\r\n\tFurthermore, during the preparation of high-quality dairy products, several physical, chemical, enzymatic, and microbial transformations take place. We will consciously focus on this interaction of different constituents of milk under different processing conditions for the development of the products.
",isbn:"978-1-83768-093-1",printIsbn:"978-1-83768-092-4",pdfIsbn:"978-1-83768-094-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"420e687768b56ca7b3238d77f63f1302",bookSignature:"Dr. Neelam Upadhyay",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/12173.jpg",keywords:"Protein, Fat, Lactose, Carbohydrates, Milk Processing, Milk Products, Milk Constituents, Acid Coagulated, Enzyme Treated, Heat Treated, Dairy Products, Protocols of Manufacturing",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 18th 2022",dateEndSecondStepPublish:"June 15th 2022",dateEndThirdStepPublish:"August 14th 2022",dateEndFourthStepPublish:"November 2nd 2022",dateEndFifthStepPublish:"January 1st 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"21 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Upadhyay has received many awards most notable being the Young Woman Scientist Award 2020 from the Agro-Environmental Development Society and the Best Poster Award 2021 from the National Conference on Moringa Food Conclave 2021. She is a dedicated researcher in food and dairy processing and has published many research articles and papers in both national and international journals and publications.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"269538",title:"Dr.",name:"Neelam",middleName:null,surname:"Upadhyay",slug:"neelam-upadhyay",fullName:"Neelam Upadhyay",profilePictureURL:"https://mts.intechopen.com/storage/users/269538/images/system/269538.jpg",biography:"BRIEF BIODATA\n1.\tName in full: Neelam Upadhyay \n2.\tDate & Place of Birth: 29th December, 1987 at Delhi\n3.\tField of specialization: Food Technology\n4.\tPresent Position/ Designation: Scientist- Senior Scale\n5.\tAddress:\t(a)\tOfficial:\tTel. No.:0184-2259258\n\t\t\t\tE-mail: \ticar.neelam@gmail.com; neelam.upadhyay@icar.gov.in \n\t\t\t\tAddress: \tLaboratory No. 146, Dairy Technology Division, ICAR- \n\t\t\t\t\t\tNational Dairy Research Institute, Karnal \n\t\t\t(b)\tResidential: Tel. No.: +91-9255772587\n\tAddress (Permanent): 41-D, MIG DDA Flats, Shivam Enclave, Delhi-110032\n6.\t(a) Academic career and (b) professional attainments\n(a) Examination\tClass/ Percentage\tYear of Passing\tSubjects Taken\tName of University / Board\nXth \t1st/83\n(415/500)\t2003\tMathematics, Social Science, Science, English, Hindi\tK.V., Mumbai (CBSE)\nXIIth\t1st/78.2 \n(391/500)\t2005\tPhysics, Mathematics, Chemistry, Biology, English\tK.V., Delhi (CBSE)\nB.A.Sc. (Hons.)\t1st/83.43 (2044/2450)\n(3rd position)\t2008\tFood Technology\tSRCASW, University of Delhi, Delhi\nM.Sc.\t1st/8.62\n(1st position)\t2010\tFood Science & Technology\tCCS Har. Agri. Uni., Hisar, Haryana\nTitle of Research:\tDevelopment of flavoured whey-soya milk beverage\nMajor Advisor:\tDr. R. S. Dabur (Professor and Head)\nPh.D.\t1st/8.0\n(1st position)\t2014\tDairy Chemistry\tNational Dairy Research Institute, Karnal, Haryana\nTitle of Research: \tDetection of vegetable oil and animal body fat adulteration in ghee using solvent fractionation technique\nMajor Advisor:\tDr. Darshan Lal (Principal Scientist and Ex-Head)\nDistinctions during Academics\nDegree\tDistinctions\nBachelor of Applied Science (Hons.)\ti.\tY.K. Kapoor Memorial Scholarship 2006 by All India Food Processor’s Association \nii.\t3rd position in university\niii.\tReceived highest attendance award\niv.\tReceived trophy for ‘Most Disciplined Student’ for the graduation period 2005-2008\nv.\tCertificate of Honor from Honb’le Mr. Justice K.G. Balakrishnan, Chief Justice of India\nMaster of Science\ti.\t1st position in discipline and 2nd position in college\nii.\tReceived recognition for academic excellence from Jawaharlal Nehru Memorial Fund; \niii.\tQualified GATE\niv.\t2nd in inter-college yoga competition\nv.\tParticipated in various events of All India Youth Festival organized at UAS, Bangalore.\nDoctor of Philosophy\ti.\tReceived Merit Certificate for Academic Excellence in PhD course work\nii.\tReceived Certificate of Appreciation for outstanding work in the field of Dairy Processing during PhD\niii.\tQualified ICAR’s National Eligibility Test in 2010; Qualified the ICAR’s All India Examination, ICAR-SRF (PGS_-2011-2012 for award of ICAR-SRF (PGS) with 2nd rank (both in first attempt) \niv.\tQualified Agricultural Research Service Examination-2013 conducted by Agricultural Scientist Recruitment Board against the single vacancy (for UR) in the discipline of Food Technology\nv.\tStage Management Secretary of student’s council 2010-11\nvi.\tLiterary secretary of Student’s Council 2011-12\nvii.\tCompleted certificate e-course on “Publishing a Journal Manuscript - the Groundwork” directed by Springer in 2013\nviii.\tHave successfully completed certificate e-course – “Peer Review Academy” directed by Springer in 2013\nix.\tReceived a certificate on accomplishment IRIS 4-2 Information Literacy Plagiarism Quiz (on-line) in 2013 developed by Distance Learning Council of Washington, USA \n (b) Position Held\tInstitution \tPeriod of Appointment\tNature of Appointment\nScientist (Food Technology)\tICAR- National Academy of Agricultural Research Management, Hyderabad\t3 months\n(1st January, 2015 till 31st March, 2015)\tPermanent\n(Received ‘A’ grade for FOCARS)\nScientist \n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t10th March, 2015 till 31st December, 2018\n(after availing 10 days of transfer period)\tPermanent\nScientist-Senior Scale\n(Food Technology)\tICAR- National Dairy Research Institute, Karnal\t1st January, 2019 till date\tPermanent\n\n7. Special attainments in Research\n(https://scholar.google.co.in/citations?hl=en&user=PRz0Tz4AAAAJ&view_op=list_works&sortby=pubdate)\nPublications\tNumbers\tRemarks \nResearch Articles\t35\n(24 Intl, 9 National, 2 others)\tTotal Impact: 72.302\n\nBook Chapters\t7\t5 APA/CRC Press; 1 InTech Open; \n1 National\nReview Articles\t2\tTotal Impact:8.327\nTechnical Articles\t7\tCompendium of trainings, seminars, etc\nInstitute publication\t1\t\nPopular Article\t12\t6 in English; 5 in hindi\nCitations \t1066\t(as per googlescholar)\nH-index/ i10-index\t15/ 17\t\n.\n.\nJournal\tNumber of publications\tImpact factor\nResearch Articles\t35\t72.302\nInternational\t24 (15 as either corresponding or first author)\t72.302\nNational\t9 (3 as first or corresponding author)\tNAAS score\nOthers\t2\t\nReview article (International)\t2\t8.327\nInternational\t2\t8.327\n.\n \n\n\n\nRESEARCH ARTICLES\nInternational Journals \n1.\tTiwari, S., Upadhyay, N.*, Singh, A. K. (2022). Stability assessment of emulsion of carotenoids extracted from carrot bio-waste in flaxseed oil and its application in food model system. Food Bioscience, 47, 101631. https://doi.org/10.1016/j.fbio.2022.101631.\n2.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Singh, A. K., & Borad, S. G. (2021). Buffalo milk protein concentrate 60: Effect of skim milk heat treatment on its reconstitutability and functionality. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 148, 111638. \n3.\tUttamrao, H. J., Meena, G. S., Khetra, Y., Upadhyay, N., Singh, A. K., Arora, S., & Borad, S. G. (2022). Homogenization and sodium hydrogen phosphate induced effect on physical and rheological properties of ultrafilterd concentrated milk. Journal of Food Science and Technology, 59(3), 956-967. \n4.\tTiwari, S., Upadhyay, N.*, Malhotra, R. (2021). Three way ANOVA for emulsion of carotenoids extracted in flaxseed oil from carrot bio-waste. Waste Management, 121, 67-76. \n5.\tRanvir, S., Sharma, R., Gandhi, K., Upadhyay, N., Mann, B. (2020). Assessment of proteolysis in ultra-high temperature milk using attenuated total reflectance–Fourier transform infrared spectroscopy. International Journal of Dairy Technology. 73(2): 366-375. doi: 10.1111/1471-0307.12683. \n6.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). High performance liquid chromatographic (HPLC) determination of available lysine in milk protein-maize composite extrudates and its stability during storage. Journal of the Indian Chemical Society, 97(11a), 2344-2350\n7.\tTiwari, S., Upadhyay, N.*, Singh, A. K., Meena, G. S., & Arora, S. (2019). Organic solvent-free extraction of carotenoids from carrot bio-waste and its physico-chemical properties. Journal of Food Science and Technology, 1-10. 10.1007/s13197-019-03920-5\n8.\tBaria, B., Upadhyay, N.*, Singh, A. K., & Malhotra, R. K. (2019). Optimization of ‘green’extraction of carotenoids from mango pulp using split plot design and its characterization. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 104, 186-194. \n9.\tPatil, A. T., Meena, G. S., Upadhyay, N., Khetra, Y., Borad, S. G., & Singh, A. K. (2019). Effect of change in pH, heat treatment and diafiltration on properties of medium protein buffalo milk protein concentrate. Journal of Food Science and Technology, 56(3), 1462-1472. \n10.\tUttamrao, H. J., Meena, G. S., Borad, S. G., Punjaram, S. A., Khetra, Y., Upadhyay, N., & Singh, A. K. (2019). Effect of disodium phosphate and homogenization on physico-chemical and rheological properties of buffalo skim milk based ultrafiltered retentate. Journal of food science and technology, 56(5), 2426-2435. \n11.\tMeena, G.S., Dewan, A., Upadhyay, N., Barapatre, R., Kumar, N., Singh, A.K., & Rana, J.S. (2019). Fuzzy Analysis of Sensory Attributes of Gluten Free Pasta Prepared From Brown Rice, Amaranth, Flaxseed Flours and Whey Protein Concentrates. Journal of Food Science and Nutrition Research, 2(1), 022-037. DOI: 10.26502/jfsnr.2642-1100006\n12.\tPatil, A. T., Meena, G. S., Upadhyay, N.*, Khetra, Y., Borad, S., & Singh, A. K. (2018). Production and characterization of milk protein concentrates 60 (MPC60) from buffalo milk. Food Science & Technology – Lebensmittel -Wissenschaft & Tech, 91, 368-374. https://doi.org/10.1016/j.lwt.2018.01.028 \n13.\tUpadhyay, N.*, Jaiswal, P., & Jha, S. N. (2018). Application of attenuated total reflectance Fourier Transform Infrared spectroscopy (ATR–FTIR) in MIR range coupled with chemometrics for detection of pig body fat in pure ghee (heat clarified milk fat). Journal of Molecular Structure, 1153, 275-281. \n14.