Infected Urinary Stones, Endotoxins and Urosepsis. LPS. Lipopolysaccharide; SWL. Extracorporeal shock wave lithotripsy; SIRS. Systemic inflammatory response syndrome; MOF. Multiple organ failure.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{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"}]},book:{item:{type:"book",id:"4483",leadTitle:null,fullTitle:"Biodiversity in Ecosystems - Linking Structure and Function",title:"Biodiversity in Ecosystems",subtitle:"Linking Structure and Function",reviewType:"peer-reviewed",abstract:"The term biodiversity has become a mainstream concept that can be found in any newspaper at any given time. Concerns on biodiversity protection are usually linked to species protection and extinction risks for iconic species, such as whales, pandas and so on. However, conserving biodiversity has much deeper implications than preserving a few (although important) species. Biodiversity in ecosystems is tightly linked to ecosystem functions such as biomass production, organic matter decomposition, ecosystem resilience, and others. Many of these ecological processes are also directly implied in services that the humankind obtains from ecosystems. The first part of this book will introduce different concepts and theories important to understand the links between ecosystem function and ecosystem biodiversity. The second part of the book provides a wide range of different studies showcasing the evidence and practical implications of such relationships.",isbn:null,printIsbn:"978-953-51-2028-5",pdfIsbn:"978-953-51-4226-3",doi:"10.5772/58494",price:159,priceEur:175,priceUsd:205,slug:"biodiversity-in-ecosystems-linking-structure-and-function",numberOfPages:642,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"d488928dfd93614e6a94950be7131fa0",bookSignature:"Yueh-Hsin Lo, Juan A. Blanco and Shovonlal Roy",publishedDate:"April 17th 2015",coverURL:"https://cdn.intechopen.com/books/images_new/4483.jpg",numberOfDownloads:56708,numberOfWosCitations:157,numberOfCrossrefCitations:68,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:168,numberOfDimensionsCitationsByBook:7,hasAltmetrics:1,numberOfTotalCitations:393,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 7th 2014",dateEndSecondStepPublish:"April 28th 2014",dateEndThirdStepPublish:"August 2nd 2014",dateEndFourthStepPublish:"October 31st 2014",dateEndFifthStepPublish:"November 30th 2014",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"51995",title:"Dr.",name:"Juan",middleName:"A.",surname:"Blanco",slug:"juan-blanco",fullName:"Juan Blanco",profilePictureURL:"https://mts.intechopen.com/storage/users/51995/images/1076_n.jpg",biography:"Dr. Blanco is an Assistant Professor at the Public University of Navarre. His work is focused on the development and evaluation of ecological models to simulate the influences of management, climate and other ecological factors on tree growth. He is currently collaborating with research teams from Canada, Taiwan, USA, Spain, Cuba, and China in using ecological models to explore the effects of climate change, atmospheric pollution and alternative forest practices in natural and planted forest in boreal, temperate and tropical forests. His research has been applied in mining to optimize reclamation plans, in forestry to assess the potential for carbon sequestration and by government agencies to define local guidelines for long-term sustainable forest management. Among other topics related to forest ecology, Dr. Blanco has studied the influence of climate variations on tree growth and estimated the possible ecological consequences of climate change in forest ecosystems. He has also co-authored the first book dedicated exclusively to the use of hybrid ecological models in forest management, entitled 'Forecasting Forest Futures” (Earthscan, London), edited three books on Climate Change effects, mitigation and adaptation (InTech, Rijeka), and three more on Forest Ecosystems, Biodiversity and Tropical Forests (InTech, Rijeka).",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Universidad Publica De Navarra",institutionURL:null,country:{name:"Spain"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"171181",title:"Dr.",name:"Yueh-Hsin",middleName:null,surname:"Lo",slug:"yueh-hsin-lo",fullName:"Yueh-Hsin Lo",profilePictureURL:"https://mts.intechopen.com/storage/users/171181/images/4956_n.jpg",biography:"Dr. Lo graduated in Forest and Natural Resource Management at the National Taiwan University, and obtained a PhD in Forest Ecology from the University of British Columbia (Canada). She is currently working as Research Associate at the Public University of Navarra (Spain). During her research, Dr. Lo has studied the influence of climate on tree growth and productivity, and developed and tested models to simulate the effects of climate change on tree productivity, combining the use of tree-ring records with field data on biogeochemical factors and tree distribution. At present, she is involved in several research lines studying the long-term influence of environmental factors on tree growth and forest development. 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As an ecological modeller, his research aims at better understanding of the mechanisms of stability and diversity in ecosystems by combining empirical data and mechanistic models. 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Shields, Ph.D., is Associate Dean, Fisher College of Science and Mathematics and a full professor in the Biological Sciences Department, Towson University, Towson, Maryland, USA. Dr. Shields’ research explores gustatory, olfactory, and visual cues in insects.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"82613",title:"Dr.",name:"Vonnie D.C.",middleName:null,surname:"Shields",slug:"vonnie-d.c.-shields",fullName:"Vonnie D.C. Shields",profilePictureURL:"https://mts.intechopen.com/storage/users/82613/images/system/82613.png",biography:"Vonnie D.C. Shields, Ph.D., is Associate Dean, Fisher College of Science and Mathematics and a full professor in the Biological Sciences Department, Towson University, Towson, Maryland, USA. Dr. Shields’ research explores gustatory, olfactory, and visual cues in insects. 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After graduating, she accepted a research associate position to conduct postdoctoral studies at the Arizona Research Laboratories Division of Neurobiology, University of Arizona, Tucson, Arizona, USA, before she joined the faculty at Towson University where she rose through the ranks from assistant to full professor.",institutionString:"Towson University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"Towson University",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"18",title:"Neuroscience",slug:"life-sciences-neuroscience"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"466998",firstName:"Dragan",lastName:"Miljak",middleName:"Anton",title:"Mr.",imageUrl:"https://mts.intechopen.com/storage/users/466998/images/21564_n.jpg",email:"dragan@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"19323",title:"Infected Urinary Stones, Endotoxins and Urosepsis",doi:"10.5772/21996",slug:"infected-urinary-stones-endotoxins-and-urosepsis",body:'\n\t\tUrinary tract infections (UTIs) and their complications represent one of the most common causes of medical consultation with high cost to medical services and high morbidity and mortality. Urinary stones are another medical challenge that represents an acute or chronic clinical setting for patients requiring most of the time active treatment, either as an invasive or as a non-invasive management, thus increasing costs and risks. The combination of both clinical scenarios —urinary tract infection and urinary stone— is common and can trigger a systemic inflammatory response syndrome (SIRS) before, during or after medical treatment (i.e. antibiotics) and/or surgical manipulation of infected urinary stones. It is believed that SIRS is due to the release of endotoxins from infected urinary stones, developing endotoxemia, bacteremia and urosepsis. If not controlled, multiple organ failure syndrome (MOF) and death of the patient may occur. Urologists are familiar with these scenarios where not only prevention and diagnosis but also an early and appropriated treatment is crucial. Unfortunately, the use of prophylactic antibiotics does not guarantee prevention of these fatalities. The aim of this chapter is to review the evidence of possible endotoxin release during invasive and non-invasive treatment of infected urinary stones as a trigger of SIRS and sepsis.
