Effect of Mouse KOs on Platelet Production and/or Platelet Clearance.
\r\n\tEqually, the interlinkages that the adrenal gland has in the human body create the premises both for the description of the intimate mechanisms that induce adrenal diseases on other tissues and organs and also for strategic considerations when it comes to treatment.
\r\n\r\n\tThis book, which is aimed at both endocrinologists and practitioners in other medical fields, therefore offers an insight into the mysteries of adrenal disease and a comprehensive overview of the current state of knowledge of this gland, providing an easy-to-follow format that focuses on the most important developments in the field of etiopathogenesis, clinical and paraclinical diagnosis, and treatment of these conditions.
",isbn:"978-1-80356-687-0",printIsbn:"978-1-80356-686-3",pdfIsbn:"978-1-80356-688-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"86c26879d83ac24206ed5476b6cde7fd",bookSignature:"Dr. Diana Loreta Paun",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11853.jpg",keywords:"Cushing Syndrome, Etiopathogenesis, Diagnosis, Treatment, Minimally Invasive Technique, Adrenalectomy, Adrenal Diseases, Perioperative Management, Adrenal Cancer, Genetics, Adrenal Mass, Imaging",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 22nd 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",remainingDaysToSecondStep:"8 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Practitioner endocrinologist, associate professor, researcher, and manager of the National Institute of Endocrinology in Romania, coordinator of investment research and training projects, funded by European funds. Dr. Paun is a member of The Romanian Association of Clinical Endocrinology, member and president(2011-2012, 2017-2019) of The Romanian Chapter of the AACE (American Association of Clinical Endocrinologists). Dr. Păun was appointed State Advise (2015) and was appointed Presidental Advisor (2019).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"190860",title:"Dr.",name:"Diana Loreta",middleName:null,surname:"Paun",slug:"diana-loreta-paun",fullName:"Diana Loreta Paun",profilePictureURL:"https://mts.intechopen.com/storage/users/190860/images/system/190860.jpg",biography:"PĂUN DIANA LORETA, MD, PhD, FACE\r\nBorn on: February 1st, 1968 on Bucharest\r\nEmployed to: “Carol Davila”, University of Medicine and Pharmacy\r\nPosition: endocrinologist, Ph.D, Associate Professor of Endocrinology\r\nFellow of the American College of Endocrinology\r\nExperience: General Manager of “CI Parhon” Institute of Endocrinology, Bucharest, 2006-2015.\r\nMaster in Public Health\r\nQualifications in: Diabetology, Osteoporosis, Endocrine Ultrasonography, Public Health. Training in molecular biology laboratory techniques – Max-Planck-Institut für Psychiatrie, Dept. of Chemie u. Endokrinologie, München, 2002\r\nOccupational field: Clinical, Educational and Research activities, Management, Healthcare services.\r\nPostgraduate courses in: Informatics, Clinical Endocrinology, Infertility, Sexology, Public Health etc.\r\nProfessional career:\r\nChemistry-Biology High School graduated on 1986, Faculty of Medicine graduated on 1992, Th.Burghele Hospital doctor on probation during 1993–1994\r\nendocrinology resident to CI Parhon Institute of Endocrinology 1994-1998\r\nendocrinologist since 1998\r\nAssistant Professor, Lecturer, Associated Professor of Endocrinology, Carol Davila University of Medicine and Pharmacy, Bucuresti, Romania\r\nPublications: papers presented on national and international meetings, articles publishised in well-known journals, author and coauthor in monographs and clinical guides book.\r\nParticipation on research projects and clinical trials: Director and member of the team in research projects and in clinical trials.",institutionString:"Carol Davila University of Medicine and Pharmacy",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree: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:"455410",firstName:"Dajana",lastName:"Jusic",middleName:null,title:"Mrs.",imageUrl:"https://mts.intechopen.com/storage/users/455410/images/20500_n.jpeg",email:"dajana.j@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:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.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"}}]},chapter:{item:{type:"chapter",id:"49161",title:"Production and Destruction of Platelets",doi:"10.5772/60678",slug:"production-and-destruction-of-platelets",body:'Platelet counts in blood are controlled by the rates of their production by megakaryocytes and the kinetics of their removal. Alterations in either process can lead to thrombocytopenia (TCP) or thrombocytosis. Under conditions of TCP, the spleen and liver are the sites for accelerated platelet destruction, and in thrombocytosis, the spleen can become a supplemental breeding ground for megakaryocytes, in addition to the bone marrow space. Humans produce and remove 1011 platelets per day. Senile or damaged platelets are detected as such and are removed from blood. Platelets must also be removed locally at diverse sites where they have discovered vascular damage, attached and become activated to prevent blood leakage. The mechanism of this local removal in the blood vascular system is not well described or understood. The removal of platelets from flowing blood mandates a system that detects changes that accumulate in the platelet surface with age and that responds by binding and removing the platelets when changes reach a critical level. Surface changes must either increase the availability of clearance ligands or remove anti-clearance signals such as CD47 [1]. Changes in the platelet surface that signal for removal include phosphatidylserine upregulation, deglycosylation of membrane glycoproteins, in particular Gp1bα of the vWf receptor, and Ig binding. Diseases that accelerate removal arbitrate their impact at the platelet surface.
This section highlights recent advancements in understanding how platelet lifetimes in blood are regulated and the discovery of a surprising feedback pathway that links platelet removal by hepatocytes in liver to platelet production in the bone marrow.
Platelet senescence is driven by both an internal proteolytic clock and through external changes that occur on the cell surface as they circulate in blood. Internally, platelets have an apoptotic mechanism that sets limits on the overall platelet lifetime at ~10 days [2]. At the time of birth, each mature platelet has a defined quota of the pro-survival protein Bcl-x that with time degrades, releasing its brake on the activities of Bak and Bax that subsequently induce mitochondrial lysis, cytochrome C release, and the activation of cytoplasmic capases. Capases disassemble the cytoskeleton and lead to the upregulation of phosphatidylserine to the platelet surface. Cells that have phosphatidylserine on their surfaces are avidly recognized and removed by the professional phagocytes, macrophages and immature dendritic cells. Multiple receptors have been identified for phosphatidylserine on phagocytes including CLM-1 or CD300f [3], Tim-4 [4], BaI1 [5], or Stabilin-1 receptor [6].
