More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
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Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
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“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
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Additionally, each book published by IntechOpen contains original content and research findings.
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We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\n
Simba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
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IntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\n
Since the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\n
Our breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n
“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\n
Additionally, each book published by IntechOpen contains original content and research findings.
\n\n
We are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n
\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"291",leadTitle:null,fullTitle:"Theoretical Biomechanics",title:"Theoretical Biomechanics",subtitle:null,reviewType:"peer-reviewed",abstract:"During last couple of years there has been an increasing recognition that problems arising in biology or related to medicine really need a multidisciplinary approach. For this reason some special branches of both applied theoretical physics and mathematics have recently emerged such as biomechanics, mechanobiology, mathematical biology, biothermodynamics. \nThis first section of the book, General notes on biomechanics and mechanobiology, comprises from theoretical contributions to Biomechanics often providing hypothesis or rationale for a given phenomenon that experiment or clinical study cannot provide. It deals with mechanical properties of living cells and tissues, mechanobiology of fracture healing or evolution of locomotor trends in extinct terrestrial giants. The second section, Biomechanical modelling, is devoted to the rapidly growing field of biomechanical models and modelling approaches to improve our understanding about processes in human body. The last section called Locomotion and joint biomechanics is a collection of works on description and analysis of human locomotion, joint stability and acting forces.",isbn:null,printIsbn:"978-953-307-851-9",pdfIsbn:"978-953-51-6721-1",doi:"10.5772/816",price:139,priceEur:155,priceUsd:179,slug:"theoretical-biomechanics",numberOfPages:416,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"2aa3a76485400839fc28dfab42fbddc2",bookSignature:"Vaclav Klika",publishedDate:"November 25th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/291.jpg",numberOfDownloads:63980,numberOfWosCitations:79,numberOfCrossrefCitations:36,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:114,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:229,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 3rd 2010",dateEndSecondStepPublish:"December 1st 2010",dateEndThirdStepPublish:"April 7th 2011",dateEndFourthStepPublish:"May 7th 2011",dateEndFifthStepPublish:"July 6th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"8254",title:"Dr.",name:"Vaclav",middleName:null,surname:"Klika",slug:"vaclav-klika",fullName:"Vaclav Klika",profilePictureURL:"https://mts.intechopen.com/storage/users/8254/images/1758_n.jpg",biography:"Dr. Václav Klika, received his MS (2006) and PhD (2009) from the Czech Technical University in Prague, FNSPE, Mathematical Engineering. Since 2004, he has gained valuable experience as a researcher at Institute of Thermomechanics, Academy of Sciences of Czech Republic. He is currently an assistant professor at Department of Mathematics, FNSPE, Czech Technical University in Prague. His research interests include non-equilibrium thermodynamics, mathematical biology, biomechanics, and analytical solutions in fluid dynamics. 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\n
1. Introduction
\n
\n
1.1 Historical background
\n
In the 1950s Italian based company; Farmitalia research laboratory began a research program in finding the anticancer compounds from soil-based microbes. In the process of research collected a soil sample from the castle named as castle Del monte, which was built in the 13th century. The collected soil sample contains new strains of bacterial species and isolated from it. The separated microbe recognised with the name Streptomyces peucetius which is typically produces a significant red pigment. The antibiotic produced from this bacterium discovered to be efficient in treating the tumours especially solid tumours while researching on mice. Since a group of French scientists found the same compound about at the same time, they agreed to call the antibiotic daunorubicin, referring to the two nations. In which, Dauni refers to the pre-Roman tribe who inhabited the position in Italy where the species of bacteria were isolated and ruby represents the colour in Italy. The clinical trials of daunorubicin were began in 1960s and confirmed as successful in treating the lymphoma and acute leukaemia [1, 2]. After a short note of the time, in 1967 daunorubicin was discovered to be cause fatal cardiotoxicity. Then, by using nitroso-N-methyl urethane, the Italian research company mutated the strains of Streptomyces peucetius and developed a new strain of bacterial species that produces 14-hydroxylated daunorubicin, also known as Adriamycin (named after the Adriatic Sea), then changed its name to doxorubicin, which has a strong therapeutic index, but cardiac toxicity remains [3].
\n
\n
\n
1.2 Doxorubicin chemical structure and properties
\n
Doxorubicin (DOX) is an anthracycline antibiotic structurally similar to Daunorubicin as natural anti-cancer antibiotic used in cancer treatment. Its anticancer effect produced intercalating with DNA and this will inhibit DNA transcription and replication; and by binding to the topoisomerase II enzyme and inhibit the resealing of the DNA fragments. The presence of sugar moiety attached to the anthracycline ring further enhances the binding to phosphate and sugar moieties in to DNA. This led to stops the proliferation of cancer cells in the host [4]. Besides, the presence of quinone moiety apart from contributing the cytolytic ability by generating the intermediate radicals, which further react with the oxygen and forms superoxide ions and these ions also shows a high tendency towards the damaging the cell membranes causes a dose-dependent the cardiac myopathy [5, 6].
\n
\n\n\n
\n\n
\n
The Doxorubicin is mainly used in case of patients suffering from Breast cancer, ovarian cancers, lung cancers, bladder cancers, leukaemia (acute lymphoblastic leukaemia, acute myeloid leukaemia) and AIDS-related Kaposi’s sarcoma and various solid tumours. DOX also used in combination with other agents in case of bone sarcomas, soft tissue sarcomas, uterus cancer, endoblastoma cancer, cervix cancer, pancreatic cancer, Ewing’s sarcoma, mesothelioma, multiple myeloma, Wilms tumour and in neuroblastoma [7, 8].
\n
\n
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2. Doxorubicin side effects
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2.1 Hepatotoxicity
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Liver is one of the essential organs of the body; it plays a major role in metabolism and detoxification of several drugs. This can explains why liver is the primary body organ affected by chemotherapy. Despite being cytostatic and cytotoxic effects on cancer cells DOX documented to accumulate in the various tissues include liver cells. In humans, it is estimated as 50% of DOX eliminated in un-exchanged form, the remainder dose metabolised through hydroxylation, semiquinone formation [9]. The major pathway for biotransformation of DOX is catalysed by the NADPH-dependent carbonyl reductase, Nitric oxide synthase, cytochrome P-450 reductase, aldo-keto reductase enzymes. The hydroxylation occurs at C-13 carbon in group commonly reaction referred as electron reduction forms the secondary alcohol metabolites [10, 11, 12, 13]. The metabolized intermediates in the presence of oxygen converted to carbonyl moieties resulting in generation of Superoxide anions and hydrogen peroxides causes peroxidation of lipids in membranes of cell, aggregation of proteins (\nFigure 1\n) [13, 14, 15].
\n
The regenerative capacity of liver is more can cure the damage caused by various agents such as DOX, which causes damage and decreases the regeneration of liver cells by increasing the oxidative stress due to the radical generation by oxidation in hepatocytes. The generated radical causes decrease in GSH levels, damages in DNA and also act as secondary metabolites in in many metabolic pathways which includes in cell proliferation and cell death [16, 17, 18]. To overcome such situations liver employs the efflux mechanisms, the efflux of DOX is achieved through from liver by ATP dependent ABC proteins (P-glycoprotein) which increase the efflux of the intracellular DOX and maintain the homeostasis. The mechanism uses large quantity of energy but with the presence of the DOX in liver cells decreases the ATP production and increases the ADP and Pi within the cells [19, 20, 21]. Due to this effect sometimes liver cells can’t able to regenerate from DOX induced effects and causes hepatotoxicity.
\n
Figure 1.
DOX mediated effects on the liver.
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2.2 Nephropathy
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Besides maintaining the homeostasis by regulating the body fluids, kidneys work to reabsorb the low concentrations general constituents in the body and also remove the foreign substances like drugs or other kinds of agents. For this kind of reasons kidneys considered as metastatic organs of human beings [22]. The regenerative capacity of the kidneys is low when compared to the liver and highly susceptible to epithelial degeneration occurs at renal glomerulus where the filtration occurs may lead to the glomerulosclerosis [23].
\n
DOX interferes with the glandular podocytes of the kidney and cause nephropathy the most accepted mechanism behind the nephropathy is an accumulation of proteinuria in the kidney by the local passage of leaked proteins [23]. Increase in the structural changes in nephrons causes hypertension, steroid resistance, high incidents of renal failure and glomerular vacuolization, inflammation, tubular dilation, intestinal fibrosis, permeability differences in the glomerulus, and certain conditions like hypoalbuminemia, dyslipidemia, hypercoagulation, size differences in kidney most likely observed [24]. A study conducted on the DOX effect on the mitochondria by the Lebrecht suggested that DOX interfere the mitochondrial mtDNA in the kidney with ROS produced from it and accelerating the damaging of the nephron. Another study reports suggesting that DOX forming an iron-mediated anthracycline complex, which produces the ROS led to an increase in the oxidative lesions in the cells causing damage to the critical cellular components [25, 26].
\n
The decreasing the levels of the GSH (Glutathione), vitamin E levels and other natural oxidant levels production from the liver cells enhances the nephropathic conditions which may initially affect the Bowman’s capsule thickness and the glomerular tuft of the nephron. The study conducted by Rook et al. [26] Reported as Angiotensin-converting enzyme is said to be one of the responsible factors for tissue damage triggered by the DOX therapy. The ACE is causing the pro-inflammatory, pro-fibrotic effects which make interference in the kidney and nephrons to maintain the glomerular pressure and filtration rate of blood [27, 28]. The cases of nephropathy and proteinuria are rare in humans susceptibility towards such condition based on the genetic makeup of the individual.
