\r\n\tRisk management aims to develop an efficient organizational development environment through risk planning, assessment, analysis, and control. This process will apply in all areas of activity, and the evaluation framework is the same regardless of the field. This volume will aim to appeal to chapters that address methods, models, evaluation frameworks, benefits, barriers, and other dimensions of risk management.
\r\n\tSustainability and the circular economy are approaches approached by many companies and have become activities of global interest. Protecting the environment, streamlining the consumption of organizational resources, reducing the amount of waste generated, and other activities are objectives of these efforts. The circular economy contributes to the sustainable development of the company or country and the achievement of the global objectives of sustainable development. This book will aim to collect various studies for organizational and global sustainability.
\r\n\tLeadership has become a globally desirable approach that can help improve organizational competitiveness and reduce organizational risks. Risks and barriers in risk-free management can be well managed through effective organizational leadership. This book will aim to bring together chapters that explore different areas of leadership.
Cancer development and fatality are gradually increasing worldwide. It is thought that the reasons are complex but associated with both aging and increase in the population [1, 2]. With the rapid global population increase and aging, the rising significance of cancer as a leading cause of death is partly correlated with a marked decline in mortality rates due to stroke and coronary heart disease in many countries. In addition, tobacco and alcohol consumption are known to be etiologically associated with carcinogenesis. Cancer is both a genetic and progressively systemic disease. In all types of cancer, somatic cells begin to divide uncontrollably and spread into surrounding tissues. Cancer cells can arise almost anywhere in the human body. Normal cells grow and divide according to the body’s needs, and when they age or become damaged, they die and are replaced by new cells. However, when cancer arises, this orderly process breaks down: as cellular abnormalities increase, old or damaged cells survive rather than being removed, and new cells form when they are not needed. These extra cells can divide uncontrollably and may form malignant tumors. Although many cancers form solid tumors composed of masses of tissue, cancers of the blood, such as leukemias, generally do not form solid tumors [2, 3, 4]. Head and neck cancer is a common neoplasm that encompasses epithelial malignant tumors of the nasopharynx, larynx, and mouth, representing about 6% of all cases and accounting for an estimated over 650,000 new cancer cases and over 350,000 cancer-related deaths worldwide every year [5, 6]. Oral cancer is the most notably frequent cancer type in the head and neck region, squamous cell carcinoma being the most common single entity. Oral cancers comprise two categories: those affecting the oral cavity (lips, inner lips, cheeks, teeth, gums, the anterior two-thirds of the tongue, the floor, and palate) and those affecting the oropharynx (middle region of the throat, including the tonsils and base of the tongue). Such cancers may arise in any location, although there are certain areas that are affected more frequently, such as the tongue and gingiva. These areas represent about 90% of all malignancies of the oral cavity [7, 8]. However, despite significant advances in surgery and chemotherapy over the last few decades [9], oral cancer is still characterized by a poor prognosis and a low survival rate [10]. The 5-year survival rate of those diagnosed is ~ 60%.
\nIn patients diagnosed with oral cancers at an advanced stage, there is a high incidence of metastasis to surrounding tissues, lymph nodes, and distant organs [5]. Metastasis is recognized as a process, whereby genetic instability in the primary tumor accelerates cell heterogeneity, allowing a few metastatic clones to eventually emerge and be positively selected to disseminate cancer at a distance [11]. This is the most annihilating stage of malignancy and the leading cause of cancer-related death. In metastasis, cancer cells break away from the primary cancer, travel through the blood or lymph system, and form new metastatic tumors elsewhere in the body. Each metastatic tumor is the same type of cancer as the primary tumor [12, 13], and the cells of each resemble each other upon microscopic observation. Moreover, they usually share common molecular features, such as the presence of specific genetic changes. It is clear that only a minority of malignant cells participate in the process of metastasis, due to interaction with host tissues and the intrinsic characteristics of the cancer cells themselves; thus, metastasis may imply an escape of these cells from the hostile environment they have created, characterized by features such as hypoxia, inflammation, and immunological surveillance [14, 15, 16].
\nThis chapter details recent findings on molecular markers that are involved in the mechanisms of proliferation and energy metabolism of oral cancer and provides new perspectives on its diagnosis and treatments.
\nCAMs are typically single-pass transmembrane receptors [17] compounded of three stored domains: an intracellular domain that interacts with a transmembrane domain, an extracellular domain, and the cytoskeleton. These domains can interact in several different ways [18]. The first way is through homophilic binding, where the same CAMs bind to each other. They are also capable of heterophilic binding, which means a CAM on one cell will bind to different CAMs on another cell. The third type of binding is that between cells and substrate, where a mutual extracellular ligand binds two different CAMs. There are four major superfamilies, or groups, of CAMs: the immunoglobulin super family of cell adhesion molecules (IgCAMs), the cadherins, the integrins, and the c-type lectin-like domain proteins (CTLDs). Proteoglycans are also believed to be a class of CAMs. One classification system involves distinction between calcium-dependent and calcium-independent CAMs [19]. The Ig-superfamily CAMs and integrins are not dependent on calcium ions, whereas selectins and cadherins are calcium-dependent. In addition, integrins participate in cell-matrix interactions, while other CAM families play some important roles in cell-to-cell interactions [20].
\nNeural cell adhesion molecule (NCAM) is a family of cell surface glycoproteins playing an important role in the development of the nervous system, fasciculation, axonal outgrowth, regulation of cell migration, and branching [21]. NCAM has several isoforms derived from alternative splicing of a single gene [22, 23, 24]. In particular, the three major isoforms with molecular weights of 120, 140, and 180 kDa have similar extracellular parts but differ in the disposition of their domains, which are cytoplasmic for the two larger polypeptides [25, 26]. Furthermore, the expression of NCAM is upregulated by transforming growth factor (TGF)-β1 [27, 28, 29]. Although NCAM was initially considered to exist only in neural tissue, it has since been observed in the human kidney, lung, fetal muscle, and colon, as well as in elements of the hemopoietic system. Furthermore, it has been described that NCAM is expressed by a variety of human tumors and associated with perineural invasion by various neoplasms, such as gallbladder cancer, melanoma, bile duct cancer, and adenoid cystic carcinoma of the head and neck [30, 31, 32, 33, 34, 35]. We have also demonstrated previously that NCAM is sporadically found in the adenoid cystic carcinoma, derived from human submandibular salivary gland,
Adenoid cystic carcinoma (ACC) is a well-known and typical malignant salivary gland tumor. ACCs are biologically aggressive and can bring metastases even when many years have passed after excision of the primary tumor. Facial paralysis is especially frequent, causing perineural and/or neural invasion. We have attempted to examine the role of NCAM by investigating the effect of anti-NCAM antibody (MAb NCAM) and TGF-β1 in human salivary gland tumor cells. The expression and distribution of NCAM were also investigated in ACC tissues. We further found that apoptotic cell death was induced via a DNA damage signal through the mitochondria, inducing release of cytochrome
Schematic representation of MAb NCAM-induced apoptotic signal transduction pathways via the DNA damage signal through the mitochondria involved in apaf-1 and caspase activation in NCAM-expressing cells.
Schematic representation of TGF-β1-induced upregulation of NCAM expression and proliferative activity involved in homophilic (NCAM-NCAM) binding mechanism in NCAM-expressing cells.
On the other hand, cimetidine, the most studied histamine type-2 receptor (H2R) antagonist used clinically, is commonly prescribed to treat gastroesophageal reflux disease as well as gastric and duodenal ulcers [39]. Cimetidine has recently been shown to possess antitumor activity against gastric, kidney, and colon cancers, as well as melanomas [40, 41, 42, 43]. A recent study has suggested that this behavior of cimetidine is mediated through three different effects: a direct inhibitory effect on tumor growth by blocking the cell growth activity of histamine via activation of H2 receptors and an indirect effect involving inhibition of tumor-associated angiogenesis, an immunomodulatory effect through augmentation of the host’s immune response to tumor cells, and an inhibitory effect on cancer cell migration and adhesion to endothelial cells, thus inhibiting tumor angiogenesis and metastasis [44]. We have also examined the NCAM-associated impact of cimetidine on tumor growth and perineural/neural invasion in salivary gland tumors using an in vitro cell culture system and an
Finally, it was suggested that NCAM might be associated with not only a cell-to-cell adhesion mechanism but also tumorigenesis, including the occurrence, development, and perineural/neural invasion of human salivary gland tumors.
\nFurther studies will be required to identify the signal transduction pathways by which treatment with cimetidine suppresses the growth of salivary gland tumors and to establish a strategy for cimetidine-based therapy for those tumors.
