isolated virus. Immunoelectron microscopy can also be done by using CPV-specific antibodies. The need of expensive electron microscope makes it out of reach for regular usage [55].
4.3 Haemagglutination test (HA)
The property of the CPV to cause agglutination of the pig, cat or rhesus monkey red blood cells at 4°C is used for detection of the CPV. The reciprocal of the maximum dilution of virus exhibiting ample agglutination of erythrocytes (mat formation) is designated as HA titer. The HA titer of more than 1:32 is usually considered as specific for CPV-2 [56].
4.4 Counter-immunoelectrophoresis (CIEP)
The use of electric current allows the rapid movement of antigen and antibody towards each other resulting into the formation of precipitation line quicker than simple diffusion reaction. This technique is not commonly used but have been utilized for the prevalence of CPV infection in clinically suspected dogs [57].
4.5 Fluorescent antibody test (FAT)
In this test, an antibody tagged with fluorescent dye is employed for detection of specific CPV antigen. Mostly it is used as direct FAT for the diagnosis of CPVE but is not used routinely for diagnostic purpose [58].
4.6 Latex agglutination test (LAT)
This is a commonly used test utilizing antigen–antibody interactions employing specific antigen or antibody and is mostly useful under the field conditions. Here, the property of agglutination of polystyrene beads coated with either specific antigen or antibody on their surface is used with anti-CPV monoclonal and polyclonal antibody to detect CPV-2 in the stool samples. Earlier it has been used for both qualitative and quantitative evaluation of CPV in suspected dog feces. Also, a recombinant VP2 protein-based LAT for determination of immune status in dogs against CPV-2. Besides LAT, a slide agglutination inhibition test has been used to detect the presence of CPV-specific antibodies by utilizing the agglutination property of CPV-2 [59].
4.7 Slide inhibition test-slide agglutination test (SIT-SAT)
This method is developed for the detection of CPV-2. SIT is an antibody typing system based on the ability of viral antibodies to bind with the virus and prevents the virus from binding to RBC. SAT is used for antigen detection by serially diluting the clinical sample and then incubating it with a fixed amount of RBC containing virus surface receptors. The virus particles in the sample bind to the RBC and form a lattice that can be seen visually [60].
4.8 Enzyme-linked immunosorbent assay (ELISA)
It is an enzyme-based immunoassay involving antigen–antibody interactions to screen a large number of samples at a time. Recombinant VP2 protein-based indirect ELISAs has been developed to detect and quantify antibodies against CPV-2. Novel polyclonal antibody-based antigen capture ELISA using rabbit anti-CPV hyperimmune sera as capture antibody and guinea pig anti-CPV hyperimmune sera as detector antibody has been also developed. IgY-based ELISA comprising of the chicken egg yolk-derived has been developed for the detection of both antigen and antibodies. Different commercial ELISA kits are currently available for CPV-2 antigen and antibody detection [61].
4.9 Immunochromatographic (IC) assays
IC assays or Lateral flow assays are strip-based devices utilized for the detection of a target analyte in test samples. Colloidal gold nanoparticles are commonly used in synthesis of the probe (conjugate) in majority of these strip-based points of care assays. Different components used are the sample pad, conjugate pad, nitrocellulose membrane, absorbent pad and a plastic cassette. These tests are now used routinely for the parvovirus diagnosis in affected dogs. A number of lateral flow assay-based commercial kits are available for rapid detection of both CPV-2 antigen in feces and antibodies in serum, which are also available in the market. These are helpful in the field and gives rapid results within 10–15 mins. Recombinant VP2 protein based immunochromatography tests has also been developed based on the rapid detection of CPV-2 [62].
4.10 Dot blot/dot-ELISA
It is an immunological test which uses charging of test antigen on to a nitrocellulose or PVDF membrane followed by detection using specific antibody against the antigen and an enzyme labeled secondary antibody which forms a color on addition of an insoluble substrate. It is helpful as on the spot assay for CPV diagnoses. It has been developed for detection of CPV-2 using hyperimmune sera raised against the whole virus/recombinant VP2 protein. Commercial dot ELISA kits are also available for evaluating IgM response against CPV-2 after vaccination or infection [63].
4.11 Polymerase chain reaction (PCR)
PCR is a molecular diagnostic assay which is used for the detection of viral nucleic acid and is relatively more sensitive than other conventional tests. Diverse antigenic types of the CPV can be distinguished by employing strain-specific primer or nested PCR or restriction enzyme analysis of the PCR. Also strain differentiation may be carried out with the help of oligonucleotide sequencing of the amplified gene [64].
4.12 Nucleic acid hybridization/dot blot
This has also been reported for the detection of CPV nucleic acid. Here hybridization with CPV-specific biotin or radiolabelled probe is carried out onto the CPV nucleic acid charged nitrocellulose paper or nylon membrane from suspected samples and then formation of color and band in the radiograph indicates the presence of the virus [65].
4.13 In situ hybridization assay
It uses an isotopic-labeled probe for both the detection and tracking of CPV nucleic acid in affected morbid tissue specimens thus,using more incubation time for development of the positive reaction [66].
4.14 Real-time polymerase chain reaction (qPCR)
This technique can be employed to quantitate CPV-2 in samples using either TaqMan probe technology or SYBR Green method. It is used for strain differentiation of concurrent infection using Multiplex Real-time PCR; and also, to differentiate vaccine strain from wild CPV strains. Different multiplex assays real-time PCR has been validated for the presence of CPV, FPV and PPV [67].
4.15 Amplification refractory mutation system PCR (ARMS-PCR)
It is used for the detection and typing of the known point mutations/single nucleotide polymorphism based on variable size of PCR-amplified products specific to a particular allele. In this PCR basically 2 pairs of primers are used (2 inner and 2 outer specific primers matching to individual allele type) in a single PCR tube and there are no post-PCR protocols used as restriction enzyme digestion (PCR-RFLP) and sequencing therefore they provide an economical confirmation. ARMS-PCR is a well-known technique frequently employed for phenotypic association and single nucleotide polymorphism (SNP) studies. This has been used for CPV detection and its antigenic typing [54].