\n
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2.3 Neurotoxicity
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The brain is the largest and most complex organ in the human body contains about 100 billion neurons with 1 trillion established connections throughout the body. DOX is not able to transfer through the blood–brain barrier (BBB), therefore DOX effects against the brain via indirect way [29, 30]. These effects include: depression, anxiety, decrease in motor functions, haemoglobin levels, perception skills affected, and menopausal status, visuospatial skills are affected through cancer chemotherapy. The recovery of the cognitive functions may take up to a year [31]. The DOX mediate increase TNF-α level (inflammatory cytokines produced by the macrophages/monocytes during the acute inflammation involved in many signalling pathways) in the brain at cortex and hippocampus of mice [32, 33, 34]. The mitochondrial activity, glutathione-S-transferase, GSH levels, and MnSOD levels in the brain are decreased and increase in levels of 4-hydroxynoneal (HNA), thiobarbituric acid reactive substances (TBARS), malondialdehyde (MDA) and increase in levels of protein carbonyl groups [35, 36, 37, 38], which causes increase the oxidative stress in the brain cells and further led to cause cell damage.
\n
The MnSOD levels in the brain generally detoxify the oxygen free radicals, inactivated by the Nitric oxide (NO). The DOX indirectly increased the concentration of NO by overexpressing the Nitric oxide synthase enzyme [37]. A study conducted on the NOS dependent brain injury with DOC reinforcing the nitric oxide tissue damage [38]. The mitochondrial activity is very important in the brain because it is a powerhouse of cells (energy production) brain uses 20% of body glucose for energy production to conduct and maintain the regular activities [39]. The DOX induces generation of MDA, TBARS, and HNA which cause the decrease the mitochondrial activities. A study conducted on the DOX-induced toxicity on rats with 10 mg/kg dose, the rats died between 10 and 50 days with observed light microscopic studies reveals that specific changes in the ganglionic cells of the peripheral nervous system [40].
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2.4 Cardiomyopathy
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This side effect found to be a dose-dependent on DOX. The DOX-induced cardiotoxicity occurs acutely and chronically. The acute effects occur within one week period the patient may experience arrhythmia, hypotension, and super ventricular tachycardia. These abnormalities are generally reversible in a noticeable period [41]. The chronic effects are shown in only 1.7% of patients with a 50% mortality rate [42, 43]. The chronic effect of DOX such as congestive heart failure reported in a study, when the patients are treated with dose 500–550 mg/m2 in more than 4% of patients when treated with the dose is 551–600 mg/m2 18% of patients cause the CHF, and almost 35% of patients observed with CHF when treated with >601 mg/m2 [44, 45].
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A study conducted by the Zordosky and EI-kadi on DOX-induced toxicity reported as the induction of Brain natriuretic peptides, atrial natriuretic peptides genes, monooxygenases, cytochrome P genes and hypertrophy markers responsible for the xenobiotics and certain endogenous substances [46]. The inductions of these genes are cause cardiac hypertrophy leading to heart failure and altered the arachidonic acid mechanisms. A study reported the DOX effects based on the concentrations, at low concentrations DOX dose (o.5–1 μM) causes the alterations in structural proteins (includes sarcomeric myosin, nuclear lamina), plasma membrane blebbing (causes change in cell shape), and mitochondrial depolarization and fragmentation. At high concentration causes (5–50 μM) causes the cytoplasm vacuolization, swelling of mitochondrial cells, promote the cellular alterations (\nFigure 2\n) at the cellular and nuclear membranes [47]. The DOX reportedly binds to the cardiolipin (a mitochondrial inner membrane component), which raises the accumulation of the DOX inside the mycoplasma when compared to the other body cells. The high concentration existence of the NADPH dehydrogenase inside the mitochondria initiates the redox reaction in the complex and promotes the production of the Reactive oxygen species. Myocytes are generally having low levels of anti-oxidants when compared to the other tissue cells, considerably DOX shows enhanced effects on the heart and cause toxicity [48, 49, 50].
\n
Figure 2.
DOX-mediated effects on the Heart.
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The antioxidant level differences were observed in rats under DOX treatment based on the age differences, younger Fischer rats contain more levels of antioxidants when compared to old Fischer rats. A recent study stated the involvement of the Toll-like receptor TLR-4 (a specific receptor in the immune system generally recognise the multiple bacterial antigens and plays a major role in the maturation of the phagosomes) [51]. The increase in TLR-4 expression in the DOX-induced Cardiomyocytes, when studied the cardiomyopathic cells in humans and animals. The deficiency of TLR shows decreased in lipid peroxidation and nitrotyrosine levels in cardiomyopathic cells. The other study on the glutathione peroxidase 1 (GPx) enzyme is present in both cytosol and mitochondria play a major role in the detoxification. The study conducted with the insertion of DOX on non-GPx and wild type mice, the results showed based on the study on myocytes of the non-GPx mice having the high concentration of the DOX deposits in cells, when compared to wild type mice [52, 53, 54].
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The oxidative stress is a major cause for the exhibiting the cardiotoxicity, involved the generation of higher amounts of ROS cause the cellar alterations and damage are referred to as oxidative stress. The ROS is countered by the anti-oxidant system in the body, in cancer patients under the DOX chemotherapy observed the decreased the levels of GSH, TRAP levels in the body. The ROS is generation is catalysed by NADPH oxidase enzyme [55, 56].
The generated oxygen radicals combine with the H2O2 and form the highly active hydroxyl radicals. The H2O2 also reacted with the ferrous ions resulting in the formation of ferric ions and reactive hydroxyl radicals [55].
Under stress conditions, oxygen radical facilitates the ferrous iron from the ferric ion. The iron, under normal conditions sequestered within the ferritin (a globular protein and forms the nanocage with the metal-protein complexes) but with regards to DOX when converted to its semi-quinone form complexes with iron-free radical and converted to DOX forms while generating the oxygen free radical. The generated complexes block the iron-free regulating proteins (IRP), and then these IRPs bound to the iron-responsive elements in mRNA ferritin. The tremendous amounts of free iron releases and gain complexes with the DOX. This specific condition magnifies the production of ROS in cells [57, 58, 59].
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The ROS acts as secondary signalling molecules shows direct effects on the lipids, proteins, DNA, and RNA in various pathways involved in cell proliferation, cell death and maintain the homeostasis. It is domineering to maintain the levels of ROS in the body, in case of the heart the effect is maximum by ROS due to lack of efficient levels of anti-oxidants in myocytes. The conditions such as cellular hypertrophy, alterations in the gene expressions, ventricular remodelling, the extracellular matrix of the mitochondria transformation, calcium transient perturbation and cell death activation such kinds of pathological changes may be observed in myocytes lead the death of cells.
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2.5 Mechanisms involved at different levels of cardio toxicity
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2.5.1 Cellular hypertrophy
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A particular disorder marked by an increase in cell size and volume. The abnormality shows an improvement in the degree of protein synthesis, increased in the organisation of sarcomere (contractile muscle fibre unit). At molecular level induction of hypertrophy associated genes are triggered by the DOX treatment which are alpha myosin heavy chain, ventricular myosin light chain-2, and atrial natriuretic peptide genes [60]. The main signalling cascades of the hypertrophy are tyrosine kinases, PI3K/Akt [61], and NF-𝜅B [62, 63], protein kinase C (PKC), mitogen-activated protein kinases (AMPK [64]; ERK1/2 [65], p38 [66], and JNK) which are increased in DOX therapy induce cellular hypertrophic conditions [67].
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2.5.2 ECM remodelling
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Extra cellular matrix is a molecular network consisting of glycol conjugates, proteins, glycosaminoglycans and adhesive receptors that associate with each other and forms frame network, where cells reside on them [68]. The ECM frame work is present in all tissues it continuously shifts in quantitative and qualitative terms on a daily basis. In case of myocytes ECM is essential for attachment, alignment and orientation facilities the cellular contractions in myocytes. Changes in the ECM of the heart found in DOX treatments, the symptoms of DOX are related to the activation of the Membrane Metalloproteinase enzymes MMP-2 & 9 in 4 weeks of treatment [69]. Changes in MMP-2 activate the Akt channels; suppress the superoxide dismutase enzyme, which raises the amount of superoxide levels, and induce caspase-3 and all other agents together promote remodelling and apoptosis [70].
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2.5.3 Impaired cardiac contraction
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The heart cells (cardiomyocytes) composed of myofibrils with typical contraction and relaxation. Pump and propel the blood to systemic circulation. Myofibrils contain multiple contractile units called sarcomere, which have actin and myosin filaments. In a calm state, actin is coated in tropomyosin and protects the myosin-binding sites. The troponin and tropomyosin are attached when the calcium enters into the cytosol from the sarcoplasmic reticulum; calcium binds to the troponin and the position of the tropomyosin and troponin changes resulting in shortening of the sarcomere. That specific condition termed as cardiac contraction controlled by calcium influx and myofilaments. DOX could affect the transcription and expression of the specific proteins [71]. Transcription factor-like GATA4 for the regulation of sarcomeric synthesis and cardiac differentiation and survival of myocytes. DOX-induced ROS decreases binding function, disrupts sarcomere structure, contractile reduction and myofibrillar deterioration [72]. DOX is believed to interact with calcium homeostasis by modifying the ion pump and modifying the ion channel movement, resulting in lipid peroxidation. ROS quickly targets the fatty acids of the membrane lipids and disrupts the mitochondrial calcium channels by increasing the activity of the voltage-sensitive L-type calcium channels on the cell membrane resulting in accumulation of calcium [73]. Calcium overload throughout cytosol, Causes the disruption in the contraction and relaxing of cardiomyocytes.
