LMWH therapeutic doses according to body weight.
\r\n\tAntiphospholipid syndrome is likely to be involved in a small percentage of infertility. It is mainly associated with repeated miscarriages, secretion of cytokines, and growth factors that affect both ovulation, fertilization, and implantation, as well as a previous ectopic pregnancy in the fallopian tubes. Ectopic pregnancy is linked to taking drugs to induce ovulation, but the exact pathogenetic mechanism associated with hormone intake and fallopian tube damage is not yet known.
\r\n\tFertilization of the egg with the sperm under normal conditions occurs in the fibrous part of the fallopian tube. After 3-4 days the fertilized egg reaches the uterus, where the blastocyst within 2 to 4 days may be in a state of immersion in the endometrial tissue. Thus, the implantation takes place on the 20th-21st day of the 4-week menstrual cycle. The pathology of the function of the fallopian tubes is most often associated with inflammatory processes of any etiology. Non-specific infection plays a predominant role, the spread of which contributes to abortion, intrauterine contraception, diagnostic intervention and the occurrence of obstetric and perinatal complications.
\r\n\tIn recent years, the increasing incidence of chlamydial infection has been linked to the occurrence of ectopic pregnancy. Along with the inflammatory nature of the structure and function of the fallopian tubes, endometriosis also seems to play an important e localization may be ovarian, cervical or intra-abdominal, but in most cases it is tubal. The incidence of ectopic pregnancies in the USΑ has at least quadrupled in recent years with the probability nowadays standing at 20 per 1000 pregnancies. Ectopic pregnancy in the USA is reported to be the cause of death in 10% of obstetric deaths, but it is important to note that most of these deaths are bleeding-related and preventable.
\r\n\tA clear trend of increasing the frequency of ectopic pregnancies has been observed in the last ten years, which is triggered by two main reasons. On the one hand, the localization of inflammatory processes in the internal genitals is constantly increasing, while at the same time, the number of surgeries on the fallopian tubes is increasing in order to improve a woman's reproductive capacity. Τhe number of women using intrauterine and hormonal methods of contraception is also increasing and ovulation inducers are increasingly being introduced into the practice of infertility treatment.
\r\n\tOn the other hand, diagnostic capabilities have been improved in recent years by allowing detection of intolerance and even remission of ectopic pregnancy. Currently, an ectopic pregnancy occurs from 0.8-2.4% of cases that are born. In 4-10% of cases, it is repeated. Ectopic pregnancy often occurs as a result of tubal pathology.
\r\n\tRisk factors include smoking, inflammation of the pelvic organs as a result of chlamydia or gonorrhea, and endometriosis, conditions that lead to the formation of scar tissue in the fallopian tubes.role.
\r\n\tThe role of invasive procedures for the treatment of the causative agents of structural abnormalities of the fallopian tubes in the occurrence of ectopic pregnancy is becoming increasingly crucial and even to such an extent that the introduction of microsurgery does not exclude the risks.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"46740c30c279d7ad0334167a63819809",bookSignature:"Prof. Panagiotis Tsikouras, Prof. Nikolaos Nikolettos, Prof. Werner Rath and Prof. Georg-Friedrich Von Tempelhoff",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11282.jpg",keywords:"Differential Diagnosis, Early Diagnosis, Abortion, Intrauterine Pregnancy, Surgery, Methotrexate, Salpingostomy, New Aspects, Markers, Endometriosis, Diagnosis, Management",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 9th 2021",dateEndSecondStepPublish:"October 7th 2021",dateEndThirdStepPublish:"December 6th 2021",dateEndFourthStepPublish:"February 24th 2022",dateEndFifthStepPublish:"April 25th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"9 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Panagiotis Tsikouras has authored and co-authored multiple peer-reviewed scientific papers and presented works at many national and international conferences. His contributions have acclaimed recognition from honorable subject experts around the world. Dr. Tsikouras has great experience in check control of high-risk pregnancies such as ART pregnancies, twin pregnancies, teenage pregnancies. Except for this, he is responsible for the termination of high pregnancies.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"48837",title:"Prof.",name:"Panagiotis",middleName:null,surname:"Tsikouras",slug:"panagiotis-tsikouras",fullName:"Panagiotis Tsikouras",profilePictureURL:"https://mts.intechopen.com/storage/users/48837/images/system/48837.jpg",biography:"Dr. Panagiotis Tsikouras is a specialist in obstetrics-gynecology,\nperinatal medicine, and contraception at the School of Medicine,\nDemocritus University of Thrace, Greece. He is also the headmaster of the Family Planning Centre and Gynecological Cytology\nLaboratory at the same university. Dr. Tsikouras is a fellow of the\nInternational Academy of Clinical and Applied Thrombosis/Hemostasis. His scientific activities focus on paediatric and adolescence medicine, gynecological oncology, high-risk pregnancies. He is a reviewer for several international journals and has numerous scientific publications to his credit, including papers and book chapters. He has also contributed to international and national guidelines on coagulation and thrombosis in obstetrics-gynecology.",institutionString:"Democritus University of Thrace, Komotini",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"11",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Democritus University of Thrace",institutionURL:null,country:{name:"Greece"}}}],coeditorOne:{id:"317103",title:"Prof.",name:"Nikolaos",middleName:null,surname:"Nikolettos",slug:"nikolaos-nikolettos",fullName:"Nikolaos Nikolettos",profilePictureURL:"https://mts.intechopen.com/storage/users/317103/images/system/317103.png",biography:"Dr. Nikos Nikolettos is a specialist in obstetrics, gynecology and\nassisted reproduction at the Democritus University of Thrace,\nGreece. He is trained in gynecological endocrinology, human\nreproduction, and in vitro fertilization. From 2007 to 2011, Dr.