Typical Absorption of CocoPLs and CocoPEs functional groups.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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The aim of this short book is to provide the reader with several informative chapters in the field of neonatal and pediatric surgery. Each chapter provides details on a specific area of this changing field. The scope of this book focuses on a few areas that are rare and challenging. For example, it covers preoperative and postoperative care of neonates. Important anesthesia considerations, including anesthesia for neonates and regional anesthesia, are discussed. A unique chapter on neonatal tumors is presented. The book provides an overview of the recent recommendations for care of infants and children that undergo cardiac surgery. The challenging aspects of caustic ingestion are explained. Each chapter stands alone as a detailed source of information for the reader. 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Neonatal care should include close attention to achieving homeostasis and stability in the perioperative period. 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The majority of neonatal tumors are benign, with malignant lesions accounting for only 2% of childhood cancers. However, histologically benign tumors can lead to detrimental effects on the fetus and newborn due to their size and location in relation to vital structures. An understanding of the incidence, appearance, and typical locations of neonatal tumors can provide important diagnostic information and guide treatment decisions. Although surgical intervention is the mainstay of therapy for many neonatal tumors, it is important to recognize that some lesions will regress spontaneously, whereas others may respond to noninvasive treatment modalities. In this chapter, we explore the epidemiology of neonatal tumors and provide a location-based classification schema to aid in diagnosis. A summary of the presentation, diagnosis, and management of the most common neonatal tumors is provided as well.",signatures:"Kenneth W. 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It often occurs as a result of uncontrolled and unsafe storage of materials used in household cleaning. Despite the various treatment proposals, optimal management of the patients remains controversial. The presentation of the depth and extent of injury with endoscopy plays a key role in treatment planning. In the absence of life-threatening complications, the general approach is conservative management in the acute period. The most common complications are esophageal stricture and gastric outlet obstruction. Different treatment methods such as bougienage, stent application, balloon dilation, or esophageal replacement are used in the treatment of the caustic esophageal strictures. 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\r\n\tPlant invasion and global climate change are major global change components. The prediction of successful invasive plant species, interactions between plant invasion and other global change factors, as well as evaluation of invasive plant impact on the introduced environments, such as soil nutrient cycling and greenhouse gas emissions, are not well understood. This book aims to gather research in plant invasion studies associated with topics on prediction of successful invasive plants, interactions between plant invasion and other global change factors, and evaluation of invasive plant impacts, providing a thorough understanding of advances in plant invasion ecology on the background of global change. A better understanding of these questions will be helpful for future management of invasive plants, especially during global change mitigation processes, which are crucial for the sustainable development of human society and the maintenance of an environment-friendly world.
",isbn:"978-1-80356-789-1",printIsbn:"978-1-80356-788-4",pdfIsbn:"978-1-80356-790-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"90828f3756aae575bdda131afdc672af",bookSignature:"Dr. Ling Zhang",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11617.jpg",keywords:"Plant Invasion, Global Change, Climate Change, Greenhouse Gas Emission, Soil Mechanism, Global Warming, Nutrient Cycling, Mineralization, Microbial Contribution, Soil Respiration, Nitrous Oxide, Methane",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 29th 2022",dateEndSecondStepPublish:"June 2nd 2022",dateEndThirdStepPublish:"August 1st 2022",dateEndFourthStepPublish:"October 20th 2022",dateEndFifthStepPublish:"December 19th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Dr. Ling Zhang is a pioneering researcher in environmental science, holder of twenty registered patents in three countries, as well as a member of the Ecological Society of America and Forestry Society of China.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"219350",title:"Dr.",name:"Ling",middleName:null,surname:"Zhang",slug:"ling-zhang",fullName:"Ling Zhang",profilePictureURL:"https://mts.intechopen.com/storage/users/219350/images/system/219350.png",biography:"Dr. Ling Zhang obtained his Ph.D. in Soil Science from Nanjing Agricultural University, China. From 2021-2013, he visited the Department of Ecology and Evolutionary Biology, Rice University, USA. He is currently working as a professor at the College of Forestry, Jiangxi Agricultural University, China, supervising graduate students. Dr. Zhang studies global change biology, forest ecology, plant invasion, and soil carbon and nitrogen cycling. He has published more than 50 papers related to global change ecology or forest ecology, and authored or co-authored several books on forest ecology or soil ecology in the recent years. He is also serving as an associate editor of ISI journal Plant Ecology and a reviewer for more than 10 ISI journals.",institutionString:"Jiangxi Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Jiangxi Agricultural University",institutionURL:null,country:{name:"China"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"478197",firstName:"Veronika",lastName:"Radosavac",middleName:null,title:"Dr.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"veronika@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"9720",title:"Advances in Forest Management under Global Change",subtitle:null,isOpenForSubmission:!1,hash:"df888eab42f96e1bd89b300edfaec25a",slug:"advances-in-forest-management-under-global-change",bookSignature:"Ling Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/9720.jpg",editedByType:"Edited by",editors:[{id:"219350",title:"Dr.",name:"Ling",surname:"Zhang",slug:"ling-zhang",fullName:"Ling Zhang"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6418",title:"Hyperspectral Imaging in Agriculture, Food and Environment",subtitle:null,isOpenForSubmission:!1,hash:"9005c36534a5dc065577a011aea13d4d",slug:"hyperspectral-imaging-in-agriculture-food-and-environment",bookSignature:"Alejandro Isabel Luna Maldonado, Humberto Rodríguez Fuentes and Juan Antonio Vidales Contreras",coverURL:"https://cdn.intechopen.com/books/images_new/6418.jpg",editedByType:"Edited by",editors:[{id:"105774",title:"Prof.",name:"Alejandro Isabel",surname:"Luna Maldonado",slug:"alejandro-isabel-luna-maldonado",fullName:"Alejandro Isabel Luna Maldonado"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10359",title:"Landraces",subtitle:"Traditional Variety and Natural Breed",isOpenForSubmission:!1,hash:"0600836fb2c422f7b624363d1e854f68",slug:"landraces-traditional-variety-and-natural-breed",bookSignature:"Amr Elkelish",coverURL:"https://cdn.intechopen.com/books/images_new/10359.jpg",editedByType:"Edited by",editors:[{id:"231337",title:"Dr.",name:"Amr",surname:"Elkelish",slug:"amr-elkelish",fullName:"Amr Elkelish"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"117",title:"Artificial Neural Networks",subtitle:"Methodological Advances and Biomedical Applications",isOpenForSubmission:!1,hash:null,slug:"artificial-neural-networks-methodological-advances-and-biomedical-applications",bookSignature:"Kenji Suzuki",coverURL:"https://cdn.intechopen.com/books/images_new/117.jpg",editedByType:"Edited by",editors:[{id:"3095",title:"Prof.",name:"Kenji",surname:"Suzuki",slug:"kenji-suzuki",fullName:"Kenji Suzuki"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"54011",title:"Introductory Chapter: From Chaos to Cosmos – Toward Precision Medicine in Osteosarcoma",doi:"10.5772/67265",slug:"introductory-chapter-from-chaos-to-cosmos-toward-precision-medicine-in-osteosarcoma",body:'In 2016, a very impressive report was published describing that osteosarcoma (OS) is the earliest human cancer in the fossil record, dating back 1.7 million years to the Homo ergaster era [1]. This demonstrated that OS is the oldest recognized malignant neoplasm with concrete (no pun intended) evidence. In general, OS is the most common malignant bone tumor and mostly affects children, adolescents, and young adults. OS shows significant genetic instability, resulting in a very complex biology with multifaceted cellular and molecular mechanisms and behaviors. This is the main reason why treatment options are still limited and the prognosis has remained unchanged for several decades, despite significant improvements in the 1980s through advancements in systemic chemotherapy and definitive surgery [2]. The prognosis for patients with relapsed and/or metastatic disease is still quite poor.