4.16 Peptide nucleic acid-based (PNA) Array
It contains a stable electrically neutral peptide backbone and the PNA-DNA hybridization assay are relatively more sensitive and specific than TaqMan-based real-time PCR for CPV differentiation [68].
The assay is a sensitive and rapid technique used for amplification of DNA and thereby pathogen detection in an hour by using the DNA polymerase by autocycling strand displacement action by boiling at persistent temperature (60–65°C) in water bath. Usually, 2 sets of primers bind to 4 to 6 different regions of target viral DNA. LAMP has field application as there is no need for any thermocycler to carry out the target gene amplification. The amplification of VP2 gene of CPV-2 by LAMP assay has been developed. LAMP assay along with lateral flow dipstick (LFD) and LAMP-ELISA are also used for CPV DNA detection [69].
4.18 Insulated isothermal PCR method
It is a convection-based method using a hydrolysis probe for detection of CPV-2 and its antigenic variants. The reaction mixture is sequentially allowed to pass in an automatic manner through variable temperature zones in a capillary tube which undergoes thermocyclic phase to amplify the DNA and the probe hydrolysis produces optical output providing the result within an hour [70].
4.19 Polymerase spiral reaction (PSR)
This technique makes use of both conventional PCR and isothermal amplification as in LAMP and is completed within one and a half hour. Here mostly an exogenous sequence from an unrelated species or of botanical origin is incorporated at the 5′ end into the primer sequences used in PSR if a human or veterinary pathogen is targeted. PSR has been successfully used to detect all CPV antigenic variants with ten-fold higher sensitivity than traditional PCR [71].
4.20 Fluorescence melting curve analysis (FMCA)
It is a probe-based assay that uses melting curve analysis to detect and differentiate between CPV-2 variants. This assay consists of 2 TaqMan probes namely FAM labeled and HEX labeled. The FAM-labeled probe sequence is perfectly complementary to CPV-2a, with a 1 bp mismatch to CPV-2b and a 2 bp mismatch to CPV-2c. The HEX-labeled probe has complete complementarity with the original CPV-2 and a 1-bp mismatch with the other variants. This method is also capable of detecting samples containing more than one variant without sequencing [72].
4.21 DNA aptamers
Aptamers emerged as a good alternative to antibodies as affinity reagents. Recently, ssDNA aptamers that specifically bind with the recombinant VP2 (rVP2) protein of CPV-2 with affinity in the nanomolar range have been reported. The ssDNA aptamers specific to CPV-2 (rVP-2) were selected by the Systematic evolution of ligands through exponential enrichment (SELEX) method and their target binding was assessed by dot blot and enzyme-linked oligonucleotide assay (ELONA). Aptamers with high binding affinity and specificity against rVP-2 could be employed in diagnostics for rapid detection of CPV-2 [73].
4.22 Nucleotide sequencing
It is primarily used for most viral genome identification and confirmation. Thus, considered as a gold standard for the antigenic typing of CPV variants. The amplified PCR product is either directly sequenced or cloned which is sequenced in a sequencer utilizing apt primers. The sequence data is analyzed using the appropriate bioinformatics database. Either nucleotide or amino acid sequence data or even both could be employed to recognize the evolutionary analysis of CPV-2 isolates from different geographical sites [74].
4.23 Biosensor
It is an analytical device which detects the DNA/RNA/protein/enzymes and alters it to the detectable electrical signals. A biosensor for CPV detection has been established by means of quartz crystal microbalance biosensor and ProLinker B [75]. Summary of different types of diagnostic assays are listed in the Table 1.
Diagnosis
Specimen
Diagnostic assay used
Feature
Remarks
CPV antigen
Feces or rectal swab
ELISA
High specificity Low sensitivity
Feces or rectal swab
Haemagglutination assay
Low-cost and rapid.
Sensitivity and specificity vary
Tissues or morbid samples
Necropsy specimens
Histopathology
Different histopathological techniques and IHC may be used.
Differential diagnosis with other enteric infections
Viral DNA
Feces or rectal swab or any tissue
Polymerase chain reaction (PCR);qPCR
Efficient in diagnosing even minute amount of viral genome, can be quantified; Antigenic typing
Sensitivity and specificity vary. Vaccine virus shedding occurs upto weeks after immunization leading to false positives results. Inhibitory components may lead to false negative results.
Virus
Feces or rectal swab or any tissue
Virus isolation
Confirmatory diagnosis
Requires special facility
Virus particles
Feces or rectal swab or any tissue
Electron microscopy
Confirmatory diagnosis
Requires special facility, expensive
Table 1.
Summary of the different types of diagnostic assays for CPVE diagnosis.
4.24 Commercially available kits
Commercially available kits are mostly based on antigen–antibody reactions, such as ELISA, dot ELISA, and immunochromatographic strip-based assays (Table 2).
List of commericially available kits for CPV-2 detection.
5. Treatment of CPV-2 infection
5.1 Recent advances in therapeutic management of CPVE
In absence of effective and appropriate antiviral drugs, the most universal therapeutic regimen for CPVE is supportive and symptomatic care until vomiting and diarrhea have resolved. Because of long-term illness of CPVE infected dogs, the challenges faced by the pet owners are cost of treatment and hospitalization. In private practice settings, the treatment cost may be huge, indicating that financial constraints may be a factor in disease-related euthanasia [81]. Therefore, fatality of CPVE is documented more in socioeconomically underprivileged areas, where level of education and financial opportunity for care and vaccination are not adequate [82]. Although the survival rate of CPVE in hospitalized and outpatient dogs is debatable, a recent prospective, randomized trial found no significant differences in survival (90% vs. 80%, P = 0.66) or duration of hospitalization (4.6d vs. 3.8d, P = 0.20) between inpatient and outpatient dogs [83]. However, given the possible risks of long-term hypoglycemia and leukopenia, aspiration pneumonia, edema, and intussusception in CPVE dogs, hospitalization appears to be the better option over outpatient treatment [84].