\n\t\tUrinary tract infections are the second most frequent infections in developed countries and uropathogenic
Urinary tract infections in Western countries are mainly caused by
To invade hosts, bacteria use a variety of substances, some of them are essential for their survival. In Gram-negative bacteria, specific molecular patterns composed of lipid and sugar moieties represent some of the most toxic virulence factors of bacterial origin. Structurally classified as lipopolysaccharides (LPS), these substances have no chemical homologs among human cells, and are known as endotoxins, to denote their ability for causing fever, shock and organ injury when released in mammalian endothelial vessels (Beutler, 2000). The presence of endotoxins in the blood-stream is named endotoxemia and can trigger SIRS. LPS have specific structural motifs which are typical of different bacterial species. However, all of them are known to induce endotoxemia and sepsis (Bochud & Calandra, 2003). Endotoxins are known to be recognized by cell-surface proteins, the LPS receptors, which are widely distributed in animals as part of their immune systems (from insects to vertebrates). However, a strong inflammatory reaction after LPS recognition is restricted to a handful of species, including humans (Beutler, 2000). According to numerous studies in cellular and animal models, recognition of LPS by their receptors initiate a cascade of intracellular signals guiding the secretion of pro-inflammatory mediators (Beutler, 2000; Triantafilou & Triantafilou, 2005). An emerging concern is the toxicity of LPS after microbial death, especially in the context of hospital-acquired infections. In fact, released LPS keep their full toxic potential, unless inactivation processes take place in the host to degrade endotoxins (Munford et al., 2009).
\n\t\t\t\tUrinary stones have been reported in human history since antiquity. Traditionally, stones have been classified according to their main mineral content. The etiology of urinary stones is wide, including chronic dehydration, urinary tract malformations, obstructed uropathy, metabolic diseases (i.e. hyperparathyroidism, gout, and obesity), foreign body inside urinary tract, infections, etc. The risk for stone disease in patients of developed countries is close to 10 % life-long. An increase in the incidence of stone disease related with changes in the life style, modifications on the diet, morbid obesity surgery syndrome and new drugs has been reported in Western countries in recent years. For example, in the United States, an increase of 37 % in stone disease was observed over the last 20 years (Straub & Hautmann, 2005). A variation in the frequency and in the composition of the minerals forming the urinary stones was also observed.
\n\t\t\tThere is a large variety of urinary stone compositions. If the main component is more than 80 % of the total mass, the stone is named “pure”. If the main component is at least 50 % of the stone, it is named mixed. In Western countries, struvite stones used to represent 15-30 % of cases. Nowadays only 2 % of stones are struvite (McALeer et al., 2003; Kramer et al., 2000). The explanation of that decrease is unknown. In developing countries and Eastern countries there is a large variation among incidence, prevalence and stone composition. For example, in India a report including 1050 urinary calculi from surgically treated patients (900 renal and 150 ureteral) revealed 93.04 % oxalate calcium stones (80 % calcium oxalate monohydrate [COM] and 20 % calcium oxalate dihydrate [COD]), 1.92 % struvite stones, 1.48 % apatite stones, 0.95 % uric acid stones and 2.96 % mixed stones. Surprisingly, 89.98 % of the staghorn stones consisted of oxalates and only 4.2 % were struvite (Ansari et al., 2005). A study in Japan showed that the most common stone composition was struvite (32.1 %) and mixed calcium oxalate phosphate (22.2 %) (Akagashi et al., 2004). These differences could be explained by variations in ethnics, epigenetics, geographical area, diet, life-style, and different metabolism.
\n\t\t\tIt has been suggested that urinary stones can be infected mainly in two ways. Stones develop due to several mechanisms which may or may not be associated to obstructive uropathy (i.e. hyperparathyroidism). The first way in which a stone can be infected is by ascending bacteria. Once the stone is formed, ascending bacteria may reach its surface, invade the interstice and become part of it (Takeuchi et al., 1984; Abrahams & Stoller, 2003). Adherence of new minerals could cover and paste bacteria layers. In this case, the stone acts as a reservoir for bacteria. Due to the poor penetration of drugs into the stone matrix the action of antibiotics is limited (Prabakharan et al., 1999). This phenomenon can be the reason of bacterial resistance, repeated, chronic or complicated UTIs in several patients, therefore increasing the risk of urosepsis. The most possible scenario according to the most frequent stone component and urinary bacteria in our Western world is a calcium stone infected with
The second scenario is that bacteria living inside the urinary tract and causing chronic UTIs produce the stones. These bacteria are named urea-splitting bacteria. Members of this group are
It has been suggested that some agents named nanobacteria could have a role in the development of calcium-based urinary stones (Kajander & Çiftçioglu, 1998); however, this is not yet well established (Kramer et al., 2000). A prevalence of nanobacteria in 0.5 % of 1000 stones was reported; but nanobacteria are still difficult to identify (Abrahams & Stoller, 2003).