\nCoxsackievirus and adenovirus receptor (CAR/CXADR), a transmembrane glycoprotein, was initially characterized as a viral attachment site on the surface of epithelial cells (Figure 3) [46]. Later it was identified as a component of the tight junction (TJ) complex, an interacting partner for a number of other TJ proteins and a regulator of TJ formation [47, 48, 49, 50, 51, 52]. Furthermore, CAR is known to be a cell-cell adhesion molecule [53, 54]. In terms of function, loss of CAR has been considered to diminish intercellular adhesion, increase proliferation, and promote the migration as well as invasion of cancer cells [55, 56]. On the basis of these observations, a tumor-suppressive role of CAR in human cancers has speculated. Although it has recently been described [55, 56, 57, 58] that CAR is observed in various organs, it is still unclear whether it is expressed in oral cancer. Therefore, we examined the role of CAR in SCC in the oral cavity (data not shown). This revealed that CAR was constitutively expressed in five oral SCC cell lines. To analyze the function of CAR, we then examined the proliferative activity of SAS cells after
Schematic representation of coxsackievirus and adenovirus receptor on the tumor cells.
(A) The positive reaction for PAb CAR was observed on the membrane of tumor cells in 19 of 40 cases (47.5%) of SCCs. (B) NF-κB immunoreactivity were clearly detected in 30 of 40 cases (100%) in the HOSCC tissues. The immunoreactivity for CAR especially tended to fade away in the invasive front of oral SCC tissues. NF-kappaB (+)/CAR (−), 15/21 cases (71.4%).
Cytokines are composed of a large family of secreted proteins that bind to and signal through defined cell surface receptors on a wide variety of target cells, playing an important role in the maintenance of homeostasis. Furthermore, many cytokines share structural features and effects during inflammation, development, or immune responses.
\nThe concept of a control mechanism for cellular growth via regulation of apoptosis has recently been erected in a wide variety of tissue systems. Changes in the balance between cell survival and death are definite signs of emergence of various tumors. Therefore, modulation of apoptosis is required so as to maintain the homeostasis of a living organism. The expression of cytokines and their receptors in human oral cancers has attracted a great deal of interest because of their potential importance in tumor immunity. In particular, it has been described that members of the tumor necrosis factor (TNF) family, including Fas/FasL and TNF-related apoptosis-inducing ligand (TRAIL), regulate the deletion of unnecessary immune cells through induction of apoptosis [59, 60, 61]. However, despite their expression of these obvious antigens, tumor evasion by the immune system is often inefficient. It is considered that tumor cells may also evade immune attack by expressing TRAIL, Fas ligand, or other molecules that induce apoptosis in activated T cells [62].
\nTRAIL, also called APO2 ligand (APO2L), is a novel member of the TNF cytokine family that was originally characterized by its ability to induce apoptosis [59, 60]. It is recognized that at least four closely related receptors bind to TRAIL: death receptor-4 (DR4) and DR5/KILLER, which contain cytoplasmic death domains and signal apoptosis [60, 61]; decoy receptor-1 (DcR1) [61, 62, 63], which lacks a cytoplasmic tail and inhibits TRAIL function; and DcR2 [64, 65], which contains a cytoplasmic region with a truncated death domain that does not transduce the death signal [67]. TRAIL interacts with its agonistic receptors DR4 and DR5, inducing apoptosis in a wide variety of cancer cell lines derived from breast carcinoma, lung carcinoma, colon carcinoma, lymphoma, malignant melanoma, and malignant glioma [59, 60, 68, 69]. Although DR4 is expressed in many normal human tissues and cells, including spleen and peripheral blood leukocytes, TRAIL induces apoptosis in various cancer cells, but not in normal cells [70]. This may be explained by the fact that TRAIL also interacts with the antagonistic decoy receptors DcR1 and DcR2, which are expressed in normal tissues but not in cancer cells (Figure 5) [66, 67]. Neither DcR1 nor DcR2 receptors induce apoptosis, but they protect cells from TRAIL-induced apoptosis [64, 65, 66]. Until now, the biological involvement of the complex TRAIL receptor system has remained unclear, and the existing data are conflicting. Nevertheless, because of its selective cytotoxicity against tumor cells, TRAIL is regarded as a promising anticancer weapon that might be highly effective
Schematic representation of the death receptors and decoy receptors on the tumor cell.
TRAIL is expressed in most normal human cells and tissues, including the peripheral blood leukocytes, spleen, lung, and prostate, but not the brain [60]. However, the expression of TRAIL in human neoplasms is largely unknown. Accordingly, we have examined whether TRAIL and its receptors are expressed in HOSCC tissues or cell lines and whether these cell lines are sensitive to TRAIL-induced apoptosis [71]. This revealed that the mRNA and protein levels of TRAIL and its receptors are co-expressed in HOSCC cell lines in the absence of paracrine fratricide or autocrine suicide. Moreover, TRAIL protein was also detected in 24 of 50 samples (48%) of HOSCC tissue, and there was no correlation among the WHO grades. These findings suggest that HOSCC has the potential to escape immune surveillance by killing host T lymphocytes via DR4/TRAIL and DR5/TRAIL interactions, as suggested for FasL [72, 73, 74].
\nThe expression of decoy receptors in cancer cells is, however, a phenomenon that objects against previous reports [62, 63]. Indeed, several authors have currently described that a decoy receptor is expressed in various cancer types and our results are consistent with their findings [75, 76, 77]. Therefore, cancer cells may also avoid TRAIL-induced apoptosis by expressing a decoy receptor.
\nOn the other hand, cells differ significantly in their response to TRAIL. As contrasted to HUVEC or other oral cancer cells, only KB cells undergo significant apoptosis following exposure to recombinant human (rh)TRAIL. The reason why KB cells, despite their expression of a decoy receptor, react to rhTRAIL remains unresolved.
\nCommonly, the most proximal step in suppression of a death receptor pathway is inhibition of ligand binding. This may be acquired by lack, or the presence of decoy receptors [65, 66, 67, 68], or mutations of death receptors [78, 79]. However, it has recently been described that there is no correlation between the expression of TRAIL receptor and susceptibility to TRAIL-induced apoptosis in various cancer types [75, 76, 77]. Furthermore, the existence of antiapoptotic proteins, such as bcl-2, bcl-xL, and/or fas-like IL-1-converting enzyme (FLICE)-like inhibitory protein [80, 81], also seems to be significant, as they are resistant to death receptor-mediated apoptosis. Holistically, our results also suggest that there may be no correlation between the expression of TRAIL receptor and sensitivity to TRAIL-induced apoptosis in HOSCC cell lines and that TRAIL-resistant cells (HSC-2, HSC-3, HSC-4, and Ca9-22) may express cytoprotective proteins that block TRAIL-induced apoptosis or that the apoptotic effect of TRAIL is regulated by other mechanisms. It has also been described that TRAIL, in combination with an anticancer drug, acts cooperatively to induce apoptosis in various cancer cells that are resistant to TRAIL or chemotherapy [75, 82, 83]. This combination of TRAIL with chemotherapeutic reagents might be a useful therapeutic strategy against TRAIL-resistant cell lines such as HSC-2, HSC-3, HSC-4, and Ca9-22 used in our investigation.
\nIn fact, we are currently investigating the synergistic effects of α-mangostin and TRAIL on induction of apoptosis via the mitochondrial pathway in squamous cell carcinoma of the oral cavity [84]. To summarize, mangosteen (
Further investigation of TRAIL-mediated cell death, including the interaction of TRAIL and its receptors in oral cancer cells under various conditions, will be required to establish a strategy for TRAIL-based oral cancer therapy, which does not cause liver toxicity.
\nThe tyrosine kinase receptor c-Met ordinarily binds with hepatocyte growth factor (HGF), which triggers its involvement in processes such as cell differentiation, cell growth, angiogenesis, and embryogenesis [85, 86]. However, c-Met activation is also associated with processes related to malignant transformation, such as invasion, tumor growth, angiogenesis, and metastasis [87, 88, 89, 90, 91]. In addition to autocrine or paracrine signaling via HGF, c-Met may also be activated via the mutation, protein overexpression or amplification, or transcriptional alteration (via microRNA-mediated dysregulation) of MET [92, 93, 94]. c-Met overexpression and MET amplification are thought to be associated with a poorer prognosis in some types of tumors, including non-small cell lung cancer and gastric cancer [94]. In HOSCC, it has also been reported that c-Met expression is associated with cisplatin resistance and a strong propensity for metastasis
Further investigations of the role of c-Met will be required to fully understand c-Met-mediated tumor proliferation and to establish a therapeutic strategy for c-Met-based oral cancer.
