",isbn:"978-1-80356-966-6",printIsbn:"978-1-80356-965-9",pdfIsbn:"978-1-80356-967-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"f86a9f720cc3ac0f1c385d0367ea89b9",bookSignature:"Dr. Fiaz Ahmad and Prof. Muhammad Sultan",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11624.jpg",keywords:"Agricultural Waste, Reuse, Reduction, Soil Health, Recycling, Agriculture and Environment, Modelling and Simulation, Agro-Industrial Waste, Bioresource Processing, Processing and Management, Crop Residue, Forest Waste",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"April 8th 2022",dateEndSecondStepPublish:"June 16th 2022",dateEndThirdStepPublish:"August 15th 2022",dateEndFourthStepPublish:"November 3rd 2022",dateEndFifthStepPublish:"January 2nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Fiaz Ahmad is a researcher in the field of Agricultural Engineering with fifteen years of field and academic experience, currently in charge of the Agricultural Machinery Design Laboratory at Bahauddin Zakariya University. He applied for two patents at the national level.",coeditorOneBiosketch:"A renowned researcher in the field of Agricultural Engineering with 14 years of academic experience at Bahauddin Zakariya University. Winner of various prestigious fellowships, awards, and research grants. Published 250+ articles along with several books and chapters. Guest editor of seven ISI-SCI journals for publishers like SAGE, MDPI, and Frontiers.",coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"338219",title:"Dr.",name:"Fiaz",middleName:null,surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad",profilePictureURL:"https://mts.intechopen.com/storage/users/338219/images/system/338219.png",biography:"Dr. Fiaz Ahmad is an assistant professor and lecturer at the Department of Agricultural Engineering, Bahauddin Zakariya University, Multan, Pakistan. He obtained his Ph.D. in Agricultural Bioenvironmental and Energy Engineering from Nanjing Agriculture University, China, in 2015, and completed his postdoctorate in Agricultural Engineering from Jiangsu University, Zhenjiang, China, in 2020. He was awarded a fellowship from the Higher Education Commission of Pakistan for Ph.D. studies and from the Chinese Government for post-doctoral studies. He earned a BSc and MSc (Hons) in Agricultural Engineering from the University of Agriculture, Faisalabad, Pakistan, in 2004 and 2007, respectively. He is the author of more than fifty journal and conference articles. He has supervised six master’s students to date, and is currently supervising six master and two doctoral students. Dr. Ahmad has completed three research projects with his research interest focusing on the design of agricultural machinery, agricultural waste management, artificial intelligence (AI), and agricultural bioenvironment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:{id:"199381",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sultan",slug:"muhammad-sultan",fullName:"Muhammad Sultan",profilePictureURL:"https://mts.intechopen.com/storage/users/199381/images/system/199381.png",biography:"Muhammad Sultan is an Assistant Professor at the Department of Agricultural\r\nEngineering, Bahauddin Zakariya University, Multan (Pakistan). He completed his Ph.D.\r\nand Postdoc from Kyushu University (Japan) in the field of Energy & Environmental\r\nEngineering. He was an awardee of MEXT and JASSO fellowships (from the Japanese\r\nGovernment) during Ph.D. and Postdoc studies, respectively. He also did a Postdoc as\r\na Canadian Queen Elizabeth Advance Scholar at Simon Fraser University (Canada) in\r\nthe field of Mechatronic Systems Engineering. He worked for Kyushu University\r\nInternational Institute for Carbon-Neutral Energy Research (WPI-I2CNER) for two years.\r\nCurrently, he is working on 4 research projects funded by the Higher Education\r\nCommission (HEC) of Pakistan. He has completed six projects in past in the field of\r\nagricultural engineering. He has supervised 10+ M.Eng. and Ph.D. thesis and 10+\r\nstudents are currently working under his supervision. He has published 120+ journal\r\narticles, 100+ conference articles, 13 book chapters, and 6 books. He is serving as guest\r\neditor for the journals like Sustainability (MDPI), Agriculture (MDPI), Energies (MDPI),\r\nAdvances in Mechanical Engineering (SAGE), Frontiers in Mechanical Engineering, and\r\nEvergreen Journal of Kyushu University. His research is focused on developing energy-\r\nefficient temperature and humidity control systems for agricultural storage, greenhouse,\r\nlivestock, and poultry applications. His research keywords include desiccant air-\r\nconditioning, evaporative cooling, adsorption heat pump, Maisotsenko cycle (M-cycle),\r\nenergy recovery ventilators; adsorption desalination; wastewater treatment.",institutionString:"Bahauddin Zakariya University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"5",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Bahauddin Zakariya University",institutionURL:null,country:{name:"Pakistan"}}},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"440212",firstName:"Elena",lastName:"Vracaric",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/440212/images/20007_n.jpg",email:"elena@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"10454",title:"Technology in Agriculture",subtitle:null,isOpenForSubmission:!1,hash:"dcfc52d92f694b0848977a3c11c13d00",slug:"technology-in-agriculture",bookSignature:"Fiaz Ahmad and Muhammad Sultan",coverURL:"https://cdn.intechopen.com/books/images_new/10454.jpg",editedByType:"Edited by",editors:[{id:"338219",title:"Dr.",name:"Fiaz",surname:"Ahmad",slug:"fiaz-ahmad",fullName:"Fiaz Ahmad"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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1. Introduction
\n
Systemic lupus erythematosus (SLE) is a chronic, inflammatory, systemic autoimmune disease of unknown etiology characterized by production of antinuclear autoantibodies. It mainly affects young women and shows a broad spectrum of manifestations such as general fatigue, skin rash, fever, and arthritis and disorders involving the kidney, heart, and central nervous system. These organ involvements occur in patients with severer disease status and indicate a poor prognosis. Glucocorticoid has been used as a first-line therapy for SLE. Glucocorticoid exerts strong anti-inflammatory effects and is widely used for the treatment of uncontrolled disease activity in patients with SLE, such as central nervous system lupus (CNS), severe lupus nephritis, and other life-threatening conditions [1]. Glucocorticoid therapy is successful in most cases when high doses are employed, and as a result the prognosis of the SLE has improved remarkably. On the other hand, as glucocorticoid has adverse side effects on many organ systems, only the minimum effective dose is used for treatment. For example, skin thinning and purpura are commonly observed, and the risk of both cataracts and glaucoma is increased. Glucocorticoid use is associated with an increased risk of ischemic heart disease and heart failure, and also an increased risk of gastritis, gastric ulcer, and gastrointestinal bleeding. In the musculoskeletal system, osteoporosis is one of the more serious adverse effects of glucocorticoid [2], and osteonecrosis is also a significant problem [3]. Bisphosphonate (BP) is a key drug used for prevention and treatment of osteoporosis. The risk of osteonecrosis caused by glucocorticoid is higher in patients with SLE. Glucocorticoid causes a dose-dependent, mild increase in the fasting glucose level and a greater increase in postprandial hyperglycemia in patients without preexisting diabetes mellitus (DM), whereas it worsens control of the blood glucose level in patients with DM. The adverse effect of glucocorticoid on atherosclerotic vascular disease is thought to be mediated in part by elevated levels of nonfunctional lipoprotein. In patients with SLE, the adverse effects of glucocorticoid on lipid profiles are dose-dependent, occurring only at prednisone doses exceeding 10 mg/day. Systemic glucocorticoid also has many effects on both innate and acquired immunity, resulting in a dose-dependent increase in the risk of infection, especially with common bacterial, viral, and fungal pathogens [4]. Conventional immunosuppressive agents such as mycophenolate mofetil, azathioprine, and cyclophosphamide are also widely used in the management of SLE, and current treatment regimens optimize the use of these agents while minimizing their potential toxicity [5]. Tacrolimus may be particularly useful as adjunctive therapy in patients with persistent proteinuria despite other therapies, and in the management of lupus nephritis in pregnancy. The advent of biological agents has advanced the treatment of SLE, particularly in patients with refractory disease. The CD20 monoclonal antibody rituximab and the anti-BLyS agent belimumab are widely used in clinical practice. The prognosis of SLE has improved markedly, and long-term survival has increased. Prior to 1955, fewer than 50% of patients survived 5 years after diagnosis whereas now, 10-year survival exceeds 90% [6 ]. Our recent data have also confirmed that the 5-year survival rates of patients diagnosed as having SLE before 1970, between 1970 and 1979, between 1980 and 1989, between 1990 and 1999, and after 2000 were 71.4, 83.1, 94.5, 93.4, and 96.4%, respectively. Previously, the causes of death in patients with SLE were mainly infection and renal disease, but recently atherosclerotic cardiovascular disease emerging in the long term has become a focus of concern. Musculoskeletal conditions that impair the quality of life have also become problematic, including osteonecrosis and atypical femoral fracture (AFF). Here we discuss osteonecrosis and AFF in patients with SLE.
\n
\n
2. Incidence, etiology, and pathogenesis
\n
Idiopathic osteonecrosis (ION) of the femoral head occurs frequently (3–40%) in patients receiving glucocorticoid for underlying conditions such as nephrotic syndrome and renal transplantation [7–10]. It is also known to occur as one of the serious complications of glucocorticoid treatment of SLE. Among several factors related to ION, glucocorticoid therapy is considered to be one of essential importance [3]. There have been a lot of reports of ION onset in SLE patients to date, but the exact incidence of ION in this group is unknown. The etiology or pathogenesis of this disorder has not been fully clarified, and no prophylaxis has been established to date. The risk of ION in SLE patients is considered to be due to both the SLE itself and the concomitant use of glucocorticoid because, in occasional cases, ION has been noted in the absence of glucocorticoid therapy [3]. In addition, the risk of developing ION has been linked to numerous factors such as glucocorticoid use, alcohol consumption, cigarette smoking, and several rheumatic diseases including SLE. Although the pathogenesis remains unclear, involvement of lipid metabolism abnormality [11], hypercoagulability [12], oxidative stress [13], and vascular endothelial dysfunction [14] has been suggested from basic and clinical research. Several studies investigating the association of ION with steroid treatment have yielded conflicting results with regard to the cumulative dosage, maximum dose, route of administration, and duration of treatment. Glucocorticoid dose and duration seem to be important factors related to ION, but there is considerable controversy about this issue [3, 15–20]. ION may develop in patients who have received high-dose, short-term, or long-term steroid. However, in the early phase, the relationship between steroid and ION has yet been not fully investigated. In our present study, the patients were treated with steroid for the first time, and our observation period was short. Additionally, the initial dose of prednisolone (PSL) for treatment of SLE has sometimes been determined according to the patient’s weight or body surface area (BSA) [21]. Therefore, we investigated the relationship of body mass index (BMI) [22] and BSA with the initial dose of PSL. We found that the initial dose of PSL, steroid pulse therapy, BMI, and BSA were not correlated with asymptomatic ION, similar to the results obtained by Sekiya et al. [23]. Also, we failed to identify any relationship between BMI, BSA, the initial dose of PSL per unit BW, the initial dose of PSL relative to BMI, or the initial dose of PSL relative to BSA. None of the factors evaluated were associated with asymptomatic ION. Recent meta-analysis data have shown that the likelihood of ION developing in patients receiving glucocorticoid at more than 20 mg/day is significantly higher than in patients receiving less than 20 mg/day. In the early phase, corticosteroid at over 20 mg/day may trigger ION. In addition, it has been revealed that increasing the steroid dose at the time of SLE recurrence is a risk factor for development of new ION [24].
\n
\n
3. Timing of osteonecrosis-related ischemia in patients with SLE
\n
Radiographically, at the earliest stage of ION, plain radiographs show normal features, whereas axial and coronal T1- and T2-weighted MR images show low-density signals in the femoral head (Figure 1).
\n
Figure 1.
A T1-weighted image demonstrates a ring-like subchondral area of osteonecrosis (white arrow) present in the femoral head.
\n
From this viewpoint, osteonecrosis associated with renal transplantation can provide important information. The band patterns on MRI correspond to repair tissue located between necrotic and intact areas [25, 26]. Thus, there is a time lag between the occurrence of ischemia and the appearance of the band pattern. It has been reported that 1 month after internal fixation of a femoral neck fracture, MRI can reveal band patterns in the femoral head away from the fracture line [27]. In patients who develop ION after renal transplantation, it is presumed that intraosseous ischemia occurs earlier than 6–12 weeks postoperatively [28, 29] when band patterns are observed on T1-weighted MRI. In experimental animal models of osteonecrosis, it has been shown that intraosseous ischemia occurs quite soon after administration of large doses of steroid, that is, on the fifth and third day, respectively. The total dose of steroid administered in the first 2 weeks after renal transplantation is related to ION development [30]. This suggests the occurrence of an event in the bone that may lead to the development of ION at a very early stage after steroid administration. The widespread use of MRI now makes it possible to detect osteonecrotic change in SLE patients soon after administration of glucocorticoid, thus facilitating early diagnosis. Nagasawa et al. reported that 33% of patients developed ION within 3 months after the start of glucocorticoid treatment and that symptomatic ION became apparent at 2 years and beyond [31]. Radiographically, a subchondral radiolucency known as the crescent sign appeared at a late stage in ION, indicating subchondral fracture. However, that study was a multicenter one, and several strategies were selected for treatment of SLE according to the clinical conditions of the patients, resulting in slight differences among the participating hospitals. Several strategies have been selected for treatment of SLE in conformity with the clinical conditions of the affected patients, and there are many differences among hospitals, such as the indications for immunosuppressants. However, for any study performed at a single institution, the strategy of treatment, the steroid selection, the initial dose of steroid, and concomitant drugs would be more uniform. In addition, the speed of steroid tapering would also be quite uniform. This would allow better clarification of the background factors associated with ION. On the basis of this concept, we investigated the early development of ION in a cohort of strictly selected SLE patients using MRI and the early changes in laboratory parameters associated with steroid therapy [32].
