Dedicated virus inactivation procedures used in IVIG production [22]
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10111",leadTitle:null,fullTitle:"Apolipoproteins, Triglycerides and Cholesterol",title:"Apolipoproteins, Triglycerides and Cholesterol",subtitle:null,reviewType:"peer-reviewed",abstract:"Lipids are one of the most important biomolecules and, given their relationship with several non-communicable diseases at large, this makes them significant to be studied both biochemically and clinically. As the title of the book suggests, apolipoproteins, triglycerides, and cholesterol are focused herein with fresh perspectives and novel insights, while certain overlooked areas are given their due attention. Although these three terms are very broad, the book aims at primarily serving as an update to existing knowledge. It is hoped that the readers will benefit from this book in advancing their understanding about the biochemical pathways, clinical applications, and remedial action in terms of ensuring health and wellbeing, as well as in identifying gaps that would help set the directions of scientific investigations in the future.",isbn:"978-1-83962-520-6",printIsbn:"978-1-83962-519-0",pdfIsbn:"978-1-83962-521-3",doi:"10.5772/intechopen.88426",price:119,priceEur:129,priceUsd:155,slug:"apolipoproteins-triglycerides-and-cholesterol",numberOfPages:238,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"29ed0d776c8e3b2af0e50b3c4cf5e415",bookSignature:"Viduranga Y. Waisundara and Miljana Z. Jovandaric",publishedDate:"June 17th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/10111.jpg",numberOfDownloads:9670,numberOfWosCitations:8,numberOfCrossrefCitations:5,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:19,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:32,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 2nd 2019",dateEndSecondStepPublish:"October 23rd 2019",dateEndThirdStepPublish:"December 22nd 2019",dateEndFourthStepPublish:"March 11th 2020",dateEndFifthStepPublish:"May 10th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",middleName:null,surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. Waisundara",profilePictureURL:"https://mts.intechopen.com/storage/users/194281/images/system/194281.jpg",biography:"Dr. Viduranga Waisundara obtained her Ph.D. in Food Science\nand Technology from the Department of Chemistry, National\nUniversity of Singapore, in 2010. She was a lecturer at Temasek Polytechnic, Singapore from July 2009 to March 2013.\nShe relocated to her motherland of Sri Lanka and spearheaded the Functional Food Product Development Project at the\nNational Institute of Fundamental Studies from April 2013 to\nOctober 2016. She was a senior lecturer on a temporary basis at the Department of\nFood Technology, Faculty of Technology, Rajarata University of Sri Lanka. She is\ncurrently Deputy Principal of the Australian College of Business and Technology –\nKandy Campus, Sri Lanka. She is also the Global Harmonization Initiative (GHI)",institutionString:"Australian College of Business & Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"13",totalChapterViews:"0",totalEditedBooks:"11",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"268043",title:"Dr.",name:"Miljana Z.",middleName:"Z",surname:"Jovandaric",slug:"miljana-z.-jovandaric",fullName:"Miljana Z. Jovandaric",profilePictureURL:"https://mts.intechopen.com/storage/users/268043/images/system/268043.jpg",biography:"Miljana Z. Jovandaric was born in Serbia. She graduated from the Faculty of Medicine, University of Belgrade, Serbia, in 1989, and completed a specialization in Pediatrics at the University Children\\'s Hospital, Belgrade, in 1999. She completed her specialization in Neonatology in 2003. Dr. Jovandaric completed her master’s thesis on 'Analysis of lipid infants of women suffering from gestational diabetes mellitus (GDM)” in 2006 and her doctoral dissertation on 'Effect of hypoxia on electrolyte and lipid levels in term newborns” in 2018, both at the School of Medicine, University of Belgrade. She is the author and co-author of eighty-four scientific papers presented at national and international conferences and published in scientific journals. Dr. Jovandaric is currently head of the Department of Sick Newborns at the Clinic for Gynecology and Obstetrics, Department of Neonatology, Clinical Centre of Serbia.",institutionString:"Klinički centar Srbije",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"Klinički centar Srbije",institutionURL:null,country:{name:"Serbia"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"43",title:"Biochemistry",slug:"biochemistry-genetics-and-molecular-biology-biochemistry"}],chapters:[{id:"71384",title:"Significance of Lipid and Lipoprotein in Organism",doi:"10.5772/intechopen.91407",slug:"significance-of-lipid-and-lipoprotein-in-organism",totalDownloads:1120,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Lipids are important energy and building compounds. Their decomposition provides a significant amount of energy required for various life processes. It can thus be deposited in triglycerides and adipocytes. Some of them, in conjunction with proteins, form the most important structural elements of cells and cellular organelles, while others are precursors for the synthesis of numerous active compounds such as some hormones or prostaglandins. Lipids are ingested but can also be synthesized in the body. In circulation, lipids are found packed in lipoprotein molecules because they are insoluble in water. Lipoproteins have a central lipid part (nucleus) containing triglycerides and cholesterol esters, and on the surface there is a sheath composed of certain proteins (apoproteins), phospholipids, and small amounts of free cholesterol. Thanks to this sheath, lipids can be transported via blood. It took a long time to determine the importance and role of lipids in the body, as well as their role in many metabolic disorders of various diseases. This field is still unexplored and is a challenge for many researchers to prevent and treat lipid metabolism disorders.",signatures:"Miljana Z. Jovandaric and Svetlana J. Milenkovic",downloadPdfUrl:"/chapter/pdf-download/71384",previewPdfUrl:"/chapter/pdf-preview/71384",authors:[{id:"268043",title:"Dr.",name:"Miljana Z.",surname:"Jovandaric",slug:"miljana-z.-jovandaric",fullName:"Miljana Z. Jovandaric"},{id:"275297",title:"Dr.",name:"Svetlana",surname:"J. Milenkovic",slug:"svetlana-j.-milenkovic",fullName:"Svetlana J. Milenkovic"}],corrections:null},{id:"70983",title:"High-Density Lipoprotein: From Biological Functions to Clinical Perspectives",doi:"10.5772/intechopen.91136",slug:"high-density-lipoprotein-from-biological-functions-to-clinical-perspectives",totalDownloads:631,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"High-density lipoprotein (HDL) is a heterogeneous particle composed of apolipoproteins, enzymes, and lipids. Besides transporting cholesterol to the liver, HDL also exerts many protections on anti-oxidation, anti-inflammation, and anti-apoptosis. Initial understandings of HDL came from its protective roles against atherosclerosis and the observation that high plasma HDL cholesterol (HDL-C) levels seemed to decrease cardiovascular disease (CVD) attack. However, those patients either with cholesterol ester transfer protein (CETP) deficiency or taking CETP inhibitors substantially elevated HDL-C levels but did not necessarily decrease CVD risk. Thus, some researchers suggested that quantitative measurements of HDL particle (HDL-P) might be more valuable than traditional HDL-C measurements. What is more bewildering is that HDL from patients with systemic inflammation decreased its protective effects and even became a pro-inflammatory factor. Recently, synthesized HDL and apolipoprotein mimetic peptides showed biological functions similar to native ones. Expectedly, lots of novel measurement methods and therapeutic agents about HDL would be established soon.",signatures:"Donghui Liu",downloadPdfUrl:"/chapter/pdf-download/70983",previewPdfUrl:"/chapter/pdf-preview/70983",authors:[{id:"314218",title:"Dr.",name:"Donghui",surname:"Liu",slug:"donghui-liu",fullName:"Donghui Liu"}],corrections:null},{id:"71779",title:"Monoglycerides as an Antifungal Agent",doi:"10.5772/intechopen.91743",slug:"monoglycerides-as-an-antifungal-agent",totalDownloads:823,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Monoglyceride is a part of a lipid group compound. As a derivative of triglycerides, monoglycerides could be produced from renewable resources like fat or vegetable oils. Structurally, monoglyceride has lipophilic and hydrophilic properties in its molecule. Lipophilic properties could be donated by an acyl group from fatty acid and hydrophilic properties from two hydroxyl residues. Therefore, it was referred to as an organic amphiphilic compound. Monoglycerides have potency as antifungal agents. Based on its chemical structure, monoglyceride allows to bind to lipid bilayer and other components on the cell membrane of fungal microorganism and damage it. In this chapter, we will describe the structure and classification, physical and chemical properties, as well as reaction path synthesis of monoglyceride from vegetable oils and mechanism of action of monoglyceride as antifungal agents.",signatures:"Febri Odel Nitbani and Jumina Jumina",downloadPdfUrl:"/chapter/pdf-download/71779",previewPdfUrl:"/chapter/pdf-preview/71779",authors:[{id:"302836",title:"Dr.",name:"Febri Odel",surname:"Nitbani",slug:"febri-odel-nitbani",fullName:"Febri Odel Nitbani"},{id:"307153",title:"Prof.",name:"Jumina",surname:null,slug:"jumina",fullName:"Jumina null"}],corrections:null},{id:"70209",title:"Multi-Scale Mathematical Modeling of Prion Aggregate Dynamics and Phenotypes in Yeast Colonies",doi:"10.5772/intechopen.88575",slug:"multi-scale-mathematical-modeling-of-prion-aggregate-dynamics-and-phenotypes-in-yeast-colonies",totalDownloads:639,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Prion diseases are a multi-scale biological phenomenon that requires understanding intracellular processes as well as how cells interact with each other and their environment. In mammals, prion diseases are progressive, untreatable, and fatal. Yeast prion phenotypes are harmless and reversible, which suggests a deep understanding of the reversal of prion phenotypes in yeast may be informative to mammalian diseases. In