Clinical radiosensitizers.
\\n\\n
These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\\n\\n\\n\\n\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"354",leadTitle:null,fullTitle:"Computed Tomography - Clinical Applications",title:"Computed Tomography",subtitle:"Clinical Applications",reviewType:"peer-reviewed",abstract:'Computed Tomography (CT), and in particular multi-detector-row computed tomography (MDCT), is a powerful non-invasive imaging tool with a number of advantages over the others non- invasive imaging techniques. CT has evolved into an indispensable imaging method in clinical routine. It was the first method to non-invasively acquire images of the inside of the human body that were not biased by superimposition of distinct anatomical structures. The first generation of CT scanners developed in the 1970s and numerous innovations have improved the utility and application field of the CT, such as the introduction of helical systems that allowed the development of the "volumetric CT" concept. In this book we want to explore the applications of CT from medical imaging to other fields like physics, archeology and computer aided diagnosis. Recently interesting technical, anthropomorphic, forensic and archeological as well as paleontological applications of computed tomography have been developed. These applications further strengthen the method as a generic diagnostic tool for non- destructive material testing and three-dimensional visualization beyond its medical use.',isbn:null,printIsbn:"978-953-307-378-1",pdfIsbn:"978-953-51-6624-5",doi:"10.5772/879",price:139,priceEur:155,priceUsd:179,slug:"computed-tomography-clinical-applications",numberOfPages:354,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"17fbe9a3e9ff839ef1c17f31a4d3c3cd",bookSignature:"Luca Saba",publishedDate:"January 5th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/354.jpg",numberOfDownloads:75511,numberOfWosCitations:44,numberOfCrossrefCitations:19,numberOfCrossrefCitationsByBook:1,numberOfDimensionsCitations:43,numberOfDimensionsCitationsByBook:3,hasAltmetrics:0,numberOfTotalCitations:106,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 15th 2010",dateEndSecondStepPublish:"December 13th 2010",dateEndThirdStepPublish:"April 19th 2011",dateEndFourthStepPublish:"May 19th 2011",dateEndFifthStepPublish:"July 18th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"57078",title:"Dr.",name:"Luca",middleName:null,surname:"Saba",slug:"luca-saba",fullName:"Luca Saba",profilePictureURL:"https://mts.intechopen.com/storage/users/57078/images/1786_n.jpg",biography:"Dr. Luca Saba’s research fields are focused on neuroradiology, multi-detector-row computed tomography, magnetic resonance, ultrasound, and diagnostics in vascular sciences. His work, as lead author, has been published more than 80 high impact factor, peer-reviewed journals as American Journal of Neuroradiology, European Radiology, European Journal of Radiology, Acta Radiologica, Cardiovascular and Interventional Radiology, Journal of Computer Assisted Tomography, American Journal of Roentgenology, Neuroradiology, Clinical Radiology, Journal of Cardiovascular Surgery, Cerebrovascular Diseases. Dr. Saba has written 7 book chapters and he presented more than 400 papers in national and international congresses (RSNA, ESGAR, ECR, ISR, AOCR, AINR, JRS, SIRM, AINR). He has also won 6 scientific and extracurricular awards during his career. Dr. Saba is member of the Italian Society of Radiology (SIRM), European Society of Radiology (ESR), Radiological Society of North America (RSNA), American Roentgen Ray Society (ARRS) and European Society of Neuroradiology (ESNR).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Cagliari",institutionURL:null,country:{name:"Italy"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1008",title:"Radiology Diagnosis",slug:"radiology-diagnosis"}],chapters:[{id:"25697",title:"Computer-Aided Diagnosis for Acute Stroke in CT Images",doi:"10.5772/22232",slug:"computer-aided-diagnosis-for-acute-stroke-in-ct-images",totalDownloads:3006,totalCrossrefCites:1,totalDimensionsCites:4,hasAltmetrics:0,abstract:null,signatures:"Yongbum Lee, Noriyuki Takahashi and Du-Yih Tsai",downloadPdfUrl:"/chapter/pdf-download/25697",previewPdfUrl:"/chapter/pdf-preview/25697",authors:[{id:"46880",title:"Dr.",name:"Yongbum",surname:"Lee",slug:"yongbum-lee",fullName:"Yongbum Lee"},{id:"59127",title:"Dr.",name:"Noriyuki",surname:"Takahashi",slug:"noriyuki-takahashi",fullName:"Noriyuki Takahashi"},{id:"59128",title:"Prof.",name:"Du-Yih",surname:"Tsai",slug:"du-yih-tsai",fullName:"Du-Yih Tsai"}],corrections:null},{id:"25698",title:"3D-CT Mammary Lymphography Facilitate the Endoscopic Sentinel Node Biopsy",doi:"10.5772/21666",slug:"3d-ct-mammary-lymphography-facilitate-the-endoscopic-sentinel-node-biopsy",totalDownloads:2202,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:null,signatures:"Koji Yamashita, Shunsuke Haga and Kazuo Shimizu",downloadPdfUrl:"/chapter/pdf-download/25698",previewPdfUrl:"/chapter/pdf-preview/25698",authors:[{id:"44172",title:"Prof.",name:"Koji",surname:"Yamashita",slug:"koji-yamashita",fullName:"Koji Yamashita"}],corrections:null},{id:"25699",title:"CT Aided Postoperative Breast Conservation Brachytherapy Irradiation",doi:"10.5772/21673",slug:"ct-aided-postoperative-breast-conservation-brachytherapy-irradiation",totalDownloads:2410,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"D. 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\r\n\tCurrently, numerous biomaterials-based studies are being conducted, including research into chitin and chitosan, the second most abundant polysaccharide after cellulose. Chitin is obtained at an industrial scale from a variety of natural sources including, crustacean and insect exoskeletons, fungi cell walls, squid pen, etc. Chitosan is biodegradable, biocompatible, non-toxic, water-soluble under acidic conditions, and linear cationic amino polysaccharide derived from the deacetylation of chitin. It contains free amino and hydroxyl groups that can be functionalized by binding with the cationic and anionic groups. It has numerous applications, especially in the environmental remediation, biomedical, pharmaceutical, agriculture, and food industries.
\r\n\r\n\tThis book will present an update of articles addressing isolation, properties, and certain applications of chitin and chitosan, including films, fibers, nanoparticles, composite materials, hydrogels, polymeric complexes, water purification, antimicrobials, textile, cosmetics, biosensors, nanoporous scaffolds, and membranes. We invite world-class researchers from around the world, industry, academia, government, and private research institutions are encouraged to publish research or review articles on chitin and chitosan.