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2.5.4 Cell death
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The general apoptosis is a process where a cell commits to suicide, damage to genetic material, protein, cellular organelles that beyond the repair would trigger the suicide to save the energy and resources. Apoptosis firmly regulated process involves intrinsic mitochondrial apoptosis, extrinsic death receptor pathways [74]. The mitochondrial pathway relays on the Trans membrane potential is a key indicator of membrane permeability. It is assumed that permeability can be either permeability-dependent or independent of the pore transition [PT]. The PT pore consists of the adenine nucleotide translocator, matrix protein cyclophilin D, and voltage-dependent anion channel. The opening of the PT pore activates the dissipation of the proton gradient produced by electron transport, resulting in the uncoupling of oxidative phosphorylation. The opening of the PT pore also allows water to penetrate the mitochondrial matrix, resulting in the swelling of the intermembrane space and the rupturing of the outer membrane allowing the release of apoptogenic proteins. Released proteins include cytochrome c, apoptosis-inducing factor and endonuclease G. Cytochrome c in conjunction with apoptosis protease activating factor (APAF-1) and pro-caspase 9 forms an apoptosome, which in turn activates effector caspases that collectively facilitate the execution of apoptosis. Due to decrease in the number of normal cardiomyocytes is significantly reduced, the heart failed to pump the blood sequentially ventricular remodelling and death of myocytes [75].
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The death receptor pathway involves the binding of death ligands such as FasL, TNF-α to their respective membrane-bound receptors. The bonded ligands signals to various proteins mediate the cascade, which leads to apoptosis of the cell [76]. In cancer therapy, DOX-induced ROS activates the p38, p53 and NF-kB pathways resulting in the differences in pro- and anti-apaptonic signalling imbalance, such imbalance cause release of cytochrome C from mitochondrial membrane proteins, subsequently lead to apoptosis of cell [77, 78].
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2.5.5 Autophagy
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Autophagy is a method of restoring or repairing the destroyed cells. It is a self-degrading mechanism (survival mechanism) to maintain a balance of life in response to dietary stress, energy depletion. Autophagy destroys malformed proteins, weakened organelles, and other cell infections, which can be unique or non-specific, but processes are not completely thought out. Under diseased environments, autophagy either facilitates cell death or induces cell death depending on the demands of different people [79, 80]. In DOX-based therapy toxicity mediated autophagy by suppressing GTAT4 expression and activating S6K1, this plays a direct and indirect role in autophagy control. Autophagy varies due to species differences; autophagy dependent on DOX is increased in mice but decreased in autophagy has been seen in mouse cases [81, 82, 83, 84]. The autophagy achieved in DOX therapy via several mechanisms, such as ATG 5 & 12 is the inhibitors of the Bcl-2 family, which regulate the cytochrome release from the mitochondria. Cytochrome C releases the caspase-9 lead to the autophagosome, can regulate the apoptosis. In some other studies, autophagy reduces the DOX-induced cardiotoxicity by decreasing mitochondrial ROS formation.
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2.6 Diagnosis
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The DOX-induced cardiomyopathy consists of a complete examination of the cardiovascular system for detecting the symptoms, such as S3 gallop and elevated jugular vapour pressure, T wave impairments; low voltage QRS complexes are measured.
Electrocardiography combined with Doopler studies used to study early diagnostic symptoms of the cardiac myopathy through the measure of latero-ventricular dysfunction.
Radionuclide ventriculography used to access the latero-ventricular systolic and diastolic function. Observes the cardiac adrenergic denervation occurs in case of doxorubicin induced cardiomyopathy.
Metaiodobenzylguanidine based nuclear imaging can be employed to assess cardiac adrenergic denervation occurred trough the DOX based cardiomyopathy.
The DOX treated patients are sensitive to the indium labelled monoclonal antimyosin antibodies (myosin an ATP dependent superfamily of motor proteins major role in muscle contraction and motility) used to detect the cardiac myopathy, myocarditis, chagas heart disease ischemic myocardium, and kawasaki heart disease [85].
The measurement of the cardiac enzymes and neurohormones are used for detecting the heart failure but not a characteristic feature of the DOX-induced cardiomyopathy [86].
The presence of endomyocardial biopsy is the best route for detecting the DOX-induced diseases, according to the grade of biopsy severity of the disease is measured [87, 88]. It is invasive and requires experience for recognising the results become a disadvantage for this technique.
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3. Management & preventive strategies for doxorubicin cardiotoxicity
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The DOX has an extreme side effect like cardiotoxicity, but is still in use because of its efficacy in the treatment of cancers. Toxicity can be avoided in several ways. Many studies have shown that cardioprotective agents can achieve a reduction in cardiotoxicity. A recent research on HSP-20 (heat-shock protein) has shown that the protection of Akt activity prevents the cardiotoxic effect caused by DOX [89, 90, 91, 92]. Different kind of agents is used to control the DOX effects such as Dexrazoxane (DZR); it contains bisdioxopiperazine rings falling under alpha-amino acid and the derivative compound also known as cardioxane or Totect or Zincard. A promising compound that activates after hydrolysis and resembles the EDTA structure after conversion makes complexes with Iron and reduces the incidence of anthracycline-iron complexes, thus preventing ROS generation in myocytes. Dexrazoxane has also been known to contain the Topoisomerase II enzyme function and inhibit the tumour cell growth. Used mainly for the activities of iron-chelating agent, cardiac protection, anti-neoplastic activities, and chemo protection. Indirectly active in chromatin remodelling complexes by activating vitamin D receptors. DZR is often known to provide up-regulation of the ERK and Akt pathways to guard against cardiomyopathy [93, 94, 95, 96] but DZR is not approved for routine use in patients with metastatic cancer and other forms of cancer, as stated by the American Clinical Oncology Society [97, 98]. DOX was analysed in association with DZR for 10 years in women with breast cancer [99]. No, people suffer from heart disease over the time and there are no records of adverse effects with respect to the heart.
\n
Diuretics are used to avoid signs of systemic and pulmonary ventricular obstruction, and medications dependent on β-adrenergic receptors are used depending on the type of systolic heart problem [100]. Metoprolol is safe and effective in the treatment of cardiac myopathy [97], angiotensin II is also recommended for advanced heart disease cases, and low-dose isosorbide dinitrate substituted angiotensin inhibitor medication is favoured and hydralazine is favoured for cardiomyopathic myopathy.
\n
The successful release of DOX at a particular site of operation is another form of preventive step. Like liposomal dosage formulations, the specified delivery mechanism passively decreases the impact caused by non-cancerous cells. For liposomes drug interaction with blood and cancer cells, structural characteristics such as vesicle size, pharmacokinetic characteristics such as stability and pharmacodynamic characteristics such as plasma clearance are important. Tumour cells have conditions that favour high-level depositions, because newly developed cells have microvasculature-permeable vessels, which contain poor lymphatic drainage, low levels of lipase enzymes and other oxidising agents. Due to these features of cancer cells shows aggregation. Once liposomes enter the tumour cells the differences in the intestinal pH favours the release of drugs constituents. The pH of cancer cells is differ from other normal cells because of this the drug is preferentially released in tumour cells and avoid the toxicity in non-cancer cells. The recently reported formulation of polyethylene glycol-coated liposomal doxorubicin (PLD) shows better pharmacokinetics relative to general formulations and has fewer side effects [101]. A phase clinical trial of 50 mg/m2 PLD administration in patients with carcinoma with a demonstrated history of platinum-based chemotherapy at intervals of 4 weeks reported low toxicity. The other formulation like poly (ethylene oxide)-b-poly (e-caprolactone-DOX) [PEO-b- P(CL-DOX)] prevents the premature release outside of the tumor cells [102].
\n
The development of analogues is another possible strategy for reducing the toxicity [96], in the case of anthracyclines nuclear targeted and Non-nuclear targeted are two kinds of strategies concerned in the development of non-toxic chemotherapeutic agents. Analogues such as Methoxymorpholinyl doxorubicin (MMDX), sabarubicin and N-Benzyladriamycin-14-valerate now under development to reduce the toxicity caused by DOX. In which, MMDX is nuclear-targeted analogue activated by the liver enzyme cytochrome P450 3A and metabolize into a cytotoxic metabolite and degrades slowly [103]. Based on gene therapy expression of cytochrome enzyme activity increased, cytochrome increases the therapeutic potency of the DOX. The sabarubicin (disaccharide analogue) is also another nuclear targeted molecule that has improved efficiency especially used in case of lung and gynaecological cancer [104]. This stimulates the NF-kB transcription factor, which happens earlier as DNA is involved with multiple tumorogenesis, regulating the expressions of differentiation, variations, cell adhesion and apoptosis [105]. N-Benzyladriamycin-14-valerate is a non-nuclear target molecule obtained by modification of the C-3 amino group and the C-14 position [106]. The compound has comparable activity to DOX but is theoretically more effective than DOX by activating the protein kinase enzyme resulting in cardio-protective activity.
\n
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4. Conclusion
\n
Even DOX used for treating several types of cancers as a result of its wide range of pharmacological activities, but at the same time it causes a wide range of side effects. The major side effects caused by DOX are: carditoxicity, neuropathy, hepatotoxicity, nephrotoxicity, alopecia, typhlitis, myelosuppression, neutropenia, anaemia, and thrombocytopenia. DOX increasing the oxidative stress, decrease the GSH, vitamin E levels, and activates the NF-kB levels causes’ hepatotoxicity. Besides, it interferes with the glandular podocytes of the kidney and cause nephropathy. Also, it induces generation of MDA, TBARS, and HNA which decrease the mitochondrial activities and increase in ROS generation causes cell necrosis. Moreover, it causes induction of brain natriuretic peptides, atrial natriuretic peptides genes, mono oxygenases, cytochrome P genes; binds to the cardiolipin, the increase in TLR-4 expression, generation of ROS led to several pathological changes in myocytes causes cardiomyopathy. Several strategies are made to manage and decrease DOX’s cardiotoxicity effects, includes a change in the dosage forms for efficacious delivery systems, administration along with anti-oxidants, DZR, diuretics and β-adrenergic agents, and development of different analogues for increasing the efficiency of DOX.
\n
\n
Acknowledgments
\n
The author is grateful to Prof. M. Sarangapani, Principal of University College of pharmaceutical sciences, Kakatiya University, Warangal.