yeast, the loss of some prion phenotypes appears to be stochastic and spatially dependent, suggesting a cell-based model of yeast prion dynamics would be a powerful tool for comparisons with experimental results and hypothesis generation. In this work, we consider the components necessary to develop such a model that depicts both the biochemical-, intracellular-, and colony-level scales in yeast prion phenotypes. We first review the literature of mathematical models of the intracellular processes of prion disease. We then review common approaches to cell-based modeling of multicellular systems and how they have led to biological insights in other systems. This chapter ends with a discussion of future studies aimed at motivating how these two types of models can be coupled to produce multi-scale models of prion phenotypes.",signatures:"Mikahl Banwarth-Kuhn and Suzanne Sindi",downloadPdfUrl:"/chapter/pdf-download/70209",previewPdfUrl:"/chapter/pdf-preview/70209",authors:[{id:"193350",title:"Dr.",name:"Suzanne",surname:"Sindi",slug:"suzanne-sindi",fullName:"Suzanne Sindi"},{id:"293200",title:"Dr.",name:"Mikahl",surname:"Banwarth-Kuhn",slug:"mikahl-banwarth-kuhn",fullName:"Mikahl Banwarth-Kuhn"}],corrections:null},{id:"72171",title:"Zeta Potential as a Diagnostic Tool to Determine the Angina Risk",doi:"10.5772/intechopen.92373",slug:"zeta-potential-as-a-diagnostic-tool-to-determine-the-angina-risk",totalDownloads:604,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Red blood cells (RBCs) moving in circulation are continuously exposed to the reactive oxygen species (ROS) that are circulating within the vascular system of body. The objective of the study is to determine the erythrocyte zeta potential and its morphological changes caused by oxidative stress in hypertensive patients in relation to the risk of development of cardiovascular disease (myocardial infarction). In this retrospective study, we investigated 186 samples, which include hypertension patients (n = 64), myocardial infarction patients (n = 52), treated myocardial infarction patients (n = 20), and normal healthy volunteers (n = 50). Morphological and electrochemical characteristics of RBCs in patients were analyzed using scanning electron microscopy and zeta potential study. These parameters were also statistically analyzed applying one way ANNOVA (Tukey’s comparison) using Graph Pad. Statistical analyses of data showed that Hypertensive (ZP-16.06 mV) and cardiac patients (ZP-9.94 mV) RBCs possessed significantly reduced zeta potential relative to that of RBCs from healthy individuals (ZP-23.39 mV) (P-value <0.0001). Microscopic imaging of Hypertensive RBCs revealed increased anisocytes and poikilocytes. These parameters were found exacerbated in patients suffering from Myocardial infarction. Hence, it can be concluded that ZP can be used as an effective diagnostic tool for detection of hypertension associated cardiovascular disorder risk.",signatures:"Swati S. Gaikwad, Jasmine G. Avari and Mansi Liladhar Patil",downloadPdfUrl:"/chapter/pdf-download/72171",previewPdfUrl:"/chapter/pdf-preview/72171",authors:[{id:"316935",title:"Dr.",name:"Swati",surname:"Gaikwad",slug:"swati-gaikwad",fullName:"Swati Gaikwad"},{id:"316936",title:"Dr.",name:"Jasmine",surname:"Avari",slug:"jasmine-avari",fullName:"Jasmine Avari"},{id:"320406",title:"Dr.",name:"Mansi Liladhar",surname:"Patil",slug:"mansi-liladhar-patil",fullName:"Mansi Liladhar Patil"}],corrections:null},{id:"71137",title:"Postprandial Triglycerides, Oxidative Stress, and Inflammation",doi:"10.5772/intechopen.91303",slug:"postprandial-triglycerides-oxidative-stress-and-inflammation",totalDownloads:720,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:"Among the most common non-communicable diseases are obesity, cardiovascular disease, and diabetes, which are responsible for the major cardiometabolic phenotypes. Together with mitochondrial alterations, oxidative stress and inflammation are key molecular mechanisms that contribute to the onset and development of these conditions. Meal consumption is a recurring daily activity that is directly linked to oxidative stress and inflammation. Acute increases in lipids, notably triglycerides, during the postabsorptive period have been suggested to induce a state of inflammation with stimulation of adhesion molecules, cytokines, oxidative stress, and leukocyte activation. Not only lipids but also meal-induced elevations in glucose have also been linked to postprandial oxidative stress and inflammation. The impact of postprandial hypertriglyceridemia and hyperglycemia on oxidative stress and inflammation is not only independent but may be cumulative. It is our hypothesis that, in a system that could not maintain homeostasis to continuous changes of the environment, repeated exposures to meals that provide modest doses of fat and glucose could potentially elicit abnormal responses that contribute to the onset and development of chronic cardiometabolic phenotypes.",signatures:"Ngoc-Anh Le",downloadPdfUrl:"/chapter/pdf-download/71137",previewPdfUrl:"/chapter/pdf-preview/71137",authors:[{id:"314977",title:"Dr.",name:"Anh",surname:"Le",slug:"anh-le",fullName:"Anh Le"}],corrections:null},{id:"70905",title:"Glycerol Conversion to Diglycerol via Etherification under Microwave Irradiation",doi:"10.5772/intechopen.90513",slug:"glycerol-conversion-to-diglycerol-via-etherification-under-microwave-irradiation",totalDownloads:715,totalCrossrefCites:0,totalDimensionsCites:3,hasAltmetrics:1,abstract:"According to Grand View Research in polyglycerol market size, demand for diglycerol is expected to grow by 50% from 2012 to 2022 due to its extensive use in various industries, thus validating the importance and value addition of producing diglycerol. Due to the volatility of refined glycerine market price and increasing demand of diglycerol, research has been conducted to upgrade glycerol via various processes. Etherification is a single-step process of catalytic conversion of glycerol into polyglycerols, involving the condensation of two glycerol molecules to form the simplest oligomer which is diglycerol with linear, branched, or cyclic isomers. Thus, this chapter will discuss on the methods of synthesizing diglycerol followed by the type of catalyst to be used. These include homogenous and heterogenous catalyst with their subdivision of acid and base type, respectively. Besides, this chapter does include on the method for the etherification process where it highlighted the advantage of advance technology microwave irradiation over conventional heating.",signatures:"Muhammad Ayoub, Wan Jie Wei, Manzoor Ahmad, Ranitha Mathialagan, Sarah Farrukh, Mohammed Danish, Sami Ullah and Salman Raza Naqvi",downloadPdfUrl:"/chapter/pdf-download/70905",previewPdfUrl:"/chapter/pdf-preview/70905",authors:[{id:"288418",title:"Dr.",name:"Salman",surname:"Raza Naqvi",slug:"salman-raza-naqvi",fullName:"Salman Raza Naqvi"},{id:"290735",title:"Dr.",name:"Muhammad",surname:"Ayoub",slug:"muhammad-ayoub",fullName:"Muhammad Ayoub"},{id:"314670",title:"Ms.",name:"Jie Wei",surname:"Wan",slug:"jie-wei-wan",fullName:"Jie Wei Wan"},{id:"314671",title:"Dr.",name:"Manzoor",surname:"Ahmad",slug:"manzoor-ahmad",fullName:"Manzoor Ahmad"},{id:"314672",title:"Mrs.",name:"Ranitha",surname:"Mathialagan",slug:"ranitha-mathialagan",fullName:"Ranitha Mathialagan"},{id:"314673",title:"Dr.",name:"Sarah",surname:"Farrukh",slug:"sarah-farrukh",fullName:"Sarah Farrukh"},{id:"314674",title:"Dr.",name:"Mohammed",surname:"Danish",slug:"mohammed-danish",fullName:"Mohammed Danish"},{id:"314675",title:"Dr.",name:"Sami",surname:"Ullah",slug:"sami-ullah",fullName:"Sami Ullah"}],corrections:null},{id:"67811",title:"Human Cholesterol Biosynthesis Defects",doi:"10.5772/intechopen.87150",slug:"human-cholesterol-biosynthesis-defects",totalDownloads:835,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Cholesterol plays an essential role in normal embryogenesis and perturbations in its de novo synthesis are responsible for organ malformations in the cholesterol biosynthesis defects. Ten distinct inherited disorders have been linked to different enzyme defects in the isoprenoid/cholesterol biosynthetic pathway: mevalonic aciduria, hyperimmunoglobulinemia syndrome, squalene synthase deficiency, lanosterol synthase deficiency, hydrops-ectopic calcification-moth-eaten (Greenberg) skeletal dysplasia, X-linked dominant chondrodysplasia punctata, congenital hemidysplasia with ichthyosiform erythroderma and limb defects syndrome, lathosterolosis, Smith-Lemli-Opitz syndrome and desmosterolosis. These Mendelian disorders are clinically heterogeneous with protean manifestations reflecting the important role of cholesterol, and its intermediary metabolites, in embryogenesis and development. Key clinical features commonly represented by the cholesterol biosynthesis defects include structural brain malformations, axial skeletal developmental anomalies and genital and cardiac malformations. The aetiology of the underlying pathophysiology is unclear and multifactorial but may be due to lowered cholesterol and/or the elevated, teratogenic levels of the intermediate sterol precursors. Herein, we will review clinical, biochemical and molecular aspects of the known human cholesterol biosynthesis defects.",signatures:"Erin Anderson and David Coman",downloadPdfUrl:"/chapter/pdf-download/67811",previewPdfUrl:"/chapter/pdf-preview/67811",authors:[{id:"187453",title:"Prof.",name:"David",surname:"Coman",slug:"david-coman",fullName:"David Coman"}],corrections:null},{id:"70774",title:"Low-Density Lipoprotein: Biochemical and Metabolic Characteristics and Its Pathogenic Mechanism",doi:"10.5772/intechopen.86872",slug:"low-density-lipoprotein-biochemical-and-metabolic-characteristics-and-its-pathogenic-mechanism",totalDownloads:775,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter mainly introduces the physicochemical properties, physiological function, and metabolic pathway of low-density lipoprotein (LDL), with emphasis on the mechanism of atherosclerosis caused by LDL and the existing treatment methods. The content of this paper is detailed and comprehensive, including the latest research results in recent years. Different from the published articles, this paper adopts an innovative “tree” structure, with the disease development process as the main line and the molecular mechanism as the branch, showing