\nIn normal tissues, adenosine triphosphate (ATP) is mainly produced in mitochondria via complete oxidative phosphorylation (OXPHOS) of glucose. Conversely, only 10% of ATP is produced from glycolysis in which glucose is replaced to lactate [97]. Interestingly, cancer tissues possess high levels of glycolysis in the cytosol even under aerobic conditions, which is upregulated by PI3K/Akt signaling in the mitochondria, a phenomenon known as the “Warburg effect” or “aerobic glycolysis” [98, 99, 100, 101, 102, 103]. More than 80 years ago, Otto Warburg found that cancer cells expended much more glucose to generate lactic acid than normal cells even under conditions of O2 sufficiency. This finding was the first indication that cancer cells have an alteration of glucose metabolism. Warburg [99] considered that these defects of respiration caused a form of metabolic disturbance that was significant for carcinogenesis. After Warburg, many biologists attempted to clarify the molecular basis of aerobic glycolysis occurring in tumor cells. Accumulated evidence suggested that many cancer-related genes, such as p53, c-Myc, and Ras, are all associated with modulation of the Warburg effect [104]. As a master regulator of the cancer hypoxic response, hypoxia-inducible factor (HIF)-1 plays very important roles in modulating aerobic glycolysis to meet the biosynthetic demands of cancer cells and to protect them from damage due to hypoxic stress [105]. Warburg theorized that cancer cells shift from oxygen-dependent efficient ATP production via OXPHOS in mitochondria to the less efficient cytoplasmic glycolysis. As a result, cancer cells need to burn up more glucose to maintain their energy requirements for survival and growth. It has been reported that HIF-1α activates the expression of glucose transporter 1, 3 (Glut1, Glut3) under hypoxic conditions [106, 107], which acquires sufficient glucose uptake by tumor cells. We also examined HIF, and details can be found in Chapter 10 of the InTech book
Schematic representation of the connecting glucose and lipid metabolism in cancer cells.
Lipids are composed of phospholipids, triglycerides, cholesterol esters, cholesterol, fatty acids, sphingolipids, and other molecules, which are critical components of cellular membranes [109, 110, 111, 112, 113]. In addition to their role as structural components, lipids also act as energy resources and as signaling molecules to sustain cell growth [114, 115, 116]. Lipid metabolism is known to be largely altered in cancers [117, 118, 119, 120], and worsening lipogenesis has been indicated to be a predominant characteristic of most tumors [114, 115, 121]. In oral cancer, cancer tissues include higher levels of unsaturated fatty acids than those in normal tissue (data not shown). Recent studies have revealed intrinsic molecular alterations in lipid metabolism. Especially, fatty acid synthase (FAS) is a key enzyme for synthesis of fatty acid from acetyl CoA, which is expressed at high levels in the adipose tissue and liver but at low levels in other tissues in humans [122]. FAS is overexpressed in several human cancers, including those of the ovary, bladder, stomach, breast, lung, prostate, oral cavity, and melanoma, and this overexpression is associated with poor prognosis [123, 124]. Furthermore, glutathione peroxidase 4 (GPX4) expression in tumors is positively correlated with tumor survival and linked to pathways that regulate cell proliferation, motility, and tissue remodeling [125]. Knockdown of GPX4 suppresses the formation and progression of cancer and leads to non-apoptotic cell death, ferroptosis. We have also examined the role of GPX4 in HOSCC (data not shown). Ferroptosis is a non-apoptotic form of cell death that can be triggered by conditions or small molecules that inhibit the glutathione-dependent antioxidant enzyme GPX4 or glutathione biosynthesis. This lethal process is defined by depletion of plasma membrane polyunsaturated fatty acids and the iron-dependent accumulation of lipid reactive oxygen species. It has also been reported that GPX4 is negatively regulated by the p53 gene [126]. These data suggest that GPX4 plays a significant role in proliferation and progression and may serve as a potential therapeutic target in HOSCC. Thus, GPX4 would be useful as a predictor of poor outcome in patients with oral cancer, and its antibody might be applicable as an inhibitor of oral cancer progression. Identification of the signaling pathways underlying these events might help to elucidate the mechanism of development of oral cancer. Further investigations into the role of GPX4 will be required to fully understand GPX4-mediated cancer proliferation and to establish a GPX4-based therapeutic strategy for oral cancer.
\nUnlike surgery, chemotherapy, and radiotherapy, which can have serious side effects on the human body, the use of agents that have no such side effects, such as TRAIL, cimetidine, mangostin, and antibodies, for cancer therapy mobilizes and regulates systemic functions, enhancing the body’s ability to fight cancer. Therefore, these medicines may be more appropriate for patients with inoperable advanced cancer, those in periods of chemotherapy intermission, or those during postoperative recovery. There has been an increased emphasis on such agents for prevention of cancer and inhibition of cancer metastasis. There has been an impressive renaissance in the search for semi-synthetic drugs or derivatives from natural compounds. Progress in this regard not only adds to the chemical bank but also leads to a better comprehension of the chemical basis of treatments lacking side effects for the treatment of cancers using drugs obtained from natural sources.
\nFurther studies will be required to establish a strategy for basic molecular and clinical approaches for effective oral cancer therapy, which should be tailored to individual patients.
\nWe have no financial relationships to disclose.
\nSeveral serotypes of Botulinum neurotoxin (BoNT) are produced by the bacterium Clostridium botulinum, including BoNT-A, B, C, D, E, F and, G [1]. Currently, only BoNT-A and B are commercially available and, the most widely used isoform in both cosmetic and clinical dermatology is BoNT-A.
To date, only four BoNT-A formulations have received FDA approval for several indications. These include OnabotulinumtoxinA, AbobotulinumtoxinA, IncobotulinumtoxinA and, ProatobotulinumtoxinA [2, 3].
Following the initial approval of BoNT-A for glabellar wrinkles by the US Food and Drug administration in 2002, it has been widely used in cosmetic dermatology, for the treatment of hyperdynamic lines and the rebalancing of facial muscles. BoNT-A is currently the leading non-surgical cosmetic procedure, world -wide [2].
The mechanism of action of importance to the aesthetic use of the neurotoxin is chemical denervation and consequent relaxation of skeletal muscle. Post injection, BoNT-A binds to specific presynaptic receptors on the nerve terminal and subsequently becomes internalised into the presynaptic nerve by receptor-mediated endocytosis. Within the nerve terminal, the light and heavy chain of BoNT-A dissociate by the breakage of the disulfide bonds. The light chain, responsible for the action of the neurotoxin, cleaves SNAP-25 docking protein on the internal neuronal membrane, which plays a key role in the release of acetylcholine during nerve stimulation. Consequently, acetylcholine can no longer be released into the synaptic cleft and muscle stimulation is inhibited until such time as the function of the neuromuscular junction is restored, which normally requires 3 to 6 months [2].
In the past few years, the neuromodulator has gained attention in the field of a clinical dermatology, as an off-label treatment for inflammatory skin diseases and wound healing [4]. The skin is known to interact with the nervous system and there is accumulating evidence that the neurological system has a direct impact on cutaneous inflammation and wound healing. Hence a number of research groups have shown the benefit of BoNT-A injections in acne, rosacea, psoriasis, scar prevention and hypertophic scar treatment, androgenic alopecia and alopecia aerate as well as hyperhidrosis and several conditions exacerbated by sweating [4, 5].
Apart from chemical denervation of cholinergic nerves, other mechanisms have also been postulated as being responsible for the treatment of these conditions includes the inhibition of substance P, glutamate release and calcitonin gene-related peptide (CGRP) and, the suppressions of mast cell activity [6, 7].
This review will address the role of BoNT-A in several non-cosmetic dermatological conditions for which there is current evidence.
Oily skin is a common dermatological condition reported by many patients, with and without acne. Clinically, the skin appears greasy and unclean with large open pores. Oily skin is troublesome and despite the several topical and systemic treatment options available, it is often difficult to control excessive serum secretion.
The treatment of oily skin with BoNT-A skin was first reported by Shah et al. in 2008 [8]. Twenty subjects with oily skin and large pores were injected intradermally with BoNT-A in the T-zone and evaluated one month post treatment. Photographic evidence of improvement in sebum secretion as well as patient satisfaction was noted in 17 of the 20 subjects [8].
In a prospective study, 25 patients were treated with intradermal injection of BoNT-A on the forehead and followed up for to three months. Sebum production, measured with a sebumeter, revealed a significant reduction in sebum secretion at 1 week and 1, 2 and 3 months after treatment [9]. Furthermore, twenty-one patients (91%) reported that they were satisfied (50–75% improvement) with intradermal botulinum toxin as a treatment for oily skin [9].
A recent split face-controlled study with BoNT-A on one cheek and saline on the other cheek showed a significant decrease in pore size and sebum score at four months in the BoNT-A side as compared to the saline control [10].