",isbn:"978-1-80356-693-1",printIsbn:"978-1-80356-692-4",pdfIsbn:"978-1-80356-694-8",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"69f009be08998711eecfb200adc7deca",bookSignature:"Dr. Brajesh Kumar",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11670.jpg",keywords:"Solvent, Acidic, Microwave, Binding, Biodegradable, Biocompatible, FTIR, NMR, XRD, Fibers, Nanoparticles, Composite Materials",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 23rd 2022",dateEndSecondStepPublish:"May 26th 2022",dateEndThirdStepPublish:"July 25th 2022",dateEndFourthStepPublish:"October 13th 2022",dateEndFifthStepPublish:"December 12th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Brajesh Kumar is a pioneering researcher in nanoscience and green chemistry. He is a member of the American Chemical Society, Indian Society of Chemists and Biologists, Indian Science Congress Association, Dr. Kumar, and holder of two registered patents. Dr. Kumar is also included in the top 2% of the scientist list prepared by experts at Stanford University, USA.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"176093",title:"Dr.",name:"Brajesh",middleName:null,surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar",profilePictureURL:"https://mts.intechopen.com/storage/users/176093/images/system/176093.JPG",biography:"Dr. Brajesh Kumar is currently working as an Assistant Professor and Head in the Post Graduate Department of Chemistry, TATA College, Chaibasa, India. He received a Ph.D. in Chemistry from the University of Delhi, India. His research interest is in the development of sustainable and eco-friendly techniques for (a) nanoparticles synthesis and their applications for environmental remediation, (b) active films of organic solar cells, (c) nanomedicine, (d) sensors, (e) natural product extraction, purification, and analysis,(f) natural polymers, (g) peptide chemistry, (h) microwave and ultrasound-assisted organic synthesis and (i) organic synthesis. Dr. Brajesh Kumar has been credited for different national and international fellowships and he has also worked as a faculty member in various universities of India, Ecuador, and South Korea. He has also published numerous SCI/ SCIE/ Scopus research articles (h index = 28, Citations 2690) and is also an active reviewer of more than 50 Journals. 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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:"62675",title:"Urinary Tract Infections in Neuro-Patients",doi:"10.5772/intechopen.79690",slug:"urinary-tract-infections-in-neuro-patients",body:'The normal functioning of the urinary system is closely related to the functional integrity of the central nervous system (CNS). Neuro-urological symptoms may be caused by a variety of diseases and events affecting the nervous system controlling the lower urinary tract (LUT). The resulting neuro-urological symptoms depend predominantly on the location and the extent of the neurological lesion. There are no exact figures on the overall prevalence of neuro-urological disorders in the general population, but data are available on the prevalence of the underlying conditions and the relative risk of these for the development of neuro-urological symptoms. The majority of the data show a very wide range of prevalence/incidence. This reflects the variability in the cohort (e.g. early or late stage disease) and the frequently small sample sizes, resulting in a low level of evidence in most published data. Spinal cord injury patients may be the most studied group among neurogenic patients.
Spinal cord injury (SCI) is a damage to the spinal cord from traumatic or nontraumatic etiology, as defined by the International Spinal Cord Society (ISCoS) [1]. It is difficult to accurately calculate the worldwide prevalence and incidence of SCI due to the lack of standardized methods of assessment across regions and limited information in the data collected. The incidence varies from 12 to more than 65 cases/million per year. Data from Olmsted County, Minnesota, United States, from 1975 to 1981, showed an age- and sex-adjusted incidence rate of 71 spinal cord injuries/million [2]. The annual incidence of SCI reported for the year 1991 was around 30.0–32.1 persons/million population in the United States, meaning 7500 and 8000 new cases per year at that time [3]. In 2016, the estimated annual incidence of SCI was approximately 54 cases/million population or 17,000 new SCI cases each year [4]. The annual incidence varies widely by country. From 27 per million persons in Japan, 8–13.4 in Switzerland, 12.7 in France, and 16.7 in South Africa [5]. A systematic review in 2010 by Van den Berg et al. showed up to threefold variation in incidence rates between developed countries. The highest rates reported in Canada and Portugal. Most traumatic SCI studies show a bimodal age distribution. The first peak was found in young men between 15 and 29 years of age and the second peak in older adults (mostly ≥65 years old and women) [6]. The National Spinal Cord Injury Statistical Center at the University of Alabama at Birmingham reported approximately 12,000 new cases each year, with 4:1 male-to-female ratio. The average age at injury was 40 years. The most common injury was incomplete tetraplegia at 30%, followed by 25.6% for complete paraplegia, 20.4% for complete tetraplegia, and 18.5% for incomplete paraplegia. In the past, the leading cause of death among SCI patients was the renal failure while nowadays, is pneumonia, pulmonary emboli, and septicemia supersede renal failure. SCI patients seem to have a higher prevalence of several comorbidities than the general population. It is reported high blood pressure (49% vs. 26%, respectively), high cholesterol (47% vs. 30%), and diabetes (19% vs. 7%). Obesity is also a significant problem for individuals with SCI (25%).
Spinal cord injury (SCI) patients clinically face urinary incontinence during the bladder filling phase and incomplete emptying during the micturition phase. The main aggravating factors are the increased intravesical pressure and the residual urine. These may result in vesicoureteral reflux, bladder diverticula, and urinary stones formation. These conditions also lead to an increased risk of urinary tract infection (UTI) [7, 8]. Despite improved treatment methods, UTI is considered the second leading cause of death in SCI patients [9]. It is known that UTIs are the most common hospital infections with known repercussions for the patient and the national economy. Approximately 5–10% of patients admitted to hospital are infected during their hospitalization and UTIs account for the highest (40–50%) [10, 11]. In addition, SCI patients usually have asymptomatic bacteriuria. In this way, positive urine culture is not the foundation stone for the diagnosis of urinary tract infection. The clinical signs and symptoms of urinary tract infection are differentiated in these individuals as the neural sensation is affected or absent. The review of the following literature aims to highlight the specificities of urinary tract infections in people with SCI or other neurogenic conditions in order to prevent and treat the infections and recognize asymptomatic bacteriuria without treatment necessity.
The physiological function of the lower urinary tract is characterized by the central control of the urinary reflexes (inhibition or removal of reflex inhibition) from the upper cortical centers of the cortex. Urine concentration within the bladder results in an increase in intravesical pressure that causes stimulation of the thoracic-lymphatic sympathetic center (T10-L2) via transient and adductor nerve fibers. Adjacent nerve fibers transfer the stimulus to the breech centers of urination and from there to the upper centers of the cerebral cortex. Then, if there is no central depression, the urinary reflex is manifested through the contraction of the detrusor resulting in the sympathetic nerves. However, if urination is undesirable, this reflex is inhibited as cationic signals inhibit sympathetic stimulation at the level of the thoracic-lumbar sympathetic center and increase the muscular tone of the external sphincter by suture from the pelvic neural mesh formed by the S2–S4 level. From the above, it is clear that any damage at any level of SC results in disorders of lower urinary function. These disorders vary according to level [11, 12], the degree (complete or incomplete) [13] and the extent of the damage.