\nNikos served as director of the In Vitro Fertilization Unit, University Regional General Hospital of Alexandroupolis, Greece. From\n2012 to 2018, he was director of the Laboratory of Reproductive\nPhysiology - Artificial Fertilization. In 2018 he became Professor of Assisted Reproduction at the Democritus University of Thrace, Greece. In 2019 he took over the\nmanagement of the University Obstetrics-Gynecology Clinic, Medical Department,\nDemocritus University of Thrace. His scientific work includes more than 100 publications in international journals and many lectures by invitation to international and Greek conferences.",institutionString:"Democritus University of Thrcae",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Democritus University of Thrace",institutionURL:null,country:{name:"Greece"}}},coeditorTwo:{id:"290374",title:"Dr.",name:"Werner",middleName:null,surname:"Rath",slug:"werner-rath",fullName:"Werner Rath",profilePictureURL:"https://mts.intechopen.com/storage/users/290374/images/system/290374.jpg",biography:"Dr. Werner Rath is a specialist in obstetrics and gynecology, gynecologic oncology, perinatal medicine, and hemostaseology. He is currently a professor in the Gynecology and Obstetrics Faculty of Medicine, University of Kiel, Germany, and an honorary doctor at the Democritus University of Thrace, Alexandroupoli University Hospital He previously served as chief of the Department of Gynecology and Obstetrics at University Hospital RWTH Aachen,\r\nGermany. Dr. Rath is a reviewer for numerous journals and chief editor of Geburtshilfe und Frauenheilkunde (GebFra). He has several publications, including thirteen book chapters, to his credit.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Kiel University",institutionURL:null,country:{name:"Germany"}}},coeditorThree:{id:"299669",title:"Prof.",name:"Georg-Friedrich",middleName:null,surname:"Von Tempelhoff",slug:"georg-friedrich-von-tempelhoff",fullName:"Georg-Friedrich Von Tempelhoff",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:"St. Vinzenz Krankenhaus",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"301331",firstName:"Mia",lastName:"Vulovic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/301331/images/8498_n.jpg",email:"mia.v@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"10460",title:"Current Topics in Caesarean Section",subtitle:null,isOpenForSubmission:!1,hash:"e59550fca39fd09ff4addfe39ca822a0",slug:"current-topics-in-caesarean-section",bookSignature:"Panagiotis Tsikouras, Nikolaos Nikolettos, Werner Rath and Georg Friedrich Von Tempelhoff",coverURL:"https://cdn.intechopen.com/books/images_new/10460.jpg",editedByType:"Edited by",editors:[{id:"48837",title:"Prof.",name:"Panagiotis",surname:"Tsikouras",slug:"panagiotis-tsikouras",fullName:"Panagiotis Tsikouras"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. 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Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9500",title:"Recent Advances in Bone Tumours and Osteoarthritis",subtitle:null,isOpenForSubmission:!1,hash:"ea4ec0d6ee01b88e264178886e3210ed",slug:"recent-advances-in-bone-tumours-and-osteoarthritis",bookSignature:"Hiran Amarasekera",coverURL:"https://cdn.intechopen.com/books/images_new/9500.jpg",editedByType:"Edited by",editors:[{id:"67634",title:"Dr.",name:"Hiran",surname:"Amarasekera",slug:"hiran-amarasekera",fullName:"Hiran Amarasekera"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"62091",title:"An Overview of the Anticoagulant Drugs Used in Routine Clinical Practice",doi:"10.5772/intechopen.76206",slug:"an-overview-of-the-anticoagulant-drugs-used-in-routine-clinical-practice",body:'Anticoagulant drugs directly or indirectly influence coagulation factors and thus inhibit the initiation and progress of coagulation and fibrin-clot formation. They are classified into two groups according to the mode of application, namely parenteral and oral drugs. Among the latter, vitamin K antagonists (most often warfarin) were the only available oral anticoagulants and were widely used for almost a century. In recent years, new oral anticoagulant drugs became available that directly target either factor IIa or Xa [1].
This chapter provides an overview of both parenteral and oral anticoagulant drugs used in clinical practice with a description of the mode of action and management of therapy in different clinical settings.
Unfractionated heparin (UFH) binds antithrombin—a physiological inhibitor of coagulation—and accelerates its inhibitory action against coagulation factors II and X and in minor degrees also factors IX, XI and XII [2, 3]. UFH is active in a parenteral form only and therefore administered by intravenous (i.v.) infusion [2]. It is used for the treatment of acute thromboembolic events. One of the major disadvantages of UFH is its binding to plasma proteins and endothelial cells making its anticoagulant effect unpredictable [2, 3]. Treatment with UFH must, therefore, be regularly monitored with activated partial thromboplastin time (APTT). Due to different sensitivities of APTT reagents the therapeutic APTT range must be determined by each laboratory and must correspond to heparin anti-factor Xa activity between 0.3 and 0.7 IU/mL [4, 5, 6]. Treatment is initiated with UFH bolus of 80 U/kg i.v. and continued with continuous infusion of 18 U/kg body mass/h [7]. Dosage must be adjusted according to the APTT result. At the beginning of treatment, laboratory monitoring is needed several times a day, the first one 6 h after UFH initiation. The two most important non-hemorrhagic side effects of UFH treatment are osteoporosis and thrombocytopenia [2].