\n
\n
4. Classification of osteonecrosis
\n
Diagnosis of ION of the femoral head relies on the combination of clinical symptoms and radiographs and/or magnetic resonance imaging (MRI) changes. To evaluate the evolution of ION of the femoral head, the Ficat (Table 1) [33] and the Association Research Circulation Osseous (ARCO) classification (Table 2) [34] are generally used to evaluate both imaging modalities. For comparative purposes, these classifications need to be reliable and uniform definition to provide sufficient therapy options for the patient.
\n
\n
\n
\n
\n\n
\n
Stage
\n
Radiographic signs
\n
Clinical features
\n\n
\n
0
\n
Inconspicuous/normal findings
\n
0 (“silent hip”)
\n
\n
I
\n
Inconspicuous findings or minor changes (slight patchy osteoporosis, blurring of trabecular pattern, subtle loss of clarity)
Radiograph: flattening of femoral head and osteoarthritic changes: decreased joint space and acetabular changes
\n
+++
\n
(b)
\n
\n
VI
\n
Complete joint destruction
\n
−
\n
Table 2.
Scheme of ARCO classification system (1992).
Note: (a) Location of femoral head necrosis: (1) medial third, (2) median third, and (3) lateral third. Size of femoral head necrosis: (A) <15%, (B) 15–30%, (C) >30%.
(b) Intrusion degree of femoral head contour: (A) <2 mm, (B) 2–4 mm, and (C) >4 mm.
\n
\n
5. Early changes in MRI features and laboratory parameters of SLE patients
\n
In previous multicenter studies, several strategies were selected for treatment of SLE according to the clinical conditions of the patients, resulting in slight differences among the participating hospitals. This allowed us to investigate the very early development of ION at 3 months after the start of steroid therapy using MRI imaging to clarify the background factors associated with ION. We found that the prevalence of asymptomatic ION among our patients was 26.9%, similar to that described previously [23]. We found no differences in the clinical characteristics of the patients, such as sex, age, height, and body weight and clinical features. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) is shown to be a valid and reliable measure of disease activity of SLE patients [35]. The SLEDAI score is assessed using a combination of clinical history, physical examination, organ-specific function test and serological test. Almost all of our patients showed high or very high disease activity at the time of steroid initiation. However, the SLEDAI score was not correlated with asymptomatic ION [32]. In SLE, as is the case for antiphospholipid syndrome (APS), about 30–40% of patients have detectable antiphospholipid antibodies [36] and a positive lupus anticoagulant test and anticardiolipin antibody are detected in approximately 10–30% and 20–40% of patients, respectively. The prevalence of a so-called clinically significant anticardiolipin profile is considered to be about 30–40% [37]. APS antibodies as a prothrombotic factor might predispose to ION by causing microvascular thrombosis. However, the link between APS antibodies and ION is controversial [38–41]. In our study, there was no significant association between APS antibody and ION [32]. A Japanese nationwide study revealed that cigarette smoking was an independent risk factor for ION [42]. However, in our present study, cigarette smoking was not correlated with ION in SLE patients [32].
\n
\n
6. Serological parameters and ION
\n
Serological activity of SLE was determined on the basis of decreased CH50 and increased anti-DNA antibodies. We also investigated serological parameters such as C3, C4, CH50, and anti-ds DNA antibody, as well as renal function parameters such as the serum creatinine level, estimated glomerular filtration rate, and proteinuria. However, these factors were not correlated with ION. Thus, both initial serological disease activity and initial renal function, as the most common forms of organ involvement, did not appear to be correlated with ION [32]. Similar results were obtained in a previous single-center study [23].
\n
\n
7. Lipid levels, statins, and ION
\n
Several studies of ION have indicated the association of lipid. Nagasawa et al. [31] investigated the rate of increase in serum total cholesterol (TC) levels 1 month after glucocorticoid administration in patients with new-onset SLE, and found that they were significantly high in the ION group. It was also found that lipid levels, and the rates of increase in almost all the TC and triglyceride (TG) parameters, were higher in the group that developed ION. TC levels tended to be higher than that in the non-ION group, and the maximum levels and increasing rates were significantly higher, suggesting that a rapid rise in serum lipids soon after an increase in glucocorticoid dose might affect the onset of ION [23]. Our data suggested that the level of TG both before and after the initiation of steroid therapy was higher in patients with ION [32]. The TG level before PSL therapy was associated future risk of asymptomatic ION. As the association between TG before PSL therapy and the initial dose of PSL was not significant, the effect of TG before PSL therapy on asymptomatic ION would not have been modified by the initial dose of subsequent PSL. Several studies have shown that a high TG level is a strong risk factor for stroke and ischemic heart disease [43–45]. ION is caused by partial or total interruption of blood flow to the femoral head, and SLE patients thought to develop asymptomatic ION through a similar mechanism. Additionally, it is well known that steroid therapy induces iatrogenic metabolic syndrome, and from this point of view, a high TG level is considered to be an important risk factor for asymptomatic ION. Furthermore, the TC level after steroid therapy tended to be higher in patients with asymptomatic ION. However, the levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were not correlated with asymptomatic ION. As described previously, the TC level after 1 month of steroid treatment was significantly higher in patients with asymptomatic ION. Our data are similar to those reported previously [46]. In the early phase, lipids—especially TG—play an important role in the development of ION in patients with SLE. HMG-CoA reductase inhibitors (statins) have been widely used for the treatment of dyslipidemia as well as for prevention of ischemic heart disease. According to a chicken model, Wang et al. suggested that lovastatin prevented steroid-induced ION [47], and a study by Nishida et al. using a rabbit model also revealed that pitavastatin had a similar effect [48]. In humans, it has been reported that the incidence of osteonecrosis was decreased by 1% by administration of statins in a study of 284 patients with various disorders (excluding SLE) who received glucocorticoid treatment [49]. We used pravastatin, pitavastatin, lovastatin, and atorvastatin for prevention of ION, but no such preventive effect was observed [32]. Until now, no randomized controlled trial has been reported to successfully prevent steroid-induced ION. In patients with SLE, treatment with statins alone is insufficient for prevention of ION.
\n
\n
8. Prevention of osteonecrosis
\n
In patients at risk of osteonecrosis, several factors are controllable, and thus prevention is the best approach. Hyperlipidemia and DM should be managed appropriately and alcohol consumption minimized [42]. Smoking should also be avoided, if possible [50]. The dosage of glucocorticoid should be minimized as far as possible, as described previously. Statins may help to protect against osteonecrosis. One database review found that only 1% of 284 patients developed ION after treatment with statins before glucocorticoid use. In renal transplant recipients, among 338 patients who were treated with statins, 15 (4.4%) developed ION and among 2543 patients who were not treated with statins, 180 (7%) patients developed ION [49]. Antioxidant agents have been shown to inhibit osteonecrosis in animal models [51]. Further accumulation of similar studies is needed to clarify the preventive effect of statins against SLE-associated ION.
\n
\n
9. Treatment of ION
\n
The management of ION is usually determined by the degree of femoral head involvement. If the subchondral shell remains intact, there is still a possibility of healing, but if collapse occurs, healing is impossible. If the necrotic area is small and there are no symptoms, ION should be followed up because some cases may spontaneously progress over time. If femoral head ION is diagnosed early, core depression is a commonly used form of prophylactic surgery to prevent the development of arthritis. One study has demonstrated long-term spontaneous repair of osteonecrotic lesions during low-dose glucocorticoid therapy [52]. Conservative treatment of ION involves limiting the degree of weight-bearing on the hip joint in conjunction with analgesia. In general, simple observation may be considered for asymptomatic lesions. Symptomatic lesions will likely progress to collapse, and if observation is chosen, the next joint-preserving procedure should be considered. Various forms of medication have been tried. BP is regularly used for prevention of insufficiency fractures, and several studies have shown that alendronate can reduce pain and slow the progression of collapse [53–55]. Treatment with BP is effective before subchondral collapse, but after subchondral collapse, the effects of treatment for inhibiting destruction of the femoral head are limited. Lipid-lowering agents, especially statins, are hypothesized to have a protective effect against ON. The prevalence of a clinically significant antiphospholipid profile is approximately 20% in SLE patients, and these antiphospholipid antibodies are believed to contribute to ION though hypercoagulation. Accordingly, anticoagulation therapy has been tried for prevention of ION in SLE patients, and warfarin has been modestly beneficial in this respect. One study of 60 SLE patients receiving prednisolone at more than 40 mg/day found that treatment with warfarin significantly reduced the onset of ION [31]. Among various physical modalities, extracorporeal shockwave therapy, hyperbaric oxygen, and pulsed electromagnetic therapy have yielded encouraging results, but further large prospective studies will be necessary to confirm these effects. Surgical treatments to prevent joint destruction include hip arthroplasty, core decompression, osteotomy, and vascularized bone grafting. Core decompression is commonly performed as prophylactic surgery for pre-collapse osteonecrosis of the femoral head. This decreases intramedullary pressure within the femoral head and neck, and has been postulated to improve blood circulation to the femoral head. Core decompression is often combined with bone grafting to help regenerate healthy bone and support cartilage at the hip joint. Bone grafting involves transplantation of healthy bone tissue to an area of the body where it is needed. Another option that has had some degree of success is harvesting and in vitro culture of autologous mesenchymal stem cells and their re-implantation into the core decompression site [56–58]. Long-term studies to confirm the success of this approach are still underway. Hip arthroplasty is the most commonly performed procedure for postcollapse lesions of the femoral head. Recent mid- and long-term studies have yielded satisfactory results [59]. Transtrochanteric anterior rotational osteotomy moves the symptomatic portion of the antero-superior femoral head out of the weight-bearing dome, enabling the normal posterior aspect of the head to bear weight, thus helping to preserve the joint [60]. These procedures have yielded favorable success rates, but are associated with a moderate risk of nonunion. Vascularized fibular grafting is a more complex procedure in which a segment of bone is taken from the fibula of the patient, along with the arterial and venous blood supply. This is then transplanted into a hole created in the femoral neck and head. Vascularized fibular grafting has yielded successful outcomes in patients with precollapse lesions and moderate success in those with postcollapse lesions [61]. Additionally, use of autogenic or allogeneic cortical bone grafts and cancellous bone grafts has yielded good results for the treatment of precollapse and/or early precollapse osteonecrotic lesions of the femoral head.
\n
\n
10. Atypical femoral fracture
\n
Glucocorticoid-induced osteoporosis (GIO) is an important problem in patients with SLE. BP is a key drug used for prevention and treatment of GIO. Patients with SLE often need to continue glucocorticoid and BP therapy for a long time, even if they are young. AFF has recently been recognized as a complication of long-term BP use [62, 63]. AFF is defined as a fracture located along the femoral diaphysis from just distal to the lesser trochanter to just proximal to the supracondylar flare, as distinguished from typical femoral fracture which occurs at the femoral neck or intertrochanteric area and is related to osteoporosis [63]. Diagnosis of AFF requires the presence of four of five major features (Table 3).
\n
\n
\n\n
\n
To satisfy the case definition of AFF, the fracture must be located along the femoral diaphysis from just distal to the lesser trochanter to just proximal to the supracondylar flare. In addition, at least four of the five major features must be present. None of the minor features is required but have sometimes been associated with these fractures.
\n
\n
Major features
\n
\n
The fracture is associated with minimal or no trauma, as in a fall from a standing height or less
\n
\n
The fracture line originates at the lateral cortex and is substantially transverse in its orientation, although it may become oblique as it progresses medially across the femur
\n
\n
Complete fractures extend through both cortices and may be associated with a medial spike; incomplete fractures involve only the lateral cortex
\n
\n
The fracture is noncomminuted or minimally comminuted
\n
\n
Localized periosteal or endosteal thickening of the lateral cortex is present at the fracture site (“beaking” or “flaring”)
\n
\n
Minor features
\n
\n
Generalized increase in cortical thickness of the femoral diaphyses
\n
\n
Unilateral or bilateral prodromal symptoms such as dull or aching pain in the groin or thigh
\n
\n
Bilateral incomplete or complete femoral diaphysis fractures
\n
\n
Delayed fracture healing
Table 3.
ASBMR Task Force 2013 Revised Case Definition of AFFs [63].