\tUpadhyay, N.*, Kumar A., Goyal A. and Lal, D. (2017). Complete liquification time test coupled with solvent fractionation technique to detect adulteration of foreign fats in ghee (heat-clarified milk fat). International Journal of Dairy Technology. 70(1): 110-118. doi: 10.1111/1471-0307.12323. \n15.\tUpadhyay, N.*, Goyal A., Kumar A. and Lal, D. (2017). Detection of adulteration of caprine body fat and mixture of caprine body fat and groundnut oil in bovine and buffalo ghee using Differential Scanning Calorimetry. International Journal of Dairy Technology. 70(2): 297-303. May 2017.doi:10.1111/1471-0307.12336. \n16.\tKumar, A., Upadhyay, N.*, Ghai, D.L., Kumar, A. Gandhi, K. and Sharma, V. (2016). Effect of preparation and storage of khoa on physico-chemical properties of milk fat. International Journal of Dairy Technology. 69(2): 294-300. doi: 10.1111/1471-0307.12266. \n17.\tUpadhyay, N.*, Jaiswal, P. & Jha, S.N. (2016). Detection of goat body fat adulteration in pure ghee using ATR-FTIR spectroscopy coupled with chemometric strategy. Journal of Food Science and Technology. 53 (10): 3752-3760. doi:10.1007/s13197-016-2353-2 ISSN 0022-1155\n18.\tRathi, M., Upadhyay, N.*, Dabur, R.S. and Goyal A. (2015). Formulation and physic-chemical analysis of whey –soymilk dahi. Journal of Food Science and Technology. 52(2): 968-975. doi 10.1007/s13197-013-1074-z. ISSN: 0022-1155. \n19.\tKanthale, P., Kumar, A. Upadhyay, N.*, Lal, D., Rathod G. and Sharma, V. (2015). Qualitative test for the detection of extraneous Thiocyanate in Milk. Journal of Food Science and Technology. 52(3): 1698-1704. DOI: 10.1007/s13197-013-1174-9. ISSN: 0022-1155.\n20.\tGoyal, A., Sharma, V., Upadhyay, N., Singh, A.K., Arora, S. and Ghai, D.L. (2015). Development of stable flaxseed oil emulsions as a potential delivery system of ω-3 fatty acids. Journal of Food Science and Technology. 52(7):4256-4265. \n21.\tUpadhyay, N.*, Kumar, A., Rathod, G., Goyal, A. and Lal, D. (2015). Development of a method employing reversed-phase thin-layer chromatography for establishing milk fat purity with respect to adulteration with vegetable oils. International Journal of Dairy Technology. 68(2): 207-217. doi. 10.1111/1471-0307.12178. \n22.\tGoyal, A., Siddiqui, S. Upadhyay, N., Soni, J. (2014). Effects of ultraviolet irradiation, pulsed electric field, hot water and ethanol vapours treatment on functional properties of mung bean sprouts. Journal of Food Science and Technology. 51(4): 708-714. doi 10.1007/s13197-011-0538-2. Publisher Springer. ISSN (electronic version): 0975-8402. \n23.\tKundu, H., Grewal, R.B., Goyal, A., Upadhyay, N.*, and Prakash S. (2014). Effect of incorporation of pumpkin (Cucurbita moshchata) powder and guar gum on the rheological properties of wheat flour. Journal of Food Science and Technology. 51(10):2600-2607. DOI: 10.1007/s13197-012-0777-x. ISSN: 0022-1155. \n24.\tUpadhyay, N.*, Kumar, A., Goyal, A. and Lal, D. (2014). A planar chromatographic method to detect adulteration of vegetable oils in ghee. JPC-Journal of Planar Chromatography-Modern TLC. 27 (6): 431-437. DOI: 10.1556/JPC.27.2014.6.5 \nNational Journals\n1.\tPonbhagavathi, T. R., Singh, A. K., Raju, P. N., Upadhyay, N. (2021). Textural and Sensory Characteristics of Milk Protein-Maize Flour-based Extrudates. Journal of Agricultural Engineering, 58(2), 124-136. 10.52151/jae2021581.1740\n2.\tPonbhagavathi, T.R., Singh, A.K., Raju, P.N., Upadhyay, N. (2020). Effect of Rennet Casein and Whey Protein Concentrate on Extrusion Behavior of Maize Flour. Current Journal of Applied Science and Technology. 39(33), 16-27, Article no.CJAST.57830.\n3.\tUpadhyay, N.*, Kumar, A., Lal, D., Kant, R., & Goyal, A. (2018). Detection of groundnut oil and goat body fat adulteration in ghee using principal component analysis on fatty acid profile. Indian Journal of Dairy Science. 71(5):464-472. \n4.\tUpadhyay, N.*, Kumar, A., Gandhi, K., Goyal, A. and Lal, D. (2014). Standardization of solvent fractionation technique for detection of adulteration in ghee by enriching animal body fat and vegetable oil in different fractions. Indian Journal of Dairy Science. 67 (4):323-327.\n5.\tGandhi. K., Upadhyay, N., Aghav, A.D., Sharma, V., and Lal, D. (2014). Detection of adulteration of ghee (clarified milk fat) with palmolein and sheep body fat using Reichert-Meissl (RM) value coupled with solvent fractionation technique. Indian Journal of Dairy Science. 67(5): 387-393. Received Second Best Paper Award during 44th Dairy Industry Conference organized by ICAR-NDRI, Karnal and Indian Dairy Association from 18-20, February 2016.\n6.\tAghav, A.D., Gandhi, K., Upadhyay, N., Kumar, A. and Lal, D. (2014). A study on the physico-chemical changes occurring in the milk fat during preparation of Paneer. Indian Journal of Dairy Science. 67 (5): 398-404.\n7.\tKumar, A., Upadhyay, N., Gandhi, K., Lal, D. and Sharma, V. (2013). Detection of soybean oil and buffalo depot fat in ghee using Normal-Phase Thin Layer Chromatography. Indian Journal of Dairy Science. 66(4): 294-99. ISSN: 0019-5146.\n8.\tKumar, A., Upadhyay, N., Gandhi, K., Kumar, A., Lal, D. and Sharma, V. (2013). Reverse-Phase Thin Layer Chromatography of Unsaponifiable Matter of ghee for detecting adulteration with soybean oil and buffalo depot fat. Indian Journal of Dairy Science. 66(6): 496-501. ISSN: 0019-5146.\n9.\tUpadhyay, N.*, Dabur R.S. and Rathi, M. (2011). Development and Shelf life Study of Flavoured Whey-soya milk beverage. Indian Journal of Dairy Science. 64(2): 92-101. ISSN: 0019-5146.\nOther Journals\n1.\tDewan, A., Meena, G.S., Upadhyay, N., Barapatre, R. Singh, A.K., Rana, J.S. (2017). Formulation of non-Gluten Pasta from the Optimized levels of Dairy and Non-Dairy ingredients. Madridge Journal of Food Technology. 2(2): 92–98. \n2.\tGalmessa, U., Prasad, S., Kumaresan, A., Oberoi, P. S., Baithalu, R. K., Upadhyay, N., and Dang, A. K. (2015). Modulation of Milk Fatty acid profile milk yield and composition through supplementation of omega-3 fatty acid in transition cow’s diet. Journal of Science and Sustainable Development. 3(1): 25-38. ISSN: 2070-1748\nREVIEW ARTICLES\n1.\tUpadhyay, N.*, Goyal, A. Kumar, A., Lal, D. and Singh, D. (2014). Preservation of milk and milk products for analytical purposes: A review. Food Reviews International. 30(3):203-224. DOI 10.1080/87559129.2014.913292. ISSN: 1525-6103\n2.\tGoyal, A., Sharma, V., Upadhyay, N., Gill, S. and Sihag, M. (2014). Flax and flaxseed oil: an ancient medicine & modern functional food. Journal of Food Science and Technology. 51(9): 1633-1653. DOI 10.1007/s13197-013-1247-9. ISSN: 0975-8402. \nBOOK CHAPTERS\n1.\tKumari, L., Sharma, M., & Upadhyay, N. (2021). Three-Dimensional Printing of Food Products: Printing Techniques, Novel Applications, and Printable Food Materials. Handbook of Research on Food Processing and Preservation Technologies: Volume 3: Computer-Aided Food Processing and Quality Evaluation Techniques, 55. Boca Raton, CRC Press\n2.\tUpadhyay, N.*, Harshitha, C. G., Pathak, N. K., & Sharma, R. (2021). Fourier Transform Infrared (FTIR) Spectroscopy with Chemometrics: Evaluation of Food Quality and Safety. Handbook of Research on Food Processing and Preservation Technologies: Volume 5: Emerging Techniques for Food Processing, Quality, and Safety Assurance, 271.\n3.\tNagarajappa, V., Upadhyay, N., Chawla, R., Mishra, S.K., & Nath, S. (2019). Functional Properties of Milk Proteins. In: Engineering Practices for milk products- Dairyceuticals, Novel Technologies, and Quality (pp 3-26). Apple Academic Press.\n4.\tUpadhyay, N., Kumar, M. C. T., Sharma, H., Borad, S., & Singh, A. K. (2019). Pulse Electric Field Processing of Milk and Milk Products. In: Non-thermal Processing of Foods (pp.129-144). Boca Raton, CRC Press\n5.\tUpadhyay, N., Nagaraj, V., & Singh, A. K. (2019). Advances in Fractionation of Milk Lipids: Analysis and Applications of fractions In: Recent Technologies in Dairy Science (pp. 325-344). Today and Tomorrow’s Printers and Publishers.\n6.\tNagaraj, V., Upadhyay, N.*, Nath, B. S., & Singh, A. K. (2018). Advances in Fractionation and Analysis of Milk Carbohydrates. In Technological Approaches for Novel Applications in Dairy Processing (pp. 127-147). IntechOpen. http://dx.doi.org/10.5772/intechopen.76312\n7.\tUpadhyay, N.*, Veena, N., Borad, S., & Singh, A. K. (2017). Application of Natural Antioxidants in Dairy Foods. In Natural Antioxidants (pp. 281-318). London: Apple Academic Press.\nINSTITUTE PUBLICATION\n1.\tDr. T. K. Datta, Dr. Meena Malik and Dr. Neelam Upadhyay (2017). Foundation Programme for Freshers at ICAR-NDRI 2017.\nPOPULAR AND LEAD ARTICLES\n1.\tPatil, A. T., Meena, G. S., Upadhyay, N., & Singh, A.K. (2017). Milk protein concentrates- Their Applications. Indian Dairyman, 69(9), 44-48.\n2.\tUpadhyay, N.* and R.K. Malik (2015). Nutritive Value of Milk. In: In Touch, Heinz Nutrition Foundation of India. Volume 17, Number 2&3, 2-11. (Lead Article). \n3.\tGoyal, A., Sharma, V., Upadhyay, N., Sihag, M. and Kaushik, R. (2013). High Pressure Processing and its impact on milk proteins: A Review. Research and Reviews: Journal of Dairy Science and Technology. 2 (1): 1-9. ISSN: 2319-3409.\n4.\tKumar, A., Upadhyay, N., and Naagar, S. (2012). Allergenicity of Milk Proteins, and its Management. Indian Food Industry. 31 (5&6): 45-50. ISSN: 0972-2610.\n5.\tGoyal, A. and Upadhyay, N. (2012). Nuclear Magnetic Resonance Spectroscopy in Dairy Science. Indian Food Industry. 31(1): 39-45. ISSN: 0972-2610.\n6.\tUpadhyay, N.*, Goyal, A. and Rathod, G. (2011). Microwave Spectroscopy and its applications in online processing. Indian Food Industry. 30(5&6): 63-73. ISSN: 0972-2610.\n7.\tउपाध्याय, नी*. (२०१८) भारत में कुपोषण: स्थिति और इससे निपटने के लिए रणनीतियाँ. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. २४-२९. \n8.\tउपाध्याय, नी.*, सिंह, आ.कु., गांगुली, स., सबिखी, ल. (२०१८) खाध्य और डेयरी क्षेत्र मे महिला उद्यमिता: कारण, समस्याए एवम उपलब्ध मंच. दुग्ध—गंगा (आठवाँ अंक). अप्रैल-सितम्बर. ६४-६९.\n9.\tउपाध्याय, नी*. (२०१९) ek¡ dk nw/k % f'k'kqvksa ds ekufld] 'kkjhfjd ,oa lkekftd mRFkku gsrq ve`r. दुग्ध—गंगा (नवाँ अंक). अकटूबर –मार्च १०२-१०४.\n10.\tउपाध्याय, नी*, fç;k ;koys (२०१९) [kk| inkFkksaZ esa —f=e ds cnys çk—frd jax o.kZd ds mi;ksx dh vko';drk दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १०२-१०५.