The concept of “toward precision medicine” was proposed in 2011 to bring about a new treatment paradigm in which clinicians, researchers, patients, policymakers, the pharmaceutical industry, and health care systems work together to improve human health at all levels—disease prevention, diagnosis, and treatment—through the development of more precise, individualized care [3]. Because of the chaotic genetic background of OS and its lack of treatment options, which still mainly involve radical surgery and non-specific combination chemotherapy, the concept of precision medicine could be the most highly desired platform for patients with OS. This chaos of OS biology probably started 1.7 million or even more years ago.
The complicated genetic background of OS is characterized by an extremely heterogeneous genetic alteration spectrum. The most historical and thoroughly described genetic alterations in patients with OS are aberrations of the tumor suppressors p53 and Rb, which cause hereditary dispositions to Li-Fraumeni syndrome and retinoblastoma, respectively [4]. Because both the p53 and Rb pathways are involved in cell cycle regulation, other cell cycle regulators such as p16INK4a/p19ARF and MDM2 have also been investigated [5]. These tumor suppressors and their associated pathways are still a staple of research for potential therapeutic targets in patients with OS. However, treatments targeting these pathways thus far have failed to show substantial impact.
Recent advances in next-generation sequencing, including whole-genome sequencing, whole-exome sequencing, and RNA sequencing, have revealed several possible candidate pathways involved in OS development. In a study performed at St. Jude Children’s Research Hospital, Chen et al. [6] reported that next-generation sequencing of pediatric OS specimens revealed recurrent somatic alterations: structural variations and/or single-nucleotide variation in the ATRX and DLG2 genes. Among those, the PI3K/mTOR signaling pathways, including the PTEN, PI3K/Akt, and IGF1/mTOR pathways, have emerged as possible therapeutic targets in patients with OS [7]. A genome-wide siRNA screening with a screen of therapeutically relevant small molecules have identified the dual inhibition of the PI3K-mTOR pathway as a sensitive druggable target in OS [8]. A Sleeping Beauty transposon-based forward genetic screen also highlighted that OS driver genes are enriched in the ERBB, PI3K–AKT–mTOR, MAPK, PTEN, and NF2 signaling pathways [9]. Several specific inhibitors of the PI3K–AKT–mTOR pathway have been developed, and their efficacy against OS has been investigated; some of these inhibitors have already been applied in clinical trials [10].
High-throughput screening technologies, including those that involve microRNA (miRNA), have also had a huge impact on the cancer research field. miRNAs are small non-coding RNAs that play critical roles in the regulation of gene expression at the post-transcriptional level and in the control of cellular processes such as proliferation, differentiation, initiation, and progression of various diseases including cancer. More than 2500 miRNAs have been identified, and many of them function as oncogenes or tumor suppressors that regulate gene and protein expression. Some miRNAs like miR-34a and miR-21, target genes involved in OS development such as the p53 and Rb genes as well as the PI3K/Akt/mTOR, IGF-R1, and MAPK pathways. Some miRNAs could be proposed as potential biomarkers of disease progression and metastasis, and may serve as therapeutic targets for OS [11].
For precise, personalized therapeutic approaches, especially in the prediction of the response to chemotherapy, the establishment of predictive biomarkers is a long-standing goal in OS research. The “-omics” approach at the genome, transcriptome, and proteome levels has been applied to identify the predictive biomarkers of OS, and several potential candidates have been identified [12]. Hagleitner et al. [13] recently identified the association between five-year progression-free survival and five genetic variants [the Fas Ligand (FasL), MutS homologue 2 (MSH2), ATP-binding cassette sub-family C (ABCC5), caspase 3 (CASP3), and cytochrome P450 3A4 (CYP3A4)] using a linkage disequilibrium-based tag single-nucleotide polymorphism strategy. They found that patients with fewer risk alleles showed a more favorable prognosis. They concluded that these pharmacogenetic risk factors might be useful to predict treatment outcomes and to stratify patients, thus allowing for more personalized treatment [13]. Recent studies have also uncovered the important roles of the tumor microenvironment, including tumor stromal cells and extracellular matrices, in the development of OS. Mesenchymal stromal/stem cells (MSCs) or MSC-derived lineage-specific progenitors have long been considered as the cells of origin for certain types of sarcomas, including OS [14]. Additionally, OS development is closely linked to certain oncogenic lesions, such as p53 and Rb deficiency in MSCs, and to bone microenvironment signals such as calcified substrates and bone morphogenetic protein-2 [15]. MSCs are not only the putative cells of origin for sarcomas, but are also thought to be the source of cancer-associated fibroblasts, one of the key players in the tumor microenvironment for cancer progression [16]. Several studies have proposed that the mechanism of the interaction between MSCs and tumor cells could be a potential therapeutic target against OS. A recent study by an Italian group demonstrated that MSCs in the tumor stroma driven by oxidative stress induced by OS cells could be potential modulators of the metabolism of OS cells that underwent mitochondrial biogenesis to increase the mitochondrial activity [17]. The authors suggested that this mutual metabolic reprogramming of OS cells and their stroma could also represent a possible target for OS therapies.