Low-molecular weight heparin (LMWH) is obtained by various methods of fractionation or depolymerization of polymeric UFH [8]. Because LMWHs differ in molecular mass, they also differ in pharmacological characteristics and anticoagulant effects [9]. All LMWHs inhibit coagulation factors II and X. Among the most commonly used LMWHs for treatment and the prevention of acute thromboembolic events are dalteparin (Fragmin®), enoxaparin (Clexane®) and nadroparin (Fraxiparine® and Fraxiparine forte®) in the form of subcutaneous injections. They can also be used as a bridging therapy in patients with high thromboembolic risk during a period when these patients cannot receive oral anticoagulants. Therapeutic dose is determined according to the patient’s body weight [2] (Table 1).
Therapeutic dose | ||
---|---|---|
LMWH | Twice daily | Once daily |
Dalteparin (Fragmin®) | 100 IU/kg BW/12 h sc | 200 IU/kg BW/24 h sc |
46–56 kg | 5.000 IU/12 h sc | 10.000 IU/24 h sc |
57–68 kg | 6.000 IU/12 h sc | 12.500 IU/24 h sc |
69–82 kg | 7.500 IU/12 h sc | 15.000 IU/24 h sc |
82–120 kg | 100 IU/kgBW/12 h sc | 18.000 IU/24 h sc |
Enoksaparin (Clexane®) | 1 mg/kg BW/12 h sc | 1.5 mg/kg BW/24 h sc |
45–54 kg | 50 mg/12 h sc | 80 mg/24 h sc |
55–64 kg | 60 mg/12 h sc | 90 mg/24 h sc |
65–74 kg | 70 mg/12 h sc | 100 mg/24 h sc |
75–84 kg | 80 mg/12 h sc | 120 mg/24 h sc |
85–94 kg | 90 mg/12 h sc | 135 mg/24 h sc |
94–120 kg | 100 mg/12 h sc | 150 mg/24 h sc |
Nadroparin | (Fraxiparine®) 0.1 ml/10 kg BW /12 h sc | (Fraxiparine FORTE®) 0.1 ml/10 kg BW/24 h sc |
50–59 kg | 0.5 ml/12 h sc | 0.5 ml/24 h sc |
60–69 kg | 0.6 ml/12 h sc | 0.6 ml/24 h sc |
70–79 kg | 0.7 ml/12 h sc | 0.7 ml/24 h sc |
80–89 kg | 0.8 ml/12 h sc | 0.8 ml/24 h sc |
90–120 kg | 0.9 ml/12 h sc | 0.9 ml/24 h sc |
LMWH therapeutic doses according to body weight.
IU: International Units, BW: body weight, sc: subcutaneously.
For prevention of venous thromboembolism (VTE), lower (prophylactic) doses of LMWH are used [2] (Table 2). The adequate LMWH dose is selected according to the risk. Prophylactic doses are used in some patients during the interim cessation of oral anticoagulant therapy above all in the first days after large interventions.
LMWH | Low prophylactic dose (moderate VTE risk) | High prophylactic dose (high VTE risk) |
---|---|---|
Dalteparin | 2500 IU/24 h sc | 5000 IU/24 h sc |
Enoxaparin | 20 mg/24 h sc | 40 mg/24 h sc |
Nadroparin | 0.3 ml/24 h sc | 0.4 ml/24 h sc at BW ≤ 70 kg 0.6 ml/24 h sc at BW > 70 kg |
Prophylactic doses of LMWH.
IU: International Units, BW: body weight, sc: subcutaneously, VTE: venous thromboembolism.
The most important advantage of LMWH over UFH is the lower degree of binding to plasma proteins and endothelial cells making their pharmacokinetics and anticoagulant effects predictable [10, 11]. Regular laboratory monitoring with coagulation tests is therefore not needed, except in patients with kidney disease and patients with very low (under 45 kg) or very high (above 120 kg) body weight [2]. Although APTT may be mildly prolonged during LMWH therapy it cannot be used for monitoring. The chromogenic anti-Xa is the test of choice for the determination of plasma LMWH concentration [12]. The LMWH dose should be adjusted to 0.5–1.0 IU/mL 4 h after the last LMWH dose when administered twice daily or to 1.0–2.0 IU/mL 5–6 h after the last dose when administered once daily [13, 14]. The two main non-hemorrhagic side effects of LMWH therapy are osteopenia and thrombocytopenia; however, both these side effects are considerably rarer compared to UFH therapy [2].
Fondaparin (Arixtra®) is a synthetic pentasaccharide that closely resembles the pentasaccharide naturally occurring in the UFH and LMWH. It is an antithrombin-mediated factor Xa inhibitor that is devoid of any anti-factor IIa (thrombin) activity [15]. It is used for treating patients with acute coronary syndrome and heparin-induced thrombocytopenia. It is indicated also for certain patients with thrombophlebitis in a fixed dose of 2.5 mg daily s.c. Laboratory monitoring is not needed; however, if necessary fondaparin levels should only be determined using assays that use known fondaparin concentrations to generate their calibration curve. The use of fondaparin in patients with creatinine clearance below 30 mL/min is contraindicated [2].