Within the sebaceous gland, sebocyte differentiation and sebum secretion are under the control of acetylcholine, since both immature and mature sebocytes express mucarinic acetylcholine receptors. Hence the mechanism of action of BoNT-A is postulated to be due to the inhibition of acetylcholine release into the synaptic cleft, where it normally binds to muscarinic receptors on the postsynaptic membrane [9, 10].
The initial step in Acne vulgaris is the formation of the microcomedo [12]. Several factors have been implicated including increased sebum secretion, ductal hyper-cornification and bacterial colonisation of the pilosebaceous unit by
Hence changes in sebaceous gland function and increased production of sebum are important causative factors in acne [13].
Li et al. showed immunohistochemical and immune-cytofluorescence evidence for the presence of cholinergic receptors in sebaceous glands [14]. Furthermore, the clinical relevance of these findings was assessed by a double-blind, split-face, placebo-controlled study on 20 volunteers. A marked decrease in sebum production was seen in the BoNT-A treated side as compared to the control involunteers with oily skin [14].
Therefore, the modulation of sebum secretion by blocking the activity of acetylcholine in sebocytes and suppression of the sebaceous gland may have a beneficial action in acne, especially in individuals with oily skin [14, 15]. Although there are no systematic clinical trials in this regard, there are some clinical observations to indicate that BoNT-A reduces acne flares. Patients with Tourette syndrome injected with 20–25 units of BoNT-A into the paranasal facial expression muscles, have shown a clearance of perinasal acne one to two weeks post-treatment with improvement persisting for four months [16]. An interesting outcome of a controlled study on BoNT-A treatment for facial wrinkles was the observation that the rate of acne breakouts in the treatment group was lower than that in the placebo group [17].
An additional benefit of BoNT-A in acne may be due to its inhibition of substance P, since it is known that this inflammatory intermediate stimulates lipogenesis in the sebaceous gland and contributes to the onset and aggravation of inflammation in acne [18].
Facial flushing, occurs due to the dilatation of facial capillaries which may be idiopathic or secondary to rosacea. It may be sporadic in nature, initiated by agents that act directly on blood vessels as well as due to stimuli such as alcohol, drugs, food additives, and neurological and hormonal stimuli including menopause. In the majority of cases, the treatment of flushing depends on the management of the underlying cause.
Many rosacea patients have morphological characteristics of more than one subtype of rosacea.
BoNT-A injections have been shown to be of value in the prevention of the erythema and flushing of rosacea. Case studies of two patients treated with intradermal injection of OnabotulinumtoxinA showed improvement in flushing within 2 weeks and the effect lasted for four months post treatment [22].
A case report involving mesotherapy with BoNT-A for the treatment of refractory erythematotelengiectatic and papulopustular rosacea showed significant reduction in erythema, telangiectasia and flushing [23].
In a larger double-blind split-face study, 24 participants with rosacea were randomised to receive intradermal injection of either BoNT-A or normal saline in both cheeks. On the BoNT-A treated side, the Clinician Erythema Assessment (CEA) score significantly decreased, and the Global Aesthetic Improvement Scale (GAIS) score significantly increased up to 12 weeks post treatment [24].
BoNT-A injections may also be used in combination treatment protocols with energy based devices. In a recent study by Al-Niaimi and co-workers, intradermal BoNT-A injections were used following pulsed dye laser treatments for rosacea. Evaluation of erythema index by 3D camera showed a positive synergistic effect of the treatments with a reduction in grading scores of flushing and erythema [25]. In another study, 16 patients were treated with a Tixel device which causes mechanical disruption of the stratum corneum, followed by topical application of 100iu of Abobotulinumtoxin A. significant improvement of the maxameter sore, clinical erythema assessment (CEA) and patient self-assessment was shown for up to 6 months [26].
To date, the pathogenesis of rosacea has not been fully elucidated. However, several mechanisms have been postulated as being involved including acetylcholine release, imbalance of the innate immune system and the skin microbiota as well as abnormal neurovascular signalling [22]. The release of vasoactive neuropeptides including substance P, calcitonin gene-related peptide and vascular endothelial growth factor as well as cathelicidins are believed to lead to rosacea flares. Cathelicidins are antimicrobial peptides that play a major role in the pathogenesis of rosacea [27]. Recently mast cells have been proposed as being responsible for cathelicidin-induced skin inflammation [6].
Hence the postulated mechanism of BoNT-A in the reduction of Rosacea flares could be due to inhibition of acetylcholine release from peripheral nerves in the cutaneous vasodilator system [22], the inhibition of the vasoactive neuropeptides and cathelicidins as well as the inhibition of mast cell degranulation [6, 27].
BoNT-A injections have been studied in the treatment of certain non-scarring alopecias including alopecia areata and androgenic alopecia.
Thus far, the only study in the literature on the use of BoNT-A in AA is by Cho et al. [30]. The investigation involved the intradermal injections of 10 U of the neurotoxin in seven patients with AA and the results showed that BoNT-A cannot be used as an alternative treatment for recalcitrant androgenic AA [30]. Nonetheless, since BoNT-A has an effect on neuro-immunogenic mechanisms, namely the prevention of the release of substance P and calcitonin gene-related peptide, which modulate hair growth [31], further studies concerning the treatment efficacy of BoNT-A for mild to moderate AA are warranted.
The current hypothesis for the pathophysiology of androgenetic alopecia involves the role of dihydrotestosterone (DHT), a metabolite of testosterone, as the causative factor. DHT is synthesised from testosterone via type II 5-alpha reductase enzyme (5-αR2). DHT accumulates in AGA-prone hair follicles which are sensitive to DHT resulting in the miniaturisation of the hair follicles and ultimately hair thinning, finally culminating in AGA. Consequently, most treatments for AGA target 5 alpha reductase enzyme. The commonly prescribed effective therapy for AGA is Finasteride. The drug reduces serum DHT and scalp tissue DHT by inhibiting 5-αR2. Apart from the genetic predisposition, hypoxia of the scalp is believed to increase the concentrations of DHT by reducing its clearance from the blood [33, 34, 35].
Pilot studies [33, 34, 35] have shown injections of BoNT-A in various areas of the scalp to be effective in the treatment of AA, resulting in an increase in mean hair count and a reduction in hair loss. The mechanism responsible has been postulated to be due to the relaxation of scalp muscles, thereby relieving scalp tension and resulting in a vasodilator effect. Ultimately the improved perfusion of the scalp along with the enhanced clearance of DHT are responsible for the potential efficacy in the treatment of AGA. A further benefit of the enhanced perfusion is the increased conversion of testosterone to oestradiol, which is known to enhance hair growth.
However, despite the promising results shown in these studies, further investigations such as randomised controlled trials are necessary to establish the benefit of BoNT-A in AGA.
Scars and keloids are a consequence of a dysregulation of the normal wound healing reaction. Wound healing occurs through organised sequential steps of haemostasis, inflammation, proliferation and tissue remodelling. Each of steps of the wound healing cascade is dependent upon several cytokines and growth factors. Interaction among these processes results in the synthesis of collagen over the surface of the wound. On a contrary note, an alteration in the molecular factors, complex network of pro-fibrotic, and anti-fibrotic molecules such as growth factors, proteolytic enzymes, and extracellular matrix proteins may lead to the formation of hypertrophic scars and keloids [36].
Scars have a negative effect on the patient’s quality of life as they may impact on the patient both functionally and cosmetically. There are currently various therapeutic approaches in the management of scars including silicone dressings, energy-based devices, surgical excision, cryotherapy and intralesional steroid injections. However, to date, there is not definitive cure and typically combination approaches are employed for the management of scars [37].
The mechanism of action of BoNT-A in the prevention of hypertrophic and keloid scar formation is partially believed to be due to a reduction in fibroblast proliferation and the expression of the inflammatory cytokineTGF-β, one of the main intermediates responsible for scar formation [38]. The neuromodulator also suppresses the proliferation of fibroblasts in hypertrophic scar tissue [39].
An additional contributing factor to hypertrophic scar and keloid formation is tension on the scar [40]. Hence, BoNT-A may modulate and possibly prevent scar formation by reducing muscle contraction and decreasing skin tension in the scar area.
In a double-blind, split-scar randomised controlled trial in 15 patients with post-thyroidectomy scars. Patients were injected within 10 days of surgery and evaluated at 6 months. Results showed a significant improvement in the BoNT-A treated half of the scar as compared to the saline-treated control [41].
