High methoxyl pectins (HMP) and low methoxyl pectins (LMP) from various horticultural crops.
\r\n\tWe must not forget that farming requires quite different approaches and animal feeding conditions in different farming systems. It is not the same having a larger number of animals or small herds just for family needs.
\r\n\r\n\tHowever, one thing should be common and most important: animal “well-being”, knowledge of the health status of animals, continuous monitoring and, if necessary, healing and treatment of animals. Without this knowledge, infectious diseases, feed-borne diseases and resistance to individual drugs cannot be traced, which can lead to very serious problems and, in some cases, tragedies.
",isbn:"978-1-78984-709-3",printIsbn:"978-1-78984-708-6",pdfIsbn:"978-1-78985-193-9",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"7e5d45badb49806d949ad1475e3a0ef0",bookSignature:"Prof. Sándor Kukovics",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9706.jpg",keywords:"Goats and Environment, Stress Factors, Goats Feed, Goats and Society, Economy, Meat, Skin, Fibre, Milk, Human Health Benefits, Goat Health, Goat Management",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 2nd 2020",dateEndSecondStepPublish:"December 3rd 2020",dateEndThirdStepPublish:"February 1st 2021",dateEndFourthStepPublish:"April 22nd 2021",dateEndFifthStepPublish:"June 21st 2021",remainingDaysToSecondStep:"2 months",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Kukovics is the President of the Hungarian Sheep and Goat Dairying Public Utility Association. He has been the Executive Manager of Sheep and Goat Products’ Board and Inter-professional Organisation since 2010. Between 2015 and 2019 he served as Vice President of the EU COPA-COGECA Working Party on Sheep and Goats and he has been a member of the Board of Directors of the International Goat Association since 2016.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"25894",title:"Prof.",name:"Sándor",middleName:null,surname:"Kukovics",slug:"sandor-kukovics",fullName:"Sándor Kukovics",profilePictureURL:"https://mts.intechopen.com/storage/users/25894/images/system/25894.jpeg",biography:"Prof. Dr. Sándor Kukovics spent 40 years at the Research Institute\nfor Animal Breeding and Nutrition (Herceghalom, Hungary)\nbeing responsible for the small ruminants sector. He also edited\n30 books, published more than 1,000 articles and has licences\nfor 4 products. Besides research work, he has been taking part in\nundergraduate and further education from various universities (in\nDebrecen, Mosonmagyaróvár, Gödöllő, Kaposvár). Since 1996 he\nhas been the President of the Hungarian Sheep and Goat Dairying Public Utility Association. He has been the Executive Manager of Sheep and Goat Products’ Board and\nInter-professional Organisation since 2010. Between 2015 and 2019 he served as Vice\nPresident of the EU COPA-COGECA Working Party on Sheep and Goats and he has\nbeen a member of the Board of Directors of the International Goat Association since\n2016. 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From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],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"}}]},chapter:{item:{type:"chapter",id:"55778",title:"Using Human Pluripotent Stem Cell-Derived Neural Cultures to Assess Safety of New Drugs and Chemicals",doi:"10.5772/intechopen.69434",slug:"using-human-pluripotent-stem-cell-derived-neural-cultures-to-assess-safety-of-new-drugs-and-chemical",body:'\nThe human central nervous system (CNS) is a unique structure organized in an intricate network composed of different cell types [1, 2]. Its homeostasis is maintained by an orchestrated signaling milieu composed of neurotransmitters, cell-cell interactions, and protein factors. Any compound acting upon one of the CNS components could potentially shift this delicate balance, resulting in untoward outcomes. Therefore, safety pharmacology profiling for compounds that crosses the blood-brain barrier represents a key step in the drug development process, particular prior to conducting studies in human subjects. Recently, the Biotechnology Innovation Organization (BIO) released the largest study of clinical drug development success rates to date [3]. In partnership with Amplion and Biomedtracker, BIO collected and analyzed a total of 9985 phase transitions in clinical trials between 2006 and 2015. Their data revealed a likelihood of approval being of only 9.6% for all developmental candidates. If segmented by diseases, candidates to neurology and psychiatry disorders fall under 9.6%, with 8.4 and 6.2% likelihood of approval, respectively. Moreover, adverse effects to the CNS account for a considerable proportion of all drug attrition cases. This demonstrates the poor predictability of current animal and in vitro models leveraged at the pre-clinical drug development stage.
\nAssessing the toxicological profile of new molecular entities requires extensive investigation using in vitro and in vivo models (Figure 1). This incremental accumulation of data helps to evaluate the toxicological profile and potential side effects of new compounds before moving to clinical trials. Studies to investigate the toxicity of drugs on the human central nervous system (CNS) relies mostly on animal (in vivo) and cellular (in vitro) models [4]. Although significant achievements have been accomplished using these models, there are many bottlenecks to overcome. For instance, efforts to fully recapitulate the human nervous system using animal models can be very challenging [5]. Rodents and human brains display major genetic, cellular, and anatomical differences [6]. Many compounds have failed in clinical trials even after being considered promising based on rigorous testing in animal models. Therapies to Alzheimer’s disease (AD) for example have an attrition rate of 99.6% [7]. Many potential therapeutic compounds for AD displayed unacceptable toxicity in humans. Additionally, while animal models have unquestionable importance in toxicological studies, new technologies could uniquely help to address the 3R principles of refine, reduce, and replace their use in this research space [8].
\nIn vitro and in vivo models available for toxicological screenings. As the complexity of the model increases, there is a substantial decrease in throughput. Common cellular models include immortalized cell lines, primary tissue culture and hPSC-derived cells. Organoids are 3D structures derived from hPSC differentiation toward neuroectoderm in suspension.
There are two main in vitro cellular models available for toxicology studies: primary and established cell lines [9, 10]. Primary cell lines are isolated directly from tissues. Their main advantage is that they more closely remember the in vivo counterpart, displaying many features presented in the target tissue. However, primary cell lines need fresh tissue to establish the cell culture and have limited capability of expansion in vitro. This turns impractical Studies that require large numbers of cells, especially from difficult-to-obtain tissue such as the human central nervous system. Immortalized cell lines, on the other hand, can be kept in culture for extensive periods of time and expanded through passaging. The immortalized cells have the intrinsic ability to proliferate indefinitely in culture, usually acquired by multiple mutations or transformations in their genomes. Although the proliferative potentials for immortalized cells make them amenable to large-scale production, they may significantly differ from the tissue of origin. Given the limitations imposed by these types of cell culture, human pluripotent stem cells have gained credence as a new reliable source of human tissues, with many advantages over the traditional in vitro cellular models.
\nHuman pluripotent stem cells (hPSC) have the ability to expand to large amounts and differentiate into any cellular tissue of the body [11]. Giving these extraordinary abilities, hPSC can potentially change the current paradigm in pharmacological research, offering unlimited access to a reliable source of neural tissue able to mimic early and late stages of human CNS development [2]. There are two types of hPSC: embryonic stem cells (hESC) and induced pluripotent stem cells (iPSC). Although both types share the same core features that classified them as hPSC, such as the ability of differentiating to any adult tissue, there are major differences between them. The hESC are derived from inner cell mass of blastocyst stage embryos after 5 days from the fertilization of the oocyte [12]. As of January 2017, 378 hESC lines were eligible for NIH fund research [13]. Comparatively, this library is still small to fully explore the whole human genomic diversity landscape. Moreover, giving its origin, hESC carry many ethical issues [14]. In spite of that, hESC have been pivotal on advancing the human stem cells research, permitting unlimited access to any human tissue of interest for the first time.
\nIn 2006, a scientific breakthrough introduced a technique able to generate pluripotent stem cells without the ethical controversies of embryonic stem cells [15]. The team used the technique of reprogramming to reverse an adult mouse cell (fibroblast) into a pluripotent stem stage: the induced pluripotent stem cells (iPSC). Soon after the same research group published the technique using human fibroblast to generate human-induced pluripotent stem cells (hiPSC) [16]. Once hiPSC have the same capacity as their hESC counterparts to generate human target cells in vitro, many scientists have shifted their focus into producing patient-specific iPSC to potentially validate disease phenotypes in vitro [17]. For the nervous system, many studies confirmed the great potential of hiPSC in recapitulating CNS diseases [18, 19]. Moreover, studies have revealed the potential of using hiPSC as a drug-screening platform to systematically evaluate spontaneous neurological disorders and drug-induced neurotoxicity [17]. The biggest challenge for this approach is to identify key phenotypes in vitro for reproducible outcomes. Neurodevelopmental disorders, for example, impose such a significant challenge. Recently, two studies that focused on different diseases (Rett Syndrome and MeCP2 Duplication Syndrome) successfully demonstrated the use of hiPSC-derived cells in identifying potential therapeutic candidates [20, 21]. Both neurodevelopmental disorders altered MeCP2 gene expression (loss of a functional copy in Rett Syndrome and overexpression in MeCP2 Duplication Syndrome). These studies identified core alterations in the synapses of neurons in both conditions. In the MeCP2 Duplication Syndrome study, researchers developed a simplified drug-screening platform able to quickly assess the synaptic phenotype. By using a library of epigenetic modifiers, they identified two compounds that able to reverse the synaptic phenotype in vitro. However, the study also displays an alarming finding: although both potential therapeutic compounds identified in the study induced rescue of the cellular synaptic phenotype in vitro, one of them demonstrated significant toxicity on the CNS function in selected electrophysiology assays. This study highlights the need for an extensive characterization of drug toxicity in vitro before further consideration in human studies.
\nThe extraordinary ability of hPSC to differentiate to CNS components makes them an interesting platform to better understand the deleterious effects of compounds on neural tissue [11, 22, 23]. Paired with cellular, genetic, biochemical, and functional assays, hPSC-derived neural tissue can be used to generate a comprehensive toxicological profile of drugs on the CNS and help to address decisions of go/no-go during a drug development process. Moreover, the brain undergoes significant postnatal development and its structure and function differ significantly between infantile and adult stages. Many drugs can affect the CNS differently, depending on the maturity of the subject (i.e., embryonic, infantile, or adult). Taken together, researchers may leverage hPSC-derived neural cells in different stages of differentiation to explore the safety profile of drugs on mature and immature nervous systems.