\n11.\tuhye mikè;k;, fuys'k dqekj ikBd (२०१९) d`f\"k] [kk| ,oa Ms;jh m|ksx ds Hkfo\"; eas lkSj ÅtkZ dk egRo दुग्ध—गंगा (दसवाँ अंक). अकटूबर –मार्च १२६-१३०. \n12.\tवैज्ञानिक और तकनीकी विषय के मूल हिंदी लेख जोकि गेहूँ एवम् जौ स्वर्णिमा में प्रकाशित हुए: उपाध्याय, नी*, राकेश कुमार (2020) महिला उद्यमिता के माध्यम से महिला सशक्तिकरण. गेहूँ एवम् जौ स्वर्णिमा (बारहवााँ अंक), पृष्ठ सं. 55-58; भाकृअनुप- भारतीय गेहूँ एवम् जौ अनुसंधान संस्थान, करनाल- १३२००१ द्वारा प्रकाशित\n\n8. Concepts/Processes/Products/Technologies/Patents/Others\n(i)\tConcepts \nCurrently, I am working on the integrated approach of application of green technology for the development of functional foods by utilizing under-utilized/ indigenous fruits and vegetables and/ or bio-waste. In the research projects, I am also keenly working on food chemistry and instrumental food analysis and applications of technologies/ products in dairy and non-dairy products. \nBesides this, I am working on development of functional food for addressing menopausal symptoms in osteopenic mice model. \n(ii)\tProducts/ Technologies ready for commercialization- 5\n1. Production of Milk Protein Concentrate 60 (MPC60), a high protein low lactose powder from buffalo milk (Co-Inventor)\n2. Technology for omega-3 rich mixed fat table spread (Inventor)\n3. Lipid and water soluble yellow natural colouring ingredient from bio-waste (Inventor)\n4. Technology for preparation of encapsulated flaxseed oil for its applications in foods (Inventor)\n5. Production of buffalo milk based Milk Protein Concentrate 60 (MPC60) powder with improved solubility (Co-Inventor)\n(iii) Expertise on\n1.Gas Liquid Chromatography\t5.Thin Layer Chromatography\n2.Fourier Transform Infra-red Spectroscopy\t6. Spectrophotometry\n3.Differential Scanning Calorimetry\t7.Chemical analysis including titration, distillation, etc.\n4.High Pressure Liquid Chromatography\t\n\n\n9. List of completed, on-going and submitted projects\nTitle of Project\tDuration\tRole\tFunding\tStatus\tRemarks\nEffect of storage on Baudouin test, sesamin test and RP-TLC test to detect adulteration of vanaspati and vegetable oils in ghee\t2015-2017\tCo-PI\tICAR-NDRI\n\tCompleted\tTwo research articles on RP-TLC\nPreparation and Characterization of Micro/nano delivery systems for “green” carotenoids\t2016-2019\tPI\t-Do-\t\t3 research articles+ 3 products/ technologies\nTechnology Development for the Production of Milk Protein Concentrate (MPC60) From Buffalo Milk\t2016-2019\tCo-PI\t-Do-\t\t4 research articles+ 2 products/ technologies\nTechnology of Goat Milk based Functional Beverage\t2017-2020\tCo-PI\t-Do-\t\tOne oral presentation\nTechnology for Moringa oleifera enriched cheese spread\t2020-2023\tPI\t-Do-\tOn-going\tCharacterization and incorporation of M. oleifera- pods in cheese spread is complete; shelf life study and animal trial is in progress\nDevelopment of flaxseed-rich probiotic dairy foods to address menopause symptoms\t2020-2023\tCo-PI\tDST\t\tDeveloped method -estimation of phytoestrogen; validation -in progress\nNutritional and therapeutic validation of chhachh and ghee prepared from indigenous cows by traditional method\tThree years (proposed)\tPI\tSEED Division, DST\tSubmitted \n \t\nCharacterization of Moringa oleifera leaves for functional bioactives and its application in table spread as model food system\tThree years (proposed)\tPI\tSYST, DST\t\t\nOther research work: \nDetection of adulteration of goat body fat and pig body fat in ghee using ATR-FTIR coupled with chemometrics; carried out during Professional Attachment Training at ICAR-CIPHET, Ludhiana\n\n\n\n10. Awards & honours \nName of Award\tYear\tAwarding Agency\nBest Paper Award\t2022\tGSAT (Gender Advancement for Transforming Institutions Self-Assessment Team), NDRI\nBest Poster Award\t2021\tNational Conference on Moringa Food Conclave-2021\nYoung Woman Scientist Award\t2020\tAgro Environmental Development Society during International Web-conference \nSecond Best Poster Award\t2020\tIndian Dairy Association\nCommendation certificate for Institute’s Magazine in which I am co-Editor\t2020\tTown Official Language Implementation Committee, Karnal\nLetter of Appreciation to editorial board of Institute’s magazine for receiving ICAR’s Second Prize and Trophy under Ganesh Shankar Vidyarthi Hindi Patrika Puraskar (2018-19)\t2020\tICAR- National Dairy Research Institute, Karnal\nAssociate Fellowship\t2019\tNational Academy of Dairy Science India\nFirst Prize in E-poster \t2018\tIndian Dairy Association\nOne Best oral Presentation\t2018\tHome Science Association of India\nBest Oral Presentation to my Master’s student\t2018\tICMR- National Institute of Nutrition\nBest Poster Award\t2016\tIndian Dairy Association\nSecond Best Paper Award\t2016\tIndian Dairy Association\nICAR-SRF (PGS) with 2nd rank\t2011-12\tICAR\nGATE (Engg Sciences: Food Tech; Thermodynamics)\t2010\tMHRD, GoI\nInstitution level awards\nThird prize in poster presentation \t2021\tICAR- National Dairy Research Institute, Karnal\nInstitute’s Rajbhasha Gaurav Certificate\t2020\t\nFirst prize in Scientific and Technical writing\t2019\t\nConsolation prize in Scientific and Technical writing \t2020, 2019 \t\nFirst prize in Poster Presentation- 2020, 2018, 2017\t\t\nThird prize in poster presentation\t2019\t\nFirst Prize in hindi extempore\t2017\t\nThird, first and second prize in hindi essay writing in consecutive years – 2020, 2019, 2018\t\t\n\n\n11. Teaching Assignments \n(a) Teaching: Actively involved either as course in-charge or associate \nClass\tB.Tech (DT)\tMSc/ MTech\n(FT) (till 2021)\tM.Tech (DT)\tPhD (DT/ DC/ FSQA)\nNo. of courses\t1-2\t2-3\t0-1\t2-3\nDT- Dairy Technology, DC- Dairy Chemistry, FT- Food Technology, FSQA- Food Safety Quality Assurance\n(b) Student’s guided\nDegree\tMajor Advisor \tCo-Advisory\tStatus/ Remarks\nM. Tech (DT)\t8\t2\tCompleted\n\t1\t0\tOn going\nM. Tech/ M Sc (FT/ FSN)\t2\t1\tCompleted\nM. Tech (DC)\t0\t3\tCompleted\nM. Tech (DM)\t0\t1\tCompleted\nPhD (DT)\t2 \t0\tOngoing \n\t0\t2\tCompleted\nPhD (DC)\t0\t1 \tCompleted\n\t\t1\tOn going\ni.\tThree students under my guidance as major advisor and one student as co-advisory member nominated for Best thesis award; \nii.\tOne represented NDRI at zonal-level student research convention ANVESHAN-2018\n\n12. Lectures/ member/convener of committees: \ni.\tLectures: \na.\tEntrepreneurship Development Programme (EDP) (conducted by SINED-TBI/BPD unit, ICAR-NDRI) and Online Training of Master Trainers on Fat and Oilseed processing conducted by SINED-TBI/BPD unit (ICAR-CIPHET); \nb.\tStudent’s Counselling session at SRCASW, University of Delhi, \nc.\tWorkshop conducted at DAV college, Karnal, etc\nd.\tDelivered talks at various villages on the importance of mother’s milk, nutrition in first 1000 days of an infant’s life, nutri-thali, etc\nii.\tTraining Organized: \na.\tTwenty one days Training at Centre for Advanced Faculty Training (DT Division) on ‘R & D strategies and interventions for effective agribusiness and entrepreneurship development in dairy and food sector’; \nb.\tone/two months or shorter duration trainings for students and others under BPD unit and KVK, NDRI, Karnal\nc.\tFive days training on the aspects of dairy processing to the farmers of Karnal district. \niii.\tGeneral Secretary, Staff Club, NDRI, Karnal\niv.\tMember: Student Empowerment Unit, Conferences organized from 2015 till 2018, convocation, credit seminar evaluation committees; Mera Gaon Mera Gaurav program, Farmer’s First Door programme, Swatchh Bharat Abhiyan, coordinator and mentor of different groups for organizing Foundation Program-2017, 2018, Nodal officer of Poshan Maah-2020 etc\nv.\tConvener/ Rapporteur of sessions: Conference, Dr. K. K. Iya Memorial oration; International conference of Proteomics Society of India\nvi.\tOther responsibilities: Management Representative of QMS-IS/ISO 9001:2008 and HACCP- IS 15000:2013 of Experimental Dairy (essential part of institute) until Jan 2019; one of the editors of Institute hindi magazine Dudgh Ganga which also received coveted award from ICAR (until 2019).\nvii.\tResource Generation on account of consultancy provided in field of dairy processing and by conducting sponsored trainings \nMore than ₹ 2 50 000/- (Two lakhs fifty thousand only)\nviii.\tBesides research, teaching and extension activities, I am also involved in promotion of Hindi language and have won several prizes during competitions (like extempore, essay, e-mail writing) organized by Official Language Units.\nix.\tLifetime Member of three scientific bodies: Indian Dairy Association- RE/NZ/LM/10852/HR; Association of Food Scientists & Technologists (INDIA)- AFST/LM/9-2018/KRN/2444; Lifetime member of Home Science Association of India; Membership number: HSAI-2017-HR-127-LF\nx.\tReviewed research papers of Journal of Ayurveda and Integrative Medicine (Elsevier), LWT, International Journal of Food Properties, Indian Journal of Dairy Science, Indian Journal of Natural Products and Resources, United Scientific Group, etc. \n\n\n\n\n\n\n\n\nDated: 12-04-2022\t \nNeelam Upadhyay",institutionString:"National Dairy Research Institute",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"National Dairy Research Institute",institutionURL:null,country:{name:"India"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"444312",firstName:"Sara",lastName:"Tikel",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/444312/images/20015_n.jpg",email:"sara.t@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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1. Introduction
At present the use of anticoagulants is very wide; about 0.7% of the population in the west receives anticoagulant treatment. Basic anticoagulant therapy is a vitamin K antagonist; a derivative of warfarin, which is most commonly used, is coumadin (warfarin). This drug has been used for more than 50 years and is consistently able to eliminate recurrent venous thrombosis at adequate doses. However, warfarin has disadvantages, namely, the interaction with other drugs and with food, slow onset and excessive effects, and a narrow therapeutic range. Drug responses and pharmacodynamics are varied and unpredictable, so routine monitoring is needed. For most patients who take drugs in the long term, this is quite troublesome [1].