Neurogenic urinary tract dysfunction characterized by increased intravesical pressures and/or urine residual [14]. These patients have decreased microorganism removal capacity [15]. Both incomplete emptying of the bladder [16] and high intravesical pressure [17, 18] are accompanied by an increased risk of UTI. Patients who have been using Credé maneuver for a long time to empty their bladder have had severe complications in the upper urinary tract (82% pyuria, 60% ureter dilation, 35% hydronephrosis, and 16% renal failure). Men appeared more susceptible to upper urinary tract damage than to women [19]. According to Esclarin De Ruz et al [20] in patients with SCI with detrusor overactivity, the coexistence of detrusor-sphincter dyssynergia duplicates the risk of urinary tract infections.
Under normal circumstances, the ureterovesical junction allows urine to enter the bladder but prevents urine from regurgitating into the ureter and the kidney. This results in the kidney being protected from high pressure in the bladder and from contamination by vesical bacteria. In this way, vesicoureteral reflux is considered to be an important factor in urinary tract infection [20]. It occurs in 10% of patients over 4 years of SCI [21]. Although the reflux is the result of high intravesical pressure, it must be controlled by another neurological mechanism since patients with a T10-L2 lesion exhibit more regressive effects than patients who have a level of damage above or below this level [22]. The damage at this level is probably related to the ureteral peristaltic mechanisms.
Intermittent catheterization (IC) during the recovery period appears to reduce the rate of urinary tract infections and substantially eliminate many of the complications associated with the use of an indwelling catheter [23, 24]. However, IC may also present certain complications, such as traumatic urethral injury (immediate) or urethral restenosis and recurrent epididymitis (late). In one study, SCI patients, using pure intermittent catheterization for more than 5 years, showed urine stasis at 19% and epididymitis at 28.5% [23]. The appearance of the above complications appears to be increased according to the number of years of pure IC performed [23]. Research supports the use of sterile IC technique in the acute phase of the neurogenic bladder [25] and agrees with a study in which few cases of bacteriuria and urinary tract infection were observed using sterile intermittent catheterization as compared to using a non-sterile procedure [26]. On the other hand, Shekelle et al. reported contradictory results in the value of sterile techniques or techniques without direct catheter contact compared to pure intermittent catheterization, as there is insufficient evidence of risk associated with psychological, behavioral and hygienic factors [27]. Hydrophilic catheters for clean intermittent catheterization are associated with lower rates of long-term complications (urethral stenosis) and may cause a lower degree of bacteriuria [28]. Another type of catheter, with an insertion sheath, which bypasses the first 1.5 cm of the urethra, appears to reduce the incidence of urinary tract infections in hospitalized men with SC damage [29].
Permanent indwelling catheters are the greatest risk factor for complicated UTIs [30]. They are responsible for most in-hospital UTIs, 3–10% per day and with 100% bacteriuria in their long-term use [31]. Silver-coated catheters are more effective in preventing urinary tract infections in patients who require short-term catheterization and reduce the incidence of symptomatic urinary tract infection and bacteriemia compared to simple catheters [32, 33]. For short-term catheters not exceeding 2–3 weeks, the use of nitrofurazone, minocycline, and rifampin-impeded catheters reduce the risk of urinary tract infection [34, 35] due to antibiotic overlap.
The use of a permanent suprapubic catheter is an effective way of draining the bladder in SCI patients with a low rate of urinary tract infection [36, 37]. Suprapubic catheterization may be an alternative drainage method for female patients who cannot perform self-IC [38]. The disadvantage is the continuous presence of the catheter (foreign material) within the bladder associated with the formation of urinary lithiasis as compared to intermittent catheterization at rates of 9 and 4%, respectively, over a period of more than 9 years [39]. On the other hand, this chronic irritation from the catheter is accompanied by an increased incidence of bladder cancer as compared to intermittent catheterization [40]. Nomura et al. [41] reported that 25% of patients with long-term use of suprapubic catheter showed bladder stone formation, which was accompanied by a 7.24 urine pH. Suprapubic drainage in patients with neurogenic urinary disorders is preferred (against urethral catheterization) as it appears to reduce the risk of urethritis, orchiepididymitis, testicular abscess and urethral erosion as compared to permanent catheterization [42].
Condom catheters are used in male patients to manage incontinence but not bladder emptying. Their application is accompanied by the same degree of urinary tract infection as in the use of intermittent catheterization. However, condom catheters do not ensure complete bladder drainage and can (in cases of poor application) be considered a cause of occlusion [43]. It is recommended that the condom catheter is applied daily, although no increase in infections has been reported in non-daily applications [44]. In addition, although condom catheters are external, they appear to be related to colonization of the urethra by pathogenic microbes. They are accompanied by Pseudomonas [45] and Klebsiella [46] infections due to the colonization of the regions of the urethra, perineum, penis, and rectum by the above microorganisms. In addition, the urine trap is a very good reservoir of microorganisms. In male patients using condom catheter, urine culture was 73% positive for Pseudomonas, although the degree of bacteriuria was much lower [47, 48]. Also, the colonization of the urethra with Pseudomonas is combined with the presence of the condom catheter [49]. From the above, it can be seen that the chronic use of a condom catheter drainage and urine collector predisposes to the colonization of the patient and the upward introduction of microorganisms into the anterior urethra.
According to their initial description, microorganisms are referred to as non-adherent “planktonic” cells [50] based on their developmental characteristics in enriched liquids and solids. Today, it is now known that bacteria in their natural environment are typically attached to some biological or non-surface area. It is also known that adhering microorganisms under suitable conditions form complex structures, biofilms (bio-membranes). These structures are formed as the microorganisms are surrounded by an extracellular exopolysaccharide (EPS) layer which themselves produce [50, 51]. Bacteria are the best-studied microorganisms regarding surface colonization and subsequent biofilm formation.
Fungi, protozoa, viruses, and algae have also been isolated from corresponding extracellular material in direct contact with organic or inorganic surfaces [52]. Stable microbial attachment to the underlying surfaces and the formation of biofilms creates significant and often insoluble problems both in the medical community and in the industry [53].
Bacterial biomembranes are observed in 73% [55] patients with SCI using IC, and no relationship has been found between the presence of bio-membrane and symptoms [56]. However, the presence of at least 20 bacterial adherence in each bladder cell appears to be related to the symptomatology of the infection [57]. Bacterial cells are detached individually or in groups from the upper layers of the biofilm circulating in the fluid medium, urine in this case, and attempting to adhere to a new substrate which is more conducive to their growth. These detachable bacteria can cause systemic infection [53, 58].