The principal components of supportive and symptomatic therapy include 1) fluid therapy and oncotic support, 2) antibiotics, 3) antiemetics, and 4) nutritional support. A wide range of other treatment measures including, though not limited to, antiviral treatments and pain management have been assessed in the past or are currently under investigation regarding their potential utility in CPVE.
5.2 Management of fluid and electrolyte imbalance and oncotic support
The development of severe hypovolemia is the first impact of pathophysiology in dogs with CPVE, hence re-establishment of the circulating volume is the utmost need [85]. The hypokalemia, hypochloremic metabolic alkalosis, hypoglycemia, hypoproteinemia and loss of oncotic pressure in circulation are the major fluid and electrolyte abnormalities during episode of diarrhea and vomition in acute CPVE [86]. The most aggressive therapies consisting of administration of intravenous (IV) fluids to restore intravascular fluid volume status, replenish interstitial fluid losses, maintenance of hydration and oncotic support. A balanced isotonic crystalloid solution (eg, Lactated Ringers) should be used for initial restoration of intravascular volume and rehydration, with a rate titrated to improve perfusion parameters such as capillary refill time, mucosal color, pulse character, and mean arterial pressure or lactate concentrations. Apart from fluid administration, potassium need to be supplemented in hypokalemic patients whereas, 25% dextrose at the dose rate of 1-2 mL/Kg body weight followed by addition of 2.5–5% dextrose in the crystalloid fluids will be required for hypoglycemic patients with blood glucose level < 60 mg/dL. Initially, the fluid is administered at the dose rate of 80–90 mL/kg with a boluses of 15–20 mL/kg over 15–20 minutes to counter the hypovolemic shock and, to improve the fluid perfusion. After that, the maintenance dose for daily fluid depends on the body weight (kg) and percent of dehydration. The volume (L) required to correct the daily fluid loss is calculated as body weight (Kg) × % dehydration. Generally, 40–60 mL fluid for each kg body weight is considered as ideal maintenance dose. Since fluid absorption through subcutaneous route is impaired in hypovolemic patients, intravenous access is considered as choice of fluid treatment. However, intraosseous or jugular catheter are considered as appropriate option in severe hypovolemic or interstitially dehydrated patients [87].
In CPVE, protein loosing enteropathy attributes to pronounced hypoalbuminemia (<2 g/dL) and/or hypoproteinemia (<4 g/dL) resulting in peripheral edema, pleural or abdominal effusions [88]. In that case, provision of oncotic support in the form of either natural or synthetic colloids are very important to minimize the morbidity and mortality of patients [89]. For correction of hypoalbuminemia, fresh plasma (20 mL/kg) or fresh-frozen plasma (6.6–11 mL/kg IV or 3 doses administered intraperitoneally 12 hours apart) and canine-specific albumin concentrate are used [90]. The concentrated human albumin products can also be used but the risk of immune reaction is the major limitation. If further oncotic support is required, hydroxyethyl starch (20–30 mL/kg/d) can be given, depending on clinician choice [6]. Sometimes, administrations of whole blood (20 mL/kg, within 4 hours) or packed RBCs are needed in severe anemic dogs with CPVE.
5.3 Antiemetic treatment
Apart from fluid and electrolyte imbalance, emesis is another clinical manifestation in CPVE. So, antiemetic treatment is warranted in CPVE otherwise persistent vomition may enhance the duration of hospital stay and further aggravates the condition of patient. The clinical efficacy of number of antiemetics in CPVE had been investigated with varying degree of results. The earlier studies showed that metoclopramide, a dopaminergic antagonist, was found to be effective in reducing episode of vomition by exerting a prokinetic effect in the upper intestinal tract and blocking the chemoreceptor trigger zone when administered as a bolus or as a constant-rate infusion in dogs. The ondasetron or dolasetron, the serotonin receptor antagonists, are also found effective in reducing the number of vomiting events [85]. Recently, a substantial antiemetic effect of maropitant, an antagonist of neurokinin1 receptors, by stimulation of either central or peripheral emetic pathways has been reported in dogs however, the efficacy of maropitant in CPVE has yet to be thoroughly investigated [91]. The administration of maropitant once daily, singly or in combination with metoclopramide, is very effective in reducing vomition in CPVE [5].
5.4 Antimicrobial treatment
Translocation of bacteria from intestinal compartment to systemic circulation is very common in CPVE because of villous collapse and disruption of the mucosal barrier. The translocation with concurrent marked neutropenia leads to a high risk of septicemia and endotoxemia. Additionally, hypotension from fluid loss and sepsis make dogs with CPVE at high risk of developing acute kidney injury. Therefore, parenteral administration of broad-spectrum bactericidal antibiotics is necessary in dogs with CPVE. Ampicillin and cefoxitin as single-agent treatments or in combination with enrofloxacin are the choice antimicrobials against Gram-positive and negative bacteria [85]. Aminoglycosides may also be considered in well-hydrated animals otherwise it may be avoided due to its inherent risk of nephrotoxicity. Puppies with CPVE often have comorbidities, including gastrointestinal parasitism. Hence, antiparasite therapy should be initiated once the puppy can tolerate oral therapies [6].
5.5 Nutritional support and pain management
Restoration of early mucosal integrity and prevention of bacterial translocation from gut compartment to systemic circulation are very important for faster recovery of dogs with CPVE. Enteral feeding is reported to improve the mucosal integrity and faster repair, resulting in lower possibilities for bacterial translocation [8]. In earlier study, it was demonstrated that early enteral nutrition via nasoesophageal catheter starting 12 hours post-admission led to clinical improvement, significant weight gain, and improved gut barrier function was more early as compared to withholding of the traditional food until cessation of vomiting for 12 hours [92].
Severe vomition, enteritis, and or concurrent intussusception in CPVE are the possible reasons for abdominal pain. Hence, analgesic treatment to reduce visceral pain is one the important aspect in therapeutic management in CPVE. Partial mu-agonists such as buprenorphine (0.01–0.02 mg/kg IV every 8 hours) or an agonist–antagonist such as butorphanol (0.1–0.2 mg/kg/h) are the preferred analgesics over the pure mu agonists as opioid analgesics can promote ileus and vomiting. The α-2 agonists that promote extreme vasoconstriction and limit gastrointestinal perfusion, and non-steroidal anti-inflammatory drugs that impair gastrointestinal and renal perfusion, both are not indicated [93].