\n
Beaking is one of these features, and is defined as localized periosteal or endosteal thickening of the lateral cortex at the fracture site. Since cortical thickening at the fracture site characterizes stress fracture, the mechanism of AFF is considered to involve stress [63]. The age-standardized incidence rates of AFF have been reported to be 16 per 100,000 person-years for patients treated with BPs over 5 years and 133 for those treated with BPs over 10 years [62], and AFF occurs much less frequently than osteoporosis-related fractures. However, once it occurs, it takes much time to heal [64, 65], and the daily life activities of the patient are often impaired. Risk factors for AFF other than long-term BP use include glucocorticoid therapy [66, 67], complicating connective tissue disease [67], lateral bowing of the femur [68, 69], a low level of serum 25-hydroxyvitamin D [66], and female gender [70]. Glucocorticoid therapy has been reported to have an important impact on AFF [66, 67], although no significant association has yet been proved in several studies [71, 72]. Girgis et al. reviewed 152 femoral shaft fractures and classified 20 of them as AFF; they concluded that the use of glucocorticoid therapy for more than 6 months was significantly associated with AFF [66]. In a fracture location-, age-, and gender-matched case-control study, Saita et al. reviewed 2238 hip and femoral shaft fractures and diagnosed 10 of them as AFF, concluding that glucocorticoid therapy and complicating connective tissue disease were significant risk factors for AFF [67]. We recently evaluated the incidence of latent femoral beaking (Figure 2), which may precede AFF, in 125 patients with autoimmune diseases [65 (52%) with SLE] taking BP and glucocorticoid [73].
\n
Figure 2.
X-ray of the hip joint showing beaking (white arrow).
\n
Our data revealed that the incidence of beaking was 8% and increased to 10% over 2 years. A case of complete AFF from the tip of the beaking occurred in one patient. The risk factors for beaking were BP therapy for a period of >4 years, age 40–60 years, and presence of diabetes mellitus [73]. Although few studies have investigated AFF in patients with SLE, the frequency of beaking in our study was thought to be higher than in conventional reports of AFF, possibly because all of the patients were taking BP (mean therapy duration 5.1 ± 2.7 years) and glucocorticoid (mean dose 10.0 ± 3.8 mg). Both BP and prolonged glucocorticoid therapy reduce bone remodeling [64, 74], thus, impairing the healing of microdamage occurring during normal daily life activities. BP also changes bone plasticity [75], and glucocorticoid therapy leads to a deterioration of bone quality [76]. Thus, a combination of BP and glucocorticoid therapies enhances microdamage accumulation, producing conditions in which beaking can easily occur. Generally, lateral bowing of the femur is considered to be a risk factor for AFF. Hyodo et al. indicated that AFF located in the mid femur was significantly related to femoral bowing, whereas AFF in the proximal femur was related to glucocorticoid use [68]. In our previous study of patients with autoimmune diseases taking BP and glucocorticoid, the femoral beaking was mostly located at the subtrochanter, and was not related to lateral bowing of the femur [73]. Therefore, AFF and beaking in patients taking BP and glucocorticoid may generally occur irrespective of lateral femoral bowing. In order to properly benefit from BP and to minimize the risk of AFF, a BP “drug holiday” has been proposed. Postmenopausal women treated orally with BP for over 5 years can be considered for such a break in drug therapy if they have no osteoporotic fractures, their hip T score is >−2.5 and their fracture risk is not high [62]. For patients with GIO, few studies have investigated the safety and effectiveness of temporary drug withdrawal, and further studies are required. Because of the high frequency of beaking in patients taking BP and glucocorticoid [73], regular femoral X-ray screening for beaking is strongly recommended for AFF prevention, and once beaking is detected, a BP drug holiday should be considered.
\n
\n
11. Conclusion
\n
SLE is a chronic inflammatory autoimmune disease mainly affecting young women; the mortality has recently been improved by treatments including glucocorticoid therapy. However, several adverse effects of glucocorticoid may decrease the quality of life. Even though some of these adverse effects have been overcome recently, AFF and ION are still persistent problems, and further work needs to be done to alleviate them.
\n
Acknowledgments
\n
This study was supported by a research grant from the Research Committee on Idiopathic Osteonecrosis of the Femoral Head of the Ministry of Health, Labour, and Welfare of Japan.
\n
\n',keywords:"systemic lupus erythematosus, glucocorticoid, osteonecrosis, bisphosphonate, atypical femoral fracture",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/54728.pdf",chapterXML:"https://mts.intechopen.com/source/xml/54728.xml",downloadPdfUrl:"/chapter/pdf-download/54728",previewPdfUrl:"/chapter/pdf-preview/54728",totalDownloads:1247,totalViews:311,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:3,impactScoreQuartile:1,hasAltmetrics:0,dateSubmitted:"November 7th 2016",dateReviewed:"February 27th 2017",datePrePublished:null,datePublished:"May 31st 2017",dateFinished:"April 7th 2017",readingETA:"0",abstract:"Osteonecrosis and osteoporosis are frequent adverse effects of glucocorticoid therapy of systemic lupus erythematosus (SLE). Idiopathic osteonecrosis (ION) of the femoral head occurs in 3–40% of patients receiving glucocorticoid, and can also develop in other bones. Higher doses of glucocorticoid and steroid pulse therapy are considered to be risk factors for ION of the femoral head. To analyze these risk factors, it seems important to detect early changes in the femoral head by magnetic resonance imaging and to monitor early clinical events attributable to steroid therapy. Prophylaxis with statins and warfarin remains debatable. The use of glucocorticoid is increase the risk of bone fractures. Bisphosphonate (BP) is used for its prevention and treatment of osteoporosis. Atypical femoral fracture (AFF) has been recently recognized as a complication associated with BP use. AFF is considered to be a form of stress fracture; localized periosteal thickening of the lateral cortex is often present at the fracture site. The thickening has been recently recognized as a complication associated with the use of antiresorptive agents such as BP and denosumab. As long-term BP/glucocorticoid use is a risk factor for beaking in patients with SLE , temporary withdrawal of BP administration should be considered.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/54728",risUrl:"/chapter/ris/54728",book:{id:"5875",slug:"lupus"},signatures:"Takeshi Kuroda and Hiroe Sato",authors:[{id:"59845",title:"Dr.",name:"Takeshi",middleName:null,surname:"Kuroda",fullName:"Takeshi Kuroda",slug:"takeshi-kuroda",email:"kurodat@med.niigata-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Niigata University",institutionURL:null,country:{name:"Japan"}}},{id:"200665",title:"Dr.",name:"HIroe",middleName:null,surname:"Sato",fullName:"HIroe Sato",slug:"hiroe-sato",email:"hiroes@med.niigata-u.ac.jp",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Incidence, etiology, and pathogenesis",level:"1"},{id:"sec_3",title:"3. Timing of osteonecrosis-related ischemia in patients with SLE",level:"1"},{id:"sec_4",title:"4. Classification of osteonecrosis",level:"1"},{id:"sec_5",title:"5. Early changes in MRI features and laboratory parameters of SLE patients",level:"1"},{id:"sec_6",title:"6. Serological parameters and ION",level:"1"},{id:"sec_7",title:"7. Lipid levels, statins, and ION",level:"1"},{id:"sec_8",title:"8. Prevention of osteonecrosis",level:"1"},{id:"sec_9",title:"9. Treatment of ION",level:"1"},{id:"sec_10",title:"10. Atypical femoral fracture",level:"1"},{id:"sec_11",title:"11. Conclusion",level:"1"},{id:"sec_12",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Boumpas DT, Chrousos GP, Wilder RL, Cupps TR, Balow JE. (1993). Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. 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J Bone Miner Res. 31(1): 16–35.'},{id:"B63",body:'Shane E, Burr D, Abrahamsen B, Adler RA, Brown TD, Cheung AM, Cosman F, Curtis JR, Dell R, Dempster DW, Ebeling PR, Einhorn TA, Genant HK, Geusens P, Klaushofer K, Lane JM, McKiernan F, McKinney R, Ng A, Nieves J, O\'Keefe R, Papapoulos S, Howe TS, van der Meulen MC, Weinstein RS, Whyte MP. (2014). Atypical subtrochanteric and diaphyseal femoral fractures: second report of a task force of the American society for bone and mineral research. J Bone Miner Res. 29(1): 1–23.'},{id:"B64",body:'Odvina CV, Zerwekh JE, Rao DS, Maalouf N, Gottschalk FA, Pak CY. (2005). Severely suppressed bone turnover: a potential complication of alendronate therapy. J Clin Endocrinol Metab. 90(3): 1294–1301.'},{id:"B65",body:'Kondo N, Yoda T, Fujisawa J, Arai K, Sakuma M, Ninomiya H, Sano H, Endo N. (2015). Bilateral atypical femoral subtrochanteric fractures in a premenopausal patient receiving prolonged bisphosphonate therapy: evidence of severely suppressed bone turnover. Clin Cases Miner Bone Metab. 12(3): 273–277.'},{id:"B66",body:'Girgis CM, Sher D, Seibel MJ. (2010). Atypical femoral fractures and bisphosphonate use. N Engl J Med. 362(19): 1848–1849.'},{id:"B67",body:'Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, Nagao M, Sakamoto Y, Sakai K, Homma Y, Kato R, Nagura N, Miyagawa K, Wada T, Liu L, Matsuoka J, Obayashi O, Shitoto K, Nozawa M, Kajihara H, Gen H, Kaneko K. (2015). The incidence of and risk factors for developing atypical femoral fractures in Japan. J Bone Miner Metab. 33(3): 311–318.'},{id:"B68",body:'Hyodo K, Nishino T, Kamada H, Nozawa D, Mishima H, Yamazaki M. (2017). Location of fractures and the characteristics of patients with atypical femoral fractures: analyses of 38 Japanese cases. J Bone Miner Metab. 35(2):209–214.'},{id:"B69",body:'Saita Y, Ishijima M, Mogami A, Kubota M, Baba T, Kaketa T, Nagao M, Sakamoto Y, Sakai K, Kato R, Nagura N, Miyagawa K, Wada T, Liu L, Obayashi O, Shitoto K, Nozawa M, Kajihara H, Gen H, Kaneko K. (2014). The fracture sites of atypical femoral fractures are associated with the weight-bearing lower limb alignment. Bone. 66: 105–110.'},{id:"B70",body:'Beaudouin-Bazire C, Dalmas N, Bourgeois J, Babinet A, Anract P, Chantelot C, Farizon F, Chopin F, Briot K, Roux C, Cortet B, Thomas T. (2013). Real frequency of ordinary and atypical sub-trochanteric and diaphyseal fractures in France based on X-rays and medical file analysis. Joint Bone Spine. 80(2): 201–205.'},{id:"B71",body:'Giusti A, Hamdy NA, Dekkers OM, Ramautar SR, Dijkstra S, Papapoulos SE. (2011). Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features. Bone. 48(5): 966–971.'},{id:"B72",body:'Warren C, Gilchrist N, Coates M, Frampton C, Helmore J, McKie J, Hooper G. (2012). Atypical subtrochanteric fractures, bisphosphonates, blinded radiological review. ANZ J Surg. 82(12): 908–912.'},{id:"B73",body:'Sato H, Kondo N, Wada Y, Nakatsue T, Iguchi S, Fujisawa J, Kazama JJ, Kuroda T, Nakano M, Endo N, Narita I. (2016). The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates. Osteoporos Int. 27(3): 1217–1225.'},{id:"B74",body:'Teitelbaum SL. (2012). Bone: the conundrum of glucocorticoid-induced osteoporosis. Nat Rev Endocrinol. 8(8): 451–452.'},{id:"B75",body:'Tjhia CK, Odvina CV, Rao DS, Stover SM, Wang X, Fyhrie DP. (2011). Mechanical property and tissue mineral density differences among severely suppressed bone turnover (SSBT) patients, osteoporotic patients, and normal subjects. Bone. 49(6): 1279–1289.'},{id:"B76",body:'Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R. (1995). Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis. 54(10): 801–806.'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Takeshi Kuroda",address:"kurodat@med.niigata-u.ac.jp",affiliation:'
Niigata University Health Administration Center, Nishi-ku, Niigata City, Japan
Niigata University Health Administration Center, Nishi-ku, Niigata City, Japan
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1. Introduction
Age-related macular degeneration (AMD) is a complex, degenerative, progressive, multifactorial disease with multiple genetic and environmental factors contributing to its onset and progression [1].
Age-related macular degeneration (AMD) represents damage of the retinal macula and thus the central visual field and is the leading cause of blindness and visual impairment in people over 60 years of age [2, 3]. Prevalence of an early AMD (the presence of medium-sized drusen or drusen with degeneration or hyperpigmentation of the retinal pigment epithelium (RPE)) is 18% in the elderly population between 65 and 74 years of age and as much as 30% in the population older than 74 years [4].
The initial site of damage, according to most researchers, is the retinal pigment epithelium, although some authors find primary damage in the choriocapillary or extracellular matrix of the sensory retina. Regardless of the location and mechanism of initial damage, there is an opinion that oxidative stress plays an increasingly important role in the genesis of age-related macular degeneration.
The eye is a unique organ, because it is constantly exposed to radiation, atmospheric oxygen, chemicals from the environment, but also to the physical damages [5]. Therefore, oxidative stress is one of the most important mechanisms of the onset of many eye diseases such as cataract, glaucoma, uveitis, retrolental fibroplasia, age-related macular degeneration, as well as various forms of retinopathy [6]. Most free radicals are formed as bioproducts of normal cellular physiology. The most common damage to the eye by free radicals is caused by hydroxyl radical (OH·), superoxide anion radical (O2•–) and hydrogen peroxide (H2O2). Reactive oxygen species (ROS) cause oxidative damage to cytoplasmic and nuclear elements of the cell and make changes in the extracellular matrix. The degree of oxidative cell damage is limited by the action of various types of antioxidants and reparation of damaged structures. Throughout life, persistent oxidative stress which leads to oxidative damage to macromolecules and to the accumulation of these oxidatively modified compounds is one of the most important factors of tissue ageing. The retina is a typical example of tissue where oxidative changes occur, including loss of retinal cells, accumulation of lipofuscin within the retinal pigment epithelium (RPE), drusen formation, accumulation of degrading products in the Bruch membrane and changes in choroidal capillaries. When these changes become pronounced, they contribute to the formation of macular degeneration. Recent studies have shown that antioxidants and ‘scavengers’ of free radicals have anti-inflammatory and protective effects on eye tissues, protecting them from the harmful effects of oxidants [7].