The specificity of individuals with SCI is that asymptomatic bacteriuria is usually present and the sensory disorder results in the lack of a clear symptom of urinary tract infection. The clinician should carefully evaluate the patient to decide whether a positive urine culture reveals infection or is an asymptomatic bacteriuria. Additionally, fever should not be attributed to urinary tract infection if the only positive point is bacteriuria unless other possible causes of fever are excluded. Approximately 45% of feverish conditions in these patients are thought to be due to urinary tract infections [59]. Other causes are respiratory infections as well as thromboembolic events. The septic condition in quadriplegic patients may also occur as hypothermia [60]. Approximately 10% of febrile episodes may be the result of a temperature control malfunction and not an infection [61]. The coexistence of elevated CRP and routine serum test values should be considered. UTI is accompanied by a specimen of urine blisters with microbes above 105 CFU/ml, and symptoms such as fever, back pain in the lumbar region of the kidney, upper urinary tract infection, and if the patient has a sensation at this level, urinary urgency and increased spasticity. A characteristic symptom is the reduction of cystic functional capacity and the aggravation of overactive bladder syndrome, in the case of a neurogenic overactive detrusor, or the discontinuation of response to previously well-regulated treatment for increased extravasation activity. The incidence of urinary tract infections in SCI patients is 2.5 episodes per patient per year. Bacteremia and sepsis occur in 1% of SCI patients [62]. The urinary system is considered to be the most common source of bacteremia [62, 63]. Bacteremia in SCI patients is accompanied by 90% fever, 17% hypotension, and death rate of about 15%. [62, 63]. Approximately 20–25% of episodes are characterized by polymicrobial infections. Bacteriemia is more common in quadriplegic patients and in patients with complete SCI [64]. Urogenital tube manipulations are considered as risk factors for bacteremia [65].
Urinary tract colonization often follows colonization of the urogenital tract, perineum or urethra with enteropathogenic microorganisms [66, 67]. In a study of 15 adult men with SCI and other neurogenic urinary dysfunctions, the normal flora of the perineum, penis and urethra regions was compared with the flora of 10 control men without neurogenic urinary disorders [68]. The predominant microorganisms with respect to the control group were Gram-positive granules and diphtheroids. In the individuals with the neurogenic urinary disorder, the microorganisms isolated from the skin flora include species such as Enterobacteriaceae, Pseudomonas, Acinetobacter, and Enterococcus [68]. In addition, other studies of individuals with SCI as compared to non-injured patients, the presence of
When a UTI is suspected, it is important that the urine specimen is obtained in an appropriate manner in order to prevent contamination and a potential false-positive result. For patients with indwelling catheters (either the urethral catheter or suprapubic), the indwelling catheter should be changed to a new catheter, and the specimen should be obtained from the new catheter after capping the catheter for a few minutes to allow a small amount of urine to collect in the bladder. The urine specimen should then be collected by uncapping the catheter. For patients with external catheters or those who perform IC, the specimen should be collected by catheterization with a new sterile catheter.
The significance of pyuria in neurogenic patients in combination with the use of intermittent catheterization or permanent catheter is often difficult to assess. Changing the Foley catheter in symptomatic patients causes an increase in the leucocytes without affecting the microbial strain or the number of colonies [71]. Positive urine culture (105 CFU/ml colonies), with the presence of >50 leucocytes per field of vision, is associated with an increased risk of fever. In addition, Gram-positive microorganisms such as
Comparative studies are difficult to perform in these patient groups due to different definitions of bacteriuria and urinary tract infection, different urinary tract drainage methods, as well as the severity of acute, subacute, chronic, or total and partial lesions. In 1992, according to the National Institute on Disability Rehabilitation Research, severe bacteriuria is defined as the number of colony counts of 102 CFU uropathogenic micro granules per ml of urine in samples taken by catheterization, 104 CFU/ml urine samples under pure micturition and any detectable uropathogenic concentration in samples from permanent catheter or supraventricular puncture. Other researchers continue to regard the concentration of 105 CFU/ml in urine as a criterion for significant bacteriuria even in samples after catheterization [73]. Waites et al. reported that patients with 10 CFU/ml in urine have a 10% risk of a febrile episode, while the presence of pyuria is more associated with fever and shivering [73]. In patients receiving 40% IC, the source of bacteriuria was the upper urinary tract, while in 60%, the source was the lower urinary tract [74]. Pyuria was much higher in patients with upper urinary tract infection [75].
Asymptomatic bacteriuria is defined as the presence of a significant number of urine microbes (105 CFU/ml) in patients without clinical symptoms or signs of infection. The incidence varies depending on the age of the patients, the sex and the presence or absence of functional or anatomical urinary tract abnormalities. Bladder catheterization is the most important predisposing factor for asymptomatic microbial growth. In hospitalized catheterized patients with an open urine collection system, the incidence of the asymptomatic microbial disease is 100% of the patients within 3–4 days.
Microorganisms most commonly isolated in bladder catheterized patients are
As mentioned, bacterial colonization of the skin and the urethra is an important source of bladder infection using catheters. Differences in microbial species and their presence in normal skin flora of SCI patients and other neurogenic urinary disorders in relation to individuals without neurogenic disorders may result from the use of antibiotic therapy, use of condom catheters, pH and skin temperature in the area, personal hygiene, or fecal contamination. Pseudomonas colonizes the perineum, in addition to the high pH of the skin of the area appears to contribute positively to the high risk of colonization [78, 79]. The meticulous soap wash of the perineum area only has temporary effects in reducing its colonization by Gram-negative microorganisms, whereas the use of antiseptics, such as chlorhexidine and povidone-iodine, has no effect [80, 81].
Efforts to eliminate bacteriuria due to the use of permanent or intermittent catheterization have no effect. Intensive or continuous catheterization is a frequent but not documented method of treatment to prevent sedimentation, bacteriuria, urinary tract infection and/or bacteremia. Intravenous administration with neomycin/polymyxin has no effect. Spinal hygiene, perineal wash, and frequent catheter changes have found ineffective methods in reducing urinary tract infection due to catheterization [82]. In addition, it is important for both coating and catheter composition. Prevention of
As mentioned above, a general feature of the microorganisms that form the bio-membranes is their resistance to various antimicrobial substances, as opposed to free-flowing cells. The main objective should prevent biofilm formation by the prophylactic administration of antibiotics and strict adherence to antisepsis rules when attaching any prosthetic material and in this case a catheter. It is also proposed to incorporate antimicrobial agents into the material to be implanted and to modify the physical or chemical properties of the material so as not to favor biofilm formation.
To achieve satisfactory penetration of antimicrobial drugs into the bio-membrane, experimentally liposomal forms of drugs have been tested with encouraging results. Reid et al. claimed that the daily use of cranberry helmet juice drastically reduced the formation of biofilm and reduced the adhesion of Gram-negative and -positive microorganisms to bladder cells [84]. Respectively, in more recent studies and post-analysis, the clinical benefit of using cranberry juice to reduce urinary tract infections appears to be limited to recurrent urothelial infections in women without neurogenic urinary disorders of young and middle age [85, 86].