the clinical significance of the molecular mechanism. The main purpose of the author of this paper is to take LDL as an example, establish a multidimensional knowledge system, and strive to make the complex molecular mechanism vivid.",signatures:"Jie Lin",downloadPdfUrl:"/chapter/pdf-download/70774",previewPdfUrl:"/chapter/pdf-preview/70774",authors:[{id:"297420",title:"Dr.",name:"Jie",surname:"Lin",slug:"jie-lin",fullName:"Jie Lin"}],corrections:null},{id:"72232",title:"Therapeutic Properties and Anti-Lipidemic Activity of Cordyceps sinensis",doi:"10.5772/intechopen.92616",slug:"therapeutic-properties-and-anti-lipidemic-activity-of-em-cordyceps-sinensis-em-",totalDownloads:734,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Cordyceps sinensis is an entomophagous medicinal mushroom, which is mainly endemic to the Tibetan Plateau including the adjoining high altitude areas. The fungus attacks many lepidopteran larvae caterpillars and mummifies it. The larvae along with the mummified insect are highly valued for their medicinal property. Cordyceps sinensis is one of the most efficient and expensive medicinal mushrooms in traditional medicinal systems such as those in China and Tibet, having multiple medicinal and pharmacological properties. It has been used to treat respiratory and immune disorders; pulmonary diseases; renal, liver, and cardiovascular diseases; hyposexuality; and hyperlipidemia. The extract of this mushroom and its bioactive compounds are noteworthy for their ability to regulate lipid metabolism and thereby exhibit anti-lipidemic activity. Cordycepin in particular, which is a bioactive compound existing in Cordyceps sinensis, has been identified as one of the primary compounds of interest in this aspect. Despite the global and scientific interest exerted toward Cordyceps sinensis, it appears to be of utmost importance that the price and other market factors owing to the rarity of this herb are managed through artificial means of synthesis.",signatures:"Kanchana Samarasinghe and Viduranga Y. Waisundara",downloadPdfUrl:"/chapter/pdf-download/72232",previewPdfUrl:"/chapter/pdf-preview/72232",authors:[{id:"194281",title:"Dr.",name:"Viduranga Y.",surname:"Waisundara",slug:"viduranga-y.-waisundara",fullName:"Viduranga Y. 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Commercial preparations are available for oral consumption; there are even food-grade preparations for cattle, swine and poultry. A major concern with oral intake of CoQ10 was bioavailability due to its lipophilic nature. CoQ10 has been recommended for patients under continuous statin therapy as these drugs inhibit the pathway of CoQ10 biosynthesis. The use of CoQ10 in various cardiac and tumor conditions indicates that its activity is not only due to its antioxidant activity but also due to its apoptosis property. Apart from human uses, CoQ10 is now used in food animals especially broilers as they were fed with high energy dense diet there will be leakage of electrons at electron transport chain level which adversely affects the bird’s performance and also used in treatment of ascites mortality.",signatures:"Gopi Marappan",downloadPdfUrl:"/chapter/pdf-download/71878",previewPdfUrl:"/chapter/pdf-preview/71878",authors:[{id:"269862",title:"Dr.",name:"Gopi",surname:"M",slug:"gopi-m",fullName:"Gopi M"}],corrections:null},{id:"68444",title:"Modulatory Potentials of n-3 Polyunsaturated Fatty Acids in Inflammatory Diseases",doi:"10.5772/intechopen.88394",slug:"modulatory-potentials-of-n-3-polyunsaturated-fatty-acids-in-inflammatory-diseases",totalDownloads:555,totalCrossrefCites:1,totalDimensionsCites:3,hasAltmetrics:0,abstract:"Inflammatory diseases (bronchitis, irritable bowel diseases, psoriasis, chronic obstructive pulmonary disease, rheumatoid arthritis, conjunctivitis, hepatitis, rhinitis, etc.) are increasingly becoming the cause of health concern across the world. For both developed and developing countries, the public health cost attached to the management of these complications is increasing each year. Control of diet is one of the critical strategies to improve the therapeutic potentials of clinically proven drugs. Among the dietary factors, bioactive lipids, particularly polyunsaturated fatty acids, elicit essential effects of modulating signaling pathways that could provide a beneficial effect in individuals suffering from various inflammatory complications. Among the polyunsaturated fatty acids, both n-3 and n-6 fatty acids exhibit differential effects, and their dietary ratio plays a significant role in the overall impact in an individual. This is most evident with the fact that the decrease in the n-3 intake in recent times has significantly contributed to the severity of chronic inflammation. The mechanism by which these fatty acids and bioactive unsaponifiable embedded in the dietary oils modulate the critical genes, thereby alter the pathology of inflammatory complications is under study for many decades. 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There is a large number of immunodeficient patientsrequiringlifelong IgG replacement. This review is focused on currently available Intravenous Immunoglobulin(IVIG) preparations,manufacturing procedures, dose arrangements, mechanisms of actions, benefits of antibody replacement treatment and careful administration of IVIG considering, numerous side effects. Subcutaneous IgG (SCIG) treatment has gained ground in recent years as an alternative to IVIG. Datashow that the efficacy of SCIG in preventing infections is proportional to the steady-state levels achieved and similar to that of IVIG.
Intravenous immunoglobulin (IVIG) is mainly indicated as replacement therapy for patients with primary and selected secondary immunodeficiency diseases characterized by absent or deficient antibody production. Antibody deficiencies are a heterogeneous group of diseases mainly consisting of primary immunodeficiency diseases (PID) [1-4]. Primary antibody deficiencies (PAD) can be divided into four main subgroups: X-linked agammaglobulinaemia, class-switch recombination defects (hyper-IgM syndromes (HIGM), hypogammaglobulinaemia (particularly common variable immunodeficiency (CIVD) and selective immunoglobulin deficiencies (selective IgA deficiency). Over the past 20 years, 18 genetic defects have been defined as leading causes of PAD, but no gene defects were identified in patients with hypogammaglobulinaemia and selective immunoglobulin deficiencies, because of the variability of the affected stages of B cell differentiation and maturation, and the onset time of clinical symptoms like childhood or adulthood with increased susceptibility to mainly bacterial infections [5,6].
Substitution of immunoglobulin G (IgG) is the efficient and standard treatment for many years [7-11]. Immunoglobulins pooled from thousands of healthy donors contain a wide range of antibody specificities. These immunoglobulin preparations also have anti-inflammatory and immunomodulatory effects in addition to their use as replacement therapy [12,13]. The benefits in diseases such as childhood thrombocytopenia and Kawasaki disease refractory to or intolerant of conventional treatment have been well established [14,15]. It has been 30 years since therapeutic contribution of intravenous immunoglobulin (IVIG) administration has been proven by scientists, an increasing number of immune-mediated diseases have been treated with intravenous immunoglobulin rather than corticosteroids and cytoxic drugs. IVIG has become the therapy of choice in autoimmune diseases, severe asthma, neurological diseases, transplantation, sepsis, septic shock, toxic shock syndromes and dermatologic disorders [15,16]. The recommendation of IVIG treatment in other diseases than those approved by FDA is based on limited data or some of these diseases do not have any alternative treatment regimen to compare with [16]. However, IVIG administration in the treatment of many diseases is raising the possibility of product shortages and increasing costs. Thus, concerning the shortages of products, cost and adverse reactions, definite indications for IVIG treatment are essential [12,13,16,17].The aim of immunoglobulin therapy should be to protect the patients from frequent and severe infections finally resulting in organ damage. Advances in human immunology, has led to identify responsible genes for PID, thereby particular groups of defects are associated with susceptibility to specific types of infection [18]. Improved diagnostic precision is likely to increase more specialized management strategies of patients with PID, some of which are only supported by expert consultation. However, there are no sufficient number of studies in PID, to optimize the quality and uniformity of management of PID.
Cohn et al produced the first human immunoglobulin IgG product in1946 and it was referred as immune serum globulin (ISG)[19]. This first commercial human ISG solution tended to form aggregates during storage, therefore it was delivered via the intramuscular or subcutaneous route. After diagnosing his first patient with a gamma globulinemia in 1952, Bruton began to treat his patients by subcutaneous replacement therapy with ISG [20]. After a short time, intramuscular ISG treatment became available for all patients, but the amount of Ig used for treatment was limited and not effective enough to reduce recurrent infections and the adverse effects were also high due to IgG aggregates [21]. These disadvantages were abolished by Cohn fraction II that had been developed in 1960’s by Barandum and his colleagues in collaboration with Swiss Red Cross [9,21]. The first IVIG was produced by pepsin digestion (enzymatic method: pepsin or trypsin) to reduce anticomplement activity, but this process cleaved the immunoglobulin molecule into two parts, resulting in fragments of the fc portion and Fab. Several manifacturers produced chemically modified IVIGs containing minimal anti-complement activity and no IgG fragments. Reduced bacterial opsonic activities and shortened circulating half-lives were demonstated in some antibodies of enzyme-digested or chemically modified IVIG preparations. Non-denaturating processes such as precipitation with polyethylene glycol (PEG), ion exchange chromatography, diafiltration and stabilisation of IgG at low pH, do not modify the IgG molecule and the half-life of IgG is generally 22-25 days [21].