\n
Conflict of interest
The author declares no conflict of interest.
\n',keywords:"doxorubicin, nephrotoxicity, neurotoxicity, hepatotoxicity, cardiotoxicity",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/74276.pdf",chapterXML:"https://mts.intechopen.com/source/xml/74276.xml",downloadPdfUrl:"/chapter/pdf-download/74276",previewPdfUrl:"/chapter/pdf-preview/74276",totalDownloads:503,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:2,totalAltmetricsMentions:0,impactScore:1,impactScorePercentile:68,impactScoreQuartile:3,hasAltmetrics:0,dateSubmitted:"July 14th 2020",dateReviewed:"November 4th 2020",datePrePublished:"December 2nd 2020",datePublished:"July 21st 2021",dateFinished:"December 2nd 2020",readingETA:"0",abstract:"Doxorubicin is an anthracycline antibiotic extracted from the bacterium Streptomyces peucetius. Its cytotoxic effect produced by intercalating with DNA causing breakdown of DNA strand which causes cancer cell apoptosis. Despite being an effective anticancer agent it causes several crucial side effects like carditoxicity, neuropathy, hepatotoxicity, nephrotoxicity, alopecia, typhlitis, myelosuppression, neutropenia, anaemia, thrombocytopenia, nausea, and diarrhoea were caused mainly due to the inability to distinguish between cancer cells and normal cells. This chapter mainly focuses on doxorubicin’s side effects, current understanding of the molecular mechanisms, and management and preventive strategies of doxorubicin’s cardiotoxicity during the treatment of various type of cancer.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/74276",risUrl:"/chapter/ris/74276",book:{id:"10321",slug:"advances-in-precision-medicine-oncology"},signatures:"Chittipolu Ajaykumar",authors:[{id:"327203",title:"Assistant Prof.",name:"Chittipolu",middleName:null,surname:"Ajaykumar",fullName:"Chittipolu Ajaykumar",slug:"chittipolu-ajaykumar",email:"ajay239172@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Historical background",level:"2"},{id:"sec_2_2",title:"1.2 Doxorubicin chemical structure and properties",level:"2"},{id:"sec_4",title:"2. Doxorubicin side effects",level:"1"},{id:"sec_4_2",title:"2.1 Hepatotoxicity",level:"2"},{id:"sec_5_2",title:"2.2 Nephropathy",level:"2"},{id:"sec_6_2",title:"2.3 Neurotoxicity",level:"2"},{id:"sec_7_2",title:"2.4 Cardiomyopathy",level:"2"},{id:"sec_8_2",title:"2.5 Mechanisms involved at different levels of cardio toxicity",level:"2"},{id:"sec_8_3",title:"2.5.1 Cellular hypertrophy",level:"3"},{id:"sec_9_3",title:"2.5.2 ECM remodelling",level:"3"},{id:"sec_10_3",title:"2.5.3 Impaired cardiac contraction",level:"3"},{id:"sec_11_3",title:"2.5.4 Cell death",level:"3"},{id:"sec_12_3",title:"2.5.5 Autophagy",level:"3"},{id:"sec_14_2",title:"2.6 Diagnosis",level:"2"},{id:"sec_16",title:"3. Management & preventive strategies for doxorubicin cardiotoxicity",level:"1"},{id:"sec_17",title:"4. Conclusion",level:"1"},{id:"sec_18",title:"Acknowledgments",level:"1"},{id:"sec_21",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'\nCarvalho C, Santos RX, Cardoso S, Correia S, Oliveira PJ, Santos MS, et al. Doxorubicin: the good, the bad and the ugly effect. Current medicinal chemistry. 2009 Sep 1;16(25):3267-3285\n'},{id:"B2",body:'\nWani SH. Lone SA. Cancer: Diseases. Educreation Publishing; 2018 Nov 10\n'},{id:"B3",body:'\nDanesi R, Fogli S, Gennari A, Conte P, Del Tacca M. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clinical Pharmacokinetics. 2002 May 1;41(6):431-444\n'},{id:"B4",body:'\nDanesi R, Fogli S, Gennari A, Conte P, Del Tacca M. Pharmacokinetic-pharmacodynamic relationships of the anthracycline anticancer drugs. Clinical Pharmacokinetics. 2002 May 1;41(6):431-444\n'},{id:"B5",body:'\nSong Y, Buettner GR. Thermodynamic and kinetic considerations for the reaction of semiquinone radicals to form superoxide and hydrogen peroxide. Free Radical Biology and Medicine. 2010 Sep 15;49(6):919-962\n'},{id:"B6",body:'\nChatterjee K, Zhang J, Tao R, Honbo N, Karliner JS. Vincristine attenuates doxorubicin cardiotoxicity. Biochemical and biophysical research communications. 2008 Sep 5;373(4):555-560\n'},{id:"B7",body:'\nAvailable from: http://chemocare.com/chemotherapy/drug-info/doxorubicin.aspx [accessed on 2020-10-11]\n'},{id:"B8",body:'\nAlghorabi AA, Kabel AM, Elmaaboud MA. Doxorubicin: Insights into Dynamics, Clinical Uses and Adverse Effects. J. Cancer Res. 2019;7:17-20\n'},{id:"B9",body:'\nHanna AD, Lam A, Tham S, Dulhunty AF, Beard NA. Adverse effects of doxorubicin and its metabolic product on cardiac RyR2 and SERCA2A. Molecular Pharmacology. 2014 Oct 1;86(4):438-449\n'},{id:"B10",body:'\nMaton A, Hopkins J, McLaughlin CW, Johnson S, Warner MQ, LaHart D, et al. Human biology and health. Englewood Cliffs, New Jersey, US: Prentice Hall; 1993\n'},{id:"B11",body:'\nShirani K, Yousefsani BS, Shirani M, Karimi G. Protective effects of naringin against drugs and chemical toxins induced hepatotoxicity: A review. Phytotherapy Research. 2020 Feb;17\n\n'},{id:"B12",body:'\nZhao X, Jin Y, Li L, Xu L, Tang Z, Qi Y, et al. MicroRNA-128-3p aggravates doxorubicin-induced liver injury by promoting oxidative stress via targeting Sirtuin-1. Pharmacological Research. 2019 Aug 1;146:104276\n'},{id:"B13",body:'\nYang XL, Fan CH, Zhu HS. Photo-induced cytotoxicity of malonic acid [C60] fullerene derivatives and its mechanism. Toxicology in vitro. 2002 Feb 1;16(1):41-46\n'},{id:"B14",body:'\nForrest GL, Gonzalez B, Tseng W, Li X, Mann J. Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice. Cancer research. 2000 Sep 15;60(18):5158-5164\n'},{id:"B15",body:'\nGavelová M, Hladíková J, Vildová L, Novotná R, Vondráček J, Krčmář P, et al. Reduction of doxorubicin and oracin and induction of carbonyl reductase in human breast carcinoma MCF-7 cells. Chemico-biological interactions. 2008 Oct 22;176(1):9-18\n'},{id:"B16",body:'\nAhmed OM, Abdul-Hamid MM, El-Bakry AM, Mohamed HM, Abdel Rahman ES. Camellia sinensis and epicatechin abate doxorubicin-induced hepatotoxicity in male Wistar rats via their modulatory effects on oxidative stress, inflammation, and apoptosis. J Appl Pharm Sci. 2019 Apr;9:30-44\n'},{id:"B17",body:'\nInjac R, Perse M, Obermajer N, Djordjevic-Milic V, Prijatelj M, Djordjevic A, et al. Potential hepatoprotective effects of fullerenol C60 (OH) 24 in doxorubicin-induced hepatotoxicity in rats with mammary carcinomas. Biomaterials. 2008 Aug 1;29(24-25):3451-3460\n'},{id:"B18",body:'\nLu H, Zhu ZG, Yao XX, Zhao R, Yan C, Zhang Y, et al. Hepatic preconditioning of doxorubicin in stop-flow chemotherapy: NF-κB/IκB-α pathway and expression of HSP72. World Journal of Gastroenterology: WJG. 2005 Apr 14;11(14):2136\n'},{id:"B19",body:'\nSmuder AJ. Exercise stimulates beneficial adaptations to diminish doxorubicin-induced cellular toxicity. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2019 Nov 1;317(5):R662-R672\n'},{id:"B20",body:'\nSongbo M, Lang H, Xinyong C, Bin X, Ping Z, Liang S. Oxidative stress injury in doxorubicin-induced cardiotoxicity. Toxicology letters. 2019 Jun 1;307:41-48\n'},{id:"B21",body:'\nPisoschi AM, Pop A. The role of antioxidants in the chemistry of oxidative stress: A review. European journal of medicinal chemistry. 2015 Jun 5;97:55-74\n'},{id:"B22",body:'\nS Lahoti T, Patel D, Thekkemadom V, Beckett R, D Ray S. Doxorubicin-induced in vivo nephrotoxicity involves oxidative stress-mediated multiple pro-and anti-apoptotic signaling pathways. Current neurovascular research. 2012 Nov 1;9(4):282-295\n'},{id:"B23",body:'\nOkuda S, Oh Y, Tsuruda H, Onoyama K, Fujimi S, Fujishima M. Adriamycin-induced nephropathy as a model of chronic progressive glomerular disease. Kidney international. 1986 Feb 1;29(2):502-510\n'},{id:"B24",body:'\nFogo AB. Mechanisms of progression of chronic kidney disease. Pediatric nephrology. 2007 Dec 1;22(12):2011-2022\n'},{id:"B25",body:'\nWang Y, Wang YP, Tay YC, Harris DC. Progressive adriamycin nephropathy in mice: sequence of histologic and immunohistochemical events. Kidney international. 2000 Oct 1;58(4):1797-1804\n'},{id:"B26",body:'\nRook M, Lely AT, Kramer AB, van Goor H, Navis G. Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage. Nephrology Dialysis Transplantation. 2005 Jan 1;20(1):59-64\n'},{id:"B27",body:'\nKhames A, Khalaf MM, Gad AM, Abd El-raouf OM, Kandeil MA. Nicorandil combats doxorubicin–induced nephrotoxicity via amendment of TLR4/P38 MAPK/NFκ-B signaling pathway. Chemico-biological interactions. 2019 Sep 25;311:108777\n'},{id:"B28",body:'\nKorbet SM, Schwartz MM, Lewis EJ. Primary focal segmental glomerulosclerosis: clinical course and response to therapy. American journal of kidney diseases. 