The use of antimicrobial drugs for the prevention of UTIs in people who have intermittent catheterization or carry an indwelling bladder catheter has some positive results. In some studies, prophylactic antibiotics are reported to be effective. The use of methenamine orally and intake of acidic substances contributes to the reduction of urinary tract infection in the case of intermittent catheterization [87]. A low dose of ciprofloxacin appears to be more effective than placebo in preventing urinary tract infection [88]. In a study, administration of the 500 mg twice daily dose for 10 days reduced the incidence of Gram-negative organisms in the perineum and urethra but ciprofloxacin-susceptible microorganisms were replaced by resistant microorganisms such as staphylococci, including methicillin-resistant
The efficacy of the sphincterotomy has been well documented since Emmett JL and Dunn JH described the trans-urethral resection of the bladder neck and prostate in SCI patients with outlet obstruction. Ross JC introduced the resection of the external urinary sphincter. Large series have shown that sphincterotomy is successful in the treatment of vesical outlet obstruction in certain male patients with quadriplegia, in order to reduce detrusor leak point pressure, followed by condom catheter drainage. Patients who develop UTIs after sphincterotomy are should undergo assessment of PVR to ensure adequate bladder emptying. Urodynamic testing should also be considered to assess the efficacy of the sphincterotomy. If there is evidence of urethral obstruction, repeat sphincterotomy may be indicated. Sphincterotomy can also be indicated when patients use Credé or Valsalva to empty their bladder, but first, surgeons must have assessed that the lower urinary tract is urodynamically safe and that the upper urinary tract is not damaged [91].
The aim of bladder augmentation is to reduce detrusor overactivity (DO), improve bladder compliance and reduce the pressure effect of DO [92, 93]. Complications associated with these procedures are recurrent infection, stone formation, perforation or diverticula, possible malignant changes, metabolic abnormality, mucus production and impaired bowel function [94, 95, 96]. Special attention should be paid to patients with preoperative renal scars since metabolic acidosis can develop [97]. Several different techniques have been published [98, 99, 100, 101, 102, 103, 104, 105, 106]. Bladder substitution, even by performing a supratrigonal cystectomy [93], is also indicated in patients with a severely fibrotic bladder wall. IC may become necessary after this procedure.
Following supravesical urinary diversion, pyelonephritis may occur, usually accompanied by fever, chills, leukocytosis, nausea and vomiting. Upper tract imaging should be performed, due to possible urinary obstruction. If there is an obstruction, the system should be drained via percutaneous nephrostomy. In this case, urine culture should be obtained from the nephrostomy tube.
It is the first choice for urinary diversion. The continent urinary reservoir is indicated when the native bladder and urethra are severely devastated functionally or anatomically, as well as bladder neck closure and ureteral re-implantation are not avoidable. All of the different techniques have complications such as leakage or stenosis. The short-term continence rates are >80% and good protection of the UUT is achieved [107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119].
If catheterization is impossible, incontinent diversion is indicated. The ileal conduit is the most common form of incontinent urinary diversion used. It could be considered in patients who show intractable and untreatable incontinence, in patients with LUT dysfunction, when the upper urinary tract is severely compromised and in patients who refuse other therapy [119]. An ileal segment is used for the deviation in most cases [120, 121, 122, 123, 124] and patients gain better functional status and quality of life [125]. Incontinent diversion has also an acceptable rate of complications. Especially in children, there are concerns about long-term effects on renal function, and while conduit diversion may be considered in this population, alternative methods may be preferable.
Long-standing diversions may be successfully undiverted or an incontinent diversion changed to a continent one with the cause of better techniques for control of detrusor pressure and incontinence [120]. The patient must be carefully counseled and must comply with the instructions [120]. Only then successful undiversion can be performed [126].
Some patients with spinal cord injury have difficulty or are unable to perform IC through a native urethra. In such cases, the creation of an abdominal stoma using a continent catheterizable channel (CCC) should be considered. A CCC is particularly helpful in women because their ability to access their urethra is more difficult than in men [127, 128, 129]. A concomitant bladder neck closure with a CCC becomes an option when urethral dysfunction or destruction does not result in acceptable continence over anti-incontinence surgeries.
The majority of patients with bladder augmentation or continent urinary diversion will have mucus production that can act as an incubation material for infection. Irrigation of the bladder or pouch at regular intervals with normal saline decrease the incidence of symptomatic urinary tract infection.
Generally, asymptomatic bacteriuria does not require treatment because the microorganism cannot be eliminated or will recur after the treatment is complete. In addition, antimicrobial therapy will lead to resistant strains of microorganisms [130, 131]. Therefore, there is no indication that treatment reduces virulence or mortality. Systemic antimicrobial therapy for asymptomatic bacteriuria is recommended only in special cases such as:
patients who undergo urological surgery or prosthetic graft
treatment may be a part of the control of a hospital infection due to a particular prevalent virulent microorganism
patients belonging to high-risk groups (immunosuppressed)
strains of microorganisms suspected of bacteremia such as Serratia marcescens [132, 133, 134, 135].
Symptomatic UTI in the neurogenic patient is defined as a urinary culture with ≥102 CFU bacteria/mL and symptoms including, but not limited, to LUTS, urinary incontinence, increased spasticity, autonomic dysreflexia, pelvic discomfort, fever, and decreased energy level. Moreover, it has not been shown that the type of microbe isolated in urine culture of an asymptomatic patient is the cause of infection when a symptomatic episode occurs. In 30–50% of cases, urinary catheter removal is accompanied by urinary tract purification by the microorganism [40, 134]. People with symptomatic bacteriuria—UTI should be treated with the most specific antibiotic treatment for the shortest but sufficient period. Since the urinary catheter surface, due to biofilm formation becomes a source of bacterial growth, it is justified and important to remove it and replace it with a new one before treatment of symptomatic infection [40, 136, 137, 138, 139]. The guidelines for choosing the right antimicrobial treatment are the same as those of the general population. They include the identification of the microorganism, antimicrobial susceptibility, the location of the infection, its complexity, and the risk factors.
Although there are insufficient clinical studies on the duration of treatment for urinary tract infections in neurogenic patients, the duration of treatment varies from 3 to 21 days depending on the microorganism, the accompanying factors of infection and the condition of the patient [138, 140, 141]. When oral treatment is sufficient, it is usually given for a period of 5–7 days, and when intravenous treatment is required, it remains from 7 to 14 days depending on the clinical and laboratory findings [142]. In the appearance of fungi in urethral cultures, treatment is unnecessary. In this case, either local (intravesical) or systemic antifungal treatment [143, 144] is not recommended, and it is recommended to replace the catheter with a new one. If the infection is accompanied by symptoms of the urinary tract or the presence of fungus is a symptom of systemic infection, then antifungal treatment is necessary [145].
Urinary tract infections are a grade issue for medical doctors and patients. It is even more difficult to diagnose and treat neurogenic patients rather than general population. The higher frequency of recurrent infections in these patients and resistant microorganisms remain the main problems as for this specific population. In summary, based on the criteria of evidence-based medicine, there is currently no preventive measure for recurrent urinary tract infections in neurogenic patients that can be recommended without limitations. Individualized concepts, including immunostimulation, phytotherapy, and complementary medicine, should be taken into consideration [146]. Prophylaxis is important to pursue, but there are no data favoring one approach over another. In this case, prophylaxis is essentially a trial and error approach. Nowadays, the quality of life of the neurogenic patients is the primary concern. Antibiotics, catheterization techniques and urinary diversions are the main features of treatment applied. The medical community contributes in this direction with the proper diagnosis of the diseases in this group of patients. Personalized physician and patient collaboration and the timely recognition of symptoms by the patient remain the cutting edge of early symptoms relief. The proper and efficient control of the “neurogenic bladder” is essential for the prevention and the management of the UTIs. The controlled bladder pressure and its complete periodical evacuation under a low-pressure environment can ensure that the UTIs will be less frequent and less severe.