5.6 Antiviral drugs
Like other viral infections, prophylaxis is the cornerstone for prevention of CPV in dogs. Although, an adequate number of killed and live CPV vaccines are marketed by pharmaceuticals but vaccines sometimes fail to protect completely due to poorly responding breeds (Rottweilers and Doberman pinschers), variation in genetic makeup of field and vaccine viruses, interference by presence of maternal antibodies and adjunct factors [94]. Therefore, development of some suitable antiviral drugs is utmost important for effective management of the CPVE in its acute illness stage. Till now, only few antiviral drugs have been evaluated for its clinical efficacy against CPVE. In an earlier placebo-control study, the therapeutic efficacy of Oseltamivir, a neuraminidase inhibitor, in CPVE had been evaluated and noted that Oseltamivir did not produce any additional benefit in terms of reduction of mortality or duration of hospitalization except some improvements in body weight and hemogram in dogs with CPV-illness [95]. In another study on naturally infected dogs, a promising anti-CPV activity of recombinant feline interferon-ω (rFeIFN-ω) has been recorded as compared to placebo-group. The intravenous administration of rFeIFN-ω at the dose rate of 2.5 mU/kg daily for consecutive three days remarkably reduced the clinical symptoms and mortality [96, 97]. Although the drug is currently available for use in Europe and Australia, the high price and frequent non-availability are major limitations. Recently, another antivital drug, Acyclovir, guanine analogue commonly used to treat herpes simplex virus infection, have been shown to improve the disease conditions [98]. Further, an in-vitro study on A72 cell line showed that 9-(2- hydroxyethomethyl) guanine phosphoromonomorpholidate (ACV PMMPD), a phosphorimidate analogue of acyclovir inhibits CPV-2 replication with exhibiting 50% inhibitory concentrations (IC50s) in the low-micromolar range (50 μM) [99]. Recently, broad-spectrum anti-CPV activity of some anti-parasitic drugs such as Nitazoxanide, Closantel Sodium, and Closantel have also been shown using F81 cells [100].
5.7 Passive immunotherapy
Passive immunization with specific antibodies against enteric viral infections in animals confers significant protection, reduces diarrhea and virus shedding and increase survival rates [101]. Thus, the of immunotherapeutics in viral infections is promising treatment approach because of lower adverse effects as well as no chance of any resistance as in antiviral drugs. The passive immunization by means of oral or intravenous administration of IgY specific for CPV-2 shows the protective effect in dogs challenged with the virus [102]. The reduction of clinical scores, duration of symptoms and mortality and improvement of body weight gain has been reported by anti-CPV-2 IgY therapy in experimentally produced CPVE [103]. Recent study reported that chicken IgY- single chain fragment variables (scFv) generated against the virus capsid protein could be a promising therapeutic target against CPV [104, 105]. Aside from IgY, the neutralization of CPV by anti-feline panleukopenia virus antibodies is also reported from an in-vitro study [106]. However, the prospective, randomized, placebo-controlled, double-blinded study on CPVE did not produce substantial benefits when compared with placebo group [86]. Apart from above therapeutics, plasma therapy is also another option. Although the administration of CPV-hyperimmune plasma is reported to decrease the clinical signs and improve the survival rate in dogs under experimental conditions, however the findings remain inconclusive in natural cases [107]. Another study showed that lyophilized IgG treatment reduced clinical signs and duration of hospitalization of dogs naturally infected with CPV [108].
5.8 Immunomodulators
The key physiopathological alterations of CPVE are destruction of intestinal crypts, neutropenia, secondary bacterial translocation, immunosuppression due to thymus atrophy, sepsis and systemic inflammatory response syndrome in puppies [6, 109]. Therefore, immunomodulators could be an option to enhance therapeutic efficacy of supportive treatment. A recent study demonstrated that subcutaneous administration of human dialyzable leukocyte extract-h (hDLE) along with supportive therapy in puppies with CPVE significantly increased the leukogram and reduced the clinical score, duration of hospitalization, mortality as compared to supportive therapy alone [110].
5.9 Cytokines based therapeutics
5.9.1 Granulocyte colony-stimulating factor
Leukopenia is one of the most important prognostic indicators of mortality in dogs with CPVE. Hence, stimulation of bone marrow and improvement of leukogram in peripheral circulation are considered as strategic approaches to reduce the CPVE associated mortality. Enhancement of endogenous canine G-CSF (cG-CSF) concentrations by exogenous administration of human G-CSF (hGCSF) and cG-CSF is reported to stimulate bone marrow, resulting in improvement of neutrophil counts in puppies with CPV infection [111]. However, the use of hG-CSF and cG-CSF may not necessarily improve survival [112, 113].
5.9.2 Interferons and biological response modifiers
The interferon (IFN)-ω, a type I IFN (similar to IFN-α), is known for its antiviral, anti-proliferation, and antitumor activities. A notable therapeutic effect of rIFN-ω on CPV-infected dogs is reported [114]. Additionally, the promising therapeutic potential of other type I (IFN-α, IFN-β, IFN-ε, and IFN-κ) and III (IFN-λ) IFNs in CPVE has also been reported [115].
Recently, anti-CPV activity of the serum derived transfer factors (TFs), low molecular weight (<5000 daltons) biological response modifiers has been documented. It imparts therapeutic benefit in CPVE by altering the cytokine response of the host [116].
5.10 Probiotics
Probiotics, primarily comprised of live microorganisms in fermented foods, protect gut from acute diarrhea through adherence and colonization on gut mucosa [117]. Therapeutic efficacy of probiotics has been verified in dogs with CPV associated illnesses [118]. In an earlier study, oral administration of probiotic preparations as an adjunct therapy to young dogs with CPVE has shown faster resolution of clinical signs, improved leukogram and decreased mortality as compared to supportive treatment alone [119]; whereas, no benefit with respect to length of hospital stay or case fatality was recorded in other study [120].