Despite remarkable progress in these fields, the results of studies of specific inhibitors of possible targetable pathways and specific biomarkers have not yet been applicable to the clinical setting. However, continued progress in -omics technology, next-generation sequencing, and high-throughput screening will provide new insights into the pathogenesis of OS and will help to identify novel biomarkers that will contribute to improved therapeutic strategies, prognoses, and quality of life.
The role of immunotherapy has been investigated in both the preclinical and clinical settings in OS. Immunotherapeutic techniques include the use of nonspecific immunomodulators such as muramyl tripeptide phosphatidylethanolamine [18], interferons [19], interleukin-2 [20], adoptive T-cell immunotherapy, vaccines, immunologic checkpoint blockades such as CTLA-4/PD-1 blockade, and oncolytic viral therapy. It is very important to continue the development of immunotherapeutic strategies, especially for patients with metastatic disease in whom effective systemic therapy is not a treatment option.
Advances in imaging modalities, surgical procedures, and neoadjuvant chemotherapy have allowed more limb salvaged and less amputation to be performed. Megaprosthetic replacement has become more popular for limb salvage than any other technique, including the use of allografts and vascularized autografts. However, when preoperative chemotherapy is effective and tumor locates far enough from the joint surface, joint preservation rather than megaprosthetic replacement has been utilized. Joint preservation can be achieved using so-called biological reconstruction methods including allografts, vascularized autografts, and processed autologous bone grafts. Processed autologous bone grafts have been developed to utilize the patient’s own diseased bone sterilized by irradiation, pasteurization, and liquid nitrogen freezing. However, precise evaluation and surgical planning are required for joint-preserving reconstruction.
Recent advances in three-dimensional (3D) imaging and printing techniques have already had a significant impact on orthopedic surgery. Especially for musculoskeletal tumor resection and reconstruction, 3D visualization of computed tomographic and magnetic resonance images has become an effective supportive tool for surgical planning and determination of surgical margins. In addition, a precise personalized anatomical model of the surgical site by 3D printing can be created for each patient, and personalized guiding templates fabricated by 3D printing with computer-assisted designs have been utilized for many orthopedic surgeries, including resection of OS [21]. The jaw, including the mandible and maxilla, is a region where OS is occasionally involved, representing 7% of all cases of OS and 1% of all head and neck malignancies [22]. Although definitive surgery is still the mainstay of jaw OS treatment, precise tumor resection is sometimes difficult to achieve because of the anatomical complexity of the maxillofacial region. In this clinical setting of OS of the jaw, as well as in joint-preserving surgery, 3D imaging and printing techniques will be of great help for precise surgical treatment of OS.
A multi-disciplinary approach is essential for the management of OS. Among many clinical symptoms of OS, pain is the most prominent symptom and sometimes requires multimodal treatments. Recent studies have demonstrated that molecular pathways such as the MAPK and PI3K pathways, which are closely involved in OS development as described earlier, play critical roles in regulating the cell signaling of transient receptor potential vannilloid subfamily member 1 (TRPV1), a nocioceptive receptor among peripheral nerve fibers that is closely linked in cancer pain [23, 24]. Therefore, these pathways could be possible targets for both cancer-induced pain as well as OS development.
Comparative oncology approaches through translational research involving rodent, canine, and human, models could provide new insights for OS treatment strategies. Genetically engineered mouse models of OS have been created, such as those exhibiting Cre/LoxP–mediated deletion of p53 and/or Rb [25]. A novel model of OS developed using the Sleeping Beauty transposon mutagenesis system was recently established [9]. These mouse models will be useful to identify new candidate driver genes of OS development. While the incidence of OS in humans is roughly 25 per 10 million cases per year in the US, it is about 15 times more common in dogs. The natural history of OS and the genome-wide expression profiles are very similar between humans and canines OS [26]. Comparative studies using a multi-species approach will be indispensable for OS research and will allow us to identify true driver genes and pathways that will provide novel therapeutic targets and new therapeutic strategies encompassing the fields of chemotherapy, immunotherapy, and surgery.
Precision medicine in the management of OS should be a multidisciplinary effort involving the collaboration of both medical and non-medical professions. Involved individuals should include family members, friends, teachers, and colleagues in the patients’ schools and work places. We hope that the findings provided herein will be helpful for all individuals dealing with OS, including physicians, researchers, and patients and their family members.
We thank our families, colleagues, patients, and their family members. We also express our gratitude to all participants in this book, especially Ms. Martina Usljebrka for her tremendous efforts during book editing process.
Phospholipids are major constituent of cellular membrane hence they have excellent biocompability. They are amphiphilic molecules which usually built by glycerol backbone with two different polarity groups attached to it. On the one hand is the hydrophilic group renowned as the head group which then becomes the basis of species classification of phospholipids, such as phosphatidylcholine (PC), phosphatidyletanolamine (PE), and phosphatidylserine (PS). On the other hand is the hydrophobic fatty acyl chains distinguished as the tails. The variation of the length and the saturation, the bonding position of fatty acyl chains to glycerol backbone as well as the head group type become a crucial part of their application, for instance in drug delivery systems.
The development of phospholipids based drug delivery systems have been proven prominent by the emergence of many phospholipid-related drug formulation. Among of them are doxorubicin in stealth liposomes for cancer treatment, which has been on the market since 1995 [1, 2]; Verteporfin in cationic liposomes for molecular degeneration [3] and vincristine in conventional liposome for Non-Hodgkin lymphoma [2]. They have been used in clinic, and achieve good results. Many more phospholipids based liposomal preparation have been developed to find better therapeutic results [4, 5, 6]. Furthermore various sources, synthetic and natural, have been explored [2, 7].