Platelets express CD47 on their surface. CD47, also called integrin associated protein [7], is a member of the immunoglobulin superfamily that associates with the integrins, αIIbβ3 and αvβ3, on platelets. A role for CD47 in maintaining platelets in circulation was first recognized in knockout mice, which have platelets counts reduced by ~20% compared to normal. This highly glycosylated surface protein is recognized by the SIRPα transmembrane protein on phagocytes that contains two immunoreceptor tyrosine-based inhibitory domains in its cytoplasmic domain. Hence, ligation by CD47 transmits anti-phagocytic signals to macrophages, independent of the phagocytic receptor engaged, helping to prevent macrophages for engaging phagocytic pathways involving Fc receptors.
One example where phosphatidylserine exposure can induce macrophages to remove platelets occurs with FlnA null platelets. Mice having megakaryocytes and platelets that lack FlnA are macrothrombocytopenic, with platelet counts reduced by 80-90%, compared to WT mice. FlnA null platelets are unstable because they lack FlnA’s actin filament crosslinking activity and its membrane glycoprotein attachment sites, which link the actin cytoskeleton to the plasma membrane. FlnA constitutively binds to the GP1bα chains of the vWF complex, as well as certain β-integrin chains. The high density of the vWfR-FlnA interaction, ~12,000 per platelet, stabilizes the membrane by attaching it to the underlying actin cytoskeleton. Because the vWfR is linked to the sides of actin filaments it also regulates the topology of the vWf receptor, aligning the receptor in linear arrays on the platelet surface. When studied
Sialic acid terminates the N- and O-linked glycans of all cell surface glycoproteins. Desialylation of platelet glycans was the first recognized mechanism that can target platelets for clearance. In 1975, Greenberg and colleagues [9] showed that desialylation of platelets (and erythrocytes)
The Asgr was one of the first receptors to be identified and characterized [12] over 40 years ago. Each surface Asgr is a heterotrimer composed of 2 HL-1 chains and 1 HL-2 chain. Knock out animals lacking in the expression of either chain, therefore, do not have functional Asgr receptors on their hepatocytes. The Asgr is a C-type lectin that recognizes exposed β-galactose, the underlying moiety to which sialic acid is linked in carbohydrate chains. Most glycoproteins have their glycans capped by α2,3-linked sialic acid. Galactose exposure is mediated by sialidases present in blood or released into blood by infectious bacteria. Interestingly and of high clinical impact, the Asgr can also bind to α2,6 linked sialic acid residues on glycoproteins.
Desialylated platelets are recognized and removed by the liver Asgr [13-15]. The specific function of the Asgr in platelet removal has been demonstrated by the following evidences: (1) HepG2 cells bind and ingest desialylated platelets
The importance of hepatocyte-platelet interaction extends beyond simple removal, as the recognition and ingestion of platelets by the Asgr generates cytoplasmic signals in hepatocytes that induce the formation and secretion of cytokines to promote marrow and megakaryocyte growth and maturation. In this case, the key cytokine produced in response to platelet ingestion is thrombopoietin [16]. Thus, the hepatocyte-platelet interaction directly feeds back to megakaryocytes in marrow, helping to stimulate platelet production.
In addition to its receptors that recognize phosphatidylserine, macrophage surfaces are festooned with receptors that can ingest damaged and/or diseased platelets. One group includes the lectin receptors that recognize carbohydrate alterations in platelet glycoproteins. The phagocytic integrin, αMβ2, recognizes and removes chilled and rewarmed platelets that release glycosylases causing β-GlcNAc moieties to expose on N-linked GP1bα glycans. In addition, a second domain on αMβ2 recognizes a different portion of GP1bα [17]. Mannose receptors are a second example of a receptor that detects glycan alterations, recognizing underlying mannose moieties exposed by glycosylases [18]. Fcγ receptors remove Ig-coated platelets from blood and when anti-platelet Igs are present their effectiveness leads to thrombocytopenia.
Accelerated clearance requires either the accumulation of opsonins on the platelet surface such as Igs and complement or the presence of agents in blood that remove protective molecules. Both types of mechanisms occur.
There are many examples of acquired or induced immune thrombocytopenia that cause platelet removal when anti-platelet Igs are generated, deposited on platelets, and are detected by Fcγ receptors on macrophages. These include congenital and drug or pathogen induced thrombocytopenia. In general, platelet clearance is primarily driven by splenic macrophages, a process that can result in splenomegaly. In many cases, patients having ITP, respond well to anti-Fc antibody treatment.
Bacterial-derived sialidases, released into blood during sepsis, cause platelet counts to drop precipitously. The target of the blood born bacterial sialidases is sialic acid that caps N-linked glycans on GP1bα, as demonstrated using mice lacking GP1bα [19], which are resistant to clearance induced by pneumococcal sepsis in WT mice. Cleavage of sialic acid on GP1bα exposes underlying galactose moieties that are recognized by the Asgr [13]. Animals lacking a functional Asgr do not accelerate their platelet clearance in response to sepsis.
A related process accounts for the circulation failure of platelets transfused after rewarming from refrigerated storage. Resting platelets contain sialidases that are stored in an internal compartment that can be released by activation [15, 20]. Rewarming from the cold releases a portion of the sialidase activity to the platelet surface and into the storage media, a process that mediates desialylation of the platelet surface glycoproteins. Since the accelerated clearance of chilled and rewarmed platelets is to a large extend ablated in mice lacking the Asgr (HL-2-/- mice), it is the main receptor that recognizes and removes cold damaged platelets. Ablation of macrophage function in HL-2-/- mice further restores platelet circulation by 15-20%. Hence, macrophages also participate in clearance.