Intravenous immunoglobulin (IVIG) preparations contain 16% human serum immunoglobulin and more than 95% IgG, scanty amount of IgA, IgM and other serum proteins. IgA and IgM do not have any therapeutic effects due to their short half-life and small amount [22,23]. Prognosis of patients with deficient IgG production has thoroughly improved after replacement therapy with IVIG [24]. Since 1980, it has been the most striking therapeutic agent due to its unproposed anti-inflammatory and immunomodulatory effects and used to treat a wide variety of pathologies including vasculitis, HIVinfection, autoimmune diseases and immune-mediated neurological diseases [12,14,15,25-28]. Currently, subcutaneous immunoglobulin infusions administered by a special pump has become an alternative to IVIG treatment. It has been demonstrated that this product is safe and has some clinical advantages over intravenous preparations. It has been recommended especially for selected patients with primary immunodeficiencies [29,30].
IVIG preparations are derived from plasma of a huge number of human blood donors or paid plasmapheresis donors. Since IVIG preparations are blood-derived products having the risk of transmission of infectious transfusional diseases, viral safety needs to be considered [13,21,23]. The safety of IVIG products depends on donors, validated manufacturing processes and various virus clearance steps as listed below:
recruitment of the donor
donation screening
use of validatedmanufacturingprocesses
effective viral inactivation/removal procedures
To produce a single product lot, sufficient number of donor recruitment and screening of viral markers (HBs-Ag, HIV-p24 antigen, antibodies to syphilis, HIV-1,HIV-2, HCV, HAV) are necessary to preventthe transmission of viruses [21].
FDA (Center for Biologics Evaluations and Research) and Plasma Protein Therapeutics Association recommended the number of donors to be minimum 15.000, but not more than 60.000. Manifacturing processes implemended in commercial IVIG preparations are the classical Cohn fractionations treated with solvent detergent, caprylate, acid or pepsin to inactivate pathogens [31-33].
Immunoglobulin, produced by cold ethanol fractionation method may contain trace amounts of contaminants such as prekallikrein activator, prekallikrein, activated coagulation factors, complement proteins, IgM, IgA, plasmin and plasminogen. Currently many manufacturers began to use purification with anion exchange (DEAE) chromatography adjusted to cold ethanol fractionations in order to obtain safe products.
Treatment at pH4 with trace amounts of pepsin is also validated by some manifacturers. Both, alcohol fractionation and acid treatment procedures eliminate other proteins and inactivate dangerous live viruses such as HIV, Hepatitis B, HCV.
Improved quality standards for plasma products and new blood borne pathogens such as SARS forced the scientists to develop and integrate new specific viral inactivation methods. RNA virus with lipid envelope, DNA virus with lipid envelope and non-lipid enveloped virusus must all removed by viral inactivation procedures. The heat and chemical treatment processes are able to remove and/or inactive blood-borne pathogens:
Pasteurisation: Based on heating to 60°C in an aqueous solution for 10 hours in the presence of stabilizers.
Solvent/Detergent: The solvent/detergent consists of an organic solvent (ether, 0.3% tri-n-butylphosphate (TNBT) and 0.2% detergent (Tween 80, sodium cholate or triton-100). The process lasts for 6 hours and destroys infectivity of lipid-enveloped viruses.
Nanofiltration: This procedure is effective to remove small non-enveloped (B19V, HAV) viruses.
Low pH-incubation: This incubation at elevated temperatures completely removes lipid-enveloped viruses like HIV, HBV/HCV).
Transmission of Prion diseases such as Creutzfeldt–Jakob disease (CJD) or variant CJD by administration of blood products is also possible, since the incubation period of the disease is too long leading to difficulties in risk determination. Because of this possibility, donors who have spent more than 6 months in the United Kingdom from 1986 to the present are not allowed to donate blood or plasma in the United States and Europe [21]. Some researchers demonstrated that depth filtration step that is common in all IVIG production procedures and nanofiltration removed hamster scrapie protein reactivity. The Finish Red Cross Blood Transfusion Service (FRC BTS’ Helsinki, Finland) had developed a liquid 5% IVIG product (IVIG-L) in which a nanofiltration step was incorporated into the production process [34]. Van der Meer JWM et al. evaluated efficacy and safety of that nanofiltered liquid IVIG product and showed that IVIG-L was efficacious and pharmacokinetic properties were comparable to other IVIG preparations. In addition relatively low level of adverse reactions and the absence of seroconversion were observed. Thus, this liquid form product is considered to be safe and well tolerable.Over the past years, improved manifacturing processes and integrated specific viral inactivation steps have increased the safety and quality of IVIG products (Table 1).Commercially available products represent recent advancements in IVIG product formulation, but potential transmission of emerging pathogens can still not be ruled out completely.
Currently licensed IVIG preparations aresupplied either in lyophilized powder or premixed solution, contains 95% IgG at a concentration of 16.5% (165 mg/ml), all the IgG subclasses, multiple IgG allotypes (Gm and Km), minimal anti-complement activity, broad spectrum of antibodies against viruses and bacteria, and no difference in therapeutic efficacy. Half-life of immunoglobulins is approximately 21-25 days.The osmolarity varies between 253 mOsm/L for a 5% IgG product to1250 mOsm/L for a 10% product. The final sterile product contains varying amounts of sodium, glycine, polyethylene glycol, D-mannitol, D-sorbitol, sucrose, glucose or maltose, glycerol as the stabilizer, and thiomersal as the preservative and has a pH of 6.8 (Table 2).
Dedicated virus inactivation procedures used in IVIG production [22]
CommercialIVIGProducts and properties (Data from Immune Deficiency Foundation, October 2011 and reference [17, 22])
All the available IVIG preparations approved by FDA and EMEA should at least have the following features:
Sterile
donors
>20 days of half life
>90 % monomeric IgG
EffectiveIgG subclasses, a profile similar to that of human plasma
Complete Fc functions, complement fixation, opsonophagocytosis
No pyrogenic and vasoactive agents (kinin or plasmin), protein aggregates
Low adverse effects
Trace IgA concentration
Stabile in solution
Low price
Human immunoglobulin is obtained from a large number of donors and exceeding 2.000 donors is preferred. IVIG contains large spectrum of antibody specificities such as antibodies to foreign (non-self) antigens, to self-antigens (natural autoantibodies) and to other antibodies (idiotypic antibodies which represents antibody repertoire of each donor [35]. That is the reason of the differences between immunoglobulin batches [13,21,35]. The mechanism of activity of the substituted IgG is easilyunderstood for immunodeficiency disorders considering common pathogen-specific IgG antibodies are replaced bythose from the donor pool [35]. Thereby,regular intravenous immunoglobulin therapy reduces the incidence of infection in these patients compared to their infection rates before IVIG treatment [7-13]. Immunomodulatory effect of IVIG therapy depends on several mechanisms. Proposed early immunomodulatory effects of IVIG infusion are shown below [35-37]:
Modulation of production and release of proinflammatory cytokines and cytokine antagonists
Functional blockade of Fc receptor on splenic macrophages
Neutralization of circulating autoantibodies
Neutralization of superantigens
Inhibition of complement-mediated damage
Changes in solubility and rate of clearance of immune complexes
On the other hand, IVIG infusion downregulates IVIG-reactive B cell clones in long-term. Serum IL-6, IL-8, IL-1Ra and TNFalpha concentrations were increased in patients with primary immunodeficiencies following IVIG infusion, without any difference in serum IL-beta, IFNgamma or IL-2 levels. Understanding these immunomodulatory effects of IVIG is essential to define IVIG indications in autoimmune disorders [35-37].In severe infections regarding increased catabolism of IgG, IVIG can be added to antibiotic treatments [16, 17].
The concentration of IgG is very important for its pro-inflammatory or anti-inflammatory properties. Low-dose IVIG has proinflammatory properties, but high dose IVIG has anti-inflammatory effects. The proinflammatory properties are dependent on complement activation or binding of the Fc fragment of IgG to IgGspecific (FcγR) on effector cells of the innate immunity leading to receptor clustering, activation of intracellular signaling pathways and finally to cell activation. The anti-inflammatory effect of IgG is still not clear, but IgG is known to inhibit the differentiation and maturation of human dendritic cells (DCs), expression of co-stimulatory molecules like CD80 and CD86, both leading to lower self antigen processing and presentation [8]. Fc and F(ab′)2 fragments of IgG molecule are both able to suppress of DCs. Antibodies with the intrinsic capacity to recognize foreign antigens or common pathogen-specific IgG antibodies are replaced by those from the donor pool [35].
At a lower dose, administered generally to patients with immunodeficiencies, however, IVIG exerts a contrasting effect. DCs of patients with common variable immune deficiency (CVID) differentiated in the presence of IVIG and presented with an up-regulated expression of CD1a and the co-stimulatory molecules CD80, CD86 and CD40 [38,39].Defective functions of DCs have been associated with predisposition to several pathological conditions. CVID patients display high susceptibility to recurrent infections and autoimmune diseases that could be due in part to impaired DC functions [38,39].
Advantages of IVIG administration are the following:
Painless administration
Absence of proteolysisof the product
No sterile abscess
Rapid onset of action
Easy administration of large doses
Unfortunately, there are also some disadvantages of IVIG administrations:
High cost
Requirement for a venous access
Long duration of the infusion
5-15% adverse events
Severe adverse reactions such as anaphlaxis
In recent years, manufactures aim to develop products that provide a high-yield, safe, well tolerated and stable concentrates of polyclonal IgG. Each new intravenous immunoglobulin product has to be tested for its biochemical characterization done by standart methods focusing on purity, integrity and functionality. Efficacy must be shown by opsonization, protein A affinity chromatography and mouse protection tests. Pharmacokinetics of the product, the influence of product on vital functions, acute toxicity, anaphylactoid potential, thrombogenicity should be evaluated in rats, dogs or a rabbit models. Development of new methods for fractionation, combining processes and integrating three dedicated virus clearance steps provided fulfilling the clinical requirements for intravenous administration of second-generation intravenous immunoglobulins products (Table 2)[21].