The isolation of phospholipids from natural sources cost lower than synthesizing them hence the preference is the isolation of natural phospholipids. For natural origin, the more pure they are, the greater the value is [8]. Phospholipids from natural origin can be refined into diverse levels, comprising food and pharmaceutical grade [2, 9]. In term of natural phospholipids, different source enhance the species variety of phospholipids [7]. Egg yolk and soybean phospholipids mainly consist of phosphatidylcholine species but they have differences in the tail portions which influence their physical, chemical properties and their applications. Other natural phospholipids that currently are being explored extensively are sunflower [10, 11, 12], candlenut [13], jack bean [14], sesame [13, 15, 16, 17] and coconut [13, 15, 16, 18, 19, 20, 21, 22].
Coconut is one of the native plantations in tropical countries and produces mainly copra and coconut oil. Exploration of coconut by-products such as coconut phospholipids needs to be done to increase the added value of these coconut plantations. Previous studies have found that dried coconut contain phospholipids from cephaline species with their fatty acyl chains are dodecanoic and octanoic acyl chains [15]. Purification with eluent chloroform: methanol (9:1) follows by identification using thin layer chromatography (TLC) also detects the presence of phosphatidylcholine (PC), phosphatidyletanolamine (PE), and phosphatidylserine (PS) species in coconut phospholipids (CocoPLs) [20, 21].
In the matter of its application, coconut liposomes (CocoPLs liposomes) have been used in the encapsulation of hydrophilic agent namely carboxyfluoresence and vitamin C and resulted in that CocoPLs liposomes has high efficiency of encapsulation [16, 19, 22]. The addition of cholesterol improves the encapsulation efficiency and low storage temperature reduces CocoPLs liposomes leakage. The results advocated the CocoPLs potency as drug delivery material. Moreover since we have established that CocoPLs consist of many phospholipid species therefore it would be valuable to study the component of the species and their capability as drug delivery system. In this study we explore the isolation and purification of coconut phospholipid species specifically coconut phosphatidylethanolamine (CocoPEs) and utilization of their liposomes (CocoPEs liposomes) for vitamin C encapsulation with various cholesterol concentrations. To our knowledge this is the first study of such.
Materials used in this study were ripe coconut meat purchased from local market, TLC silica gel 60 F254 plate, silica gel powder 60 G for thin layer chromatography, various solvents and regents for analytical grade.
Isolation technique was carried out based on the previous method used [20, 21]. Briefly coconut meat powder was macerated in a chloroform: methanol (2:1, v/v) mixture. The filtrate obtained was washed using 0.9% NaCl. The lipid was evaporated until thick coconut lipid extract were obtained. The extract was then subjected to solvent partition using n-hexane and ethanol 87%. The lower phase was evaporated to yield brownish yellow extract of CocoPLs.
About 5 g of CocoPLs was mixed with 5 g of silica gel in a small amount of chloroform: methanol (9:1, v/v) solution to form a silica slurry. The slurry was then stirred until the mixture was dried and formed fine powder of CocoPLs-SG.
A total of 80 mg of silica gel was poured into a chromatography column and compressed by vacuum. The column was rinsed using chloroform:methanol (9:1, v/v) eluent and vacuumed until all the eluent was eluted. The CocoPLs-SG powder was poured onto the column. Then the column was subjected to compression. Elution was performed using 10 ml of chloroform:methanol (9:1, v/v) solution. Fraction eluted from the column was collected into clean vials. The fraction was analyzed using TLC plate. The spot on the TLC plate was identified with 10% H2SO4 and ninhydrin. Elution was repeated every 10 ml of the eluent until the TLC plate did not show any spot when subjected to identification. The CocoPLs fractions contained ethanolamine species were gathered into an evaporating flask and evaporated at 40°C to obtain dark brownish gel of CocoPEs.
Both CocoPLs and CocoPEs obtained were characterized using FT-IR (Prestige 21 Shimadzu), GC-MS (Shimadzu QP2010S), and LCMSMS (Waters Xevo TQD) and DSC (Shimadzu DSC-60A). The FTIR was employed to probe the phospholipids functional groups. The GC-MS was used to determine the phospholipids fatty acyl chains. The LC-MS/MS was for identifying the chemical component of CocoPEs and the DSC analysis was carried out to explore the CocoPEs phase behavior.
In this research, vitamin C (VC) was used as a model for hydrophilic drug to be encapsulated in coconut liposome [13, 16, 17, 22]. Stock solution of 500 ppm CocoPEs with cholesterol concentration (0%, 10%, 20%, 30%, 40% w/w) were made. A total of 2 mL of each stock solution was diluted with chloroform to 10 mL and poured into a test tube. The liquid solution was evaporated using N2 gas flow to form a thin layer. After that hydration process was carried out. Around 10 mL of phosphate buffer solution was added to the thin film. The mixture was subjected to freeze-thawing process until the thin film was dispersed completely. The dispersions contained empty coconut liposome and was used as control. Other set of dispersions were prepared by adding 8 ppm (
where
A brownish yellow gel of CocoPLs was obtained from dried coconut meat (
CocoPLs.
In the separation process using vacuum column chromatography, CocoPLs was eluted continuously using chloroform:methanol (9:1, v/v). Each fraction of 10 mL eluent was collected and subjected to identification. As much as 520 fractions were obtained to elute CocoPEs from the CocoPLs samples completely. Identification by TLC using 10% H2SO4 and ninhydrin spotting agent [23] resulted in that CocoPEs were present in the 105th to the 520th fraction.
The fraction contained CocoPEs were then combined and evaporated to remove the eluent that resulted in dark brown CocoPEs gel (
CocoPEs.
The functional groups identification of CocoPLs and CocoPEs was conducted by FTIR spectra analysis. The FTIR spectra of both CocoPLs and CocoPEs were displayed on Figure 3. To analyze further the spectra were scrutinized using a deconvolution program [21, 24], at wavenumbers 3500–2800 cm−1 and 1800–700 cm−1 as presented in Figure 4.
CocoPLs and CocoPEs absorption spectra.
Deconvolution results: (a) CocoPLs at wavenumbers 1800–700 cm−1; (b) CocoPLs at wavenumbers 3500–2800 cm−1; (c) CocoPEs at wavenumbers 1800–700 cm−1; (d) CocoPEs at wavenumbers 3500–2800 cm−1.