The current world medical need is to find anticoagulants that are more effective and safer than warfarin for both doctors and patients in long-term use. Responding to this need, a new drug is needed that can change molecules that are difficult to absorb to be easily absorbed through the digestive tract; this is used as the basis for making oral preparations of unfractionated heparin (UFH). In theory the use of the oral form of heparin or low molecular weight heparin (LMWH) is given at fixed doses, two or three times a day, and does not require overly frequent coagulation monitoring checks or dosage adjustments which are too tight, and the potential for interactions between drugs and medications is also low, making this drug an anticoagulant needed for long-term use [1].
Coagulation monitoring for patients receiving heparin therapy is very important. This is intended to obtain a range of heparin therapy that is effective in reducing the incidence of thrombus and bleeding. The effective use of heparin anticoagulant therapy must increase the activated partial thromboplastin time (APTT) value from 1.5 to 2.5 times. This value is equivalent to levels of heparin 0.2–0.4 U/mL based on protamine titration and is equivalent to anti-Xa levels 0.3–0.7 U/mL [2]. This chapter will discuss laboratory tests that are used to monitor patients receiving heparin therapy.
2. Development of heparin
Heparin is the oldest anticoagulant used in medicine. Heparin was discovered by McLean in 1916 while trying to isolate thromboplastic agents. Heparin is a polysaccharide from the class of glycosaminoglycans (GAG) which naturally appears on all mast cells. Further research in 1935 resulted in clinical use of heparin. Since then, heparin has been widely studied for various applications and modifications [3].
Unfractionated heparin (UFH) is a product of GAG purified from animal tissue, most often from pig intestines. Heparin provides indirect anticoagulant properties by binding to antithrombin III (ATIII) and facilitating the inhibitory effects possessed by AT on thrombin and activated X factor (factor Xa). It is known that only UFH contains at least 18 saccharide sequences that can affect AT activity and thrombin, whereas UFH with a series of certain pentasaccharides can inhibit the activity of factor Xa [3] (Figure 1).
The heterogeneity of the structure of the UFH causes extensive bioactivity and physiological activity. Some heparin chains bind to other plasma proteins and have an effect on bone metabolism resulting in osteoporosis or heparin-induced thrombocytopenia (HIT) and other unpredictable effects that require continuous monitoring. Further research and discoveries resulted in low molecular weight heparins (LMWH) in the late 1970s to early 1980s; this was to find anticoagulants which were more predictable in their activities [4]. LMWH, such as enoxaparin, dalteparin, and tinzaparin, is made by chemical control or enzymatic cutting of UFH in a depolymerization reaction.
This controlled process produces fragments with lower molecular weight and more predictable action than UFH. As a result, side effects are lighter than UFH, monitoring needs are decreased, and bioavailability increases, making LMWH potentially used for outpatients. This makes LMWH the standard of care replacing UFH except in certain cases such as kidney failure and acute coronary syndrome where UFH is still preferred because the liver clearance is lighter and better reversible with protamine sulfate [5].
Ultralow molecular weight heparin (ULMWH) was discovered in early 2000 through a process of chemical synthesis. The reason is to get agents with lighter side effects but have the same or better anticoagulant effect which causes a higher anti-factor Xa ratio to antithrombin activity [6].
Figure 1.
Mechanism of heparin in the coagulation cascade. Box A: AT (red) binds to a heparin fragment (green) with any series length provided that certain pentasaccharide bonds can inhibit factor Xa. Box B: AT (red) binds to heparin (green) with a chain length > 17 U of disaccharide that can inhibit thrombin (factor IIa) [3].
3. Structure and biosynthesis of heparin
Heparin is a polydisperse and highly sulfated GAG with a molecular weight between 5 and 40 kDa. The structure of the complex contains repetitive disaccharide units that contain uronic acid residues (l-iduronic (IdoA) or d-glucuronic acid (GlcA)) and N-acetyl-d-glucosamine. The biosynthesis process of heparin starts in the endoplasmic reticulum and the Golgi apparatus of mast cells. The tetrasaccharide link attaches to the residue of serine in the core protein, serglycin, and then adds a unit of d-glucuronic acid (1→4) N-acetyl-d-glucosamine disaccharide. Disaccharide sulfonation and epimerization of glucoronate to iduronate are carried out by various enzymes in the biosynthetic pathway. In total there are 12 enzymes involved in this pathway, which act together to form the desired molecule. These involved enzymes have many isoforms, which cause heterogeneity of heparin and allow these enzymes to directly biosynthesize associated GAG, heparin sulfate. The degree of sulfation and sulfate residue allocation depends on the spectrum of activity of the product. In mast cell degradation, peptidoglycan heparin changes to GAG heparin through protease and β-endo glucuronidase activity [3].
Figure 2.
Heparin biosynthesis.
The first glycosaminoglycan-protein bonding region is formed due to glycotransferase activity. Repeated disaccharide units undergo elongation by GlcA and GLcNAc transferase. Modified chains include N-deacetylation and N-sulfonation, O-sulfonation, and epimerization, which then occur due to specific enzyme activity. The monosaccharide symbol in this figure follows the symbol nomenclature for glycan (SFNG) system [3] (Figure 2).
4. Mechanism of heparin as an anticoagulant
Heparin has anticoagulant effects through interactions with coagulation factors and inhibitors. Coagulation is a complex process involving proteins, platelets, and cellular components such as endothelium and monocytes. The balance of hemostasis is maintained if the activity of procoagulant can be balanced with an inhibitor. The main inhibitor of plasma coagulation factor is AT, which acts on active coagulation factors such as FXIIa, FXIa, FXa, FIXa, FVIIa, and FIIa. These coagulation factors are serine proteases, so AT is a serine protease inhibitor (serpin).
Heparin, acting as a catalyst, provides anticoagulation activity by potentiating other AT and serpin inhibitor activities (Figure 3). The interaction of heparin with AT requires a certain sequence of pentasaccharides, but not so with other serpins. Another important heparin-binding inhibitor on the extrinsic pathway is tissue factor pathway inhibitors (TFPI) [7, 8, 9].
Figure 3.
Interaction of the coagulation factor with serpin. The blue line shows the place of inhibition of each serpin [11]. TFPI, tissue factor pathway inhibitor; AT, antithrombin; HCII, heparin cofactor II.
Antithrombin (AT) under conditions when it does not bind to heparin is a slow-acting serpin, because the reactive center loop is partially folded to the center of the b-sheet structure. When binding to heparin, AT inhibition activity will increase significantly, which is a characteristic of serpin. The high-affinity pentasaccharides in heparin bind to antithrombin through two stages: first, the initial binding process involves three monosaccharide units and initiates conformational changes to AT, and then after the interaction is complete, AT conformation after activation by heparin is stabilized. This conformational change is transmitted to the AT structure, causing the opening of the reactive center loop and an increase in exosite exposure from AT which binds directly to FXa [10].
4.1 Inhibition of antithrombin in factors IIa and Xa
Active AT conformation caused by pentasaccharides is sufficient to increase inhibitory activity in FXa, a protease that converts prothrombin to thrombin (FIIa). Factor Xa interacts directly with AT in specific exosite exposed when binding to heparin. In addition, in the presence of calcium, a single heparin chain can bind directly to AT and FXa, increasing AT-FXa interactions, but this is not absolutely necessary. This calcium-dependent effect can account for reports of calcium-induced-specific molecules during the FXa inhibition process by AT [12]. Heparin-mediated FXa binds to AT, indicating the longer heparin chain will increase its affinity with the presence of Ca2+ and will strengthen inhibition [13].
Unlike FXa, the potentiation of thrombin inhibition by AT requires an additional 13 saccharide chains attached to the nonreductive end of the pentasaccharide sequence, so thrombin and AT are bound to the same heparin molecule. Thrombin interacts with heparin in exosite II, which is basically a different method with AT; no specific heparin is needed for this interaction [14].
4.2 Inhibition of antithrombin in other coagulation factors
Antithrombin also inhibits several other protease coagulant factors. The way antithrombin blocks FIXa is similar to FXa, which binds to the same exosite on AT. The high-resolution crystal structure of the pentasaccharide-FIXa-AT complex shows that one pentasaccharide binds to AT and the second binds to exosite from FXa, which allows a relationship between the two proteins with one molecule of heparin [13].
The ability of heparin to increase AT inhibition in FXI and kallikrein in the intrinsic coagulation pathway is relatively limited compared to FXa and thrombin. It should be noted that FXI activity in AT mutants that bind to the heparin site is still slightly potentiated by heparin, suggesting that there is a direct interaction between heparin and FXI involved in the binding sites of potential heparin found in the FXI catalytic domain [11].
Antithrombin inhibits the FVIIa complex in the extrinsic pathway, and this effect is reinforced by fondaparinux, LMWH, and UFH. Direct and calcium-dependent interactions are found between FVIIa and heparin [11].
4.3 Other serpins activated by heparin
Heparin cofactor II (HCII), another serpin potentiated by heparin, is a coagulation inhibitor that only inhibits thrombin. HCII is also reported to inhibit chymotrypsin and neutrophil cathepsin G. Heparin cofactor II is found in plasma at the same level as AT, but HCII cannot replace AT if there is a deficiency. HCII deficiency has no effect on the coagulation system but results in increased formation of an occlusive arterial thrombus after endothelial damage. In vivo HCII is potentiated by dermatan sulfate, which is found in the walls of blood vessels. HCII activated by dermatan sulfate may play a role in preventing excessive thrombosis of injured blood vessels [15].
Heparin and dermatan sulfate both potentiate inhibition of thrombin through HCII in several stages. Unlike AT, HCII does not require a certain series of heparin to interact. Other polyanions can also bind to HCII. The HCII bond with heparin causes conformational changes similar to AT while also releasing thrombin-binding N-terminal tail. The combination of reactive center loop expulsion initiated by GAG by exposure to exosite protease-binding is controlled by AT and HCII in the opposite way [16, 17].
Protein C inhibitors (PCI) regulate the activity of activated protein C (APC), which is the active form of zymogen protein C. Protein C is converted to APC by thrombin and in its active form acts as an anticoagulant by inactivating FVa and FVIIIa, in the presence of protein cofactors S. PCI regulates coagulation inhibitors, in this case acting more as a supporter of coagulation than inhibiting coagulation. The bond of heparin to PCI strengthens the inhibition of APC and FXa in the presence of calcium. A long chain of heparin is needed to strengthen APC inhibition, which suggests both PCI and protease require simultaneous bonding with heparin. The basic structure of the PCI complex with heparin and thrombin if separated, binding sites for heparin will appear involving the H helix, which is located close to the reactive loop [18].
The importance of protease nexin (PN)-1 in the last biology and hemostasis is known. In vitro serpin is known to have an effect of approximately 100 times faster than AT, and heparin increases about 3 times. In vivo PN-1 does not contribute to the activity of heparin as an anticoagulant because its concentration in plasma is very low; on the contrary, PN-1 is found to bind to the cell surface in several organs and tissues, including blood vessel walls. Protease nexin (PN)-1 is detected in platelet granules on the platelet surface and secreted during platelet activation. In this context, the contribution of PN-1 to antithrombotic activity from heparin in vivo is ignored [19].
The crystal structure of PN-1 is obtained from the breakdown of complexes with heparin and thrombin. This protein has a typical serpin fold with the heparin-binding site in helix D. Contrary to AT, heparin-binding site PN-1 and thrombin are not parallel when the reactive center loop of PN-1 productively interacts with the active part of thrombin. The initial formation of the ternary complex between PN-1 and thrombin and heparin can be said to be the initial phase of two-phase interaction, with loss of heparin-thrombin interactions when covalent complex PN-1 thrombin is formed. Heparin is not released when forming the PN-1-thrombin complex; this shows that the PN-1-thrombin complex is still bound to HS on the cell surface [11, 20].
Protein Z-dependent proteinase inhibitors are known to inhibit both FXa and FXIa. Heparin speeds up this reaction 20–100×. The heparin-binding site on protein Z-dependent protease inhibitors involves basic residues in helix D (such as AT) and helix C (unlike AT), and the presence of unstructured N-terminal ends can indicate similarities with HCII [21].