Mutation, truncation and/or deletion of WASp, a protein encoded on the X-chromosome and expressed by blood cells, results in a profound lymphocyte dysfunction that severely compromises the immune system. Severe thrombocytopenia (TCP) is also a signature component of the Wiskott-Aldrich syndrome; WAS platelets are small and have shortened circulatory lifetimes. WAS patients produce diverse autoantibodies and WAS platelets collect higher amounts of surface-associated immunoglobulins (Igs) than do normal platelets [21]. Many human WAS patients respond to splenectomy with increased platelet counts, despite the finding that all patients have been found to be refractory to anti-Fcγ antibodies. Unlike ITP, homologous platelets circulate normally in WAS patients strongly suggesting a more complex mechanism for removal that involves receptors other than Fc.
WASp KO mice have been shown to retain the key features of WAS disease, having T and B lymphocyte dysfunction, enlarged spleens, low platelet counts (70% of normal) and shortened platelet survival times in blood. It has been widely believed that platelet clearance is accelerated in these animals because the autoimmune aspect of the disease results in increased Igs bound to the platelets surface that led to recognition by splenic macrophages. However, as in the human conditions, normal platelets, when transfused into WASp KO mice, circulate normally indicating that a simple anti-platelet antibody mediated clearance is not the mechanism. In mice, splenectomy has been shown to be without effect on the clearance rate.
In efforts to identify the mechanism of removal, WASp Null platelets were transfused into mice lacking specific phagocytic receptors. A survey on macrophage receptors failed to reveal any in which the WASp null platelets had enhanced circulatory lifetimes. However, WASp KO platelets were found to circulate normally in Asgr null mice, a finding once again posits the Asgr as a central molecule involved in the recognition and removal of damaged platelets. The surface of WASp KO platelets is, however, not desialylated and lectin binding studies have instead revealed hypersialylation. This sialylation occurs specifically in the 2,6 linkage, not the normal 2,3 linkage. Critically, the Asgr also receptor recognizes this unique sialic linkage, leading to binding and platelet removal. The carrier of this sialic acid turns out to be surface bound Ig and sialylation of its Fc N-linked glycan shifts recognition of the Fc domain from macrophages to the hepatocytes.
Interestingly, the source of the 2,6 sialyltranferase (ST6Gal1) is liver hepatocytes, which make and secrete this enzyme into blood. This blood enzyme is an acute phase reactant protein, upregulated in liver in response to bacterial sepsis, cancer, or inflammation. In this case, platelet ingestion itself, feedbacks to upregulate ST6Gal1 mRNA transcription and translation and this increases by 3-4 fold the blood levels of this enzyme.
The modification(s) in WASp KO platelet surface that leads to Ig production by WASp KO B-lymphocytes and Ig-binding are not known. Since WT platelets do not collect Igs in WASp KO plasma or have accelerated clearance in WASp KO animals, surface alterations are specific for the WASp KO platelets. Because WASp is a protein that interacts with the actin cytoskeleton, it is likely that internal cytoskeletal changes in its absence result in an altered topology of platelet receptors or the expression of the neo-epitope. In general, platelet function in the absence of WASp is near normal although as the precision of assays increase, some differences have now been recognized. Active platelets lack small focal actin assembly sites in the absence of WASp, although spreading and filopodial formation are normal. In resting platelets, failure to express WASp alters the stability of microtubules, increasing their acetylation and slowing their turnover. How these internal changes alter the surface remains for future studies.
The basic processes involved in megakaryocyte commitment, maturation and platelet formation are well described although many precise details remain to be clarified. Megakaryocytes derive from a renewable population of hematopoietic stem cells that continuously enter the MK/platelet lineage and once committed to produce platelets, live for only a few more weeks before they are converted into hundreds of platelets. Proplatelet and platelet production requires a massive enlargement in MK size that is driven by high levels of mRNA transcription from their amplified polyploid nuclei followed by mRNA translation into platelet essential components. This includes the production of an abundant internal network of membranes called the demarcation membrane system (DMS) that dramatically increases the apparent membrane to surface ratio during proplatelet formation, platelet specific granules, and the synthesis of large amounts of the cytoskeletal machinery that is used to form and fill assembling platelets.
As MKs mature, they develop an extensive network of internal membranes called the DMS that are enriched phosphatidylinositol 4,5 bisphosphate and the vWf receptor [22] and are used as the primary membrane source for proplatelet elongation. Recent studies by Eckly et al [23] have begun to shed some light on DMS formation, describing how the DMS forms and matures. To form the DMS, the plasma membrane of megakaryocytes enfolds at specific sites and a perinuclear pre-DMS is generated. Next, the pre-DMS is expanded into its mature form by material added from golgi-derived vesicles and endoplasmic reticulum-mediated lipid transfer. This structural description is in accordance with the studies on platelet glycosyltransferases, which arrive early in the forming DMS and eventually make their way to the megakaryocyte and platelet surfaces [24]. Only a small number of proteins have been identified thus far to participate in the DMS formation process based on alterations in its structure in certain knockout animals. Gross disruptions of this network are found in megakaryocytes isolated from either filamin A knockout or pacsin2 knockout mice, the latter of which connects GP1bα to the actin cytoskeleton and binds pacsin2, a molecule that deforms membrane. The relationship between the DMS and the platelet open canalicular system (OCS) is not clear. The OCS, like the DMS, is a unique anastomosing network of internal membrane tubes that is connected to the plasma membrane at multiple points. The internal canals of the OCS can be identified because they contain vWfR, and hence can be labeled with anti-GP1bα antibodies (Kahr et al).
To release platelets, megakaryocytes in the marrow space move to and nestle the marrow sinusoids where they project their proplatelet protrusions into the blood flow [25, 26]. Whether all proplatelets are directed to grow specifically into the sinusoids or if only some of the proplatelets elaborated by a MK find their way into the sinusoids is unknown, although living MKs in marrow have been observed to have many proplatelet projections, some of which project into the marrow space while others project into the sinusoids [27]. Studies have demonstrated that proplatelet fragments considerably larger than platelets are released by MKs into blood [26, 27] and that proplatelets can be both found, and can mature into platelets, in blood [28].
The state of our current knowledge of the mechanics of proplatelet production has come primarily from studies on MKs in culture. This work has clarified the essential role of microtubules, which were recognized early as the most prominent structure found within the MK projections [29] and that proplatelet and platelet production were adversely affected by MT poisons [30]. Subsequent gene expression studies established the importance of β1-tubulin, a tubulin isoform specific for MKs, to the maturation of MKs into proplatelet producing machines [31]. More recent studies using gene deleted MKs have begun to reveal the precise roles of specific proteins in proplatelet and platelet production and these are highlighted below.