\n\t\t\t\tUrinary stone cultures from fragments retrieved during stone surgery were not a common practice until recently. Negative urine culture before urinary surgery was considered safe. In general urology it has been a routine to have a negative midstream urine culture before doing any endoscopic procedure. Recent studies suggest that voiding urine culture is not representative of upper urinary tract pelvis infection or pelvis infected stone bacteria (Mariappan & Loong, 2004; Mariappan et al., 2005a). A group of 73 patients with unilateral stone-obstructed ureter were treated with ureterorenoscopy and lithotripsy. Midstream urine (MSU) sample culture and sensitivity were performed the morning of the endoscopic surgery. During the procedure a pelvis urine sample and stone fragments were collected for culture and sensitivity with an aseptic technique in a retrograde approach. The authors reported that 25 (34.3 %) patients had positive stone culture, 43 (58.9 %) had positive pelvic urine and 21 (28.8 %) had positive MSU culture. The most common isolated bacterium was
\n\t\t\t\t\t\tMariappan and colleagues (2005a) studied a group of 54 patients with renal stones who were candidates for percutaneous nephrolithotomy (PCNL). Various specimens were collected for culture and sensitivity, i.e., MSU sample, bladder urine sample, renal pelvic urine sample and crushed stone sample. The objective of the study was to identify the most predictive analysis of urosepsis. MSU culture was positive in 11.1 % of cases, stone culture was positive in 35.2 % and pelvic urine was positive in 20.4 % of cases. A wide variety of bacteria were isolated. In 37 % of the patients SIRS was developed and 5.5 % experienced septic shock. Pelvic urine culture predicted infected stones better than bladder urine culture. Patients with infected stones or pelvic urine were found to be at a relative risk for urosepsis that was at least four times greater (P = 0.0009). The authors concluded that positive stone and pelvic urine are better predictors of potential urosepsis than bladder urine and recommend routine collections of these specimens. Stone components were not analyzed. The bacterial epidemiology of infected urinary stones also depend on differences in geographic area, strains, bacterial resistance, bacterial virulence, exposure to some kind of antibiotics and environment.
\n\t\t\t\tSepsis is an extreme health condition that threatens life of patients with a high cost for the healthcare systems. Reports from US and European surveys have estimated that severe sepsis accounts for 2–11 % of all admissions to hospitals or intensive care units. The most common microbes isolated from patients with severe sepsis and septic shock are Gram negative bacilli (mainly
Activation of local and systemic metabolic response to trauma and SIRS is mainly caused by activation of IL-1 and tumor necrosis factor-α (TNF-α). It is well established that after recognition by cognate receptors, LPS trigger the synthesis and release of pro-inflammatory cytokines (Triantafilou & Triantafilou, 2005). Once IL-1 and TNF are secreted, they activate several other reactions like complement factors, exacerbating the host inflammatory response. As a consequence, MOF or death may result.
In a study on 700 patients, the prevalence of sepsis related with obstructed uropathy and urinary stones treated surgically was 1.28 %. These nine patients developed SIRS and sepsis during 6 hours postoperative. Although males and females were treated in roughly equal proportions, all of the patients who developed severe sepsis were females. There were six deaths accounting for 66 % mortality (O\'Keeffe et al., 1993). Septic shock following urinary stone manipulation was reported with an incidence of 1 % and mortality up to 80 % (Rao et al., 1991).
\n\t\t\tIn an effort to predict septicemia following endourological manipulation for stones in the upper urinary tract, 117 patients were studied and classified according to the procedure performed (Rao et al., 1991): Percutaneous nephrolithotomy, push-back/push-bang procedure, double-J and extracorporeal shock wave lithotripsy (SWL), ureteroscopy, SWL alone and only cystoscopy. Blood samples for bacterial culture, endotoxin and tumor necrosis factor assay were collected before, at onset, at the end and one hour after completing the procedure. Preoperative bacteriuria was present in 35 % of the patients. The mean endotoxin level of the entire group —except the cystoscopy group— was 16.2 pg/mL (range 11 to 58.3 pg/mL). In the cystoscopy group the mean endotoxin level was 11.7 pg/mL (range 11 to 12.2 pg/mL). All patients (16) with preoperative endotoxemia had increased levels of endotoxin detected in subsequent samples (mean increase 15 pg/mL, range 0.5 to 64 pg/mL). The tumor necrosis factor was greater than 15 pg/mL in four cases preoperatively. Postoperatively there was elevation of the tumor necrosis factor only in 12 patients. The authors reported that in case of upper urinary tract manipulation, the risk of bacteremia was higher. The risk was greatest after performing the push-back method and least after cystoscopy. Combination of preoperative endotoxemia, bacteriuria and the type of procedure had 85 % of sensitivity, 84 % of specificity and a positive predictive value of 52 % for the development of postoperative bacteremia. A total of 41 patients had pyrexia and 17 patients had rigors and fever 2 to 3 hours after the end of the procedure. No patient suffered septic shock; however, this complication developed in a female patient one week after percutaneous nephrolithotomy. Serum endotoxin and tumor necrosis factor levels after admission of this patient to the intensive care unit were 67.7 pg/mL and 3,827.5 pg/mL, respectively (Rao et al., 1991).
\n\t\t\tMeasurements of LPS were done in 34 renal stones, stored for several months and classified as infection stones (16), i.e., struvite and calcium apatite, and non-infection stones (18) composed of 50 % calcium oxalate monohydrate (McALeer et al., 2003). All stones were weighed, aseptically crushed and aliquots were tested for endotoxins. Four stones of each group were aseptically washed and crushed separately. Washed materials and crushed stones were processed in MacConkey agar culture to recover bacteria colonizing the stones. Mean endotoxin concentration in the infection group was 12,223 ng per gram of stone and 340.3 ng per gram of stone in the non-infection group. The difference was statistically significant (P = 0.001). These results reveal an almost 36 times higher concentration of endotoxins in the infection stones. No living bacteria were recovered on the MacConkey plates from crushed stones from neither group. The authors concluded that large amounts of endotoxins can be found in infected renal stones even months after they were removed from the body, and long after viable bacteria could be detected. Furthermore, endotoxin may remain after bacteria are no longer viable or have been killed with antibiotic therapy (Munford et al., 2009). Non-infectious stones can also contain endotoxin but in a lower amount (McALeer et al., 2003). McALeer et al. (2002) published a case report of an 8 year old boy with a left staghorn calculus treated with holmium laser percutaneous nephrolithotripsy (PCNL). Culture specific antibiotic were administered to the patient, both orally and intravenously, before, during and after surgery. Intraoperative fluid and pleural fluid cultures (urologists lost percutaneous access from lower pole calyx with intraperitoneal extravasation and pleural effusions) were obtained. A urine culture was performed before and after stone manipulation. All samples grew a few colonies of
There is not a general consensus on how to best prevent sepsis in patients undergoing surgical treatment of urinary stones. Pre-surgical, trans-surgical and post-surgical strategies have been proposed. The combination of multiple factors can prevent, trigger or worsen sepsis. For example, control of metabolic or cardiopulmonary diseases is important. Although antibiotic prophylaxis does not completely avoid the risk of developing sepsis, it is a recommendation for stone surgery according to the American Urological Association (AUA) and the European Association of Urology (EAU) guidelines on urinary tract infection (Grabe et al., 2011; Wolf et al., 2010). It is suggested to define an antibiotic prophylaxis according to local bacterial populations, resistance and antibiotic sensitivity patterns. In a prospective controlled trial, Mariappan et al. (2006) and Bag et al. (2011) reported the beneficial use of one week ciprofloxacin and nitrofurantoin regimen respectively, before percutaneous nephrolithotomy. Furthermore it has been found that renal stones larger than 20 mm are more likely to be culture positive (Mariappan et al., 2005a; 2005b). Mariappan and colleagues (2005a) suggested to obtain pelvic urine and stone samples for culture and sensitivity as a routine during surgical stone procedures, with the aim of administering proper antibiotic regimen if later urosepsis develops. If an unusual urine sample (i.e. turbidity, foully) is obtained, culture and sensitivity is a must. In this case, a nephrostomy tube should be left in place and the initial procedure rescheduled until sterile urine is confirmed.