1994 Jun 1;23(6):773-783\n'},{id:"B29",body:'\nJansen C, Miaskowski C, Dodd M, Dowling G, Kramer J. Potential mechanisms for chemotherapy-induced impairments in cognitive function. InOncology nursing forum 2005 Nov 1 (Vol. 32, No. 6, p. 1151). Oncology Nursing Society\n'},{id:"B30",body:'\nFerreira A, Neves P, Gozzelino R. Multilevel impacts of Iron in the brain: the cross talk between neurophysiological mechanisms, cognition, and social behavior. Pharmaceuticals. 2019 Sep;12(3):126\n'},{id:"B31",body:'\nTangpong J, Cole MP, Sultana R, Joshi G, Estus S, Vore M, et al. Adriamycin-induced, TNF-α-mediated central nervous system toxicity. Neurobiology of Disease. 2006 Jul 1;23(1):127-139\n'},{id:"B32",body:'\nBrezden CB, Phillips KA, Abdolell M, Bunston T, Tannock IF. Cognitive function in breast cancer patients receiving adjuvant chemotherapy. Journal of Clinical Oncology. 2000 Jul 14;18(14):2695-2701\n'},{id:"B33",body:'\nAhles TA, Saykin AJ, Furstenberg CT, Cole B, Mott LA, Skalla K, et al. Neuropsychologic impact of standard-dose systemic chemotherapy in long-term survivors of breast cancer and lymphoma. Journal of Clinical Oncology. 2002 Jan 15;20(2):485-493\n'},{id:"B34",body:'\nTangpong J, Cole MP, Sultana R, Estus S, Vore M. St. Clair W, Ratanachaiyavong S, St. Clair DK, Butterfield DA. Adriamycin-mediated nitration of manganese superoxide dismutase in the central nervous system: insight into the mechanism of chemobrain. Journal of Neurochemistry. 2007 Jan;100(1):191-201\n'},{id:"B35",body:'\nPark ES, Kim SD, Lee MH, Lee HS, Lee IS, Sung JK, et al. Protective effects of N-acetylcysteine and selenium against doxorubicin toxicity in rats. Journal of veterinary science. 2003 Aug 1;4(2):129-136\n'},{id:"B36",body:'\nJoshi G, Sultana R, Tangpong J, Cole MP, St Clair DK, Vore M, et al. Free radical mediated oxidative stress and toxic side effects in brain induced by the anticancer drug adriamycin: insight into chemobrain. Free radical research. 2005 Jan 1;39(11):1147-1154\n'},{id:"B37",body:'\nJoshi G, Hardas S, Sultana R. St. Clair DK, Vore M, Butterfield DA. Glutathione elevation by γ-glutamyl cysteine ethyl ester as a potential therapeutic strategy for preventing oxidative stress in brain mediated by in vivo administration of adriamycin: Implication for chemobrain. Journal of Neuroscience Research. 2007 Feb 15;85(3):497-503\n'},{id:"B38",body:'\nÖz E, İlhan MN. Effects of melatonin in reducing the toxic effects of doxorubicin. Molecular and Cellular Biochemistry. 2006 Jun 1;286(1-2):11-15\n'},{id:"B39",body:'\nMohanty A, Tiwari-Pandey R, Pandey NR. Mitochondria: the indispensable players in innate immunity and guardians of the inflammatory response. Journal of Cell Communication and Signaling. 2019 Sep;1:1-6\n'},{id:"B40",body:'\nGorini S, De Angelis A, Berrino L, Malara N, Rosano G, Ferraro E. Chemotherapeutic drugs and mitochondrial dysfunction: focus on doxorubicin, trastuzumab, and sunitinib. Oxidative medicine and cellular longevity. 2018 Oct;2018\n\n'},{id:"B41",body:'\nMancilla TR, Iskra B, Aune GJ. Doxorubicin-Induced Cardiomyopathy in Children. Comprehensive Physiology. 2011 Jan 17;9(3):905-931\n'},{id:"B42",body:'\nArcamone F, Franceschi G, Penco S, Selva A. Adriamycin (14-hydroxydaunomycin), a novel antitumor antibiotic. Tetrahedron letters. 1969 Jan 1;10(13):1007-1010\n'},{id:"B43",body:'\nSingal PK, Iliskovic N. Doxorubicin-induced cardiomyopathy. 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Cell biology and toxicology. 2009 Jun 1;25(3):227-243\n'},{id:"B48",body:'\nGoormaghtigh E, Huart P, Praet M, Brasseur R, Ruysschaert JM. Structure of the adriamycin-cardiolipin complex: role in mitochondrial toxicity. Biophysical Chemistry. 1990 Apr 1;35(2-3):247-257\n'},{id:"B49",body:'\nChilds AC, Phaneuf SL, Dirks AJ, Phillips T, Leeuwenburgh C. Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2: Bax ratio. Cancer research. 2002 Aug 15;62(16):4592-4598\n'},{id:"B50",body:'\nOdom AL, Hatwig CA, Stanley JS, Benson AM. Biochemical determinants of adriamycin® toxicity in mouse liver, heart and intestine. Biochemical Pharmacology. 1992 Feb 18;43(4):831-836\n'},{id:"B51",body:'\nRiad A, Bien S, Gratz M, Escher F, Heimesaat MM, Bereswill S, et al. Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice. European journal of heart failure. 2008 Mar;10(3):233-243\n'},{id:"B52",body:'\nEsworthy RS, Ho YS, Chu FF. TheGpx1Gene encodes mitochondrial glutathione peroxidase in the mouse liver. Archives of biochemistry and biophysics. 1997 Apr 1;340(1):59-63\n'},{id:"B53",body:'\nLi T, Singal PK. Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol. Circulation. 2000 Oct 24;102(17):2105-2110\n'},{id:"B54",body:'\nSazuka Y, Tanizawa H, Takino Y. Effect of adriamycin on the activities of superoxide dismutase, glutathione peroxidase and catalase in tissues of mice. Japanese journal of cancer research. 1989 Jan;80(1):89-94\n'},{id:"B55",body:'\nAngsutararux P, Luanpitpong S, Issaragrisil S. Chemotherapy-induced cardiotoxicity: overview of the roles of oxidative stress. Oxidative medicine and cellular longevity. 2015 Oct;2015\n\n'},{id:"B56",body:'\nThorn CF, Oshiro C, Marsh S, Hernandez-Boussard T, McLeod H, Klein TE, et al. 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Cell Death & Differentiation. 2012 Jan;19(1):36-41\n'},{id:"B75",body:'\nSawyer DB, Peng X, Chen B, Pentassuglia L, Lim CC. Mechanisms of anthracycline cardiac injury: can we identify strategies for cardioprotection? Progress in cardiovascular diseases. 2010 Sep 1;53(2):105-113\n'},{id:"B76",body:'\nKotamraju S, Konorev EA, Joseph J, Kalyanaraman B. Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen role of reactive oxygen and nitrogen species. Journal of Biological Chemistry. 2000 Oct 27;275(43):33585-33592\n'},{id:"B77",body:'\nNitobe J, Yamaguchi S, Okuyama M, Nozaki N, Sata M, Miyamoto T, et al. Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes. Cardiovascular Research. 2003 Jan 1;57(1):119-128\n'},{id:"B78",body:'\nLien YC, Noel T, Liu H, Stromberg AJ, Chen KC, Clair DK. Phospholipase C-δ1 Is a Critical Target for Tumor Necrosis Factor Receptor–Mediated Protection against Adriamycin-Induced Cardiac Injury. Cancer research. 2006 Apr 15;66(8):4329-4338\n'},{id:"B79",body:'\nLu L, Wu W, Yan J, Li X, Yu H, Yu X. Adriamycin-induced autophagic cardiomyocyte death plays a pathogenic role in a rat model of heart failure. International journal of cardiology. 2009 May 1;134(1):82-90\n'},{id:"B80",body:'\nDimitrakis P, Romay-Ogando MI, Timolati F, Suter TM, Zuppinger C. Effects of doxorubicin cancer therapy on autophagy and the ubiquitin-proteasome system in long-term cultured adult rat cardiomyocytes. Cell and tissue research. 2012 Nov 1;350(2):361-372\n'},{id:"B81",body:'\nKawaguchi T, Takemura G, Kanamori H, Takeyama T, Watanabe T, Morishita K, et al. Prior starvation mitigates acute doxorubicin cardiotoxicity through restoration of autophagy in affected cardiomyocytes. Cardiovascular Research. 2012 Dec 1;96(3):456-465\n'},{id:"B82",body:'\nSmuder AJ, Kavazis AN, Min K, Powers SK. Doxorubicin-induced markers of myocardial autophagic signaling in sedentary and exercise trained animals. Journal of Applied Physiology. 2013 Jul 15;115(2):176-185\n'},{id:"B83",body:'\nZhang YY, Meng C, Zhang XM, Yuan CH, Wen MD, Chen Z, et al. Ophiopogonin D attenuates doxorubicin-induced autophagic cell death by relieving mitochondrial damage in vitro and in vivo. Journal of Pharmacology and Experimental Therapeutics. 2015 Jan 1;352(1):166-174\n'},{id:"B84",body:'\nShabalala S, Muller CJ, Louw J, Johnson R. Polyphenols, autophagy and doxorubicin-induced cardiotoxicity. Life Sciences. 2017 Jul 1;180:160-170\n'},{id:"B85",body:'\nWakasugi S, Fischman AJ, Babich JW, Callahan RJ, Elmaleh DR, Wilkinson R, et al. Myocardial substrate utilization and left ventricular function in adriamycin cardiomyopathy. Journal of Nuclear Medicine. 1993 Sep 1;34(9):1529-1535\n'},{id:"B86",body:'\nSuzuki T, Hayashi D, Yamazaki T, Mizuno T, Kanda Y, Komuro I, et al. Elevated B-type natriuretic peptide levels after anthracycline administration. American heart journal. 1998 Aug 1;136(2):362-363\n'},{id:"B87",body:'\nTakemura G, Fujiwara H. Doxorubicin-induced cardiomyopathy: from the cardiotoxic mechanisms to management. Progress in cardiovascular diseases. 2007 Mar 1;49(5):330-352\n'},{id:"B88",body:'\nBristow MR, Sageman WS, Scott RH, Billingham ME, Bowden RE, Kernoff RS, et al. Acute and chronic cardiovascular effects of doxorubicin in the dog: the cardiovascular pharmacology of drug-induced histamine release. Journal of cardiovascular pharmacology. 1980 Sep 1;2(5):487-516\n'},{id:"B89",body:'\nTakemura G, Fujiwara H. Doxorubicin-induced cardiomyopathy: from the cardiotoxic mechanisms to management. Progress in cardiovascular diseases. 2007 Mar 1;49(5):330-352\n'},{id:"B90",body:'\nZHU YH, MA TM, Wang X. Gene transfer of heat-shock protein 20 protects against ischemia/reperfusion injury in rat hearts 1. Acta Pharmacologica Sinica. 