Signals that initiate proplatelet formation, if present, remain undefined and it remains possible that the program to make platelets starts when the synthesis of cytoskeletal proteins for this process reaches a critical mass. From a mechanical view, centrosome dissolution precedes proplatelet extension, and the release of MTs from these multiple nucleating sites correlates best with the start of proplatelet elaboration. Released MTs first collect as bundles in the MK cortex where they are driven apart by their associated motor protein, dynein. These MT-dynein reactions deform the membrane outward and generate the structural motor of the proplatelet, which is a MT bundle that folds over in the proplatelet tip and runs back into the shafts. Each bundle is composed of many MTs that are continuously growing and shrinking from their ends. Six types of behaviors characterize the elaboration of proplatelets: elongation, branching, pausing, fusions, fragmentations, and retractions. While the average elongation rate for proplatelets over time is ~1 µm/min, extension normally occurs in bursts and pauses. Burst rates greatly exceed the average rates and under flow, and rates of >30 µm/min have been observed. These rates correlate well with the sliding rates of MTs within the bundles. Pauses in proplatelet extension are not caused by a stoppage in MT sliding, which continues at a 1-6 µm/min rate. Sliding reactions in paused proplatelets appear to build tension into the bundle which when released leads to branching and/or fragmentation. This implies that there are regions within the bundles where MTs are crosslinked to increase resistance or they are pushing against resistive structures. Branching is a modified form of extension derived from tension asymmetry where a portion of the MT bundle detaches from the mother bundle and elongates rapidly forming a new tear shaped structure and proplatelet shaft. Retraction, where the sliding could either reverse or all crosslinking derived tension releases, could serve to subfragment the proplatelets.
In addition to playing a crucial role in proplatelet elongation, the microtubules lining the shafts of proplatelets serve a secondary function — tracks for the transport of membrane, organelles, and granules into proplatelets and assembling platelets at proplatelet ends [32]. Individual organelles are sent from the cell body into the proplatelets, where they move bidirectionally until they are captured at proplatelet ends. Immunofluorescence and electron microscopy studies indicate that organelles are in direct contact with microtubules, and actin poisons do not diminish organelle motion. Therefore, movement appears to involve microtubule-based forces. Bidirectional organelle movement is conveyed in part by the bipolar organization of microtubules within the proplatelet, as kinesin-coated beads move bidirectionally over the microtubule arrays of permeabilized proplatelets. Of the two major microtubule motors — kinesin and dynein — only the plus-end-directed kinesin is situated in a pattern similar to organelles and granules, and is likely responsible for transporting these elements along microtubules. It appears that a twofold mechanism of organelle and granule movement occurs in platelet assembly. First, organelles and granules travel along microtubules and, second, the microtubules themselves can slide bidirectionally in relation to other motile filaments to indirectly move organelles along proplatelets in a “piggyback” fashion
Although microtubules and associated motor and regulatory proteins power proplatelet motility, elimination of certain actin cytoskeletal-associated proteins have now been demonstrated to modulate this process. These include a number of actin-associated proteins, membrane contouring proteins, and signaling proteins.
Since proplatelets elongate, but do not branch, in the presence of the actin disrupting drug cytochalasin B, it is surprising that the deletion of certain actin associated proteins from the megakaryocyte lineage leads to macrothrombocytopenia. It seems likely that the removal of actin modulating proteins, alters and/or increases filamentous actin (F-actin) and cytoskeletal structure to have a dominant inhibitory effect proplatelet maturation and/or platelet release from proplatelets.
Three proteins, filamin A (FlnA), actinin 1 (Actn1) and spectrin, that crosslink F-actin using a related F-actin binding site, are critical components of the mature platelet cytoskeleton and regulate proplatelet formation and motility.
Platelet specific RhoA deficiency causes macrothrombocytopenia with platelet counts reduced by ~50% from normal. The RhoA-/- platelets have many functional defects that cause animals to readily bleed, but they have normal lifetimes in blood [39]. One pathway by which RhoA deficiency may affect MK maturation and platelet formation is through ROCK modulation of myosin 2a activity in MKs. RhoA activates ROCK, inhibiting myosin LC phosphatase and hence leading to increased myosin LC phosphorylation. This activity is thought to restrain proplatelet elaboration and thus RhoA deficiency to release this brake, causing premature proplatelet formation and leading to enlarged and dysfunctional platelets.
