Selected substrates, inducers and modulators of P-gp.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\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:"7991",leadTitle:null,fullTitle:"Understanding the Molecular Crosstalk in Biological Processes",title:"Understanding the Molecular Crosstalk in Biological Processes",subtitle:null,reviewType:"peer-reviewed",abstract:"It is essential to address the aspects related to the crosstalk approach in understanding complex biological processes in different organisms, including plants, microorganisms, animals, and humans. This will definitely provide the information required to achieve the biological advancements. Therefore, this book highlights the advances made in the research field covering crosstalk in different biological processes. Current research trends, future research directions, and challenges are also addressed. This book will provoke the interest of various readers, researchers, and scientists who will find this information useful for the advancement of their research on biological processes in living organisms.",isbn:"978-1-78984-893-9",printIsbn:"978-1-78984-892-2",pdfIsbn:"978-1-83881-965-1",doi:"10.5772/intechopen.77821",price:100,priceEur:109,priceUsd:129,slug:"understanding-the-molecular-crosstalk-in-biological-processes",numberOfPages:90,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"a4b678bab3a6334187a4fb5bb44a3811",bookSignature:"Mohamed A. El-Esawi",publishedDate:"June 24th 2020",coverURL:"https://cdn.intechopen.com/books/images_new/7991.jpg",numberOfDownloads:3779,numberOfWosCitations:0,numberOfCrossrefCitations:6,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:7,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:13,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 29th 2018",dateEndSecondStepPublish:"February 13th 2019",dateEndThirdStepPublish:"April 14th 2019",dateEndFourthStepPublish:"July 3rd 2019",dateEndFifthStepPublish:"September 1st 2019",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"191770",title:"Dr.",name:"Mohamed A.",middleName:null,surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. El-Esawi",profilePictureURL:"https://mts.intechopen.com/storage/users/191770/images/system/191770.jpeg",biography:"Dr. Mohamed A. El-Esawi is a visiting research fellow at the University of Cambridge, United Kingdom, and Associate Professor of Molecular Genetics, Botany Department, Faculty of Science, Tanta University, Egypt. Dr. El-Esawi received his BSc and MSc from Tanta University, and his Ph.D. degree in Plant Genetics and Molecular Biology from Dublin Institute of Technology, Technological University Dublin, Ireland. After obtaining his Ph.D., Dr. El-Esawi joined the University of Warwick, United Kingdom; University of Sorbonne, France; and University of Leuven (KU Leuven), Belgium as a visiting research fellow. His research focuses on plant genetics, genomics, molecular biology, molecular physiology, developmental biology, plant-microbe interaction, and bioinformatics. He has authored several international peer-reviewed articles, book chapters, and books, and has participated in more than sixty conferences and workshops worldwide. Dr. El-Esawi is currently involved in several biological science research projects.",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"9",institution:{name:"Tanta University",institutionURL:null,country:{name:"Egypt"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"171",title:"Cell Biology",slug:"medicine-cell-biology"}],chapters:[{id:"70482",title:"Introductory Chapter: Crosstalk Approach for a Deeper Understanding of the Biological Processes",doi:"10.5772/intechopen.90561",slug:"introductory-chapter-crosstalk-approach-for-a-deeper-understanding-of-the-biological-processes",totalDownloads:476,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Mohamed A. El-Esawi",downloadPdfUrl:"/chapter/pdf-download/70482",previewPdfUrl:"/chapter/pdf-preview/70482",authors:[{id:"191770",title:"Dr.",name:"Mohamed A.",surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. El-Esawi"}],corrections:null},{id:"66864",title:"Crossroad between Obesity and Cancer: A Defective Signaling Function of Heavily Lipid-Laden Adipocytes",doi:"10.5772/intechopen.85995",slug:"crossroad-between-obesity-and-cancer-a-defective-signaling-function-of-heavily-lipid-laden-adipocyte",totalDownloads:932,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:1,abstract:"Obesity and its comorbidities exhibit a gender-related dimorphism. Obese males tend to accrue more visceral fat leading to abdominal adiposity, which shows a strong correlation with serious obesity-associated comorbidities, cardiovascular diseases and cancers. In contrast, obese females accumulate excessive fatty tissue predominantly subcutaneously enjoying strong protection from the obesity-related diseases. The health advantage of obese women as compared with obese men may be attributed to their higher estrogen production and an increased transactivation of estrogen receptors (ERs). The recently clarified intracrine, paracrine, and endocrine functions of adipose tissue illuminate that concentrations of estrogens and the suitable expression and activity of ERs strongly define all regulatory functions in both men and women. All well-known cancer risk factors are in correlation with defects of estrogen signaling in partnership with glucose intolerance as estrogen regulates all steps of glucose uptake. In central obesity, increased secretions of cytokines and growth factors are not causal factors of developing insulin resistance, and unrestrained cell proliferation, but rather, they are compensatory processes so as to increase estrogen synthesis and ER transactivation. In conclusion, a causal therapy against obesity and obesity-related diseases aims to improve estrogen signaling in both men and women.",signatures:"Zsuzsanna Suba",downloadPdfUrl:"/chapter/pdf-download/66864",previewPdfUrl:"/chapter/pdf-preview/66864",authors:[{id:"290038",title:"Prof.",name:"Zsuzsanna",surname:"Suba",slug:"zsuzsanna-suba",fullName:"Zsuzsanna Suba"}],corrections:null},{id:"66554",title:"Oral Health and Cardiovascular Disorders",doi:"10.5772/intechopen.85708",slug:"oral-health-and-cardiovascular-disorders",totalDownloads:854,totalCrossrefCites:3,totalDimensionsCites:4,hasAltmetrics:1,abstract:"Several studies reported the cross talk between oral health and cardiovascular disorders. The aim of the present chapter is to review the main mechanisms linking oral and cardiovascular disorders, the main pathologies which could be linked, and possibilities for prophylactic and therapeutic interventions. Periodontitis was associated with cardiovascular risk, and the links between the two entities are represented by bacteria and their toxins released into the blood, causing endothelial dysfunction and providing a proatherogenic and prothrombotic effect and an inflammatory and immune reaction. The mentioned mechanisms explain the reported associations of periodontitis with stroke, coronary heart disease, and peripheral vascular disease. Periodontitis was also associated with diabetes mellitus and impaired lipid metabolism. Not all studies confirmed the association between periodontitis and coronary artery disease or stroke. Tooth loss, the most important consequence of periodontitis, has been also associated with cardiovascular disease. Dental and pulpal caries were also found to be independent risk factors for atherosclerosis, while restorations were inversely related to an atherosclerotic burden. Sucrose is involved in both cariogenesis and atherosclerosis. Fluorides prevent aortic calcifications and enamel demineralization and inhibit bacterial metabolism but are cardiotoxic. Heightening awareness of good dental hygiene can improve cardiovascular health.",signatures:"Ioana Mozos and Dana Stoian",downloadPdfUrl:"/chapter/pdf-download/66554",previewPdfUrl:"/chapter/pdf-preview/66554",authors:[{id:"63258",title:"Prof.",name:"Ioana",surname:"Mozos",slug:"ioana-mozos",fullName:"Ioana Mozos"},{id:"182103",title:"Dr.",name:"Dana",surname:"Stoian",slug:"dana-stoian",fullName:"Dana Stoian"}],corrections:null},{id:"68073",title:"The “Weight” of Obesity on Arterial Hypertension",doi:"10.5772/intechopen.87774",slug:"the-weight-of-obesity-on-arterial-hypertension",totalDownloads:903,totalCrossrefCites:2,totalDimensionsCites:2,hasAltmetrics:0,abstract:"The prevalence of obesity and its related diseases are increasing worldwide. This phenomenon has been observed not only in adults but also in adolescents and children. Numerous scientific studies have revealed a direct correlation between the increase in blood pressure and weight gain. In fact, visceral fat can contribute to the rise in blood pressure because it is associated with an increased production of inflammatory cytokines (such as interleukin-1-β, tumor necrosis factor-α and interleukin-6) and inflammatory factors (such as C-reactive protein), inducing endothelial dysfunction and consequently arterial hypertension (AH). Insulin resistance, which develops in obese individuals, may represent an additional risk factor in the onset of AH. Postprandial hyperglycemia is not able to inhibit lipolysis, inducing a greater release of free fatty acids causing metabolic abnormalities, oxidative stress and vascular dysfunction. In this chapter, we will examine the mechanisms that correlate obesity to hypertension, such as the involvement of the sympathetic nervous system, metabolic and renal alterations. Finally, the pharmacological and nutritional treatment of obesity-related hypertension will be described.",signatures:"Annalisa Noce and Nicola Di Daniele",downloadPdfUrl:"/chapter/pdf-download/68073",previewPdfUrl:"/chapter/pdf-preview/68073",authors:[{id:"292924",title:"Prof.",name:"Nicola",surname:"Di Daniele",slug:"nicola-di-daniele",fullName:"Nicola Di Daniele"},{id:"292925",title:"Prof.",name:"Annalisa",surname:"Noce",slug:"annalisa-noce",fullName:"Annalisa Noce"}],corrections:null},{id:"68293",title:"Predictors of Resistance Hypertension and Achievement of Target Blood Pressure Levels in Patients with Resistant Hypertension",doi:"10.5772/intechopen.88126",slug:"predictors-of-resistance-hypertension-and-achievement-of-target-blood-pressure-levels-in-patients-wi",totalDownloads:617,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Uncontrolled arterial pressure is associated with a fourfold increase in the risk of developing cardiovascular events compared to patients with hypertension who have reached the target blood pressure level. The aim of this study is to evaluate the characteristics of patients with resistant arterial hypertension undergoing inpatient treatment at the Department of Symptomatic Hypertension and assess the prevalence of true resistant hypertension in a cohort of patients who take 3 and more antihypertensive agents, the clinical predictors of resistant hypertension. The study included 1146 patients with resistant AH who received 3 or more antihypertensive drugs with the level of office blood pressure at admission ≥140/90 mm Hg. Patients were followed by the next examinations: body height and body measurements, office blood pressure, echocardiography, sleep apnea determination, blood biochemical analysis, determination of levels of TTH, T3, T4, blood renin, blood aldosterone, metanephrine urine, and cortisol. Our data showed that 31% of patients who received 3 or more antihypertensive drugs had true resistant hypertension. Fixed combinations were taken by 71.9% of patients. We have found which factors were significantly associated with the treatment regimen with ≥3 or 4 drugs. Also we have demonstrated predictors for blood pressure reduction.",signatures:"Yuriy Mykolayovych Sirenko, Oksana Leonidivna Rekovets and Olena Oleksandrivna Torbas",downloadPdfUrl:"/chapter/pdf-download/68293",previewPdfUrl:"/chapter/pdf-preview/68293",authors:[{id:"226677",title:"Prof.",name:"Yuriy",surname:"Sirenko",slug:"yuriy-sirenko",fullName:"Yuriy Sirenko"},{id:"297325",title:"Dr.",name:"Oksana",surname:"Rekovets",slug:"oksana-rekovets",fullName:"Oksana Rekovets"},{id:"297830",title:"Dr.",name:"Olena",surname:"Torbas",slug:"olena-torbas",fullName:"Olena Torbas"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5781",title:"Phytohormones",subtitle:"Signaling Mechanisms and Crosstalk in Plant Development and Stress Responses",isOpenForSubmission:!1,hash:"054eaa85c13ebe3d04fb8852005d2bad",slug:"phytohormones-signaling-mechanisms-and-crosstalk-in-plant-development-and-stress-responses",bookSignature:"Mohamed El-Esawi",coverURL:"https://cdn.intechopen.com/books/images_new/5781.jpg",editedByType:"Edited by",editors:[{id:"191770",title:"Dr.",name:"Mohamed A.",surname:"El-Esawi",slug:"mohamed-a.-el-esawi",fullName:"Mohamed A. 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\r\n\tThis book is going to be an excellent overview of duodenal physiology, pathology, and therapeutic aspects. Duodenum is the most metabolically active part of the small intestine. It is the site of active absorption of many nutrients. It is also the source of many hormones which not only control biliary and pancreatic secretions but also different metabolic activities in our body. It is also the commonest site of peptic ulcer disease and peptic ulcer bleeding. Giardiasis and many opportunistic infections like cryptosporidium, microsporidium, and mycobacterium avium intracellulare infection can occur in the duodenum. Duodenal adenoma, ampullary adenoma, gastrointestinal stromal tumors, neuroendocrine tumors, and duodenal carcinoma are occasionally seen in our clinical practice. Different diagnostic and therapeutic modalities of these topics will be discussed in this book. With the epidemic of obesity throughout the world, the duodenum has now become one of the therapeutic targets. Roux-en-Y Gastric bypass surgery is done to bypass the duodenum so nutrient absorption cannot occur. Now duodenal resurfacing is done to control obesity and type II diabetes mellitus.