2005 Oct;26(10):1193-1200\n'},{id:"B91",body:'\nFan GC, Zhou X, Wang X, Song G, Qian J, Nicolaou P, et al. Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity. Circulation research. 2008 Nov 21;103(11):1270-1279\n'},{id:"B92",body:'\n\nKim KH, Oudit GY, Backx PH. Erythropoietin protects against doxorubicin-induced cardiomyopathy via a phosphatidylinositol 3-kinase-dependent pathway. Journal of Pharmacology and Experimental Therapeutics. 2008 Jan 1;324(1):160-169\n'},{id:"B93",body:'\nMarty M, Espie M, Llombart A, Monnier A, Rapoport BL, Stahalova V. Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane®) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Annals of Oncology. 2006 Apr 1;17(4):614-622\n'},{id:"B94",body:'\nvan Dalen EC, Caron HN, Dickinson HO, Kremer LC. Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane database of systematic reviews. 2011;6\n\n'},{id:"B95",body:'\nIn U, Hensley LM, Hagerty KL, Kewalramani T, Green DM, Meropol NJ, et al. American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants. Journal of Clinical Oncology. 2008;27:127-132\n'},{id:"B96",body:'\nTestore F, Milanese S, Ceste M, de Conciliis E, Parello G, Lanfranco C, et al. Cardioprotective effect of dexrazoxane in patients with breast cancer treated with anthracyclines in adjuvant setting. American journal of cardiovascular drugs. 2008 Jul 1;8(4):257-263\n'},{id:"B97",body:'\nShaddy RE, Olsen SL, Bristow MR, Taylor DO, Bullock EA, Tani LY, et al. Efficacy and safety of metoprolol in the treatment of doxorubicin-induced cardiomyopathy in pediatric patients. American heart journal. 1995 Jan 1;129(1):197-199\n'},{id:"B98",body:'\nLotrionte M, Palazzoni G, Natali R, Comerci G, Abbate A, Di Persio S, et al. Appraising cardiotoxicity associated with liposomal doxorubicin by means of tissue Doppler echocardiography end-points: Rationale and design of the LITE (Liposomal doxorubicin–Investigational chemotherapy–Tissue Doppler imaging Evaluation) randomized pilot study. International journal of cardiology. 2009 Jun 12;135(1):72-77\n'},{id:"B99",body:'\nWildiers H, Jurcut R, Ganame J, Herbots L, Neven P, De Backer J, et al. A pilot study to investigate the feasibility and cardiac effects of pegylated liposomal doxorubicin (PL-DOX) as adjuvant therapy in medically fit elderly breast cancer patients. Critical reviews in oncology/hematology. 2008 Aug 1;67(2):133-138\n'},{id:"B100",body:'\nArnold JM, Howlett JG, Ducharme A, Ezekowitz JA, Gardner MJ, Giannetti N, et al. Canadian Cardiovascular Society Consensus Conference guidelines on heart failure–2008 update: best practices for the transition of care of heart failure patients, and the recognition, investigation and treatment of cardiomyopathies. Canadian Journal of Cardiology. 2008 Jan 1;24(1):21-40\n'},{id:"B101",body:'\nCulty M, Nguyen HA, Underhill CB. The hyaluronan receptor (CD44) participates in the uptake and degradation of hyaluronan. The Journal of cell biology. 1992 Feb 15;116(4):1055-1062\n'},{id:"B102",body:'\nLewis AD, Lau DH, Durán GE, Wolf CR, Sikic BI. Role of cytochrome P-450 from the human CYP3A gene family in the potentiation of morpholino doxorubicin by human liver microsomes. Cancer research. 1992 Aug 15;52(16):4379-4384\n'},{id:"B103",body:'\nBaldwin A, Huang Z, Jounaidi Y, Waxman DJ. Identification of novel enzyme–prodrug combinations for use in cytochrome P450-based gene therapy for cancer. Archives of biochemistry and biophysics. 2003 Jan 1;409(1):197-206\n'},{id:"B104",body:'\nMichael JB, Tannock IF. Lysosomes, lysosomal enzymes and cancer. Advances in Cancer Research. 1993;60:269-291\n'},{id:"B105",body:'\nRoca-Alonso L, Castellano L, Mills A, Dabrowska AF, Sikkel MB, Pellegrino L, Jacob J, Frampton AE, Krell J, Coombes RC, Harding SE. Myocardial MiR-30 downregulation triggered by doxorubicin drives alterations in β-adrenergic signaling and enhances apoptosis. Cell death & disease. 2015 May;6(5):e1754-\n'},{id:"B106",body:'\nMa ZG, Dai J, Yuan YP, Bian ZY, Xu SC, Jin YG, et al. T-bet deficiency attenuates cardiac remodelling in rats. Basic Research in Cardiology. 2018 May 1;113(3):19\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Chittipolu Ajaykumar",address:"ajay239172@gmail.com",affiliation:'
Vision College of Pharmaceutical Sciences and Research, Hyderabad, India
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1. Introduction
The increase in the prevalence of non-communicable diseases has been widely reported, and among these is the category of mental disorders. Recent literature has reported that mental disorders have been on the rise exponentially, and account for an estimated 25% of all health-related disability worldwide [1], which highlights the need to prioritize treatment for this group of disorders. Although some health systems in some world regions and countries have acknowledged and have started to respond to this need, others lag behind. Health care systems are generally ideally organized to treat more people at lower levels of care, and decrease the proportion as the level of care increases. This is feasible because the less severity of illness can be easier managed at lower levels of care, where the illness requires less specialization and treatment costs are less because at this level most illnesses have not yet complicated. This approach has resulted in the globally accepted and promoted approach of placing Primary Health Care (PHC) services to offer optimal health services to the majority of citizens of a country. Primary healthcare (PHC) is thus acknowledged to be the foundation of well-functioning healthcare systems, and is the success indicator of attempts to improve health provision services. In fact, the 1978 Alma Ata declaration confirmed this view, by establishing and promoting PHC as a cornerstone of global health services provision [2]. The significance of the position of PHC services applies despite differences in regional and country wealth, and if well resourced and well run, PHC services can improve the offering of health services for the poor, and so decrease the differences in health outcomes across wealth bands. The South African government envisages the provision of primary health care as a service that should be provided to the whole population, which includes communities of low socio-economic status. During the Millennium Development Goals (MDG) era, and transcending to the Sustainable Development Goals (SDG) era, countries that were able to make strides towards achieving their goals, such as Brazil and Thailand, are those that prioritized the improvement of their PHC systems [3]. It is for that reason that PHC should be the focus of service provision for the increasing scourge of mental illness.
1.1 Substance abuse within mental disorders
The use of psychoactive substances affects mental function at both the short and long- term basis, hence the treatment of substance abuse disorders by mental health professionals. Moreover, literature also shows a bilateral association between the use of psychoactive substances and mental disorders [4], which implies that not only is mental illness a risk factor for later substance abuse [5], but substance abuse is also a risk factor for the development of mental illness [6]. This makes interventions for the prevention of substance dependence an important secondary outcome of interventions for early-onset mental disorders. For purposes of this chapter, reference to mental disorders includes substance abuse.
2. Cues and guidelines from the National Development Plan 2030
The South African National Development Plan (NDP) is the blueprint of how the South African government plans to improve the quality of services to achieve transformation that will improve the lives of the majority of people who were previously marginalized [7]. The NDP further identifies the need for a functional monitoring process as the basis of offering and improving the envisaged outcomes because without monitoring, it is not possible to determine the progress made towards any one goal. Chapter 10 of the National Development Plan acknowledges the promotion of health as a key to speed up transformation. The NDP further proposes to address a variety of social determinants of health, including mental health and substance abuse trends. The NDP further acknowledges the importance of considering the needs of the community, as well as embracing and elevating the role of society in addressing community needs. The scourge of mental disorders fits the category of community needs, and addressing them is an example of using the NDP to guide government responses to service delivery. The NDP further promotes the systematic use of data incorporating community health, prevention and environmental concerns, which is a focus area of the Primary health Care programme.