The objective of this review was to describe the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.
2. The classification of AMD
Based on the Beckman AMD classification system, the disease is classified into early-stage AMD, intermediate-stage AMD and late-stage AMD [8]. Early-stage AMD encompasses the presence of medium-sized drusen (63–125 μm) without any impairment of visual function. Intermediate-stage AMD is defined by the presence of large drusen (>125 μm) or/and abnormalities in the RPE. Late-stage AMD (advanced AMD) is classified into two clinical entities: central geographic atrophy (GA, dry or nonexudative AMD) and neovascular AMD (wet or exudative AMD) [9]. Irreversible loss of vision occurs in geographic atrophy when there is an irreversible loss of RPE and photoreceptor cells, usually in the perifoveal region of the macula. In the neovascular form of AMD, there is an invasion of new choroidal blood vessels (choroidal neovascularization-CNV), followed by retinal detachment and RPE and vision loss [9].
3. Oxidative processes and the onset of AMD
Oxidative processes participate in almost all pathological processes in the eye. The presence of oxidative stress has also been registered in uveitis, diabetic retinopathy, various forms of glaucoma, cataractogenesis and other degenerative processes [10]. As highly reactive intermediates, free radicals can lead to oxidative tissue damage through a number of mechanisms such as peroxidation of unsaturated fatty acids leading to disturbances in the permeability and fluidity of biological membranes, which is accompanied by increased membrane permeability. Oxidation of thiol groups of enzymes leads to a decrease in their activity and even inactivation of enzymes. Fragmentation of fatty acid chains leads to loss of membrane integrity, while disruption of lysosomal membrane continuity leads to release of hydrolytic enzymes and cell damage [11].
The oxidation of polyunsaturated fatty acids in the phospholipids of the cell membranes could damage the cell integrity and function. In addition to negative and destructive effects, this process may have important physiological functions such as: the lipid metabolism regulation, and changes in their physicochemical properties and permeability. Under controlled conditions, ROS enables the control of synthesis of biologically active prostaglandins and leukotrienes, proliferation and initiation of cell death.
Proteins are also targeted by free radicals’ action that could change their primary, secondary and even tertiary structure. Oxidative modifications of the primary structure of proteins resulting from the modification or loss of some amino acids or aggregation and fragmentation of proteins, which are reflected in changes in solubility and charge, are described [12]. These processes affect the integrity of the cell and its function and lead to oxidative tissue damage.
Oxidation of nucleic acids leads to changes in DNA structure, gene mutations, synthesis of inadequate genes or lack of synthesis of other genes. As a result of such processes, malignant cell transformations occur. Mitochondrial DNA is particularly sensitive to such transformations.
The degree of biomolecule damage depends on their vulnerability and intensity of oxidative stress. The repair of primarily damaged molecules results in structural changes that remain at the molecular, i.e. at the cellular level. At one point, the damage becomes so great that it exceeds the critical mass. At that moment, the symptoms of illness appear [13].
Eye damages caused by these changes as well as the mechanisms of antioxidant protection show certain specifics, not only in the eye as a special organ but also in its highly differentiated and specialised structures. Oxidative stress in epithelial cells occurs mainly as a consequence of a photodynamic process or as a by-product of oxidative phosphorylation in mitochondria.
The retina is very complex in its structure, and it is one of the highest oxygen-consuming tissues that continuously transforms light into vision, generating reactive oxygen species (ROS), such as the superoxide (O2•−), the hydroxyl radical (•OH), hydrogen peroxide (H2O2) and singlet oxygen (1O2) as normal metabolic by-products [14]. Generally, ROS are produced during oxidative metabolism under physiological conditions and participate in normal cellular metabolism [15]. Retinal photoreceptor membranes are rich in polyunsaturated fatty acids.
Photooxidative retinal damage is in the function of duration of intensity and wavelength of light. Changes that occur in the pigment layer of the retina are considered to be initial in the process of genesis of age-related macular degeneration. During ageing, functions of all senses gradually weaken. Degenerative processes in the eye and especially in the lens are the first signs of ageing that are noticed [10].
4. The synthesis of free radicals during light exposure
It is well established that light exposure has the potential to cause detrimental effects in RPE and retina as well as in many other organs and tissues, such as the skin, cornea, conjunctiva and lens [16].
Large quantities of ROS are produced by exposure to ultraviolet light (λ = 100–400 nm) and to blue light (λ = 400–500 nm) [17]. The photoreceptors in the macula absorb parts of the light spectrum through rhodopsin, a photoreceptor molecule in rods [18].
Roehlecke and Schumann [19] suggested that the synthesis of ROS occurred directly in outer segments of photoreceptors in the reaction catalysed by the enzyme nicotinamide adenine dinucleotide phosphate oxidase (NOX) as well as by the mitochondrial activity of the outer segments after absorption of visible blue light (λ = 405 nm) with an output power of 1 mW/cm2 [19]. The authors found that the generation of ROS is highly increased in the photoreceptors of retinal explants after 0.5–1 h of blue light absorption, due to increased NOX activity (especially NOX2 and NOX4). Under these conditions (light exposure of 1 mW/cm2), it is possible to do the following extrapolation to the superoxide anion [20]: 1) One granule of lipofuscin can synthesise 8 x 10−19 mol of superoxide anion/min; 2) since 1 mol contains 6.02 x 1023 molecules, then 1 granule is capable of producing 4.8 x 105 molecules of superoxide/min; and 3) if we take into account that the average cell volume is 2000 μm3 and if up to 19% of that volume is occupied by lipofuscin granules 1 μm in diameter, then each RPE cell has a synthesis capacity of 3.5 x 108 superoxide anions/per cell per minute [21].
This high level of free radical synthesis may explain why RPE cells contain a high concentration of various antioxidants [22]. The spectral dependence of lipofuscin explains the so-called ‘blue light hazard’ on retina. Light with a wavelength of 550 nm or less can cause ‘actin’ or photochemical damage, but is too low to cause thermal effects [23]. These photochemical lesions are expressed at the level of RPE, where the action spectrum of ‘blue light’ is similar to the bandwidth of the absorption spectrum of melanin [24] and lipofuscin [22, 25]. Photoreactivity analysis of blue light in freshly isolated RPE cells shows a high level of oxygen uptake with increasing age of the donor and that this ‘photo-uptake’ is predominantly related to lipofuscin [26]. These observations suggest a different function of lipofuscin in cells that may explain the association between high levels of lipofuscin and AMD. RPE cells are rich in antioxidants which may be enough to detoxify any reactive oxygen species [27]. Conversely, antioxidants may be insufficient to detoxify all radicals throughout life so that oxidative damage can manifest at some point in life (for example, in old age).
It has also been observed that lipofuscin photosensitivity reactions lead to increased intragranular lipid peroxidation, measured through the accumulation of lipid peroxides and malondialdehyde in pigment granules [26, 28]. Moreover, lipofuscin can perform extracellular lipid peroxidation and enzyme inactivation. Freshly isolated lipofuscin granules incubated with visible light induced up to a 30% increase in lipid peroxidation, compared with the control. Granules incubation with catalase (antioxidant) and lysosomal enzymes (acid phosphatase), in the presence of light, causes as much as 30–50% reduction in enzyme activity. Lipid peroxidation and loss of enzyme activity can be prevented by antioxidants which indicate that lipofuscin photodamage is a product of action of free reactive oxygen species. It is generally accepted that RPE cell dysfunction is an early, crucial moment in the pathogenesis of AMD [29, 30].
RPE cells have a variety of functions from metabolic to supportive, and they are vital for photoreceptors including maintenance of the blood-retinal barrier, participation in the visual cycle (uptake, transport and release of vitamin A and its metabolites) as well as in degradation and uptake of apical phagocited parts of the photoreceptor outer segments [31]. One of the leading factors of RPE cell dysfunction is age-related phagocytic and metabolic insufficiency of postmitotic RPE cells, leading to progressive accumulation of lipofuscin granules which are mainly composed of lipids (~50%) and protein (~44%) of phagosomal, lysosomal and photoreceptor origin (including the retinoid transporter-cellular retinaldehyde binding protein/CRALBP). These substances from the lipofuscin composition can be oxidatively modified either as a result of exposure to UV light or high doses of oxygen in the eye [29, 30].
The well-known cytotoxic constituent of lipofuscin is fluorophore bisretinoid which consists of two retinoid chains derived from the pyridinium ring (A2E) which together with other photoreactive molecules is a powerful photoinducible ROS generator with a strong effect on oxidative damage of lipids, proteins and DNA [31]. N-retinyl-N-retinyldiene-ethanolamine 2-(2,6-dimethyl-8-(2,6,6- trimethyl-1-cyclohexene-1-yl) -1E, 3E, 5E, 7E-octyltetraenyl]-1-(2-hydroxyethyl)-4-[4- methyl-6-(2,6,6-trimethyl] or A2E increases the RPE sensitivity to blue light and exhibits several toxic effects on RPE cells [32, 33]. By the action of light of wavelength, λ = 430 nm, A2E is converted to A2E-epoxide by binding to oxygen. The resulting epoxide can destabilise the membranes of mitochondria and lysosomes [34] and can also inhibit cytochrome oxidase, leading to disruption of electron flow in the respiratory chain [35]. This process, in addition to producing more ROS (reactive oxygen species), reduces the efficiency of energy metabolism. An alternative A2E toxic pathway has been described by Finnemann [36], who in a study with A2E-laden RPE cells demonstrated the presence of destabilised lysosomes, resulting in incomplete digestion of phagocited photoreceptors of the outer segments during 24 h. Since phagocytosis is a circadian regulated process, this will constantly increase the non-degraded phospholipids that are a source of ROS. Mitochondrial destabilisation and incomplete digestion of lipids and proteins caused by lysosome destabilisation lead to increased free radical accumulation. In a closed circle, this mechanism destabilises RPE cells, leading to their loss and this process conditions the initiation of drusen formation [37].
Although lipid peroxidation products are considered to be the main substrates for the genesis of lipofuscin and its cytotoxic constituents, other identified lipofuscin proteins also play a significant role in cytotoxicity [30, 31].
The study of King et al. conducted on the human adult RPE cell line-19 (ARPE-19) revealed that the mitochondrial electron transport chain was an important source of ROS which played a critical role in the death of cells exposed to short-wavelength blue light (425 ± 20 nm) [38].
Except lipofuscin, several other retinal pigments, such as rhodopsin and melanin, were shown to be involved in the oxidative stress process [39]. Grimm et al. reported rhodopsin-mediated blue-light-induced damage in the retina, which occurred after short time exposure to the blue light [40].
In the RPE, lipofuscin is derived primarily from phagocytosis of shed photoreceptor outer segments and is considered a heterogeneous waste material that accumulates with age in active postmitotic cells, such as those of the RPE [41]. The RPE cells are able to phagocyte the photoreceptors of outer segments (POSs) that contain a high amounts of unsaturated fatty acids [42]. During phagocytosis, a high quantity of oxygen is consumed and a significant production of ROS occurs (generated by NOX or peroxidase) via the oxidation of fatty acids in the POSs [43]. Mitter et al. in their study have shown that autophagy plays a significant role in protection of the RPE from oxidative stress [44]. Recent evidence showed that dysfunctional autophagy/mitophagy in the RPE may lead to mitochondrial disintegration by affecting the mitochondrial fission/fusion ratio, resulting in excessive amounts of ROS [45].
5. The synthesis of oxidatively modified compounds in the eye, by the action of free radicals
Excessive synthesis of free radicals in the eye is associated with the production of oxidatively modified compounds and cytotoxic damage of ocular structures. The cell types with relatively high levels of polyunsaturated fatty acids (PUFAs), such as retinal cells, are highly sensitive to lipid peroxidation. Polyunsaturated fatty acids in phospholipids and glycolipids are the basic substrate of oxidative damage to lipids caused by free radicals.
Lipid peroxidation, a complex process involving the interaction of oxygen-derived free radicals with polyunsaturated fatty acids, finally results in a variety of primary compounds: highly reactive compounds (alkyl radicals, conjugated dienes, peroxy and alkoxy/oxyl radicals and lipid hydroperoxide). During further decomposition of primary compounds, a series of secondary products are produced such as: short-chain evaporable hydrocarbons, aldehydes and end products of lipid peroxidation (i.e. isoprostanes, MDA, 4-hydroxy-2,3, trans nonenal and 4,5-dihydroxydecenal) [46, 47].
MDA is a secondary product of peroxidation of unsaturated fatty acids, (particularly arachidonic acid) and is a physiological ketoaldehyde [48]. In a higher concentration, it reacts with free amino groups of proteins (especially with lysine cysteine or histidine residue). Such modified protein structures have immunogenic features. Some studies have shown that an increased titre of these autoantibodies directly correlates with the extent of oxidative damage and may predict the progression of some diseases. It was suggested that reduced ability to protein proteolysis after their oxidative modification with MDA and 4-HNE represents one of the main factors of lipofuscin synthesis during the development of AMD [49].