The US Food and Drug Administration (FDA) standardized clinical trials with IVIG in patients with primary immunodeficiencies. FDA has proposed to measure the rate of serious bacterial infections during regular infusions of investigational IVIG for 12 months to avoid seasonal variations. Serious bacterial infection term has to be well defined, thusbacteremia/sepsis, bacterial meningitis, osteomyelitis/septic arthritis, bacterial pneumonia, and visceral abscess were defined as serious infections [8].
The guidelines for clinical Investigation of human normal Immunoglobulin for Intravenous administration of the European Medicines Agency (EMA/CHMP/BPWP/94033/2007 rev.2) and FDA recommended that an immunoglobulin product is effective if treated patients experience less than 1.0 serious infection per year [21,34]. A new IVIG product must have ‘intact IgG’ which means pharmacokinetic properties of Immunoglobulin G is similar to endogeneous IgG and available other immunoglobulin preparations.
IVIG, has been licensed by FDA for only 6 clinical indications [8,22,23]:
Treatment of primary immunodeficiencies
Prevention of bacterial infections in patients with hypogammaglobulinemia and recurrent bacterial infections caused by B-cell chronic lymphocytic leukemia
Prevention of coronary artery aneurysms in Kawasaki disease
Prevention of infections, pneumonitis, and acute graft-versus-host disease (GVHD) after bone marrow transplantation
Reduction of serious and minor bacterial infections, to decrease the frequency of hospitalisation in children with HIV
Increase of platelet counts in idiopathic thrombocytopenic purpura to prevent or control bleeding
IVIG therapy has been evaluated in a number of clinical conditions mentioned above and categorization of evidence, basis of recommendation and strength of recommendation have beenestablished (Table 3 and Table 4)[16].
Categorization of evidence and basis of recommendation and strength of recommendation [17]
Recommendation of IVIG in primary and secondary immunodeficiencies [17]
Primary antibody deficiencies [25], account for approximately 65-50% of primary immunodeficiencies (PID) [3,40]. Due to defects in critical stages of B cell development, B cells areabsent/reduced and B cell functions are impaired in patients with PAD [41]. B cell defects are a heterogeneous group of disorders consisting of patients presenting a wide variety of clinical conditions ranging from asymptomatic to severe and recurrent infections.Patients with selective IgA and IgG subclass deficiencies are often asymptomatic, while children with agammaglobulinemia present encapsulated bacterial infections initiating at 6 months of age. Reduced immunoglobulin concentrations and lack of antibody response against protein antigens (diphtheria, tetanus toxoids) or polysaccharide antigens(pneumococcal polysaccharide) are well defined in patients with agammaglobulinemia or hypogammaglobulinemia [40-42]. Although these patients have frequent or recurrent bacterial infections, they could not mount IgG antibody responses against antigens and this condition is a clear indication for immunoglobulin replacement therapy (Table 5) [21, 42].
Therefore, the aim of replacement therapy is to avoid acute infections, respiratory complications such as bronchiectasis, gastrointestinal complications, to improve quality of life and to increase life expectancy of patients [17, 22]. The delay in diagnosis of primary immunodeficiencies remains a significant problem, as a consequence of delay recurrent pneumonias results in structural lung damage such as bronchiectasis, pulmonary hypertension and finally cor pulmonale [10].
Primary Immuno deficiencies benefit IVIG treatment
Evaluation of IVIG use in patients lacking immunoglobulin has demonstrated reduction of acute and chronic bacterial infections frequency, pneumonia, days of antibiotic usage, days of fever and hospital admission [16]. Retrospective studies in patients with XLA revealed that severity and number of infections are decreased depending on IVIG dose. Serious bacterial illnesses and enteroviral meningoancephalitis were prevented when maintained IgG levels were above 800mg/dL [16,21,42,43].
Barıs S et al. evaluated the efficacy of IVIG treatment (500 mg/kg every 3 weeks) in 29 children diagnosed with CVID. During therapy, median serum IgG levels increased from 410 to 900 mg/dL. The mean number of respiratory infections per patient per year decreased significantly from 10.2 to 2.5. The annual number and length of hospital stays decreased significantly from 1.36 to 0.21 and 16.35 to 6.33 days per patient, respectively. The mean annual number of antibiotics used decreased significantly from 8.27 to 2.50 per patient. Twelve patients had developed bronchiectasis before initiation of IVIG [44].
Intravenous immunoglobulin therapy has to be started without any delay in patients with CVID predisposed to chronic lung diseases. Appropriate replacement therapy in these patients, reduced the incidence of pneumonia and prevent progression of lung involvement [17, 42-47].
A 5-year multicenter prospective study on 201 patients with CVID and 101 patients with XLA was conducted to identify the effects of long-term immunoglobulin treatment and the IgG trough level to be maintained over time required to minimise infection risk. Overall, 21% of the patients with CVID and 24% of patients with XLA remained infection free during the study. Pneumonia episodes had been reduced. Patients with pneumonia did not have significant lower IgG trough levels than patients without pneumonia, with the exception of patients whose IgG trough levels were persistently <400 mg/dL. In addition, in XLA co-morbidity risk factor identified for pneumonia was the presence of bronchiectasis [10,23].
Studies have shown that 10 years survival of CVID patients receiving IVIG treatment was 78%; while expected survival in the general population at ten year was 97% [28].
Patients with severe combined immunodeficiency(SCID) syndromes are also agammaglobulinemic and have significant inability to produce antibody against antigens. Hematopoietic stem cell transplantation is choise of therapy for these patients, but functional B-cell reconstitution often fail following marrow engraftment and these patients could not produce antibodies. Regular replacement therapy with IVIG is indicated for these patients.
Hyper IgM syndromes are usually defined with reduced levels of IgG and IgA, but high or normal IgM. These patients have normal B cell counts, but defective class switching do not allow to generate specific antibodies, thus these children experience frequent infections like agammaglobulinemic individuals.Adequate replacement of IVIG has been shown to reduce the incidence of pneumonia from 7.6% to 1.4% per year and patients did not have meningitis [10, 25, 48].
Selective antibody deficiencies or normogammaglobulinemia with impaired specific antibody production are group of disorders characterized by impaired production of specific antibody with normal serum IgG levels. Evidence of recurrent infection and absent or reduced specific antibody production against polysaccharide antigens after vaccination, are requirements for IVIG therapy. Therapy can be stopped after clinical improvement and the immune response of patient should be re-evaluated at least 5 months later. Usually antibody response to antigens, improve in growing children, but in conditions of unresponsiveness to antigens, restart to IVIG treatment is appropriate due to recurrence of infections.
Immunoglobulin treatment is not commonly recommended to patients with selective IgA deficiency unless poor specific antibody or IgG2 subclass deficiency exists [21].
Replacement therapy is also recommended in patients with combined immune deficiencies, other well-defined immunodeficiency syndromes and X-linked lymphoproliferative syndrome (XLP)(Table 5).
There are several factors required for selection of an IVIG brand:
To obtain enough information about the IVIG product: lyophilized powder or premixed solution, amount of sodium, IgG and IgA, stabilizing sugar, preservative, viral inactivation methods, concentration, osmolarity
Safety and tolerability
Price
Regarding lyophilized or liquid forms, sugar content, amount of IgA (varies between <0.4 μg/mL and 720 μg/mL), used antimicrobial processes and stabilizing agent, an appropriate commercial immunoglobulin preparation should be selected for treatment of immunodeficient patients(Table 1). The patients with diabetes may have high blood glucose levels due to maltose-containing products therefore they have to adjust doses of insulin [5, 8, 21, 23, 49].
Patients with selective IgA deficiency carry the risk of anaphylaxis due to production of anti-IgA antibodies.Selective IgA deficient patients having high anti-IgA (>1/1000) titers should not be treated with IVIG or a IgA-free immunoglobulin product should be chosen for the treatment [8, 21, 50, 51]. Since IVIG administration is a life-saving therapy, the treatment should be supported by scientific clinical evidence regardless the economic impact of therapy [52]. Therefore considering scarcity of resource for IVIG, its judicious use must be promoted for the diseases FDA approved.
The common recommended dose of IVIG treatment for antibody replacement is between 0.3 and 0.6 g/kg, administered every 2 to 4 weeks via the intravenous route. The first dose of IVIG infusion usually results more frequently in adverse reactions compared to the following second or third doses.Thus, the first IVIG infusion to a patient with antibody deficiency must be given slowly as a 5% solution, starting with a rate of 0.5 to 1.0 mg/kg per minute.Patient should be monitored closely for any adverse reactions during infusion.If the patient tolerates well, the infusion rate may be increased to 1.5 to 2.5 mg/kg per minute after 15 to 30 minutes. The maximal infusion rate is 4 mg/kg per minute.Infusion of an IVIG product should last 2 to 4 hours. For subsequent infusions IVIG concentrations of 10% and 12% can be used, with rates 4 mg/kg per minute.The aim of IVIG therapy in patients with PID is to maintain serum IgG levels between 350 mg/dl and 500 mg/dl [7,10,16,17,25,42,43,45,48,51].
Since, there is large variation in individual IgG elimination rates, periodic measurement of serum IgG concentration is critical to monitor the adequacy of replacement during therapy.