Hirudin is a naturally occurring peptide in the salivary glands of medicinal leeches that irreversibly inhibits thrombin. Lepirudin, a recombinant hirudin derived from yeast cells, was used in clinical practice but is no longer available. Instead, the synthetic analog—bivalirudin (Angiox®)—with a short half-life is used at percutaneous coronary interventions and for treating patients with heparin-induced thrombocytopenia. The use of bivalirudin in patients with creatinine clearance below 30 mL/min is contraindicated [16].
Argatroban (Argatra®) is a synthetic reversible direct thrombin inhibitor. It is metabolized solely in the liver and is, therefore, suitable for patients with renal failure. It is used in patients with heparin-induced thrombocytopenia. Treatment with argatroban requires laboratory monitoring with activated partial thromboplastin time (APTT) and the dose adjusted to reach 1.5–3.0 times prolonged baseline APTT, but should not exceed 100 s [17].
The vitamin K-dependent coagulation factors II, VII, IX and X require γ-carboxylation for their procoagulant activity. Treatment with vitamin K antagonists results in the hepatic production of partially carboxylated and decarboxylated proteins with reduced coagulant activity. Among the most commonly used vitamin K antagonists are warfarin and acenocoumarol. Although vitamin K antagonists are absorbed quickly their full effect develops after about 5 days when the activity of all vitamin K-dependent coagulation factors is reduced [1].
Warfarin therapy requires regular laboratory monitoring with prothrombin time (PT). Due to different sensitivities of thromboplastin reagents used for PT measurement the results are expressed as the International Normalized Ratio (INR). For the majority of indications the target INR range falls between 2.0 and 3.0. In certain patient populations, for example, in patients with mechanical heart valves, the target range is 2.5–3.5 INR. A rare non-hemorrhagic side effect of vitamin K antagonist therapy is skin necrosis that develops at therapy initiation and is a consequence of acute thrombosis of subcutaneous venules and capillaries [1].
Dabigatran etexilate (Pradaxa®) is a low-molecular weight prodrug that exhibits no pharmacological activity. After oral administration, dabigatran etexilate is converted to its active form, dabigatran, a potent, competitive and reversible direct thrombin inhibitor [18]. The binding of dabigatran to thrombin is specific and selective and includes both free and thrombus-bound thrombin. Maximal blood concentration of dabigatran is reached after 1–3 h after the intake [18]. About 35% of the drug is bound to plasma proteins. Eighty percent of dabigatran is excreted through the kidneys [18]. Dabigatran half-life is 14–17 h [18]. It is given in fixed doses of either 150 or 110 mg twice daily in patients with atrial fibrillation and 150 mg twice daily in patients with VTE [19, 20]. Prophylactic doses after total hip or knee replacement are 220 or 150 mg once daily with only half the dose given as the first dose after surgery [21].
The anticoagulant effect of dabigatran is predictive and, therefore, requires no regular laboratory monitoring. During dabigatran therapy, APTT and thrombin time (TT) are prolonged, but these two tests can only offer a rough approximation of dabigatran blood concentration. In certain situations when dabigatran concentration needs to be assessed, a specific test must be used, such as modified thrombin time or a chromogenic assay [22, 23].
Rivaroxaban (Xarelto®) directly inhibits factor Xa. It selectively binds both free and prothrombin complex bound factor Xa and in this way inhibits thrombin and clot formation. Peak blood concentration is achieved after 1–3 h after drug ingestion. As much as 95% of the drug is bound to plasma protein. One-third of the drug is excreted through kidneys, the other two-thirds are metabolized in the liver. The drug half-life is 8–13 h [1, 24]. Therapeutic doses are 20 and 15 mg once daily for patients with atrial fibrillation [25]. Patients with VTE are treated with 15 mg twice daily for the first 3 weeks, followed by 20 mg once daily [26, 27]. The drug must always be ingested with food. The prophylactic dose for patients with total hip or knee replacement is 10 mg once daily [28, 29].
No laboratory monitoring of therapy is needed due to the predictive effect of the drug. Rivaroxaban prolongs PT; however, when an assessment of the drug blood level is needed, an anti-Xa test calibrated to rivaroxaban should be used [30].
Apixaban (Eliquis®) directly and reversibly inhibits factor Xa. Maximal blood concentration of the drug is achieved 3–4 h after ingestion. As much as 87% of the drug is bound to blood protein. Twenty-seven percent of the drug is excreted through kidneys and the remainder through the liver. The drug half-life is 12 h [31]. Patients with atrial fibrillation are treated with 5 or 2.5 mg twice daily [32]. Patients with VTE are treated with 10 mg twice daily for the first 7 days followed by 5 mg daily [33]. The prophylactic dose for patients with total hip or knee replacement is 2.5 mg twice daily [34].
No laboratory monitoring of therapy is needed due to the predictive effect of the drug. Apixaban unreliably prolongs APTT and PT. When an assessment of the drug blood level is needed, an anti-Xa test calibrated to apixaban should be used [35].