Lipid peroxidation highly reactive end products, such as 4-hydroxylnonenal (4-HNE), malondialdehyde (MDA), oxidised nucleotides and carboxyethyl pyrrole (CEP), have been demonstrated to be associated with drusen formation and RPE atrophic modifications in both human and animal eye [50].
Recently, Kim et al. [51] found that the injection of hydroperoxy-octadecadienoic acid (HpODE), (a peroxidized lipid) into the subretinal space of a murine AMD model, could initiate an early increase in the expression of markers of oxidative stress and lipid peroxidation, especially high levels of 4-HNE and MDA [51]. Zor et al. [52] documented a significantly increased MDA values (~15%) in patients with neovascular AMD compared with the controls [53].
F2-isoprostane (F2-IsoPs) is another marker of lipid peroxidation which is considered to be an important ‘in vivo’ marker of oxidative damage in AMD [54, 55]. Sabanayagam et al. [56] demonstrated that the presence of F2-IsoPs in urine was positively associated with AMD.
Oxidative DNA damage of both nuclear and mitochondrial genomes can result in strand breaks, base modifications and DNA-protein cross linkages which are all strongly implicated in ageing and age-related diseases [57, 58]. Over 20 base modifications related to ROS attack of DNA are identified, with the following oxidative DNA damage products: 8-oxo-7,8-dihydroadenine, 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 5,6-dihydroxy-5,6-dihydrothymine as well as the ring-opened lesions of 4,6-diamino-5-formamido-pyrimidine and 2,6-diamino-4-hydroxy-5-formamido-pyrimidine [59]. The 8-oxodG, which is formed through the oxidation of guanine at the C8 position in the guanine base, serves as a reliable biomarker of oxidative stress and oxidative modification of DNA, and it is associated with ageing and ageing-related diseases [58].
Age-related increases in lipofuscin, 8-oxoguanine, CEP, 4-HNE and MDA expression have been observed in the ageing retina [60, 61, 62] which have been reported to cause inflammatory responses and AMD features [63].
6. The pathophisiology of AMD-Drusen formation
Age-related macular degeneration is characterised by degenerative changes involving the outer portion of the retina, RPE, Bruch’s membrane and choriocapillaris. Drusen are considered as a hallmark of AMD and as an amorphous deposit that accumulates extracellularly in the zone between the RPE and the inner collagen zone of the Bruch’s membrane [64]. Clinically, they are divided into two main phenotypes: ‘soft and hard’, depending on their relative size and shape. A few smaller hard drusen (<65 μm) can be found in at least 95% of the elderly population, but do not represent AMD. Only the presence of larger drusen (>125 μm), especially soft drusen (> 125–250 μm) in the macula, is considered as a major risk factor for the development of advanced forms of AMD, i.e. exudative-neovascular forms, especially if they are combined with pigmentation disorders [65].
In the later stage of AMD, neovascularization, exudative changes or disciform scars can occur. In the atrophic form of AMD, there is a loss of pigment epithelium or ‘attenuation’ of the choriocapillaris but without neovascularization [66]. Early pathological changes include basal deposits in the Bruch’s membrane which occur exclusively in pathological samples and have two types: a) basal laminar deposits consisting of basement membrane proteins and long collagen filaments located between RPE and basement membrane and b) basal linear deposits that are more specific for early AMD changes and consist mainly of membrane material located in the Bruch membrane, externally from the RPE basement membrane. The combination of these deposits with secondary changes in RPE results in the formation of drusen [67].
Many different molecules have been identified in drusen, including glycoconjugates and other compounds also found in atherosclerotic plaque (hence the link between atherosclerosis and AMD formation by some authors), including vitronectin, apoprotein B and E, α-crystalline, HtrA1 and lipids [68, 69, 70]. Macrophages found in drusen regression suggest a possible hypothesis that macrophages are involved in the process of degradation of deposits within the Bruch membrane [71]. Activated microglias have also been found in AMD degenerative lesions [72]. Discrete nodules or hard drusen deposits consisting of hyaline-like material were found between the RPE and the Bruch membrane. Soft drusen are usually large and occur with detachment of RPE cells and diffuse changes of the Bruch membrane. They can occur in deeper damages of the RPE and choroids and lead to choroidal neovascularization or cell death in the RPE as well as geographical atrophy. Autofluorescent pigments, such as lipofuscin, which are accumulated in RPE cells, reach a size that often leads to decreased cellular function, retinal ageing and degeneration, mostly in the form of geographic atrophy [73].
Lipofuscin in RPE is the most common cause of fundus autofluorescence. These are spherical particles of micrometre size with characteristic yellow fluorescence when exposed to blue light. The main component of lipofuscin is N-retinylidine-N-retinyletanol-amine (A2E), a quaternary amine and retinoid bioproduct of visual cycle [74]. Lipofuscin synthesis is a pathogenic reaction in which the resulting A2E interferes with the function of RPE cells and leads to their apoptosis. Choroidal neovascularization can occur in the macular, peripapillary and peripheral regions. Early choroidal neovascularization occurs below the RPE cells to later break through the RPE layer and develop an exudative, haemorrhagic or disciform form of AMD. In the neovascular form of AMD, lipid accumulation occurs below the RPE or neuroretin. In the haemorrhagic form of AMD, blood penetrates through the RPE into the subretinal space and sometimes through the retina to the vitreous. In the disciform form of AMD, fibrous tissue with neovascularization and changes in RPE cells proliferates and may partially or totally replace neuroretin [75]. Additional pathological lesions include serous exudation, haemorrhage, gliosis and calcification. Macrophages have been proven both morphologically and functionally in the neovascular form of AMD [76]. Activated macrophages and microglias can secrete chemokines and cytokines, causing further cell damage, degradation of the Bruch’s membrane and angiogenesis [77].
7. Oxidative stress and choroidal vascular changes in AMD
Among AMD cases, approximately 10–15% have neovascular AMD characterised by abnormal vascular morphology and growth [8]. Vascular endothelial growth factor (VEGF) upregulation plays a crucial role in the development of neovascular AMD. Yi and assoc. [78] documented an increased VEGF expression in a study using laser to induce choroidal neovascularization (CNV) in rats. This author suggests that the macrophages could be probably the most important source of VEGF in the early phase of AMD [78]. VEGF expression in subfoveal fibrovascular membranes was concentrated in cells resembling fibroblasts, implicating a significant role of fibroblasts in the progression of CNV [79]. The results showed that even temporary overexpression of VEGF in RPE cells was sufficient to induce CNV in the rat eye [80]. Wang et al. reported that IQ protein motif-containing GTPase activating protein 1 (IQGAP1), scaffold protein with a Rac1-binding domain, regulated VEGF activation by binding to Rac1GTP in choroidal endothelial cells, activating their migration [81]. IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein that is involved in multiple cellular functions such as cell survival and trafficking [82].
The vascular endothelial dysfunction is considered as a crucial event in development and progression of choroidal vascular dysfunction [82]. Nitric oxide and nitric oxide synthase enzymes have been shown to be involved in the upregulation of VEGF. Nitric oxide synthases (NOSs) are a family of enzymes that catalyse the conversion of L-arginine into nitric oxide (NO). They are classified into three isoforms: endothelial NOS (eNOS), neuronal NOS (nNOS) and inducible NOS (iNOS) [83]. The eNOS maintains the physiological function of the vascular endothelium [84]. It was demonstrated that eNOS mediated endothelium-dependent vasodilation in retinal arterioles and ophthalmic arteries [85]. NO is considered not only a mediator of vasodilation, but also a regulator of various vascular functions. For example, physiologically, NO can dilate a blood vessel, inducing relaxation of vascular smooth muscle cells (VSMCs), inhibiting cell proliferation and regulating angiogenesis and vascular permeability [86]. Bhutto et al. [87] reported that eNOS and nNOS expression was significantly decreased in the eyes of AMD patients. This author suggested that the decreased expression of eNOS and nNOS might reduce the NO production that could induce hemodynamic changes in CNV [87].
It was documented that excessive amounts of NO can have detrimental effects on cells and tissues, implicated that the production of NO is not always beneficial. In that case, NO can be an important stimulator of CNV. Ando et al. suggested that blockade of nNOS and iNOS could reduce CNV formation [88]. Excessive amounts of nitric oxide can react with the superoxide anion to form peroxynitrite, a very toxic and reactive radical which compromises vascular endothelial function [89].
There is some evidence that ROS and vascular dysfunction may together contribute to the pathology of neovascular AMD. It was demonstrated that NOX was the connection between VEGF and ROS in human choroidal endothelial cells [90]. The family of NOX consists of seven isoforms such as: NOX1, NOX2, NOX3, NOX4, NOX5, dual oxidase (Duox) 1 and Duox2) which are differentially expressed in tissues and cells [91]. NOX1, NOX2 and NOX4 are expressed in choroidal vascular endothelial cells [92]. ROS generated by NOX function as signalling molecule promoting endothelial cell proliferation, migration and tube formation [92]. Some studies documented that ROS generated from NOX2 could activate the transcription factors NF-κB and activator protein 1 (AP-1) and increase the expression of intracellular adhesion molecule (ICAM)-1 and VEGF leading to vascular hyperpermeability and retinal neovascularization [93]. Moreover, NOX4-derived ROS generation is essential for the expression of hypoxia-inducible factor 1-alpha (HIF-1α) which was linked to cell proliferation and migration of vascular smooth muscle cells [94].
8. Other mechanisms involved in the development of neovascular AMD
One of the risk factors for AMD may be increased collagen synthesis in the choriocapillaris which is then incorporated into the Bruch’s membrane, creating thickenings that precede the appearance of linear deposits [95]. Chromatographic analysis of the drusen showed that they contained more than a hundred different proteins originated from retinal pigment epithelial cells, neuronal retinas and choriocapillaris. However, their composition differs depending on the existence i.e. absence of AMD. It is thought that certain ingredients can promote angiogenesis. The integrity of the RPE cellular structures in a culture that is chronically exposed to oxidative stress is impaired by the action of hydrogen peroxide due to the interruption of intercellular compounds. This is one of the possible mechanisms of breaking the blood-brain barrier in the pathogenesis of AMD [96].
Programmed cell death (apoptosis) is an essential protective mechanism of the organism against the accumulation and spread of damaged or unnecessary cells. An increased degree of apoptosis is observed in most ageing cell populations. A similar thing happens in RPE cells. There is an opinion that mitochondria play a key role in the regulation of apoptosis. Reactive oxygen metabolites that are formed in RPE cells exposed to the blue part of the spectrum originate in mitochondrial processes [97]. Oxidative stress can reduce the sensitivity of senescent cells to apoptosis through defective oxidative phosphorylation. The process of drusen formation is very similar to apoptotic process in the retina and predisposes the development of neovascularization during the progression of AMD [98].
In postmitotic tissues, during ageing, the oxidatively modified and damaged mitochondrial DNA are accumulated in mitochondria. It is believed that their genetic material is the main substrate of oxidative damage in the retinal pigment epithelium. With inefficient damage repair, redox potential of mitochondria in the human RPE retinal cells is compromised over time in photoreceptors as well [99].
It was suggested that other types of regulated cell death (e.g. pyroptosis, necroptosis and autophagy) may contribute to development of AMD [100]. Ferroptosis is a newly discovered, iron-dependent, regulated cell death pathway that is initiated by lipid peroxidation. It is implicated in neurodegeneration, ischemia–reperfusion injury and myocardial infarction [101]. It is characterised by iron-dependent accumulation [102, 103]. In contrast to apoptosis, ferroptosis is a pro-inflammatory condition that arises due to the release of intracellular content after the rupture of plasma membrane [104]. Under normal conditions, ferroptosis is a mechanism that protects cellular integrity, but leads to cell death when cellular integrity is compromised, while apoptosis represents a suicide mechanism that eliminates certain types of cells from the whole organism at specific time points [105].
It was documented that angiotensin II (Ang II) was implicated in the pathology of AMD. It was shown that Ang II can mediate various pathological processes in ocular blood vessels such as proliferation and migration of smooth muscle cells and pericytes, increase of VEGF expression and potentiation of VEGF-dependent angiogenic activity [106, 107]. Receptors for AngII have been identified in retinal and optic nerve blood vessels. Some studies have shown that blocking the renin-angiotensin system may delay the breakdown of the blood-retinal barrier and prevent retinal neovascularization and the development of AMD [108].
9. Conclusion
In this review, we tried to highlight the pathways of oxidative stress and their implication in the pathogenesis of AMD. Considering the unique structure and function of the retina in the eye, as well as the environment in which it is located, it indicates a significant synthesis of free radicals during normal physiological processes as well as during light absorption. The presence of free fatty acids and their exposure to free radicals make lipid peroxidation processes a daily occurrence in the eye. This was confirmed by many studies that found high concentrations of MDA, 4-HNE and other lipid peroxidation products in the eyes (and blood) of AMD patients. Oxidative damage of mitochondria and nuclear DNA was also observed in AMD patients, as well as increased products of oxidative damage of proteins. An impairment of autophagy and other types of cell death such as pyroptosis, necroptosis and ferroptosis were also described in AMD patients. The upregulation of VEGF and isoforms of NOX with impairment of NO synthesis have significant implications in the development of new blood vessels and the onset of choroidal neovascularization (CNV) in the pathogenesis of advanced-wet AMD. In view of all the above, further research is certainly needed in order to find adequate methods for disease prevention as well as adequate drugs for the treatment of various forms of AMD.