The absorption data obtained from both FTIR spectra and deconvolution analysis were compared (see Table 1) to the specific infrared absorption area for phospholipids proposed by Stuart [25] and Hudiyanti et al. [20, 21]. The presence of a typical spectrum of phospholipids was clearly revealed. Significant differences between CocoPLs and CocoPEs spectra was disclosed by the typical absorption of choline and ethanolamine groups on both spectra of CocoPLs and CocoPEs. The choline group absorptions; (CH3)3N+ asymmetric bending and (CH3)3N+ asymmetry stretching; were not present on the CocoPEs spectra. The typical absorption that indicate the presence of ethanolamine species by N-H vibration absorptions was displayed on CocoPLs and CocoPEs spectra. This evident indicated that CocoPLs contained choline and ethanolamine species while CocoPEs did not contain choline species. From The FTIR spectra point of view this data disclosed that the CocoPEs separation from CocoPLs was successful.
No. | Absorption type | References [15, 20, 21, 25] (cm−1) | CocoPLs (cm−1) | CocoPEs (cm−1) | CocoPLs Deconvolution (cm−1) | CocoPEs Deconvolution (cm−1) |
---|---|---|---|---|---|---|
1. | ||||||
2. | =C-H stretching | 3010 | — | — | 3001 | 3002 |
3. | CH3 asymmetric stretching | 2956 | — | — | 2958 | 2956 |
4. | CH2 asymmetric stretching | 2920 | 2924 | 2924 | 2923 | 2919 |
5. | CH3 symmetric stretching | 2870 | — | — | 2885 | 2890 |
6. | CH2 symmetric stretching | 2850 | 2854 | 2854 | 2850 | 2848 |
7. | C=O stretching, sn-1 chain trans-conformation | 1730 | 1735 | 1735 | 1738 | 1739 |
8. | ||||||
9. | CH2 scissoring | 1473, 1472, 1468, 1463 | — | — | — | — |
10. | CH3 asymmetric bending | 1460 | 1458 | 1458 | 1461 | 1464 |
11. | (CH3)3N+ symmetric bending | 1405 | — | — | — | — |
12. | CH3 symmetric bending | 1378 | 1373 | 1373 | 1376 | 1378 |
13. | CH3 rocking ribbon progression | 1400–1200 | — | — | 1333 | 1266 |
14. | PO2−asymmetric stretching | 1228 | 1226 | 1242 | 1225 | 1222 |
15. | CO-O-C asymmetric stretching | 1170 | 1165 | — | 1150 | 1165 |
16. | PO2− symmetric stretching | 1085 | — | 1080 | 1106 | 1107 |
17. | CO-O-C symmetric stretching | 1070 | 1072 | — | 1071 | 1070 |
18. | C-O-P stretching | 1047 | — | — | 1020 | 1003 |
19. | ||||||
20. | P-O asymmetric stretching | 820 | 817 | — | 813 | 819 |
21. | CH2 rocking | 730, 720, 718 | 717 | 725 | 714 | 713 |
Typical Absorption of CocoPLs and CocoPEs functional groups.
Bold entries represented the typical absorption of choline and ethanolamine groups on both spectra of CocoPLs and CocoPEs.
The fatty acyl chains content of CocoPLs and CocoPEs was analyzed by GC-MS. The CocoPLs chromatogram was presented on Figure 5. A total of nine peaks was recognized. Seven peaks were with abundance above 1%. The chromatogram suggested that there were at least 9 types of fatty acyl chains present on the CocoPLs. The MS reading revealed the identity of these fatty acyl chains. Three fatty acyl chains worth mentioning with the abundance more than 10%, i.e., lauric acid, palmitic acid and oleic acid which were indicated by peak number 3 (abundance of 11.31%); peak number 5 (15.26%); and peak number 7 (55.18%). The result was in agreement with previous research [15, 20, 21]. The seven fatty acyl chains recognized in CocoPLs was displayed on Table 2.
CocoPLs chromatogram.
Peak number | tR (min) | Fatty acyl chains | Area (%) |
---|---|---|---|
3. | 29.164 | Lauric acid, C12:0 (dodecanoic acid) | 11.31 |
4. | 34.037 | Myristic acid, C14:0 (tetradecanoic acid) | 5.71 |
5. | 38.497 | Palmitic acid, C16:0 (hexadecanoic acid) | 15.26 |
6. | 41.872 | Linoleic acid, C18:2 (9(Z),12(Z)-octadecadienoic acid) | 6.00 |
7. | 42.117 | Oleic acid, C18:1 (9(Z)-octadecenoic acid) | 55.18 |
8. | 42.482 | Stearic acid, C18:0 (octadecanoic acid) | 3.97 |
9. | 52.794 | Lignoceric acid, C24:0 (tetracosanoic acid) | 1.49 |
The fatty acyl chains of CocoPLs.
The chromatogram of CocoPEs was disclosed on Figure 6. The resulting chromatogram exposed the presence of five peaks with abundance above 1% which suggested the presence of five types of fatty acyl chains in the CocoPEs. Three of them had great abundance i.e. capric, linoleic and oleic acids as indicated by peak number 2, 3 and 4 and with abundance of 17.09%, 43.17% and 31.88% respectively. The MS reading of fatty acyl chains content in the CocoPEs was tabulated on Table 3.
CocoPEs chromatogram.
Peak number | tR (min) | Fatty acyl chains | Area (%) |
---|---|---|---|
2. | 38.566 | Capric acid, C10:0 (decanoic acid) | 17.09 |
3. | 42.041 | Linoleic acid, C18:2 (9(Z),12(Z)-octadecadienoic acid) | 43.17 |
4. | 42.198 | Oleic acid, C18:1 (9(Z)-octadecenoic acid) | 31.88 |
5. | 42.555 | Stearic acid, C18: 0 (octadecanoic acid) | 5.93 |
8. | 46.186 | Arachidic acid, C20:0 (eicosanoic acid) | 1.04 |
The Fatty acyl chains of CocoPEs.
Tables 2 and 3 revealed differences to some extent in fatty acyl chains composition between CocoPLs and CocoPEs. CocoPLs had more variation in fatty acyl chains type compared to CocoPEs. This fact plausible considering that CocoPEs was obtained from the separation of CocoPLs. The separation was mainly based on the common head group namely ethanolamine that reflected on the polarity of the separated CocoPEs molecules hence the choice of the separation eluent. More over fatty acyl chains profile were closely related to the position of phospholipid species in the bio-membrane bilayer [26, 27, 28]. Phosphatidylethanolamine (PE) species generally would be positioned in the inner leaflet of bilayer due to their molecular geometry, i.e. cylinder [2]. The PE species molecular shape was supported by more abundance composition of unsaturated fatty acyl chains in the CocoPEs extract, Table 3.