Edoxaban directly inhibits factor Xa. Maximal blood concentration of the drug is achieved 1–2 h after the ingestion. About 40–59% of the drug is bound to plasma protein. Roughly 35% of the drug is excreted through the kidneys and the remainder through the liver. The drug half-life is 9–14 h. Therapeutic doses are 60 and 30 mg daily for patients with atrial fibrillation and VTE. The prophylactic dose for patients with total hip or knee replacement is 30 mg once daily. Edoxaban prolongs APTT and PT, but for a quantitative assessment of the drug level, an anti-Xa test calibrated to edoxaban must be utilized [36, 37].
Papillary neoplasm of the breast is a broad range of heterogeneous group of lesions that are characterized by presence of papillae supported by fibrovascular cores lined by epithelial cells with or without myoepithelial cell layer. These neoplasms may be benign, atypical or malignant and are difficult to diagnose. The main diagnostic concern is differentiating benign and malignant lesions, which can be challenging both on imaging as well as on histopathological examination [1].
World health organization (WHO) in 2021 classified breast intraductal papillary neoplasm as intraductal papillomas (intraductal papilloma with atypical hyperplasia, intraductal papilloma with ductual carcinoma in situ (DCIS), intraductal papilloma with lobular carcinoma in situ), intraductal papillary carcinoma (solid papillary carcinoma, encapsulated carcinoma) and invasive carcinoma [1, 2].
The benign conditions are commonly seen in between 30 and 50 years of age and PC commonly affects postmenopausal age group. Papillary neoplasms have sex predilection for females though intracystic papillary carcinoma (IPC) is rarely seen in males too. The clinical presentation in males and females is similar except for a higher median age in males [3, 4].
Papillary neoplasms are less commonly seen and account for less than 3% of breast tumors and PC of the breast accounts for 0.5–1% of breast cancer [5]. The frequency of lymph node involvement in invasive papillary carcinoma, its local recurrence and distant recurrence may be 0–11%, 3–70% and 0–4%, respectively. Solid papillary carcinoma (SPC) constitutes only 1% of all the breast carcinomas, presenting as localized mass in approximately 90% of the cases, lymph node metastases in 8%, and distant metastases in less than 0.8% only. Intracystic papillary carcinoma also has localized involvement in approximately 89.6% of the cases with 0.4% distant metastases [6, 7].
Many researchers have analyzed the risk factors for malignant transformation in benign papilloma of breast, however the results remain inconsistent. Some investigators considered same attributable factors for carcinoma arising in papillary neoplasm as that of other carcinomas. The contributing predisposing risk factors are age, family history, genetic predilection, diet and weight gain, alcoholism, and endocrine factors [8, 9].
Papillary neoplasms may be central and peripheral in location and solitary or multiple in number. And most papillomas are centrally located with a wide age distribution and originate in the large ducts, and are typically solitary. The most common clinical presentation is serous or serosanguineous nipple discharge. The benign solitary papilloma has 1.5 to 2.0 times high risk of breast carcinoma whereas four times increased risk of malignant transformation is noted in atypical papillomas. The peripheral papillomas arise in the terminal duct lobular units and are often discovered incidentally on imaging studies and risk of carcinoma is even higher than solitary papilloma. And very rarely, benign papillomas of breast presenting with local or distant metastases have been reported [10, 11, 12, 13, 14, 15, 16, 17, 18]. However, behavior and management of papillary carcinoma whether in situ or invasive remain a matter of debate. The lymph node involvement, local recurrence and distant recurrence may be seen. Solid papillary carcinoma are localized lesions and may involve lymph node however distant metastasis is rare [6, 7]. Common clinical features include nipple discharge and palpable masses in some cases, however papillary lesions may be diagnosed in asymptomatic women or on screening [19].
Treatment of benign papillary neoplasms require careful evaluation as the presence of papillary architecture is known to be associated with a higher risk of carcinoma breast [20]. The precise diagnosis of papillary neoplasm of the breast is difficult on cytomorphological charaterstics alone. A benign diagnosis on fine needle aspiration or core needle biopsy may not completely exclude malignancy especially if it manifests as focal carcinoma in-situ or abruption of the myoepithelial layer. Microcalcification is an important factor in the management of breast intraductal papillomas diagnosed on core biopsy [21, 22, 23, 24]. The benign papillary lesions can be diagnosed with sonographically guided 14-gauge core needle biopsy. The sensitivity for detecting papillary lesions is greater by ultrasound than mammography. The USG findings of papillary neoplasm are found to be correlated with pathologic findings [13, 25]. Recently, automated breast ultrasound scanners have been developed, and the ultrasound volume data set of the whole breast can be acquired in a standard manner [26]. MRI features including a mass size exceeding 10 mm may indicate a papilloma with high-risk or malignant lesions [27].
However, histopathological examination is the gold standard tool for the diagnosis. Nevertheless, the morphology is more important than the immunostaining pattern, and diagnosis of neoplastic proliferation should not be made on the immunostaining pattern alone. For intraductal papillary neoplasm CK5/6 is good marker to differentiate between intraductal hyperplasia (CK5/6 positive) and intraductal proliferation resembling DCIS or ADH (CK5/6 negative). Immunohistochemical examination with CK5/6 and a panel of two myoepithelial markers (p63, SMA, CD10, calponin) acts as useful tool in assessing papillary neoplasms of the breast [28, 29].