\n\t\t\t\t | \n\t\t\t\n\t\t\t\t \n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t\t\n\t\t\t\t | \n\t\t
GP1ba KO | \n\t\t\t\n\t\t\t | \n\t\t\t | Large, fragile | \n\t\t\t\n\t\t\t | [19] | \n\t\t
Filamin A KO | \n\t\t\tAccelerated proplatelet elaboration, altered DMS | \n\t\t\tAccelerated | \n\t\t\t10-20% of normal: Large, fragile | \n\t\t\t\n\t\t\t | [8] | \n\t\t
Actinin 1 ABD mutants | \n\t\t\tDecreased proplatelet number, increased proplatelet thickness | \n\t\t\tReduced, thickened | \n\t\t\tLarge | \n\t\t\t\n\t\t\t | [36] | \n\t\t
Nonmuscle myosin HC IIA KO | \n\t\t\t\n\t\t\t | Increased, formation accelerated | \n\t\t\tHeterogenous, Reduced by 70% | \n\t\t\tNormal | \n\t\t\t[41] | \n\t\t
Dynamin 2 KO | \n\t\t\t\n\t\t\t | Reduced, thickened | \n\t\t\t20% of normal, size highly variable | \n\t\t\t\n\t\t\t | \n\t\t |
CIP4 KO | \n\t\t\t\n\t\t\t | Reduced | \n\t\t\t\n\t\t\t | \n\t\t\t | [42] | \n\t\t
Pacsin 2 KO | \n\t\t\t\n\t\t\t | \n\t\t\t | Normal | \n\t\t\t\n\t\t\t | \n\t\t |
WASp or WIP KO | \n\t\t\t\n\t\t\t | Accelerated | \n\t\t\tSlightly small | \n\t\t\tAccelerated | \n\t\t\t[43] | \n\t\t
β1-tubulin | \n\t\t\tCompensate by upregulating β2 and β5-tubulin | \n\t\t\tProplatelet formation blocked | \n\t\t\tAmorphic, reduced by 70-75% | \n\t\t\t\n\t\t\t | [44] | \n\t\t
Rab27b | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t\t | \n\t\t\t | [45] | \n\t\t
Cofilin-1 | \n\t\t\t\n\t\t\t | \n\t\t\t | Large | \n\t\t\t\n\t\t\t | [46] | \n\t\t
ADF | \n\t\t\tnormal | \n\t\t\t\n\t\t\t | 90% of normal, size normal | \n\t\t\t\n\t\t\t | [46] | \n\t\t
ADF/Cofilin1 | \n\t\t\tNumbers increased 3X; DMS and cytoplasmic structure altered | \n\t\t\tdecreased | \n\t\t\t5% of normal count; sizes variable, amorphic | \n\t\t\t\n\t\t\t | [46] | \n\t\t
Actin interacting protein (Aip1/Wdr1) | \n\t\t\tDefective megakaryo- poiesis: small, DMS abnormalities | \n\t\t\t\n\t\t\t | 20% of normal: large | \n\t\t\tNormal | \n\t\t\t[40] | \n\t\t
Profilin 1 | \n\t\t\t\n\t\t\t | \n\t\t\t | Large, size variable | \n\t\t\t\n\t\t\t | [47] | \n\t\t
RhoA | \n\t\t\t\n\t\t\t | \n\t\t\t | 50% of normal, large -125% | \n\t\t\tSlight increase in turnover rate | \n\t\t\t[39] | \n\t\t
Spectrin | \n\t\t\t\n\t\t\t | Proplatelets disrupted by dimer-dimer self-association inhibitor | \n\t\t\t\n\t\t\t | \n\t\t\t | [48] | \n\t\t
Tmod3 | \n\t\t\tAltered DMS | \n\t\t\tEnlarged tips | \n\t\t\tLarge, decreased count | \n\t\t\t\n\t\t\t | [49] | \n\t\t
Effect of Mouse KOs on Platelet Production and/or Platelet Clearance.
Cofilin is regulated by Aip1, a protein that binds and enhances filament severing /actin depolymerization activity. The importance of this protein to platelet production has been demonstrated [40]. N-ethyl-N-nitrosourea mutagenesis generated mice with profound thrombocytopenia, bleeding, and enlarged, amorphic platelets contain a gene mutation that was mapped to Wdr1 gene. The high degree of similarity to the phenotype of in the ADF/cofilin double knockout, strongly suggests both proteins are in the same thrombogenesis effector pathway.
In certain ways, the profilin 1 KO phenotype is similar to the behavior of platelets in Wiskott-Aldrich syndrome, or in WASp or WIP KO mice. WASp is a signaling protein promotes actin assembly system, binding to Arp2/3 when activated by binding of GTP-cdc42. However, the bulk of studies performed on human WAS platelets or platelets derived from KO mice revealed normal and ever hyper-function for the WASp null platelets. Human patients have low platelet counts that are caused by accelerated platelet clearance, a process that lowers the platelet count in the Wasp/Wip KO mice. Recently studies have shown the MT ring in platelets from WAS patients to be hyper-acetylated, like the profilin 1 KO platelets. However, in the WAS syndrome, platelets in the circulation are small, not large, as is found in the Profilin null animals.
Neglected tropical diseases (NTDs) include a collection of chronic, disabling, and physically disfiguring infectious diseases that usually affect dwellers of poor rural populations in tropical and sub-tropical countries of the world [1]. Apart from their negative impact on the health of victims, NTDs exert an immense socio-economic burden on the society as a result of the social stigma and physical disabilities associated with them. These interrelated negative outcomes perpetuate a cycle of poverty and unproductivity resulting in a consistent decline in economic growth [2]. As a major element of the Millennium Development Goals (MDGs), much effort is being put in for the elimination of the NTDs [3].
Among the NTDs, helminth infections especially soil-transmitted helminthiasis (STHs) and schistosomiasis are among the most prevalent afflictions of humans [4]. About 2 billion people are estimated to suffer from helminth infections worldwide, out of whom 300 million suffer from severe morbidity [5]. The negative impact of helminth infections on human growth and development (including cognitive development in childhood and nutritional status), pregnancy and work performance cannot be overemphasized. Though considered as acute health problems in some developed parts of the world, chronic parasitic infections are common and recurrent in poor communities and usually result in long-lasting complications making them a significant health threat to the populations who are continuously at risk for infection [6].
Over the years, many highly effective chemotherapeutic agents have been developed for treating helminth infections. Unfortunately in the setting of rural poverty where these diseases are mostly prevalent, access to healthcare facilities and the cost of medications are a challenge [7, 8]. Additionally, environmental factors and unavoidable domestic or occupational exposures, strongly favor the process of re-infection even after a successful therapy [9, 10]. Given that these infections also require lengthy treatment regimens with related costs which cannot be afforded by the affected victims, many patients seek for alternative treatment options especially the use of herbal medicines which are readily available and less expensive [9, 11].
Herbal extracts have been used in traditional medicines since ancient times for the effective treatment of human diseases [12]. Ethnobotanical studies in various regions of the world have documented medicinal plants used for the treatment of various parasitic infections. Scientific investigations of selected plants have also revealed remarkable activity of medicinal plants against specific human parasites [13, 14]. In Ghana, numerous medicinal plants play an important role in the healthcare system of rural communities. The Ghanaian flora provides a ready source for new therapeutic interventions for the local population [15, 16, 17]. This chapter provides a review with special focus on medicinal plants collected from Ghana with anthelmintic and anti-schistosomal activity.
Soil transmitted helminth (STH) infections are a group of infections which are acquired by the ingestion of, or contact with, soil containing infectious worm eggs or larvae [18]. STHs have been reported as the most common parasitic infections encountered in humans with an estimation of more than 1 billion people infected with at least one or more helminth parasites. They constitute an important global health challenge in resource deprived parts of the world and are prevalent in areas of poor sanitary conditions [19].