There are two main risks of immunoglobulin treatment: Infusion related adverse effects and transmission of blood–borne viruses [5,7,22,23]. Incidence of adverse reactions, have been found 44% in more than 1.000 patients with PID, in a study done by Immune Deficiency Foundation (IDF) [16]. This rate was surprisingly higher than those observed in licensing studies (Table 6). The IDF survey showed that 34% of patients experienced adverse reactions during the first administration of IVIG and who has had a recent bacterial infection. Reactions may develop 1 to 15% in the first 30 minutes of IVIG infusions. After second or third doses of the same IVIG product additionial infusion dependent reactions become less likely. Most IVIG reactions are mild, however anaphylaxis may occur occasionally. Adverse reactions are characterized by chills, headache, low grade fever, back or abdominal pain, nausea, vomiting, myalgias, rhinitis, asthma, flushing on face, vertigo, anxiety, conjunctival congestion, occasional rash and drop of arterial pressure. Varying rates of adverse events have been reported (Table 6) [53-56]. Thus, close monitoring of a patient during infusion is essential to identify and manage reactions [8,24,53]. Recently, manufacturing processes of immunoglobulins have been improved and new IVIG products have beendeveloped. Several trials with these products demonstrated that the infusion related adverse reactions were reduced[24,53]. IVIG infusions have to be done at hospital or home by professionally educated staff if possible. Local anesthetic cream (EMLA Cream) could be applied on skin prior infusion to reduce pain in small children. Administration IVIG via indewelling venous catheter is not encouraged because of additional adverse events such as thrombotic and infectious complications.
Clinical trials in patients with primary immunodeficiency disorders [22]
A variety of side effects due to IVIG therapy have been reported in different tissues [7-11,21-25,27,28,57]:
Central nervous system:rarely aseptic menengitis
Hematologic: hemolytic anemia, leukopenia, neutropenia, monocytopenia, disseminated intravascular coagulation and changes in blood rheology
Cardiovascular system: rarely heart attack, most commonly, drop in arterial blood pressure
Urogenital system: During the period between June 1985 and November 1998, 88 cases of kidney injuries had been reported to FDA. Acute renal failure occured with IVIG preparations stabilized with sucrose, where as those stabilized with D-sorbitol did not cause such an effect. Patients whose urinary output decreases, who suddenly gain weight with edeme on feet and ankles and those who experience dyspnea should be monitored very closely.
Liver Disease: The risk of Hepatitis C, Hepatitis B, HIV infection, prion disease disappeared after the initiation of viral inactivation (solvent-detergent or pasteurization) methods and PCR studies which took place after CDC’s confirmation of 88 infections among 137 suspected hepatitis C cases (occuring after IVIG) in 1994. Therefore they are reliable preparations.
Skin: severe cutaneus vasculitis, dermatitis (egzema) and hair loss
Other:Life threatening parvovirus B19 has occured due to IVIG, hyperproteinemia, increased serum viscosity, pseudo-hyponatremia during infusions,transient serum sickness.
An expert monitoring is necessary for prompt diagnosis and treatment of adverse reactions. Most side effects resolve by themselves and are usually due to the speed of infusion. Infusion should temporarily be stopped 15 to 30 minutes if the symptoms appear or should be continued with slower rate once the symptoms disappear. Since the side effects are usually non-IgE dependent, the use of antihistamines is controversial, but diphenhydramine, acetaminophen or ibuprofen may be helpful. More severe reactions can be treated with 50 to 100 mg of hydrocortisone in adults and intravenous hydration is helpful.
Those whoare reactive to IVIG should receive premedication. Thirty minutes prior to IVIG administration, oral nonsteroid anti-inflamatory agent (acetaminophen 15 mg/kg), antihistaminic agent (Benadryl 1mg/kg) or one hour prior to infusion intravenous hydrocortisone (6 mg/kg) should be administered [8,24].
As an alternative to intravenous immunoglobulin treatment, immunoglobulins can be administered subcutaneously to patients with primary immunodeficiencies, Subcutaneous infusion of IgG was introduced more than 20 years ago but has gained ground in recent years [29,30,58-64]. Three ready-to-use liquid preparations of human IgG specifically formulated for subcutaneous infusions have been lisenced in US (Table 7). It can be stored at a temperature up to 25°C.
Commercial subcutaneous IG Products(Immune deficiency Foundation, October 2011)
The infusion can be applied through fine butterfly needles under the skin into the abdomen or thighs. Infusion pumps are used to administer the infusions and usually take 45 to 90 minutes. The amount of fluid given weekly to babies and children is 10 mls per site and 30 mls per site for older children. Subcutaneous infusion of 10-20% immunoglobulin, with the rate of 0.05-0.20 ml/kg/hour is advised.The recommended maintenance dose is 100 mg/kg/week. Immunoglobulin trough levels should be >5 g/L for patients with agammaglobulinaemia and 3 g/L greater than the initial IgG level for patients with CVID; however, the clinical response should be consider in choosing the dose and trough level [24]. Parents and patients can be educated on how to infuse the preparation at home. These infusions are better tolerated compared to IVIG and time sparing (home administration). Subcutaneous infusions are recommended to patients who are small children or reactive to IVIG or have poor veins.
Bioavailability and pharmacokinetics properties of subcutaneous IgG (SCIG) differs from intravenous IgG (IVIG).There are still debates about how the dose should be adjusted when switching from IVIG to SCIG. Berger M et al reported that the doses that will yield desired serum levels for IVIG and SCIG may be estimated with the help of pharmacokinetic studies [8]. Area under the curve (AUC) of serum IgG versus time and trough level ratios (TLRs) on SCIG/IVIG were evaluated as guides for adjusting the dose. The mean dose adjustments required for non-inferior AUCs with 2 different SCIG preparations were 137% (± 12%) and 153% (± 16%). However, there were wide variations between adjustments required by different subjects, and in the resulting TLRs. Recent studies allow estimation of the ratio of IgG levels with different dose adjustments, and of the steady state serum levels with different SCIG doses [8]. When switching a patient from IVIG to SCIG, practising immunologistcan tailorthe dosage based on measured serum IgG levels and the clinical response Skoda-Smith S et al recommended a sample calculation process for converting from IVIG to subcutaneous IG, thus weekly dose for subcutaneous Ig should calculate as 1.37 X IVIg dose [65].
Safety and therapeutic efficacy of subcutaneous immunoglobulin products has been demonstrated in children and pregnant women. Therapeutic efficacy of intravenous or subcutaneous immunoglobulin treatment in reducing infections was equal [5,28,57,65,66]. In an international study performed by Chapel et al. the efficacy of immunoglobulin replacement therapy given via intravenously or subcutaneously in patients with PAD was compared [60]. Forty patients received subcutaneous or intravenous immunoglobulin for the first year and switched to the alternative treatment in the second year, and the study showed that there was no difference in efficacy and adverse reactions between both routes. In another study, Fasth A et al. used a 16%, ready-to-use human normal immunoglobulin solution subcutaneously in children with PID previously receiving regular IVIG treatment, and the study showed that mild injection reactions were the adverse effects of the treatment, and the rate of bacterial infections was not different between both IVIG treatments. In the at home treatment there were fewer missed school days, low healthcare expenses [62].
The cost effectiveness of the use of subcutaneous IG compared to IVIG therapy had been investigated in several studies [67,68]. The mean cost of both immunoglobulins was evaluated in the study performed by Beaute J et al. and they showed that monthly doses were equal for both routes of administration. In addition SCIG and IVIG (hospital-based) costs were also similar, but the costs may differ from one country to another [52]. Although this theoretical model showed little difference between the costs, SCIG seems to be expensive compared to IVIG due to the doses of immunoglobulin, but further studies are needed. Overall costs may be higher in CVID, because these patients need higher doses of immunoglobulin [21,52].
The SCIG home therapy was reported to give better health and improved school/social functioning for the children, reduced emotional distress and limitations on personal time for the parents and fewer limitations on family activities [58-64]. Pharmacokinetic studies reveal a more physiologic profile, in peak and trough levels of serum IgG [62,66]. Local tissue reactions are more frequent but the systemic side effect profile is low. Local tissue reactions are often mild and tend to improve over time. Adults switching therapy reported improved vitality, mental health, and social functioning. Treatment satisfaction (TS) scores and health-related quality of life (HRQOL) was improved in adults and children with immunodeficiency [69].
According to ESID registry (http://www.esid.org), 4462 of 10,039 patients with PID receive IgG replacement (74% intravenous, 26% subcutaneous, <0.5% intramuscular). There is a wide variety of frequency of subcutaneous IgG replacement therapy in European countries. Sweden was the first countryto deliver IgG via the SC route, therefore more than 80% of all patients with antibody deficiencies receive SCIg [3].
Replacement therapy with immunoglobulin either via intravenous or via subcutaneous is in patients with immunodeficiencies are associated with reduced infection frequency and organ damage and increased life expectancy. IVIG has been widely used in US and Europe for many years. Monthly IVIG treatment offered steady-state IgG level throughout the dosing cycle, dedicated viral inactivation steps improved safety concerns, pooled analyses confirmed the efficacy and safety, benefits of therapy and adverse events has been well established.
Recent advances in the basic science of immunoglobulins and meta-analyses of patient data have provided new approaches in using polyclonal IgG to treat patients with primary immunodeficiencies. The old fashion subcutaneuos IG infusion reintroduced to treat patients with immunodeficiencies. The subcutaneous-IG therapy was reported to be effective, safe and well tolerated in children and adults. In addition, the SCIG home therapy high treatment satisfaction(TS) scores and health-related quality of life (HRQOL) was advantages of SCIG. Subcutaneous infusions are recommended to patients who are small children or reactive to IVIG or have problem with vascular access. Practicing immunologists can use new concepts in tailoring their approach to treat patients with primary immunodeficiencies.