5.11 Antioxidants
The disturbance in oxidant/antioxidant equilibrium is evident in CPV-gastroenteritis and oxidative stress is believed to link with pathogenesis of CPVE [121]. Hence, addition of antioxidants in supportive therapy has emerged as a promising therapeutic option to improve the response of treatment in viral diseases. Treatment with N-acetylcysteine (NAC), a precursor to glutathione and the body’s primary cellular antioxidant, along with supportive therapy markedly improved the leukogram in dogs with CPVE when compared with supportive therapy alone [122].
5.12 Herbals
An interest in natural products including herbs, plants and their extracts/metabolites as antiviral drug candidates has increased in the last few decades especially due to rising emergence of antimicrobial resistance globally and potential side-effects of many antimicrobials [123]. Very recently, anti-parvoviral activity of propolis, a traditional Chinese medicine, prepared from honeybee hives has been documented [124]. The in vitro study on PK-15 cells showed that ferulic acid (FA), an important component of propolis attenuates the replication of porcine parvovirus by blocking proapoptotic factors (Bid, Bcl-2 and Mcl-1), and inhibiting the mitochondria-mediated response by hindering the activation of the Bid-related signaling pathway. The FA may serve as potential antiviral against CPV [124].
5.13 Fecal microbiota transplantation
Alteration in the gut microbiome is reported in enteric viral diseases including CPVE and other gastrointestinal diseases in dogs [125]. The disruption of gut microbiota leads to impediment in the enterocyte nutrition, immune regulation, protective barrier function, and gastrointestinal motility [126]. Therefore, restoration or re-establishment of the microbiota could have a good interest therapeutically. Recently, a randomized clinical trial showed that administration of fecal microbiota (10 g feces diluted in 10 mL of sterile 0.9% saline) obtained from healthy donor rectally at 6–12 hours post-admission caused faster resolution of diarrhea, shortened the duration of hospitalization and reduced the mortality in young dogs with CPVE when compared with standard therapy alone [126].
6. Prevention
A modified live virus (MLV) and an inactivated vaccine are the two types of CPV-2 vaccines currently available [94]. Administration of the vaccine should start at 6 to 8 weeks of age and then every 2–4 weeks until 16 weeks of age or older. For dogs that are 16 weeks or older, 2 doses of vaccination are recommended with an interval of 2–4 weeks [127]. A recombinant vaccine based on virus-like particles (VLPs) is being developed, which has the advantage of becoming highly immunogenic and safe [128]. Peptide vaccines containing major antigen neutralizing region N terminal of VP2 are also under developmental stage [129]. A single-dose vaccination of Vaccinia virus encoding CPV2-VP2 elicited substantial antibody responses and provided comparable protection for dogs with attenuated CPV2 vaccine. This vaccine could be used as a promising vaccine candidate to prevent CPV-2 infection in dogs [130].
7. Conclusion
CPV-2 is one of the most significant viral enteropathogens of canines causing high morbidity and mortality and manifested by vomition and severe acute haemorhagic gastroenteritis. Prompt symptomatic therapy will increase survivability of infected puppies but vaccination is best way to prevent the disease in dogs. Despite the pups are protected through vaccination from the pregnant bitch, it is more vulunerable to CPV-2 infection as maternal antibody titers started declining. Despite the availability of high sensitive and specific diagnostic approaches and the effective prophylactics such as modified live virus and inactivated vaccines, a large number of outbreaks are still reported in wide geographical areas across the globe in both vaccinated and unvaccinated dogs. The future studies should be taken up towards vaccination failures, occurrence of CPV-2 in different canine species and the emergence of antigenic variants of the CPV-2 involved in the outbreaks.
Acknowledgments
All the authors acknowledge and thank to their Institute.
Conflict of interest
The authors declare no conflict of interest.
Funding
This compilation is a book chapter written by its authors and required no substantial funding to be stated.
\n',keywords:"Canine parvovirus-2, CPVE, myocarditis, young dogs and antigenic variants",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/81793.pdf",chapterXML:"https://mts.intechopen.com/source/xml/81793.xml",downloadPdfUrl:"/chapter/pdf-download/81793",previewPdfUrl:"/chapter/pdf-preview/81793",totalDownloads:34,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 12th 2021",dateReviewed:"April 7th 2022",datePrePublished:"May 14th 2022",datePublished:null,dateFinished:"May 14th 2022",readingETA:"0",abstract:"Canine parvovirus-2 (CPV-2) is a highly contagious and key enteropathogen affecting the canine population around the globe by causing canine parvoviral enteritis (CPVE) and vomition. CPVE is one of the the leading causes of morbidity and mortality in puppies and young dogs. Over the years, five distinct antigenic variants of CPV-2, namely CPV-2a, CPV-2b, new CPV-2a, new CPV-2b, and CPV-2c, have emerged throughout the world. CPV-2 infects a diverse range of wild animals, and the newer variants of CPV-2 have expanded their host range to include felines. Despite the availability of highly specific diagnostics and efficacious vaccines, CPV-2 outbreaks have been reported globally due to the emergence of newer antigenic variants, expansion of the viral host range, and vaccination failures. The present chapter describes the latest information pertaining to virus properties and replication, disease manifestations in animals, and an additional recent updates on diagnostic, prevention and control strategies of CPV-2.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/81793",risUrl:"/chapter/ris/81793",signatures:"Mithilesh Singh, Rajendran Manikandan, Ujjwal Kumar De, Vishal Chander, Babul Rudra Paul, Saravanan Ramakrishnan and Darshini Maramreddy",book:{id:"11580",type:"book",title:"Recent Advances in Canine Medicine",subtitle:null,fullTitle:"Recent Advances in Canine Medicine",slug:null,publishedDate:null,bookSignature:"Dr. Carlos Eduardo Fonseca-Alves",coverURL:"https://cdn.intechopen.com/books/images_new/11580.