A recent randomised controlled trial in 24 patients with keloids revealed that 5 iu/sq.cm of BoNT-A, injected every 8 weeks for a total of three session, was as effective in softening the keloids and reducing their volume, as intralesional corticosteroids, which are considered the first-line treatment for keloids [42]. Both lesion height and volume were decreased in both cases, however BoNT-A was found to be superior in reducing pain and itch associated with keloids [42]. However, in a prospective uncontrolled study by Gauglitz, patients were injected every 2 months for up to 6 months and the results showed no differences in expression of markers and no regression of keloid tissue was found [43].
Despite the inconsistency in results found in the various studies to date, the role of BoNT-A in the prevention and treatment of hypertrophic scars and keloids does show potential. As such, more structured large- scale double-blind, controlled trials and long-term follow up are warranted to determine the value of BoNT-A in the management and prevention of hypertrophic scars and keloids.
Postherpetic neuralgia (PHN) is a very painful conditions which typically occurs post herpes zoster virus infection and can last up to three months, following the initial viral infection. The local neuropathic pain and the sleep disturbances associated with PHN, impacts negatively on the patients quality of life. Conventional treatment approaches include topical agents such as capsaicin and topical anaesthetics as well as nonsteroidal anti-inflammatory drugs, gabapentin and tricyclic antidepressants [44]. However the pain and discomfort may be resistant to all of these drugs.
Xiao et all enrolled 60 patients in a randomised, double-blind, placebo-controlled study whereby patients were divided into three groups; BoNT-A group, saline group and 0.5% lidocaine group. All patients were treated once, with the BoNT-A group receiving a maximum dose of 200iu by intra and subcutaneous injections. The patients were followed up for a period of three months. Of the three groups, the BoNT-A group exhibited the most significant improvement in the Visual Analog Scale (VAS) and sleep quality [45].
In another randomised control trial where 30 patients with PHN were treated with either placebo or a total dose of 200iu BoNT-A, the BoNT-A patients showed a significant reduction in Visual Analog Scale pain sores and which lasted for 16 weeks [46].
The mechanism of pain reduction by BoNT-A is believed to be due to the inhibition of various inflammatory intermediates including calcitonin gene-related peptide, glutamate and substance P.
BoNT-A is an established treatment option for primary axillary and focal idiopathic hyperhydrosis and in 2004 OnabotulinumtoxinA received FDA approval for severe primary axillary hyperhidrosis [47, 48]. BoNT-A inhibits the release of acetylcholine from sympathetic nerve fibres that stimulate the eccrine sweat glands and leads to a decrease in sweat production. Several dermatological conditions are exacerbated by sweat and these include Hidradenitis suppurativa, pompholyx, and several genodermatoses including Haily-Haily disease, Darrier disease, Epidermolysis bullosa simplex and Epidemolysis bullosa simples Weber-Cockayne Type, and Pachyonychia Congenita.
The first case report of HS of the axillae treated with BoNT-A was in 2005 in a young female who was successfully treated with a single dose of the neurotoxin and remained symptom free for ten months [50].
Thereafter, other case reports confirmed the efficacy of BoNT-A in cases of recalcitrant HS [51, 52, 53].
The precise mechanism of action of BoNT-A in HS is unclear but it is believed to be due to the inhibition of sweat production. A moist environment in the inguinal folds and axillae predisposes to maceration and the proliferation of bacteria that precipitate the inflammation and symptoms of HS. Hence the maintenance of a dry environment in the affected areas reduces the population of skin flora and potentially relieves the condition [54].
Improvement in vesiculation and itch has been shown with intradermal injections of BoNT-A in seven out of ten patients, where one hand was injected with 100 iu of the neurotoxin and the other hand was injected with a saline control. The efficacy of BoNT-A in pompholyx is not solely due to its anhidrotic action but due to its inhibition of substance P [55].
Certain genodermatoses such as
Recently a retrospective study of eight patients who were treated with topical BoNT-A post application of the Tixel thermo-mechanical ablative system, showed positive results, with seven patients (87.5%) experiencing good or partial response [59].
A recent systematic review of sixteen publications including a total of 38 patients revealed that of all the cases, only one patient did not have a response while all the other patients had partial or complete remission.
BoNT-A was found to be an encouraging treatment option in recalcitrant HH disease [60].
Case reports on the use of BoNT-A injections have been shown to significantly improve the lesions and symptoms of Dariers disease.
A recent open label 6-month interventional study in three patients with the neurotoxin resulted in a reduction in skin lesions in the affected area and consequently had a positive impact on the patients quality of life [58].
In a case series, three patients with PC injected with BoNT-A, experienced decrease in pain and discomfort [64]. A report of two cases treated with plantar injection of BoNT-A for PC, resulted in marked improvement for a duration of six months with no adverse effects or tachyphylaxis [65].
In a recent study, Koren et al. treated five patients with PC and found significant improvement of between 20 and 72% in the PC specific quality of life questionnaire. The duration of effect lasted between 3 and 4 months [66].
Plaque Psoriasis is an inflammatory disease that presents as small to large, well-demarcated dry and red scaly plaques covered with silvery flakes, which may be painful and itchy. Typically, the lower back, trunk, elbows and knees are involved but it may occur on any part of the body. Inverse psoriasis, sometimes also known as intertriginous psoriasis, is a form of psoriasis that affects skin folds.
Psoriasis is often associated with nail and scalp psoriasis. The condition is associated with multiple comorbidities and markedly diminishes the patients’ quality of life.
Whilst topical therapies remain the basis for treating mild psoriasis, currently, biologics that inhibit inflammatory intermediates such as TNF-α and IL-17 are the treatments of choice for moderate to severe disease [67].
Psoriasis is associated with high levels of Calcitonin Gene-related peptide and Substance P and consequently BoNT-A has been shown to be effective in managing both, consequently reducing both itch and pain [68, 69].
G Gonzales et al. treated eight patients with stable and recalcitrant plaque psoriasis, with subcutaneous injections of AbobotulinumtoxinA at a dose of 5 units every square cm. The patients were then evaluated at 2 and 4 weeks after treatment. The outcome was a significant improvement in all patients, 4 weeks after treatment, with no significant side effects [70].
In a split body comparative study, thirty five patients with chronic plaque psoriasis were treated with either intradermal BoNT-A or 5-fluorouracil (5-FU). Treatment outcomes were assessed by two blinded observers and the criteria included induction scores, erythema, scaling and induration were evaluated. No significant difference was found between the two sides regarding the clinical response. The response rate was found to be 85% on the BoNT-A side and 90% on the 5-FU side [71].
In this chapter the current off-label use of BoNT-A in various clinical, non-cosmetic dermatological conditions, has been reviewed. The neuromodulator has a complex mechanism of action, which to date has not been fully elucidated. However, it is clear that there is great potential for its therapeutic use in various skin condition associated with pain, inflammation and with hyperhydrosis.
Many of these disorders are chronic conditions and consequently will require repeat injections of BoNT-A, hence it is important to establish the long-term safety and efficacy of the neuromodulator.
The long-term safety of BoNT-A is well-established, yet there remains the potential for tachyphylaxis with cyclical treatments since we know that BoNT-A has an immunogenic potential.
Experience with BoNT-A for cosmetic indications, where doses of up to 100 units are injected every 4–6 months, has shown a very low incidence of immunoresistance. Hence we may assume that the development of neutralising antibodies to BoNT-A is very rare. However, it appears that the key factors in this regard may be the treatment frequency and the dose injected per session.
The evidence to date for the clinical efficacy of BoNT-A in many of these conditions is based on Level V case reports, with diverse treatment protocols, and a very few randomised controlled trials.
Hence further systematic double-blind randomised trials with larger patient populations are warranted to establish the role of BoNT-A in these clinical non-cosmetic dermatological conditions. Furthermore, basic research into the role of BoNT-A in the modulation of neuropeptides and hence it effects on the cutaneous neuroimmune system are required. In conclusion, a consensus on the injection protocol and dosing regimen for each indication is essential.