3. The scourge of mental disorders
As the prevalence on non-communicable diseases increase, mental health and wellbeing have been identified as central to reducing the global burden of this group of diseases [8]. The World Health Organization’s mental health action plan for 2013-2020 advocates for this integration because of the significant associations between common mental health disorders and other cardio cardiovascular diseases and common mental disorders, as well as the two groups sharing risk factors. The integration of mental health services seems to be so natural that their separation is regarded as a false divide [1]. Primary health care services present opportunities to offer universal health care to Africa [9]. However, this can be achieved if such services are well planned and adequately resourced with the right quantity of the right categories of staff [10].
3.1 Substance abuse in schools as a mental health issue
There are reports of an increasing prevalence of substance abuse in schools in South Africa [11], both in rural [12], as well as urban areas [13, 14], which calls for prevention as well as treatment interventions to address the challenges of substance abuse in schools. However, the focus of schools is mainly on academic development and outcomes. This often leaves both short and long-term impacts of other behaviors such as substance abuse, not receiving adequate attention.
On their own, schools are not equipped to deal with substance abuse, which identified a gap, which can and should be met by primary health care services. The inability of the school system to address the challenges related to substance abuse is demonstrated by the existence of the National Policy on Drug Abuse Management in Schools of 2002, which was meant to counteract the use of substances by learners. However, a study to assess the extent to which this policy was being implemented by schools found that the policy is not even known, let alone used by schools [15]. For most communities and schools, there is nothing that has been put in place for the prevention, screening or treatment of substance abuse, and upgrading primary health care services to provide these services will be a highly beneficial asset.
4. The urgency of addressing mental disorders
As the prevalence of mental disorders increase, related mental health services remain chronically under-resourced. The impact of mental illness is not limited to the patient, but also extends to the family, as mental distress has been identified among family members of psychiatric patients [16]. Additionally, those family members also need health care services, thus a continuous addition of people who need mental health services. On the other hand, the high prevalence of substance abuse in South Africa increases demands for mental health services [17]. Mental health services remain chronically under-resourced [18], which implies major unmet needs for mental health care. The lack of adequate resources has been interpreted as apathy by governments and funders to mitigate this human, social and economic costs of mental illness [19].
As in other countries, and in the absence of a well developed primary health care system to address mental illness, the current system of relying on mental hospitals as a mode of service provision is dominant in South Africa. Not only is this mode unrealistic for resource-constrained countries, but it limits the extent to which mental illness needs are met, as these hospitals are too few and expensive to meet the needs of the people who need such services. Moreover, the dependence on this mode contributes to non-prioritization of development of community-based resources and infrastructure.
Primary care delivery platform has been identified as ideal to address behavioral health, including substance abuse and mental disorders, as this level can be enhanced to effectively address these conditions [20]. Due to inadequate access to specialty substance use disorders, it is estimated that only 10% of people with substance use disorders (SUD) actually receive treatment [21], and this could be improved if such disorders were treated at primary health care levels, which is, by design, able to treat a greater proportion of the population. Delays in treating such patients contributes to major poor prognosis.
5. Qualities of a responsive health care system
Optimal health systems are those that respond to the needs of the people who rely on such services, which explains the regional and country variations of availability of services. As an example, when the global number of HIV infections were rising, HIV related services at primary health care levels were strengthened, which enabled an increased number of patients to access treatment nearer their homes and communities. Primary health care services were also improved to offer comprehensive HIV related services, which were not limited to the contracting the virus, but included services such as prevention of HIV, promotion of positive behavior change and health literacy about HIV [22]. The development of extensive community health services were also trained at this level, which further increased access to PHC services and cater for community health needs [23]. This approach was effective because it utilized local community workers who were able to identify relevant community needs [24], and the model can be duplicated for the promotion of mental health and prevention of mental disorders.
6. The appropriateness of primary health care services for mental health services
The advantages of the PHC as appropriate for the delivery of health services are many, including that most of such facilities are in communities and many clients are within walking distance to the nearest clinic. However, the availability of a structure does not necessarily guarantee optimal health services, as some of the clinics fall short of providing intended basic services. This implies that there is a need to continuously assess the functionality of primary health care services, to determine their relevance and effectiveness in providing services that are determined by community needs and priorities. An example of this gap is the increase in substance abuse and mental health challenges that have been prevalent in the last few years, and the failure of the health system to respond to the needs in the context of related services. As with other African countries, the South African Primary health care (PHC) nurse led [25], which is confirmed by the proportion of nurses compared to other health professionals, and the services rendered at PHC levels. It is for that reason that government can afford to offer services at no cost to the client as the State bears such costs [26].
What substance abuse and mental health have in common is that both are significantly impacted upon by social issues, which means that failure to respond appropriately may subject more members of the affected communities to similar challenges, which just increases the community burden of substance abuse and mental disorders. The increasing prevalence in both substance abuse and mental disorders has been well documented, but there is silence on how the PHC system has been prepared to respond in the appropriate manner. On the contrary, there is inequitable access to substance abuse treatment services in South Africa, and that, even among those that have access, the quality of services is often not ascertained. This is demonstrated by the action of government limiting itself to ensuring access but not putting adequate efforts to ensure quality that will improve treatment outcomes [27, 28]. The strengthening of PHC services in the area of mental health will thus increase access to the benefit of those that lacked such access. The monitoring of substance abuse services at PHC level, which is essential for making decisions, is not optimal [29].
7. The importance of the 1978 Alma Ata declaration in health service provision
The 1978 Alma Ata declaration envisaged primary health care to be the vehicle to achieve health for all. However, this outcome can only be achieved if the key principles of the Alma Ata are implemented, which include the requirement that services be driven by community needs and priorities, which will encourage and enable community participation, and the strengthening of the capacity of the district management system [30]. Because the cost of care increases with the level of care, primary health care services are at the most cost effective level for offering health care, which is ideal for a resource-constrained country like South Africa. However, failing to offer such services increases health care costs because of additional complications which needs to be addressed at a higher level of care, and which comes with higher costs and requires longer treatment periods.
8. Re-engineering of primary health care
Although the health budget of South Africa is on the upper end if compared to some of its neighbors, its health outcomes do not reflect that. This discordant has been attributed to a weak primary health care system [31]. The purpose of the re-engineering of Primary Health Care (PHC) is to improve both access and quality of health services to the general public. The need for the re-engineering was identified when the South African government acknowledged that although PHC services have been in existence for many years, they did not meet acceptable levels of both access and quality of services. The re-engineering of PHC was based on the three pillars as described below:
Ward based PHC outreach teams, which supports the provision of home and community based health services, which are linked to the fixed PHC facilities.
School health services, which supported health services in schools.
District based specialist teams, which supports the provision of district level specialists to improve health services at clinic level.
Evaluation of PHC services in South Africa have reported psycho-social support to be low [32], which can be improved by the integration of community health workers, who were specifically tasked with providing follow-up clinic and hospital care, as well as psychosocial support for patients and their family members [33]. Moreover, the re-engineering of primary health care purposed to, among others, to offer health promotion and prevention services at community level, which is needed for all disease categories offered at PHC level [34].
Primary healthcare is the first contact a person has with the health system for any health problem, and if well functional, the PHC re-engineering was expected to be a mechanism of relieving overburdened tertiary hospitals in South Africa [35] as most patients’ problems will be resolved at that level. A well-functioning district health system is the intended outcome of the re-engineering of primary health care process, which will result in a greater emphasis on health promotion, disease prevention, and community participation and empowerment [36]. Mental health services should therefore benefit for these intended good.
9. Advocating for primary health care for mental disorders
Traditionally, substance use services have not been provided by South African primary health care facilities, which has led to chronic limiting of access to treatment for people who use such services. A lack of mental health workers has slowed plans to integrate these services into the primary health care system [37]. However, careful consideration of how service delivery for mental disorders can be obtained for the majority, confirms the PHC model as being ideal for the prevention and management of mental disorders. Moreover, the low cost and increased access are advantageous for services at this level.
9.1 The cost
Primary health care services are offered at a lower cost, which is important for resource- constrained country like South Africa. This low cost can therefore enable more people to access mental health services. Institutionalization model of mental health services is much more costly, even for well-resourced countries like the USA, compared to primary health [38].
9.2 Improved accessibility of services
By its nature, PHC services are designed to be accessed by the majority of citizens, and resourcing and integrating extending such services to mental health will contribute to the improvement in treatment outcomes for the patients who need such services. That is why the need for interdisciplinary models of primary healthcare is likely to improve accessibility and quality of care for the broader population [39].
10. Examples of success of treating mental health disorders at PHC level
A number of countries have successfully integrated mental health services to mainstream primary health care services, with tremendous gains for both the country health system and the patients who receive such care. In Zimbabwe, the primary health care services for mental disorders include the use of lay health workers, which is advantageous for resource-constrained countries. The services they offer include screening for mental health disorders and administering primary care-based problem solving therapy with education and support for the clients [40]. In India, a similar program has been used for several years, and it has been found to be not only cost-effective, but also cost-saving [41]. The use of a lower cadre of health workers require task-shifting which, if properly utilized with effective training of the workers, can substantially reduce the number of high level health professionals, and thus close the mental health service gaps at primary health care level in South Africa at a minimal cost [42, 43].
10.1 Status of PHC services for mental health
Despite the high prevalence of mental health disorders in South Africa, mental health services at primary health care level are not prioritized. With the high level of stigmatization of mental illness, the health-seeking behaviors are compromised, despite the high prevalence of such disorders. This low prioritization also contributes to poor capacity planning and implementation of mental health care plans, scarcity of trained generalists in mental health care, poor integration of mental health into integrated care, and lack of dedicated mental health budget [44]. Specifically, the resource limitations need to be addressed, by allocation of more funding for PHC services and to upgrade mental health legislation and policies [45].