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-381-7",printIsbn:"978-1-80356-380-0",pdfIsbn:"978-1-80356-382-4",isAvailableForWebshopOrdering:!0,editors:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Virology of CPV-2",level:"1"},{id:"sec_3",title:"3. Canine parvovirus enteritis (CPVE)",level:"1"},{id:"sec_4",title:"4. Diagnostic approaches",level:"1"},{id:"sec_4_2",title:"4.1 Virus isolation",level:"2"},{id:"sec_5_2",title:"4.2 Electron microscopy",level:"2"},{id:"sec_6_2",title:"4.3 Haemagglutination test (HA)",level:"2"},{id:"sec_7_2",title:"4.4 Counter-immunoelectrophoresis (CIEP)",level:"2"},{id:"sec_8_2",title:"4.5 Fluorescent antibody test (FAT)",level:"2"},{id:"sec_9_2",title:"4.6 Latex agglutination test (LAT)",level:"2"},{id:"sec_10_2",title:"4.7 Slide inhibition test-slide agglutination test (SIT-SAT)",level:"2"},{id:"sec_11_2",title:"4.8 Enzyme-linked immunosorbent assay (ELISA)",level:"2"},{id:"sec_12_2",title:"4.9 Immunochromatographic (IC) assays",level:"2"},{id:"sec_13_2",title:"4.10 Dot blot/dot-ELISA",level:"2"},{id:"sec_14_2",title:"4.11 Polymerase chain reaction (PCR)",level:"2"},{id:"sec_15_2",title:"4.12 Nucleic acid hybridization/dot blot",level:"2"},{id:"sec_16_2",title:"4.13 In situ hybridization assay",level:"2"},{id:"sec_17_2",title:"4.14 Real-time polymerase chain reaction (qPCR)",level:"2"},{id:"sec_18_2",title:"4.15 Amplification refractory mutation system PCR (ARMS-PCR)",level:"2"},{id:"sec_19_2",title:"4.16 Peptide nucleic acid-based (PNA) Array",level:"2"},{id:"sec_20_2",title:"4.17 Loop-mediated isothermal amplification assay (LAMP assay)",level:"2"},{id:"sec_21_2",title:"4.18 Insulated isothermal PCR method",level:"2"},{id:"sec_22_2",title:"4.19 Polymerase spiral reaction (PSR)",level:"2"},{id:"sec_23_2",title:"4.20 Fluorescence melting curve analysis (FMCA)",level:"2"},{id:"sec_24_2",title:"4.21 DNA aptamers",level:"2"},{id:"sec_25_2",title:"4.22 Nucleotide sequencing",level:"2"},{id:"sec_26_2",title:"4.23 Biosensor",level:"2"},{id:"sec_27_2",title:"4.24 Commercially available kits",level:"2"},{id:"sec_29",title:"5. Treatment of CPV-2 infection",level:"1"},{id:"sec_29_2",title:"5.1 Recent advances in therapeutic management of CPVE",level:"2"},{id:"sec_30_2",title:"5.2 Management of fluid and electrolyte imbalance and oncotic support",level:"2"},{id:"sec_31_2",title:"5.3 Antiemetic treatment",level:"2"},{id:"sec_32_2",title:"5.4 Antimicrobial treatment",level:"2"},{id:"sec_33_2",title:"5.5 Nutritional support and pain management",level:"2"},{id:"sec_34_2",title:"5.6 Antiviral drugs",level:"2"},{id:"sec_35_2",title:"5.7 Passive immunotherapy",level:"2"},{id:"sec_36_2",title:"5.8 Immunomodulators",level:"2"},{id:"sec_37_2",title:"5.9 Cytokines based therapeutics",level:"2"},{id:"sec_37_3",title:"5.9.1 Granulocyte colony-stimulating factor",level:"3"},{id:"sec_38_3",title:"5.9.2 Interferons and biological response modifiers",level:"3"},{id:"sec_40_2",title:"5.10 Probiotics",level:"2"},{id:"sec_41_2",title:"5.11 Antioxidants",level:"2"},{id:"sec_42_2",title:"5.12 Herbals",level:"2"},{id:"sec_43_2",title:"5.13 Fecal microbiota transplantation",level:"2"},{id:"sec_45",title:"6. Prevention",level:"1"},{id:"sec_46",title:"7. Conclusion",level:"1"},{id:"sec_47",title:"Acknowledgments",level:"1"},{id:"sec_51",title:"Conflict of interest",level:"1"},{id:"sec_47",title:"Funding",level:"1"}],chapterReferences:[{id:"B1",body:'Khatri R, Poonam MH, Minakshi PC. Epidemiology, pathogenesis, diagnosis and treatment of canine parvovirus disease in dogs: A mini review abstract. Journal of Veteinary Science & Medical Diagnosis. 2017;3:2'},{id:"B2",body:'DL MC, Hoskins JD. Canine viral enteritis. In: Greene CE, editor. Infectious Diseases of the Dog and Cat. third ed. Philadelphia: WB Saunders; 2006. pp. 63-73'},{id:"B3",body:'Decaro N, Buonavoglia C. Canine parvovirus--a review of epidemiological and diagnostic aspects, with emphasis on type 2c. Veterinary Microbiology. 2012;155:1-12. DOI: 10.1016/j.vetmic.2011.09.007'},{id:"B4",body:'Singh M, Chander V, Nandi S. Canine Parvovirus. In: Malik YS, Singh RK, Yadav MP, editors. Recent Advances in Animal Virology. 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DOI: 10.1111/jvim.15072'},{id:"B127",body:'Day MJ, Horzinek MC, Schultz RD, Squires RA. Vaccination guidelines group (VGG) of the world small animal veterinary association (WSAVA). WSAVA guidelines for the vaccination of dogs and cats. Journal of Small Animal Practice. 2016;57:E1-E45. DOI: 10.1111/jsap.2_12431'},{id:"B128",body:'Jin H, Xia X, Liu B, Fu Y, Chen X, Wang H, et al. High-yield production of canine parvovirus virus-like particles in a baculovirus expression system. Archives of Virology. 2016;161:705-710. DOI: 10.1007/s00705-015-2719-1'},{id:"B129",body:'Casal JI, Langeveld JP, Cortés E, Schaaper WW, van Dijk E, Vela C, et al. Peptide vaccine against canine parvovirus: Identification of two neutralization subsites in the N terminus of VP2 and optimization of the amino acid sequence. Journal of Virology. 1995;69:7274-7277. DOI: 10.1128/JVI.69.11.7274-7277.1995'},{id:"B130",body:'Zhao W, Wang X, Li Y, Li Y. 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Immunology Section, ICAR-Indian Veterinary Research Institute, India
Immunology Section, ICAR-Indian Veterinary Research Institute, India
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Zanthoxylum species have been used in traditional for the treatment of tooth decay, snakebites, blood circulation problems, stomach problems, inflammation, rheumatic, and parasitic diseases. The chemical investigations of Zanthoxylum have been studied by many scientists over the world. Several classes of compounds have been isolated from this genus such as alkaloids, coumarins, and monoterpenes. Of these, alkaloids are the main components and play an important role in Zanthoxylum species. Alkaloids have been shown the potential promise about biological activities: cytotoxic, antimalarial, leishmanicidal, anti-inflammatory, analgesic, antiviral, and antibacterial activities. This chapter will focus on the structure elucidation and pharmacological activities of alkaloids from Zanthoxylum species. 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Substantially contribute to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work
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Authors are responsible for ensuring all addresses and emails provided are correct. Under affiliation(s) all Authors should indicate where the research was conducted. Please note that no changes to the affiliation(s) can be made after the chapter has been published.