For decades, radiobiologists and physician-scientists have collaborated to develop effective combination therapies with ionizing radiation and radiosensitizing agents to reduce the overall dose of radiation required in cancer therapy. This minimizes adverse side-effects observed in normal tissues and increases the efficacy of radiation in reducing tumor burden. Here, we discuss the pros and cons of radiosensitizing agents used in the clinic in comparison with NAD(P)H quinone oxidoreductase-1 (NQO1)-bioactivatable drugs. β-Lapachone (β-Lap) is a clinical chemotherapeutic agent discovered to be a potent DNA repair inhibitor in the late 1980s. It has since been shown to be bioactivated by NQO1, an enzyme elevated more than 20-fold in most solid human cancers, e.g., non-small cell lung, pancreas, prostate, head and neck, and breast cancers, and shows promise as a potent radiosensitizer.
The late 19th-century discovery of the X-ray by Wilhelm Roentgen led to diagnostic tools and therapies for diseases such as blood disorders and benign and malignant growths [1, 2]. Initially, radiation was delivered using unfocused beams, causing skin and blood malignancies in both patients and radiologists [1, 2]. Today, patients benefit from vast technological improvements, allowing for focused radiation beams, which markedly increased patient survival. Current approaches include conformal radiation therapy, proton beam radiation therapy, stereotactic radiation therapy (using linear accelerators or gamma knife devices), and intraoperative therapy [3]. Despite improvements in targeting tumors and reducing normal tissue damage, high doses of radiation are still required for a curative effect. Some tumors can also be resistant to radiotherapy, including hypoxic tumors and dormant cancer cells that regrow when the optimal tumor microenvironment presents itself. Thus, methods to improve the safety and efficacy of ionizing radiation were initiated, including combination with chemotherapeutics or radiosensitizers.
Radiosensitizing agents are molecules that enhance the dose of ionizing radiation delivered to a patient’s tumor. The optimal clinical radiosensitizer (a) lowers the required dose of ionizing radiation, (b) increases its antitumor effect, and (c) synergistically kills cancer cells. To date, no radiosensitizer has met these demands. Many radiosensitizers have been used clinically (Table 1, normal text) with limited success, or are currently in clinical trial (Table 1, bold text). These include suppressors of radioprotectors (e.g., thiol) [4], molecules releasing cytotoxic substances when radiolyzed [5], thymine/cytidine analogs [6], oxygen mimic sensitizers [7], and DNA repair inhibitors [8].
Radiosensitizer | Tumor type | Mechanism |
---|---|---|
Hyperbaric oxygen | Brain tumors | Oxygenation |
Nicotinamide | Glioblastoma | Oxygenation |
Metronidazole | Cervical cancer | Oxygenation |
Mitomycin-C | Breast cancer | Kills hypoxic cells |
5-fluorouracil (5FU) | Gastrointestinal | S-phase check points |
Bromodeoxyuridine (BrDU) | Breast | Repair inhibition |
Topo-inhibitors | Breast, cervical | DNA damage |
Solid tumors | Direct | |
Head and neck | Modifies hypoxia | |
Glioblastoma | Oxygenation | |
Glioblastoma | Oxygenation |
Clinical radiosensitizers.
List of commonly used radiosensitizing methods/agents for combination with radiotherapy in various tumor types. The last four are
In the late 1980s, our laboratory began searching for DNA repair modulators that synergize with ionizing radiation to kill cancer cells more effectively. The goal was to thwart cancer cells’ ability to repair IR damage, to avoid the survival of IR-resistant malignant cells that have undergone potentially lethal damage repair (PLDR). One of those compounds was (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione), also known as β-lapachone [9].
We found that just four micromolar β-lapachone inhibited single-strand DNA break repair in cancer cells exposed to DNA-damaging agent methyl methane sulfonate [9, 10], killing 99% of cells at an exposure time 90–120 min [11]. Additionally, we found that combining β-lapachone with ionizing radiation in Hep2 cells increased double-strand breaks and dramatically lowered the dose of radiation required for cell death, highlighting β-lapachone as a potent radiosensitizer [12].
In the 1990s and early 2000s, we conducted subtraction-hybridization screening to isolate X-ray inducible genes to investigate ionizing radiation resistance and found Xip3, also known as NQO1 [13]. Dicoumarol, an NQO1 inhibitor, specifically blocked β-lapachone’s toxicity, indicating that the radiosensitizer may be bioactivated by this enzyme. As NQO1 is specifically expressed in tumor cells, this indicated a promising use of β-lapachone as a cancer therapeutic with or without ionizing radiation.
NQO1 is a Phase II detoxification enzyme that reduces ROS levels in cancer cells. NQO1 converts quinones into stable intermediate hydroquinones that are exported out of the cell by conjugation [10]. Most solid cancers, including non-small cell lung and pancreatic cancers (>85%), prostate, colon, and breast cancers (60%) and head and neck cancers (40%) overexpress NQO1 5- to 200- fold above normal tissue. Corresponding levels of catalase in these cancers were strikingly reduced, impacting the ability of cancer cells to eliminate ROS [14]. Overexpression of NQO1 appears to stabilize HIF-1alpha and promotes metastasis [15].
Though NQO1 detoxifies most quinones through two-electron oxidoreduction, a few quinones undergo a rapid futile redox cycle response, generating an unstable intermediate hydroquinone that spontaneously reverts back to its original form using two oxygenation steps and creating two superoxides. Deoxynyboquiones (DNQ), KP372 agents, and β-lapachone are three classes of NQO1-bioactivatable drugs currently known [16]. Recently, Napabucasin, an orphan drug in clinical trials for pancreatic and cervical cancer, has also been reported to be bioactivated by NQO1 [17]. Though mitomycin C and streptonigrin are metabolized by NQO1, these agents can also be activated by other drug metabolizing enzymes [18]. Human cancer cells overexpressing NQO1 have been shown to be sensitive to NQO1-bioactivatable drugs alone and in combination with PARP inhibitors, cisplatin, radiation, and NAMPT inhibitors both in cell culture and xenograft models [14, 19].