\nNeural precursor cells (NPCs) are multipotent cells, with the potential to generate multiple mature CNS cells, such as neurons, astrocytes, and oligodendrocytes [2, 24]. They are able to self-renew and proliferate, being pivotal players in the developing human brain. Toxicity to these cells at young stages of development can predispose the CNS to the onset of neurodevelopmental disorders and neurological impairments [25]. NPCs can be expanded in vitro, which makes them amenable to incorporation into large-scale studies. Protocols to maintain and differentiate NPCs in their CNS derivatives are well established, with great consistency and reproducibility [2, 26]. Moreover, hiPSC from different individuals can be used to obtain a progenitor cell bank representative of genetic differences found on our population. Assessing toxicological profile in such a heterogeneous genomic population could improve predictability of safety profiles of drugs on different individuals.
\nPublications with human NPCs started to demonstrate their use in assessing toxicological profile of drugs [25, 27]. Using hESC-derived NPCs, a research group described a platform for detection of toxicity to neuronal induction in embryonic development [28]. Researchers exposed differentiating cells to methylmercury (MeHg) and found that it could disrupt early stages of neural differentiation. In another approach, researchers described the use of hESC-derived NPCs in identifying compounds that were selectively toxic to progenitor, but innocuous to terminally differentiated cells (neurons and astrocytes) [29]. Although the work was primarily envisioned as a platform to identify compounds able to deplete proliferation cells from heterogeneous neural populations in vitro, with applications in purifying populations for regenerative medicine, similar approach could also be used to elucidate the safety profile of chemical compounds on the CNS.
\nDifferentiated populations of neurons have also been used to assess the toxicological profile of compounds [11]. Phenotypic assays such as neurite outgrowth and neuronal morphology have been used to investigate the effect of chemical entities on these populations. In a recent study, a library of 80 compounds was screened for their ability to inhibit neurite outgrowth in iPSC-derived neurons using a high-content screening platform [30]. From the compounds tested, 16 selectively inhibited neurite outgrowth, confirming the usefulness of hiPSC-derived neurons in neurotoxicity screenings. Although this study represents a step forward in developing a relevant humanized safety screening platform, it still relies on dissociated neurons plated at low density in vitro, which does not represent well the developed brain. Additionally, more sophisticated platforms, able to capture functional phenotypes, such as electrical activity of the neural circuitry, and the interplay between different CNS cell types will greatly help to improve the predictability of safety screenings.
\nGiven the easy accessibility to CNS cells that hPSC offer, we have witnessed in the recent years the rediscovery of three-dimensional (3D) cell culture technologies as a powerful tool to study the brain [31, 32]. Organoids are 3D agglomerates of tissue-specific cells self-organized in structures that more closely resemble the target organ. Once organoids exhibit key structural and functional properties of a target tissue, they hold great promise in advancing the studies of complex organs such as the brain, where the interaction of many different cells organized in a defined structure is pivotal for its functions (Figure 2). Moreover, giving the complex interplay between neuronal and non-neuronal cells in the CNS, the deleterious effect of drugs may rely on non-neuronal cells (and not directly on neurons) but still lead to a pronounced effect on the nervous system. In this scenario, brain organoids could better capture any deviation from the homeostatic balance of the interaction between different neural cells.
\nIn vitro models derived from hPSC. The main advantages and bottlenecks are listed. Brain organoids are 3D structures derived from hPSC differentiation toward neuroectoderm.
Two different types of cells can be used to obtain organoids: hPSC (using either ESC or iPSC) or multipotent adult stem cells [32]. Both approaches rely on the potential for expansion and self-organization of these precursors in vitro. Many recent studies have confirmed the used of brain organoids in the modeling of diseases by recapitulating in vitro the intricate and complex processes occurring during human brain development. Moreover, brain organoid constructs incorporating many different cell types (such as neurons, astrocytes, endothelial, and microglia) can be obtained and used in developmental neurotoxicity screenings [33]. By using the described model, a recent study assessed the neurotoxicity profile of a library of 60 compounds and correctly classified 9 of 10 chemicals. Although organoids containing different tissues would be a model more representative of the organ in vivo, the different tissue-specific cells lack the structural organization found in vivo and may not fully recapitulate the organ function or multi-tissue interactions.
\nCell viability, gene expression and neurite outgrowth assays with neurons have been the standard methods in vitro to measure deleterious effects of compounds on the CNS. In spite of their importance, they have limited predictability, especially with drugs able to evoke a deleterious functional change but without noticeable biochemical or cellular changes. Electrophysiology techniques exploit ionic conductance of ion channels and transient modulation of the membrane potential of a neuron, being able to assess the functional status of the neural network in vitro [34]. There are many different techniques to record neuronal activity in vitro, with the most commonly used being the patch-clamp method. Although very sensitive, its low throughput and limitation of assessing only one or few neurons at a time precludes its use in investigating large neuronal circuitry dynamics [34]. Recently, new technologies of extracellular recordings have been developed. They have many advantages over traditional patch-clamp techniques, such as being noninvasive, capable of monitoring the culture for long periods of time, and able to record multiple cells at once, allowing large-scale assessment of neuronal circuitry dynamics [35]. This allows their use to better understand neuronal communication, information encoding, propagation, processing, and computation of neuronal circuits in vitro [36].
\nOne of the most promising technologies to record extracellular signaling is the microelectrode arrays (MEA). Uniquely, MEA platforms consist of hundreds to thousands of electrodes integrated in a cell culture dish and enable recordings of neural activity by sensing extracellular field potentials [37]. This technology has been used to investigate the neural network dynamics of hESC- and hiPSC-derived neuronal cultures, organotypic slice cultures and acute brain slices [34]. By combining multiple arrays, the MEA technology allows to investigate several conditions at the time in a high-throughput fashion. Moreover, because MEA is a noninvasive technology and the neurons are cultured directly onto the electrodes, this technology enables the repeated monitoring of intrinsic and inducible changes in neuronal network dynamics for several days which is extremely useful to investigate the relative effects of chronic drug exposure in a dish [35, 38].
\nFunctional electrophysiology of neurons represents a powerful tool to investigate the safety pharmacology of drugs prior to first-in-human studies. It needs to be noted though that the human brain contains hundreds of different types of neurons, each with unique properties and pharmacological signal transduction pathways which may not be fully recapitulated in vitro. When mimicking the human brain in vitro, it is imperative to select the most appropriate cellular model to ensure unequivocally adequate and highly reproducible predictability [34]. Although mouse and rat primary neuronal cultures are the gold standard in MEA electrophysiology, interspecies differences in ion-channel expression profile and neuronal response can be significantly different; therefore, translation of data to the human brain is very challenging in many situations [39]. The potential of using human PSC as a source of neuronal circuitry mimicking the human brain just started to be explored [40]. While preliminary results are confirming the use of hiPSC-derived neural culture as a powerful tool to explore neurotoxicity of compounds on the human brain, more studies are warranted to address the variability and heterogeneity of such cell culture models.
\nGiving the high degree of complexity of the CNS cellular components, full translation from in vitro studies of compound-induced neurotoxicity can be challenging [40]. In the recent years, the stem cell field has produced diverse protocols for obtaining hiPSC-derived neurons in vitro, making any attempt to standardize the field complicate once each laboratory uses its own protocol. Moreover, the field is also subjected to batch-to-batch variation and long period of time differentiation protocols, which introduce additional challenges in reproducibility and hampers its full adoption by screening companies. Recently, however, a number of hiPSC-derived neurons became commercially available. Homogenous populations of neurons with specific neurotransmitter profiles are an attractive alternative to study the human physiology. The reduced variability from batch-to-batch and controlled differentiation process make possible the reproducible use of these cells to investigate neurotoxicity on the CNS. One thing to be noted though is the difference between hiPSC-derived products offered by different companies. Additionally, while most companies focus on highly pure populations of neurons, depleted of glia cells, this model may not be ideal to mimic the CNS complexity. The presence of astrocytes, for example, are important to modulate the response of neurons to neurotransmitters and can affect the vulnerability of neuronal cultures to toxic insults [41, 42]. Moreover, co-culture with astrocytes enhances synaptic maturation, with consequences on firing frequency and bursting behavior [43, 44]. Although still an emerging field with many questions to be answered, commercially available hiPSC-derived neurons and astrocytes will be pivotal in validating this model as a suitable solution to reduce (or even replace) animal experimentation in toxicology studies.
\nIn February of 2016 the World Health Organization (WHO) declared the Zika virus infection a Public Health Emergency of International Concern (PHEIC), which prompted scientist worldwide to an urgent and coordinated response to this new global threat. Zika virus was first identified in 1947, but only recently received public attention after being associated with microcephaly in newborns and Guillain-Barré syndrome in adults [45, 46]. Two recent studies screened libraries of FDA-approved drugs and identified potential therapeutics with novel activity against the Zika virus [47, 48]. Repurposing FDA-approved drugs can potentially accelerate the discovery of cures to diseases, reducing time, and costs. However, both studies lack extensive neurotoxicity characterization of the potential therapeutics. Although the library consisted of FDA-approved compounds, the active concentrations against the virus were relatively high and not necessarily safe to human use. Moreover, it is pivotal to assess the safety of these compounds in early stages of the CNS development before considering them to treat pregnant women or newborns. In a recent scientific communication, our group demonstrated that many of the compounds identified on the mentioned studies were in fact toxic at their effective concentrations against Zika virus [49]. We investigated the toxicological profile of 29 compounds described as potential therapeutic against Zika virus infection. By testing hiPSC-derived cells at different stages of the CNS development, we observed greater toxicity at early stages of the nervous system, with decreasing toxicity as the cells matured in vitro. Interestingly, Emricasan (a compound highlighted in a previous publication) demonstrated a safe toxicological profile in all stages of the CNS and did not interfere with the normal function of mature neural cultures, as assessed by calcium mobilization assays using a fluorescent imaging plate reader (FLIPR) platform and electrophysiology using MEA [48]. Nonetheless, this study emphasized the need for extensive early characterization of repurposed compounds before considering them to potentially alleviate new diseases.