Based on the fatty acyl chains of the CocoPEs we conducted parent ion screening using LCMSMS. The CocoPEs parent ion spectrogram was presented on Figure 7. The spectrogram gave us a representation of the molecular species composing CocoPEs extract. At least 11 molecular species of CocoPEs were found. The CocoPEs molecular species was tabulated on Table 4. The molecular species was predicted based on the head group and combination of two fatty acyl chains for the nonpolar part of CocoPEs species. These similar species would govern the CocoPEs phase behavior and other properties as well.
CocoPEs spectrogram.
No. | m/z (M-H) | Molecular weight | CocoPEs molecular species | |
---|---|---|---|---|
Head group | Fatty acyl chains | |||
1. | 554 | 555 | Ethanolamine | Capric acid Capric acid |
2. | 662 | 663 | Ethanolamine | Capric acid Linoleic acid |
3. | 664 | 665 | Ethanolamine | Capric acid Oleic acid |
4. | 666 | 667 | Ethanolamine | Capric acid Stearic acid |
5. | 694 | 695 | Ethanolamine | Capric acid Arachidic acid |
6. | 770 | 771 | Ethanolamine | Linoleic acid Linoleic acid |
7. | 774 | 775 | Ethanolamine | Oleic acid Oleic acid |
8. | 776 | 777 | Ethanolamine | Oleic acid Stearic acid |
9. | 802 | 803 | Ethanolamine | Linoleic acid Arachidic acid |
10. | 806 | 807 | Ethanolamine | Stearic acid Arachidic acid |
11. | 834 | 835 | Ethanolamine | Arachidic acid Arachidic acid |
CocoPEs molecular species prediction.
Every phospholipid species has unique phase behavior that related to their molecular structure and phase behavior. The phase behavior of CocoPLs and CocoPEs were investigated by thermal analysis using DSC. The thermogram for CocoPLs, Figure 8, exhibited a small peak at 28.85°C and larger peak at 83.95°C. These peaks indicated that CocoPLs underwent phase changes as temperature changes. A pre-transition process from planar-shaped gel (Lb′) to the rippling phase (Pb′) was at a temperature of 28.85°C (Tp), then proceed with the main transition from gel (Lb′) to the liquid crystal phase (La) at a temperature of 83.95°C (Tm) [29, 30, 31]. Tp and Tm were the pre-transition and melting temperature correspondingly.
Thermal analysis of CocoPLs.
Different phase behavior of CocoPEs was exhibited in Figure 9. The thermogram for CocoPEs was more complex than CocoPLs indicated that CocoPEs had more complex phase transition than CocoPLs. CocoPEs displayed pre-transition process from planar-shaped gel (Lb′) to a rippling phase (Pb′) at a temperature of 25.29°C (Tp), followed by a major transition from gel (Lb′) to liquid crystal phase (La) at a temperature of 32.62°C (Tm), and then a transition from the liquid crystal phase (La) to hexagonal phase (H) at a temperature of 65.53°C (Th) [32]. The hexagonal phase formation was consistent to cylindrical molecular shape attributed to CocoPEs. The CocoPEs gradual change of phase was estimated because of the similar molecular species composing CocoPEs.
Thermal analysis of CocoPEs.
The phase behavior of CocoPEs dan CocoPLs above indicated that they were both had complex self-assembly structures which would be beneficial for future applications [2].
Phospholipids has long been known as drug delivery substance due to their liposome forming ability. Liposome was a spherical aggregation structure with bilayer phospholipid as its shell surrounding aqueous core. This unique structure was especially a perfect vehicle for delivering hydrophilic and hydrophobic drugs with storage and controlled release purposes. In this paper as a preliminary study for further application of coconut phospholipid as drug delivery material we used vitamin C as a hydrophilic drug model to be encapsulated in coconut liposomes. Vitamin C was a hydrophilic drug and would be encapsulated inside the aqueous core of liposome. The study lead to that encapsulation efficiency of vitamin C in CocoPEs were higher than CocoPLs i.e. 94.44% and 92.40% respectively, Figure 10.
Encapsulation efficiency of CocoPLs and CocoPEs liposomes with cholesterol composition variation.
In relation to their application as drug delivery, liposomes were usually made from phospholipid and a small amount of cholesterol. Cholesterol was added to the liposome membrane to control liposome rigidity and penetrability [33]. Therefore to explore the effect of cholesterol on the encapsulation efficiency of coconut liposomes we also prepared coconut liposomes with several different concentration of cholesterol namely 10%, 20%, 30% and 40%. The encapsulation efficiency of the liposomes were presented on Figure 10. The results suggested that addition of cholesterol up to 40% in the liposome’s membrane reduced the encapsulation efficiency of CocoPEs and CocoPLs liposomes. Furthermore CocoPEs liposomes demonstrated slighter reduction than CocoPLs liposomes. The encapsulation efficiency of CocoPEs diminished gradually as the cholesterol concentration increased while for CocoPLs liposomes the decline was arbitrary. Addition up to 30% of cholesterol only reduced the CocoPEs encapsulation efficiency to around 80% while CocoPLs was as low as 52%. Cholesterol effect on the encapsulation efficiency of CocoPEs liposomes more consistent than CocoPLs. We suspected it was due to the molecular composition of the phospholipid in the membrane. The molecular composition was represented by the composition of functional group and fatty acyl chains in the CocoPEs and CocoPLs, Tables 1–3. In the liposome membrane cholesterol interacted with CocoPEs and CocoPLs through their functional groups and fatty acyl chains. Cholesterol with small hydrophilic head group i.e., –OH and big and rigid hydrophobic steroid ring would interact better with small head group phospholipid species like CocoPEs than CocoPLs which had big spherical choline group and possibly other head groups as well. The composition of fatty acyl with double bonds also suspected would give more room for cholesterol hydrophobic moiety. The fatty acyl chains would assume “kink” structure at the double bond position [34, 35] and allocate more space hence more comfortable for cholesterol to integrate. With smaller number of fatty acyl chains type and higher concentration of double bond made cholesterol effect became more systematic in the CocoPEs liposome membrane. The data gave an insight about the application of CocoPEs as encapsulation material. CocoPEs was a good candidate for encapsulation hydrophilic material.