\r\n\t
Multidrug resistance (MDR) is one of the major factors contributing to a failure of doxorubicin for cancer treatment. Typically, the loss of cell sensitivity to chemotherapy is not limit to only doxorubicin and anthracycline derivatives. The MDR phenomenon evidently extends across various structurally-unrelated anticancer drugs, regardless of their molecular targets [1, 2, 3]. Hence, MDR development in cancer cells can simultaneously reduce the effectiveness of several cytotoxic drugs, leading to chemotherapeutic failure. Consequently, patients need higher doses of the anticancer agents to achieve therapeutic success. Either intrinsic or acquired resistance to doxorubicin-based chemotherapy has been attributed to various mechanisms including high expression of the drug efflux transporters, alteration of cell cycle checkpoints and apoptotic signals, increased drug detoxification and DNA repair processes [4, 5, 6]. Regarding this, MDR reversal can be one of the strategic approaches to enhance the efficacy, without increased adverse events, of doxorubicin.
This chapter focused on the most studied drug efflux transporter P-glycoprotein (P-gp) and its role in doxorubicin resistance in chemotherapy. In addition, some strategic approaches to conquer P-gp-based MDR in cancer treatment were also described.
Drug transporters can be grouped, according to their transport direction, into uptake and efflux pumps. Most of the known efflux transporters particularly P-glycoprotein (P-gp or MDR1; encoded by
Among the ABC efflux transporters, P-gp is the first and most studied transporter for MDR development in chemotherapy and drug-transporter-related interaction issues. This transporter was first identified from its involvement with multidrug-resistance in cancer cells. Particularly, overexpression of P-gp in cancer cells, either intrinsic or acquired, has been strongly associated with MDR occurrence, thereby P-gp becomes a promising target for development of chemosensitizers.
P-gp (MW approximately 170 kDa) is a single polypeptide with 1280 amino acids arranging in two duplicated units of a 6 α-helix structure hydrophobic TMD with linkage to a hydrophilic NBD (Figure 1) [1, 2, 7]. These two TMD with the total of 12 helices forms together into one channel as the membrane crossing passage. A substrate binds to the drug-binding site in the TMD whereas an ATP binds to the NBD. After ATP binding, ATP undergoes hydrolysis into ADP for energy to activate P-gp action through protein conformational alteration [7, 8]. This transporter, then, is able to move its substrates across lipid bilayer structure of plasma membrane to extracellular environment.
The key ABC drug efflux transporters and their selected anticancer drug substrates.
P-gp is constitutively located in the apical surface of either epithelial or endothelial linings of various normal tissues/organs such as adrenal glands, intestine, liver, kidney, pancreas, placenta, capillary vessels in the brain and testes [2, 7, 8, 9, 10]. Some organs such as prostate, skin, heart and skeletal muscle have low constitutive expression of P-gp. It should be noting that expression level of P-gp varies in each organ. For example, the numbers of P-gp in colon and ileum are higher than those in jejunum, duodenum and stomach [11, 12]. The tissue distribution of P-gp indicates that this transporter normally serves as an intrinsic determinant of oral drug bioavailability and drug disposition [13, 14, 15, 16, 17, 18]. Intestinal P-gp can influence the absorptive amount of its drug substrates, except those in BCS class I (i.e., high permeability and high solubility drugs such as verapamil), into the body after orally taken [13, 19, 20, 21]. The constitutive expression of P-gp at the mucosal surface in the lower gastrointestinal (GI) tract (i.e. jejunum, ileum, and colon) may prevent an uptake of its substrate, and perhaps also facilitate GI excretion. Moreover, the interplay between P-gp and the major phase I drug metabolizing enzymes (e.g. cytochrome P450, CYP450) can be anticipated due to their substrate similarity [22]. As such, P-gp and CYP3A4 act in concert to affect metabolic biotransformation of their substrates such as paclitaxel in intestine and liver, influencing the oral drug bioavailability [22, 23, 24]. Localization of P-gp in the blood-organ barriers such as brain or testis prevents drug penetration into such organ systems such as brain, testes [13, 23, 25, 26]. The presence of P-gp on the brush border of nephron proximal tubule and hepatocytes involve with excretion of drugs and endogenous substrates into the urine and bile [13, 27]. To this end, P-gp can be considered as the protective mechanism against xenobiotics as well as pharmacokinetic influencer particularly on absorption, distribution and disposition.
Expression of P-gp at plasma membrane involves several cellular processes that linking to P-gp mRNA and protein expression. The regulatory mechanisms have been largely associated with (1) activation or inactivation of oncogenes (e.g., Ras, c-Raf) and transcriptional process, (2) MDR1 translation into P-gp and post translational modification, protein trafficking, and (3) P-gp turn over. It has been reported that the dysregulated microRNA levels (e.g., miR-21, -27a, -451, -130a, -298) could cause MDR development in various cancer cells [28, 29, 30, 31, 32, 33, 34]. For example, miR-130 was correlated to MDR1/P-gp overexpression, and cisplatin resistance in SKOV3/CIS cells [32]. Overexpression of miR-27a and miR-451 was linked to increased MDR1 expression and MDR phenotype in resistant cancer cells A2780DX5 and KB-V1 [28].
Overexpression of P-gp particularly in MDR phenomenon has been evidently connected to up-regulation of MDR1 gene through alteration of various signaling pathways and transcription factors. Example of the transcriptional factors involving in MDR1 transcription are nuclear factor-κB (NF-𝂻) [35, 36], Y-box binding protein-1 (YB-1) [37, 38], activator protein-1 (AP-1) [39], and hypoxia-inducible factor-1 (HIF-1) [38, 40]. The activities of these transcription factors have been linked to various signal transduction pathways, particularly the two major cell survival signaling cascades i.e. (1) the mitogen-activated protein kinase (MAPK) [37, 41], and (2) the phosphatidylinositol 3-kinase (PI3K) pathways [42, 43]. It has been shown that hyperactivation of either MAPK/ERK1/2 or PI3K/Akt/NF-𝂻 signaling pathways results in overexpression of P-gp in doxorubicin-resistant cells such as lung, breast and ovarian cancer cells [44, 45, 46, 47, 48, 49]. An up-regulation of P-gp expression in vincristine-resistant human gastric cancer cells was associated with activation of the p-38/MAPK pathway [50].
After activation and translocation into nucleus, transcription factors such as NF-kB and YB-1 (Y-box binding protein) bind to MDR1 promoter region, leading to initiation of MDR1 transcription. Increase in YB-1 nuclear activity is related to P-gp-mediated development of MDR in several cancers including breast cancer, lung cancer, ovarian cancer, colorectal cancer, prostate cancer and osteosarcoma [38]. In response to cell stress such as hyperthermia, viral infection and chemical assault, the survival Akt and MAPKs signaling would be activated, and subsequently increase YB-1 expression and translocation into nucleus for its MDR1-transcription activity [51]. Doxorubicin is a known P-gp inducer in various cancer cells. Doxorubicin up-regulates MDR1 gene expression via the MAPK/ERK1/2 signaling that linked to activation of YB-1 in B-cell lymphoma [37]. Moreover, upregulation of P-gp has been reported after prolonged exposure to various functional unrelated compounds, leading to the loss of drug efficacy and safety [52]. Examples of the known P-gp inducers include anticancer (e.g., cisplatin, doxorubicin, etoposide vinblastine), antidepressants (e.g., trazodone, St. John’s Wort), anticonvulsants (e.g., carbamazepine, phenytoin), anti-HIV (e.g., saquinavir, indinarvir, tenofovir), immunosuppressants (e.g., cyclosporine, tacrolimus), steroids (e.g., dexamethasone) [52, 53, 54]. It is worth noting that certain CYP450 inducers such as rifampin and St. John’s Wort are able to up-regulate P-gp expression, possible sharing through the PXR regulation [55, 56]. Prolonged exposure to rifampin and St. John’s Wort in human led to increased intestinal P-gp level, and increased digoxin absorption [57, 58]. Since, P-gp-mediated MDR in cancer is largely due to up-regulation of P-gp expression, better understanding of the signaling proteins and transcription factors will provide a promising targets in overcoming MDR for anticancer chemotherapy.