\n\t\t\tAn increase of pressure inside the urinary tract system generated by the irrigation fluid results in a potential bacterial and endotoxin translocation into the bloodstream. Auge et al. (2004) reported significant reduction in urinary tract pressures using ureteral access sheath if working both in distal ureter and inside the renal pelvis. Bacteria and likely endotoxins may emerge from several kinds of urinary stones and not exclusively from struvite stones (Hugosson et al., 1990; McALeer et al., 2003). In post-surgical stage, the most critical evidences of SIRS are during the first 6 hours post-procedure and seem to correlate with cytokines release into the bloodstream after endotoxin stimulus (Dandona et al., 1994; O\'Keeffe et al., 1993; Rao et al., 1991; Taudorf et al., 2007). It has been suggested that if other causes of SIRS different than infection (i.e. cardiogenic or pulmonary events, atelectasis, hypovolemia and pain) have been ruled out and if SIRS persists, then sepsis could be the explanation (Monga, 2005). Close vital signs and symptoms monitoring and high suspicious index for sepsis is crucial at this stage. Once urosepsis is diagnosed, an early tissue oxygenation, appropriate initial antibiotic therapy, inotropic and nutritional support with invasive monitoring at intensive therapy unit is required. Empirical broad-spectrum antibiotics regimen is prescribed according to local bacteria, sensitivity and resistance patterns. If cultures were performed from bladder urine, pelvis urine or stone sample, direct therapy must be installed as soon as results are obtained (Mariappan et al., 2005b). Wagenlehner and his group (2007) reported that the treatment of urosepsis comprises four major aspects: Early goal-directed therapy, optimal pharmacodynamics exposure to antimicrobials both in blood and in the urinary tract, control of complicating factors in the urinary tract and specific sepsis therapy. They considered that interdisciplinary approach is necessary to achieve an optimal goal of treatment. At any of these stages, it is very important to act as soon as possible if any evidence of initial SIRS and urosepsis is addressed. It is necessary to instruct the patient and relatives once discharged from the hospital, that if SIRS develops, urgent evaluation in an emergency unit is crucial (Rao et al., 1991). There is no doubt that further research is required and that several other issues have to be considered; however, these do not fall within the scope of this chapter.
\n\t\tSeveral articles report the bactericidal effect of shock waves
Efforts to develop an ideal stone model have been done worldwide to perform
Only a few authors report results on the interaction of infected urinary stones with intracorporeal lithotripters. Artificial kidney stones, infected with
Photograph of the special lucite test tube with copper mesh bottom (not seen) placed inside a standard glass laboratory test tube during
Our group also studied the effect of the four above-mentioned intracorporeal lithotripters on the bacterial inactivation of artificial struvite stones inoculated with
In conclusion, it seems that the stone material plays a minor role regarding bacterial inactivation due to intracorporeal lithotripsy. Furthermore, according to our results, intracorporeal lithotripters are very harmful to bacteria; however, whether bacterial destruction is desirable or not is still unknown.
\n\t\t\tA reduction in bacteriuria and resolution of urinary tract infection after SWL has been reported by several authors (Beck & Riehle, 1991; Gerdesmeyer et al., 2005; Michaels et al., 1988; Pode et al., 1988); however, it is not known if the stone protects bacteria or if other mechanisms, such as shear, contribute to the bactericidal effect of shock waves. To answer these questions, infected stones were exposed
Sepsis is a serious health condition with high mortality and cost. Advances in the manufacture of standardized infected stone models and
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t
During sepsis, a 25 - 50 pg/mL LPS concentration has been reported in the bloodstream. LPS concentrations of up to 285,600 pg per gram stone have been reported in a fatal case of urosepsis. Release of LPS has been observed after \n\t\t\t\t\t\t\t \n\t\t\t\t\t\t\t \n\t\t\t\t\t\t\t The bactericidal effect of both extra- and intracorporeal lithotripsy should be studied carefully due the possible release of large amounts of LPS. Under certain circumstances, this initial evidence could explain triggering of SIRS, urosepsis and MOF. \n\t\t\t\t\t\t | \n\t\t\t\t\t
Infected Urinary Stones, Endotoxins and Urosepsis. LPS. Lipopolysaccharide; SWL. Extracorporeal shock wave lithotripsy; SIRS. Systemic inflammatory response syndrome; MOF. Multiple organ failure.
The authors would like to thank Carmen Clapp, Carmen Wacher-Rodarte, Eduardo Fernández-Escartín, Concepción Arredondo, Olivia Vázquez, Marisol Moreno, Daniel Marín, Mauricio Díaz-Muñóz, Rodolfo Galeana, Arturo Méndez, and René Preza for important assistance. This research was supported by the PAPIIT-UNAM grant IN108410.
\n\t\tNanotechnology allows the development of nanomaterials with controllable physical, chemical, and biological properties [1, 2, 3, 4]. These properties are controlled according to the nanomaterials’ size and shape, enabling the development of new innovative technologies, from new device development to tools in the health field [4, 5, 6, 7, 8, 9]. In this context, nanobiotechnology is a recent field emerging from science, which establishes an interface between biology and nanotechnology, evaluating and assigning new functionalized nano biosystems [8]. Thus, this multidisciplinary research field has great potential in developing improved medical engineering [1, 10].
Nanoparticles can be amorphous or crystalline (nanocrystals), and this difference reflects directly on the physical, chemical, and biological properties. Spanó et al. demonstrated that zinc oxide (ZnO) nanocrystals are more biocompatible when compared to amorphous nanoparticles [11]. Amorphous nanoparticles have a long-range disorder of their atoms and are more reactive [12]. On the other hand, nanocrystals show the periodicity of atoms forming crystalline arrangements and consequently fewer defects and less reactivity [13, 14, 15].