Other serpins, c1inh, inhibit both the complement cascade and the intrinsic pathway, where the coagulation system and innate immune system interact. Clinical deficiency leads to congenital angioedema through excessive contact system activity. The effects of c1inh are not limited to complement and contact systems. Heparin potentiates the activity of the c1inh, and the crystal structure of the c1inh indicates a different model of activity against different protease and heparin-binding sites against AT [22].
Tissue factor pathway inhibitors (TFPI) are structurally serpin, but not serine protease inhibitors. Tissue factor pathway inhibitors (TFPI) are major inhibitors in the extrinsic pathway. The heparin-binding TFPIα isoform contains an acidic N-terminal region, three Kunitz domain pairs, and a basic C-terminal end. Kunitz domain is involved in anticoagulant activity, with the first domain inhibiting the FVIIa-tissue factor complex and the second domain inhibiting FXa. The C-terminal circuit in TFPI has a high affinity for heparin. Heparin injection releases TFPI bound to the endothelium to the circulation. Heparin bound to TFPI potentiates inhibitory activity in both free FXa and FXa in the FVIIa-TF-FXa complex [11].
5. The drug derivate heparin
5.1 Unfractionated heparin
Unfractionated heparin (UFH) is one of the most commonly used parenteral anticoagulants to treat or prevent thromboembolism and has been used for almost a century. This drug is used in various methods, such as systemic use, through a catheter, extracorporeal, or on the surface of a medical device to prevent thrombotic complications. Heparin depends on the presence of antithrombin (AT) to inhibit clotting factors, so heparin is called an anticoagulant which acts indirectly. Heparin does not have fibrinolytic activity and will not lyse the thrombus [23].
Heparin contains an active pentasaccharide sequence that binds AT. The active pentasaccharide sequence responsible for catalyzing AT is found in one third and one tenth of the UFH and LMWH chains. After heparin binds and activates AT, heparin can release AT and bind other ATs, thus providing a continuous anticoagulant effect. This bond produces conformational changes that accelerate binding of AT and inactivation of coagulation factors XIIa, XIa, Xa, and IXa and thrombin (IIa). Thrombin and factor Xa are the most sensitive to inhibition by the heparin/AT, and tenfold thrombin complex is more sensitive to inhibition than factor Xa [23, 24].
The inhibition of UFH on thrombin requires binding of coagulation enzymes and AT through high-affinity pentasaccharides, whereas inhibition of factor Xa requires only heparin binding to AT. By deactivating thrombin, heparin not only prevents fibrin formation but also inhibits platelet activation induced by thrombin and coagulation factors V and VIII. In addition to its anticoagulation effects, heparin increases the permeability of blood vessel walls, suppresses smooth muscle proliferation, suppresses osteoblast formation, and activates osteoclasts [23, 24].
5.1.1 Pharmacokinetics and pharmacodynamics
Intravenous (IV) or subcutaneous (SC) injection is the route available for UFH administration, and IV is the most frequently used route. When given by SC injection for therapeutic anticoagulation, the dose must be large enough (30,000 U/day) to compensate for the low bioavailability of UFH, as can be seen inTable 1. UFH is already bound to plasma proteins, which results in variations in anticoagulant responses [25].
Characteristics
Heparin
LMWH
Origin
Pig intestine
Pig intestine
Molecular weight (Da)
15,000
5000
Target
Xa:IIa
Xa > IIa
Bioavailability (%)
30
90
Half-life (h)a
IV depends on doses 1–3
3–7
SC depends on doses 2–5
Reversal by protamine
Complete
Partial (60–80%)
Renal excretion
Depends on dose
Yes
Occurrence of heparin-induced thrombocytopenia (%)
UFH clearance depends on the dose and occurs through two independent mechanisms. The initial phase is a fast and saturated bond in endothelial cells, macrophages, and local proteins where UFH is depolymerized. The second phase is slower and unsaturated clearance through the kidneys. At therapeutic doses, UFH is cleared mainly through depolymerization, where higher molecular weight chains are cleared faster than those with lower weight. When clearance tends to the kidneys, an increase or extension of the dose of UFH provides a disproportionate increase in both the intensity and duration of the anticoagulant effect. Anticoagulant responses to UFH administration are usually monitored using activated partial thromboplastin time (APTT). APTT must be measured every 6 hours with IV administration and the dose adjusted until the patient has reached a stable level of therapy. After a stable condition is reached, the frequency of monitoring can be extended [24, 26].
5.1.2 Monitoring
The UFH anticoagulant response is monitored using APTT, a measurement that is sensitive to inhibition of thrombin and FXa. APTT examinations have a large variety of reagents (even the same reagents have different lots) so that they have varying sensitivity to the anticoagulant effect of UFH. Each laboratory must ensure that their therapeutic range of heparin and APTT is based on levels of heparin measured by anti-Xa (target range 0.3–0.7 U/mL) or protamine titration (0.2–0.4 U/mL). APTT must be measured every 6 h based on UFH half-life and the dose adjusted until the patient reaches the therapeutic level based on the APTT target range. When APTT values are obtained in the treatment range twice in a row, monitoring can be extended to one or two times a day depending on the clinical scenario. Weight-based dose nomograms, consisting of bolus doses and infusion droplet speeds with regular monitoring using APTT, are recommended for the treatment of thromboembolic disease [25].
The UFH dose nomogram differs in each hospital due to differences in thromboplastin reagents, calibration, and interlaboratory standards in APTT measurements. This causes the need for alternative monitoring methods. Functional heparin, also known as anti-Xa, has been promoted as a more reliable measure of UFH because it is not sensitive to factors other than UFH, such as concomitant use of warfarin, sodium citrate in the sample tube, impaired lupus anticoagulant (LA), increased factor activity VIII, and liver disease [25].
Acquired inhibitors, such as LA, cause an extension of APTT, which results in not being able to accurately measure the level of anticoagulation due to UFH. In this case, if APTT is maintained within the usual therapeutic range, it may result in underdose of UFH and cause development or recurrence of thrombosis. Simultaneous testing of APTT and anti-Xa levels is needed to estimate the APTT value of therapy in patients receiving heparin [27].
5.2 Low molecular weight heparin (LMWH)
LMWH is a polysaccharide derived from the pig’s intestine containing an active pentasaccharide sequence which is needed for anticoagulant activity as in UFH. LMWH is produced from UFH through chemical or enzymatic degradation. Each LMWH product is prepared by a different method. Clinical development of LMWH driven by certain observations includes the reduction of thrombin activity in relation to anti-factor Xa activity, the ratio of benefits or risks that are more favorable in animal studies, and good pharmacokinetic properties. The molecular weight of the LMWH is approximately one third of the molecular weight of UFH (4000–5000 Da). Because of their smaller size, LMWH has a lower affinity for thrombin because they cannot bind AT and thrombin together. However, LMWH has the same affinity as UFH for FXa [23].
Factor Xa does not require heparin to stabilize its interaction with AT, so smaller molecules such as LMWH deactivate factor Xa equivalent to larger molecules such as UFH. The length of the polysaccharide chain of at least 18 saccharides, including the order of active pentasaccharides, is needed to bridge between AT and thrombin. About 25–50% of LMWH molecules are above the length of this chain. All LMWH chains contain active pentasaccharide sequences, so 100% can inactivate factor Xa [23].
5.2.1 Pharmacodynamics and pharmacokinetics
There are several biological consequences of the small size of LMWH compared to UFH, a decrease in binding of LMWH to other plasma proteins, macrophages, and endothelial cells. This resulted in a more predictable dose-response relationship and a longer plasma half-life for LMWH. In contrast to UFH, routine plasma monitoring is not needed which makes it easier for outpatient management. The lower incidence of HIT has also been investigated because of the reduced bond to PF4 and platelets. LMWH has also reduced bonds in osteoblasts resulting in decreased incidence of osteoclast activation and lower bone destruction [23].
All LMWH products have half-lives ranging from 3 to 7 h and bioavailability 87–90%. Anti-Xa peak activity occurs 3–5 h after SC injection with predictable dose-based responses. All agents are metabolized through desulfation or depolymerization, and all agents metabolized are excreted through the kidneys [25].
5.3 Pentasaccharides (fondaparinux)
Fondaparinux is a chemically synthesized anticoagulant that is specifically developed as a selective indirect inhibitor for FXa. Factor Xa is an important target for anticoagulant therapy given its position at the meeting of the intrinsic and extrinsic coagulation pathways. Its inhibition significantly decreases thrombin formation [28] (Figure 4).
Figure 4.
Formation of antithrombin complexes with FIIa and FXa. (1) Antithrombin (AT), active thrombin (FIIa), active X factor (FXa). (2) UFH (chain shape) forms a complex with AT both in FIIa and FXa. (3) Shorter polysaccharides of 18 U form AT complex with FXa but not with FIIa. (4) The sequence of pentasaccharides forms a bond with FXa only [30].
Factor Xa has one function in the coagulation cascade, as a gatekeeper to the path along the coagulation cascade. Conversely, thrombin (FIIa) has many roles in the coagulation process, including activation and mediation of endogenous anticoagulation by binding to thrombomodulin and activation of protein C. Factor Xa may be a purer target than thrombin [29].
5.3.1 Pharmacodynamics and pharmacokinetics
Fondaparinux binds non-covalently and reversibly to AT, increasing AT anticoagulant activity by up to 300 times. The AT-fondaparinux complex then binds and neutralizes FXa, which reduces prothrombin (FII) conversion to thrombin (FIIa), thereby inhibiting clot formation. Fondaparinux is then released and can catalyze other AT molecules. When AT plasma becomes saturated, excess unbound circulating fondaparinux (which has no anticoagulant activity) is excreted through the kidneys.
Because it does not affect pre-existing thrombin circulation, fondaparinux may in theory have some residual hemostatics, if needed, at the site of injury. Fondaparinux has no effect on the examination of fibrinogen platelet function, thrombin time, or antithrombin tests. Fondaparinux can affect PT and APTT and can interfere with factor VIII testing. Although not routinely recommended, if measurements of fondaparinux are needed (e.g., changes in kidney function, weight, or extreme age), the most accurate plasma concentration is measured using the anti-factor Xa test. The results of this examination are in IU/mL, which is directly proportional to the plasma concentration of fondaparinux. The results were extrapolated to the mcg/mL plasma concentration using a standard curve calibrated by fondaparinux. The test must be calibrated specifically for fondaparinux, because the use of calibration for UFH or LMWH will produce inaccurate results.
The use of fondaparinux and drugs that affect concomitant coagulation (e.g., antiplatelet, NSAIDs) results in pharmacodynamic drug interactions that can increase the risk of bleeding and should be avoided as much as possible. After stopping fondaparinux, the anticoagulant effect will last up to 4 days and even longer in patients with low clearance [31].
Fondaparinux is not absorbed through the gastrointestinal mucosa, so it must be given parenterally. Subcutaneous administration showed rapid absorption and complete absorption with 100% bioavailability. The peak plasma concentration is reached about 2–3 h after subcutaneous administration. A stable state is achieved after 3–4 doses of administering fondaparinux once a day [25].
Fondaparinux is highly protein bound and cannot be distributed to tissues without binding to proteins. The volume of distribution is 7–11 L, which is close to blood volume. Fondaparinux does not undergo metabolism in the liver and is not susceptible to the pharmacokinetics of drug interactions with the cytochrome P450 isoenzyme system substrate [25].
Reduced bonding with macrophages and endothelial cells increases the half-life of plasma fondaparinux compared to UFH and LMWH. Elimination of fondaparinux is influenced by several patient parameters, including kidney function, age, and low body weight. These factors must be evaluated regularly, because they can block the use of fondaparinux or require increased monitoring for signs and symptoms of drug accumulation [25].