\nThere is an urgency to accelerate and streamline the process of the development of new drugs. From devastating neurodegenerative disorders, such as Alzheimer’s, to global threats, epidemics from known and unknown viruses, we need to be able to rapidly identify safe therapeutic compounds. The average time to translate a drug from the bench to the clinic is 10 years, with an approximate cost of $2.6 billion dollars. One contributor for this is the fact that the current drug development process is very inefficient, with fewer than 10% of the drugs in development being approved for use [50]. Adverse drug reactions to CNS are responsible for a large amount of all drug attrition cases [51]. To change the current scenario, it is crucial to have available a toolbox able to quickly assess the toxicological profile in early steps of drug development. The incredible potential of hPSC to expand in vitro and differentiate toward any adult cell type makes them ideal tools to large-scale toxicology studies. Together with techniques able to assess functional phenotype in real time, such as MEA technology, terminally differentiated neurons derived from hPSC could help to improve clinical outcome predictability in early steps of the clinical trial, reducing overall costs and turnover of the drug development process.
\nIn an attempt to streamline the discovery, development, and delivery of new cures, the House of Representatives of the United States of America recently passed the 21st Century Cures Act [52]. The bill will allocate funds to the National Institute of Health (NIH) and help to fast track the approval of new drugs by the Food and Drug Administration (FDA). The Cures Act will also provide funding for three innovative scientific initiatives: the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative, the Precision Medicine Initiative (PMI) and the Beau Biden Cancer Moonshot Initiative [53]. Moreover, the Cures Act also simplifies the process of data sharing, allowing the quick use of data by the scientific community. The BRAIN initiative aims to elucidate how the neural network works in health brains and what is altered in neurological disorders. The building of knowledge on these brain states is pivotal to any drug development workflow. However, although initiatives as the BRAIN are required to advance our medical knowledge about the CNS, it is crucial to develop new platforms able to recapitulate these findings in vitro. To this end, platforms to assess adverse drug effects on the CNS using hiPSC are pointed as the most promising and currently being developed [17].
\nHuman iPSC already started to revolutionize disease modeling in vitro, revealing disease mechanisms otherwise not seen using classical animal models. Moreover, once hiPSC can be derived from any individual, it enables their use in personalized medicine, including toxicological screening in individual-specific tissues to reveal the potential side effects of drugs before their use. One caveat though is the simplified representation of the nervous system tissue architecture that can be obtained in vitro using hiPSC-derived cell culture techniques. In an attempt to overcome this limitation, the field is seen as a re-emergence of 3D organoids. Recent studies with brain organoids have confirmed their potential in recapitulating steps of the human brain development and organization. The development of new 3D high-content screening technologies, such as Light Sheet Microscopy, and improved differentiation protocols will be critical to a broad adoption of this technology in drug development screenings. Moreover, they can be an attractive alternative in replacing animal use in certain applications as well in guiding conventional clinical trial studies for dose tolerance in humans. In principle, the use of brain organoids in screenings could help to provide a more fine-tuned and multipronged approach to understand the risks and benefits of new therapies [10].
\nIn addition to hPSC, the repurposing of old drugs to new diseases have gained attention in the recent years and promise to revolutionize the drug discovery field [54]. Repurposing drugs could significantly decrease the time and costs to find new therapies. However, it is still crucial to re-evaluate their toxicological profile. When redirecting compounds to new diseases, their new efficacy dosage need to be extensively tested to assure safety on the clinic, once many redirected compounds present a higher effective concentration for 50% of the maximum response (IC50) and may not be clinically relevant. The recent example of repurposing drugs to Zika virus found many hits with a higher IC50 than the safest dosage identified in a toxicological screening using hiPSC-derived neural progenitor cells, preventing their use in newborns and pregnant women [48, 49]. Drug combination therapy, using two or three compounds found in the repurposing screening, could potentially increase the success rate of such screening by synergistic effects of the combination [54]. Successfully synergistic combinations of drugs would enable the reduction of each drug dosage to nontoxic levels and allow to use a therapeutic concentration that is below or equal to their achievable human blood concentrations.
\nFinally, the Zika virus prompted the scientific community to react and collaborate in a fashion not seen before. Different fields joined forces sharing a common goal: discover new therapies and vaccines to an emerging global threat. It also highlighted the need to change the current drug development workflow. In face of such threats, new tools are needed allowing researchers to quickly identify new therapeutic compounds. Elements discussed on this chapter, such as hPSCs and their derivatives, combined with MEA electrophysiology will streamline this process and be the standard toxicological assays in the future.
\nThis chapter was greatly improved with critical advisement from Ana Paula Diniz Mendes.
\nPectin is the major constituent of all plants and makes up approximately two-third of the dry mass of plant primary cell walls. It provides structural integrity, strength, and flexibility to the cell wall and acts as barrier to the external environment [1]. Pectin is also a natural component of all omnivorous diet and is an important source of dietary fiber. Due to the resistant in digestive system and lack of pectin digestive enzymes, human beings are not able to digest pectin directly but microorganism present in large intestine can easily assimilate the pectin and convert it into soluble fibers. These oligosaccharides promote beneficial microbiota in gut and also help in lipid and fat metabolism, glycemic regulation, etc. [2]. Being complex and highly diverse in structure, role of pectin is not only limited to the biological and physiological functions, but it has tremendous potential and contributes substantially in other applications ranging from food processing to pharmaceuticals. Pectin is a water-soluble fiber and used in various food as emulsifier, stabilizer, gelling, and thickening agent.
\nCommercial pectins are extracted from citrus and apple fruit. On the basis of dry mass, apple pomace contains 10–15% pectin, whereas citrus peel possesses 20–30% pectin. However, pectin has also been extracted in higher amount from several other fruits and their by-products, such as sunflower head, mango peal, soybean hull [3], passion fruit peel [4], sugar beet pulp [5], Akebia trifoliata peel [6], peach pomace [7], banana peel [8], chickpea husk [9], and many more [10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23]. Table 1 summarizes the different types of pectin extracted from various horticultural crops. But detection and extraction of pectin in higher concentration is not sufficient to qualify that fruit as a source of commercial pectin because of the structural variation and modification in side-chain sugars, and also that pectin from different sources has different gelling properties.
\nS. No | \nSource | \nParts used | \nExtraction method used | \nPectin yield (%) | \nType of pectin (HMP/LMP) | \nRef | \n
---|---|---|---|---|---|---|
1 | \nPassion fruit | \nPeel | \nAPP | \n14.8% | \nHMP | \n[4] | \n
2 | \nBanana | \nPeel | \nAPP | \n5–21% | \nHMP (DE, 50–80%) | \n[8] | \n
3 | \nChick pea | \nHusk | \nAcid extraction, APP, and freeze dried | \n8% | \nLMP (DE, 10%) | \n[9] | \n
4 | \nKrueo Ma Noy | \nLeaves | \nAPP, DPP | \n21–28% | \nLMP (DE, 34–42%) | \n[11] | \n
5 | \nYellow Passion | \nFruit rind | \nAPP, DPP, MPP | \n3–16% | \nHMP (DE, 54–59%) | \n[12] | \n
6 | \nDurian | \nRind | \nAPP | \n2–10.25% | \nHMP (DE, 50–64%) | \n[13] | \n
7 | \nMulberry | \nMulberry bark with epidermis (MBE) and without epidermis (MB) | \nExtracted using 60–100% isopropanol | \n11.88% | \nHMP (MB–DE, 71.13%); LMP (MBE–DE, 24.27%) | \n[14] | \n
8 | \nYuzu, citrus family | \nPomace | \nExtracted with APP and enzyme (Viscozyme® L with 1.2 × 10−4 fungal β-glucanase | \nDPP, APP (7.3–8%) | \nLMP (APP–DE, 41%; DPP–DE, 46.3%) | \n[16] | \n
9 | \nCacao pods | \nHusk | \nExtracted with 1 N HNO3 at different pH and precipitated by ethanol and acetone | \n3.7–8.6% | \nLMP (DE 36.7% @ pH 1, DE 44.3% @ pH 3); HMP (DE 52.4% @ pH 2) | \n[17] | \n
10 | \nCashew apple | \nPomace | \nAOP at different pH (1.0, 1.5, and 2.0) | \n10.7–25.3% | \nLMP (DE, 28–46%) | \n[18] | \n
11 | \nCyclea barbata Miers (CBM) | \nLeaves | \nExtracted with acid and alkali, precipitated the pectin by ethanol | \n4–8% | \nHMP (acid treated: 65–75% DE) LMP (Alkali treated: 36% DE) | \n[19] | \n
12 | \nDragon fruit | \nPeel | \nExtracted using HCl, precipitated and purified with 70 and 99.6% isopropanol. | \n18.59% | \nLMP (DE, 46.95%) | \n[20] | \n
13 | \nJackfruit | \nPeel | \nUltrasonic-microwave-assisted extracted (UMAE) pectin | \n21.5% | \nHMP (DE, 62.5%) | \n[22] | \n
14 | \nPotato | \nPulp | \nExtracted with different acids and precipitated by ethanol | \n4.08–14.34% | \nLMP (DE, 21.51–37.45%) | \n[23] | \n
High methoxyl pectins (HMP) and low methoxyl pectins (LMP) from various horticultural crops.
APP, alcohol-precipitated pectin; MPP, metal ion-precipitated pectin; DPP, dialyzed precipitated pectin.
Pectin is a highly complex plant cell wall polysaccharide that plays a significant role in plant growth and development. It is predominantly present in fruits and vegetables and constitutes approximately 35–40% of the primary cell wall in all the dicot plants [24]. The composition and structure of pectin is influenced by the developmental stages of plants [25, 26]. Structural analysis of pectin revealed that it is a polymer comprised of chain-like configuration of approximately 100–1000 saccharide units; therefore, it does not possess a defined structure. In general, pectin is illustrated as a heteropolysaccharide of three components namely, homogalacturonan (HG), rhamnogalacturonan-I (RGI), and rhamnogalacturonan-II (RGII) [28, 29]. The Backbone structure may branch with other neutral sugar chains such as arabinan, xylogalacturonan (XGA), arabinogalactan I (AG-I), and arabinogalactan II (AG-II).