Overexpression of P-gp has been strongly correlated with chemo-resistance and cancer relapses in several cancer patients such as breast cancer, adult acute myeloid leukemia, pheochromocytoma patients, leading to poor prognosis from therapeutic failure in patients receiving chemotherapy [1, 59, 60, 61, 62]. Accordingly, P-gp is intrinsically expressed in various cancer types, particularly those derived from tissues with high basal MDR1 expression levels such as colon, kidney and liver tissues. Being a transmembrane efflux pump, P-gp serves as a cellular defense mechanism against drug assault by limiting intracellular drug accumulation up to toxic threshold level. Regarding this, the susceptibility of cancer to anticancer drugs being P-gp substrate varies, depending on intrinsic expressed P-gp levels. Certain types of cancers may be classified as poor responder showing their unresponsiveness to chemotherapy regimens containing P-gp substrates. For example, prostate cancer appears to be better responder to chemotherapy, as compared to colorectal or renal cancers [63, 64]. Moreover, some cancers such as leukemia, lymphoma and breast cancer having low levels of intrinsic P-gp expression, and thus initially respond well to chemotherapy. Later, after repeated treatment, the expression level of P-gp markedly increases, and those cancers display multi-drug resistance (MDR) phenotype [1, 65, 66]. This acquired MDR phenomenon can be viewed as cellular adaptive survival response to cytotoxic challenge.
Examples of substrates and modulators of P-gp are listed in Table 1.
Substrates (Anti-cancer drugs) | Inducers (Anti-cancer drugs) | P-gp modulators | |
---|---|---|---|
Direct inhibitors | Suppressors of expression | ||
Actinomycin D Colchicine Docetaxel Doxorubicin Daunorubicin Epirubicin Etoposide Idarubicin Imatinib Methotrexate Paclitaxel Teniposide Topotecan Vinblastine Vincristine | Daunorubicin Docetaxel Doxorubicin Flutamide Paclitaxel Vinblastine Vincristine | Small molecule inhibitors Cyclosporin A Verapamil VX-710 (Biricodar) Dexverapamil PSC833 (Valspodar) GF120918 (Elacridar) XR9576 (Tariquidar) LY335979 (Zosuquidar) Capsaisin Curcumin Limonin Piperine Quercetin Monoclonal antibodies MRK 16 MRK 17 UIC 2 | Small molecule inhibitors Curcumin Dasatinib Dexverapamil Reserpine Imatinib Nilotinib Sorafenib Trifluoperazine Toremifene PSC833 (Valspodar) RNA interference Antisense oligonucleotides |
Selected substrates, inducers and modulators of P-gp.
Human ABC efflux transporters demonstrate their broad substrate specificity toward structurally diverse lipophilic compounds. Most of their substrates are weakly amphipathic and hydrophobic planar structure with aromatic ring and positively charged nitrogen atom [52, 54, 67, 68]. Examples of P-gp substrates are anticancer drugs (vinca alkaloids, anthracyclines, and epipodophyllotoxins), cardiovascular drugs (e.g., digoxin, quinidine, talinolol, diltiazem, losartan, verapamil), anti-microbial agents (e.g., doxycycline, erythromycin, itraconazole, rifampin), anti-viral drugs (e.g., indinavir), anticonvulsants (e.g., phenytoin), acid blockers (e.g., cimetidine), immunosuppressants (e.g., cyclosporine, tacrolimus), steroids (e.g., aldosterone, cortisol, dexamethasone), opioids (loperamide, morphine).
Modulators suppress P-gp activity through either (1) direct inhibition of P-gp function by either competitive or non-competitive inhibitors; or (2) suppression of P-gp expression levels by interferences with either transcription, translation/post-translation, and degradation processes.
The direct inhibition of active P-gp can be attributed to the interaction between chemicals and P-gp at either TMB or NBD [67, 68, 69]. Any compound such as tyrosine Kinase Inhibitors interferes with ATP binding or hydrolysis in NBD site can reduce P-gp transport action [70]. Chemicals identified as small molecule P-gp inhibitors such as amiodarone, diltiazem, verapamil bind to substrate binding sites or allosteric sites in TMB, resulting in interference on substrate binding and transport. It has been reported that certain compounds such as cyclosporine A could exert their inhibitory action by interfering with substrate recognition and ATP hydrolysis [8, 67, 68, 69]. It is not surprising that these TMB type inhibitors and substrates share many common molecular features such as hydrophobic planar structure. In addition, due to the diversity in chemical structure of P-gp inhibitors, establishment of the structure activity relationship (SAR) of P-gp inhibitors is very challenging. The structure pattern of the inhibitors contains planar rings and basic nitrogen atom within an extended side chain of the aromatic ring. The presence of tertiary amino groups, in comparison with primary and secondary amine, increases the anti-MDR potency considerably. Furthermore, the presence of nitrogen atom in non-aromatic ring apparently increases inhibitory action of the compounds [71]. Examples of P-gp inhibitors are calcium channel blockers (verapamil, diltiazem), and various phytochemicals such as flavonoid and steroidal compounds (e.g., quercetin, resveratrol), indole alkaloids and polycyclic compounds (e.g., capsaicin, piperine, rhinacanthin C) [66, 72, 73, 74].
Ideally, the P-gp inhibitors should be potent and selective to P-gp function at target cells/tissues, with no systemic side effects. To date, there are four generations of small molecule inhibitors. The first generation inhibitors are known drug substrates of the ABC transporters such as verapamil, cyclosporine A, tamoxifen and quinidine [75]. They were not specifically designed to be P-gp inhibitors, and could not display good clinical outcomes in their MDR reversal activity. The clinical disappointment could be due to their weak inhibitory potency against the MDR transporters including P-gp, and their pharmacokinetic interactions with chemotherapeutic agents, leading to the need of high doses and intolerable adverse effects [1, 76]. Next, the second generation inhibitors such as valspodar (cyclosporine A derivative) were developed, based on structure activity relationships of the first generation compounds, in order to improve potency, specificity, and to reduce systemic toxicity. Although this group of inhibitors demonstrated their improvement in inhibitory potency, their clinical outcomes were still unsatisfied due to their pharmacokinetic interaction with the anti-cancer drugs via inhibition of cytochrome P450, and their severe toxicity [75, 77]. Subsequently, the third generation P-gp inhibitors such as elacridar, tariquidar and zosuquidar were developed in order to address the limitations of the second generation compounds. These inhibitors elicit no effect on CYP P450 metabolism, therefore they are unlikely to affect the plasma concentrations of anti-cancer drugs. They were also more potent and selective P-gp inhibitors, effectively working in nanomolar concentration range. However, the potent P-gp inhibitor tariquidar can be either substrate or inhibitor of P-gp depending on its given dose [78]. To date, the clinical efficacy for MDR reversal of this generation has yet completely satisfied, its effectiveness possibly also depends on given dosage and intrinsic tumor properties.
Currently, phytochemicals or natural compounds with MDR reversal activity have been subject of interest in searching for new effective chemo-sensitizer against cancer. This group of inhibitors obtained from natural sources is classified as the fourth generation inhibitor. Numerous phytochemical researches on pharmacological activities and pharmacokinetics have revealed that plant-based compounds elicit a broad spectrum of pharmacological actions such as anti-cancer, anti-oxidant, anti-microbial, anti-inflammation, etc. In addition, these plant-based compounds, depending upon its molecular structure, may interfere with P-gp and metabolizing enzymes, leading to the concerning issues in drug bioavailability and pharmacokinetic drug interactions. The advantages of the fourth generation inhibitors in part rely on their natural origin with long history of uses in dietary or health supplements and in traditional medicine. It may be able to presume that this group of inhibitors derived from known edible products possessed less toxicity and more tolerable than those of the previous generation compounds. Evidently, even vegetables (e.g., bitter melon), spices (e.g., black pepper, turmeric) or fruits (e.g., orange, grapefruit) also contain substances that could inhibit P-gp and other efflux transporters in the ABC superfamily [72, 73, 74, 75, 77, 79, 80, 81, 82]. Their competitive inhibition against the efflux transporters enhance cytotoxicity of anticancer drugs such as doxorubicin and vinblastine, leading to potential MDR reversal in various cancer cells. However, the inhibitory potency of these plant-based compounds against P-gp activity might be low. Their IC50 values obtained from the in vitro cell culture models appear to be in micromolar range. Thus, this group of inhibitors is unlikely a good MDR reversing agent through direct P-gp inhibition at MDR cancer cells in clinical setting. In addition, the interference of P-gp activity of these compounds in pharmacokinetic aspect may influence on P-gp-related ADME and bioavailability of chemotherapeutic drugs that concomitantly given. Nevertheless, the opportunities of further development into effective chemosensitizers cannot be excluded. Better understanding of QSAR may enable to facilitate chemical modification of these identified plant-based P-gp inhibitors to generate more potent and high selective P-gp inhibitors. Furthermore, several plant-based compounds (e.g, curcumin, resveratrol, quercetin) have been demonstrated their potential in down-regulation of P-gp and other key regulators in transporter-independent MDR mechanisms [75, 82, 83, 84, 85, 86].
In addition to small molecule inhibitors, monoclonal antibodies can be another alternative approach in inhibiting P-gp activity. Theoretically, any agents that specifically affect lipid-protein interactions or protein structure of targeted P-gp can be developed into P-gp inhibitor. Typically, monoclonal antibody can be developed to specifically recognize and bind to its target protein, leading to inhibition of changes in protein conformation. Regarding this, human P-gp-specific antibodies UIC2, MRK-16 and 4E3 reacted specifically to the extracellular loop of both halves of P-gp, and disabled P-gp transport activity [87]. Consequently, treatment cancer cells with these antibodies resulted in increased concentrations of anticancer drugs (e.g., vincristine, actinomycin D, doxorubicin, paclitaxel) within the cells, and improve drug effectiveness [87, 88, 89, 90, 91]. In athymic mice model, MRK16 was demonstrated its ability to significantly reduce tumor mass [92]. Further clinical studies of human P-gp-specific antibodies are needed to conduct in terms of safety and efficacy.