The treatment of benign and atypical papilloma is being evolved. The surgical excision of all papillary lesions is recommended for definitive diagnosis and standard management for malignant papillary lesions [24, 30]. Li X et al. suggested the vacuum assisted excision is applicable for complete excision of small papillomas, even papillomas with atypical hyperplasia [31]. Bianchi et al. also emphasized that, in addition to surgery, vacuum assisted excision of beingn intraductal papilloma may be done [32]. However, some authors have recommended that benign papillary lesions diagnosed by core needle biopsy (CNB) might not require immediate excision, but may be safely managed with imaging follow-up for at least 5 years rather than with surgical excision [33, 34]. Accurate results and coordination between a trained radiologist and pathology are of utmost importance in the decision making between follow-up or surgery [35]. However, Fatima K et al. have observed no reliable clinical or imaging features that can pre-surgically predict atypical upgradation or malignant potential [30]. Tokiniwa H and fellows detected surgical excision advantageous for papillary lesions especially for the lesions located far from the nipple [36]. The atypical papillary lesions should be excised surgically (Figure 1) [37].
Surgically excised specimen of papillary neoplasm.
Intraductal carcinomas like encapsulated papillary carcinoma (EPC) with presence of myoepithelial cells at the periphery should be treated as DCIS and with lack of myoepithelial cells may behave in an indolent invasive pattern with reported lymphnode metastasis and lymphovascular invasion. The present harmony is to manage EPC as in situ disease, though recurrence may be seen associated with aggressive behavior (Figure 2).
Surgically excised specimen of EPC.
Due to lack of evidence of behavior and criterion of diagnosis, SPC is difficult to categorize as benign or malignant and current consensus is to consider it as an in-situ disease. Consensus is to treat these types of neoplasms for local control without axillary node sampling or systemic therapy. Inspite of very low risk of metastatic potential, evidence does not support use of conventional forms of adjuvant systemic therapy. IPC is known to have benign behavior with 100% disease-specific survival rate so to be treated with similar way to other types of carcinoma breast except in cases with moderate nuclear atypia [7, 38].
Papillary neoplasm is difficult to detect and diagnose, if diagnosed, surgical excision is the treatment of choice. Encysted and solid papillary carcinoma should be treated as DCIS, irrespective of nuclear grading. Amongst imaging studies ultrasoography is better than mammography. In difficult cases immunohistochemical markers (CK 5/6 and minimum two myeloepithelial markers provide the support. Invasive papillary carcinoma may be treated as per guidelines of invasive carcinoma breast and shows good prognosis.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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Within academia, it has frequently been seen as the bastion of medical teaching, even as a handmaid of surgery. To the general public over recent years, it is represented by the enormously popular public exhibitions of plastinated cadavers and body parts. Increasingly within medical teaching, it has acquired a far more humanistic face, epitomized by ceremonies at the start and end of dissection to connect the dead body with the once living individual and his/her families. Modern anatomy has also developed a strong research ethos. These movements can be traced in the many editions of Gray’s Anatomy, from 1858 to the present day. However, the humanistic side of anatomy reminds us that anatomy is not merely a science, since its ethical dimensions are legion as it has transformed from a dubiously moral and barely legal activity to one that now aims to manifest the highest of ethical standards. Nevertheless, it continues to have challenging dimensions, such as its ongoing dependence upon the use of unclaimed bodies in many societies. These challenges are reminders that anatomy does not remain stationary.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"David Gareth Jones",authors:[{id:"35851",title:"Prof.",name:"Gareth",middleName:null,surname:"Jones",slug:"gareth-jones",fullName:"Gareth Jones"}]},{id:"55203",doi:"10.5772/intechopen.68775",title:"Innovative Technologies for Medical Education",slug:"innovative-technologies-for-medical-education",totalDownloads:2124,totalCrossrefCites:3,totalDimensionsCites:4,abstract:"This chapter aims to assess the current practices of anatomy education technology and provides future directions for medical education. It begins by presenting a historical synopsis of the current paradigms for anatomy learning followed by listing their limitations. Then, it focuses on several innovative educational technologies, which have been introduced over the past years to enhance the learning. These include E-learning, mobile apps, and mixed reality. The chapter concludes by highlighting future directions and addressing the barriers to fully integrating the technologies in the medical curriculum. As new technologies continue to arise, this process-oriented understanding and outcome-based expectations of educational technology should be embraced. With this view, educational technology should be valued in terms of how well the technological process informs and facilitates learning, and the acquisition and maintenance of clinical expertise.