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Furthermore, as global warming and pollution worsen, the development of renewable energy sources is becoming more essential. Hydrogen is one of the most promising clean and sustainable energy carriers because it emits only water as a byproduct without carbon emission and has the highest energy efficiency. Hydrogen can be produced from a variety of raw resources, including water and biomass. Water electrolysis is one of many hydrogen production technologies that is highly recommended due to its eco-friendliness, high hydrogen generation rate, and high purity. However, in terms of long-term viability and environmental effect, Polymer Electrolyte Membrane water electrolysis has been identified as a potential approach for producing high-purity, high-efficiency hydrogen from renewable energy sources. Furthermore, the hydrogen (H2) and oxygen (O2) produced are directly employed in fuel cells and other industrial uses. As a result, an attempt has been made in this work to investigate hydrogen synthesis and utilization in fuel cell vehicles. Low-temperature combustion technology has recently been applied in engine technology to reduce smoke and NOx emissions at the same time. The advantages and limitations of homogeneous charge compression ignition, partially premixed charge compression ignition, premixed charge compression ignition, and reactivity regulated compression ignition are described separately in low-temperature combustion strategy.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Babu Dharmalingam, Ramakrishna Reddy Ramireddy, Santhoshkumar Annamalai, Malinee Sriariyanun, Deepakkumar Rajagopal and Venkata Ramana Katla"},{id:"82176",title:"Replacement of Diesel Fuel by DME in Compression Ignition Engines: Case for India",slug:"replacement-of-diesel-fuel-by-dme-in-compression-ignition-engines-case-for-india",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104969",abstract:"Decarbonising of transport, industrial and all sectors of economy is a necessity to stop or reverse global warming. Use of batteries, fuel-cells, hybrid topographies with smaller IC engines and use of alternative fuels like methanol, ethanol, DME in the IC engines are some of the ways through which emission of green-house gases can reduced/eliminated. Diesel engines are highly efficient due to higher compression ratios and are used in the heavy-duty transportation vehicles. DME is a single molecule fuel having high cetane number and which can be used as a drop-in fuel on the diesel engines albeit with retro-fitment of these engines with a new pressurized fuel system. DME with a chemical formula CH3-O-CH3 can be produced by different feedstocks such as coal, natural gas, biomass and bio-waste and municipal solid waste. India has a large reserve of high ash coal and generates high quantities of biomass and MSW, all of which can be converted to DME by use of clean production technologies. India’s transport and industrial sectors consume about 100 billion liters of diesel fuel per year produced entirely from imported petroleum. This amount of diesel can be replaced by indigenously produced DME from locally available coal, biomass and MSW.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Anirudh Gautam and Ankita Singh"},{id:"81979",title:"The Influence of Exhaust Gas Recirculation on Performance and Emission Characteristics of a Diesel Engine Using Waste Plastic Pyrolysis Oil Blends and Conventional Diesel",slug:"the-influence-of-exhaust-gas-recirculation-on-performance-and-emission-characteristics-of-a-diesel-e",totalDownloads:7,totalDimensionsCites:0,doi:"10.5772/intechopen.105011",abstract:"Through an experimental study, this work focused on finding the influence of exhaust gas recirculation (EGR) on waste plastic pyrolysis oils (WPPOs) with diesel as a base comparison fuel. The results show the amount of carbon monoxide emissions seemed to decrease at low engine loads up to intermediate loads of (50%), thereafter continued to increase significantly but marginally. Among fuels tested, blend WPPOB100 reported the highest BSFC, at 0% EGR flow rate. The value was 0.4751g/kW.hr. compared with 0.7235 g/kW.hr. at 30% EGR flow rate. Increased blend ratio had a direct decrease in brake power linearly. At 30% engine load, CD, WPPOB10, WPPOB20, WPPOB30 and WPPOB40 recorded values of 2.125 kW, 2.15 kW, 2.05 kW, 1.98 kW, 1.86 kW and 1.75 kW, respectively. Exhaust gas temperature (EGT) at 30% EGR flow rate, blend WPPOB10 had the highest reduction in temperature compared with the any other WPPO blends at 320°C. Increased blend ratio and EGR percentage flow rate increased smoke emissions within the test fuels blends. At 15% EGR flow rate, the following data were recorded: 7.53%, 7.1%, 6.72%, 6.25%, 6.0% and 5.4% for CD, WWPO10, WPPO20, WPPO30, WPPO40 and WPPO100, respectively.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Semakula Maroa and Freddie L. Inambao"},{id:"81895",title:"Performance and Emission Characteristics of Hydrogenation Derived Renewable Diesel as Diesel Engine Fuel",slug:"performance-and-emission-characteristics-of-hydrogenation-derived-renewable-diesel-as-diesel-engine-",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.104820",abstract:"Growing anxieties about the continued depletion of fossil fuel reserves, improving the performance of diesel engines, and mandates to reduce greenhouse gas emissions have made the search for alternative fuels for diesel engines more imperative. Hydrogenation Derived Renewable Diesel (HDRD) is recognized as a sustainable, reliable, and cost-effective alternative to petroleum-based diesel (PBD) fuel for compression ignition (CI) engines. This may be because the physicochemical properties of HDRD are similar to that of PBD fuel. The current effort examines the performance and emission characteristics of HDRD in unmodified CI engines. Performance emissions characteristics such as power, torque, brake specific fuel consumption, thermal efficiency, nitrogen oxides, carbon monoxide, carbon dioxide, particulate matter, and exhaust gas temperature were interrogated and compared with that of PBD fuel in a CI engine. The outcome of the study shows that HDRD is better than biodiesel and a sustainable replacement for PDB fuel to achieve improved performance and reduced emissions of CI engines. Going forward, more investigations are needed to further simplify the preparation and democratize the utilization of HDRD as CI fuels for various applications.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Omojola Awogbemi, Daramy Vandi Von Kallon and Josiah Pelemo"},{id:"81114",title:"Research and Innovation to Improve the Efficiency of Modern Diesel Engines",slug:"research-and-innovation-to-improve-the-efficiency-of-modern-diesel-engines",totalDownloads:9,totalDimensionsCites:0,doi:"10.5772/intechopen.102759",abstract:"Modern diesel engines are one of the main mobile energy sources and are characterized by a high degree of workflow completeness, design, and manufacturing technology. The chapter summarizes the authors’ experience in improving diesel engines, increasing specific volume power, and reliability, ensuring a low level of environmental pollution emissions. The results of research using industry 4.0 technologies for systematization, choice of directions, and the search for rational ways to improve the efficiency of diesel engines are presented. The application of anergo-exergy method for analyzing the efficiency of the working process of the engine and its systems is considered. Taking into consideration the operating conditions, technical solutions are proposed to improve the reliability of the most heat-stressed parts of high-powered engines. The possibilities for a comprehensive assessment of the fuel efficiency and environmental qualities of diesel engines have been expanded taking into account CO2 emissions when using traditional, alternative, and hybrid diesel fuel.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Andriy Marchenko, Igor Parsadanov, Volodymyr Pylyov, Oleksandr Osetrov, Linkov Oleh, Serhii Kravchenko, Oleksandr Trynov, Denys Meshkov, Serhii Bilyk, Anatolii Savchenko, Inna Rykova and Rasoul Aryan"},{id:"81849",title:"A Comparative Evaluation of Biodiesel and Used Cooking Oil as Feedstock for HDRD Application: A Review",slug:"a-comparative-evaluation-of-biodiesel-and-used-cooking-oil-as-feedstock-for-hdrd-application-a-revie",totalDownloads:23,totalDimensionsCites:0,doi:"10.5772/intechopen.104393",abstract:"The search for clean energy for transportation fuel across the globe has grown in intensity. The use of biodiesel as a fuel for compression ignition (CI) engines has shown some deficiencies, e.g., poor storage, and poor pour point. The carbon chain of biodiesel is one of the factors to be considered; the longer carbon chain length leads to decreased ignition delay, which leads to the formation of OH during the premixed combustion phase. The major challenges that render biodiesel inefficient are discussed, like higher viscosity, lower energy content, higher nitrogen oxide (NOX) emissions, lower engine speed and power, injector coking, engine compatibility, high cost, and higher engine wear. The novelty of this work is that it shows that biodiesel conversion to green diesel is possible using a biowaste heterogeneous catalyst to obtain quality and high yield of HDRD with lower cost. This renewable energy (HDRD) possesses properties that are directly compatible with CI engines and transportation engines. This research reviewed biodiesel and UCO as feedstocks for the production of HDRD, including the cost–benefit of these feedstocks. Hydrogenation of biodiesel has the potential to overcome the drawbacks of conventional chemically catalyzed processes.",book:{id:"11164",title:"Diesel Engines and Biodiesel Engines Technologies",coverURL:"https://cdn.intechopen.com/books/images_new/11164.jpg"},signatures:"Josiah Pelemo, Kayode Timothy Akindeji, Freddie