Substantially contribute to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work
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Participate in drafting or revising the work
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Approve the final version of the work to be published.
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All contributors who meet these criteria are listed as Authors. Their exact contributions should be described in the manuscript at the time of submission.
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Conversely, all contributors who do not meet these criteria should be listed in the Acknowledgments section of the manuscript, along with a short description of their specific contributions.
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CHANGES IN AUTHORSHIP
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If it is felt necessary to make changes to the list of Authors after a manuscript has been submitted or published, it is the responsibility of the Author concerned to provide a valid reason to amend the published list. Additionally, all listed Authors must verify and approve the proposed changes in order for any amendments to be made.
\n\n
AFFILIATION
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Authors are responsible for ensuring all addresses and emails provided are correct. Under affiliation(s) all Authors should indicate where the research was conducted. Please note that no changes to the affiliation(s) can be made after the chapter has been published.
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Early studies are focusing on the miRNA profile as a biomarker in disease. As discovery of human miRNAs increased in the setting of disease, the research focus was gradually shifted towards miRNA therapeutic strategy for diagnostic and treatment of disease. Increasing evidences suggest that miRNAs are the next important class of antisense therapeutic molecules, which have significant advantage over antisense such as siRNAs because miRNAs are naturally occurring endogenous molecules. Aberrant alteration of the endogenous miRNAs has been linked to the development of certain diseases. Correcting these altered miRNAs by their mimics or inhibitors has been developed as potential therapeutic approaches. Some of the miRNA-based therapeutics are processed in preclinical and clinical trial for treatment hepatitis C, liver cancer, and other diseases. Currently, the major focus in the development of miRNA-based therapeutics is how to increase the miRNA stability and optimize delivery systems for specific disease with minimal off-target effect. This chapter will first overview the miRNA biogenesis, patho- and physiologic function, and regulation of miRNA molecules. Then, we discuss the miRNA-based potential therapeutic approaches and implication in disease.",book:{id:"6987",slug:"antisense-therapy",title:"Antisense Therapy",fullTitle:"Antisense Therapy"},signatures:"Andrew Walayat, Meizi Yang and DaLiao Xiao",authors:[{id:"188957",title:"Dr.",name:"DaLiao",middleName:null,surname:"Xiao",slug:"daliao-xiao",fullName:"DaLiao Xiao"},{id:"269866",title:"Ph.D. Student",name:"Andrew",middleName:null,surname:"Walayat",slug:"andrew-walayat",fullName:"Andrew Walayat"},{id:"283826",title:"Dr.",name:"Meizi",middleName:null,surname:"Yang",slug:"meizi-yang",fullName:"Meizi Yang"}]},{id:"65601",doi:"10.5772/intechopen.84455",title:"Epigenetic Modifications in Plants under Abiotic Stress",slug:"epigenetic-modifications-in-plants-under-abiotic-stress",totalDownloads:1590,totalCrossrefCites:13,totalDimensionsCites:17,abstract:"Plants face a plethora of biotic and abiotic stresses ranging from extreme temperatures to salinity, drought, nutritional deficiencies, chemical toxicity, and pathogen attacks. As a consequence, plants have acquired several sophisticated regulatory mechanisms that allow them to cope with such adverse conditions. Epigenetic regulation plays a key role in the mechanisms of plant response to the environment, without altering DNA sequences. Epigenetics refers to heritable alterations in chromatin architecture that do not involve changes in the underlying DNA sequence but alter gene expression through DNA methylation or histone modifications. The epigenetic regulation of the plant genome is a highly dynamic process that fine-tunes the expression of a pertinent set of genes under certain environmental or developmental conditions. Over the past two decades rapid advancements in the field of high throughput sequencing unveil epigenetic information at genome wide level in various plant species. In view of the adverse effects of global climatic change, utilizing epigenetic differences for developing improved crop varieties is of paramount importance.",book:{id:"7995",slug:"epigenetics",title:"Epigenetics",fullTitle:"Epigenetics"},signatures:"Garima Singroha and Pradeep Sharma",authors:[{id:"142882",title:"Dr.",name:"Pradeep",middleName:null,surname:"Sharma",slug:"pradeep-sharma",fullName:"Pradeep Sharma"},{id:"281215",title:"Dr.",name:"Garima",middleName:null,surname:"Singroha",slug:"garima-singroha",fullName:"Garima Singroha"}]},{id:"32799",doi:"10.5772/33525",title:"GC3 Biology in Eukaryotes and Prokaryotes",slug:"gc3-biology-in-eukaryotes-and-prokaryotes",totalDownloads:1990,totalCrossrefCites:7,totalDimensionsCites:15,abstract:null,book:{id:"1723",slug:"dna-methylation-from-genomics-to-technology",title:"DNA Methylation",fullTitle:"DNA Methylation - From Genomics to Technology"},signatures:"Eran Elhaik and Tatiana Tatarinova",authors:[{id:"95992",title:"Dr.",name:"Tatiana",middleName:"Valerievna",surname:"Tatarinova",slug:"tatiana-tatarinova",fullName:"Tatiana Tatarinova"},{id:"105570",title:"Dr.",name:"Eran",middleName:null,surname:"Elhaik",slug:"eran-elhaik",fullName:"Eran Elhaik"}]},{id:"63488",doi:"10.5772/intechopen.80874",title:"Nontransformative Strategies for RNAi in Crop Protection",slug:"nontransformative-strategies-for-rnai-in-crop-protection",totalDownloads:2088,totalCrossrefCites:5,totalDimensionsCites:14,abstract:"RNAi in crop protection can be achieved