Nanocrystals (NCs) are often and successfully applied in several sensors, such as colorimetric, fluorescence, surface plasmon resonance, and electrochemical [16]. Regarding electroanalytical chemistry, conductive nanostructured crystals are interesting for application in electrochemical sensing due to their well-known ability to improve the catalytic activity, the electron transfer speed, and the conductivity of the sensors. Furthermore, the deposition of nanocrystals over electronic surfaces can increase the superficial area and amplify the analytical signal, enhancing the sensitivity regarding the detection of target analytes [17]. Nowadays, nanocrystal-based sensors have been widely explored in various applications and attracted the attention of several researchers [18].
Nanoparticle drug delivery can be used to target the tissue, promote the slow-release, protect against degradation, and diminish toxicity [19, 20]. The pharmacokinetic properties of a compound of biological activity are, among other factors, related to its solubility. The low solubility will result in problems from absorption until elimination. So, it is essential to search for alternatives, and they can increase the solubility of drugs without interfering in their pharmacological activity. Several active compounds are usually poorly soluble in aqueous media [21, 22]. A vast literature reports the possibility of complexation between lipophilic organic molecules appropriately sized, inorganic ions, and other species, with cyclodextrin, dendrimers, and liposomes. Whether for the drug’s application for pharmaceutical use, the nanocrystal compounds are essential on the medical and economic side [23, 24].
The development of biomaterials arouses tremendous scientific and clinical interest, given the possibility of replacing, in part or whole, human bones and/or favoring bone regeneration, both in the craniofacial complex and in other parts of the skeleton. Therefore, it is expected that the materials have osteoconductive properties (materials that function as a support surface for adhesion and proliferation of osteoblastic cells, which promote the formation of mineralized bone tissue), osteoinduction (materials that contain inductive proteins present in the matrix bone tissue and are capable of inducing differentiation of undifferentiated mesenchymal cells into chondroblasts or osteoblasts), osteogenesis (materials that have viable osteoblasts, capable of determining the formation of the new bone when grafted into the host tissue) and/or osteopromotion (materials that constitute physical barriers for the anatomical isolation of the site under repair, aiming at the selection of cells that promote the restoration, while excluding competing for inhibitory cells) [25]. This chapter book will comment specifically on titanium dioxide nanocrystals in dental and orthopedic applications.
Therefore, this chapter shows the innovative results obtained by the group of carbon-based, semiconductor, and magnetic nanocrystals that can be used in biosensors and biomedical applications, further strengthening the development of new tools.
This section shows nanocrystals’ results in improved electrochemical sensors and their use as theranostic tools in biomedical applications. We will demonstrate how graphene nanostructures and CdSe/CdS MSQDs can improve sensors sensitivity. In the biomedical applications, we will show CdSe/CdS MSQDs and cobalt ferrite (CoFe2O4) NCs to drug deliveries and biocompatible titanium dioxide (TiO2) NCs in osseointegration processes and their bio-location.
Graphene has been the nanostructured material most utilized in electroanalytical applications due to its unique features [26]. Graphene consists of a single layer of carbon atoms in the sp2 hybridization organized in a honeycomb structure with six-membered rings, yielding 2D nanocrystals [27]. Some advantages of using graphene in electrochemical sensors are enhanced conductivity, decreased overpotentials, increased electroactive areas, and enhanced charge transfer rate [28]. Graphene is usually synthesized by the chemical reduction of graphene oxide [29, 30].
In this field, the advantages of using graphene-based nanocrystals in electroanalytical sensing have been previously demonstrated by several researchers and our research group [31]. We have reported the modification of a glassy carbon rod electrode (GCRE) with reduced graphene oxide doped with copper nanoparticles (RGO-CuNP). The synthesis of the RGO used in this work was carried out by the modified Hummers’ method [32]. This GCRE modified with RGO-CuNP was coupled, for the first time, to a paper-based electrochemical platform and applied in the electroanalysis of analytes of clinical interest, as illustrated in Figure 1.
Representation of the modification of the GCRE with RGO-CuNP, coupling of the modified sensor to the paper-based electrochemical platform such as used in work, and voltammetric responses of unmodified and modified electrodes in the simultaneous electroanalysis of paracetamol and caffeine.
The modified sensor was thoroughly studied, optimized, and characterized. The results showed that the modification with RGO-CuNP significantly improved the electrochemical properties of the working electrode. In comparison with the unmodified GCRE, the RGO-CuNP sensor presented lower peak potentials, better sensitivity (ca. two-fold higher), lower electron transfer resistance (857 vs. 21,497 Ω), and larger electroactive area (0.067 vs. 0.040 cm2). These improvements are directly related to the modification with RGO-Cu nanocrystals, which are responsible for enhancing the conductivity and increasing the superficial area of the GCRE. As proof of concept, this modified sensor was employed to determine paracetamol and caffeine in real urine samples simultaneously. These two analytes were successfully quantified in low levels without matrix interferences, and the results showed excellent concordance with high-performance liquid chromatography used to validate the method. So, it evidences some of the advantages of using graphene-based nanocrystal in sensing platforms.
In this context, quantum dots (QDs) are among the most explored nanomaterials nowadays. The synthesis and practical application of QDs are among the main focuses in the development directions of nanotechnology [33]. QDs are semiconductor nanocrystals with optical and electrical properties that are widely employed in sensing applications. Another exciting feature of QDs is that properties such as size, shape, composition, and structure can be controlled and tuned. It allows obtaining QDs with unique properties according to the desired application [34, 35].
Although, promising, conventional QDs have some drawbacks that include moderate stability, limited luminescence spectra, and large size to some applications. At this point, the magic-sized quantum dots (MSQDs) are a class of nanocrystals that show smaller particle sizes, broader spectra, and more excellent stability than conventional QDs [36]. Among other applications, the MSQDs are a promising nanomaterial for electrochemical sensing use. The small size (in nanometric scale) and the electrical properties of these nanocrystals can significantly increase the surface area and the conductivity of the sensors.
Our research group recently explored, for the first time, the application of MSQDs for the modification of electrochemical sensors [37]. This pioneering work proposed a simple and inexpensive paper electrochemical device (PED) whose carbon-based working electrode was modified with CdSe/CdS MSQDs. The three-electrode setup (working, counter, and pseudo-reference) was fabricated on the paper substrate by a simple pencil-drawing method. At the same time, the CdSe/CdS MSQDs were synthesized according to the method described by Silva et al. [36, 38, 39]. This PED was modified with CdSe/CdS MSQDs to demonstrate the analytical feasibility and applied for clinical quantification of dopamine in biological samples, as represented in Figure 2.