Cancer cells overexpressing NQO1 and exposed to NQO1-bioactivatable drugs, such as β-lapachone, DNQ or IB-DNQ , acquire extensive DNA lesions as evidenced by alkaline comet assays [11]. The unstable hydroquinone form of these NQO1 bioactivatable drugs reacts with two oxygen molecules spontaneously to regenerate the original compound [20]. This futile redox cycle consumes ~60 moles of NADPH to generate ~120 moles of ROS in ~2 min for β-lapachone, leading to the generation of permeable hydrogen peroxide (H2O2). This diffuses into the nucleus and causes massive oxidative stress and SSBs [16]. Initial DNA damage is mainly through the formation of altered bases, SSBs, and apurinic/apyrimidinic (AP) sites generated through incorporation of 8-oxo-deoxyguanine [21]. Ultimately, damage caused by H2O2 results in extensive SSBs and DSBs. These lesions lead to PARP hyperactivation that can be prevented by BAPTA-AM (chelates Ca2+), PARP inhibitors, or the NQO1 inhibitor dicoumarol, in NQO1+ cells. In contrast, cells deficient in NQO1 due to NQO1 polymorphisms, *2[C609T] or *3[C465T], are unaffected by exposure to NQO1-bioactivatable compounds [14], lacking the enzyme activity for redox cycling Hyperactivation of PARP rapidly degrades the increased NAD+ pools generated as a result of the oxidation of NADH in the futile cycle [11, 20, 22]. NAD+ loss is not seen in cells treated with PARP1 inhibitors; instead, cells exposed to PARP inhibitors in combination with NQO1-bioactivatable drugs undergo a synergistic apoptotic cell death response [14].
One of the key components in the cell death response by NQO1-bioactivatable drugs is the release of calcium from the core endoplasmic reticulum (ER) stores, which is otherwise inert [11, 23]. This results in specific programmed necrosis referred to as NAD+ -Keresis. Pre-treatment, with the calcium chelator, BAPTA-AM, suppresses PARP hyperactivation and results in specific inhibition of NQO1-dependent cell death by NQO1-bioactivatable drugs. Extensive DNA damage along with Ca2+ release from the ER results in the hyperactivation of PARP1 in NQO1+ cancer cells. PARP1 hyperactivation rapidly degrades the NAD+ and causes concomitant ATP losses within 30–40 min of drug treatment. μ-Calpain activation is observed upon treatment with NQO1-bioactivatable drugs within 8–24 h [16, 24]. The multitude of damage caused by treatment with these drugs overwhelms DNA repair machinery and depletes the cells of the energy resources, culminating in cell death [10, 11, 16, 20, 24, 25, 26, 27].
Treatment with NQO1-bioactivatable drugs causes wide-scale metabolic changes in the cell, which can be attributed to cell death overwhelming the cellular machinery. Altering key enzymes in NAD metabolism results in synergy with NQO1-bioactivatable drugs. NAMPT is an important source of reducing equivalents for redox balance in cancer cells. Pretreatment with FK866, a NAMPT inhibitor, leads to accelerated cell death due to decrease in NAD+/NADH levels and reduced doses of NQO1-bioactivatable drugs [28]. NAMPT knockdown has also been shown to sensitize cancer cells to ROS induction through ionizing radiation [29, 30].
Cancer cells, tissues, and organs subjected to ionizing radiation experience a wide spectrum of DNA lesions including SSBs, DSBs, AP sites and DNA-protein crosslinks. One unrepaired DSB is lethal to the cell [21, 31]. Hence, NQO1-bioactivatable drugs, when combined with IR (Figure 1), synergistically kill cancer cells due to the combined effect of DNA damage and PARP1 hyperactivation [21, 32]. Sublethal doses of NQO1 drugs and IR combine to release massive amounts of ROS due to their synergy, resulting in PARP hyperactivation, loss of nucleotides and increased programmed necrosis (Figures 2 and 3), beyond the capabilities of the single agents (IR or NQO1-bioactivatable drug) alone. Head and neck cancers, PDA and NSCLC have been shown to be sensitive to nontoxic doses of β-lapachone when combined with IR [21, 32]. Using NQO1-bioactivatable drugs as radiosensitizers leads to increases in ROS, γH2AX formation, hyperactivation of PARP1, massive NAD+ and ATP losses, inhibition of DSB repair, perturbation in carbon flux pathways and μ-Calpain mediated programmed necrosis known as NAD + -Keresis. The cell death responses observed are independent of any oncogenic drivers [21, 31, 32, 33]. This lethal combination between radiation therapy and NQO1-bioactivatable drugs prolongs long-term survival and promotes enhanced tumor shrinkage at non-toxic doses of each agent (IR and Drug, Figure 4). Thus, combining NQO1-bioactivatable drugs with radiation therapy, should be a long-standing treatment modality for tumors overexpressing NQO1.
Radiation sensitization by NQO1 bioactivatable drugs: sublethal doses of β-lapachone when bioactivated by NQO1 release massive amounts of ROS, resulting in synergy with IR and increased programmed necrosis. NQO1 bioactivatable drugs in combination with IR show tremendous synergy even at low doses. The combined effect of DNA damage and PARP hyperactivation provides more lethality to a cancer cell whereas NQO1 provides the specificity. This leads to increased ROS, gH2AX formation, hyperactivation of PARP, massive NAD and ATP losses, prevention of DSB repair, perturbations in the metabolic pathways, and μ-Calpain-mediated programmed necrosis known as NAD + -Keresis.
Sublethal doses of IR and β-lap in NQO1+ LNCaP cells cause PARP-1 hyper-activation and dramatic ATP loss: A, LNCaP cells expressing or lacking NQO1 were treated with IR + β-lap and monitored for PAR formation—UT, untreated control for IR; V, vehicle; DMSO only. B, Synergistic ATP loss was noted after IR + β-lap compared to single treatments alone. Results are means ± SE for experiments performed three times in duplicate. Student’s t-tests compared single to combined treatments. ***p < 0.001, **p < 0.01.
β-Lap inhibits DNA double strand break repair: A. log-phase A549 NSCLC cells were treated with or without β-lap (6 μM) and cell extracts prepared at various times during treatment to detect PAR-PARP formation, γ-H2AX (pS139), pS1981 ATM, total ATM (t-ATM) and α-tubulin steady-state levels by Western blot. A549 cells were also exposed or not to IR (8 Gy) and analyzed 1 h later. Mock, non-irradiated cells. DM, media alone. B. Graphical representation of data shown in
β-Lap radiosensitizes subcutaneous A549-luc xenografts in athymic nude mice: A. subcutaneous A549-luc xenografts (400 mm3) were generated in athymic nude mice and then treated with or without IR (2 Gy) then immediately with or without β-lap (20 mg/kg) for 5 treatments every other day. Representative antitumor responses (at day 20 post-treatment) are demonstrated for β-lap alone, IR alone, and the IR + β-lap combination. B. Antitumor responses (tumor volumes, mm3) over time are shown for the treatments described in
The major advantage of using NQO1-bioactivatable drugs as radiosensitizers is the tumor selectivity afforded by the drugs themselves. Synergy is afforded by a number of tumor-selective responses to the drugs. First, the dependence of the drugs on NQO1 levels is perfect for the specific treatment of various difficult-to-treat human cancers, including non-small cell lung, pancreatic, breast, prostate, and head and neck cancers. Tumor selectivity requires approximately 100 units of enzyme activity, whereas lower levels of NQO1 results in mild metabolomic alterations used for the treatment of metabolic syndromes [34]. Second, the minimum time of exposure of 30–120 min fits the pharmacokinetics of the drug. It should be noted that all studies thus far indicate that the drugs have to be available immediately after or at the same time as exposure with IR. Pre-treatment prior to IR is ineffective. Third, synergy between NQO1-bioactivatable drugs and IR occurs due to PARP1 hyperactivation causing massive NAD+ and ATP loss, preventing repair of the DNA damage created by IR. NQO1-bioactivatable drugs are highly specific to tumors, causing little normal tissue toxicity, which is unaffected by IR treatment [14, 16, 20, 25, 31]. Preclinical in vivo data suggest that radiosensitization trials with NQO1-bioactivatable drugs are warranted for non-small cell lung, pancreatic, breast prostate, and head and neck cancers.