L. Inambao, Omojola Awogbemi and Emmanuel Idoko Onuh"}],onlineFirstChaptersTotal:12},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:139,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:122,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:21,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517",scope:"Paralleling similar advances in the medical field, astounding advances occurred in Veterinary Medicine and Science in recent decades. These advances have helped foster better support for animal health, more humane animal production, and a better understanding of the physiology of endangered species to improve the assisted reproductive technologies or the pathogenesis of certain diseases, where animals can be used as models for human diseases (like cancer, degenerative diseases or fertility), and even as a guarantee of public health. Bridging Human, Animal, and Environmental health, the holistic and integrative “One Health” concept intimately associates the developments within those fields, projecting its advancements into practice. This book series aims to tackle various animal-related medicine and sciences fields, providing thematic volumes consisting of high-quality significant research directed to researchers and postgraduates. It aims to give us a glimpse into the new accomplishments in the Veterinary Medicine and Science field. By addressing hot topics in veterinary sciences, we aim to gather authoritative texts within each issue of this series, providing in-depth overviews and analysis for graduates, academics, and practitioners and foreseeing a deeper understanding of the subject. Forthcoming texts, written and edited by experienced researchers from both industry and academia, will also discuss scientific challenges faced today in Veterinary Medicine and Science. In brief, we hope that books in this series will provide accessible references for those interested or working in this field and encourage learning in a range of different topics.",coverUrl:"https://cdn.intechopen.com/series/covers/13.jpg",latestPublicationDate:"August 7th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",institutionURL:null,country:{name:"Portugal"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:5,paginationItems:[{id:"19",title:"Animal Science",coverUrl:"https://cdn.intechopen.com/series_topics/covers/19.jpg",editor:{id:"259298",title:"Dr.",name:"Edward",middleName:null,surname:"Narayan",slug:"edward-narayan",fullName:"Edward Narayan",profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",biography:"Dr. Edward Narayan graduated with Ph.D. degree in Biology from the University of the South Pacific and pioneered non-invasive reproductive and stress endocrinology tools for amphibians - the novel development and validation of non-invasive enzyme immunoassays for the evaluation of reproductive hormonal cycle and stress hormone responses to environmental stressors. \nDr. Narayan leads the Stress Lab (Comparative Physiology and Endocrinology) at the University of Queensland. A dynamic career research platform which is based on the thematic areas of comparative vertebrate physiology, stress endocrinology, reproductive endocrinology, animal health and welfare, and conservation biology. \nEdward has supervised 40 research students and published over 60 peer reviewed research.",institutionString:null,institution:{name:"University of Queensland",institutionURL:null,country:{name:"Australia"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",institutionString:null,institution:{name:"Universidade Paulista",institutionURL:null,country:{name:"Brazil"}}},{id:"191123",title:"Dr.",name:"Juan José",middleName:null,surname:"Valdez-Alarcón",slug:"juan-jose-valdez-alarcon",fullName:"Juan José Valdez-Alarcón",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBfcQAG/Profile_Picture_1631354558068",institutionString:"Universidad Michoacana de San Nicolás de Hidalgo",institution:{name:"Universidad Michoacana de San Nicolás de Hidalgo",institutionURL:null,country:{name:"Mexico"}}},{id:"161556",title:"Dr.",name:"Maria Dos Anjos",middleName:null,surname:"Pires",slug:"maria-dos-anjos-pires",fullName:"Maria Dos Anjos Pires",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS8q2QAC/Profile_Picture_1633432838418",institutionString:null,institution:{name:"University of Trás-os-Montes and Alto Douro",institutionURL:null,country:{name:"Portugal"}}},{id:"209839",title:"Dr.",name:"Marina",middleName:null,surname:"Spinu",slug:"marina-spinu",fullName:"Marina Spinu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRLXpQAO/Profile_Picture_1630044895475",institutionString:null,institution:{name:"University of Agricultural Sciences and Veterinary Medicine of Cluj-Napoca",institutionURL:null,country:{name:"Romania"}}},{id:"92185",title:"Dr.",name:"Sara",middleName:null,surname:"Savic",slug:"sara-savic",fullName:"Sara Savic",profilePictureURL:"https://mts.intechopen.com/storage/users/92185/images/system/92185.jfif",institutionString:'Scientific Veterinary Institute "Novi Sad"',institution:{name:'Scientific Veterinary Institute "Novi Sad"',institutionURL:null,country:{name:"Serbia"}}}]},{id:"20",title:"Animal Nutrition",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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She is the head of the Reproduction and Embryology Laboratories and was lecturer of Reproduction and Reproductive Biotechnologies at Veterinary Medicine Faculty. She has over 25 years of experience working in reproductive biology and biotechnology areas with a special emphasis on embryo and gamete cryopreservation, for research and animal genetic resources conservation, leading research projects with several peer-reviewed papers. Rosa Pereira is member of the ERFP-FAO Ex situ Working Group and of the Management Commission of the Portuguese Animal Germplasm Bank.",institutionString:"The National Institute for Agricultural and Veterinary Research. Portugal",institution:null},editorTwo:null,editorThree:null,editorialBoard:[{id:"90066",title:"Dr.",name:"Alexandre",middleName:"Rodrigues",surname:"Silva",slug:"alexandre-silva",fullName:"Alexandre Silva",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRt8pQAC/Profile_Picture_1622531020756",institutionString:null,institution:{name:"Universidade Federal Rural do Semi-Árido",institutionURL:null,country:{name:"Brazil"}}},{id:"176987",title:"Ph.D.",name:"María-José",middleName:"Carrascosa",surname:"Argente",slug:"maria-jose-argente",fullName:"María-José Argente",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bS9vOQAS/Profile_Picture_1630330499537",institutionString:null,institution:{name:"Miguel Hernandez University",institutionURL:null,country:{name:"Spain"}}},{id:"321396",title:"Prof.",name:"Muhammad Subhan",middleName:null,surname:"Qureshi",slug:"muhammad-subhan-qureshi",fullName:"Muhammad Subhan Qureshi",profilePictureURL:"https://mts.intechopen.com/storage/users/321396/images/system/321396.jpg",institutionString:null,institution:{name:"University of Agriculture",institutionURL:null,country:{name:"Pakistan"}}},{id:"183723",title:"Dr.",name:"Xiaojun",middleName:null,surname:"Liu",slug:"xiaojun-liu",fullName:"Xiaojun Liu",profilePictureURL:"https://mts.intechopen.com/storage/users/183723/images/system/183723.jpg",institutionString:null,institution:null}]}]},overviewPageOFChapters:{paginationCount:20,paginationItems:[{id:"82526",title:"Deep Multiagent Reinforcement Learning Methods Addressing the Scalability Challenge",doi:"10.5772/intechopen.105627",signatures:"Theocharis Kravaris and George A. 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He is an academic staff member of the Department of Reproduction and Artificial Insemination, Selçuk University, Turkey. He manages several studies on sperms and embryos and is an editorial board member for several international journals. His studies include sperm cryobiology, in vitro fertilization, and embryo production in animals.",institutionString:"Selçuk University, Faculty of Veterinary Medicine",institution:null},{id:"90846",title:"Prof.",name:"Yusuf",middleName:null,surname:"Bozkurt",slug:"yusuf-bozkurt",fullName:"Yusuf Bozkurt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/90846/images/system/90846.jpg",biography:"Yusuf Bozkurt has a BSc, MSc, and Ph.D. from Ankara University, Turkey. He is currently a Professor of Biotechnology of Reproduction in the field of Aquaculture, İskenderun Technical University, Turkey. His research interests include reproductive biology and biotechnology with an emphasis on cryo-conservation. He is on the editorial board of several international peer-reviewed journals and has published many papers. Additionally, he has participated in many international and national congresses, seminars, and workshops with oral and poster presentations. He is an active member of many local and international organizations.",institutionString:"İskenderun Technical University",institution:{name:"İskenderun Technical University",country:{name:"Turkey"}}},{id:"61139",title:"Dr.",name:"Sergey",middleName:null,surname:"Tkachev",slug:"sergey-tkachev",fullName:"Sergey Tkachev",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/61139/images/system/61139.png",biography:"Dr. Sergey Tkachev is a senior research scientist at the Institute of Fundamental Medicine and Biology, Kazan Federal University, Russia, and at the Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia. He received his Ph.D. in Molecular Biology with his thesis “Genetic variability of the tick-borne encephalitis virus in natural foci of Novosibirsk city and its suburbs.” His primary field is molecular virology with research emphasis on vector-borne viruses, especially tick-borne encephalitis virus, Kemerovo virus and Omsk hemorrhagic fever virus, rabies virus, molecular genetics, biology, and epidemiology of virus pathogens.",institutionString:"Russian Academy of Sciences",institution:{name:"Russian Academy of