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Pascal Fallavollita",authors:[{id:"85455",title:"Prof.",name:"Pascal",middleName:null,surname:"Fallavollita",slug:"pascal-fallavollita",fullName:"Pascal Fallavollita"}]},{id:"54586",doi:"10.5772/67897",title:"Human Brain Anatomy: Prospective, Microgravity, Hemispheric Brain Specialisation and Death of a Person",slug:"human-brain-anatomy-prospective-microgravity-hemispheric-brain-specialisation-and-death-of-a-person",totalDownloads:1557,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Central nervous system seems to float inside a craniospinal space despite having miniscule amount of CSF. This buoyancy environment seems to have been existing since embryogenesis. This indicates central nervous system always need microgravity environment to function optimally. Presence of buoyancy also causes major flexure to occur at midbrain level and this deep bending area of the brain, better known as greater limbic system seems to regulate brain functions and site for cortical brainwave origin. These special features have made it as a possible site for seat of human soul and form a crucial part in discussion related to death. Besides exploring deep anatomical areas of the brain, superficial cortical areas were also studied. The brainwaves of thirteen clinical patients were analysed. Topographical, equivalent current dipoles and spectral analysis for somatosensory, motor, auditory, visual and language evoked magnetic fields were performed. Data were further analysed using matrix laboratory method for bilateral hemispheric activity and specialization. The results disclosed silent word and picture naming were bilaterally represented, but stronger responses were in the left frontal lobe and in the right parieto-temporal lobes respectively. The sensorimotor responses also showed bilateral hemispheric responses, but stronger in the contralateral hemisphere to the induced sensation or movements. For auditory-visual brainwave responses, bilateral activities were again observed, but their lateralization was mild and could be in any hemisphere. The conclusions drawn from this study are brainwaves associated with cognitive-language, sensorimotor and auditory-visual functions are represented in both hemispheres; and they are efficiently integrated via commissure systems, resulting in one hemispheric specialization. Therefore, this chapter covers superficial, integrative and deep parts of human brain anatomy with emphasis on brainwaves, brain functions, seat of human soul and death.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Zamzuri Idris, Faruque Reza and Jafri Malin Abdullah",authors:[{id:"42580",title:"Prof.",name:"Jafri",middleName:"Malin",surname:"Abdullah",slug:"jafri-abdullah",fullName:"Jafri Abdullah"},{id:"73844",title:"Prof.",name:"Zamzuri",middleName:null,surname:"Idris",slug:"zamzuri-idris",fullName:"Zamzuri Idris"},{id:"200214",title:"Dr.",name:"Faruque",middleName:null,surname:"Reza",slug:"faruque-reza",fullName:"Faruque Reza"}]},{id:"66388",doi:"10.5772/intechopen.85177",title:"Orexin System and Avian Muscle Mitochondria",slug:"orexin-system-and-avian-muscle-mitochondria",totalDownloads:864,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"In mammals, orexin A and B (also known as hypocretin 1 and 2) are two orexigenic peptides produced primarily by the lateral hypothalamus that signal through two G-protein-coupled receptors, orexin receptors 1/2, and have been implicated in the regulation of several physiological processes. However, the physiological roles of orexin are not well defined in avian (non-mammalian vertebrate) species. Recently, we made a breakthrough by identifying that orexin and its related receptors 1/2 (ORXR1/2) are expressed in avian muscle tissue and cell line, and appears to be a secretory protein. Functional in vitro studies showed that orexin A and B differentially regulated expression of the orexin system, suggesting that orexins might have autocrine, paracrine, and/or endocrine roles. Administration of recombinant orexin modulated mitochondrial biogenesis, dynamics, function, and bioenergetics. In this chapter, we include a brief overview of the (patho) physiological role of orexin, comparative findings between mammalian and avian orexin, and in-depth analysis of orexin’s action on avian muscle mitochondria.",book:{id:"7870",slug:"muscle-cells-recent-advances-and-future-perspectives",title:"Muscle Cells",fullTitle:"Muscle Cells - Recent Advances and Future Perspectives"},signatures:"Kentu Lassiter and Sami Dridi",authors:[{id:"274577",title:"Ph.D. Student",name:"Kentu",middleName:null,surname:"Lassiter",slug:"kentu-lassiter",fullName:"Kentu Lassiter"},{id:"274579",title:"Dr.",name:"Sami",middleName:null,surname:"Dridi",slug:"sami-dridi",fullName:"Sami Dridi"}]},{id:"66964",doi:"10.5772/intechopen.85903",title:"Vascularisation of Skeletal Muscle",slug:"vascularisation-of-skeletal-muscle",totalDownloads:926,totalCrossrefCites:0,totalDimensionsCites:3,abstract:"Skeletal muscle is mainly involved in physical activity and movement, which requires a large amount of glucose, fatty acids, and oxygen. These materials are supplied by blood vessels and incorporated into the muscle fiber through the cell membrane. In contrast, metabolic waste is discarded outside the cell membrane and removed by blood vessels. The formation of a functional, integrated vascular network is a fundamental process in the growth and maintenance of skeletal muscle. On the other hand, vascularization is one of the main central components in skeletal muscle regeneration. In order for regeneration to occur, blood vessels must invade the transplanted muscle. This is confirmed by the fact that muscle regeneration occurred from the outside of the muscle bundle toward the inner regions. In fact, it is likely that capillary formation is a key process to start muscle regeneration. Thus, vascularization activates muscle regeneration, and a decrease in vascularization could lead to disruption the process of muscle regeneration. Also, a better understanding of vascularization of skeletal muscle necessary for the successful formation of collateral arteries and recovery of injured skeletal muscle may lead to more successful strategies for skeletal muscle regeneration and engineering. So, in this chapter, we want to review vascularization in skeletal muscle.",book:{id:"7870",slug:"muscle-cells-recent-advances-and-future-perspectives",title:"Muscle Cells",fullTitle:"Muscle Cells - Recent Advances and Future Perspectives"},signatures:"Kamal Ranjbar and Bayan Fayazi",authors:[{id:"143655",title:"Ph.D. Student",name:"Kamal",middleName:null,surname:"Ranjbar",slug:"kamal-ranjbar",fullName:"Kamal Ranjbar"},{id:"299168",title:"Dr.",name:"Bayan",middleName:null,surname:"Fayazi",slug:"bayan-fayazi",fullName:"Bayan