When compared to non-pregnant women, the risk of urinary tract infection (UTI) with bacteriuria increases considerably during pregnancy. Infection with bacteriuria during pregnancy has been linked to an increased risk of pyelonephritis [1]. Several physiological changes occur during normal pregnancy, including an increase in the volume of vascular and interstitial of the renal system, which results in a rise in kidney dimension of roughly 1 cm and a 30% rise in renal volume. In addition, by mid-pregnancy, around 80% of women will have dilated upper urinary tracts, ureters, pelvis, and calycle area. The right side of the body experiences dilation more frequently than the left [2]. Hydronephrosis and hydroureter, respectively, are dilations of the kidney and ureter that occur most commonly during the second trimester and last until birth. This dilation can be caused by both hormonal and mechanical factors; an increase in progesterone hormone levels causes a decrease in bladder and ureteral tone [3]. Urinary stasis was caused by mechanical causes such as gravid uterine compression paired with smooth muscle relaxation, which slowed ureter peristalsis and increased bladder volume capacity. Pregnancy-induced alterations in urine pH, osmolality, and glycosuria may further amplify bacterial growth [2]. Symptomatic infections (acute cystitis, acute pyelonephritis) occur when bacteria invade urinary tract tissues and trigger an inflammatory reaction, whereas asymptomatic bacteriuria (ASB) occurs when bacteria grow in urine without presenting symptoms of acute UTI [1]. Asymptomatic bacteriuria is more common in pregnant women than in non-pregnant women, and it is frequently underreported since diagnosis is difficult owing to the lack of particular symptoms or signs, whereas symptomatic bacteriuria creates no concerns because diagnosis and treatment are simple [1]. The most prevalent medical complication during pregnancy is urinary tract infection (UTI), which accounts for 20% of pregnancies and 10% of antepartum hospitalizations [4, 5, 6]. The most common bacterium that causes UTI in pregnant and nonpregnant women is
This case–control research comprised 30 pregnant women and 30 non-pregnant women who visited Al-zahraa Teaching Hospital’s outpatient clinic on a regular basis. As a result of a randomized selection (where every member of a population has an equal probability of being included in the sample and where all feasible samples of a given size have an equal probability of being chosen), selected participants were assessed individually using a plate form questioner and agreed to participate in this study for three months, starting in July and ending in September 2019.
Women who visited the al-Zahraa teaching hospital’s outpatient clinic, pregnant or not, were asked to provide their verbal agreement. For roughly 10 minutes, each woman was interrogated (Women who declined to participate were not questioned, and the next lady was chosen). Age, mother socioeconomic circumstances, obstetrical history, medical history, and patient complaint are all taken into account in the case history. Patients were taught how to collect urine samples in a sterile urine container under aseptic circumstances and then send them for a general urine examination. The sample was then given a name, a number, and was quickly taken to the lab for additional analysis.
Data of this study were statistically analyzed using IBM SPSS version 22.0 and descriptive statistic was used to summaries the data, like tables, figures, and measures of central tendency. Analytic statistics were used to compare between the variables. Chi-square (x2) was used, significance was assumed at p ≤ 0.05.
The Ethical Committee of Wasit University’s College of Medicine examined the study protocol and approved it.
In this study the prevalence of bacteriuria in women was found to be 13.3%, in pregnant women 16.7% and in non-pregnant women 10%. Asymptomatic bacteriuria in all women was 5/60 cases 8.3%. This indicates that about 16.7% of pregnant women are at risk of development of acute episode of UTI during pregnancy if they are not properly treated [17, 18].
In this study the prevalence of bacteriuria in women was found to be 13.3% (8/60), in pregnant women 16.7% (5/30), and in non-pregnant women 10% (3/30). Asymptomatic bacteriuria in all women was 8.3% (5/60), in pregnant women was 11.7% (4/30), and in non-pregnant women was 5% (2/30). This indicates that about 16.7% of pregnant women are at risk of development of acute episode of UTI during pregnancy if they are not properly treated. These findings are similar to that of Uncu who reported the prevalence of asymptomatic bacteriuria in pregnant women 9.3% [19]. In a study performed in turkey, the prevalence of asymptomatic bacteriuria was reported to be 8.1% [20]. The results of the present study found significantly high relation between age and bacteriuria (p = 0.00) (Table 1) and revealed that the bacteriuria in women was commonest in the age group 25–30 years 62.5%, and these result agreed with study by Buzayan in Libya [21], but contrast with study in Yemen that observed the bacteriuria was more in the age group 15–24 years 53.7% [22]. The difference may be due to social factors such as early age of marriage and sexual activity. There is no significant relationship between level of education and bacteriuria (p = 0.147) (Table 2), the prevalence of bacteriuria was 30.8% in illiterate, 18.5% in primary, 11.1% in secondary and 5.7% in university level of education However, as the level of education increases there is decrease in bacteriuria among women and these findings are similar with Samad [23]. The prevalence of bacteriuria was 14.7% in married women, and 8% in unmarried women, differences are founded apparently but no statistical difference (p = 0.562) (Table 2), while Krcmery et al., showed that the risk factors for bacteriuria in women include sexual intercourse and having a marital history [24] (Table 3). The bacteriuria in the pregnant women was observed more in the third trimester 21.4% than in the first trimester 6.3%, and second trimester 20%. But no significant (p = 0.423) (Table 4). Similar with Haddad who found that the bacteriuria was more in the third trimester 48.8% [22]. In contrast Buzayan [21], in this study the most frequent isolates were
Bacteriuria | Cases with Bacteriuria | Cases without Bacteriuria | Total | |||
---|---|---|---|---|---|---|
Age / year | NO | % | NO | % | NO | % |
X2 = 13.744 df = 4 p = 0.0001 S | ||||||
18–24 | 1 | 18.75 | 8 | 15.3 | 9 | 15.8 |
25–30 | 5 | 62.5 | 11 | 22.1 | 16 | 27.5 |
31–36 | 1 | 6.25 | 18 | 34.7 | 19 | 30.8 |
37–42 | 1 | 12.5 | 10 | 18.3 | 11 | 17.6 |
43–48 | 0 | 0 | 5 | 9.6 | 5 | 8.3 |
Total | 8 | 13.3 | 52 | 86.7 | 60 | 100 |
The distribution of cases of bacteriuria according to the age of the studied groups.
Level of Education | Cases with Bacteriuria | Cases without Bacteriuria | Total | |||
---|---|---|---|---|---|---|
NO | % | NO | % | NO | % | |
X2 = 5.999 df = 3 p = 0.147 N.S. | ||||||
Illiterate | 2 | 30.8 | 5 | 69.2 | 7 | 10.8 |
Primary | 3 | 18.5 | 11 | 81.5 | 14 | 22.5 |
Secondary | 2 | 11.1 | 20 | 88.9 | 22 | 37.5 |
University | 1 | 5.7 | 16 | 94.3 | 17 | 29.2 |
Marital status | X2 = 0.304 df = 1 p = 0.562 N.S. | |||||
Married | 7 | 14.7 | 40 | 85.3 | 47 | 100 |
Un married | 1 | 8 | 12 | 92 | 13 | 100 |
Total | 8 | 13.3% | 52 | 86.7% | 60 | 100% |
The distribution of cases of bacteriuria in the studied population according to their education level, marital status and UTI.
Bacteriuria | Symptomatic Bacteriuria | Asymptomatic Bacteriuria | Cases without Bacteriuria | Total | ||||
---|---|---|---|---|---|---|---|---|
NO | % | NO | % | NO | % | NO | % | |
Pregnancy | X2 = 1.754 df = 2 p = 0.416 N.S. | |||||||
Pregnant | 1 | 3.3 | 4 | 13.3 | 25 | 83.4 | 30 | 100 |
Non Pregnant | 2 | 6.7 | 1 | 3.3 | 17 | 90 | 30 | 100 |
Total | 3 | 5 | 5 | 8.3 | 52 | 86.7 | 60 | 100 |
The distribution of cases of bacteriuria in relation to the pregnancy and UTI conditions.
Bacteriuria | Cases with Bacteriuria | Cases without Bacteriuria | Total | |||
---|---|---|---|---|---|---|
NO | % | NO | % | NO | % | |
Pregnancy Trimester | X2 = 1.719 df = 2 p = 0.423 N.S. | |||||
First Trimester | 1 | 6.3 | 15 | 93.7 | 16 | 26.7 |
Second Trimester | 6 | 20 | 24 | 80 | 30 | 50 |
Third Trimester | 3 | 21.4 | 11 | 78.6 | 14 | 23.3 |
Total | 10 | 16.7 | 50 | 83.3 | 60 | 100 |
The distribution of cases of bacteriuria in relation to the pregnancy age and UTI.
The percentage of isolated bacteria responsible for bacteriuria.
The results of this work indirectly supported the hypothesis of an association of bacteriuria with age and gravidity. In addition, UTI appears to be multifactorial. A screening for bacteriuria in women especially pregnant women must be done to discover the infected cases, which would allow early treatment to avoid the complications.
The most prevalent risk factors for UTI during pregnancy were poor personal cleanliness, a history of UTI, diabetes mellitus, and anemia. The study recommends training in personal hygiene and health education about the type and frequency of changes in underwear, the number of showers per week, the use of soap, and the use of water to wash genitalia, genital dries, the frequency of micturition, precoital washing, postictal washing, and precoital micturition.
I would like to express my gratitude to the O&G seniors at the outpatient’s clinic in the Al Zahraa teaching hospital for their great assistance in a achieving this research, along with al zahraa teaching hospital internal laboratory staff for their role in conducting GUE and urine culture for each participant in this study.
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\n\nNote: All data represented above was collected by IntechOpen from 2013 to 2017.