In addition to direct inhibition, reduction of P-gp activity can arise from decrease of protein expression at plasma membrane. Interference on transcription and translation of MDR1 gene, resulting in reduction of P-gp expression, can be another approach to overcome MDR in cancer. Several innovative tools targeting at MDR transcription or mRNA including small molecules, antisense oligonucleotides, hammerhead ribozymes and RNA interference strategies have been employed.
Application of microRNA and RNAi technologies with either small-interfering RNA (siRNA) or small hairpin RNA (shRNA) to specific silence MDR1 expression in cancer cells with MDR phenotype has been demonstrated their effectiveness in down-regulation of MDR1 and P gp expression with paralleled increases drug accumulation and improved sensitivity to treatment. MicroRNAs (miRNAs) are small non-coding RNA molecules that can inhibit ABCB1 mRNA translation processes [93, 94]. A number of miRNAs have been studied on their ability to down-regulate P-gp expression and restore cell sensitivity to P-gp drug substrates in drug resistant cells [34]. For example, miRNA-4539 could increase doxorubicin-mediated cell death in MDA-MB-231 breast cancer cells [93, 94].
The RNAi technologies involve either transient gene-silencing by siRNA or stable inhibition by MDR1 shRNA-transfected on plasmid DNA of MDR cancer cells. Treatment with siRNA against MDR1 increases drug-mediated cytotoxicity in various MDR cancer cells such as paclitaxel in MDR1 ovarian cancer cells and doxorubicin in doxorubicin-resistant breast cancer cells [95]. In addition, siRNA was able to significant reduced size of doxorubicin-resistant xenograft in a mouse model [96]. MDR1 ShRNA transfected in taxol-resistant human ovarian cancer cell line A2780 effectively down-regulated P-gp expression, and enhanced paclitaxel-mediated toxicity in this cells [97].
Selective suppression of P-gp/MDR1 expression with either microRNA or RNAi technologies offers the novel approach to specifically combat P-gp-based MDR in cancer, and re-sensitize the MDR cells to chemotherapeutic agents. However, for their therapeutic applications, there are several challenges required especially the effective miR/RNAi delivery to target cancer cells, design of expression vectors for shRNA, systemic stability and degradation, and safety of patients.
Numerous small molecules particularly those in the fourth generation of P-gp inhibitors such as curcumin, ginsenoside, quercetin and resveratrol have been demonstrated their ability to reduce P-gp function in the MDR cancer cells via down-regulation of P-gp expression [83, 84, 85]. By targeting at the signaling pathways related to transcription process of MDR1, several plant-based compounds suppress P-gp expression in the resistance cells and improve chemo-sensitivity to anticancer drugs. For instance, the P-gp modulating effect of asiatic acid, ginsenoside, isoquinoline alkaloids (e.g. cepharantine, tetrandine) resulted from their blockade of MAPK/ERK1/2 or PI3K/Akt pathways in MDR cancer cells [86, 98, 99, 100, 101]. Another isoquinoline alkaloid berberine inhibited P-gp expression and enhanced doxorubicin-mediated toxicity in MCF-7 cells through down-regulation of AMPK-HIF1α signaling cascade [102]. Anti-MDR property of natural curcuminoids (e.g., curcumin, bisdemethoxycurcumin) involved with inhibition of human MDR1 gene expression in MDR cervical carcinoma KB-V1 cells [103]. In addition, certain compounds such as a natural marine product Et743 inhibit MDR1 transcription via blocking its promoter activation [104].
Doxorubicin is one of the most effective cytotoxic anticancer drugs. This drug has been used for combating various types of cancers such as cancers of breast, ovary, prostate, stomach, thyroid; small cell cancer of lung; squamous cell cancer of head and neck; multiple myeloma; Hodgkin’s disease; lymphomas; acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML). Unfortunately, the uses of doxorubicin can be limited because of its dose-related toxicity (e.g., nausea, vomiting, hair loss, leucopenia, cardiomyopathy, heart failure) and high MDR incidence [105, 106]. Despite the good clinical therapeutic responses are seen in patients receiving doxorubicin in the earliest stage of treatment, multi-drug resistance may later develop and lead to treatment failure.
One of the major mechanisms responsible for doxorubicin-induced MDR is up-regulation of MDR1/P-gp expression. Doxorubicin is an anthracycline derivative with a four-membered ring system containing an anthraquinone chromophore, and an aminoglycoside (Figure 1). This molecular structure accommodates its interaction with major MDR efflux transporters in the ABC superfamily proteins. It has been well established that doxorubicin and other anthracycline derivatives are P-gp substrates with ability to up-regulate P-gp/MDR1 expression after repeated exposure in various cancer cells such as breast and lung cancers as well as in vivo and in clinical settings [66, 107, 108]. For instance, lung perfusion with doxorubicin resulted in an increase of MDR1 RNA in patients with sarcoma pulmonary metastases [18]. The P-gp-overexpressed cancer cells would have intracellular doxorubicin concentration below its effective threshold level. Consequently, cancer cells increasingly survive from doxorubicin-mediated cytotoxity. In this circumstance, titrating dose up to overcome MDR may not enable to achieve a successful outcome due to dose-limiting toxicity. Because the adverse effects of doxorubicin and other anti-cancer drugs are mostly concentration-dependent, increasing doses can produce higher degree of severity and unendurable adverse events, leading to patient’s intolerability and even fatal outcome. Addition of other cytotoxic drugs into doxorubicin-based regimens may not also enable to obtain a chemotherapeutic success, if those drugs are also substrates of the MDR transporters.
Generally, clinical efficacy of doxorubicin depends on its pharmacokinetics after systemic exposure influencing (1) the therapeutic concentration at target organs, and (2) the homogeneity of drug distribution in the cancerous tissues particularly solid tumor. In addition, it is very critical that doxorubicin accumulates within the targeted cancer cells at the level greater than its cytotoxic threshold to elicit its pharmacological actions.
Doxorubicin is poorly absorbed through GI with low bioavailability (approximately 5%) after orally taken, due to its instability in stomach acidic pH and CYP450 biotransformation in liver. In addition, doxorubicin can induce cytotoxicity in normal tissue. Currently, doxorubicin is commercially available for cancer treatment in injection dosage form. Due to its lipophilicity, doxorubicin moves through plasma membrane into the cells via passive diffusion, and its extent of tissues/cellular permeation and cellular retention can be limit by the existence of efflux transporters particularly P-gp. Apparently, doxorubicin is extensively distributed to several organs such as liver, heart, kidney after injection. Being the efflux transporters, P-gp has a significant impact on doxorubicin distribution to certain target tissues such as brain, testes [109, 110]. Certain P-gp inhibitors such as PSC-833, piperine capsaicin, resveratrol, silymarin and quercetin were reported their influence on the pharmacokinetics and tissue distribution of doxorubicin in animal models [85, 110]. Capsaicin was reported to significantly increase the extent of doxorubicin accumulation in mice brain after iv injection probably through inhibition of P-gp at blood brain barrier [110]. In addition, piperine and capsaincin, through P-gp inhibition, reduced drug excretion into bile and urine, leading to increased drug levels in liver and kidney [110].
Critically, overexpression of P-gp on the plasma membrane of cancer cells is a major determinant in preventing intracellular doxorubicin accumulation up to its cytotoxic level. Doxorubicin resistant cancer cells clearly display significant lower intracellular doxorubicin retention with more tolerable to doxorubicin exposure than their parental sensitive cells [65, 66]. Thus, P-gp can be a potential therapeutic target for either MDR reversal or bio-enhancing effect in cancer therapy. The presence of P-gp modulators clearly demonstrates their abilities to restore doxorubicin-mediated killing effect in various cancer cells by increasing intracellular level of doxorubicin [66, 111]. Several plant-based compounds such as limonin, quercetin, resveratrol, curcumin and rhinacanthin-C at their non-cytotoxic concentration have been reported to significantly enhance doxorubicin-mediated cytotoxicity in various cancer resistance cells through modulation of P-gp function [66, 112]. These phytochemical P-gp modulators may suppress P-gp function either by direct inhibition of activity or down-regulation of protein expression.
Moreover, the influence of P-gp on clinical resistance to doxorubicin-based treatment has been reported in cancer patients [113, 114, 115, 116]. In order to improve drug efficacy and patient tolerability, several approaches targeting at the P-gp function and expression have been introduced to increase cellular doxorubicin drug level and restore drug sensitivity without the need of higher concentration or additional chemotherapeutic drugs in the therapeutic regimen.
Taken that doxorubicin is a known substrate of P-gp, the drug efflux transporters in the ATP binding cassette (ABC) family. Hence, any approaches target at the function of these transporters can be presumed to increase therapeutic success for doxorubicin-based chemotherapeutic regimens. Regarding this, the strategies are as follows:
Increases in dose of doxorubicin or number of cytotoxic drugs to achieve therapeutic success. This has not been a satisfactory approach due to drug toxicity and patients’ intolerability.
Utilization of P-gp modulators to inhibit either function or expression.
Development of better drug delivery platforms to bypass P-gp activity, leading to increase intracellular retention of doxorubicin within target cells.
The current MDR reversal strategy has been exploited P-gp modulators that either directly inhibit P-gp activity or down-regulate P-gp expression in order to restore cell chemo-sensitivity to doxorubicin [107]. With the encapsulation technology, P-gp modulators can be co-administered with doxorubicin in the same drug delivery platform, and enhance intracellular doxorubicin accumulation. This approach can be accomplished if the potent, non-cytotoxic P-gp modulators that specifically target at cancer cells are implemented. In addition, the P-gp modulators that also target at non-transporter based resistance such as activation of cellular survival pathways can exert potentially synergistic impact on MDR reversal effect and better response to doxorubicin treatment. Collectively, the combined doxorubicin and P-gp modulators with multiple-hit targets is a promising strategy to achieve chemotherapeutic efficacy without the need of high dose or additional cytotoxic drugs in the therapeutic regimen.