Fayazi"}]}],mostDownloadedChaptersLast30Days:[{id:"70162",title:"Rehabilitation of Lateral Ankle Sprains in Sports",slug:"rehabilitation-of-lateral-ankle-sprains-in-sports",totalDownloads:1246,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Lateral ankle sprains are one of the most common injuries in athletes. The rate of injury is as high as 70%. The most commonly involved ligament is the anterior talofibular ligament (ATFL), followed by the calcaneofibular (CFL) and posterior talofibular ligament (PTFL). The common mechanism of injury is inversion with excessive ankle supination in forced plantarflexion when the ankle joint is in its most unstable position. There are three grades of ankle sprains: Grade I, mild with an incomplete tear of ATFL; Grade II, moderate with a complete tear of ATFL with or without an incomplete tear of CFL; and Grade III, severe with complete tear of ATFL and CFL. Grades I and II respond well to functional treatment. Functional treatment includes RICE protocol, i.e., rest, ice, compression, and elevation. It also includes range of motion and strengthening exercises, proprioceptive training, and sports-specific exercises. Bracing and taping of the ankle joint help in preventing the sprains and also reduce the recurrence of the injury. Grade III ankle injury may be treated with surgery if the symptoms persist post functional treatment. The guidelines provided for the treatment of ankle sprains are of general validity, but each athlete is different with different needs. Hence, a personalized exercise protocol should be followed to achieve best results.",book:{id:"9413",slug:"essentials-in-hip-and-ankle",title:"Essentials in Hip and Ankle",fullTitle:"Essentials in Hip and Ankle"},signatures:"Rachana Dabadghav",authors:[{id:"305115",title:"M.Sc.",name:"Rachana",middleName:null,surname:"Dabadghav",slug:"rachana-dabadghav",fullName:"Rachana Dabadghav"}]},{id:"55330",title:"Mesencephalon; Midbrain",slug:"mesencephalon-midbrain",totalDownloads:3385,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"The mesencephalon is the most rostral part of the brainstem and sits above the pons and is adjoined rostrally to the thalamus. It comprises two lateral halves, called the cerebral peduncles; which is again divided into an anterior part, the crus cerebri, and a posterior part, tegmentum. The tectum is lay dorsal to an oblique coronal plane which includes the aquaduct, and consist of pretectal area and the corpora quadrigemina. In transvers section, the cerebral peduncles are seen to be composed of dorsal and ventral regions separated by the substantia nigra. Tegmentum mesencephali contains red nucleus, oculomotor nucleus, thochlear nucleus, reticular nuclei, medial lemnisci, lateral lemnisci and medial longitudinal fasciculus. In tectum, the inferior colliculus and superior colliculus have main nucleus, which are continuous with the periaqueductal grey matter. The mesencephalon serves important functions in motor movement, particularly movements of the eye, and in auditory and visual processing. The mesencephalic syndrome cause tremor, spastic paresis or paralysis, opisthotonos, nystagmus and depression or coma. In addition cranial trauma, brain tumors, thiamin deficiency and inflammatory or degenerative disorders of the mesencephalon have also been associated with the midbrain syndrome.",book:{id:"5933",slug:"human-anatomy-reviews-and-medical-advances",title:"Human Anatomy",fullTitle:"Human Anatomy - Reviews and Medical Advances"},signatures:"Ayla Kurkcuoglu",authors:[{id:"200913",title:"Prof.",name:"Ayla",middleName:null,surname:"Kurkcuoglu",slug:"ayla-kurkcuoglu",fullName:"Ayla Kurkcuoglu"}]},{id:"64758",title:"Introductory Chapter: Histological Microtechniques",slug:"introductory-chapter-histological-microtechniques",totalDownloads:2281,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"7329",slug:"histology",title:"Histology",fullTitle:"Histology"},signatures:"Vonnie D.C. Shields and Thomas Heinbockel",authors:[{id:"70569",title:"Dr.",name:"Thomas",middleName:null,surname:"Heinbockel",slug:"thomas-heinbockel",fullName:"Thomas Heinbockel"}]},{id:"63843",title:"Salivary Glands",slug:"salivary-glands",totalDownloads:3945,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Saliva is a fluid secreted by the salivary glands that keeps the oral cavity moist and also coats the teeth along with mucosa. The salivary gland possesses tubuloacinar units, and these are merocrine. The functional unit of the salivary glands is the terminal secretory piece called acini with a roughly spherical or tubular shape. It also consists of branched ducts for the passage of the saliva and also plays an important role in the production and modification of saliva. Each type of duct is lined by different types of epithelia, on the basis of its location. Myoepithelial cells are contractile cells with respect to intercalated and secretory endpieces. Parotid, submandibular, and sublingual glands are the major salivary glands. The minor salivary glands are labial and buccal gland, glossopalatine gland, and palatine and lingual glands. Saliva plays an important role in mastication, speech, protection, deglutition, digestion, excretion, tissue repair, etc. Secretion stimulated in response to sympathetic stimulation will differ in protein and electrolyte from that due to parasympathetic stimulation. The concentration of saliva depends only on the rate of flow and not on the nature of stimulus. 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Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. 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",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,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:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,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},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"26",type:"subseries",title:"Machine Learning and Data Mining",keywords:"Intelligent Systems, Machine Learning, Data Science, Data Mining, Artificial Intelligence",scope:"The scope of machine learning and data mining is immense and is growing every day. 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