The main species of clinical importance are the intestinal roundworm (
Anthelmintics are a group of antiparasitic drugs that expel worms and other internal parasites out of the body by either stunting or killing them. For the treatment of STHs, the benzimidazoles specifically albendazole and mebendazole are the current treatment drugs of choice [19]. The main challenge with these anthelminthics is the development of resistance due to the intensive use of drugs in both human and live-stock [22]. With few new drugs evolving against helminth infections over the years, the fight against these parasites could become a losing battle, thus the need to search for new alternatives.
Schistosomiasis, widely known as bilharzia, is caused by infection with blood flukes of the genus
Five species of the schistosome parasite namely:
For the eradication of schistosomiasis, control programmes have been based on preventive chemotherapy. The WHO endorsed and advocated for mass drug administration (MDA) especially among school children utilizing a single oral dose of 40 mg/kg praziquantel [27]. Unfortunately, the unavailability of the drugs due to cost, poor drug coverage, inequity of access to chemotherapy and non-compliance to therapy due to adverse side effects have impeded the progress of this approach [7, 28]. The expansion of preventive chemotherapy has also raised concerns about the potential development of resistance to praziquantel (PZQ) which remains the only commercially readily available drug for the control of schistosomiasis [29]. Some studies have reported low cure rates of PZQ attributing this to possible mutation of the schistosome parasite as well as inactivity of PZQ against early stages of the worms [30, 31]. It is thus not a satisfactory situation to have only one single effective treatment. Ideally, other anti-schistosome drugs should be developed so that the classical strategy of avoiding development of resistance could be followed.
Reported anthelmintic and anti-schistosomal activities of medicinal plants collected from various parts of Ghana were obtained from electronic databases including PubMed, SciFinder and Google Scholar. The inclusion criteria were that: (i) plants should be used in Ghanaian traditional medicine for treatment of worm infestations or expulsion of worms and schistosomiasis (urinary and intestinal) or other condition characterized by the symptoms of the above diseases (ii) plant should have been investigated for anthelmintic or anti-schistosomal (cercarididal) activity using one or more validated
The anthelmintic activity of plant extracts was mostly studied by evaluating their effect on worms after direct exposure for a period of time. Earthworms including
The anthelminthic potency of the petroleum ether, chloroform and methanol extracts of
The methanol extracts (50–150 mg/mL) of the stem bark and roots of
In another study, the aqueous and ethanolic stem bark extracts (50–200 mg/mL) of
The anthelmintic activity of the ethanolic extract of
The pawpaw tree is well known for its nutritional and medicinal values. The leaf decoction is used as a galactogogue and in the treatment of tonsillitis, ulcerative stomatitis, hemorrhoids, asthma, urinary tract infections, as poultice for sores and gingivitis and in the treatment of helminth infections. The roots are used as antidote to various poisons. The fruits are used to treat indigestion, chronic diarrhea, ringworm infections, bleeding piles, and amoebic dysentery [39]. Almost all parts of the plant are documented to be used for managing helminth infections. In Ghana, 74% traditional healers used this plant for treating helminth infections [40].
In a comparative assessment of the anthelminthic activity of various parts of the plant, the hydroethanolic extracts of the leaves, stem bark, and seeds of
Ethnopharmacological reports from parts of Ghana revealed the extensive use of the leaves of
In a previous study, the alcoholic leaf extract of
In another study, fractions and purified compounds from
The anthelmintic and helminth resistance modifying activities of methanol extract of
Further the extract at 1, 2 and 5 mg/mL significantly potentiated the activity of albendazole, mebendazole and levamisole against the test organism. In the presence of 2 mg/mL of the extract the paralysis and death times of albendazole (8 mg/mL) against
In a previous study, the methanol stem bark extract of
In a previous study, the methanol stem bark extract of
The foliage of
The hydroethanolic extract of the roots of
In another study, the 70% aqueous acetone extract, solvent fractions and isolated compounds from the roots of
In a previous, observations were made for the time taken for different solvent extracts of the leaves of
The leaves and stem bark of
The anthelmintic activity of the aqueous and ethanolic extracts of the roots of
In a previous study, the anthelmintic activity
In another study, the stem bark extracts (ethanol and chloroform extracts) of
The methanol extracts of the leaves and stem bark
The ethanolic extract of the dried fruits and leaves (300–300 mg/mL) were investigated for anthelmintic activity against earth worms. The anthelmintic activity of the fruit extract was more potent that the leaf extract. Both extracts demonstrated a concentration dependent activity with the fruit extract demonstrating significant paralytic and death times (
See Table 1.
Plant | Family | Common name | Part Investigated | Activity Type |
---|---|---|---|---|
Euphorbiaceae | Christmas Bush | Leaves | Anthelmintic activity against | |
Apocynaceae | Alstonia | Roots, stem bark | Anthelmintic activity against | |
Meliaceae | Neem | Seeds Leaves | Anthelmintic activity against Cercaricidal and adulticidal activity against | |
Caricaceae | Pawpaw | Leaves, stem bark, seeds | Anthelmintic activity against | |
Combretaceae | — | Leaves | Anthelmintic activity against | |
Cyperaceae | — | Whole plant | Anthelmintic activity against | |
Dichapeltaceae | — | Stems, roots | Anti-schistosomal activity against eggs obtained from clinical isolates of | |
— | Leaves, stem bark Roots | Cercaricidal activity against post-infective larvae (schistosomule) and adult parasite of Cercaricidal activity against freshly shed cercariae from | ||
Gutifferae | Bitter kola | Stem bark | Anthelmintic activity against | |
Apocynaceae | — | Stem bark | Cercariae from | |
Rubiaceae | — | Stem bark | Anthelmintic activity against Cercaricidal activity against Adulticidal effect against | |
Moringaceae | Moringa | Foliage | Anthelmintic activity against | |
Rubiaceae | African peach | Stem bark | Cercaricidal activity against Adulticidal effect against | |
Lamiaceae | Basil | Fruits | Anthelmintic activity against | |
Euphorbiaceae | — | Roots | Anthelmintic activity against the free-living nematode | |
Plumbaginaceae | — | Leaves | Anthelmintic activity against | |
Euphorbiaceae | — | Leaves | Cercaricidal activity against | |
Apocynaceae | Snakeroot | Leaves, roots Roots, stem bark | Anthelmintic activity against Cercaricidal activity against Adulticidal effect against | |
Anacardiaceae | Roots | Anthelmintic activity against | ||
Asteraceae | Bitter leaf | Leaves, stem bark Leaves | Anthelmintic activity against Cercaricidal activity against Adulticidal effect against | |
Apocynaceae | — | Leaf, stem bark | Anthelmintic activity against | |
Apocynaceae | African black pepper | Fruits, leaves | Anthelmintic activity against |
Medicinal plants from Ghana with anthelmintic and anti-schistosomal activity.