This approach aims to suppress P-gp activity at plasma membrane of target cancer cells. Several P-gp modulators in combination with anti-cancer drugs have been evaluated for safety and efficacy in clinical trials. The clinical outcomes from the first three generations of ABC inhibitors such as quinine, verapamil, cyclosporine-A, tariquitor, PSC 833, LY335979, and GF120918 were quite disappointed, partly because of their dose-limiting adverse events. Most of the P-gp inhibitors required high doses for their clinical MDR reversal effects. In addition, their interference on the P-gp or other ABC transporters at non-target tissues such as brain and kidney could adversely increase accumulation of cytotoxic drugs in these tissues.
The fourth generation of P-gp modulators which are mostly natural products have gained a great interest as potential chemosensitizers in MDR cancer treatment. The advantages of being natural products with long history of use are inclined to the known safety profiles in human and potential hit multiple targets that can restore cell sensitivity to doxorubicin. In addition to direct inhibition of P-gp activity, a number of the natural compounds at non-cytotoxic concentration elicit their chemo sensitizing effects through down-regulation of MDR1 and signaling proteins in cell adaptive survival mechanisms. The higher degree of synergism between doxorubicin and a P-gp modulator can be anticipated with potential therapeutic success. Synergistic outcomes between doxorubicin and natural compounds such as resveratrol, quercetin, silymarin, gallic acid, curcumin, epigallocatechin-3-gallate have been demonstrated in various cancer cell models [82, 83, 103, 111, 117, 118, 119, 120]. In addition to P-gp modulatory activity (inhibiting both P-gp function and expression), these natural compounds have a broad spectrum of pharmacological activities such as antioxidant, anticancer, anti-inflammation, possible through multiple signaling pathways. For example, the biological effects of curcumin have been related to multiple signaling pathways including NF-kB, Akt, MAPK, Nrf2, AMPK, JAK/STAT that involve in MDR1 expression, cell inflammation, and apoptosis [121]. Co-administration of doxorubicin and curcumin significantly improved doxorubicin-mediated cytotoxicity in vitro cell models and in vivo hepatic xenograft mice model, compared with doxorubicin alone [121, 122, 123, 124, 125].
In addition to chemical-based modulators, the uses of specific antibody against P-gp or RNA interference (RNAi) technology to silence P-gp expression may be effective approach to suppress P-gp activity and restore chemo-sensitivity to doxorubicin treatment. Clinical studies on these MDR reversing methods should be extensively conducted to support their uses and benefits in cancer patients.
This approach aims to develop targeted delivery platforms for improving the permeation of doxorubicin/P-gp modulators/ chemo-sensitizers (e.g., antibodies against ABCB1, siRNA) into target cancer cells, leading to an increased intracellular doxorubicin concentration [3, 89, 96, 126, 127, 128]. Various nano-drug delivery platforms such as polymeric and solid lipid nanoparticle (SLNs), liposomes, micelles, mesoporous silica nanoparticles, nanostructured lipid carriers, dendrimers have been constructed to better targeting drug delivery to site of action. This approach in couple with utilization of P-gp modulators can overcome MDR and enhance therapeutic efficacy of doxorubicin. Furthermore, with cancer-targeting ability, this target specific delivery would limit the adverse effect to normal tissues. With the encapsulation technology, nanoparticles (NPs) loaded with doxorubicin and P-gp modulators or other molecules (e.g., siRNAs) has been reported their effectiveness in target delivery into the cells. For examples, aerosol OT (AOT)-alginate NPs enhanced cellular delivery of doxorubicin in MCF-7 cells [129]. Lipid-modified dextran-based NPs loaded with doxorubicin and MDR1 siRNA significantly increased intracellular doxorubicin and reduced P-gp expression levels in osteosarcoma cell line, as compared to doxorubicin alone [130]. Doxorubicin-curcumin composite NPs (e.g., NanoDoxCurc, pegylated-DOX-CUR NPs) could enhance effects of doxorubicin both in vitro and in vivo models of DOX-resistant cancers (e.g., multiple myeloma, acute leukemia, prostate and ovarian cancers). In addition, doxorubicin-curcumin NPs did not cause cardiac toxicity and bone marrow suppression in mice model [131].
Doxorubicin is an effective anti-cancer drug that has high MDR incidence. High expression of an efflux transporter P-gp is one established mechanism responsible for the loss of drug effectiveness and MDR development. This can be due to the P-gp function in preventing intracellular accumulation of doxorubicin up to its effective level. Several approaches have been introduced in order to increase the efficacy of doxorubicin-based chemotherapy and overcome MDR. The combination of doxorubicin and non-cytotoxic P-gp modulators, particularly when given to the specific target cancer can be a promising approach to increase cancer sensitivity to doxorubicin through suppression of P-gp function. With the novel encapsulation technologies, it is very possible to develop the drug delivery platforms with specific targeted cancer cells as well as improvement of doxorubicin delivery into the cells. By these means, enhancement of doxorubicin-mediated cytotoxicity can be achieved with minimal dosing of the anti-cancer drugs. After clinically approval, it will provide a great benefit to patients receiving doxorubicin-based chemotherapy.
The author gratefully thanks IntechOpen Limited for the sponsorship program in publishing this work.
The Author declares no conflicts of interest.
Two approaches have recently emerged in the psychoanalysis of “identity politics”: on one hand, a series of indictments have been leveraged against identity politics through the avenues of Freudian [1] and Lacano-Marxist analyses [2], and, on the other hand, a series of segmented, fractured forays have facilitated the analysis of identity categories through psychoanalytic constructs [3, 4]. The former undermines the validity of identity politics as a sociopolitical enterprise for comprehending oppression, and the latter renders the phrase “X is a social construct” intelligible in piecemeal psychoanalytic fashion, addressing each identity category (e.g., race, gender, ability, sexual orientation, nationality, and so on) without necessarily considering the intersection of these categories. Neither pathway for theorizing identity politics encounters the Real: the ungraspable, elusive, and traumatic center resisted by identity-based discourse but around which it fundamentally revolves. Through a Derridean-inspired deconstruction, I have developed an “aporia of identity” within which two forces ineluctably conflict with one another for determining the content of marginalized identities, namely intersubjectivity and intersectionality. The Real of identity politics resides here: the irresolvable, unsymbolizable clash between the push-and-pull of identification and disidentification with the symbolic register.
“Identity politics” refers to the progressive Leftist discursive formation that foregrounds the political experience of peripheral subject positions. It forges a binarized system for responding to the fundamental question of identity-based movements: “What does it mean to be X (e.g., black, a woman, disabled/differently-abled, and so on)?” The first type of response submits the individual’s identity to an agreed-upon signifier for collective organization against oppressive apparatuses; that is, individuals identify as “being-black” and “being-a-woman” through intersubjective engagement with political groups. These groups, however, inexorably cultivate a particular image, ideal, or paradigm of being-black and being-a-woman, such that individuals who might not “fit the description” cannot completely or sufficiently identify with the group’s implicit representation of being-X. In the case of “being-a-woman,” the politically-crafted image of womanness often assumes the positionality of white feminists, which, in the mid-to-late twentieth century, implied the positionality of being confined to (re)productive labor within their own homes. Women of color, conversely, labored outside their domiciles for decades, if not centuries, before white feminists demanded the capacity to leave the home for professional reasons [5]. The demands of white feminists in political organizations, thus, neglected the marginalized location of black women, introducing another type of response to the meaning of being-a-woman: intersectionality.
Intersectionality, as the second type of response, emerges at the crossing of the individual’s various marginalized identities, taking into account someone’s situatedness at the intersection of being-black, being-a-woman, being-impoverished, and so on [6]. In order to understand the meaning of being-X, we must also understand the meaning of being-A, being-B, being-C, etc. The aforementioned example of white feminists monopolizing the signification of “woman” demonstrates the necessity of interrogating such a signifier from a multitude of standpoints, including race and class. Even within the available categories of identification, individuals vary along further experiential axes: phenotypic expressions of color, gendered expressions of masculinity/femininity, and economic expressions of affluence/pennilessness to name a few. Discovering the intersection from which an individual’s political experience can be (re)constructed, traced, and investigated, therefore, does not guarantee the capacity to adequately signify the individual’s political experience in the social order. The meaning of being-X within the intersectional refusal of signification reveals the antinomic pole, movement, and determination of identity in the context of political engagement. The first type of response (i.e., submission to the signifier) firmly positions the individual as a political subject with respect to an established symbolic identification, and the second type of response (i.e., resistance to the signifier) loosely positions the individual as a political subject with respect to established symbolic identifications. To be clear, the intersectional inclination to constantly revise signification does not completely dissociate the individual from subjectification; rather, the intersectional push away from identity always corresponds to an intersubjective pull toward identification with additional signifiers.
The Derridean [7, 8] formulation of the “aporia of identity” appears as follows: the conditions for the possibility of being-X are simultaneously the conditions for the impossibility of being-X. The conditions for (im)possibility nominalize the action of identifying with political signifiers, which illuminate the individual’s political experience in the social order while also obscuring it. Invoking signifiers to describe one’s marginalized position, if the aim of identity politics has been accurately formulated, will never suffice: the individual always-already exceeds semiotic circumscription in the symbolic order. There is a remainder, a leftover, a stain evading assimilation into extant identity categories; indeed, the escaping excess should not be condemned, loathed, or castigated because, after all, it fuels the discursive formation of identity politics. Imagine the culmination of identity politics; that is, through a series of hard-nosed, social scientific decisions, we accurately determine the political experience of each and every subject position. In turn, the social order could clearly and distinctly designate individuals as “being-black” or “being-a-woman,” arriving at a definitive framework for assessing whether, for instance, Rachel Dolezal is black or Caitlyn Jenner is a woman. Spelling doom for identity politics, the definitive establishment of meaning for categorical designations inspires a teleological paradox: on the surface, identity politics strives for its dissolution through the clearcut determination of individual experience, but, at its core, identity politics conceals its underlying drive for incompletion, indeterminacy, and gappiness.