\n',keywords:"age-related macular degeneration, antioxidants, oxidative stress",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/82291.pdf",chapterXML:"https://mts.intechopen.com/source/xml/82291.xml",downloadPdfUrl:"/chapter/pdf-download/82291",previewPdfUrl:"/chapter/pdf-preview/82291",totalDownloads:14,totalViews:0,totalCrossrefCites:0,dateSubmitted:"April 8th 2022",dateReviewed:"May 29th 2022",datePrePublished:"July 5th 2022",datePublished:null,dateFinished:"June 17th 2022",readingETA:"0",abstract:"Age-related macular degeneration (AMD) is a complex, degenerative and progressive chronic disease that leads to severe visual loss. The prevalence of early AMD accounts for 18% in the population between 65 and 74 years of age and even 30% in subjects older than 74 years. The articles published in the last decade point out to a significant role of oxidative stress in the onset and development of age-related macular degeneration. Generally, reactive oxygen species (ROS) are produced in the eye during light absorption and physiological metabolic processes. The level of oxidative stress is kept under control by the action of antioxidants and reparative enzymes. Excessive synthesis of ROS leads to increased oxidative modification of lipids, proteins and DNA, causing oxidative damage of cytoplasmic and nuclear cell elements and changes of the extracellular matrix. The accumulation of oxidatively modified compounds in drusen deposits will initiate the onset and development of AMD. The objective of this review was to highlight the mechanisms of oxidative stress in order to elucidate their significance and association with the pathogenesis of AMD.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/82291",risUrl:"/chapter/ris/82291",signatures:"Emina Čolak, Lepša Žorić, Miloš Mirković, Jana Mirković, Ilija Dragojević, Dijana Mirić, Bojana Kisić and Ljubinka Nikolić",book:{id:"11671",type:"book",title:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",subtitle:null,fullTitle:"Importance of Oxidative Stress and Antioxidant System in Health and Disease",slug:null,publishedDate:null,bookSignature:"Associate Prof. Suna Sabuncuoglu and Dr. Ahmet Yalcinkaya",coverURL:"https://cdn.intechopen.com/books/images_new/11671.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80356-330-5",printIsbn:"978-1-80356-329-9",pdfIsbn:"978-1-80356-331-2",isAvailableForWebshopOrdering:!0,editors:[{id:"270856",title:"Associate Prof.",name:"Suna",middleName:null,surname:"Sabuncuoglu",slug:"suna-sabuncuoglu",fullName:"Suna Sabuncuoglu"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The classification of AMD",level:"1"},{id:"sec_3",title:"3. Oxidative processes and the onset of AMD",level:"1"},{id:"sec_4",title:"4. The synthesis of free radicals during light exposure",level:"1"},{id:"sec_5",title:"5. The synthesis of oxidatively modified compounds in the eye, by the action of free radicals",level:"1"},{id:"sec_6",title:"6. The pathophisiology of AMD-Drusen formation",level:"1"},{id:"sec_7",title:"7. Oxidative stress and choroidal vascular changes in AMD",level:"1"},{id:"sec_8",title:"8. Other mechanisms involved in the development of neovascular AMD",level:"1"},{id:"sec_9",title:"9. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Čolak E, Majkić-Singh N, Žorić L, Radosavljević A, Kosanović-Jaković N. The role of CRP and inflammation in the pathogenesis of age-related macular degeneration. Biochemia Medica (Zagreb). 2012;22:39-48'},{id:"B2",body:'Klein R, Klein BE, Jensen SC, Meuer SM. 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British Journal of Pharmacology. 2008;29:621-628'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Emina Čolak",address:"emina.colak.bg@gmail.com",affiliation:'
University Clinical Centre of Serbia, Institute of Medical Biochemistry, Serbia
Department for Haematology and Transfusion, University Clinical Centre of Serbia, Clinic for Gynaecology and Obstetrics, Serbia
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As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
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The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
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OAPF Publishing Options
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1,400 GBP Chapter - Edited Volume
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850 GBP Chapter - Book Series Topic (Annual Volume)
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10,000 GBP Monograph - Long Form
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4,000 GBP Compacts Monograph - Short Form
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850 GBP Journal Article (Across Portfolio)
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During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
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*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\\n\\n
Services included are:
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An online manuscript tracking system to facilitate your work
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Personal contact and support throughout the publishing process from your dedicated Author Service Manager
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English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
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XML Typesetting and pagination - web (PDF, HTML) and print files preparation
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Discoverability - electronic citation and linking via DOI
\\n\\t
Permanent and unrestricted online access to your work
\\n
\\n\\n
What isn't covered by the Open Access Publishing Fee?
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If your manuscript:
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\\n\\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
\\n\\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\\n
\\n\\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\\n\\n
Open Access Funding
\\n\\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\\n\\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\\n\\n
Added Value of Publishing with IntechOpen
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Choosing to publish with IntechOpen ensures the following benefits:
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Indexing and listing across major repositories, see details ...
\\n\\t
Long-term archiving
\\n\\t
Visibility on the world's strongest OA platform
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Live Performance Metrics to track readership and the impact of your chapter
\\n\\t
Dissemination and Promotion
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\\n\\n
Benefits of Publishing with IntechOpen
\\n\\n
\\n\\t
Proven world leader in Open Access book publishing with over 10 years experience
\\n\\t
+5,700 OA books published
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Most competitive prices in the market
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Fully compliant with OA funding requirements
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Optimized processes that assure your research is made available to the scientific community without delay
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Personal support during every step of the publication process
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+184,650 citations in Web of Science databases
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Currently strongest OA platform with over 175 million downloads
As a gold Open Access publisher, an Open Access Publishing Fee is payable on acceptance following peer review of the manuscript. In return, we provide high quality publishing services and exclusive benefits for all contributors. IntechOpen is the trusted publishing partner of over 140,000 international scientists and researchers.
\n\n
The Open Access Publishing Fee (OAPF) is payable only after your book chapter, monograph or journal article is accepted for publication.
\n\n
OAPF Publishing Options
\n\n
\n\t
1,400 GBP Chapter - Edited Volume
\n\t
850 GBP Chapter - Book Series Topic (Annual Volume)
\n\t
10,000 GBP Monograph - Long Form
\n\t
4,000 GBP Compacts Monograph - Short Form
\n\t
850 GBP Journal Article (Across Portfolio)
\n
\n\n
During the launching phase journals do not charge an APC, rather they will be funded by IntechOpen.
\n\n
*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
\n\n
Services included are:
\n\n
\n\t
An online manuscript tracking system to facilitate your work
\n\t
Personal contact and support throughout the publishing process from your dedicated Author Service Manager
\n\t
Assurance that your manuscript meets the highest publishing standards
\n\t
English language copyediting and proofreading, including the correction of grammatical, spelling, and other common errors
\n\t
XML Typesetting and pagination - web (PDF, HTML) and print files preparation
\n\t
Discoverability - electronic citation and linking via DOI
\n\t
Permanent and unrestricted online access to your work
\n
\n\n
What isn't covered by the Open Access Publishing Fee?
\n\n
If your manuscript:
\n\n
\n\t
Exceeds the number of pages defined by the publishing guidelines, an additional fee per page may be required
\n\t
If a manuscript requires Heavy Editing or Language Polishing, this will incur additional fees.
\n
\n\n
Your Author Service Manager will inform you of any items not covered by the OAPF and provide exact information regarding those additional costs before proceeding.
\n\n
Open Access Funding
\n\n
To explore funding opportunities and learn more about how you can finance your IntechOpen publication, go to our Open Access Funding page. IntechOpen offers expert assistance to all of its Authors. We can support you in approaching funding bodies and institutions in relation to publishing fees by providing information about compliance with the Open Access policies of your funder or institution. We can also assist with communicating the benefits of Open Access in order to support and strengthen your funding request and provide personal guidance through your application process. You can contact us at funders@intechopen.com for further details or assistance.
\n\n
For Authors who are still unable to obtain funding from their institutions or research funding bodies for individual projects, IntechOpen does offer the possibility of applying for a Waiver to offset some or all processing feed. Details regarding our Waiver Policy can be found here.
\n\n
Added Value of Publishing with IntechOpen
\n\n
Choosing to publish with IntechOpen ensures the following benefits:
\n\n
\n\t
Indexing and listing across major repositories, see details ...
\n\t
Long-term archiving
\n\t
Visibility on the world's strongest OA platform
\n\t
Live Performance Metrics to track readership and the impact of your chapter
\n\t
Dissemination and Promotion
\n
\n\n
Benefits of Publishing with IntechOpen
\n\n
\n\t
Proven world leader in Open Access book publishing with over 10 years experience
\n\t
+5,700 OA books published
\n\t
Most competitive prices in the market
\n\t
Fully compliant with OA funding requirements
\n\t
Optimized processes that assure your research is made available to the scientific community without delay
\n\t
Personal support during every step of the publication process
\n\t
+184,650 citations in Web of Science databases
\n\t
Currently strongest OA platform with over 175 million downloads
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This has compromised the ability of the environment to foster life and render its intrinsic values. Heavy metals are known to be naturally occurring compounds, but anthropogenic activities introduce them in large quantities in different environmental compartments. This leads to the environment’s ability to foster life being reduced as human, animal, and plant health become threatened. This occurs due to bioaccumulation in the food chains as a result of the nondegradable state of the heavy metals. Remediation of heavy metals requires special attention to protect soil quality, air quality, water quality, human health, animal health, and all spheres as a collection. Developed physical and chemical heavy metal remediation technologies are demanding costs which are not feasible, time-consuming, and release additional waste to the environment. This chapter summarises the problems related to heavy metal pollution and various remediation technologies. A case study in South Africa mines were also used.",book:{id:"6534",slug:"heavy-metals",title:"Heavy Metals",fullTitle:"Heavy Metals"},signatures:"Vhahangwele Masindi and Khathutshelo L. 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H. Gulrez, Saphwan Al-Assaf and Glyn O Phillips",authors:[{id:"58120",title:"Prof.",name:"Saphwan",middleName:null,surname:"Al-Assaf",slug:"saphwan-al-assaf",fullName:"Saphwan Al-Assaf"}]}],mostDownloadedChaptersLast30Days:[{id:"35255",title:"Mechanical Transmissions Parameter Modelling",slug:"mechanical-transmissions-parameter-modelling",totalDownloads:7458,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"1982",slug:"mechanical-engineering",title:"Mechanical Engineering",fullTitle:"Mechanical Engineering"},signatures:"Isad Saric, Nedzad Repcic and Adil Muminovic",authors:[{id:"101313",title:"Prof.",name:"Isad",middleName:null,surname:"Saric",slug:"isad-saric",fullName:"Isad Saric"}]},{id:"68505",title:"Research Design and Methodology",slug:"research-design-and-methodology",totalDownloads:25181,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"There are a number of approaches used in this research method design. The purpose of this chapter is to design the methodology of the research approach through mixed types of research techniques. The research approach also supports the researcher on how to come across the research result findings. In this chapter, the general design of the research and the methods used for data collection are explained in detail. It includes three main parts. The first part gives a highlight about the dissertation design. The second part discusses about qualitative and quantitative data collection methods. The last part illustrates the general research framework. The purpose of this section is to indicate how the research was conducted throughout the study periods.",book:{id:"8511",slug:"cyberspace",title:"Cyberspace",fullTitle:"Cyberspace"},signatures:"Kassu Jilcha Sileyew",authors:[{id:"292841",title:"Ph.D.",name:"Kassu",middleName:null,surname:"Jilcha Sileyew",slug:"kassu-jilcha-sileyew",fullName:"Kassu Jilcha Sileyew"}]},{id:"67558",title:"Polymerase Chain Reaction (PCR): Principle and Applications",slug:"polymerase-chain-reaction-pcr-principle-and-applications",totalDownloads:10685,totalCrossrefCites:8,totalDimensionsCites:18,abstract:"The characterization of the diversity of species living within ecosystems is of major scientific interest to understand the functioning of these ecosystems. It is also becoming a societal issue since it is necessary to implement the conservation or even the restoration of biodiversity. Historically, species have been described and characterized on the basis of morphological criteria, which are closely linked by environmental conditions or which find their limits especially in groups where they are difficult to access, as is the case for many species of microorganisms. The need to understand the molecular mechanisms in species has made the PCR an indispensable tool for understanding the functioning of these biological systems. A number of markers are now available to detect nuclear DNA polymorphisms. In genetic diversity studies, the most frequently used markers are microsatellites. The study of biological complexity is a new frontier that requires high-throughput molecular technology, high speed computer memory, new approaches to data analysis, and the integration of interdisciplinary skills.",book:{id:"7728",slug:"synthetic-biology-new-interdisciplinary-science",title:"Synthetic Biology",fullTitle:"Synthetic Biology - New Interdisciplinary Science"},signatures:"Karim Kadri",authors:[{id:"290766",title:"Dr.",name:"Kadri",middleName:null,surname:"Karim",slug:"kadri-karim",fullName:"Kadri Karim"}]},{id:"62059",title:"Types of HVAC Systems",slug:"types-of-hvac-systems",totalDownloads:12466,totalCrossrefCites:9,totalDimensionsCites:15,abstract:"HVAC systems are milestones of building mechanical systems that provide thermal comfort for occupants accompanied with indoor air quality. HVAC systems can be classified into central and local systems according to multiple zones, location, and distribution. Primary HVAC equipment includes heating equipment, ventilation equipment, and cooling or air-conditioning equipment. Central HVAC systems locate away from buildings in a central equipment room and deliver the conditioned air by a delivery ductwork system. Central HVAC systems contain all-air, air-water, all-water systems. Two systems should be considered as central such as heating and cooling panels and water-source heat pumps. Local HVAC systems can be located inside a conditioned zone or adjacent to it and no requirement for ductwork. Local systems include local heating, local air-conditioning, local ventilation, and split systems.",book:{id:"6807",slug:"hvac-system",title:"HVAC System",fullTitle:"HVAC System"},signatures:"Shaimaa Seyam",authors:[{id:"247650",title:"M.Sc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"257733",title:"MSc.