A clinical trial of radiation sensitization effects of the new drug, isobutyldeoxynyboquione (IB-DNQ), against non-small cell lung (NSCLC) and/or pancreatic adenocarcinomas (PDAC) is warranted. These cancers are almost uniformly NOQ1 over-expressive and they have routinely low levels of catalase [14]. We have developed CLIA assessments of NQO1 status and enzymatic levels for these studies. The pharmacokinetics of IB-DNQ in these cancers, particularly in NSCLC and PDAC cancers, is relatively short at about 6 h, but long enough for sensitization of tumors to the NQO1-bioactivatable drug + IR. Biomarker and DSB repair kinetics are ongoing in our laboratory in preparation for these radiosensitization studies.
This work was supported by NIH/NCI R01s - CA210489 and CA224493 to David A. Boothman.
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\n\n\r\n\tEducation and Human Development is an interdisciplinary research area that aims to shed light on topics related to both learning and development. This Series is intended for researchers, practitioners, and students who are interested in understanding more about these fields and their applications.
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Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. 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. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. 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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",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11401,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"188881",title:"Dr.",name:"Fernando José",middleName:null,surname:"Andrade-Narváez",slug:"fernando-jose-andrade-narvaez",fullName:"Fernando José Andrade-Narváez",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRIV7QAO/Profile_Picture_1628834308121",institutionString:null,institution:{name:"Autonomous University of Yucatán",institutionURL:null,country:{name:"Mexico"}}},{id:"269120",title:"Dr.",name:"Rajeev",middleName:"K.",surname:"Tyagi",slug:"rajeev-tyagi",fullName:"Rajeev Tyagi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRaBqQAK/Profile_Picture_1644331884726",institutionString:"CSIR - Institute of Microbial Technology, India",institution:null},{id:"336849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Izurieta",slug:"ricardo-izurieta",fullName:"Ricardo Izurieta",profilePictureURL:"https://mts.intechopen.com/storage/users/293169/images/system/293169.png",institutionString:null,institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"78849",title:"Application of Vermicompost Fertilizer in Aquaculture Nutrition: Review",doi:"10.5772/intechopen.100326",signatures:"Sonnia Nzilani Musyoka and Rita Nairuti",slug:"application-of-vermicompost-fertilizer-in-aquaculture-nutrition-review",totalDownloads:71,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Animal Nutrition - Annual Volume 2022",coverURL:"https://cdn.intechopen.com/books/images_new/11416.jpg",subseries:{id:"20",title:"Animal Nutrition"}}}]},publishedBooks:{paginationCount:4,paginationItems:[{type:"book",id:"9528",title:"Current Topics and Emerging Issues in Malaria Elimination",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/9528.jpg",slug:"current-topics-and-emerging-issues-in-malaria-elimination",publishedDate:"July 21st 2021",editedByType:"Edited by",bookSignature:"Alfonso J. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"June 29th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:318,numberOfPublishedBooks:32,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},subseries:[{id:"14",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",annualVolume:11410,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},{id:"15",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",annualVolume:11411,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null,editorialBoard:[{id:"241413",title:"Dr.",name:"Azhar",middleName:null,surname:"Rasul",fullName:"Azhar Rasul",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRT1oQAG/Profile_Picture_1635251978933",institutionString:null,institution:{name:"Government College University, Faisalabad",institutionURL:null,country:{name:"Pakistan"}}},{id:"178316",title:"Ph.D.",name:"Sergey",middleName:null,surname:"Sedykh",fullName:"Sergey Sedykh",profilePictureURL:"https://mts.intechopen.com/storage/users/178316/images/system/178316.jfif",institutionString:null,institution:{name:"Novosibirsk State University",institutionURL:null,country:{name:"Russia"}}}]},{id:"17",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",annualVolume:11413,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"243049",title:"Dr.",name:"Anca",middleName:null,surname:"Pantea Stoian",fullName:"Anca Pantea Stoian",profilePictureURL:"https://mts.intechopen.com/storage/users/243049/images/system/243049.jpg",institutionString:null,institution:{name:"Carol Davila University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"203824",title:"Dr.",name:"Attilio",middleName:null,surname:"Rigotti",fullName:"Attilio Rigotti",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"Pontifical Catholic University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"300470",title:"Dr.",name:"Yanfei (Jacob)",middleName:null,surname:"Qi",fullName:"Yanfei (Jacob) Qi",profilePictureURL:"https://mts.intechopen.com/storage/users/300470/images/system/300470.jpg",institutionString:null,institution:{name:"Centenary Institute of Cancer Medicine and Cell Biology",institutionURL:null,country:{name:"Australia"}}}]},{id:"18",title:"Proteomics",keywords:"Mono- and Two-Dimensional Gel Electrophoresis (1-and 2-DE), Liquid Chromatography (LC), Mass Spectrometry/Tandem Mass Spectrometry (MS; MS/MS), Proteins",scope:"With the recognition that the human genome cannot provide answers to the etiology of a disorder, changes in the proteins expressed by a genome became a focus in research. Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. The Proteomics topic aims to attract contributions on all aspects of MS-based proteomics that, by pushing the boundaries of MS capabilities, may address biological problems that have not been resolved yet.",annualVolume:11414,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorThree:null,editorialBoard:[{id:"72288",title:"Dr.",name:"Arli Aditya",middleName:null,surname:"Parikesit",fullName:"Arli Aditya Parikesit",profilePictureURL:"https://mts.intechopen.com/storage/users/72288/images/system/72288.jpg",institutionString:null,institution:{name:"Indonesia International Institute for Life Sciences",institutionURL:null,country:{name:"Indonesia"}}},{id:"40928",title:"Dr.",name:"Cesar",middleName:null,surname:"Lopez-Camarillo",fullName:"Cesar Lopez-Camarillo",profilePictureURL:"https://mts.intechopen.com/storage/users/40928/images/3884_n.png",institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",institutionURL:null,country:{name:"Mexico"}}},{id:"81926",title:"Dr.",name:"Shymaa",middleName:null,surname:"Enany",fullName:"Shymaa Enany",profilePictureURL:"https://mts.intechopen.com/storage/users/81926/images/system/81926.png",institutionString:"Suez Canal University",institution:{name:"Suez Canal University",institutionURL:null,country:{name:"Egypt"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"chapter.detail",path:"/chapters/62675",hash:"",query:{},params:{id:"62675"},fullPath:"/chapters/62675",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)}()