The surface-level desire communicates a Sisyphean task: following the establishment of definitions for identity categories, the objectively-excluded remainders will subjectively identify with “improper” categories, re-creating the zero-point of identity politics. The discursive formation of identity politics explicates the political experience of the excluded, those pushed to the periphery by bias, prejudice, and discrimination. Any hard-and-fast categorical demarcation of the excluded, thus, requires the conceptual distinction between extensional (i.e., those falling underneath the signifier/category) and non-extensional content (i.e., those falling outside the signifier/category), perpetually creating an excluded set of people. Trans-exclusionary radical feminists (TERFs), for example, determine the boundaries of “being-a-woman” on the basis of innate physiological characteristics for womanness, informed by the primary and secondary sexual characteristics usually attributed to “biological” women. The exclusion concomitant with the biological significance of “woman” represents the form of violence contested by identity politics, which appears at the juncture of every definition for any identity category. The completion of identity politics, in turn, is impossible: the conceptual distinctions required to neatly demarcate political experience would only perpetuate further pockets of exclusion, mandating more conceptual distinctions and categorical designations ad infinitum. What, then, is the goal of identity politics? How can we understand the progression of identity politics in relation to the oppressive organization of the social order? Psychoanalytic allusions to “the Real,” as put forth in Lacanian contexts, offer conceptual resources for pinpointing the positionality and teleology of identity politics with respect to the symbolic register.
The progressive deconstruction of identity categories (network of signifiers) through the invocation of individual experience (the Real) mostly occurs at the precipice of identification with marginalized groups. Consider the following excerpt from Rebecca Tuvel’s “In Defense of Transracialism” (2017) [9]: “[A]s MSNBC contributor Touré put it, [Rachel] Dolezal doesn’t share in ‘the one thing that binds black people,’ namely ‘the experience of racism’” (270). Even though Dolezal appeared to be black through her phenotypic presentation and organizational involvement in the NAACP, those who abhor her racial masquerading often cite a lack of oppression as the reason for her inability to don the signifier “black.” Yet, the chain of signification cascading from “black” encompasses more than “an experience of racism,” especially when non-black racial minorities also confront the oppressive reality of the social order. Other semiotic sources for justifying one’s placement within a racial category might include: self-awareness of ancestry, public awareness of ancestry, self-identification, and culture (ibid). Beyond these indicators for belonging to a particular racial group, the experiential element referenced by the aforementioned MSNBC contributor explodes into an unbounded multiplicity at the intersection of racism with ableism, sexism, homophobia, transphobia, xenophobia, and so on. There seem to be endless possibilities for exploring the meaning of being-black in the various contexts of racism tinged with other forms of oppression, including, potentially, Dolezal’s invention of “being-trans-black” as an excluded category against which discrimination runs rampant [10]. The inexhaustible plenitude of signifiers attributed to any singular identity category raises the following question: within the discursive formation of identity politics, is there any discernible limit to the signification of being-X?
If identity politics maintains its sincere acknowledgement of intersectional modes of oppression, the answer must be “no.” Individual experience, although constrained by the existing order of signifiers for describing marginalized political experience, always-already pushes the prevailing field of signifiers to the Real’s ineffability. Therein resides the (unconscious) death drive of identity politics, continuously overlooked and neglected by previous psychoanalytic forays into the discursive formation; that is, identity politics collides with the Real in its movement toward a fundamental Lacanian doctrine: there is no Other of the Other [11]. Kalpana Seshadri-Crooks [4], in
The unconscious desire of whiteness, thus, discloses the inclination for racial discourse to legitimize oppression in the disguise of non-symbolic, Real distinctions, which Seshadri-Crooks captures with her analysis of phenotypic designations (i.e., hair color, hair texture, facial features, bone structure, etc.) (59). Through the history of racial classification, disparate grounds have been offered for differentiating one race from another: blood (i.e., kinship), phrenology (i.e., skull size/shape), genetics, culture, and physiognomy. The objective foundation of race, in other words, has steadily shifted in its discursive manifestation, and Seshadri-Crooks locates the prevailing justification for racial categorization in phenotypic characteristics. The symbolic identities of “white,” “black,” “Asian,” etc. only maintain their legitimacy if they are perceived to carve nature at its joints, demarcating the Real within the symbolic order. By contrast, if racial categories are purely symbolic (i.e., a network of signifiers assigned to groups on the basis of pre-existing symbolic distinctions), the thin veneer concealing the classification of non-white groups for the sake of oppression would be exposed. Underneath the supposedly, naturally-existing physiological differences, therefore, is the assumed and presupposed superiority of whiteness; that is, Western standards for humanity are revealed as being predicated on the prescription of domineering white comportments (i.e., societal injunctions to write, speak, behave, and think in bourgeois modalities) [4]. Whiteness, ultimately, strives for a wholeness, completeness, and coherency that forecloses the possibility of disruption by the Real: the unconscious drive of whiteness implies the death of the subject (i.e., the site of shifting, changing, and fluctuating signification).
As mentioned earlier, the unconscious desire of whiteness inverts the death drive associated with identity politics. I offer a two-level differentiation of “death drive,” namely in the contexts of accessing jouissance, on one hand, through transgressing an established organization of signification and, on the other hand, through the replication of loss (at the inception of subjectivity) within the drive itself. The inversion between whiteness and identity politics, to invoke the aforementioned schema, occurs at the level of “disorderly conduct” in the symbolic order, as whiteness transgresses the incompleteness of the racial order (e.g., a belief in respecting each and every culture, such as multiculturalism) and identity politics transgresses the completeness of the sociopolitical order. Instead of effacing differences by adhering to a universal regime of (white) humanity, identity politics affirms the fundamental indeterminacy of the social order, or the impossibility of the social order to complete, fulfill, or satisfy itself. No sense-making apparatus can cohesively and coherently package the social order into a unitary entity; rather, a remainder will always-already slip through the cracks, saturate the boundary, and overflow the cup. Intersectionality, as the unlimited, inexhaustible reservoir for individual political experience, continually problematizes the extensionality of the extant field of signifiers, perpetuating the discursive mandate to consider the “inclusivity” of categories for various marginalized groups. To be clear, though, intersectionality remains inextricably tied to the intersubjective regime of sociopolitical signifiers, establishing long-lasting anchoring points in the symbolic order.
Two notable psychoanalytic interrogations of identity politics, however, dispute the existence of its intersubjective dimension: Howard Schwartz’s
Schwartz [1], in short, disagrees with the anti-Oedipal (non-)logic of political correctness and identity politics: “What the paternal function accomplishes, the creation of social order based on mutual comprehensibility … the doctrine of microaggression, playing out the anti-Oedipal dynamics of political correctness, undoes” (55). In the process of eschewing the comprehensible structure of intersubjective reality, so the thinking goes, identity politics enables and justifies individualistic determinations of meaning based on marginalized subject positions: microaggressions, implicit biases, hidden prejudices, etc. The meaning of language is displaced from explicit linguistic content to implicit linguistic suggestions, such that an attribution of “articulateness” and “intelligence” to a person of color is interpreted as offensive rather than complimentary. Marginalized individuals determine the meaning of expressions, imputing and definitively establishing a particular interpretation of language based on background presuppositions. As a result, the individual becomes the fount of meaning, truth, and reality, recalling the pre-Oedipal position of primary narcissism: “The imaginary is presided over by the primitive mother, whose love validates us in our individuality” [1]. If the marginalized individual perceives, experiences, confronts, or encounters intersubjective reality in a specific manner, the individual’s interpretation trumps any contrasting intersubjective interpretation (i.e., esse est. percipi). As Schwartz notes, “Political correctness is a bid for hegemony in the name of this primitive mother, expelling the father and undermining the paternal function. As such, it is a bid for the destruction of the symbolic” (ibid).
In particular, Schwartz rejects the arbitrary, individualized re-signification of “man” and “woman” for transgender identity. He refuses to acknowledge the legitimacy of Caitlyn Jenner’s status as a (trans-)woman: “Consider the case of Bruce Jenner, who now declares that he wants to be called Catelyn [sic] … He is a woman in a man’s body, he says … What can it mean to say that a body is a woman’s body if the person with that body can be a man? … It seems that the words ‘man’ and ‘woman’ have lost their meaning” (37-38). The tension within the intersectional, experiential disruption of established, intersubjective signification appears in the aforementioned case; that is, Caitlyn Jenner asserts her feeling of being-a-woman in contrast to her subjectification by the signifier “man,” which diametrically opposes the identification with womanness in the Western binary of gender. Schwartz detests the intersectional modification of signifiers in the symbolic order because the undisturbed, prevailing organization of signification makes meaning, identification, and intelligibility possible in general. If children are not presented with clear-cut, defined gender roles for emulation, they will inevitably lack a sense of self and situatedness within the world: “Am I a boy or girl, the child wants to know, and the answer to this helps him to build a sense of himself in relation to the world, and an idea of what he is supposed to do in it” (38). Unfortunately for Schwartz, his idealistic conception of the post-Oedipal symbolic order closely resembles his psychoanalytic caricature of identity politics as a replication of pre-Oedipal primary narcissism.
First and foremost, though, Schwartz downplays the intersubjective “pull” implicit within the intersectional “push” of identity politics discourse. Even if Schwartz cannot coherently envision a “man” identifying as a “woman,” he poses a false dichotomy for the meaning of signifiers, namely signifiers are either meaningful (i.e., retain the original signified) or meaningless (i.e., retain no durable, long-lasting signified). He simply excludes any semiotic process of garnering newfound meaning for signifiers. Instead of making the signifiers of “man” and “woman” meaningless, the identity category of transgender adds and subtracts a series of significations originally residing within the overarching chain of gender binarization, which conceals the discursive mandate that someone is either a man or a woman for the duration of his or her life, and these dichotomous positions cannot be exchanged with one another. The intersectional modification of gender, thus, is merely a re-signification, involving the maintenance of extant terms for describing gender while altering their linguistic content. Schwartz overlooks the intersubjective dimension baked into the intersectional process of resignification itself. Second, as mentioned above, Schwartz idealizes the post-Oedipal symbolic order in such a manner that mimics the alleged pre-Oedipal primary narcissism attributed to identity politics discourse. Both resist the destabilizing register of the Real, such that Schwartz staticizes the social order to the same degree that the narcissistic child idealizes the primordial mother.