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"},{id:"395618",title:"Dr.",name:"Shaimaa",middleName:null,surname:"Seyam",slug:"shaimaa-seyam",fullName:"Shaimaa Seyam"}]},{id:"70315",title:"Some Basic and Key Issues of Switched-Reluctance Machine Systems",slug:"some-basic-and-key-issues-of-switched-reluctance-machine-systems",totalDownloads:1268,totalCrossrefCites:0,totalDimensionsCites:1,abstract:"Although switched-reluctance machine (SRM) possesses many structural advantages and application potential, it is rather difficult to successfully control with high performance being comparable to other machines. Many critical affairs must be properly treated to obtain the improved operating characteristics. This chapter presents the basic and key technologies of switched-reluctance machine in motor and generator operations. The contents in this chapter include: (1) structures and governing equations of SRM; (2) some commonly used SRM converters; (3) estimation of key parameters and performance evaluation of SRM drive; (4) commutation scheme, current control scheme, and speed control scheme of SRM drive; (5) some commonly used front-end converters and their operation controls for SRM drive; (6) reversible and regenerative braking operation controls for SRM drive; (7) some tuning issues for SRM drive; (8) operation control and some tuning issues of switched-reluctance generators; and (9) experimental application exploration for SRM systems—(a) wind generator and microgrid and (b) EV SRM drive.",book:{id:"8899",slug:"modelling-and-control-of-switched-reluctance-machines",title:"Modelling and Control of Switched Reluctance Machines",fullTitle:"Modelling and Control of Switched Reluctance Machines"},signatures:"Chang-Ming Liaw, Min-Ze Lu, Ping-Hong Jhou and Kuan-Yu Chou",authors:[{id:"37616",title:"Prof.",name:"Chang-Ming",middleName:null,surname:"Liaw",slug:"chang-ming-liaw",fullName:"Chang-Ming Liaw"},{id:"306461",title:"Mr.",name:"Min-Ze",middleName:null,surname:"Lu",slug:"min-ze-lu",fullName:"Min-Ze Lu"},{id:"306463",title:"Mr.",name:"Ping-Hong",middleName:null,surname:"Jhou",slug:"ping-hong-jhou",fullName:"Ping-Hong Jhou"},{id:"306464",title:"Mr.",name:"Kuan-Yu",middleName:null,surname:"Chou",slug:"kuan-yu-chou",fullName:"Kuan-Yu Chou"}]}],onlineFirstChaptersFilter:{topicId:"1",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"83153",title:"Perspective Chapter: Cryptocurrencies Effectiveness for Nature",slug:"perspective-chapter-cryptocurrencies-effectiveness-for-nature",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106493",abstract:"The rise of cryptocurrencies based on Blockchain platforms have provided multiple solutions for social and nature projects supported by concerned investors with sustainable development initiatives. Speculation and unclear uses of a cryptocurrency plays a negative role for the projects they claim to support. A positive relationship between coin investors and supported projects must position the coin value on the scale of the community involvement among the coin and project issues, thus placing the project results above speculative moves. Coin nature and social based projects may include a decentralized autonomous organization (DAO), combined with a digital currency to contribute to social and nature improvements. This organization provides a framework for the engagement of investors, beneficiaries, and implementation partners, with results measured by reliable third parties. The potential funding from non fiduciary sources for sustainable development targets may be framed under the fundraising and financial solutions models, addressing the cryptocurrency volatility risks with responsible tokenomics in attention to transaction and regulatory issues. Overall, the more clear are the object and transaction issues of a nature conservation project supported by a currency, the more successful it will be in terms of nature and social improvements and the currency valuation for all parties involved.",book:{id:"11551",title:"Blockchain",coverURL:"https://cdn.intechopen.com/books/images_new/11551.jpg"},signatures:"Luiz Cruz Villares"},{id:"83163",title:"Robust Control Algorithm for Drones",slug:"robust-control-algorithm-for-drones",totalDownloads:0,totalDimensionsCites:0,doi:"10.5772/intechopen.105966",abstract:"Drones, also known as Crewless Aircrafts (CAs), are by far the most multi - level and multi developing technologies of the modern period. This technology has recently found various uses in the transportation area, spanning from traffic monitoring applicability to traffic engineering for overall traffic flow and efficiency improvements. Because of its non-linear characteristics and under-actuated design, the CA seems to be an excellent platform to control systems study. Following a brief overview of the system, the various evolutionary and robust control algorithms were examined, along with their benefits and drawbacks. In this chapter, a mathematical and theoretical model of a CA’s dynamics is derived, using Euler’s and Newton’s laws. The result is a linearized version of the model, from which a linear controller, the Linear Quadratic Regulator (LQR), is generated. Furthermore, the performance of these nonlinear control techniques is compared to that of the LQR. Feedback-linearization controller when implemented in the simulation for the chapter, the results for the same was better than any other algorithm when compared with. The suggested regulatory paradigm of the CA-based monitoring system and analysis study will be the subject of future research, with a particular emphasis on practical applications.",book:{id:"11522",title:"Aeronautics - New Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11522.jpg"},signatures:"Parul Priya and Sushma S. Kamlu"},{id:"83171",title:"Some Results on the Non-Homogeneous Hofmann Process",slug:"some-results-on-the-non-homogeneous-hofmann-process",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106422",abstract:"The classical counting processes (Poisson and negative binomial) are the most traditional discrete counting processes (DCPs); however, these are based on a set of rigid assumptions. We consider a non-homogeneous counting process (which we name non-homogeneous Hofmann process – NHP) that can generate the classical counting processes (CCPs) as special cases, and also allows modeling counting processes for event history data, which usually exhibit under- or over-dispersion. We present some results of this process that will allow us to use it in other areas and establish both the probability mass function (pmf) and the cumulative distribution function (cdf) using transition intensities. This counting process (CP) will allow other researchers to work on modelling the CP, where data dispersion exists in an efficient and more flexible way.",book:{id:"12021",title:"Applied Probability Theory - New Perspectives, Recent Advances and Trends",coverURL:"https://cdn.intechopen.com/books/images_new/12021.jpg"},signatures:"Gerson Yahir Palomino Velandia and José Alfredo Jiménez Moscoso"},{id:"83152",title:"Recycled Synthetic Polymer-Based Electrospun Membranes for Filtering Applications",slug:"recycled-synthetic-polymer-based-electrospun-membranes-for-filtering-applications",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106683",abstract:"Synthetic polymers have been widely applied in various commercial and household applications owing to their fascinating properties of low-cost, lightweight, and processability. However, increasing population and living standards and rising demand for non-biodegradable polymers have led to the accumulation of plastic pollution resulting in the current environmental crisis. Current waste management methods such as landfilling or incineration do not solve these environmental issues. On the other hand, recycling plastic waste is the most valuable strategy for dealing with waste as raw material for high-value products. One of such products is filter membranes. Polymer fiber membranes as masks in pandemics have been one of the most sought-after products in recent years. Some types of plastic waste became a material source for the development of filter materials, which could contribute to the protection of human health. Utilizing the simple, cheap, and industrially available technological solution is also needed. Given the number of advantages, electrospinning is such a beneficial solution. The electrospun polymer waste-based membranes show excellent filtration performance and can carry many other functionalities. Therefore, this review article presents a brief overview of electrospun nanofibrous membranes based on synthetic plastic waste and summarizes the filtration performance of such membranes. This review will discuss the future perspectives of electrospun membranes as well.",book:{id:"11462",title:"Recent Developments in Nanofibers Research",coverURL:"https://cdn.intechopen.com/books/images_new/11462.jpg"},signatures:"Alena Opálková Šišková, Heba M. Abdallah, Smaher Mosad Elbayomi and Anita Eckstein Andicsová"},{id:"83166",title:"General Drag Correlations for Particle-Fluid System",slug:"general-drag-correlations-for-particle-fluid-system",totalDownloads:0,totalDimensionsCites:null,doi:"10.5772/intechopen.106427",abstract:"Particle-fluid flows are commonly encountered in industrial applications. It is of great importance to understand the fundamentals governing the behavior of such a flow system for better process design, control, and optimization. Generally, the particle-fluid flow behavior is strongly influenced by the interaction forces between fluid and particles. Among the various kinds of particle-fluid interaction forces, the drag force is the most essential. This chapter reviews the modeling of drag force for particle-fluid systems: from single particle to multiple particles, monosize to multisize, spherical to nonspherical, and Newtonian fluid to non-Newtonian fluid. Typical drag correlations in the literature are compared and assessed in terms of physical meaning, consistency, and generality.",book:{id:"11498",title:"Boundary Layer Flows - Modelling, Computation, and Applications of Laminar, Turbulent Incompressible and Compressible Flows",coverURL:"https://cdn.intechopen.com/books/images_new/11498.jpg"},signatures:"Zheng Qi, Shibo Kuang, Liangwan Rong, Kejun Dong and Aibing Yu"},{id:"82272",title:"Landslide Movement Monitoring with InSAR Technologies",slug:"landslide-movement-monitoring-with-insar-technologies",totalDownloads:2,totalDimensionsCites:0,doi:"10.5772/intechopen.105058",abstract:"Synthetic aperture radar interferometry (InSAR) is a technology that has been widely used in many areas, such as topographic mapping, land and resource survey, geological exploration, disaster prevention and mitigation, volcanic and seismic monitor and so on. Landslide, as a representative geohazard, include a wide range of phenomena involving downhill ground movement. InSAR, a technology which can measure surface deformation at the millimeter level over serveral days or years, is suitable to detect landslides with chronical and widespread movements. In this chapter, we introduce main process methods of InSAR data, including Persistent Scatter Interferometry (PSInSAR) and Distributed Scatter Interferometry (DSInSAR). A study area, Daguan County Town, one of the most landslide-prone areas in China is induced to demonstrate the practicability of InSAR in detecting landslides. Combined InSAR results with geological, geotechnical and meterological data, the distribution of landslide in Daguan County in spatial and temporal dimensions would be displayed. We also coupling numerical modeling and InSAR for characterizing landslide movements under multiple loads. 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The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). Topics will include general overviews of infections, immunopathology, diagnosis, treatment, epidemiology, etiology, and current clinical recommendations for managing infectious diseases. Ongoing issues, recent advances, and future diagnostic approaches and therapeutic strategies will also be discussed. This book series will focus on various aspects and properties of infectious diseases whose deep understanding is essential for safeguarding the human race from losing resources and economies due to pathogens.",coverUrl:"https://cdn.intechopen.com/series/covers/6.jpg",latestPublicationDate:"August 18th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:13,editor:{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. 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He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"3",title:"Bacterial Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",isOpenForSubmission:!0,annualVolume:11399,editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",slug:"tomas-jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",biography:"Tomasz Jarzembowski was born in 1968 in Gdansk, Poland. He obtained his Ph.D. degree in 2000 from the Medical University of Gdańsk (UG). After specialization in clinical microbiology in 2003, he started studying biofilm formation and antibiotic resistance at the single-cell level. In 2015, he obtained his D.Sc. degree. His later study in cooperation with experts in nephrology and immunology resulted in the designation of the new diagnostic method of UTI, patented in 2017. He is currently working at the Department of Microbiology, Medical University of Gdańsk (GUMed), Poland. Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null},{id:"4",title:"Fungal Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",isOpenForSubmission:!0,annualVolume:11400,editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",slug:"yuping-ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",biography:"Dr. Yuping Ran, Professor, Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China. Completed the Course Medical Mycology, the Centraalbureau voor Schimmelcultures (CBS), Fungal Biodiversity Centre, Netherlands (2006). International Union of Microbiological Societies (IUMS) Fellow, and International Emerging Infectious Diseases (IEID) Fellow, Centers for Diseases Control and Prevention (CDC), Atlanta, USA. Diploma of Dermatological Scientist, Japanese Society for Investigative Dermatology. Ph.D. of Juntendo University, Japan. Bachelor’s and Master’s degree, Medicine, West China University of Medical Sciences. Chair of Sichuan Medical Association Dermatology Committee. General Secretary of The 19th Annual Meeting of Chinese Society of Dermatology and the Asia Pacific Society for Medical Mycology (2013). In charge of the Annual Medical Mycology Course over 20-years authorized by National Continue Medical Education Committee of China. Member of the board of directors of the Asia-Pacific Society for Medical Mycology (APSMM). Associate editor of Mycopathologia. Vice-chief of the editorial board of Chinses Journal of Mycology, China. Board Member and Chair of Mycology Group of Chinese Society of Dermatology.",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null},{id:"5",title:"Parasitic Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",isOpenForSubmission:!0,annualVolume:11401,editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",slug:"amidou-samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",biography:"Dr. Amidou Samie is an Associate Professor of Microbiology at the University of Venda, in South Africa, where he graduated for his PhD in May 2008. He joined the Department of Microbiology the same year and has been giving lectures on topics covering parasitology, immunology, molecular biology and industrial microbiology. He is currently a rated researcher by the National Research Foundation of South Africa at category C2. He has published widely in the field of infectious diseases and has overseen several MSc’s and PhDs. His research activities mostly cover topics on infectious diseases from epidemiology to control. His particular interest lies in the study of intestinal protozoan parasites and opportunistic infections among HIV patients as well as the potential impact of childhood diarrhoea on growth and child development. He also conducts research on water-borne diseases and water quality and is involved in the evaluation of point-of-use water treatment technologies using silver and copper nanoparticles in collaboration with the University of Virginia, USA. He also studies the use of medicinal plants for the control of infectious diseases as well as antimicrobial drug resistance.",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},{id:"6",title:"Viral Infectious Diseases",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",isOpenForSubmission:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:14,paginationItems:[{id:"83117",title:"Endothelial Secretome",doi:"10.5772/intechopen.106550",signatures:"Luiza Rusu",slug:"endothelial-secretome",totalDownloads:0,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Luiza",surname:"Rusu"}],book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"83087",title:"Role of Cellular Responses in Periodontal Tissue Destruction",doi:"10.5772/intechopen.106645",signatures:"Nam Cong-Nhat Huynh",slug:"role-of-cellular-responses-in-periodontal-tissue-destruction",totalDownloads:8,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Periodontology - New Insights",coverURL:"https://cdn.intechopen.com/books/images_new/11566.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"83073",title:"Dental and Orofacial Trauma Impacts on Oral-Health-Related—Quality of Life in Children: Low- and Middle-Income Countries",doi:"10.5772/intechopen.105845",signatures:"Yolanda Malele-Kolisa, Nazia Khan, Mpho P. 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She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7139",title:"Current Approaches in Orthodontics",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7139.jpg",slug:"current-approaches-in-orthodontics",publishedDate:"April 10th 2019",editedByType:"Edited by",bookSignature:"Belma Işık Aslan and Fatma Deniz Uzuner",hash:"2c77384eeb748cf05a898d65b9dcb48a",volumeInSeries:2,fullTitle:"Current Approaches in Orthodontics",editors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null}]},{type:"book",id:"7572",title:"Trauma in Dentistry",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7572.jpg",slug:"trauma-in-dentistry",publishedDate:"July 3rd 2019",editedByType:"Edited by",bookSignature:"Serdar Gözler",hash:"7cb94732cfb315f8d1e70ebf500eb8a9",volumeInSeries:3,fullTitle:"Trauma in Dentistry",editors:[{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",institutionURL:null,country:{name:"Turkey"}}}]},{type:"book",id:"7060",title:"Gingival Disease",subtitle:"A Professional Approach for Treatment and Prevention",coverURL:"https://cdn.intechopen.com/books/images_new/7060.jpg",slug:"gingival-disease-a-professional-approach-for-treatment-and-prevention",publishedDate:"October 23rd 2019",editedByType:"Edited by",bookSignature:"Alaa Eddin Omar Al Ostwani",hash:"b81d39988cba3a3cf746c1616912cf41",volumeInSeries:4,fullTitle:"Gingival Disease - A Professional Approach for Treatment and Prevention",editors:[{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. 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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. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. 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 scientist and Principal Investigator 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 the 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 artificial intelligence-based analyses of exosomal Raman signatures. Dr. Paul also works on spatial multiplex immunofluorescence-based tissue mapping to understand the immune repertoire in lung cancer. Dr. Paul has published in more than sixty-five peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award and the 2022 AAISCR-R Vijayalaxmi Award for Innovative Cancer Research. He is 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:"14",type:"subseries",title:"Cell and Molecular Biology",keywords:"Omics (Transcriptomics; Proteomics; Metabolomics), Molecular Biology, Cell Biology, Signal Transduction and Regulation, Cell Growth and Differentiation, Apoptosis, Necroptosis, Ferroptosis, Autophagy, Cell Cycle, Macromolecules and Complexes, Gene Expression",scope:"The Cell and Molecular Biology topic within the IntechOpen Biochemistry Series aims to rapidly publish contributions on all aspects of cell and molecular biology, including aspects related to biochemical and genetic research (not only in humans but all living beings). We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics include, but are not limited to: Advanced techniques of cellular and molecular biology (Molecular methodologies, imaging techniques, and bioinformatics); Biological activities at the molecular level; Biological processes of cell functions, cell division, senescence, maintenance, and cell death; Biomolecules interactions; Cancer; Cell biology; Chemical biology; Computational biology; Cytochemistry; Developmental biology; Disease mechanisms and therapeutics; DNA, and RNA metabolism; Gene functions, genetics, and genomics; Genetics; Immunology; Medical microbiology; Molecular biology; Molecular genetics; Molecular processes of cell and organelle dynamics; Neuroscience; Protein biosynthesis, degradation, and functions; Regulation of molecular interactions in a cell; Signalling networks and system biology; Structural biology; Virology and microbiology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11410,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Rosa María Martínez-Espinosa is a Full Professor of Biochemistry and Molecular Biology at the University of Alicante, Spain, and has been the vice president of International Relations and Development Cooperation at this university since 2010. She created the research group in applied biochemistry in 2017 (https://web.ua.es/en/appbiochem/), and from 1999 to the present has made more than 200 contributions to Spanish and international conferences. Furthermore, she has around seventy-five scientific publications in indexed journals, eighty book chapters, and one patent to her credit. Her research work focuses on microbial metabolism (particularly on extremophile microorganisms), purification and characterization of enzymes with potential industrial and biotechnological applications, protocol optimization for genetically manipulating microorganisms, gene regulation characterization, carotenoid (pigment) production, and design and development of contaminated water and soil bioremediation processes by means of microorganisms. This research has received competitive public grants from the European Commission, the Spanish Ministry of Economy and Competitiveness, the Valencia Region Government, and the University of Alicante.",institutionString:"University of Alicante",institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null,series:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983"},editorialBoard:[{id:"79367",title:"Dr.",name:"Ana Isabel",middleName:null,surname:"Flores",slug:"ana-isabel-flores",fullName:"Ana Isabel Flores",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRpIOQA0/Profile_Picture_1632418099564",institutionString:null,institution:{name:"Hospital Universitario 12 De Octubre",institutionURL:null,country:{name:"Spain"}}},{id:"328234",title:"Ph.D.",name:"Christian",middleName:null,surname:"Palavecino",slug:"christian-palavecino",fullName:"Christian Palavecino",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000030DhEhQAK/Profile_Picture_1628835318625",institutionString:null,institution:{name:"Central University of Chile",institutionURL:null,country:{name:"Chile"}}},{id:"186585",title:"Dr.",name:"Francisco Javier",middleName:null,surname:"Martin-Romero",slug:"francisco-javier-martin-romero",fullName:"Francisco Javier Martin-Romero",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSB3HQAW/Profile_Picture_1631258137641",institutionString:null,institution:{name:"University of Extremadura",institutionURL:null,country:{name:"Spain"}}}]},onlineFirstChapters:{paginationCount:1,paginationItems:[{id:"82380",title:"Evolution of Parasitism and Pathogenic Adaptations in Certain Medically Important Fungi",doi:"10.5772/intechopen.105206",signatures:"Gokul Shankar Sabesan, Ranjit Singh AJA, Ranjith Mehenderkar and Basanta Kumar Mohanty",slug:"evolution-of-parasitism-and-pathogenic-adaptations-in-certain-medically-important-fungi",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Fungal Infectious Diseases - 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\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
\r\n
\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
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Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. 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Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction"}],annualVolumeBook:{},thematicCollection:[],selectedSeries:{title:"Infectious Diseases",id:"6"},selectedSubseries:null},seriesLanding:{item:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188",scope:"This series will provide a comprehensive overview of recent research trends in various Infectious Diseases (as per the most recent Baltimore classification). 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He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},subseries:[{id:"3",title:"Bacterial Infectious Diseases",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools",scope:"
\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
\r\n
\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
",annualVolume:11399,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",editor:{id:"205604",title:"Dr.",name:"Tomas",middleName:null,surname:"Jarzembowski",fullName:"Tomas Jarzembowski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKriQAG/Profile_Picture_2022-06-16T11:01:31.jpg",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null,editorialBoard:[{id:"190041",title:"Dr.",name:"Jose",middleName:null,surname:"Gutierrez Fernandez",fullName:"Jose Gutierrez Fernandez",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"156556",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Mascellino",fullName:"Maria Teresa Mascellino",profilePictureURL:"https://mts.intechopen.com/storage/users/156556/images/system/156556.jpg",institutionString:"Sapienza University",institution:{name:"Sapienza University of Rome",institutionURL:null,country:{name:"Italy"}}},{id:"164933",title:"Prof.",name:"Mónica Alexandra",middleName:null,surname:"Sousa Oleastro",fullName:"Mónica Alexandra Sousa Oleastro",profilePictureURL:"https://mts.intechopen.com/storage/users/164933/images/system/164933.jpeg",institutionString:"National Institute of Health Dr Ricardo Jorge",institution:{name:"National Institute of Health Dr. Ricardo Jorge",institutionURL:null,country:{name:"Portugal"}}}]},{id:"4",title:"Fungal Infectious Diseases",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",annualVolume:11400,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",editor:{id:"174134",title:"Dr.",name:"Yuping",middleName:null,surname:"Ran",fullName:"Yuping Ran",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9d6QAC/Profile_Picture_1630330675373",institutionString:null,institution:{name:"Sichuan University",institutionURL:null,country:{name:"China"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"302145",title:"Dr.",name:"Felix",middleName:null,surname:"Bongomin",fullName:"Felix Bongomin",profilePictureURL:"https://mts.intechopen.com/storage/users/302145/images/system/302145.jpg",institutionString:null,institution:{name:"Gulu University",institutionURL:null,country:{name:"Uganda"}}},{id:"45803",title:"Ph.D.",name:"Payam",middleName:null,surname:"Behzadi",fullName:"Payam Behzadi",profilePictureURL:"https://mts.intechopen.com/storage/users/45803/images/system/45803.jpg",institutionString:"Islamic Azad University, Tehran",institution:{name:"Islamic Azad University, Tehran",institutionURL:null,country:{name:"Iran"}}}]},{id:"5",title:"Parasitic Infectious Diseases",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",annualVolume:11401,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",editor:{id:"67907",title:"Dr.",name:"Amidou",middleName:null,surname:"Samie",fullName:"Amidou Samie",profilePictureURL:"https://mts.intechopen.com/storage/users/67907/images/system/67907.jpg",institutionString:null,institution:{name:"University of Venda",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"188881",title:"Dr.",name:"Fernando José",middleName:null,surname:"Andrade-Narváez",fullName:"Fernando José Andrade-Narváez",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRIV7QAO/Profile_Picture_1628834308121",institutionString:null,institution:{name:"Autonomous University of Yucatán",institutionURL:null,country:{name:"Mexico"}}},{id:"269120",title:"Dr.",name:"Rajeev",middleName:"K.",surname:"Tyagi",fullName:"Rajeev Tyagi",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRaBqQAK/Profile_Picture_1644331884726",institutionString:"CSIR - Institute of Microbial Technology, India",institution:null},{id:"336849",title:"Prof.",name:"Ricardo",middleName:null,surname:"Izurieta",fullName:"Ricardo Izurieta",profilePictureURL:"https://mts.intechopen.com/storage/users/293169/images/system/293169.png",institutionString:null,institution:{name:"University of South Florida",institutionURL:null,country:{name:"United States of America"}}}]},{id:"6",title:"Viral Infectious Diseases",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",annualVolume:11402,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",fullName:"Emmanuel Drouet",profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",institutionString:null,institution:{name:"Grenoble Alpes University",institutionURL:null,country:{name:"France"}}},{id:"188219",title:"Prof.",name:"Imran",middleName:null,surname:"Shahid",fullName:"Imran Shahid",profilePictureURL:"https://mts.intechopen.com/storage/users/188219/images/system/188219.jpeg",institutionString:null,institution:{name:"Umm al-Qura University",institutionURL:null,country:{name:"Saudi Arabia"}}},{id:"214235",title:"Dr.",name:"Lynn",middleName:"S.",surname:"Zijenah",fullName:"Lynn Zijenah",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSEJGQA4/Profile_Picture_1636699126852",institutionString:null,institution:{name:"University of Zimbabwe",institutionURL:null,country:{name:"Zimbabwe"}}},{id:"178641",title:"Dr.",name:"Samuel Ikwaras",middleName:null,surname:"Okware",fullName:"Samuel Ikwaras Okware",profilePictureURL:"https://mts.intechopen.com/storage/users/178641/images/system/178641.jpg",institutionString:null,institution:{name:"Uganda Christian University",institutionURL:null,country:{name:"Uganda"}}}]}]}},libraryRecommendation:{success:null,errors:{},institutions:[]},route:{name:"profile.detail",path:"/profiles/149526",hash:"",query:{},params:{id:"149526"},fullPath:"/profiles/149526",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var e;(e=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(e)}()