Picture of the paper electrochemical device containing the pencil-drawn carbon electrodes used in work, representing a modification of the working electrode with CdSe/CdS MSQDs, and the voltammetric dopamine response regarding the unmodified and modified electrodes.
Electrochemical and morphological techniques investigated the miniaturized CdSe/CdS MSQDs-based PED. This modified PED presented improved analytical signal (ca. 46% higher), lower charge transfer resistance (32 vs. 169 Ω), and larger superficial area (0.28 vs. 0.14 cm2) in comparison with the unmodified PED. It can be attributed to CdSe/CdS nanocrystals in the sensor, which was also confirmed by microscopy analysis. The electroanalysis of dopamine in real human blood serum samples was successfully carried out, and the limit of detection obtained was lower than other recent reports that utilize more complex electrochemical platforms for detecting the same analyte. In this way, MSQDs have been shown as a promising nanomaterial to be explored in electrochemical sensing.
In the last decade, several nanostructured systems for the delivery of chemotherapeutic agents have been developed to eliminate tumor cells. However, most of these systems cannot reach specific tumor cells without adequate control of these drug release processes, resulting in serious side effects [40, 41]. It is necessary to direct efforts to improve ideal drug distribution systems to release stimuli and selectively target cancer cells. Thus, quantum dots, liposomes, magnetic nanoparticles, and TiO2 nanocrystals have enormous potential.
Quantum dots have been the subject of extensive investigations in different science and technology areas in the past years [42, 43]. There are few studies of MSQDs, even though they exhibit features such as tiny size, higher fluorescence quantum efficiency, molar absorptivity greater than traditional QDs, and highly stable luminescence in theranostic, which refers to the simultaneous integration of diagnosis and therapy [36, 39, 44, 45].
Our group investigated the first study about the core-shell MSQDs by analyzing the electrochemical behavior of CdSe/CdS MSQDs immobilized on a gold electrode modified with a self-assembled cyclodextrin monolayer using cyclic voltammetry and electrochemical impedance spectroscopy techniques [46]. The work showed a good interaction between the thiol group from thiolated cyclodextrin and CdSe/CdS MSQDs (Figure 3a). The proposed method was successfully applied to encapsulation studies of Mangiferin, a natural antioxidant compound, and cyclodextrin associated with the CdSe/CdS MSQDs, and the response was compared with that of the modified electrode without MSQDs. The fluorescence study revealed that CdSe/CdS MSQDs emit blue light when excited by an optical source of the wavelength of 350 nm, and a significant increase in fluorescence and absorbance intensity is observed from the core-shell CdSe/CdS MSQDs when quantities of Mangiferin are added to the solution containing thiolated cyclodextrin. CdSe/CdS MSQDs are optically and electrochemically sensitive and can be used to detect and interact with compounds encapsulated in cyclodextrin and can be applied in theranostic.
(a) CdSe/CdS MSQDs immobilized on a gold electrode modified with a self-assembled cyclodextrin to encapsulation studies of Mangiferin, and (b) illustration of liposome with MSQDs (top panel) when MSQDs are (i) inside or (ii) outside and optical image the scale bar is 1 mm (bottom panel).
Because of their reduced size, lipophilic nanoparticles of less than 100 nm can cross the brain-blood barrier by diffusion, allowing the drug delivery directly to the Central Nervous System (CNS) [47]. Neurodegenerative diseases (ND) such as Alzheimer’s, Parkinson’s, strokes, glioblastoma, Huntington’s, amyotrophic lateral sclerosis may be treated differently with this approach [19]. Just like liposomes, polymeric nanoparticles may be environmentally sensitive to drug release, such as temperature change, pH change, among others. These systems may be combined therapy, delivering two or more drugs, allowing different therapy combinations.
The group has also been developing liposomes containing CdSe/CdS MSQDs aiming at a new luminescent tool for drug delivery. Figure 3b shows the illustration of liposomes with MSQDs (top panel); when MSQDs are (i) inside or (ii) outside and optical image, the scale bar is 1 mm (bottom panel). Therefore, we demonstrate that CdSe/CdS MSQDs can be used in drug delivery systems, which serve as photostable fluorescent reporters. A combination of MSQDs with liposomes is a powerful theranostic tool since it is possible to monitor their location via luminescence in addition to drug delivery.
Since the 1990’s Liposomal Amphotericin B has been available in the market, being one of the oldest and most clinical used nanoparticle formulations in the treatment of leishmaniasis. In 1978, Alvin et al. proved that the use of liposomal leishmanicidal drugs could enhance 700 times the efficacy [48]. Liposome functionalization is another advance that can enhance circulation time and release drugs according to temperature change and pH change; magnetic prepared liposomes can be target-directed by applying a magnetic field, and ligands in the lipidic bilayer can actively target cellular types [49]. Thus, the group has been working to develop drug systems containing liposomes and nanocrystals.
The study of bioactive substances by electrochemical and UV-visible spectroscopic methods is already very conceptual. The association of magnetic nanoparticles has emerged as a new bias of these techniques. We group reported the interaction between the molecule LQM10, a derivative of guanylhydrazone, with the CoFe2O4 NCs coated with polyamidoamine dendrimer (PAMAM), generating a nanocarrier to benefit LQM10 (Figure 4). The PAMAM dendrimer has empty spaces that change according to its generation. In these places, as well as cyclodextrins, “guest-host” interactions can occur, where the hydrophobic molecule can interact with dendrimers by hydrogen bonds, ionic bonding, or hydrophobic interactions, being possible interaction with LQM10 due to the tert-butyl group attached to its ring, which gives it a hydrophobic character, as well as with CoFe2O4 NCs. In addition to this type of interaction. PAMAM can make covalent and non-covalent bonds through its primary and tertiary amine groups, which would also be possible by observing the structure of LQM10. Both interactions can occur in an isolated or simultaneous way, making it possible for a single molecule of PAMAM to interact with several other substances, which enables its association with CoFe2O4 NCs, producing a better nanocarrier for LQM10 [50].
Illustrative scheme of the nanocarrier composed by the PAMAN molecule, the black spheres represent the CoFe2O4 NCs and the LQM10 molecule.
The magnetic properties of CoFe2O4 NCs and each nanocarrier were confirmed by a vibrating sample magnetometer and field-effect calorimetry. LQM10 showed good interaction corroborating with the results of UV-visible and electrochemistry data. The heat generation by magnetic hyperthermia of CoFe2O4 NCs in the presence of PAMAM G3 and LQM10 was observed, demonstrating the association of promising nanocarriers (PAMAM G3 and CoFe2O4 NCs) with anticancer substances and their applicability as magnetic hyperthermia [50].