\nHomogalacturonan (HG) is a polymer of galacturonic acid (GalA), in which Gal A residues are linked together by α-1-4 glycosidic bond and the number of GalA residues in HG may vary from 72 to 100% depending on the source of pectin [30]. For instance, the HG backbone of cashew apple pectin, C. maxima pectin, sunflower pectin, citrus pectin, comprises of 69.9–85%, 71–75%, 77–85%, 80–95%, GalA residues, respectively. Amaranth pectin contains more than 80% GalA residues in HG backbone structure. Furthermore, it was also observed that HG may be methoxy-esterified at C-6 and/or O-acetylated at the O-2 and/or O-3. Some exception has also been reported in the detailed structural analysis of HG region of pectin such as C-3 substitution of the galacturonic acids of HG with xylose in pea, apple, carrot, duck weed, etc. [31], and C-2 or C-3 with apiose in duck weeds (Lemna minor) [32]. HG is susceptible to both mechanical and enzymatic deesterification and degradation.
\nRhamnogalacturonan I represents approximately 20–35% of the pectin polysaccharides. It is the highly branched and heterogeneous polysaccharide which is characterized as repeating units of α-(1 → 2)-linked rhamnose and α-(1 → 4)-linked GalA residues. It can be O-acetylated at O-2 and/or O-3 positions of GalA residues [33, 34]. Pectin from citrus peels, mung bean, kidney bean, apple fruit, and flax hypocotyls has been reported 100% methyl esterified in the RGI region [35, 36]. The composition of RGI varies in pectin extracted from different sources. In sugar beet pectin, 80 repeating units of [→2] –α-L-Rha-(1–4)- α-D-GalA-(1→) comprised the backbone of rhamnogalacturonan I (RG-I), whereas citrus pectin contains only 15–40 repeating units [37]. The polymeric side chains of galactans and arabinans are substituted at the O-4 position of RG-I backbone. Arabinogalactan I (AG-I) and arabinogalactan II (AG-II) are also reported to be present as polymeric side chains [38, 39, 40]. The side chains are often referred to as “hairs” and believed to play an important role in pectin functionality. The loss of side chains may increase the solubility of the pectin [41]. PGI is prone to enzymatic depolymerization. However, protease and acid-catalyzed cleavage of RGI has also been reported [28, 42, 43].
\nThe highly conserved polysaccharide of pectin is rhamnogalacturonan II which constitutes about 10% of the pectin polymer [44]. This polysaccharide is made up of (1 → 4)-linked-α-D-GalA units containing 12 monosaccharide such as apiose, acetic acid, 3-deoxy-manno-2-octulosonic acid (KDO), and 3-deoxy-lyxo-2-heptulosaric acid (DHA) as side chains [30, 39]. GalA present in backbone of rhamnogalacturonan II (RG-II) may be methyl esterified at the C-6 position. The percentage of esterified GalA and acetylated groups in HG chain is termed as the DE and DAc, respectively. It is proposed that in the early developmental stages of plants, highly esterified pectin is formed that undergoes some deesterification in the cell wall or middle lamella. In general, tissue pectin ranges from 60 to 90% DE [45]. Both the DE and the DAc of pectin may vary depending on the method of extraction and plant origin [30, 46]. The functional properties of the pectin are determined by the amount and the distribution of esterified GalA residues in the linear backbone. Presence and distribution of esterified and nonmethylated GalA in pectin define the charge on pectin molecules. Based on their degree of esterification (DE), pectins are classified as high methoxy pectins (HMP) or low methoxy pectins (LMP). DE values of HM pectin range from 60 to 75%, whereas pectin with 20–40% of DE is referred as LM pectin. It was also observed that solubility, viscosity, and gelation properties of pectin are correlated and highly dependent on structural features [47, 48]. Pectin and monovalent salts of pectins are generally soluble in water but di- and trivalent ions are insoluble. The solubility of pectin in water increases with decrease in polymer size and increase in methoxy contents. Pectin powder gets hydrated very fast in water and forms clumps. The solubility of these clumps is very slow. As the pectin molecules come in contact with water, deesterification and depolymerization of pectins start spontaneously. The rate of decomposition of pectin depends on pH and temperature of the solution. As the pH of the solution decreased, with elevated temperature, ionization of carboxylate groups also reduced, which suppresses the hydration and repulsion between the polysaccharide molecules and results in the association of molecules in the form of gels. During thermal processing, solubilization of pectin is affected by β-elimination which depolymerized the pectin molecule and reduced its chain length. Small polymers have poor affinity with cell wall framework and solubilize easily. However, preheating, as well as reduced moisture contents in thermal processing, adversely affects the solubility of pectin in water [49, 50].
\nFood additives that are used in food processing to blend two immiscible liquids to produce a desirable product are known as food emulsifier or emulgent. These additives act as surface-active agents on the border of immiscible layers and reduce oil crystallization and prevent water separation. Emulsifiers are used in large number of food products such as ice creams, low-fat spreads, yoghurts, margarine, salad dressings, salty spreads, bakery products, and many other creamy sauces, to keep them in stable emulsion [27]. Emulsifiers increase the whip-ability of batters, enhance mouthfeel of the products, and improve texture and shape of the dough. Moreover, emulsions also help to encapsulate the bioactives [51]. Based on the disperse phase, there are two types of emulsion: oil in water (O/W) and water in oil (W/O). Milk, mayonnaise, dressings, and various beverages are some examples of O/W emulsion, whereas butter and margarine are the typical examples of W/O emulsion. Progress in hydrocolloid chemistry has resulted in the development of multitype emulsion such as O/W/O and O/W/O type emulsion (Figure 1). These emulsions are very important for fat reduction or encapsulation of bioactives and are used in preparation and stabilization of various low-fat creams, seasoning, and flavoring of sauces [52].
\nTypes of emulsions.
Commonly used emulsifiers in food processing are (i) small-molecular surfactant such as lectithins, derivatives of mono- and diglycerides prepared by mixing edible oils with glycerin or ethylene oxide, fatty acid derivatives such as glycol esters, sorbitan esters, polysorbates and (ii) macromolecular emulsifiers that include proteins and plant-based polymers such as soy polysaccharide, guar gum, modified starch, pectin, etc. [53]. As far as the properties of food emulsifier are concern, a good emulsifier should be low in molecular weight, capable to reduce the surface tension rapidly at interface, and should be soluble in continuous phase [54]. Research on food additives revealed the adverse effect of synthetic food additives on human being. Chassaing et al. found that polysorbate 80(P80) or carboxy methyl cellulose (CMC) had adverse effects on gut microbiota and their continuous use triggered the weight gain and metabolic syndrome after 12 weeks of administration in mouse [55]. A recent research carried out on mice shows that regular use of P80 and CMC triggers low-grade intestinal inflammation which may ultimately lead to the development of colon cancer [56]. Therefore, safety issues with the synthetic food additives and consumer’s demand for all natural food ingredients have necessitated the use of plant-based emulsifiers and stabilizers in food.
\nPectin is a natural hydrocolloid which exhibits wide spectrum of functional properties. Because of the gelling ability of pectin, it is used as viscosity enhancer. During emulsification process, pectin molecules adsorb at the fine oil droplets from at O/W interface and protect the droplet from coalescing with adjacent drops (short-term stability). The quality of emulsifier is defined by its ability to provide long-term stability against flocculation and coalescence [27]. Figure 2 depicts the stages in long-term emulsion formation using pectin as emulgent. When the viscosity of the continuous phase is increased, the movements of oil droplets become restricted which improves the shelf life of emulsion [57]. In the past decade, some pectin has also been reported to exhibit surface active behavior in oil-water interface and thereby stabilizing the fine oil droplets in emulsion [42, 58]. These functions of pectin are determined by its source, structural modification during processing, distribution of functional groups in pectin backbone, and also by various extrinsic factors such as pH, temperature, ionic strength, cosolute concentration, etc. The emulsification or surface active properties of pectin, i.e., formation of fine oil droplets, are mainly contributed due to the high hydrophobicity of protein residue present in pectin [46, 59] and also by hydrophobic nature of acetyl, methyl, and feruloyl esters [42, 60], whereas emulsion-stabilizing ability is attributed to the carbohydrate moieties and their conformational features [61].
\nEmulsion formation and stabilization using polymer as emulgent.
The mechanism of emulsion formation is shown in Figure 3. Different models explain the emulsion formation as covalently bound protein moieties in pectin are adsorbed onto the oil-water interface [46], form anchor points at the interface, and reduce the interfacial tension while the charged carbohydrate units extend into the aqueous phase [62] and stabilize by steric and viscosity effects in the aqueous phase(Figure 3a). Now, it is a well-established fact that pectin from different source shows variability in structure and protein contents. Leroux et al. identified many anchor points in sugar beet pectin (SBP) molecules [46], and proposed a loop-and-tail model (Figure 3b). According to the authors, only a limited amount of protein is adsorbed at the oil surface and acts as main moiety in the stabilization of the emulsion. This model was further confirmed by Siew and others [62]. The study was carried out to measure the thickness of the adsorbed SBP on oil-water interface layer, proposed a multilayer adsorption model (Figure 3c). Electrostatic interactions between the positively charged protein moiety and the negatively charged carbohydrate moiety were also reported.
\nDifferent models showing pectin adsorption at oil/water interface during emulsion formation.