not only by plant-incorporated protectants through plant transformation (transgenic) but also by nontransformative strategies such as formulations of sprayable dsRNAs used as direct control agents, resistance factor repressors, or developmental disruptors. Therefore, the RNAi-based biopesticides are expected to reach the market also in the form of nontransgenic strategies such as sprayable products, stem injection, root drenching, seed treatment, or powder/granule. While the delivery of dsRNA by transgenic expression is well established, it requires generations of crop plants and is costly, which may take years and delays for practical application, depending on the regulatory rules, plant transformability, genetic stability, and public acceptance of genetically modified crop species. DsRNA delivery as a nontransgenic approach was already published as a proof-of-concept work, so it is time to point out some directions on how the real potential for agriculture and crop protection is.",book:{id:"7331",slug:"modulating-gene-expression-abridging-the-rnai-and-crispr-cas9-technologies",title:"Modulating Gene Expression",fullTitle:"Modulating Gene Expression - Abridging the RNAi and CRISPR-Cas9 Technologies"},signatures:"Deise Cagliari, Ericmar Avila dos Santos, Naymã Dias, Guy Smagghe\nand Moises Zotti",authors:null},{id:"64492",doi:"10.5772/intechopen.82105",title:"Antisense Oligonucleotides, A Novel Developing Targeting Therapy",slug:"antisense-oligonucleotides-a-novel-developing-targeting-therapy",totalDownloads:3426,totalCrossrefCites:7,totalDimensionsCites:13,abstract:"Antisense oligonucleotides (ASOs) have been validated as therapeutic agents and an important tool in molecular biology. 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Nucleic acids, as encoding information for all forms of life, are excellent biomarkers for detecting pathogens, hereditary diseases, and cancers. To date, many techniques have been developed to detect nucleic acids. However, most of them are based on polymerase chain reaction (PCR) technology. These methods are sensitive and robust, but they require expensive instruments and trained personnel. DNA strand displacement amplification is carried out under isothermal conditions and therefore does not need expensive instruments. It is simple, fast, sensitive, specific, and inexpensive. In this chapter, we introduce the principles, methods, and updated applications of DNA strand displacement technology in the detection of infectious diseases. 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",coverUrl:"https://cdn.intechopen.com/series/covers/25.jpg",latestPublicationDate:"August 8th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"197485",title:"Dr.",name:"J. Kevin",middleName:null,surname:"Summers",slug:"j.-kevin-summers",fullName:"J. Kevin Summers",profilePictureURL:"https://mts.intechopen.com/storage/users/197485/images/system/197485.jpg",biography:"J. Kevin Summers is a Senior Research Ecologist at the Environmental Protection Agency’s (EPA) Gulf Ecosystem Measurement and Modeling Division. He is currently working with colleagues in the Sustainable and Healthy Communities Program to develop an index of community resilience to natural hazards, an index of human well-being that can be linked to changes in the ecosystem, social and economic services, and a community sustainability tool for communities with populations under 40,000. He leads research efforts for indicator and indices development. Dr. Summers is a systems ecologist and began his career at the EPA in 1989 and has worked in various programs and capacities. This includes leading the National Coastal Assessment in collaboration with the Office of Water which culminated in the award-winning National Coastal Condition Report series (four volumes between 2001 and 2012), and which integrates water quality, sediment quality, habitat, and biological data to assess the ecosystem condition of the United States estuaries. He was acting National Program Director for Ecology for the EPA between 2004 and 2006. He has authored approximately 150 peer-reviewed journal articles, book chapters, and reports and has received many awards for technical accomplishments from the EPA and from outside of the agency. 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He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). Besides, he has an M.Sc. degree in Applied Chemistry and a B.Sc. degree in Chemistry, all from the University of Chittagong, Bangladesh. \nDr. Rahman’s research interest includes the study of the fate and behavior of environmental pollutants in the biosphere; design of low energy and low burden environmental improvement (remediation) technology; implementation of sustainable waste management practices for treatment, handling, reuse, and ultimate residual disposition of solid wastes; nature and type of interactions in organic liquid mixtures for process engineering design applications.",institutionString:null,institution:{name:"Fukushima University",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"201020",title:"Dr.",name:"Zinnat Ara",middleName:null,surname:"Begum",slug:"zinnat-ara-begum",fullName:"Zinnat Ara Begum",profilePictureURL:"https://mts.intechopen.com/storage/users/201020/images/system/201020.jpeg",biography:"Zinnat A. 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Graduate in Sciences (Chemist), graduate in Geography and History (Geography), master in Water Management, Treatment, master in Fertilizers and Environment and master in Environmental Management; Ph.D. in Environmental Sciences. His research is focused on soil-water and waste-environment relations, mainly on soil-water and soil-waste interactions under different management and waste reuse. His work is reflected in more than 230 communications presented in national and international conferences and congresses, 29 invited lectures from universities, associations and government agencies. 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My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. 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