The implantation of material inside biological tissues must meet a minimum requirement, called biocompatibility, defined as a biomaterial’s ability to perform the desired therapeutic function without triggering any undesirable local or systemic effect, generating the most cellular or tissue response. Therefore, optimizing clinical therapeutic performance should be as beneficial as possible [51]. After application, an interaction occurs between the host’s immune system and the implanted biomaterial, leading to a specific cellular reaction to the biomaterial [52]. Proteins play a crucial role in the interaction between biomaterials and cells or tissues. Thus, the absorption of proteins on the material surface is the first event of this interaction, which is decisive for the subsequent cell growth processes, differentiation, and extracellular matrix formation [53].
The deliberate, accidental implantation of any foreign material into living tissues causes a response, and it is not the response itself but the extent, intensity, and duration that define biocompatibility. The ideal response of biological tissues to a biomaterial is when the initial inflammatory response resulting from the surgical procedure is quickly resolved, without the presence of a chronic inflammatory infiltrate or the development of an immune response. Thus, the biomaterial must be biocompatible and have characteristics that include predictability, clinical applicability, absence of transoperative risks and minimal postoperative sequelae, and acceptance by the patient. It is also expected that this biomaterial is not carcinogenic, that it presents adequate chemical and biological stability, mechanical and elastic resistance, and has low cost [54].
The biomaterial is a natural or synthetic material intended to interact with biological systems to assess, treat, augment, or replace an organism’s organ, tissue, or function [51]. The primary function of biomaterials is to replace damaged tissue and passively assume its function, selection, and manufacture, based on the imitation of the chemical and physical properties of natural tissue, causing minimal response as a foreign body [53].
Since the early 1970s, various synthetic bone substitutes have been developed to minimize the difficulties inherent in using autogenous bone grafts and homogeneous and heterogeneous bone implants [25]. The main advantages of grafts created from synthetic materials through bioengineering are biocompatibility and good reabsorption [55]. The alloplastic materials most commonly used in the medical-dental field are metals or metal alloys, ceramics, polymers, composites, and bioactive glasses [25]. Despite the wide variety of organic and synthetic materials capable of replacing bone tissue or stimulating reparational osteogenesis, there is still no material that meets all the desired requirements.
Titanium dioxide (TiO2) is a semiconductor that absorbs and emits in the ultraviolet region with numerous applications in biomedical fields such as cosmetics, medicines, and pharmaceutical products [56, 57, 58]. This material has three crystalline phases: anatase, brookite, rutile, and physical and biological properties [59]. The anatase phase is more electroactive than the rutile phase, having greater genotoxicity and photocatalytic effects [60, 61, 62, 63]. The TiO2 NCs have shown great potential for use in implants due to their excellent physical, chemical, and biological properties, such as high specific surface area, ability to provoke positive cellular response and stability in body fluids, is suitable for the propagation, proliferation, and differentiation of osteoblast cells [56, 64]. Thus, will show exciting results obtained by the group using TiO2 nanocrystals as well as their luminescence bio-location.
The porous structure of TiO2 nanotubes increases bone regeneration and repair, presenting good osteointegration, being used as a graft and biological fixation element for implants [57, 65, 66, 67, 68, 69, 70]. In an experimental study carried out by our research group using TiO2 NCs, adequate osteointegration in bone failure in the calvary of rats was evidenced, with the presence of a large amount of newly formed tissue, suggesting effective osteoinductive action, as can be seen in Figure 5.
Histological section of rats’ calvaria: (a) fibrous connective tissue (asterisk); bone tissue (arrow); and (b) TiO2 NCs (arrows), bone tissue (arrow), and neoformed fibrous connective tissue (asterisk) (hematoxylin and eosin staining, 400×).
Despite the promising findings with TiO2 NCs, it is essential to report that there may be a high contamination rate and post-surgical infection since, currently, the spread of antibiotic-resistant bacteria is a worrying threat to human health.
In this context, it is essential to establish new antimicrobial strategies, in which the idea of coating device surfaces with active antimicrobial metals is considered one of the essential strategies. Therefore, bimetallic corrosion is inevitable, in which TiO2 photocatalytic nanomaterials, in the anatase form, offer more significant advantages for antimicrobial purposes [71]. Still, the photocatalytic activity of TiO2 under exposure to ultraviolet radiation results in disinfectant properties, mainly related to the generation of reactive oxygen species [72].
In this perspective, the sensitive and accurate detection of biological analytes in low concentrations is another application of TiO2 nanostructures that is beneficial for biomedical research and clinical diagnosis. There has been significant interest in applying TiO2 detection in biosensors [57, 67]. Therefore, those reported in the literature point out that TiO2 nanocrystals are inert and safe structures when exposed to the human organism, thus contributing to new promising nanotechnologies with the biomedical application.
Luminescence is related to some materials’ ability to light emissions. This excitation energy (absorbed energy) can be obtained from different sources: photons usually in the ultraviolet region of the electromagnetic spectrum (emission called photoluminescence), electrical energy (electroluminescence), electron beam (cathodoluminescence), physical impact (gives rise to triboluminescence) and heating the luminophore (results in thermoluminescence) [73, 74]. Photoluminescent materials are often called phosphors or luminophores [73]. Efficient luminophore requirements are efficient absorption of light in a suitable spectral region; chemical stability of the excited electronic state populated after light absorption; high conversion efficiency to the excited luminescent state; a long lifetime of excited state luminescence; high luminescent efficiency [75].
Photoluminescent materials require a host crystalline matrix, such as TiO2, as well as an activating ion, such as lanthanides. Lanthanide ions are known to have characteristic luminescence (high color purity). Among lanthanides, the europium ion (Eu3+) is one of the most used for biomarking due to its intrinsic electronic spectroscopic properties in the visible region under excitation in the ultraviolet region [76, 77].
Compounds with trivalent europium ions emit red light, with emission spectra of thin bands of approximately 614 nm. Therefore, it has been applied to investigate the properties and functions of biochemical systems and the determination of biologically active substances. In this context, we find reports of its application mainly as spectroscopic probes in the study of biomolecules [78]; in biological tracers to follow the path taken by medicines in the human organism and animals; as markers in immunology (fluoroimmunoassays) [79], as well as contrast agents in non-invasive diagnosis of pathologies in tissues by nuclear magnetic resonance imaging [80].