5.4 Ultralow molecular heparin
Therapy using LMWH provides clear pharmacokinetic advantages over UFH, so LMWH has become the standard of care for prevention and treatment of venous thromboembolism (VTE) in patients with and without cancer. The development of the ULMWH drug is based on the theory that, because of the much higher ratio of anti-Xa and anti-IIa activity, ULMWH will be associated with similar or better antithrombotic efficacy from the efficacy achieved by LMWH products but with lower bleeding and HIT risks. ULMWH has a molecular weight of <4000 Da and an increase in anti-factor Xa activity compared to LMWH. There is only one ULMWH marketed outside the United States (bemiparin), and another, RO-14, is currently in clinical development [32].
5.4.1 Pharmacokinetics and pharmacodynamics
Bemiparin was approved for once-daily use of subcutaneous VTE primary prophylaxis in medical patients and patients undergoing general or orthopedic surgery and for prophylaxis in patients with deep vein thrombosis (DVT). Bemiparin originates from alkaline depolymerization and UFH fractionation from pig intestinal mucosa. Pharmacokinetic studies in healthy volunteers given bemiparin showed an increase in anti-factor Xa activity depending on the dose given [32].
6. Heparin therapy monitoring
Treatment using UFH requires routine monitoring to see its functional activity due to the high variation in plasma concentrations and functional activities after fixed doses in each patient. This is due to several reasons, including AT levels in plasma that are different in each patient, UFH elimination with two mechanisms that also differ in each individual, and neutralization and bonding of heparin with various activated plasma proteins and platelets. It is estimated that 10% of people are not sensitive to heparin. The nonlinear pharmacodynamics of UFH make it difficult to predict. Unfractionated heparin (UFH) is usually measured by APTT or activated coagulation time (for high levels of heparin), but this examination has a low sensitivity and is not standardized; besides, this examination is also not sensitive to the use of low-dose UFH as prophylaxis. The results also depend on the reagent and the instrument used. The reference value for this examination must be determined by each laboratory, so it is difficult to compare the results obtained from each laboratory [33].
Monitoring the therapy of coagulation UFH activity should be measured 6 h after bolus and 6 h after dose change. It takes 6 h for the heparin to reach a stable phase, so monitoring heparin therapy less than 6 h after administration gives the wrong results for determining the dose. Protamine titration is the gold standard for heparin monitoring, but this examination is not widely available and expensive, so it is only used for research [34].
Unlike UFH, LMWH has a more stable pharmacokinetics, and its bioavailability reaches 100% at any dose with subcutaneous administration. The maximum LMWH concentration in plasma is directly proportional to the LMWH dose, and many experts believe that routine coagulation monitoring during therapy is not necessary because the clinical dose of LMWH can be corrected based solely on the patient’s body weight. In a healthy population after a fixed dose of LMWH, it turns out that heparin concentration varies and only partially correlates with the patient’s body weight. More precisely correction needs to be done in some cases (e.g., low or high BMI; critical condition; kidney failure (creatinine clearance <30 ml/min); when changing anticoagulants; age (children or elderly >75 years); and pregnancy) [35].
Anti-Xa activity measurement is the most widely used examination for LMWH therapy management. This examination has a high sensitivity (lower limit of determination using chromogenic substrate is <0.03 anti-Xa IU/mL). This method is not a method of global coagulation examination because it only measures the concentration of one factor (Xa) but does not react with AT deficiency or changes in concentration from other factors that influence patient hemostasis. This method is difficult to predict thrombosis or bleeding. Until now there is still no universal and reliable method for monitoring heparin properly [30].
6.1 Activated partial thromboplastin time (APTT)
The APTT examination is currently used by most laboratories for monitoring UFH therapy. This examination uses plasma citrate from the patient and is measured based on clot formation. Phospholipids and activators are added to platelet-poor plasma (PPP) patients and then incubated. Calcium is added and then the clotting time is measured. This examination has several advantages, fast, inexpensive, and widely available, but this does not directly measure the level of heparin. Many APTT reagents are available, and each reagent has a varied response to heparin therapy, and besides that several physiological factors can influence the results of this examination [36].
The clinical condition of patients can also affect the results of APTT, but it does not correlate with the presence of bleeding or thrombosis. The most frequent cases are patients receiving vitamin K antagonist therapy. Patients with international normalized ratio (INR) of more than 1.3 because warfarin therapy can also affect APTT results in heparin monitoring. Other cases that also affected were patients with antiphospholipid antibodies, which could affect clotting tests. Coagulation factor deficiencies, such as in patients with liver disease, or consumptive coagulopathy in disseminated intravascular coagulopathy (DIC) will affect APTT results. These conditions cause heparin anticoagulation activity not to be measured properly [36].
The conditions mentioned above can prolong the APTT results and result in underdose anticoagulant doses. Factor VIII and fibrinogen are the most frequent causes and can significantly extend or shorten the APTT baseline. Patients with acute disease are also known to have a deficiency in antithrombin. This condition can lead to excessive anticoagulation when using APTT for monitoring [36].
Preanalytic variables also play a role in the APTT response in monitoring heparin. The wrong APTT results can be due to improper sampling, and less samples also make too much citrate concentration in the tube. Underdose therapy causes a high risk of thrombosis [37].
Basu et al. [38] conducted a study on patients with venous thromboembolism who received heparin therapy and found the risk of recurrent thromboembolism associated with the APTT ratio which did not reach 1.5–2.5 times the normal value. This ratio is used as a standard for therapeutic ranges. Based on this study, the authors mention that the ratio is equivalent to levels of heparin 0.2–0.4 U/mL based on protamine titration and is equivalent to anti-Xa levels of 0.3–0.7 U/mL. The range of anti-Xa levels is higher because of heparin clearance. Smaller heparin molecules are cleared more slowly, so LMWH has a stronger inhibitory effect on factor Xa than thrombin. Examinations that measure anti-factor Xa activity, such as anti-Xa examination, will detect higher levels than examinations that measure antithrombin activity, such as protamine titration, which utilizes thrombin time [30].
Other studies evaluated the upper limit of anti-Xa examinations related to the incidence of bleeding. This study produced anti-Xa levels of more than 0.74–0.88 U/mL related to the incidence of bleeding complications [30]. The use of the APTT standard ratio for the range of heparin therapy is difficult to apply because the response of each APTT reagent to heparin is different. Researchers from the joint study found that APTT corresponds to a concentration of heparin 0.2–0.4 U/mL with protamine titration, based on the APTT reagent used. APTT reagents from other laboratories showed different sensitivity to heparin, and a ratio of 1.5–2.5 times the normal value did not correlate with the concentration of heparin in the therapeutic range. Various types of laboratories and reagents can produce an APTT ratio of 1.6–3.7 times the normal value, which is equivalent to a level of heparin 0.3 U/mL to a ratio of 2.4–6.2 times the normal value equivalent to the level of heparin 0.7 U/mL with anti-Xa [39].
6.2 Anti-Xa activity assay
Variations in results were also obtained for each anti-Xa examination if compared with protamine titration as a reference but far smaller compared to APTT. The therapeutic range for this examination will remain to be 0.3–0.7 U/mL, although with different machines and reagents. In contrast to APTT, anti-Xa results are not affected by poor sampling, also are not affected by factor VIII or fibrinogen, and are not affected by deficiency factors in patients with liver disease and consumptive coagulopathy [30].
Anti-Xa assay is not a test of factor X activity or factor X level antigen. This examination is also called an anti-factor Xa test or a functional test of heparin. The principle of this examination is to monitor indirect factor Xa inhibitors, such as LMWH and fondaparinux, or direct factor Xa inhibitor drugs such as rivaroxaban. These anticoagulants require monitoring in certain patient populations and in certain clinical settings. Each anticoagulant requires its own anti-X curve, and this must be done by each laboratory [37].
Anti-Xa activity assay uses the chromogenic method. The known factor Xa is added to platelet-poor plasma, wherein there is heparin. Heparin strengthens the inhibition of antithrombin to factor Xa, and the uninhibited factor Xa chromogenic substrate is added. This process produces color detected by a spectrophotometer and directly proportional to the level of factor Xa. The amount of color correlates with the level of heparin in the plasma with the correct heparin curve [36].
Like other tests, the anti-Xa assay is imperfect, with the chromogenic method; this examination will be affected by the conditions of the hemolysis, jaundice, and lipemic samples, which will affect the ability of the machine to measure and distinguish chromogenic reactions. Anti-Xa reagents which are not added with antithrombin will make false low heparin concentrations in the condition of patients with severe antithrombin deficiency, but there can be a misdiagnosis of antithrombin deficiency if antithrombin is added. Viewed from the laboratory side, anti-Xa assay is considered expensive and needs special attention in the process [36].
6.3 Protamine titration
Protamine is a small protein, rich in arginine, and positively charged, has a similarity to histones, and is involved in folding and stabilizing DNA in sperm heads. Protamine can neutralize the effects of heparin through electrostatic bonds between cation arginine groups from protamine and heparin anions with a ratio of 1:1. This results in a neutral protamine-heparin aggregate which can be seen in the form of a white suspense formed in a few seconds. Binding of heparin by protamine will release the AT-heparin complex, resulting in AT activity returning to its original state [40].
Protamine titration is the gold standard for measuring UFH concentrations in plasma. The results of this examination are quite promising, but it is still not considered a good examination in terms of clinical management of UFH because it is still not automatic. UFH clinical trials determined that heparin concentrations of 0.2–0.4 U/mL with protamine titration were equivalent to APTT lengthening 1.5–2.5 times the normal values, providing safe UFH levels and good patient outcomes [41].
The principle of this examination is to measure thrombin clotting time (TCT), which is the time required for clot formation after the addition of thrombin to plasma. The presence of UFH in plasma will result in TCT prolongation depending on the dose used. Protamine competed in binding to UFH, and the results of protamine titration measurements showed the amount of protamine needed to restore TCT to baseline [42].
This method is neither expensive nor difficult, but because it is done manually, the workload is quite heavy. The results given by this examination are very dependent on two important factors, the operator that works and the origin of thrombin. Protamine titration measurements depend on the operator when identifying clot formation in the test tube, so efforts to standardize this are difficult. The reproducibility of results can be achieved by limiting operators who work on checks and equating perceptions between operators about the process of forming clots and when the test is certain to be completed.
First time this method was found, thrombin used came from rabbits or young cattle. Its concentration is determined by identifying the amount of thrombin which results in TCT 18–20 s. At present the thrombin used is from humans, so it can increase the specificity of this test. Thrombin originating from humans has different interactions with plasma patients than thrombin from rabbits and young cattle. Thrombin originating from humans also needs to be determined by calculating the amount of thrombin needed to achieve TCT 18–20 s. Each laboratory must determine the concentration of thrombin that is needed based on thrombin available in each lab [41].
UFH therapy is optimal if the levels are 0.2–0.4 IU/mL based on protamine titration. Recommendations from the American College of Chest Physicians (ACCP) suggest that the APTT target for the UFH therapy range is equivalent to 0.2–0.4 IU/mL with protamine titration of 0.35–0.7 IU/mL with anti-Xa assay [23].
This method is carried out at room temperature, plasma samples and protamine solutions that have been titrated at each concentration, and thrombin stored in ice until it is transferred to the test tube. First take a normal plasma, and leave it at room temperature for 30 s. Then the titration solution is added, and thrombin is then calculated when the clot is formed. The time obtained will be used as TCT baseline. Assay was repeated using a sample of patients with different protamine concentrations starting from the highest concentration first (0.9 IU/mL). After finding the smallest concentration that still provides TCT baseline, this result illustrates the level of heparin in the blood [41].