Why does Schwartz imagine the social order, prior to the introduction of political correctness and identity politics, as a synchronized, harmonious, and infallible system? In this sense, political correctness and identity politics represent the only obstacle to society’s smooth functionality. This cannot possibly be true. There are plenty of institutional factors that prevent the smooth functionality of society (e.g., bureaucratic red tape, corruption, miscommunication, etc.), but Schwartz has latched onto the factor (i.e., political correctness and identity politics) that most acutely threatens his access to the primordial mother, the institutional legitimacy associated with his academic accolades. Schwartz reveals his personal stake in the project of discrediting and dismantling identity-based discourse: his strategy for attaining mother’s love (i.e., identification with the post-Oedipal father) is invalidated by political correctness and identity politics. If the academy is fraught with white privilege and racism, Schwartz’s accomplishments suddenly become impugned, which, in turn, calls into question his entire career. This should explain, for the most part, why Schwartz’s first scholarly foray into political correctness studied its impact on the university [12]. Just as Seshadri-Crooks’s [4] account of whiteness demonstrates its unconscious desire for achieving wholeness through a particular image of humanity, Schwartz unconsciously desires a complete symbolic order that denies the existence of Reality (i.e., the destabilizing, disruptive force of jouissance) and ensures the death of the subject (i.e., the lack of a lack or a missing signifier). In general, he violently assimilates the remainder of subjectivity into the extant identity categories of the symbolic order, foreclosing the possibility of the subject’s engagement in the political from her individual standpoint.
Albeit not advocating for the preservation of the extant social order, Žižek [2]takes issue with the “individual standpoint” of identity-based discourse from which demands are made upon the political. In
Žižek, thus, neglects the unconscious desire residing within the discursive formation of identity politics, involving the exposure of the social order’s incompleteness (in contrast to suturing – that is, attempting to complete, finalize, or totally and definitively determine – the social order in a manner that resembles the discursive formation of whiteness). Even though identity-based discourse presupposes the pervasiveness and ubiquitous nature of oppression experienced by marginalized groups (i.e., enabling its identification of transnational forms of marginalization), intersectionality routinely usurps the intersubjective agreement underlying individuals’ identifications with existing categorization schemas. In turn, identity politics undercuts itself through the destabilization of agreed-upon narratives concerning oppression, such that racism, xenophobia, transphobia, ableism, etc. function in a similar fashion across disparate contexts but differ in functionality at the intersection of individual political experience. To put otherwise, the extimate aspect of the Real belonging to identity politics, at its zero-point, structures the semiotic field of differential relations while also, at the same level, representing the discursive point at which the semiotic field loses coherency.
The neologism of “extimacy” signifies the most intimate aspect of a discursive formation, organizing and managing the semiotic relations between each term’s signified and the master signifier, and the excluded middle from the core of a discursive formation, representing the Thing around which a discourse revolves and from which a discourse requires the greatest amount of distance to maintain the fantasy of consistency. Žižek [13], in
Intersectionality introduces an aleatory element into the discursive formation of identity politics, unknowingly yet always residing in the background of signification (i.e., the unconscious). Žižek’s imputation of sterility to identity politics, then, misses the death drive lurking underneath the facade of a tranquil exterior. It is not the case that identity politics merely leaves things as they are; instead, it contains a disruptive force (i.e., intersectionality) that impugns the field of signification within the extant social order. For a similar reason, the piecemeal approach that filters identity categories (e.g., race and gender) through existing psychoanalytic concepts excludes the extimacy of identity politics, or the intersectional indeterminacy of meaning according to individual experience. Seshadri-Crooks’s [4] psychoanalytic intervention into the concept of “race,” albeit instructive and facilitative for expressing the extimacy of whiteness, emblematizes the problematic character of the gradual approach to psychoanalyzing identity politics, such that Seshadri-Crooks reveals the purely symbolic character of racial distinctions in a vacuum (i.e., abstracted from other forms of identification that constitute the meaning of racial distinctions). Her (dis)closure of racial signification within the social order denies the complexity associated with the Real of intersectionality. Furthermore, her analysis of “whiteness” unwittingly reproduces its unconscious desire by obscuring the Real(ity) of identity politics; that is, after exposing the lack of the Real at the heart of whiteness (i.e., the unfounded character of phenotypic distinctions between racial groups), Seshadri-Crooks does not necessarily produce an “anxious” reaction in its adherents (i.e., an encounter with the lack of a lack) because the Real of identity politics remains a feasible option for whiteness to legitimize itself.
In turn, a more comprehensive psychoanalysis of the relationship between systems of oppression, including whiteness, and the dimensions of identity politics, including intersectionality, must be conducted. Even though Seshadri-Crooks and others (e.g., Juliet Flower MacCannell [3], Joan Copjec [14], etc.) have blazed the trail for the psychoanalysis of identity-based discourse, intersectionality offers a novel pathway for understanding its intricacies while also, unfortunately, providing a dangerous source of justification for oppressive apparatuses. For instance, the analyses of race and gender undertaken by psychoanalysts illuminate the heinous characters of whiteness, patriarchy, and neoliberalism, but the intersectional analysis of “being-black,” “being-a-man,” and “being-impoverished,” for instance, has inspired a rational calculus for coding and assessing the likelihood of an individual’s deviance from the mandates of the social order. To put otherwise, the Real of identity politics enables resistance against oppressive apparatuses by tracing patterns of marginalization, but it also enables the smooth functionality of these apparatuses by isolating and identifying potential “threats” to its reproduction. As Seshadri-Crooks [4] notes, whiteness appropriates the Real for the sake of fortifying its logic of domination, and the discursive element of intersectionality represents another avenue for co-opting the Real in order to bolster itself (59). I will pursue a contemporary pathway to make sense of the aforementioned phenomenon: a (psycho)analysis of racism in American public discourse with respect to the murder of an unarmed black man.
A series of questions are asked by the American public when a police officer kills an unarmed black citizen. Each of these questions reveals a network of signifiers within which the prevailing ideological apparatus makes sense of the killing; that is, these questions disclose an underlying layer of assumptions pertaining to the (wrongful) actions of the deceased. The field of signification, in short, is always-already predisposed to attribute blame, guilt, and fault to the “suspect” as opposed to the law enforcer. In particular, I will analyze the case of Ahmaud Arbery, who was killed by an ex-police officer and his son while jogging through a suburban neighborhood in Brunswick, Georgia. Due to spatial constraints, I will only address one of the questions normally asked by the American public in the aftermath of a provocative civilian/law enforcement interaction. This question, however, most centrally relates to the aforementioned problem of the symbolic appropriation of the Real, namely the ways in which the master signifier claims the Real for itself and its logic of domination.
After the lethal encounter between law enforcers and unarmed black citizens, some might ask: could the deceased have avoided the encounter with law enforcement? Instead of exhibiting a pattern of racial animus, as the thinking goes, the policing apparatus coincidentally kills unarmed black citizens. It is merely a case of being “at the wrong place at the wrong time.” If Arbery had not jogged through that particular residential area on that particular day, according to the modal assumptions underlying the question, he would not have been killed. This mode of rationalizing the death of Arbery, however, fails to pierce the veil of contingency that conceals the necessity of policing in its targeting and racial profiling of black citizens. In other words, the chain of signification linking “black” with “criminality” makes the racist attributions of “dangerous,” “aggressive,” and “unreasonable” possible across every context within which a law enforcer interacts with black citizens. The motivation for the shooters pursuing Arbery after spotting him in their neighborhood, after all, was the universal instantiation of blackness in the particular body of Ahmaud Arbery. The irrelevant spatiotemporal particularity obscures the relevant particularity of Arbery’s embodiment; that is, the relevant particular is mediated by the universal and vice versa. Arbery’s exhibition of blackness sufficiently incited the shooters’ mobilization and persecution without consideration for his particular manifestation of blackness. Indeed, one of the shooters was accused of using racial epithets while standing over Arbery’s deceased body, indicating his general racial animus in contrast to a specific concern for Arbery’s presence in the neighborhood [15].
As particularity serves as an ideological conduit for universality, contingency serves as an ideological conduit for necessity. The former case demonstrates the intimate connection between the universal property of “blackness” and the particular subject who happens to bear the universal property, such that the latter becomes the central locus for explicating the authority of law enforcement and the former becomes a secondary, coincidental concern. Similarly, as Žižek [13] notes, the contingent and necessary co-constitute one another in a dialectical fashion, but the pinnacle of necessity presents itself as contingency: “the acme of the dialectic of necessity and contingency arrives in the assertion of the contingent character of necessity as such” (36). By making sense of Arbery’s death through the “wrong place, wrong time” explanation, the invocation of contingency masks the underlying necessity associated with the semiotics of policing. Neither the place nor the time captures the fatal confluence of events leading to Arbery’s death; rather, an explanation beginning from the standpoint of Arbery’s particular manifestation of the universal property of “blackness” more accurately pinpoints the causal chain of events culminating in Arbery’s death. Additionally, the dialectical interaction between necessity and contingency appears in the context of, what I call, “statistical intersectionality.” At the conclusion of the previous section, I discussed the ways in which the Real often becomes coopted by the symbolic order for the sake of fortifying itself against dissension. Seshadri-Crooks [4], for instance, identified the appropriation of phenotypic differences between races in order to validate the persistence of racial classifications in naturalistic discourse. The symbolic, in short, shapes the Real to justify its supremacy, and the Real of identity politics (i.e., intersectionality) is no different.
With the advent of intersectional analyses of oppression, the assailed symbolic order has incorporated the categorical designations of intersectionality into statistical descriptions of criminality, violence, and aggression. “Black-on-black crime” is a striking example of the symbolic appropriation of intersectionality by whiteness [16]. Intersectionality, to reiterate, foregrounds an analysis of identity-based oppression at the crossing-point of marginalized signifiers; in turn, black-on-black crime (which also carries the assumption of male-on-male violence) adopts the perspective of intersectionality (through a concerted effort to understand the political situation of black identity in America) in order to demonstrate the extraordinary violence within black communities, absolving whiteness of any historical or contemporary role. Racial injustice is not the problem, as black-on-black crime indicates; instead, the black community sows the seeds of its own destruction. There is a litany of issues with the signifier at issue, but I would like to focus on the position of black-on-black crime within the dialectic of necessity and contingency. In Lacanian terms, “contingency” represents the saturation point, remainder, and leftover component of “necessity” as an ideological narrative, an implicit extension of Žižek’s Hegelian analysis. Necessity disguises itself through the semblance of contingency: black-on-black crime highlights the violence emanating from within the black community, an internal chain of cause and effect wholly unaffected by external factors (i.e., racism, over-policing, poverty, etc.). Black communities, to fully present the racist presupposition underneath the signifier at hand, are said to ultimately introduce, choose, and foster criminality within their neighborhoods, selecting a non-necessary, contingent formation of social organization.