[Refer to Section 2.3 for plant description].
The methanol leaf extract of
The effect of
The effect of the extract on the weight of spleen and liver of infected mice were all significantly lesser in the
Crude extracts (pet-ether, ethyl acetate and methanol) and isolated triterpenoids from the stems and roots of
For the stem extracts, the ovicidal potency was in the following order petroleum ether (IC50 = 443.70) > EtOAc (IC50 = 638.00) > MeOH (IC50 = 893.70 μg/mL). The IC50 values for the root extracts were 248.60, 546.40, and 566.30 μg/mL respectively for the EtOAc, pet-ether and MeOH extracts.
The isolated compounds (Friedelan-3-one, β-Sitosterol/stigmasterol, Dichapetalin M and Dichapetalin A) showed higher ovicidal activity than the extracts though activities for both extracts and compounds were lower compared to the standard drug, praziquantel. The highest ovicidal potency was exhibited by β-sitosterol/stigmasterol mixture with an IC50 of 177.90 μg/mL which was about 11 times less potent than praziquantel (15.47 ± 0.06 μg/mL). The next highest was dichapetalin A (151.10 μg/mL) whiles friedelan-3-one showed the least potency with IC50 of 378.10 μg/mL. From the root extract, Dichapetalin M showed ovicidal effect with IC50 of 191.00 μg/mL [75].
The cercaricidal activity of the leaf and stem bark extracts of
In another study, the
The hydroethanolic and alkaloidal extracts from the stem bark of
[Refer to Section 2.8 for plant description].
In a previous study, the cercaricidal activity of the methanol stem bark extract of
Previous studies on the cercaricidal activity the methanolic extract of stem bark of
The methanolic extract (250 μg/mL) of
[Refer to Section 2.13 for plant description].
The root and stem bark of
The ethanolic extract of the root and stem bark were both found to be active against the cercariae and adult worms. At a concentration range of 62.5–1000 𝜇g/mL the stem bark extract exhibited significant anti-cercarial activity (
[Refer to Section 2.15 for plant description].
In a previous study, the evaluation of the cercaricidal and schistosomicidal activities of the methanol extract of the leaves of
The ability of the leaf extract (500 mg/kg
The anthelmintic and anti-schistosomal activities of some medicinal plants employed in Ghanaian traditional medicine have been validated. For most of these plants however, the specific bioactive constituents are not yet identified. It is therefore imperative that further studies to isolate and verify the constituents responsible for the observed activities be performed. Further, the evaluation of safety profiles will add substantial value to the reported bioactivities and make these plants attractive for adaptation to pharmaceutical companies for further development.
Authors have no conflict of interest to declare.
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It is an acute exaggerated clinical manifestation of thyrotoxic state. The exact incidence is unknown. It occurs in 1–2% of patients admitted for thyrotoxicosis. It has a mortality of 10–20%. This chapter would help us to understand its clinical manifestations, pathophysiology, and effective treatment. Terminal learning objective would be to diagnose impending storm early and start prompt treatment in day-to-day practice. The chapter would cover pathophysiology including triggers, clinical features including various diagnostic criteria, diagnosis, and treatment of thyroid storm. Indications of surgical treatment in storm will be discussed.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Rahul Pandey, Sanjeev Kumar and Narendra Kotwal",authors:[{id:"309356",title:"Dr.",name:"Rahul",middleName:null,surname:"Pandey",slug:"rahul-pandey",fullName:"Rahul Pandey"},{id:"310903",title:"Dr.",name:"Sanjeev",middleName:null,surname:"Kumar",slug:"sanjeev-kumar",fullName:"Sanjeev Kumar"},{id:"310904",title:"Dr.",name:"Narendra",middleName:null,surname:"Kotwal",slug:"narendra-kotwal",fullName:"Narendra Kotwal"}]},{id:"70705",title:"Multinodular Goiter",slug:"multinodular-goiter",totalDownloads:932,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Multinodular goiter (MNG) is the most common disorder of the thyroid gland. It is highly endemic in iodine-deficient areas; MNG can be seen in almost all individuals with severe iodine-deficient areas. It starts as a diffuse enlargement of the thyroid gland and ends in a nodular enlarged thyroid. Though MNG can be sporadic, there is a strong correlation between occurrence of MNG and iodine deficiency. The characteristic feature of MNG is its functional and structural heterogeneity. The MNG usually presents as neck swelling; rarely it may produce pressure symptoms, i.e., dyspnea, hoarseness of voice, and dysphagia. It can also present with symptoms of hyperthyroidism particularly in long-standing goiter. Imaging particularly ultrasound is very useful to define characteristic of MNG and surrounding structure. The incidence of malignancy in MNG is 4–14%, and risk factors are family history of thyroid carcinoma, history of neck radiation, prior surgery, and presence of cervical lymphadenopathies. Management of MNG can be done by drugs, surgery, and radioiodine (I-131) depending on results of diagnostic evaluation and associated complications.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Sanjay Saran",authors:[{id:"242737",title:"Dr.",name:"Sanjay",middleName:null,surname:"Saran",slug:"sanjay-saran",fullName:"Sanjay Saran"}]},{id:"61473",title:"Nuclear Medicine in the Assessment of Thyrotoxicosis Associated with Increased Thyroid Function and Radioiodine 131 Ablative Therapies",slug:"nuclear-medicine-in-the-assessment-of-thyrotoxicosis-associated-with-increased-thyroid-function-and-",totalDownloads:1422,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Nuclear medicine is directly involved in both the diagnosis and treatment of benign thyroid disease. Thyroid scintigraphy (most commonly with technetium-99 m pertechnetate) should be used as the imaging modality of choice for assessment of thyrotoxicosis, since it demonstrates the functional state of the thyroid gland. An adequate understanding of the pathophysiological mechanisms and characteristics of the patient is essential, as well as the different treatments of thyroid disorders that present with hyperthyroidism (Graves’ disease, toxic