Pectin O/W emulsion is generally stabilized through steric and electrostatic interaction. The carbohydrate moieties and neutral sugar side chains of RG I region of pectin confer the stability to the pectin emulsions through steric properties of the adsorbed polymers, when pectin is used as monoemulsifiers. In addition, pectin reversible association with galactan/arabinogalactan prior to emulsification also improves the emulsion stability [42, 63]. Electrostatic stabilization of emulsion is ascribed to sugar moieties and structural features of the HG units of pectin. If the pH of dispersion medium is above 3.5, nonmethylated carboxylic group of HG region gets ionized and confers charge on the pectin surface. Interaction of an ionic surfactant with oil droplets results in electrostatic stabilization [64]. Pectin viscosity also plays an important role in controlling the emulsion stability. HG region-rich pectin shows higher intrinsic viscosity ([η]); therefore, HG and RG ratio of pectin and molecular interactions that improve the intrinsic viscosity ([η]) of pectin solution also contributes in shelf life of emulsion [65, 66]. It has also observed that structural features of pectin such as pectin protein content, molecular mass, and presence of ferulic acid, and acetyl group in carbohydrate moieties of pectin also affect pectin’s emulsifying and emulsion stabilization properties [15]. Williams et al. showed that ferulic acid-rich pectin did not show significant difference in emulsifying ability of pectin when compared with pectin poor in ferulic acid [67]. Digestion of sugar beet pectin(SBP) with acidic proteases resulted in formation of larger size of oil droplet, lower creaming stability, and loss of emulsifying activity of SBP which confirms that protein contents of SBP play an important role in emulsifying ability of the polymer [42]. Nevertheless, in other research, it was also found that protein-rich fractions of SBP did not necessarily displayed better emulsifying ability; therefore, it was concluded that both protein with carbohydrate moiety together help in controlling emulsifying ability of SBP. Castellani et al. further suggest that both the carbohydrate and protein moieties function together as unit and affect the hydrophilic-hydrophobic equilibrium of the SBP molecule [68]. Therefore, when SBP is digested with proteases or other enzyme, a single moiety may function differently. Furthermore, it was also proposed that protein folding may also mask the hydrophobic effect of protein and thus affect the overall properties of the polymers [69].
\nMolecular weight of pectin has also been reported to affect the emulsifying capacity of pectin. Pectin with low molecular weight was more efficient in stabilizing small emulsion droplets than high-molecular weight pectin. However, very small size of citrus pectin had negative effect on emulsion-stabilizing ability of pectin. It could be due to the poor steric stabilization of depolymerized polymer [59].
\nEmulsion-based food products can be defined as a network of pectin-protein molecules entrapping the oil droplet in between. Nowadays, a large number of pectin- and polysaccharide-based emulsified low-fat dairy products, meat products, spreads or desserts, bakery products, sauces, etc., are available in market. Low-fat and low-cholesterol mayonnaise, low-fat cottage cheese, low-fat drinking yogurt, and flavored oil-containing acidified milk drinks are the few examples of pectin-based emulsified products. These products are prepared by replacing full-fat milk from skimmed milk, emulsified oil, and whey proteins [70, 71]. A low-fat cheese was prepared using skimmed milk and water-in-oil-in-water (W1/O/W2) emulsified canola oil. Different emulsifiers such as amidated low-methoxyl pectins (LMP), gum arabic (GA), carboxymethylcellulose (CMC), and combinations of GA-CMC or GA-LMP were used to stabilize the emulsion. Textural characteristics and sensory evaluation of low-fat cheese show that polymers used to stabilize the emulsion affected both microcrystalline structure and organoleptic properties. The cheese prepared using GA and LMP was almost similar in textural characteristics to the full-fat milk cheese [72]. In another study, Liu et al. compared the textural and structural features and sensory quality of full-fat and low-fat cheese analogs prepared with or without the incorporation of pectin [71]. Microstructure analysis using scanning electron microscopy revealed that full-fat cheese was denser and contained higher concentration of fat globules than low-fat cheese made with or without pectin. Comparison within the low-fat cheese analogs showed clear difference in their hardness, gumminess, chewiness, and adhesiveness. Addition of pectin had positive effect on textural and sensory attribute and scored better in mouthfeel also.
\nLow-fat (Lf) mayonnaise was prepared by partial replacement of egg yolk and incorporation of pectin as emulsifier [73, 74]. Pectin weak gel, pectin microencapsulation, and whey protein isolate were used in preparation of low-fat (Lf) mayonnaise. Physicochemical and sensory properties of Lf mayonnaise were compared with full-fat (Ff) mayonnaise; Lf mayonnaise had low energy and more water contents than Ff. Textural features and rheological properties of the Lf and Ff mayonnaise were similar and both displayed thixotropic shear thinning behavior and categorized as weak gels. Moreover, Lf mayonnaise prepared using pectin had better acceptability than whey protein incorporation [75]. Emulsified oil is used as an effective delivery system of active compound in functional foods, and also serves as milk fat replacer in fat-free dairy products. To improve the nutritional value of food, low-fat dairy products are produced, whereas saturated milk fat is generally replaced with emulsified-unsaturated vegetable oils [76].
\nIn recent year, pectin in combination with inulin has been reported to prepare low-fat meat batter. Méndez-Zamora et al. studied the effect of substitution of animal fat with different formulations of pectin and inulin on chemical composition, textural, and sensory properties of frankfurter sausages [77]. Finding of the research showed that fracturability, gumminess, and chewiness of the low-fat sauces were slightly lower than those of the control. However, addition of 15% inulin improves the sensory properties. In a similar work, replacement of pork back fat with 15% pectin and 15% inulin was found effective in maintaining the physicochemical properties and emulsion stability of the low-fat meat batter [78].
\nThe use of pectin in food products as a gelling agent is a long tradition. Later on, it was discovered that pectin forms different types of viscoelastic solution under suitable conditions. This property of pectin is commercially exploited in preparation of jams, jellies, and marmalades. Rheological behaviors of pectin depend on pectin source, its degree of methylation, distribution of nonmethylated GalA unit on pectin backbone, and degree of acetylation, and also on various extrinsic factors such as temperature, pH, concentration, and presence of divalent ions. At a constant pH, the setting time of pectin increases with decreasing DM and degree of blockiness (DB) in the absence of bivalent ions [79]. Therefore, on the basis of gelling process, pectin is classified as rapid, medium, and slow set pectin [80].
\nGelling process of pectin and its stabilization follows different mechanisms for different types of pectin. HMP form gels in a narrow pH range (2.0–3.5) in the presence of sucrose at a concentration higher than 55% w/v in medium. During the gelatin process of HMP, junction zones are formed due to the cross-linking of two or more pectin molecules. These junctions are stabilized by weak molecular interaction such as hydrogen and hydrophobic bonds between polar and nonpolar methyl-esterified groups and require high sugar concentration and low pH [81]. These gels are thermally reversible. LMP can form gel over a wide pH range (2.0–6.0) independent of sucrose, but requires divalent ion, such as calcium [82, 83]. LMP follow the eggbox model for its gelation, where positively charged calcium ions (Ca2+) are entrapped in between the negatively charged carboxylic group of pectin. The zigzag network of Ca2+ ion and GalA molecules looks like eggbox, and therefore, model is named as eggbox model [80]. These gels are stabilized by electrostatic bonds. In the presence of Ca2+, calcium bridges are formed with pectin molecules that make the solution more viscous. At the higher pH, the ionic strength of the solution is increased and thus more Ca2+ is needed for gelation. In case of highly acetylated pectin such as sugar beet, acetyl groups cause steric hindrances and interfere with the Ca2+ ion and GalA bond formation, thus preventing gel formation. Kuuva et al. [84] reported that enzymatic modification in pectin structure, i.e., removal of acetyl groups using α-arabinofuranosidase (α-Afases) and acetyl esterase enzymes, can improve the gelling property of acetylated pectin.
\nHMP are generally used in preparation of standard jams where sugar contents are above 55%, high-quality, tender confectionary jellies, fruit pastes, etc. LMP do not require sugar for its gelatin and therefore preferred choice for the production of low-calorie food products such as milk desserts, jams, jellies, and preserves, [28, 85]. LM pectins are more stable in low pH and high temperature conditions as compare to HM pectins and can be stored for more than a year.
\nFood packaging is one of the fastest growing segments of food industry. Traditionally, packaging system was limited to the containers and packaging material to transport the food items from manufacturer to the retail market and then to the consumers. Such type of packaging was unable to contribute in the extension of the shelf life and maintenance of the quality of the products. Due to the globalization of food market and increasing demand of shelf-stable processed food that retains the natural properties of food, the need of functional/active packaging material is increasing. To meet the industrial demand, a number of polymers are being synthesized and used in food packaging because of their flexibility, versatility, and cost effectiveness. Although, synthetic materials are able to fulfill all the industrial needs and keep food fresh and safe by protecting them from abiotic factors such as moisture, heat, oxygen, unpleasant odor, and biotic components such as micro- and macroorganisms. But, disposal of nonbiodegradable packaging material is a serious problem which poses a threat to the environment. Therefore, more research has been focused on the development of biodegradable packaging for food packaging applications using poly(lactic acid) (PLA), poly(hydroxyalkanoates) (PHAs), starch, etc. [86]. Among all the natural polymers, polysaccharides are gaining more attention as they are versatile in nature and easily available in relatively low cost.
\nA variety of natural polysaccharides, such as pectin, chitosan derivatives, alginate, cellulose, seaweed extract, and starch are usually used in the preparation of edible films and coatings [87]. Pectin is one of the most significant renewable natural polymers which are the main component of all the biomass and ubiquitous in nature. Being flexible in nature, pectin and its derivatives are used in many biodegradable packaging materials that serve as moisture, oil, and aroma barrier, reduce respiration rate and oxidation of food [88]. Pectin along with food grade emulsifiers is also used in the preparation of edible films. These films are used in fresh and minimally processed, fruits and vegetables, foods and food products as pectin is the main component of the omnivorous diet and can be metabolized. Edible coating protects the nutritional properties of the food and also saves highly perishable food from the enzymatic browning, off-flavor development, aroma loss, retards lipid migration, and reduces pathogen attack during storage.