Historical forces that constitute the overwhelming influence of “necessity” on the formation of black communities (e.g., slavery, redlining, segregation, etc.) become blurred by the rationalization of black-on-black crime as a “contingent” explication of troublesome conditions in black communities. As contingency entirely supplants necessity, black communities (in accordance with the aforementioned narrative) could have constructed themselves in a different fashion, but they simply chose to be violent, dangerous, and crime-ridden. Black-on-black crime, in effect, effaces the historical discrimination preceding and currently surrounding the construction of black communities, localizing criminality within the black body itself and again completing the chain of signification linking those signifiers. Arbery’s case does not stray from the demonstrated play of necessity and contingency. The fantastical motto of “wrong place, wrong time” shifts blame from a racially-motivated law enforcement system (necessity) to a black man jogging through a neighborhood (contingency), such that citizens can inquire into the contingency of Arbery’s actions while, in the background, hinting at the necessity of his vulnerability: “what was he even doing there?,” “why didn’t he jog in his own neighborhood?,” “couldn’t he have jogged elsewhere?”
I have briefly indicated the subtle manner through which the symbolic order of whiteness weaponizes the Real for its own justification (i.e., statistical intersectionality). This analysis only arises from the presuppositions presented at the beginning of my investigation. First, identity politics taps into the Real through its dialectic of intersubjectivity and intersectionality, as the latter represents the death drive of the former. Second, recent psychoanalytic forays into the discursive formation of identity politics have proven woefully insufficient for capturing its unconscious machinations: a surface-level affirmation to discern the meaning of being-X with, simultaneously, the undermining, subterranean negation of any discernible meaning for being-X. Those who deny the validity of identity politics (Schwartz and Žižek) overlook its destabilizing tendencies, and those who embrace the validity of identity politics (Seshadri-Crooks and MacCannell) overlook the importance of intersectionality in determining (and making indeterminate) the meaning of identity in the political. Finally, the Real of identity politics has become the instrument for legitimizing the symbolic order: through intersectional analyses of violence (e.g., black-on-black crime), a series of oppressive apparatuses, such as over-policing, have been thoroughly legitimized. Future psychoanalytic investigations should adopt a similar methodological approach, namely through a recognition of identity politics as a destabilizing force in relation to the symbolic order and, resultantly, an acknowledgement of the symbolic order’s manipulation of identity politics.
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\n\nIntechOpen works with award winning print-houses and we hold to the fact that all of our printed products are of the highest quality.
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\n\nIf you do not receive your order within 30 days from the date your order is shipped, please contact us to inquire about the shipping status at orders@intechopen.com.
\n\nTax: Residents of European Union countries need to add a Book Value-Added Tax Rate based on their country of residence. Institutions and companies, registered as VAT taxable entities in their own EU member state, will not pay VAT by providing IntechOpen with their VAT registration number. This is made possible by the EU reverse charge method.
\n\nCustoms: free shipping does not include any duties, taxes or clearing charges levied by the destination country. These charges are the responsibility of the customer and will vary from country to country.
\n\nP.O. Boxes cannot be used as a Ship-To Address.
\n\nIntechOpen partners do not provide shipping service from Europe to the countries listed below. Please refrain from mailing items addressed to the countries listed below, until further notice.
\n\nWhen ordering our books from the countries listed below, please provide an alternative mailing address. For any further assistance, please contact us at orders@intechopen.com.
\n\nRestricted Ship-to Countries:
\n\nPOD products are non-returnable and non-refundable, except in the event of poor print quality or an error in quantity. If we delivered the item to you in error or the item is faulty, please contact us.
\n\nInspect your order carefully when it arrives. Any problems should be immediately reported to orders@intechopen.com.
\n\nPrint copies of our publications are most often purchased by universities, libraries, institutions and academia personnel, hence increasing the visibility and outreach of our authors' published work among science communities and institutions.
\n\nOur books are available at our direct Print Sales Department and through selected representatives throughout the world.
\n\nBooks International
\n\nRepresentative for: Brunei, Cambodia, Indonesia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, Vietnam (ASEAN)
\n\nChina Publishers Services Ltd - CPS
\n\nRepresentative for: China, Taiwan, Hong Kong
\n\nIndia - CBS Publishers & Distributors Pvt. Ltd.
\n\nRepresentative for: India, Bangladesh, Pakistan, Sri Lanka, Bhutan, Nepal, Maldives, Iran, Algeria, Bahrain, Egypt, Iraq, Israel, Jordan, Kuwait, Lebanon, Libya, Malta, Morocco, Oman, Qatar, Saudi Arabia, Syria, Tunis, United Arab Emirates and Yemen
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\n\nFor partnership opportunities, please contact orders@intechopen.com.
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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Noteworthy, the stroke — related brain tissue metabolic damages involve an essential ATP deplete clash along with a suppression of brain specific nucleotide — associated kinases and ATP synthase, both Mg2+ — dependent complex enzyme “machineries”. This itself makes the latter’s a legitimate target for some advanced pharmaceuticals as long as the drug — induced overstimulation of corresponding enzymatic activity is the case. Thus, magnetic isotope effects (MIE) of the nuclear spin possessing paramagnetic 25Mg2+ ions might modulate the brain creatine kinase, alfa-glycerophosphate kinase and pyruvate kinase catalytic activities in a way of a remarkable ATP hyperproduction required to compensate the hypoxia caused acute metabolic breakdown. To realize the Magnesium-25 pharmacological potential, a low-toxic amphiphilic cationite nanoparticles were introduced lately. 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He is the author of several scientific articles, book chapters, and books.",institutionString:"University of Hassan II Casablanca",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"7",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"University of Hassan II Casablanca",institutionURL:null,country:{name:"Morocco"}}},equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7060",title:"Gingival Disease",subtitle:"A Professional Approach for Treatment and Prevention",coverURL:"https://cdn.intechopen.com/books/images_new/7060.jpg",slug:"gingival-disease-a-professional-approach-for-treatment-and-prevention",publishedDate:"October 23rd 2019",editedByType:"Edited by",bookSignature:"Alaa Eddin Omar Al Ostwani",hash:"b81d39988cba3a3cf746c1616912cf41",volumeInSeries:4,fullTitle:"Gingival Disease - A Professional Approach for Treatment and Prevention",editors:[{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"6668",title:"Dental Caries",subtitle:"Diagnosis, Prevention and Management",coverURL:"https://cdn.intechopen.com/books/images_new/6668.jpg",slug:"dental-caries-diagnosis-prevention-and-management",publishedDate:"September 19th 2018",editedByType:"Edited by",bookSignature:"Zühre Akarslan",hash:"b0f7667770a391f772726c3013c1b9ba",volumeInSeries:1,fullTitle:"Dental Caries - Diagnosis, Prevention and Management",editors:[{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Prosthodontics and Implant Dentistry",value:2,count:2},{group:"subseries",caption:"Oral Health",value:1,count:6}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2020",value:2020,count:2},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:250,paginationItems:[{id:"274452",title:"Dr.",name:"Yousif",middleName:"Mohamed",surname:"Abdallah",slug:"yousif-abdallah",fullName:"Yousif Abdallah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274452/images/8324_n.jpg",biography:"I certainly enjoyed my experience in Radiotherapy and Nuclear Medicine, particularly it has been in different institutions and hospitals with different Medical Cultures and allocated resources. Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!1,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. He has served as guest editor for a number of special issues of peer-reviewed international journals.",institutionString:null,institution:{name:"University of the West of England",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null,series:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403"},editorialBoard:[{id:"275140",title:"Dr.",name:"Dinh Hoa",middleName:null,surname:"Nguyen",slug:"dinh-hoa-nguyen",fullName:"Dinh Hoa Nguyen",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRbnKQAS/Profile_Picture_1622204093453",institutionString:null,institution:{name:"Kyushu University",institutionURL:null,country:{name:"Japan"}}},{id:"20259",title:"Dr.",name:"Hongbin",middleName:null,surname:"Ma",slug:"hongbin-ma",fullName:"Hongbin Ma",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRhDJQA0/Profile_Picture_2022-05-02T08:25:21.jpg",institutionString:null,institution:{name:"Beijing Institute of Technology",institutionURL:null,country:{name:"China"}}},{id:"28640",title:"Prof.",name:"Yasushi",middleName:null,surname:"Kambayashi",slug:"yasushi-kambayashi",fullName:"Yasushi Kambayashi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYOQxQAO/Profile_Picture_1625660525470",institutionString:null,institution:{name:"Nippon Institute of Technology",institutionURL:null,country:{name:"Japan"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. Adetoro and Olusegun Awotoye",slug:"assessment-of-diversity-growth-characteristics-and-aboveground-biomass-of-tree-species-in-selected-u",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}}]},publishedBooks:{paginationCount:1,paginationItems:[{type:"book",id:"7726",title:"Swarm Intelligence",subtitle:"Recent Advances, New Perspectives and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/7726.jpg",slug:"swarm-intelligence-recent-advances-new-perspectives-and-applications",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Javier Del Ser, Esther Villar and Eneko Osaba",hash:"e7ea7e74ce7a7a8e5359629e07c68d31",volumeInSeries:2,fullTitle:"Swarm Intelligence - Recent Advances, New Perspectives and 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possibility to collaborate with more research groups interested in animal nutrition, leading to the development of new feeding strategies and food valuation while being more sustainable with the environment, allowing more readers to learn about the subject.",author:{id:"175967",name:"Manuel",surname:"Gonzalez Ronquillo",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",slug:"manuel-gonzalez-ronquillo",institution:{id:"6221",name:"Universidad Autónoma del Estado de México",country:{id:null,name:"Mexico"}}}},{id:"18",text:"It was great publishing with IntechOpen, the process was straightforward and I had support all along.",author:{id:"71579",name:"Berend",surname:"Olivier",institutionString:"Utrecht University",profilePictureURL:"https://mts.intechopen.com/storage/users/71579/images/system/71579.png",slug:"berend-olivier",institution:{id:"253",name:"Utrecht 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The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine"},{id:"8",title:"Bioinspired Technology and Biomechanics",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. 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Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Biomedical Engineering",id:"7"},selectedSubseries:null},seriesLanding:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. 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 24th, 2022",hasOnlineFirst:!0,numberOfOpenTopics:4,numberOfPublishedChapters:314,numberOfPublishedBooks:31,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. 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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. 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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. 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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:"profile.detail",path:"/profiles/178385",hash:"",query:{},params:{id:"178385"},fullPath:"/profiles/178385",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)}()