multinodular goiter, and toxic adenoma-Plummer’s disease). Therapeutic modalities include antithyroid drugs, radioiodine and surgery. Antithyroid drugs are the first line of therapy and regarding the use of radioiodine, current recommendations consider it a safe and effective therapeutic alternative in hyperthyroidism. Finally, we highlight the existence of some special situations (children, pregnancy, thyroid eye disease, chronic renal failure and dialysis patients) and the importance of radiation protection measures to the patient, the public and professionals.",book:{id:"6791",slug:"thyroid-disorders",title:"Thyroid Disorders",fullTitle:"Thyroid Disorders"},signatures:"Elena Espinosa Muñoz",authors:[{id:"241332",title:"M.Sc.",name:"Elena",middleName:null,surname:"Espinosa Muñoz",slug:"elena-espinosa-munoz",fullName:"Elena Espinosa Muñoz"}]},{id:"71040",title:"Hyperthyroidism",slug:"hyperthyroidism",totalDownloads:881,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Excess level of thyroid hormones in blood is thyrotoxicosis, which is responsible for clinical syndrome of hypermetabolism, sympathetic hyperactivity. Hyperthyroidism is the term used to denote the overproduction of thyroid hormones from the thyroid gland. Hyperthyroidism is possible with hyperactive thyroid gland due to multi/solitary nodular thyroid disease or Grave’s disease. Thyrotoxicosis associated with thyroiditis is not hyperthyroidism. Treatment of hyperthyroidism is with anti-thyroid drugs (ATT), radio-active iodine ablation (RAI), or thyroid surgery; whereas, treatment of thyroiditis is symptomatic.",book:{id:"9077",slug:"goiter-causes-and-treatment",title:"Goiter",fullTitle:"Goiter - Causes and Treatment"},signatures:"Rushikesh Maheshwari",authors:[{id:"300029",title:"Dr.",name:"Rushikesh",middleName:null,surname:"Maheshwari",slug:"rushikesh-maheshwari",fullName:"Rushikesh Maheshwari"}]},{id:"61460",title:"Thyroid Cancer: Diagnosis, Treatment and Follow-Up",slug:"thyroid-cancer-diagnosis-treatment-and-follow-up",totalDownloads:1525,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Thyroid cancer is the most common malignancy of the endocrine system and it is usually presented as nodular goiter, the last being extremely a common clinical and ultrasound finding. The widespread use of ultrasonography during the last decades has resulted in a dramatic increase in the prevalence of clinically inapparent thyroid nodules, which only in 5.0–10.0% harbor thyroid carcinoma. The goal of the initial sonographic assessment of thyroid nodules is to distinguish benign nodules that could be managed conservatively from those with suspicious or malignant features requiring further management, including fine needle aspiration biopsy (FNAB), some axillary molecular techniques and thyroid surgery. Since over 90% of malignant thyroid nodules are differentiated thyroid carcinomas (DTCs) with good prognosis, it is necessary to establish strict criteria for diagnosis, treatment and follow-up in order to minimize the potential harm of over-treatment of low-risk patients and to provide adequate therapy to patients at high risk. This often requires an interdisciplinary approach involving endocrinologists, surgeons, pathologists, radiologists and oncologists.",book:{id:"6791",slug:"thyroid-disorders",title:"Thyroid Disorders",fullTitle:"Thyroid Disorders"},signatures:"Mira Siderova",authors:[{id:"242582",title:"Associate Prof.",name:"Mira",middleName:null,surname:"Siderova",slug:"mira-siderova",fullName:"Mira Siderova"}]}],onlineFirstChaptersFilter:{topicId:"1011",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:8,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:286,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:9,numberOfPublishedChapters:101,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. 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. 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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. 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Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:null,selectedSubseries:null},seriesLanding:{item:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343",scope:"Biomedical Engineering is one of the fastest-growing interdisciplinary branches of science and industry. The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. This series is intended for doctors, engineers, and scientists involved in biomedical engineering or those wanting to start working in this field.",coverUrl:"https://cdn.intechopen.com/series/covers/7.jpg",latestPublicationDate:"May 7th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:3,numberOfPublishedChapters:96,numberOfPublishedBooks:12,editor:{id:"50150",title:"Prof.",name:"Robert",middleName:null,surname:"Koprowski",fullName:"Robert Koprowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTYNQA4/Profile_Picture_1630478535317",biography:"Robert Koprowski, MD (1997), PhD (2003), Habilitation (2015), is an employee of the University of Silesia, Poland, Institute of Computer Science, Department of Biomedical Computer Systems. For 20 years, he has studied the analysis and processing of biomedical images, emphasizing the full automation of measurement for a large inter-individual variability of patients. Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. Osma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDv7QAG/Profile_Picture_1626602531691",institutionString:null,institution:{name:"Universidad de Los Andes",institutionURL:null,country:{name:"Colombia"}}},{id:"69697",title:"Dr.",name:"Mani T.",middleName:null,surname:"Valarmathi",fullName:"Mani T. Valarmathi",profilePictureURL:"https://mts.intechopen.com/storage/users/69697/images/system/69697.jpg",institutionString:"Religen Inc. | A Life Science Company, United States of America",institution:null},{id:"205081",title:"Dr.",name:"Marco",middleName:"Vinícius",surname:"Chaud",fullName:"Marco Chaud",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSDGeQAO/Profile_Picture_1622624307737",institutionString:null,institution:{name:"Universidade de Sorocaba",institutionURL:null,country:{name:"Brazil"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/435367",hash:"",query:{},params:{id:"435367"},fullPath:"/profiles/435367",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()