In order for primary care providers to diagnose substance abuse and mental illness among clinic attendees, they need to receive specific training, specifically in the use of self-reported screening tools which are easy to administer and efficient to make a substance abuse diagnosis in primary care settings. Early diagnosis and a brief behavioral change counseling are effective in managing substance abuse before it develops into dependency.
The acknowledgement of increasing prevalence of mental disorders which include substance abuse in South Africa, renders them to be a priority in the offering of primary health care services, and literature has reported that mental health care can be effectively integrated into primary health care [46]. However, in order to do this, governance should be improved [44]. This improved governance is what this chapter regards as a major intervention to improve PHC services and to set them to adequately address mental health matters.
10.2 Integrating mental health into mainstream primary health care services
Integration of mental health services into mainstream services has been recommended globally [47], and this has been found to be both effective for intended treatment outcomes, as well as economically cost-effective [21, 48]. While treatment effectiveness benefits the patients, cost-effectiveness has a direct benefit on the health system and an indirect benefit to the patients as the quality of treatment can be improved as more resources are available. Although compared to other African countries, South Africa is reported to be doing better in offering mental health services [49], a lot still needs to be done to implement integration of mental health services to reap envisaged health system benefits. With the high prevalence of mental disorders, which are ranked third as contributors to disability-adjusted life-years [50], integration of mental health into primary health care remains incomplete, which contributes to inconsistent care and difficulties such as unidentified symptoms, defaulting treatment and the revolving-door phenomenon [47, 51].
The integration of mental health services requires a vision contained in the South African Mental Health Policy and Strategy Plan, whose implementation can make a difference to the quality of services required by mental health care users [52]. Additionally, strong political will can assist in providing the resources required.
11. Recommended primary health care mental health services
A functional primary health care system should provide adequate services for most patients, so that only a selected few of these need referrals to higher levels of care. For that reason, primary healthcare services should be able to provide the following comprehensive mental health services:
11.1 Screening
The purpose of screening is for early detection, which is essential for both substance abuse and mental disorders, because if left unattended, these conditions tend to worsen and complicate, with poor treatment outcomes. Screening is therefore essential as it can assist with the early identification of both substance-related problems and mental illness, and guide the provision of appropriate services [53].
One of the key examples of failure to screen for pregnant mothers is the Fetal Alcohol Spectrum Disorders, which are often only detected after the child is born [54]. Specifically, the continuous neglect of screening for maternal depression has major negative implications for the children of such mothers, to the extent that the children’s constitutional rights are violated [55].
11.2 Prevention of mental illness and promotion of mental health
Both the prevention of mental illness and active promotion of mental health interventions are public health interventions for holistic approach for positive health outcomes [56]. This requires the identification of associated risk factors, and act on them. Because key contributors to mental illness are mostly socially derived, the negative social factors operational in communities need to be considered as points of attention. Prevention of mental illness and promotion of mental health has an economic value [57], hence the need to put efforts for their promotion.
11.3 Treatment
Although a few PHC clinics offer some mental services, the quality of treatment received does not meet the recommended mental health guidelines, and is therefore compromised [58]. In particular, promotion of mental health is often missing. Within the re-engineered primary health care package, which includes the utilization of a well-resourced district-based specialist teams, primary health care services will be enhanced to offer quality and effective treatment. However, not all clinics have functional district-based specialist teams, which needs to be improved.
With political commitment and following the spirit of the National Development plan and the core principles of Primary Health care, PHC services in South Africa can be an effective strategy in achieving the goal of health for all, including mental health services. This also applies to other African countries, which can use this strategy to coordinated efforts to achieve the health care components of the SDGs [9].
11.4 Ongoing support
A key success indicator for the treatment of chronic mental illness is the ability of the health system to provide ongoing support. This is necessitated to counteract possible relapse, which is common as the patients often experience treatment fatigue. Patients with chronic mental illness also often move residence, due to various social problems, which exposes them to discontinuity of treatment [59]. In the absence of any efforts for ongoing support, they are often lost to follow-up, with negative outcomes. In the South African setting, the existence of the Ward based PHC outreach teams can be effectively utilized for this service.
12. Conclusion
The chapter acknowledges the major problem of high prevalence of mental disorders in South Africa, as well as inadequate resources to address the problem. However, moderate changes to the primary health care model currently used in South Africa can result in major achievements in offering mental health services, which in turn will benefit the patients and assist health services to address the increasing scourge of mental disorders. This can be achieved by utilizing community health workers (CHWs), who are able to work effectively with marginalized communities, where the need for services is greatest [60]. With proper training, these community health workers can change the landscape of provision of mental health services, with resultant positive health outcomes for affected communities [61].
It is recommended that primary health care services be strengthened to provide comprehensive mental health and mental health services that include screening, brief interventions, referral to treatment and ongoing support [62], which will go a long way in addressing mental health and substance abuse needs for South Africa. Such services are likely to improve the mental disorder treatment needs across the spectrum, and provide the much needed continuity of care across levels [3]. With the integration of community health workers in primary health care service provision, the broader community participation is enabled, which is likely to result in an increased number of mental health activists, and better treatment outcomes for patients.
Acknowledgments
This chapter was jointly-funded by the National Research Foundation, through the NRF Chair in Substance Abuse and Population Mental Health grant, as well as the South African Medical Research Council, through the Substance Abuse and Adolescent Mental Health grant.
\n',keywords:"Primary health care re-engineering, South Africa, mental health, substance abuse, screening",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78257.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78257.xml",downloadPdfUrl:"/chapter/pdf-download/78257",previewPdfUrl:"/chapter/pdf-preview/78257",totalDownloads:62,totalViews:0,totalCrossrefCites:0,dateSubmitted:"July 30th 2021",dateReviewed:"August 3rd 2021",datePrePublished:"February 15th 2022",datePublished:"March 16th 2022",dateFinished:"August 26th 2021",readingETA:"0",abstract:"Despite the reported increase in the prevalence of mental disorders, including substance abuse disorders, required services in South Africa have not been improved to meet the demands for these challenges. Although South Africa has invested in a process to conduct a re-engineering of primary health care services to address a range of common health challenges in communities, this process has not demonstrated adequate policy and practice changes toaddress emerging challenges in providing services for mental health disorders at primary health care level. In particular, primary health care services do not include routine screening for common mental disorders, which include depression, anxiety, postnatal depression and substance abuse, although there are easy to use tools for such screening. This has resulted in a failure for early detection of these mental health challenges by the health system. The chapter argues that making moderate changes to the current offerings of primary health care can result in major achievements in offering mental health services, which in turn will benefit the patients and assist health services to address the increasing scourge of mental disorders, which include substance abuse.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78257",risUrl:"/chapter/ris/78257",signatures:"Kebogile Elizabeth Mokwena and Velaphi Anthony Mokwena",book:{id:"10707",type:"book",title:"Primary Health Care",subtitle:null,fullTitle:"Primary Health Care",slug:"primary-health-care",publishedDate:"March 16th 2022",bookSignature:"Ayşe Emel Önal",coverURL:"https://cdn.intechopen.com/books/images_new/10707.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-807-1",printIsbn:"978-1-83969-806-4",pdfIsbn:"978-1-83969-808-8",isAvailableForWebshopOrdering:!0,editors:[{id:"25840",title:"Prof.",name:"Ayse Emel",middleName:null,surname:"Onal",slug:"ayse-emel-onal",fullName:"Ayse Emel Onal"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"261452",title:"Prof.",name:"Kebogile",middleName:null,surname:"Elizabeth Mokwena",fullName:"Kebogile Elizabeth Mokwena",slug:"kebogile-elizabeth-mokwena",email:"kebogile.mokwena@smu.ac.za",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Sefako Makgatho Health Sciences University",institutionURL:null,country:{name:"South Africa"}}},{id:"417209",title:"Mr.",name:"Velaphi",middleName:null,surname:"Anthony Mokwena",fullName:"Velaphi Anthony Mokwena",slug:"velaphi-anthony-mokwena",email:"bra.veli@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Sefako Makgatho Health Sciences University",institutionURL:null,country:{name:"South Africa"}}}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_1_2",title:"1.1 Substance abuse within mental disorders",level:"2"},{id:"sec_3",title:"2. Cues and guidelines from the National Development Plan 2030",level:"1"},{id:"sec_4",title:"3. The scourge of mental disorders",level:"1"},{id:"sec_4_2",title:"3.1 Substance abuse in schools as a mental health issue",level:"2"},{id:"sec_6",title:"4. The urgency of addressing mental disorders",level:"1"},{id:"sec_7",title:"5. Qualities of a responsive health care system",level:"1"},{id:"sec_8",title:"6. The appropriateness of primary health care services for mental health services",level:"1"},{id:"sec_9",title:"7. The importance of the 1978 Alma Ata declaration in health service provision",level:"1"},{id:"sec_10",title:"8. Re-engineering of primary health care",level:"1"},{id:"sec_11",title:"9. Advocating for primary health care for mental disorders",level:"1"},{id:"sec_11_2",title:"9.1 The cost",level:"2"},{id:"sec_12_2",title:"9.2 Improved accessibility of services",level:"2"},{id:"sec_14",title:"10. Examples of success of treating mental health disorders at PHC level",level:"1"},{id:"sec_14_2",title:"10.1 Status of PHC services for mental health",level:"2"},{id:"sec_15_2",title:"10.2 Integrating mental health into mainstream primary health care services",level:"2"},{id:"sec_17",title:"11. Recommended primary health care mental health services",level:"1"},{id:"sec_17_2",title:"11.1 Screening",level:"2"},{id:"sec_18_2",title:"11.2 Prevention of mental illness and promotion of mental health",level:"2"},{id:"sec_19_2",title:"11.3 Treatment",level:"2"},{id:"sec_20_2",title:"11.4 Ongoing support",level:"2"},{id:"sec_22",title:"12. Conclusion",level:"1"},{id:"sec_23",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'Kroenke K, Unutzer J. 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My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"15",type:"subseries",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. 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