\nAt low pH, LM pectins are cross-linked with calcium cations and form hard gels. These gels have highly stable structure and act as water barriers. Because of these properties, LM pectin films are used as edible coatings [88, 89]. Extension of shelf life of avocado fruits was also reported to over a month at 10°C by using edible pectin films. It was found that when avocados were coated with edible pectin films and stored at 10°C, rate of oxygen absorption and rate of respiration decreased which results in delaying of texture and color change of fruits [90]. Oms-Oliu et al. used calcium chloride and sunflower oil cross-linked with LM pectin films onto fresh-cut melon to see the effect on extension of shelf life of cut fruits [91]. It was observed that edible pectin films maintained the initial firmness, decrease the wounding stress of fresh-cut fruits, and prevent the dehydration during storage up to 15 days at 4°C but could not reduce the microbial growth onto the fresh melon. It has been observed that to reduce the respiration rate and to prevent the off-flavor development, different pectin and emulsifier formations are required for different fruits. Edible coating film formulation consisted on pectin, sorbitol, and bee wax was successfully used by Moalemiyan et al. to keep the fresh-cut mangoes in original state for over 2 weeks [92]. Whereas in a similar study, pectin coating containing sucrose and calcium lactate was able to prevent the fruits’ respiration rate and maintain sensory properties in fresh melon fruits for up to 14 days storage at 5°C. In a similar study [93], pectin edible coating solution containing pectin (3%), glycerol (2.5%), polyvinyl alcohol (1.25%), and citric acid (1%) was prepared and applied on sapota fruits by dipping method and uncoated sapota fruits were used as control. Both the treated and control fruits were stored at 30 ± 3°C. Physicochemical parameters namely, weight, color, firmness, acidity, TSS, pH, and ascorbic acid contents of both the coated and control fruits were measured at regular interval up to 11th day of the storage at 30 ± 3°C. Reduced rate of change in weight loss and other parameters were reported in pectin-coated sapota as compared to control fruits and it was observed that pectin film formulation was able to maintain good quality attributes and extend the shelf life of pectin-coated sapota fruits up to 11 days of storage at room temperature, whereas control fruits were edible up to 6 days. Furthermore, it was also observed that sapota fruits dipped in sodium alginate containing 2% pectin solution for 2 min were more effective in maintaining the organoleptic properties up to 30 days of refrigerated storage as compared to sapota fruits dipped for 4 min and untreated sapota fruits [94]. Bayarri et al. developed antimicrobial films using lysozyme and LM pectin complex. The main purpose of the study was to control the release of lysozyme in packaged food and to target lysozyme-sensitive bacteria such as Bacillus and Clostridium. It was observed that in the presence of fungal pectinase, due to the dissociation of pectin linkage, lysozyme activity of films increased remarkably. Many food-contaminating bacteria are pectinase producing and such type of films may be used to control food contaminants. These results have opened new avenues for custom-made biodegradable film [95].
\nIn last few years, some researchers have focused on pectin-based coating containing edible essential to improve the antimicrobial properties and to enhance the efficiency of the pectin films. Edible coating formulation containing sodium alginate and pectin (PE) enriched with eugenol (Eug) and citral (Cit) essential oil at different concentrations was used to increase the shelf life of strawberries. Physical and organoleptic parameters of coated fruits stored at 10°C for 14 days show that formulation containing PE 2% + Eug 0.1%; PE 2% + Cit 0.15% was more suitable than sodium alginate-based formulations [96]. Pectin coating containing lemon and orange peel essential oils was reported to increase the shelf life and quality attributes of the strawberry fruits up to 12 days when stored at 5°C. It was also observed that fruits coated with pectin + 1% orange essence showed less weight loss and soluble solids as compare to their control during the storage [97]. Sanchís et al. studied the combined effect of edible pectin coating with active modified atmospheric packaging on fresh-cut “Rojo Brillante” persimmon. Persimmon fruit slices were coated by dipping in the pectin-based emulsion or in water as control. Both the treated and control slices were packed under 5 kPa O2 (MAP) or under ambient atmosphere for up to 9 days at 5°C. Various parameters, such as package gas composition, color and firmness of slice, polyphenol oxidase activity, were measured during storage. It was observed that edible coating along with MAP significantly reduced the CO2 emission and O2 consumption in the packaged fruits. Furthermore, coating was also effective in controlling microbial growth and reducing enzymatic browning and maintains good sensory parameters up to 10 days on storage [98].
\nDrying is the traditional and oldest method of fruit and vegetable preservation. It decreases the enzymatic activity, reduces the moisture contents, and protects the food from microbial attack. However, drying results in loss of nutrients, vitamins, heat-labile enzymes, modifies the texture, color, and organoleptic quality of dried fruits and vegetables and therefore diminishes the market value also. Pretreatment of food products with pectin coatings containing other bioactive compound such as ascorbic acid, CaCl2, edible gum, etc., before drying or blanching has been proposed as an effective method to preserve the nutritional as well as organoleptic quality of dried food [99]. Recent researches have shown that application of pectin coating could protect the moisture and vitamin C loss in pretreated papaya slice and osmotic dehydrated pineapple. In one of the research [100], pineapple slice was pretreated with pectin coating formulation containing (50%)/calcium lactate (4%)/ascorbic acid (2%) solutions and then dried by hot-air-drying method. Physicochemical analysis of dried product showed less reduction in vitamin C contents as compared to untreated pineapple slice. In a similar work, pectin coating supplement with vitamin C (1%) was used for precoating of papaya slice. It was found that incorporation of vitamin C did not affect the drying process. However, significant increase in vitamin C content was observed in final product [101].
\nFrying is a method of cooking that causes changes in chemical and physical parameters of food and enhances the taste. However, high temperature vaporizes the water of food and affects the nutritional properties due to protein denaturation and starch gelatinization. The oil uptake during frying is affected by various parameters such as type of oil used, frying temperature and duration, product moisture content, shape, porosity, prefrying treatment, etc. [102]. Surface area and pretreatment of products are the major factors that determine the oil absorbed. Edible coating has also been used successfully, to reduce the oil uptake during frying in various deep-fried products. Reduction in oil uptake and improvement of texture and quality of potato slices was reported by Daraei Garmakhany et al. in 2008. Authors found that coating of potato slices with pectin, guar, and CMC solutions can reduce the oil uptake when compared with nontreated potato chips [103]. Similar results were also obtained by Khalil, where a combination of pectin or sodium alginate with calcium chlorides significantly reduces the oil uptake of French fries. Coating formulation of 0.5% calcium chloride and 5% pectin was most effective in reducing the oil uptake [104]. Kizito et al. used different edible coatings (pectin, carboxy methyl cellulose, agar, and chitosan) at a concentration of 1–2% for pretreatment of potato chips, followed by deep frying of chips. Fried chips were analyzed biochemically and organoleptically to investigate the quality attributes of the products. It was revealed that all the coating polymers were successful in reducing the oil uptake but pectin was most effective and reduced oil uptake up to 12.93%, followed by CMC (11.71%), chitosan (8.28%), and agar (5.25%) and significantly improved moisture retention of strips (p < 0.05) [105].
\nThe application of natural polymers in food industry is increasing day by day. Researchers are focusing more and more toward the pectin because of the ease-of-availability, structural flexibility, and versatile composition. Pectin can be sourced from a number of easily available horticulture crops (Table 1). Pectin is a hydrocolloid which is used as a food emulsifier, gelling agent, thickener, and stabilizer. It is the preferred choice of most of the food processors as fat or sugar replacer in low-calorie foods. In the recent years, increasing demand of ready-to-serve foods, fresh-cut fruits, and vegetable has opened a new market for edible films. Being biodegradable and recyclable, a lot of research is being done on pectin-based edible film formulations. These films reduce the exchange of moisture, gases, lipids, and volatiles between food and environment, and also serve as protective barrier for microorganisms.
\nEven though a lot of information is available regarding pectin structure and many pectin-based products are available in market, role of many carbohydrate moieties and their effect on various function of pectin are not yet well defined. Therefore, it is necessary to understand the structural-function relationship of pectin and its interactions for developing functional food products.
\nThe authors thank Director, CSIR-CFTRI for the encouragement.
\nThe authors declare no conflict of interest.
\nIntechOpen implements a robust policy to minimize and deal with instances of fraud or misconduct. As part of our general commitment to transparency and openness, and in order to maintain high scientific standards, we have a well-defined editorial policy regarding Retractions and Corrections.
",metaTitle:"Retraction and Correction Policy",metaDescription:"Retraction and Correction Policy",metaKeywords:null,canonicalURL:"/page/retraction-and-correction-policy",contentRaw:'[{"type":"htmlEditorComponent","content":"IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\\n\\n1. RETRACTIONS
\\n\\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\\n\\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\\n\\nPublishing of a Retraction Notice will adhere to the following guidelines:
\\n\\n1.2. REMOVALS AND CANCELLATIONS
\\n\\n2. STATEMENTS OF CONCERN
\\n\\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\\n\\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\\n\\n3. CORRECTIONS
\\n\\nA Correction will be issued by the Academic Editor when:
\\n\\n3.1. ERRATUM
\\n\\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\\n\\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n3.2. CORRIGENDUM
\\n\\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\\n\\n4. FINAL REMARKS
\\n\\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\\n\\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\\n\\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\\n\\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\\n\\nPolicy last updated: 2017-09-11
\\n"}]'},components:[{type:"htmlEditorComponent",content:'IntechOpen’s Retraction and Correction Policy has been developed in accordance with the Committee on Publication Ethics (COPE) publication guidelines relating to scientific misconduct and research ethics:
\n\n1. RETRACTIONS
\n\nA Retraction of a Chapter will be issued by the Academic Editor, either following an Author’s request to do so or when there is a 3rd party report of scientific misconduct. Upon receipt of a report by a 3rd party, the Academic Editor will investigate any allegations of scientific misconduct, working in cooperation with the Author(s) and their institution(s).
\n\nA formal Retraction will be issued when there is clear and conclusive evidence of any of the following:
\n\nPublishing of a Retraction Notice will adhere to the following guidelines:
\n\n1.2. REMOVALS AND CANCELLATIONS
\n\n2. STATEMENTS OF CONCERN
\n\nA Statement of Concern detailing alleged misconduct will be issued by the Academic Editor or publisher following a 3rd party report of scientific misconduct when:
\n\nIntechOpen believes that the number of occasions on which a Statement of Concern is issued will be very few in number. In all cases when such a decision has been taken by the Academic Editor the decision will be reviewed by another editor to whom the author can make representations.