A total of (
DH and KA would like to express their gratitude of financial support by DIPA Selain APBN FSM UNDIP Riset Madya, 2018.
The authors declare that there is no conflict of interests regarding the publication of this chapter.
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',metaTitle:"Odredbe i uvjeti",metaDescription:"Ove Odredbe i uvjeti ističu pravila i regulacije u svezi korištenja IntechOpenove stranice www.intechopen.com i svih poddomena u vlasništvu IntechOpena, tvrtke sa sjedištem u 5 Princes Gate Court, London, SW7 2QJ, Ujedinjeno Kraljevstvo.",metaKeywords:null,canonicalURL:"/page/cro-terms-and-conditions",contentRaw:'[{"type":"htmlEditorComponent","content":"Pristupom na stranicu www.intechopen.com slažete se s ovim odredbama, sa svim primjenjivim zakonskim odredbama, te se slažete s poštovanjem svih lokalnih zakona. Korištenje i/ili pristup ovoj stranici temelji se na potpunom prihvaćanju ovih odredbi. Svi materijali na ovoj stranici zaštićeni su primjenjivim zakonima o autorskim pravima i žigu.
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\n"}]},successStories:{items:[]},authorsAndEditors:{filterParams:{},profiles:[{id:"396",title:"Dr.",name:"Vedran",middleName:null,surname:"Kordic",slug:"vedran-kordic",fullName:"Vedran Kordic",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/396/images/7281_n.png",biography:"After obtaining his Master's degree in Mechanical Engineering he continued his education at the Vienna University of Technology where he obtained his PhD degree in 2004. He worked as a researcher at the Automation and Control Institute, Faculty of Electrical Engineering, Vienna University of Technology until 2008. His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"57717",doi:"10.5772/intechopen.71923",title:"In Vitro Cytotoxicity and Cell Viability Assays: Principles, Advantages, and Disadvantages",slug:"in-vitro-cytotoxicity-and-cell-viability-assays-principles-advantages-and-disadvantages",totalDownloads:14810,totalCrossrefCites:77,totalDimensionsCites:156,abstract:"Cytotoxicity is one of the most important indicators for biological evaluation in vitro studies. In vitro, chemicals such as drugs and pesticides have different cytotoxicity mechanisms such as destruction of cell membranes, prevention of protein synthesis, irreversible binding to receptors etc. In order to determine the cell death caused by these damages, there is a need for cheap, reliable and reproducible short-term cytotoxicity and cell viability assays. Cytotoxicity and cell viability assays are based on various cell functions. A broad spectrum of cytotoxicity assays is currently used in the fields of toxicology and pharmacology. There are different classifications for these assays: (i) dye exclusion assays; (ii) colorimetric assays; (iii) fluorometric assays; and (iv) luminometric assays. Choosing the appropriate method among these assays is important for obtaining accurate and reliable results. When selecting the cytotoxicity and cell viability assays to be used in the study, different parameters have to be considered such as the availability in the laboratory where the study is to be performed, test compounds, detection mechanism, specificity, and sensitivity. In this chapter, information will be given about in vitro cytotoxicity and viability assays, these assays will be classified and their advantages and disadvantages will be emphasized. The aim of this chapter is to guide the researcher interested in this subject to select the appropriate assay for their study.",book:{id:"6310",slug:"genotoxicity-a-predictable-risk-to-our-actual-world",title:"Genotoxicity",fullTitle:"Genotoxicity - A Predictable Risk to Our Actual World"},signatures:"Özlem Sultan Aslantürk",authors:[{id:"211212",title:"Dr.",name:"Özlem Sultan",middleName:null,surname:"Aslantürk",slug:"ozlem-sultan-aslanturk",fullName:"Özlem Sultan Aslantürk"}]},{id:"42016",doi:"10.5772/55187",title:"Why are Early Life Stages of Aquatic Organisms more Sensitive to Toxicants than Adults?",slug:"why-are-early-life-stages-of-aquatic-organisms-more-sensitive-to-toxicants-than-adults-",totalDownloads:3490,totalCrossrefCites:38,totalDimensionsCites:103,abstract:null,book:{id:"3408",slug:"new-insights-into-toxicity-and-drug-testing",title:"New Insights into Toxicity and Drug Testing",fullTitle:"New Insights into Toxicity and Drug Testing"},signatures:"Azad Mohammed",authors:[{id:"147061",title:"Dr.",name:"Azad",middleName:null,surname:"Mohammed",slug:"azad-mohammed",fullName:"Azad Mohammed"}]},{id:"28120",doi:"10.5772/19206",title:"Experimental and Computational Methods Pertaining to Drug Solubility",slug:"experimental-and-computational-methods-pertaining-to-drug-solubility",totalDownloads:7301,totalCrossrefCites:21,totalDimensionsCites:86,abstract:null,book:{id:"1507",slug:"toxicity-and-drug-testing",title:"Toxicity and Drug Testing",fullTitle:"Toxicity and Drug Testing"},signatures:"Abolghasem Jouyban and Mohammad A. A. 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Among these heavy metals, a few have direct or indirect impact on the human body. Some of these heavy metals such as copper, cobalt, iron, nickel, magnesium, molybdenum, chromium, selenium, manganese and zinc have functional roles which are essential for various diverse physiological and biochemical activities in the body. However, some of these heavy metals in high doses can be harmful to the body while others such as cadmium, mercury, lead, chromium, silver, and arsenic in minute quantities have delirious effects in the body causing acute and chronic toxicities in humans. The focus of this chapter is to describe the various mechanism of intoxication of some selected heavy metals in humans along with their health effects. Therefore it aims to highlight on biochemical mechanisms of heavy metal intoxication which involves binding to proteins and enzymes, altering their activity and causing damage. More so, the mechanism by which heavy metals cause neurotoxicity, generate free radical which promotes oxidative stress damaging lipids, proteins and DNA molecules and how these free radicals propagate carcinogenesis are discussed. Alongside these mechanisms, the noxious health effects of these heavy metals are discussed.",book:{id:"7111",slug:"poisoning-in-the-modern-world-new-tricks-for-an-old-dog-",title:"Poisoning in the Modern World",fullTitle:"Poisoning in the Modern World - New Tricks for an Old Dog?"