6.4 Thrombodynamics
A new examination for the coagulation function, thrombodynamics (TD), is examined under different circumstances. This TD measures the level of clot formation. Coagulation is triggered on the surface of an activator which is bound to a space and extends to the plasma layer. The scattered beam increases in the area formed by the clot, so clot formation and time needed can be measured. This method is considered most able to mimic the coagulation process that occurs in vivo compared to other examinations. This examination is very sensitive to the conditions of either hypocoagulation or hypercoagulation. Figure 5 shows the test tube scheme used in TD examination and the formation of clots and compared with the process of clot in vivo [43].
Figure 5.
Examination of thrombodynamics simulates the in vivo coagulation process. (a) Plastic cuvette schemes and activators that have been added for TD measurements. (b) Photos of the sequence of clot growth from spontaneous activator in vitro and clot in a portion of the sample. (c) Schematic image of clot growth from damage to blood vessel walls in vivo [44].
Clot formation curve depends on several parameters obtained: Tlag (time of formation of clot); Vi (initial speed of formation of clots) and V (speed of formation of clots) in clot formation (slope of clot formation curve versus time at 2–6 min and 15–25 min from the initial formation of clots for Vi and V); and CS (clot size 30 min after the coagulation process is activated). Other important parameters that are also measured are the maximum optical density of the formed clot (D) which shows the quality of the clot and the time required for the appearance of spontaneous clot (Tsp). The last two parameters have important clinical values because spontaneous clot (which grows not from activators on the surface) is only found in serious hypercoagulability states [44].
Heparin anticoagulants form complexes with ATIII and inhibit factors II, X, and IX. Research by Sinauridze et al. measure Tlag, Vi, and V parameters in post hip surgery patients who get heparin. The result is only Vi and V have significant different results, whereas Tlag has results that are not much different before and after heparin is given [44].
7. Conclusion
Heparin monitoring is needed to achieve an adequate dose. Laboratory tests for heparin monitoring include APTT examinations especially for UFH, anti-FXa activity assays especially for LMWH, protamine titration especially for UFH, and thrombodynamic tests that better reflect in vivo conditions.
Abbreviations
ACCP
American College of Chest Physicians
APC
activated protein C
APTT
activated partial thromboplastin time
AT
antithrombin
C1inh
C1 inhibitor
DIC
disseminated intravascular coagulopathy
DNA
deoxyribonucleic acid
GAG
glycosaminoglycans
HC II
heparin cofactor II
HIT
heparin-induced thrombocytopenia
INR
international normalized ratio
IV
intravenous
LMWH
low molecular weight heparin
NSAID
nonsteroid anti-inflammatory drug
PCI
percutaneous coronary intervention
PCI
protein C inhibitor
PF4
platelet factor 4
PN-1
protein nexin-1
PPP
platelet-poor plasma
SC
subcutaneous
Serpin
serine protease inhibitor
SFNG
symbol nomenclature for glycans
STEMI
ST-segment elevation myocardial infarction
TCT
thrombin clotting time
TD
thrombodynamics
TFPI
tissue factor pathway inhibitor
UFH
unfractionated heparin
ULMWH
ultralow molecular weight heparin
VTE
venous thromboembolism
Nomenclature
Symbols
CS
clot size at 30th minute of the measurement (μm)
D
clot density, it is an optical parameter, which is equal to intensity of light scattering from a fibrin clot (au)
Tlag
time between contact of plasma sample with activator and start of clot growth. Tlag characterizes the initiation phase of blood coagulation (min)
Tsp
time of spontaneous clot formation in plasma sample volume, which had no initial contact with activating insert. Spontaneous clotting is induced by circulating activators, active coagulation factors, and microparticles (min)
V
average rate of clot growth. The parameter characterizing the propagation phase of blood coagulation (μm/min)
Vi
initial rate, it characterizes the initiation phase of clot growth (μm/min)
Superscript
a
in normal renal function
\n',keywords:"heparin, anticoagulant, PPT, APTT, anti-Xa, protamine, thrombodynamics",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/68788.pdf",chapterXML:"https://mts.intechopen.com/source/xml/68788.xml",downloadPdfUrl:"/chapter/pdf-download/68788",previewPdfUrl:"/chapter/pdf-preview/68788",totalDownloads:1207,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 6th 2019",dateReviewed:"July 4th 2019",datePrePublished:"September 27th 2019",datePublished:"March 18th 2020",dateFinished:"August 26th 2019",readingETA:"0",abstract:"Heparin-derivative anticoagulants include unfractionated heparin (UFH), low molecular weight heparin (LMWH), pentasaccharide (fondaparinux), and ultralow molecular weight heparin (ULMWH). Heparin contains an active pentasaccharide sequence that binds to antithrombin (AT). This bond produces conformational changes that accelerate its binding with AT and inactivation of coagulation factors XIIa, XIa, Xa, and IXa and thrombin (IIa). Thrombin and factor Xa are the most sensitive to inhibition by the heparin-AT complex, and the strength of inhibiting thrombin is ten times more sensitive than factor Xa. The UFH anticoagulant response is monitored using activated partial thromboplastin time (APTT), a measurement that is sensitive to inhibition of thrombin and factor Xa. Protamine titration examination is the standard for measuring UFH concentrations in plasma. Recommendations from the American College of Chest Physicians (ACCP) suggest that the APTT target range for the UFH therapy is equivalent to 0.2–0.4 IU/mL with protamine titration or 0.35–0.7 IU/mL with an anti-Xa examination. A new examination is thrombodynamics (TD), measuring the level of development of clots. This method is considered most able to mimic the coagulation process that occurs in vivo compared to other examinations.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/68788",risUrl:"/chapter/ris/68788",signatures:"Yetti Hernaningsih and Ersa Bayung Maulidan",book:{id:"8700",type:"book",title:"Anticoagulation Drugs",subtitle:"the Current State of the Art",fullTitle:"Anticoagulation Drugs - the Current State of the Art",slug:"anticoagulation-drugs-the-current-state-of-the-art",publishedDate:"March 18th 2020",bookSignature:"Mina Kelleni",coverURL:"https://cdn.intechopen.com/books/images_new/8700.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-78985-076-5",printIsbn:"978-1-78985-075-8",pdfIsbn:"978-1-83880-145-8",isAvailableForWebshopOrdering:!0,editors:[{id:"247606",title:"Dr.",name:"Mina",middleName:"T.",surname:"Kelleni",slug:"mina-kelleni",fullName:"Mina Kelleni"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"267801",title:"Dr.",name:"Yetti",middleName:null,surname:"Hernaningsih",fullName:"Yetti Hernaningsih",slug:"yetti-hernaningsih",email:"yettihernaningsih@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"299155",title:"Dr.",name:"Ersa",middleName:null,surname:"Bayung Maulidan",fullName:"Ersa Bayung Maulidan",slug:"ersa-bayung-maulidan",email:"ersabm08@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Development of heparin",level:"1"},{id:"sec_3",title:"3. Structure and biosynthesis of heparin",level:"1"},{id:"sec_4",title:"4. Mechanism of heparin as an anticoagulant",level:"1"},{id:"sec_4_2",title:"4.1 Inhibition of antithrombin in factors IIa and Xa",level:"2"},{id:"sec_5_2",title:"4.2 Inhibition of antithrombin in other coagulation factors",level:"2"},{id:"sec_6_2",title:"4.3 Other serpins activated by heparin",level:"2"},{id:"sec_7_2",title:"4.4 Non-serpin inhibitors: tissue factor pathway inhibitors",level:"2"},{id:"sec_9",title:"5. The drug derivate heparin",level:"1"},{id:"sec_9_2",title:"5.1 Unfractionated heparin",level:"2"},{id:"sec_9_3",title:"Table 1.",level:"3"},{id:"sec_10_3",title:"5.1.2 Monitoring",level:"3"},{id:"sec_12_2",title:"5.2 Low molecular weight heparin (LMWH)",level:"2"},{id:"sec_12_3",title:"5.2.1 Pharmacodynamics and pharmacokinetics",level:"3"},{id:"sec_14_2",title:"5.3 Pentasaccharides (fondaparinux)",level:"2"},{id:"sec_14_3",title:"5.3.1 Pharmacodynamics and pharmacokinetics",level:"3"},{id:"sec_16_2",title:"5.4 Ultralow molecular heparin",level:"2"},{id:"sec_16_3",title:"5.4.1 Pharmacokinetics and pharmacodynamics",level:"3"},{id:"sec_19",title:"6. Heparin therapy monitoring",level:"1"},{id:"sec_19_2",title:"6.1 Activated partial thromboplastin time (APTT)",level:"2"},{id:"sec_20_2",title:"6.2 Anti-Xa activity assay",level:"2"},{id:"sec_21_2",title:"6.3 Protamine titration",level:"2"},{id:"sec_22_2",title:"6.4 Thrombodynamics",level:"2"},{id:"sec_23_2",title:"7. Conclusion",level:"2"},{id:"sec_27",title:"Abbreviations",level:"1"},{id:"sec_27",title:"Nomenclature",level:"1"}],chapterReferences:[{id:"B1",body:'Arbit E, Goldberg M, Gomez-orellana I, Majuru S. Oral heparin: Status review. Thrombosis Journal. 2006;4:6'},{id:"B2",body:'Zmuda K, Ascp MT, Neofotistos D, Ts C. Effects of unfractionated heparin, low-molecular-weight heparin, and heparinoid on thromboelastographic assay of blood coagulation. Coagulation and Transfusion Medicine. 2000;113:725-731'},{id:"B3",body:'Oduah EI, Linhardt RJ, Sharfstein ST. Heparin: Past, present, and future. Pharmateuticals. 2016;9(38):1-12'},{id:"B4",body:'Garcia DA, Baglin TP, Weitz JI, Michel M. Parenteral Anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141(June)'},{id:"B5",body:'Gray E, Mulloy B, Barrowcliffe TW. Heparin and low-molecular-weight heparin. 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Review of fondaparinux sodium injection for the prevention of venous thromboembolism in patients undergoing surgery. Vascular Health and Risk Management. 2006;2(4):365-370'},{id:"B32",body:'Walenga JM, Lyman GH. Evolution of heparin anticoagulants to ultra-low-molecular-weight heparins: A review of pharmacologic and clinical differences and applications in patients with cancer. Critical Reviews in Oncology/Hematology. 2013;88(1):1-18. DOI: 10.1016/j.critrevonc.2013.06.007'},{id:"B33",body:'Takemoto CM, Streiff MB, Shermock KM, Kraus PS, Chen J, Jani J, et al. Activated partial thromboplastin time and anti-Xa measurements in heparin monitoring. Biochemical basis for discordance. Coagulation and transfusion Medicine. 2013;139:450-456'},{id:"B34",body:'Kinnard T. Anti-Xa Assay for Heparin Monitoring [Internet]. Mayo Clinic Laboratory; 2016. pp. 1-12. 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Circulation. 2001;103(February):2994-3018'},{id:"B40",body:'Boer C, Meesters MI, Veerhoek D, Vonk ABA. Anticoagulant and side-effects of protamine in cardiac surgery. British Journal of Anaesthesia. 2018;14(January). DOI: 10.1016/j.bja.2018.01.023'},{id:"B41",body:'Walker JM. Haemostasis Methods and Protocols. Australia MP Department of PU of MPV, editor. Humana Press; 2013'},{id:"B42",body:'Bain BJ, Bates I, Laffan MA. Dacie and Lewis Practical Haematology. Elsevier Inc; 2017. 599 p'},{id:"B43",body:'Soshitova NP, Karamzin SS, Balandina AN, Fadeeva OA, Kretchetova AV, Galstian GM. Predicting prothrombotic tendencies in sepsis using spatial clot growth dynamics. Blood Coagulation & Fibrinolysis. 2012;23(February):498-507'},{id:"B44",body:'Sinauridze EI, Vuimo TA, Tarandovskiy ID, Ovsepyan RA, Surov SS, Korotina NG, et al. Thrombodynamics, a new global coagulation test: Measurement of heparin efficiency. Talanta. 2018;180(December):282-291'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Yetti Hernaningsih",address:"yettihernaningsih@gmail.com",affiliation:'
Department of Clinical Pathology, Faculty of Medicine, Dr. Soetomo General Academic Hospital, Universitas Airlangga, Surabaya, Indonesia
Department of Clinical Pathology, Faculty of Medicine, Dr. Soetomo General Academic Hospital, Universitas Airlangga, Surabaya, Indonesia
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His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},{id:"199984",title:"Prof.",name:"Mikhail",surname:"Kostinov",slug:"mikhail-kostinov",fullName:"Mikhail Kostinov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"232191",title:"Prof.",name:"Vsevolod",surname:"Zinserling",slug:"vsevolod-zinserling",fullName:"Vsevolod Zinserling",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"232749",title:"Dr.",name:"Eita",surname:"Sasaki",slug:"eita-sasaki",fullName:"Eita Sasaki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"233433",title:"Dr.",name:"Yulia",surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"240653",title:"M.D.",name:"Yuji",surname:"Takemoto",slug:"yuji-takemoto",fullName:"Yuji Takemoto",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"241561",title:"Ph.D.",name:"Binod",surname:"Kumar",slug:"binod-kumar",fullName:"Binod Kumar",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"our-story",title:"Our story",intro:"
The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.