\n\n3. CORRECTIONS
\n\nA Correction will be issued by the Academic Editor when:
\n\n3.1. ERRATUM
\n\nAn Erratum will be issued by the Academic Editor when it is determined that a mistake in a Chapter originates from the production process handled by the publisher.
\n\nA published Erratum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n3.2. CORRIGENDUM
\n\nA Corrigendum will be issued by the Academic Editor when it is determined that a mistake in a Chapter is a result of an Author’s miscalculation or oversight. A published Corrigendum will adhere to the Retraction Notice publishing guidelines outlined above.
\n\n4. FINAL REMARKS
\n\nIntechOpen wishes to emphasize that the final decision on whether a Retraction, Statement of Concern, or a Correction will be issued rests with the Academic Editor. The publisher is obliged to act upon any reports of scientific misconduct in its publications and to make a reasonable effort to facilitate any subsequent investigation of such claims.
\n\nIn the case of Retraction or removal of the Work, the publisher will be under no obligation to refund the APC.
\n\nThe general principles set out above apply to Retractions and Corrections issued in all IntechOpen publications.
\n\nAny suggestions or comments on this Policy are welcome and may be sent to permissions@intechopen.com.
\n\nPolicy last updated: 2017-09-11
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"105746",title:"Dr.",name:"A.W.M.M.",middleName:null,surname:"Koopman-van Gemert",slug:"a.w.m.m.-koopman-van-gemert",fullName:"A.W.M.M. Koopman-van Gemert",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105746/images/5803_n.jpg",biography:"Dr. Anna Wilhelmina Margaretha Maria Koopman-van Gemert MD, PhD, became anaesthesiologist-intensivist from the Radboud University Nijmegen (the Netherlands) in 1987. She worked for a couple of years also as a blood bank director in Nijmegen and introduced in the Netherlands the Cell Saver and blood transfusion alternatives. She performed research in perioperative autotransfusion and obtained the degree of PhD in 1993 publishing Peri-operative autotransfusion by means of a blood cell separator.\nBlood transfusion had her special interest being the president of the Haemovigilance Chamber TRIP and performing several tasks in local and national blood bank and anticoagulant-blood transfusion guidelines committees. Currently, she is working as an associate professor and up till recently was the dean at the Albert Schweitzer Hospital Dordrecht. She performed (inter)national tasks as vice-president of the Concilium Anaesthesia and related committees. \nShe performed research in several fields, with over 100 publications in (inter)national journals and numerous papers on scientific conferences. \nShe received several awards and is a member of Honour of the Dutch Society of Anaesthesia.",institutionString:null,institution:{name:"Albert Schweitzer Hospital",country:{name:"Gabon"}}},{id:"83089",title:"Prof.",name:"Aaron",middleName:null,surname:"Ojule",slug:"aaron-ojule",fullName:"Aaron Ojule",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Port Harcourt",country:{name:"Nigeria"}}},{id:"295748",title:"Mr.",name:"Abayomi",middleName:null,surname:"Modupe",slug:"abayomi-modupe",fullName:"Abayomi Modupe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/no_image.jpg",biography:null,institutionString:null,institution:{name:"Landmark University",country:{name:"Nigeria"}}},{id:"94191",title:"Prof.",name:"Abbas",middleName:null,surname:"Moustafa",slug:"abbas-moustafa",fullName:"Abbas Moustafa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94191/images/96_n.jpg",biography:"Prof. Moustafa got his doctoral degree in earthquake engineering and structural safety from Indian Institute of Science in 2002. He is currently an associate professor at Department of Civil Engineering, Minia University, Egypt and the chairman of Department of Civil Engineering, High Institute of Engineering and Technology, Giza, Egypt. He is also a consultant engineer and head of structural group at Hamza Associates, Giza, Egypt. Dr. Moustafa was a senior research associate at Vanderbilt University and a JSPS fellow at Kyoto and Nagasaki Universities. He has more than 40 research papers published in international journals and conferences. He acts as an editorial board member and a reviewer for several regional and international journals. His research interest includes earthquake engineering, seismic design, nonlinear dynamics, random vibration, structural reliability, structural health monitoring and uncertainty modeling.",institutionString:null,institution:{name:"Minia University",country:{name:"Egypt"}}},{id:"84562",title:"Dr.",name:"Abbyssinia",middleName:null,surname:"Mushunje",slug:"abbyssinia-mushunje",fullName:"Abbyssinia Mushunje",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Fort Hare",country:{name:"South Africa"}}},{id:"202206",title:"Associate Prof.",name:"Abd Elmoniem",middleName:"Ahmed",surname:"Elzain",slug:"abd-elmoniem-elzain",fullName:"Abd Elmoniem Elzain",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Kassala University",country:{name:"Sudan"}}},{id:"98127",title:"Dr.",name:"Abdallah",middleName:null,surname:"Handoura",slug:"abdallah-handoura",fullName:"Abdallah Handoura",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Supérieure des Télécommunications",country:{name:"Morocco"}}},{id:"91404",title:"Prof.",name:"Abdecharif",middleName:null,surname:"Boumaza",slug:"abdecharif-boumaza",fullName:"Abdecharif Boumaza",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Abbès Laghrour University of Khenchela",country:{name:"Algeria"}}},{id:"105795",title:"Prof.",name:"Abdel Ghani",middleName:null,surname:"Aissaoui",slug:"abdel-ghani-aissaoui",fullName:"Abdel Ghani Aissaoui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/105795/images/system/105795.jpeg",biography:"Abdel Ghani AISSAOUI is a Full Professor of electrical engineering at University of Bechar (ALGERIA). He was born in 1969 in Naama, Algeria. He received his BS degree in 1993, the MS degree in 1997, the PhD degree in 2007 from the Electrical Engineering Institute of Djilali Liabes University of Sidi Bel Abbes (ALGERIA). He is an active member of IRECOM (Interaction Réseaux Electriques - COnvertisseurs Machines) Laboratory and IEEE senior member. He is an editor member for many international journals (IJET, RSE, MER, IJECE, etc.), he serves as a reviewer in international journals (IJAC, ECPS, COMPEL, etc.). He serves as member in technical committee (TPC) and reviewer in international conferences (CHUSER 2011, SHUSER 2012, PECON 2012, SAI 2013, SCSE2013, SDM2014, SEB2014, PEMC2014, PEAM2014, SEB (2014, 2015), ICRERA (2015, 2016, 2017, 2018,-2019), etc.). His current research interest includes power electronics, control of electrical machines, artificial intelligence and Renewable energies.",institutionString:"University of Béchar",institution:{name:"University of Béchar",country:{name:"Algeria"}}},{id:"99749",title:"Dr.",name:"Abdel Hafid",middleName:null,surname:"Essadki",slug:"abdel-hafid-essadki",fullName:"Abdel Hafid Essadki",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"École Nationale Supérieure de Technologie",country:{name:"Algeria"}}},{id:"101208",title:"Prof.",name:"Abdel Karim",middleName:"Mohamad",surname:"El Hemaly",slug:"abdel-karim-el-hemaly",fullName:"Abdel Karim El Hemaly",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/101208/images/733_n.jpg",biography:"OBGYN.net Editorial Advisor Urogynecology.\nAbdel Karim M. A. El-Hemaly, MRCOG, FRCS � Egypt.\n \nAbdel Karim M. A. El-Hemaly\nProfessor OB/GYN & Urogynecology\nFaculty of medicine, Al-Azhar University \nPersonal Information: \nMarried with two children\nWife: Professor Laila A. Moussa MD.\nSons: Mohamad A. M. El-Hemaly Jr. MD. Died March 25-2007\nMostafa A. M. El-Hemaly, Computer Scientist working at Microsoft Seatle, USA. \nQualifications: \n1.\tM.B.-Bch Cairo Univ. June 1963. \n2.\tDiploma Ob./Gyn. Cairo Univ. April 1966. \n3.\tDiploma Surgery Cairo Univ. Oct. 1966. \n4.\tMRCOG London Feb. 1975. \n5.\tF.R.C.S. Glasgow June 1976. \n6.\tPopulation Study Johns Hopkins 1981. \n7.\tGyn. Oncology Johns Hopkins 1983. \n8.\tAdvanced Laparoscopic Surgery, with Prof. Paulson, Alexandria, Virginia USA 1993. \nSocieties & Associations: \n1.\t Member of the Royal College of Ob./Gyn. London. \n2.\tFellow of the Royal College of Surgeons Glasgow UK. \n3.\tMember of the advisory board on urogyn. FIGO. \n4.\tMember of the New York Academy of Sciences. \n5.\tMember of the American Association for the Advancement of Science. \n6.\tFeatured in �Who is Who in the World� from the 16th edition to the 20th edition. \n7.\tFeatured in �Who is Who in Science and Engineering� in the 7th edition. \n8.\tMember of the Egyptian Fertility & Sterility Society. \n9.\tMember of the Egyptian Society of Ob./Gyn. \n10.\tMember of the Egyptian Society of Urogyn. \n\nScientific Publications & Communications:\n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Asim Kurjak, Ahmad G. Serour, Laila A. S. Mousa, Amr M. Zaied, Khalid Z. El Sheikha. \nImaging the Internal Urethral Sphincter and the Vagina in Normal Women and Women Suffering from Stress Urinary Incontinence and Vaginal Prolapse. Gynaecologia Et Perinatologia, Vol18, No 4; 169-286 October-December 2009.\n2- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nFecal Incontinence, A Novel Concept: The Role of the internal Anal sphincter (IAS) in defecation and fecal incontinence. Gynaecologia Et Perinatologia, Vol19, No 2; 79-85 April -June 2010.\n3- Abdel Karim M. El Hemaly*, Laila A. S. Mousa Ibrahim M. Kandil, Fatma S. El Sokkary, Ahmad G. Serour, Hossam Hussein.\nSurgical Treatment of Stress Urinary Incontinence, Fecal Incontinence and Vaginal Prolapse By A Novel Operation \n"Urethro-Ano-Vaginoplasty"\n Gynaecologia Et Perinatologia, Vol19, No 3; 129-188 July-September 2010.