In a study carried out by our research group with TiO2 NCs doped with Eu3+, in the culture of mesenchymal stem cells, isolated from bone marrow cells, the presence of these nanocrystals was observed in the cytoplasm of the cells after 24 hours of incubation, not being found in the cell nucleus, suggesting the absence of cytotoxicity and genotoxicity (Figure 6).
Fluorescence microscopy of mesenchymal stem cells treated with europium doped TiO2 NCs: (a) culture medium with 50 μg of mesenchymal stem cells; and (b) culture medium with 100 μg of mesenchymal stem cells.
Therefore, this chapter showed nanocrystals inserted in biosensors and their use in drug delivery tools or biomaterials. Graphene and magic-sized quantum dots into biosensors enable an increase in sensitivity and specificity, making the development of nanotechnological platforms in biological diagnosis possible. In theranostic applications, magic-sized quantum dots, magnetic nanoparticles, and TiO2 nanocrystals can be innovative drug delivery tools and dental and orthopedic applications. Thus, the fabrication of nanomaterials with interesting properties makes it possible to generate several potential tools to improve electrochemical sensors and in theranostic applications.
This work was supported by CNPq, CAPES, FAPEAL, and FAPEMIG.
The authors declare no conflict of interest.
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All published Book Chapters are licensed under a Creative Commons Attribution 3.0 Unported License. Monographs are licensed under the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) license granted to all others. Our Copyright Policy aims to guarantee that original material is published while at the same time giving significant freedom to our Authors. IntechOpen upholds a flexible Copyright Policy meaning that there is no copyright transfer to the publisher and Authors hold exclusive copyright to their work.
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\n\n\n\nIntechOpen publishes different types of publications.
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His present research includes organic synthesis, drug discovery and development, biochemistry, nanoscience, and nanotechnology.",institutionString:"Visiting Scientist at Lipid Nanostructures Laboratory, Centre for Smart Materials, School of Natural Sciences, University of Central Lancashire",institution:null},{id:"428125",title:"Dr.",name:"Vinayak",middleName:null,surname:"Adimule",slug:"vinayak-adimule",fullName:"Vinayak Adimule",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/428125/images/system/428125.jpg",biography:"Dr. Vinayak Adimule, MSc, Ph.D., is a professor and dean of R&D, Angadi Institute of Technology and Management, India. He has 15 years of research experience as a senior research scientist and associate research scientist in R&D organizations. He has published more than fifty research articles as well as several book chapters. He has two Indian patents and two international patents to his credit. Dr. Adimule has attended, chaired, and presented papers at national and international conferences. He is a guest editor for Topics in Catalysis and other journals. He is also an editorial board member, life member, and associate member for many international societies and research institutions. His research interests include nanoelectronics, material chemistry, artificial intelligence, sensors and actuators, bio-nanomaterials, and medicinal chemistry.",institutionString:"Angadi Institute of Technology and Management",institution:null},{id:"284317",title:"Prof.",name:"Kantharaju",middleName:null,surname:"Kamanna",slug:"kantharaju-kamanna",fullName:"Kantharaju Kamanna",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284317/images/21050_n.jpg",biography:"Prof. K. Kantharaju has received Bachelor of science (PCM), master of science (Organic Chemistry) and Doctor of Philosophy in Chemistry from Bangalore University. He worked as a Executive Research & Development @ Cadila Pharmaceuticals Ltd, Ahmedabad. He received DBT-postdoc fellow @ Molecular Biophysics Unit, Indian Institute of Science, Bangalore under the supervision of Prof. P. Balaram, later he moved to NIH-postdoc researcher at Drexel University College of Medicine, Philadelphia, USA, after his return from postdoc joined NITK-Surthakal as a Adhoc faculty at department of chemistry. Since from August 2013 working as a Associate Professor, and in 2016 promoted to Profeesor in the School of Basic Sciences: Department of Chemistry and having 20 years of teaching and research experiences.",institutionString:null,institution:{name:"Rani Channamma University, Belagavi",country:{name:"India"}}},{id:"158492",title:"Prof.",name:"Yusuf",middleName:null,surname:"Tutar",slug:"yusuf-tutar",fullName:"Yusuf Tutar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/158492/images/system/158492.jpeg",biography:"Prof. Dr. Yusuf Tutar conducts his research at the Hamidiye Faculty of Pharmacy, Department of Basic Pharmaceutical Sciences, Division of Biochemistry, University of Health Sciences, Turkey. He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"94311",title:"Prof.",name:"Martins",middleName:"Ochubiojo",surname:"Ochubiojo Emeje",slug:"martins-ochubiojo-emeje",fullName:"Martins Ochubiojo Emeje",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94311/images/system/94311.jpeg",biography:"Martins Emeje obtained a BPharm with distinction from Ahmadu Bello University, Nigeria, and an MPharm and Ph.D. from the University of Nigeria (UNN), where he received the best Ph.D. award and was enlisted as UNN’s “Face of Research.” He established the first nanomedicine center in Nigeria and was the pioneer head of the intellectual property and technology transfer as well as the technology innovation and support center. Prof. Emeje’s several international fellowships include the prestigious Raman fellowship. He has published more than 150 articles and patents. He is also the head of R&D at NIPRD and holds a visiting professor position at Nnamdi Azikiwe University, Nigeria. He has a postgraduate certificate in Project Management from Walden University, Minnesota, as well as a professional teaching certificate and a World Bank certification in Public Procurement. 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He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. 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He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals. He is currently working on the protective activity of phenolic compounds in disorders associated with oxidative stress and inflammation.",institutionString:null,institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Dr.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/system/329795.png",biography:"Dr. Mohd Aftab Siddiqui is an assistant professor in the Faculty of Pharmacy, Integral University, Lucknow, India, where he obtained a Ph.D. in Pharmacology in 2020. He also obtained a BPharm and MPharm from the same university in 2013 and 2015, respectively. His area of research is the pharmacological screening of herbal drugs/natural products in liver cancer and cardiac diseases. He is a member of many professional bodies and has guided many MPharm and PharmD research projects. Dr. Siddiqui has many national and international publications and one German patent to his credit.",institutionString:"Integral University",institution:null}]}},subseries:{item:{id:"22",type:"subseries",title:"Applied Intelligence",keywords:"Machine Learning, Intelligence Algorithms, Data Science, Artificial Intelligence, Applications on Applied Intelligence",scope:"This field is the key in the current industrial revolution (Industry 4.0), where the new models and developments are based on the knowledge generation on applied intelligence. The motor of the society is the industry and the research of this topic has to be empowered in order to increase and improve the quality of our lives.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11418,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). 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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.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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