",metaTitle:"Our story",metaDescription:"The company was founded in Vienna in 2004 by Alex Lazinica and Vedran Kordic, two PhD students researching robotics. While completing our PhDs, we found it difficult to access the research we needed. So, we decided to create a new Open Access publisher. A better one, where researchers like us could find the information they needed easily. The result is IntechOpen, an Open Access publisher that puts the academic needs of the researchers before the business interests of publishers.",metaKeywords:null,canonicalURL:"/page/our-story",contentRaw:'[{"type":"htmlEditorComponent","content":"
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\\n\\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\\n\\n
The IntechOpen timeline
\\n\\n
2004
\\n\\n
\\n\\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\\n\\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\\n
\\n\\n
2005
\\n\\n
\\n\\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\\n
\\n\\n
2006
\\n\\n
\\n\\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\\n
\\n\\n
2008
\\n\\n
\\n\\t
Downloads milestone: 200,000 downloads reached
\\n
\\n\\n
2009
\\n\\n
\\n\\t
Publishing milestone: the first 100 Open Access STM books are published
\\n
\\n\\n
2010
\\n\\n
\\n\\t
Downloads milestone: one million downloads reached
\\n\\t
IntechOpen expands its book publishing into a new field: medicine.
\\n
\\n\\n
2011
\\n\\n
\\n\\t
Publishing milestone: More than five million downloads reached
\\n\\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\\n\\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\\n\\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\\n
\\n\\n
2012
\\n\\n
\\n\\t
Publishing milestone: 10 million downloads reached
\\n\\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\\n
\\n\\n
2013
\\n\\n
\\n\\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\\n
\\n\\n
2014
\\n\\n
\\n\\t
IntechOpen turns 10, with more than 30 million downloads to date.
\\n\\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\\n
\\n\\n
2015
\\n\\n
\\n\\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\\n\\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\\n\\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\\n\\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\\n
\\n\\n
2016
\\n\\n
\\n\\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\\n
\\n\\n
2017
\\n\\n
\\n\\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\\n\\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
We started by publishing journals and books from the fields of science we were most familiar with - AI, robotics, manufacturing and operations research. Through our growing network of institutions and authors, we soon expanded into related fields like environmental engineering, nanotechnology, computer science, renewable energy and electrical engineering, Today, we are the world’s largest Open Access publisher of scientific research, with over 4,200 books and 54,000 scientific works including peer-reviewed content from more than 116,000 scientists spanning 161 countries. Our authors range from globally-renowned Nobel Prize winners to up-and-coming researchers at the cutting edge of scientific discovery.
\n\n
In the same year that IntechOpen was founded, we launched what was at the time the first ever Open Access, peer-reviewed journal in its field: the International Journal of Advanced Robotic Systems (IJARS).
\n\n
The IntechOpen timeline
\n\n
2004
\n\n
\n\t
Intech Open is founded in Vienna, Austria, by Alex Lazinica and Vedran Kordic, two PhD students, and their first Open Access journals and books are published.
\n\t
Alex and Vedran launch the first Open Access, peer-reviewed robotics journal and IntechOpen’s flagship publication, the International Journal of Advanced Robotic Systems (IJARS).
\n
\n\n
2005
\n\n
\n\t
IntechOpen publishes its first Open Access book: Cutting Edge Robotics.
\n
\n\n
2006
\n\n
\n\t
IntechOpen publishes a special issue of IJARS, featuring contributions from NASA scientists regarding the Mars Exploration Rover missions.
\n
\n\n
2008
\n\n
\n\t
Downloads milestone: 200,000 downloads reached
\n
\n\n
2009
\n\n
\n\t
Publishing milestone: the first 100 Open Access STM books are published
\n
\n\n
2010
\n\n
\n\t
Downloads milestone: one million downloads reached
\n\t
IntechOpen expands its book publishing into a new field: medicine.
\n
\n\n
2011
\n\n
\n\t
Publishing milestone: More than five million downloads reached
\n\t
IntechOpen publishes 1996 Nobel Prize in Chemistry winner Harold W. Kroto’s “Strategies to Successfully Cross-Link Carbon Nanotubes”. Find it here.
\n\t
IntechOpen and TBI collaborate on a project to explore the changing needs of researchers and the evolving ways that they discover, publish and exchange information. The result is the survey “Author Attitudes Towards Open Access Publishing: A Market Research Program”.
\n\t
IntechOpen hosts SHOW - Share Open Access Worldwide; a series of lectures, debates, round-tables and events to bring people together in discussion of open source principles, intellectual property, content licensing innovations, remixed and shared culture and free knowledge.
\n
\n\n
2012
\n\n
\n\t
Publishing milestone: 10 million downloads reached
\n\t
IntechOpen holds Interact2012, a free series of workshops held by figureheads of the scientific community including Professor Hiroshi Ishiguro, director of the Intelligent Robotics Laboratory, who took the audience through some of the most impressive human-robot interactions observed in his lab.
\n
\n\n
2013
\n\n
\n\t
IntechOpen joins the Committee on Publication Ethics (COPE) as part of a commitment to guaranteeing the highest standards of publishing.
\n
\n\n
2014
\n\n
\n\t
IntechOpen turns 10, with more than 30 million downloads to date.
\n\t
IntechOpen appoints its first Regional Representatives - members of the team situated around the world dedicated to increasing the visibility of our authors’ published work within their local scientific communities.
\n
\n\n
2015
\n\n
\n\t
Downloads milestone: More than 70 million downloads reached, more than doubling since the previous year.
\n\t
Publishing milestone: IntechOpen publishes its 2,500th book and 40,000th Open Access chapter, reaching 20,000 citations in Thomson Reuters ISI Web of Science.
\n\t
40 IntechOpen authors are included in the top one per cent of the world’s most-cited researchers.
\n\t
Thomson Reuters’ ISI Web of Science Book Citation Index begins indexing IntechOpen’s books in its database.
\n
\n\n
2016
\n\n
\n\t
IntechOpen is identified as a world leader in Simba Information’s Open Access Book Publishing 2016-2020 report and forecast. IntechOpen came in as the world’s largest Open Access book publisher by title count.
\n
\n\n
2017
\n\n
\n\t
Downloads milestone: IntechOpen reaches more than 100 million downloads
\n\t
Publishing milestone: IntechOpen publishes its 3,000th Open Access book, making it the largest Open Access book collection in the world
\n
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. His current research interests are in the fields of intelligent control and robotics.",institutionString:null,institution:{name:"Technical University of Sofia",country:{name:"Bulgaria"}}},{id:"585",title:"Prof.",name:"Munir",middleName:null,surname:"Merdan",slug:"munir-merdan",fullName:"Munir Merdan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/585/images/system/585.jpg",biography:"Munir Merdan received the M.Sc. degree in mechanical engineering from the Technical University of Sarajevo, Bosnia and Herzegovina, in 2001, and the Ph.D. degree in electrical engineering from the Vienna University of Technology, Vienna, Austria, in 2009.Since 2005, he has been at the Automation and Control Institute, Vienna University of Technology, where he is currently a Senior Researcher. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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In this work, the most used thermoplastic foams with closed cells such as polypropylene, polyethylene, and polystyrene or polylactic acid have been focused. Their melt strength, degree of crystallinity for semi-crystalline ones, and viscosity have great importance on cell morphology. Cells in small diameter with high dense in polymer matrix are preferable. However, obtaining fine cells is not easy in each case, and it is still under investigation for some polymers. There are several ways to improve cell morphology, and one of them is addition of nanoparticle to the polymer. During foaming process, nanoparticles behave like nucleating agent that cells nucleate at the boundary between polymer and the nanoparticle. Besides, foaming agents contribute the homogenous dispersion of the nanoparticles in the polymer matrix, and this improves the properties of the polymer foams and generates multifunctional material as polymer nanocomposite foams.",book:{id:"6141",slug:"recent-research-in-polymerization",title:"Polymerization",fullTitle:"Recent Research in Polymerization"},signatures:"Mihrigul Altan",authors:[{id:"209557",title:"Associate Prof.",name:"Mihrigul",middleName:null,surname:"Altan",slug:"mihrigul-altan",fullName:"Mihrigul Altan"}]},{id:"57833",title:"Emulsion Polymerization Mechanism",slug:"emulsion-polymerization-mechanism",totalDownloads:3769,totalCrossrefCites:3,totalDimensionsCites:11,abstract:"Emulsion polymerization is a polymerization process with different applications on the industrial and academic scale. 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A typical of particle consist of 1–10,000 macromolecules, where macromolecule contains about 100–106 monomer units.",book:{id:"6141",slug:"recent-research-in-polymerization",title:"Polymerization",fullTitle:"Recent Research in Polymerization"},signatures:"Abdelaziz Nasr Moawed Bakr El-hoshoudy",authors:[{id:"201556",title:"Dr.",name:"Abdelaziz",middleName:"Nasr",surname:"El-Hoshoudy",slug:"abdelaziz-el-hoshoudy",fullName:"Abdelaziz El-Hoshoudy"}]},{id:"34877",title:"Advanced Techniques in TEM Specimen Preparation",slug:"advanced-techniques-in-tem-specimen-preparation",totalDownloads:4829,totalCrossrefCites:1,totalDimensionsCites:6,abstract:null,book:{id:"1508",slug:"the-transmission-electron-microscope",title:"The Transmission Electron Microscope",fullTitle:"The Transmission Electron Microscope"},signatures:"Jian Li",authors:[{id:"112508",title:"Dr.",name:"Jian",middleName:null,surname:"Li",slug:"jian-li",fullName:"Jian Li"}]},{id:"57574",title:"Polymerizable Materials for Diffractive Optical Elements Recording",slug:"polymerizable-materials-for-diffractive-optical-elements-recording",totalDownloads:1478,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"The technologies based on holographic and photonic techniques related to the optical storage and optical processing of information are rapidly evolving. One of the key points of this evolution are the new recording materials able to perform under the most specific situations and applications. In this sense, the importance of the photopolymers is growing spectacularly. This is mainly due to their versatility in terms of composition and design together with other interesting properties such as self-processing capabilities. In this chapter, we introduce the diffractive optical elements (DOE) generation in these materials and some of the most important parameters involved in this process. The deep knowledge of the material is essential to model its behavior during and after the recording process and we present different techniques to characterize the recording materials. We also present a 3D theoretical diffusion model able to reproduce and predict the experimental behavior of the recording process of any kind of DOE onto the photopolymers. 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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:230,paginationItems:[{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. 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. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. 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. 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