\n4- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n5- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n6- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n7-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n8-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n9-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n10-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n11-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n12- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n13-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n14- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n15-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n\n16-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n17- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis\n\n18-Maternal Mortality in Egypt, a cry for help and attention. The Second International Conference of the African Society of Organization & Gestosis, 1998, 3rd Annual International Conference of Ob/Gyn Department � Sohag Faculty of Medicine University. Feb. 11-13. Luxor, Egypt. \n19-Postmenopausal Osteprosis. The 2nd annual conference of Health Insurance Organization on Family Planning and its role in primary health care. Zagaziz, Egypt, February 26-27, 1997, Center of Complementary Services for Maternity and childhood care. \n20-Laparoscopic Assisted vaginal hysterectomy. 10th International Annual Congress Modern Trends in Reproductive Techniques 23-24 March 1995. Alexandria, Egypt. \n21-Immunological Studies in Pre-eclamptic Toxaemia. Proceedings of 10th Annual Ain Shams Medical Congress. Cairo, Egypt, March 6-10, 1987. \n22-Socio-demographic factorse affecting acceptability of the long-acting contraceptive injections in a rural Egyptian community. Journal of Biosocial Science 29:305, 1987. \n23-Plasma fibronectin levels hypertension during pregnancy. The Journal of the Egypt. Soc. of Ob./Gyn. 13:1, 17-21, Jan. 1987. \n24-Effect of smoking on pregnancy. Journal of Egypt. Soc. of Ob./Gyn. 12:3, 111-121, Sept 1986. \n25-Socio-demographic aspects of nausea and vomiting in early pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 35-42, Sept. 1986. \n26-Effect of intrapartum oxygen inhalation on maternofetal blood gases and pH. Journal of the Egypt. Soc. of Ob./Gyn. 12:3, 57-64, Sept. 1986. \n27-The effect of severe pre-eclampsia on serum transaminases. The Egypt. J. Med. Sci. 7(2): 479-485, 1986. \n28-A study of placental immunoreceptors in pre-eclampsia. The Egypt. J. Med. Sci. 7(2): 211-216, 1986. \n29-Serum human placental lactogen (hpl) in normal, toxaemic and diabetic pregnant women, during pregnancy and its relation to the outcome of pregnancy. Journal of the Egypt. Soc. of Ob./Gyn. 12:2, 11-23, May 1986. \n30-Pregnancy specific B1 Glycoprotein and free estriol in the serum of normal, toxaemic and diabetic pregnant women during pregnancy and after delivery. Journal of the Egypt. Soc. of Ob./Gyn. 12:1, 63-70, Jan. 1986. Also was accepted and presented at Xith World Congress of Gynecology and Obstetrics, Berlin (West), September 15-20, 1985. \n31-Pregnancy and labor in women over the age of forty years. Accepted and presented at Al-Azhar International Medical Conference, Cairo 28-31 Dec. 1985. \n32-Effect of Copper T intra-uterine device on cervico-vaginal flora. Int. J. Gynaecol. Obstet. 23:2, 153-156, April 1985. \n33-Factors affecting the occurrence of post-Caesarean section febrile morbidity. Population Sciences, 6, 139-149, 1985. \n34-Pre-eclamptic toxaemia and its relation to H.L.A. system. Population Sciences, 6, 131-139, 1985. \n35-The menstrual pattern and occurrence of pregnancy one year after discontinuation of Depo-medroxy progesterone acetate as a postpartum contraceptive. Population Sciences, 6, 105-111, 1985. \n36-The menstrual pattern and side effects of Depo-medroxy progesterone acetate as postpartum contraceptive. Population Sciences, 6, 97-105, 1985. \n37-Actinomyces in the vaginas of women with and without intrauterine contraceptive devices. Population Sciences, 6, 77-85, 1985. \n38-Comparative efficacy of ibuprofen and etamsylate in the treatment of I.U.D. menorrhagia. Population Sciences, 6, 63-77, 1985. \n39-Changes in cervical mucus copper and zinc in women using I.U.D.�s. Population Sciences, 6, 35-41, 1985. \n40-Histochemical study of the endometrium of infertile women. Egypt. J. Histol. 8(1) 63-66, 1985. \n41-Genital flora in pre- and post-menopausal women. Egypt. J. Med. Sci. 4(2), 165-172, 1983. \n42-Evaluation of the vaginal rugae and thickness in 8 different groups. Journal of the Egypt. Soc. of Ob./Gyn. 9:2, 101-114, May 1983. \n43-The effect of menopausal status and conjugated oestrogen therapy on serum cholesterol, triglycerides and electrophoretic lipoprotein patterns. Al-Azhar Medical Journal, 12:2, 113-119, April 1983. \n44-Laparoscopic ventrosuspension: A New Technique. Int. J. Gynaecol. Obstet., 20, 129-31, 1982. \n45-The laparoscope: A useful diagnostic tool in general surgery. Al-Azhar Medical Journal, 11:4, 397-401, Oct. 1982. \n46-The value of the laparoscope in the diagnosis of polycystic ovary. Al-Azhar Medical Journal, 11:2, 153-159, April 1982. \n47-An anaesthetic approach to the management of eclampsia. Ain Shams Medical Journal, accepted for publication 1981. \n48-Laparoscopy on patients with previous lower abdominal surgery. Fertility management edited by E. Osman and M. Wahba 1981. \n49-Heart diseases with pregnancy. Population Sciences, 11, 121-130, 1981. \n50-A study of the biosocial factors affecting perinatal mortality in an Egyptian maternity hospital. Population Sciences, 6, 71-90, 1981. \n51-Pregnancy Wastage. Journal of the Egypt. Soc. of Ob./Gyn. 11:3, 57-67, Sept. 1980. \n52-Analysis of maternal deaths in Egyptian maternity hospitals. Population Sciences, 1, 59-65, 1979. \nArticles published on OBGYN.net: \n1- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Laila A. S. Mousa and Mohamad A.K.M.El Hemaly.\nUrethro-vaginoplasty, an innovated operation for the treatment of: Stress Urinary Incontinence (SUI), Detursor Overactivity (DO), Mixed Urinary Incontinence and Anterior Vaginal Wall Descent. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/ urethro-vaginoplasty_01\n\n2- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamed M. Radwan.\n Urethro-raphy a new technique for surgical management of Stress Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/\nnew-tech-urethro\n\n3- Abdel Karim M. El Hemaly, Ibrahim M Kandil, Mohamad A. Rizk, Nabil Abdel Maksoud H., Mohamad M. Radwan, Khalid Z. El Shieka, Mohamad A. K. M. El Hemaly, and Ahmad T. El Saban.\nUrethro-raphy The New Operation for the treatment of stress urinary incontinence, SUI, detrusor instability, DI, and mixed-type of urinary incontinence; short and long term results. \nhttp://www.obgyn.net/urogyn/urogyn.asp?page=urogyn/articles/\nurethroraphy-09280\n\n4-Abdel Karim M. El Hemaly, Ibrahim M Kandil, and Bahaa E. El Mohamady. Menopause, and Voiding troubles. \nhttp://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly03/el-hemaly03-ss\n\n5-El Hemaly AKMA, Mousa L.A. Micturition and Urinary\tContinence. Int J Gynecol Obstet 1996; 42: 291-2. \n\n6-Abdel Karim M. El Hemaly.\n Urinary incontinence in gynecology, a review article.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/abs-urinary_incotinence_gyn_ehemaly \n\n7-El Hemaly AKMA. Nocturnal Enuresis: Pathogenesis and Treatment. \nInt Urogynecol J Pelvic Floor Dysfunct 1998;9: 129-31.\n \n8-El Hemaly AKMA, Mousa L.A.E. Stress Urinary Incontinence, a New Concept. Eur J Obstet Gynecol Reprod Biol 1996; 68: 129-35. \n\n9- El Hemaly AKMA, Kandil I. M. Stress Urinary Incontinence SUI facts and fiction. Is SUI a puzzle?! http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly/el-hemaly-ss\n\n10-Abdel Karim El Hemaly, Nabil Abdel Maksoud, Laila A. Mousa, Ibrahim M. Kandil, Asem Anwar, M.A.K El Hemaly and Bahaa E. El Mohamady. \nEvidence based Facts on the Pathogenesis and Management of SUI. http://www.obgyn.net/displayppt.asp?page=/English/pubs/features/presentations/El-Hemaly02/el-hemaly02-ss\n\n11- Abdel Karim M. El Hemaly*, Ibrahim M. Kandil, Mohamad A. Rizk and Mohamad A.K.M.El Hemaly.\n Urethro-plasty, a Novel Operation based on a New Concept, for the Treatment of Stress Urinary Incontinence, S.U.I., Detrusor Instability, D.I., and Mixed-type of Urinary Incontinence.\nhttp://www.obgyn.net/urogyn/urogyn.asp?page=/urogyn/articles/urethro-plasty_01\n\n12-Ibrahim M. Kandil, Abdel Karim M. El Hemaly, Mohamad M. Radwan: Ultrasonic Assessment of the Internal Urethral Sphincter in Stress Urinary Incontinence. The Internet Journal of Gynecology and Obstetrics. 2003. Volume 2 Number 1. \n\n13-Abdel Karim M. El Hemaly. Nocturnal Enureses: A Novel Concept on its pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecolgy/?page=articles/nocturnal_enuresis\n\n14- Abdel Karim M. El Hemaly. Nocturnal Enureses: An Update on the pathogenesis and Treatment.\nhttp://www.obgyn.net/urogynecology/?page=/ENHLIDH/PUBD/FEATURES/\nPresentations/ Nocturnal_Enuresis/nocturnal_enuresis",institutionString:null,institution:{name:"Al Azhar University",country:{name:"Egypt"}}},{id:"113313",title:"Dr.",name:"Abdel-Aal",middleName:null,surname:"Mantawy",slug:"abdel-aal-mantawy",fullName:"Abdel-Aal Mantawy",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ain Shams University",country:{name:"Egypt"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:1683},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"qngrRaqGuveqFgrcChoyvfu"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:18},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:63},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. 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