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It is a leading cause of disability in children. Congenitally infected neonates often appear asymptomatic at birth or have nonspecific symptoms. An early diagnosis and subsequent early antiviral therapy associated to nonpharmacological therapy (e.g., hearing rehabilitation, speech-language therapy, and cochlear implants) can reduce long-term disability. Much research has been done in this field, but further studies are still necessary. Looking back at the most recent papers, we will draw a review on this topic trying to answer to the question: could universal CMV screening be a useful and cost-effective diagnostic tool?",book:{id:"8728",slug:"update-on-critical-issues-on-infant-and-neonatal-care",title:"Update on Critical Issues on Infant and Neonatal Care",fullTitle:"Update on Critical Issues on Infant and Neonatal Care"},signatures:"Sara Lunardi, Francesca Lorenzoni and Paolo Ghirri",authors:null},{id:"44446",doi:"10.5772/54310",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14749,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"38034",doi:"10.5772/34698",title:"Maternal Socio-economic Status and Childhood Birth weight: A Health Survey in Ghana.",slug:"maternal-socio-economic-status-and-childhood-birth-weight-a-health-survey-in-ghana-",totalDownloads:3608,totalCrossrefCites:2,totalDimensionsCites:3,abstract:null,book:{id:"741",slug:"neonatal-care",title:"Neonatal Care",fullTitle:"Neonatal Care"},signatures:"Edward Nketiah-Amponsah, Aaron Abuosi and Eric Arthur",authors:[{id:"101268",title:"Dr.",name:"Edward",middleName:null,surname:"Nketiah-Amponsah",slug:"edward-nketiah-amponsah",fullName:"Edward Nketiah-Amponsah"}]}],mostDownloadedChaptersLast30Days:[{id:"44446",title:"Neonatal Pneumonia",slug:"neonatal-pneumonia",totalDownloads:14749,totalCrossrefCites:1,totalDimensionsCites:5,abstract:null,book:{id:"2990",slug:"neonatal-bacterial-infection",title:"Neonatal Bacterial Infection",fullTitle:"Neonatal Bacterial Infection"},signatures:"Friedrich Reiterer",authors:[{id:"152025",title:"Prof.",name:"Friedrich",middleName:null,surname:"Reiterer",slug:"friedrich-reiterer",fullName:"Friedrich Reiterer"}]},{id:"53683",title:"Pre and Postoperative Management of Pediatric Patients with Congenital Heart Diseases",slug:"pre-and-postoperative-management-of-pediatric-patients-with-congenital-heart-diseases",totalDownloads:4889,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Stabilization during preoperative cardiac surgery especially in neonates has an important role to predict outcome for pediatric congenital heart surgery. We tried to elaborate general guidelines on how to diagnose and some anticipations for emergency treatments tailored by the type of congenital heart disease in neonates. Stabilization consists of medical treatment including emergent prostaglandin institution in some types of duct dependent lesion. The role of interventional catheterization such as patent ductus arteriosus (PDA) stent, balloon pulmonary valvotomy, etc. as modalities for stabilization before surgery was also elaborated. Some general and specific guidelines based on the type of surgeries for postoperative management were also discussed.",book:{id:"5473",slug:"pediatric-and-neonatal-surgery",title:"Pediatric and Neonatal Surgery",fullTitle:"Pediatric and Neonatal Surgery"},signatures:"Eva Miranda Marwali, Beatrice Heineking and Nikolaus A. 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It is more common during the neonatal period than at any other age with the estimated incidence of 0.25 per 1000 live births. The absence of specific clinical presentation makes diagnosis of meningitis more difficult in neonates than in older children. Culture of cerebrospinal fluid is the traditional gold standard for diagnosis of bacterial meningitis, so all newborn infants with proven or suspected sepsis should undergo lumbar puncture. However, deciding when to perform lumbar puncture and interpretation of the results are challenging. Although the pathophysiology of neonatal meningitis is complex and not fully understood, researches on diagnostic and prognostic tools are ongoing. Prevention of neonatal sepsis, early recognition of infants at risk, development of novel, rapid diagnostics and adjunctive therapies, and appropriate and aggressive antimicrobial treatment to sterilize cerebrospinal fluid as soon as possible may prevent the lifelong squeal of bacterial meningitis in newborn infants.",book:{id:"7527",slug:"neonatal-medicine",title:"Neonatal Medicine",fullTitle:"Neonatal Medicine"},signatures:"Mehmet Şah İpek",authors:[{id:"267903",title:"Associate Prof.",name:"Mehmet Şah",middleName:null,surname:"İpek",slug:"mehmet-sah-ipek",fullName:"Mehmet Şah İpek"}]},{id:"71427",title:"Factors Influencing Maternal Decision-Making on Infant Feeding Practices",slug:"factors-influencing-maternal-decision-making-on-infant-feeding-practices",totalDownloads:984,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The decision to formula feed or breastfeed a child typically begins with an established prenatal intention. This chapter will examine the multiple dimensions influencing maternal decision-making in regards to the feeding practices of infants including 1) individual maternal characteristics, 2) organizational factors, 3) hospital/provider recommendations, and 4) systematic/policy factors. The chapter will also examine the impact of infant feeding practices on early infant and childhood health outcomes. Research has demonstrated the benefits of breastfeeding on infants and early childhood which includes but is not limited to protection against common illnesses and infections, improved IQ , and even increased school attendance. Moreover, the World Health Assembly global nutrition objectives focus on encouraging breastfeeding support across all sectors in addition to implementing tailored community-based approaches, limiting the excessive marketing of infant formula, and enforcing supportive breastfeeding legislation. 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Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. 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He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,annualVolume:11421,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. 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He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. 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Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón",slug:"juan-carlos-gardon",fullName:"Juan Carlos Gardón",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:"Catholic University of Valencia San Vicente Mártir, Spain",institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain. She is a Full Professor at the Department of Medicine and Animal Surgery at the same University. She developed her research activity in the field of Endocrinology, Hematology, Biochemistry and Immunology of horses. She is a scientific reviewer of several international journals : American Journal of Obstetrics and Gynecology, Comparative Clinical Pathology, Veterinary Clinical Pathology, Journal of Equine Veterinary Science, Reproduction in Domestic Animals, Research Veterinary Science, Brazilian Journal of Medical and Biological Research, Livestock Production Science and Theriogenology. Since 2014, she has been the Head of the Clinical Analysis Laboratory of the Hospital Clínico Veterinario from the Faculty of Veterinary, CEU-Cardenal Herrera University.",institutionString:"CEU-Cardenal Herrera University",institution:{name:"CEU Cardinal Herrera University",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"201721",title:"Dr.",name:"Beatrice",middleName:null,surname:"Funiciello",slug:"beatrice-funiciello",fullName:"Beatrice Funiciello",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201721/images/11089_n.jpg",biography:"Graduated from the University of Milan in 2011, my post-graduate education included CertAVP modules mainly on equines (dermatology and internal medicine) and a few on small animal (dermatology and anaesthesia) at the University of Liverpool. After a general CertAVP (2015) I gained the designated Certificate in Veterinary Dermatology (2017) after taking the synoptic examination and then applied for the RCVS ADvanced Practitioner status. After that, I completed the Postgraduate Diploma in Veterinary Professional Studies at the University of Liverpool (2018). My main area of work is cross-species veterinary dermatology.",institutionString:null,institution:null},{id:"291226",title:"Dr.",name:"Monica",middleName:null,surname:"Cassel",slug:"monica-cassel",fullName:"Monica Cassel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/291226/images/8232_n.jpg",biography:'Degree in Biological Sciences at the Federal University of Mato Grosso with scholarship for Scientific Initiation by FAPEMAT (2008/1) and CNPq (2008/2-2009/2): Project \\"Histological evidence of reproductive activity in lizards of the Manso region, Chapada dos Guimarães, Mato Grosso, Brazil\\". Master\\\'s degree in Ecology and Biodiversity Conservation at Federal University of Mato Grosso with a scholarship by CAPES/REUNI program: Project \\"Reproductive biology of Melanorivulus punctatus\\". PhD\\\'s degree in Science (Cell and Tissue Biology Area) \n at University of Sao Paulo with scholarship granted by FAPESP; Project \\"Development of morphofunctional changes in ovary of Astyanax altiparanae Garutti & Britski, 2000 (Teleostei, Characidae)\\". She has experience in Reproduction of vertebrates and Morphology, with emphasis in Cellular Biology and Histology. She is currently a teacher in the medium / technical level courses at IFMT-Alta Floresta, as well as in the Bachelor\\\'s degree in Animal Science and in the Bachelor\\\'s degree in Business.',institutionString:null,institution:null},{id:"442807",title:"Dr.",name:"Busani",middleName:null,surname:"Moyo",slug:"busani-moyo",fullName:"Busani Moyo",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Gwanda State University",country:{name:"Zimbabwe"}}},{id:"423023",title:"Dr.",name:"Yosra",middleName:null,surname:"Soltan",slug:"yosra-soltan",fullName:"Yosra Soltan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"349788",title:"Dr.",name:"Florencia Nery",middleName:null,surname:"Sompie",slug:"florencia-nery-sompie",fullName:"Florencia Nery Sompie",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Sam Ratulangi University",country:{name:"Indonesia"}}},{id:"208123",title:"Dr.",name:"Mari-Carmen",middleName:null,surname:"Uribe",slug:"mari-carmen-uribe",fullName:"Mari-Carmen Uribe",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"345713",title:"Dr.",name:"Csaba",middleName:null,surname:"Szabó",slug:"csaba-szabo",fullName:"Csaba Szabó",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"345719",title:"Mrs.",name:"Márta",middleName:null,surname:"Horváth",slug:"marta-horvath",fullName:"Márta Horváth",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"420151",title:"Prof.",name:"Novirman",middleName:null,surname:"Jamarun",slug:"novirman-jamarun",fullName:"Novirman Jamarun",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Andalas University",country:{name:"Indonesia"}}}]}},subseries:{item:{id:"15",type:"subseries",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors"},{id:"17",title:"Metabolism",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation"},{id:"18",title:"Proteomics",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:null},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/322572",hash:"",query:{},params:{id:"322572"},fullPath:"/profiles/322572",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()