},signatures:"Godwill Azeh Engwa, Paschaline Udoka Ferdinand, Friday Nweke Nwalo and Marian N. Unachukwu",authors:[{id:"241837",title:"Mr.",name:"Godwill Azeh",middleName:null,surname:"Engwa",slug:"godwill-azeh-engwa",fullName:"Godwill Azeh Engwa"},{id:"274194",title:"BSc.",name:"Paschaline Ferdinand",middleName:null,surname:"Okeke",slug:"paschaline-ferdinand-okeke",fullName:"Paschaline Ferdinand Okeke"},{id:"286975",title:"Dr.",name:"Friday",middleName:null,surname:"Nweke Nwalo",slug:"friday-nweke-nwalo",fullName:"Friday Nweke Nwalo"},{id:"286976",title:"Dr.",name:"Marian",middleName:null,surname:"Unachukwu",slug:"marian-unachukwu",fullName:"Marian Unachukwu"}]},{id:"48230",title:"Mitochondrial Targeting for Drug Development",slug:"mitochondrial-targeting-for-drug-development",totalDownloads:6870,totalCrossrefCites:1,totalDimensionsCites:6,abstract:null,book:{id:"4557",slug:"toxicology-studies-cells-drugs-and-environment",title:"Toxicology Studies",fullTitle:"Toxicology Studies - Cells, Drugs and Environment"},signatures:"Jalal Pourahmad, Ahmad Salimi and Enayatollah Seydi",authors:[{id:"172672",title:"Prof.",name:"Jalal",middleName:null,surname:"Pourahmad",slug:"jalal-pourahmad",fullName:"Jalal Pourahmad"}]},{id:"48406",title:"Impact of Pesticides on Environmental and Human Health",slug:"impact-of-pesticides-on-environmental-and-human-health",totalDownloads:7426,totalCrossrefCites:26,totalDimensionsCites:69,abstract:null,book:{id:"4557",slug:"toxicology-studies-cells-drugs-and-environment",title:"Toxicology Studies",fullTitle:"Toxicology Studies - Cells, Drugs and Environment"},signatures:"Mariana Furio Franco Bernardes, Murilo Pazin, Lilian Cristina Pereira\nand Daniel Junqueira Dorta",authors:[{id:"172524",title:"Dr.",name:"Daniel",middleName:null,surname:"Dorta",slug:"daniel-dorta",fullName:"Daniel Dorta"}]},{id:"69028",title:"Aflatoxin B1: Chemistry, Environmental and Diet Sources and Potential Exposure in Human in Kenya",slug:"aflatoxin-b1-chemistry-environmental-and-diet-sources-and-potential-exposure-in-human-in-kenya",totalDownloads:1393,totalCrossrefCites:0,totalDimensionsCites:6,abstract:"Cancer incidences and mortality in Kenya are increasing according to recent reports and now number among the top five causes of mortality in the country. The risk factors responsible for this increase in cancer incidences are assumed to be genetic and/or environmental in nature. The environmental factors include exposure to carcinogenic contaminants such aflatoxins (AFs). However, the exact causes of the increase in cancer incidences and prevalence in many developing countries are not fully known. Aflatoxins are known contaminants produced by the common fungi Aspergillus flavus and the closely related Aspergillus parasiticus which grow as moulds in human foods. Aflatoxin B1 (AFB1) is most common in food and is 1000 times more potent when compared with benzo(a)pyrene, the most potent carcinogenic polycyclic aromatic hydrocarbon (PAH). Aflatoxins have therefore drawn a lot of interest in research from food safety and human health point of view. In this chapter, the chemistry, synthesis, identification, toxicology and potential human health risks of AFB1 in Kenya are discussed.",book:{id:"8094",slug:"aflatoxin-b1-occurrence-detection-and-toxicological-effects",title:"Aflatoxin B1 Occurrence, Detection and Toxicological Effects",fullTitle:"Aflatoxin B1 Occurrence, Detection and Toxicological Effects"},signatures:"Joseph Owuor Lalah, Solomon Omwoma and Dora A.O. Orony",authors:[{id:"301744",title:"Dr.",name:"Joseph",middleName:null,surname:"Lalah",slug:"joseph-lalah",fullName:"Joseph Lalah"}]},{id:"68822",title:"Heavy Metal Removal Techniques Using Response Surface Methodology: Water/Wastewater Treatment",slug:"heavy-metal-removal-techniques-using-response-surface-methodology-water-wastewater-treatment",totalDownloads:2218,totalCrossrefCites:10,totalDimensionsCites:19,abstract:"Advanced water/wastewater treatment techniques including ion exchange separation, filtration separation, and adsorption are essential in the removal of nonbiodegradable toxic wastes from water. In the current study, removal of heavy metal ions from water/wastewater and the use of response surface methodology (RSM) for experimental optimization were examined thoroughly. The objective of this work was to summarize the removal of heavy metal ions from water/wastewater using various chemical techniques and to emphasize the superiority of RSM in these studies.",book:{id:"9407",slug:"biochemical-toxicology-heavy-metals-and-nanomaterials",title:"Biochemical Toxicology",fullTitle:"Biochemical Toxicology - Heavy Metals and Nanomaterials"},signatures:"Muharrem Ince and Olcay Kaplan Ince",authors:[{id:"258431",title:"Prof.",name:"Muharrem",middleName:null,surname:"Ince",slug:"muharrem-ince",fullName:"Muharrem Ince"},{id:"266549",title:"Dr.",name:"Olcay",middleName:null,surname:"Kaplan Ince",slug:"olcay-kaplan-ince",fullName:"Olcay Kaplan Ince"}]}],onlineFirstChaptersFilter:{topicId:"220",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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He is currently the Director of the Postgraduate Program in Implantology of the Bioface/UCAM/PgO (Montevideo, Uruguay), Director of the Cathedra of Biotechnology of the Catholic University of Murcia (Murcia, Spain), an Extraordinary Full Professor of the Catholic University of Murcia (Murcia, Spain) as well as the Director of the private center of research Biotecnos – Technology and Science (Montevideo, Uruguay). Applied biomaterials, cellular and molecular biology, and dental implants are among his research interests. He has published several original papers in renowned journals. In addition, he is also a Collaborating Professor in several Postgraduate programs at different universities all over the world.",institutionString:null,institution:{name:"Universidad Católica San Antonio de Murcia",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. 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At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. 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