Sciences",country:{name:"Russia"}}},{id:"310962",title:"Dr.",name:"Amlan",middleName:"Kumar",surname:"Patra",slug:"amlan-patra",fullName:"Amlan Patra",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/310962/images/system/310962.jpg",biography:"Amlan K. Patra, FRSB, obtained a Ph.D. in Animal Nutrition from Indian Veterinary Research Institute, India, in 2002. He is currently an associate professor at West Bengal University of Animal and Fishery Sciences. He has more than twenty years of research and teaching experience. He held previous positions at the American Institute for Goat Research, The Ohio State University, Columbus, USA, and Free University of Berlin, Germany. His research focuses on animal nutrition, particularly ruminants and poultry nutrition, gastrointestinal electrophysiology, meta-analysis and modeling in nutrition, and livestock–environment interaction. He has authored around 175 articles in journals, book chapters, and proceedings. Dr. Patra serves on the editorial boards of several reputed journals.",institutionString:null,institution:{name:"West Bengal University of Animal and Fishery Sciences",country:{name:"India"}}},{id:"53998",title:"Prof.",name:"László",middleName:null,surname:"Babinszky",slug:"laszlo-babinszky",fullName:"László Babinszky",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/53998/images/system/53998.png",biography:"László Babinszky is Professor Emeritus, Department of Animal Nutrition Physiology, University of Debrecen, Hungary. He has also worked in the Department of Animal Nutrition, University of Wageningen, Netherlands; the Institute for Livestock Feeding and Nutrition (IVVO), Lelystad, Netherlands; the Agricultural University of Vienna (BOKU); the Institute for Animal Breeding and Nutrition, Austria; and the Oscar Kellner Research Institute for Animal Nutrition, Rostock, Germany. In 1992, Dr. Babinszky obtained a Ph.D. in Animal Nutrition from the University of Wageningen. His main research areas are swine and poultry nutrition. He has authored more than 300 publications (papers, book chapters) and edited four books and fourteen international conference proceedings.",institutionString:"University of Debrecen",institution:{name:"University of Debrecen",country:{name:"Hungary"}}},{id:"201830",title:"Dr.",name:"Fernando",middleName:"Sanchez",surname:"Davila",slug:"fernando-davila",fullName:"Fernando Davila",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/201830/images/5017_n.jpg",biography:"I am a professor at UANL since 1988. My research lines are the development of reproductive techniques in small ruminants. We also conducted research on sexual and social behavior in males.\nI am Mexican and study my professional career as an engineer in agriculture and animal science at UANL. Then take a masters degree in science in Germany (Animal breeding). Take a doctorate in animal science at the UANL.",institutionString:null,institution:{name:"Universidad Autónoma de Nuevo León",country:{name:"Mexico"}}},{id:"309250",title:"Dr.",name:"Miguel",middleName:null,surname:"Quaresma",slug:"miguel-quaresma",fullName:"Miguel Quaresma",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309250/images/9059_n.jpg",biography:"Miguel Nuno Pinheiro Quaresma was born on May 26, 1974 in Dili, Timor Island. He is married with two children: a boy and a girl, and he is a resident in Vila Real, Portugal. He graduated in Veterinary Medicine in August 1998 and obtained his Ph.D. degree in Veterinary Sciences -Clinical Area in February 2015, both from the University of Trás-os-Montes e Alto Douro. He is currently enrolled in the Alternative Residency of the European College of Animal Reproduction. He works as a Senior Clinician at the Veterinary Teaching Hospital of UTAD (HVUTAD) with a role in clinical activity in the area of livestock and equine species as well as to support teaching and research in related areas. He teaches as an Invited Professor in Reproduction Medicine I and II of the Master\\'s in Veterinary Medicine degree at UTAD. Currently, he holds the position of Chairman of the Portuguese Buiatrics Association. He is a member of the Consultive Group on Production Animals of the OMV. He has 19 publications in indexed international journals (ISIS), as well as over 60 publications and oral presentations in both Portuguese and international journals and congresses.",institutionString:"University of Trás-os-Montes and Alto Douro",institution:{name:"University of Trás-os-Montes and Alto Douro",country:{name:"Portugal"}}},{id:"38652",title:"Prof.",name:"Rita",middleName:null,surname:"Payan-Carreira",slug:"rita-payan-carreira",fullName:"Rita Payan-Carreira",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRiFPQA0/Profile_Picture_1614601496313",biography:"Rita Payan Carreira earned her Veterinary Degree from the Faculty of Veterinary Medicine in Lisbon, Portugal, in 1985. She obtained her Ph.D. in Veterinary Sciences from the University of Trás-os-Montes e Alto Douro, Portugal. After almost 32 years of teaching at the University of Trás-os-Montes and Alto Douro, she recently moved to the University of Évora, Department of Veterinary Medicine, where she teaches in the field of Animal Reproduction and Clinics. Her primary research areas include the molecular markers of the endometrial cycle and the embryo–maternal interaction, including oxidative stress and the reproductive physiology and disorders of sexual development, besides the molecular determinants of male and female fertility. She often supervises students preparing their master's or doctoral theses. She is also a frequent referee for various journals.",institutionString:null,institution:{name:"University of Évora",country:{name:"Portugal"}}},{id:"283019",title:"Dr.",name:"Oudessa",middleName:null,surname:"Kerro Dego",slug:"oudessa-kerro-dego",fullName:"Oudessa Kerro Dego",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/283019/images/system/283019.png",biography:"Dr. Kerro Dego is a veterinary microbiologist with training in veterinary medicine, microbiology, and anatomic pathology. Dr. Kerro Dego is an assistant professor of dairy health in the department of animal science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. He received his D.V.M. (1997), M.S. (2002), and Ph.D. (2008) degrees in Veterinary Medicine, Animal Pathology and Veterinary Microbiology from College of Veterinary Medicine, Addis Ababa University, Ethiopia; College of Veterinary Medicine, Utrecht University, the Netherlands and Western College of Veterinary Medicine, University of Saskatchewan, Canada respectively. He did his Postdoctoral training in microbial pathogenesis (2009 - 2015) in the Department of Animal Science, the University of Tennessee, Institute of Agriculture, Knoxville, Tennessee. Dr. Kerro Dego’s research focuses on the prevention and control of infectious diseases of farm animals, particularly mastitis, improving dairy food safety, and mitigation of antimicrobial resistance. Dr. Kerro Dego has extensive experience in studying the pathogenesis of bacterial infections, identification of virulence factors, and vaccine development and efficacy testing against major bacterial mastitis pathogens. Dr. Kerro Dego conducted numerous controlled experimental and field vaccine efficacy studies, vaccination, and evaluation of immunological responses in several species of animals, including rodents (mice) and large animals (bovine and ovine).",institutionString:"University of Tennessee at Knoxville",institution:{name:"University of Tennessee at Knoxville",country:{name:"United States of America"}}},{id:"251314",title:"Dr.",name:"Juan Carlos",middleName:null,surname:"Gardón Poggi",slug:"juan-carlos-gardon-poggi",fullName:"Juan Carlos Gardón Poggi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/251314/images/system/251314.jpeg",biography:"Juan Carlos Gardón Poggi received University degree from the Faculty of Agrarian Science in Argentina, in 1983. Also he received Masters Degree and PhD from Córdoba University, Spain. He is currently a Professor at the Catholic University of Valencia San Vicente Mártir, at the Department of Medicine and Animal Surgery. He teaches diverse courses in the field of Animal Reproduction and he is the Director of the Veterinary Farm. He also participates in academic postgraduate activities at the Veterinary Faculty of Murcia University, Spain. His research areas include animal physiology, physiology and biotechnology of reproduction either in males or females, the study of gametes under in vitro conditions and the use of ultrasound as a complement to physiological studies and development of applied biotechnologies. Routinely, he supervises students preparing their doctoral, master thesis or final degree projects.",institutionString:null,institution:{name:"Valencia Catholic University Saint Vincent Martyr",country:{name:"Spain"}}},{id:"309529",title:"Dr.",name:"Albert",middleName:null,surname:"Rizvanov",slug:"albert-rizvanov",fullName:"Albert Rizvanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/309529/images/9189_n.jpg",biography:'Albert A. Rizvanov is a Professor and Director of the Center for Precision and Regenerative Medicine at the Institute of Fundamental Medicine and Biology, Kazan Federal University (KFU), Russia. He is the Head of the Center of Excellence “Regenerative Medicine” and Vice-Director of Strategic Academic Unit \\"Translational 7P Medicine\\". Albert completed his Ph.D. at the University of Nevada, Reno, USA and Dr.Sci. at KFU. He is a corresponding member of the Tatarstan Academy of Sciences, Russian Federation. Albert is an author of more than 300 peer-reviewed journal articles and 22 patents. He has supervised 11 Ph.D. and 2 Dr.Sci. dissertations. Albert is the Head of the Dissertation Committee on Biochemistry, Microbiology, and Genetics at KFU.\nORCID https://orcid.org/0000-0002-9427-5739\nWebsite https://kpfu.ru/Albert.Rizvanov?p_lang=2',institutionString:"Kazan Federal University",institution:{name:"Kazan Federal University",country:{name:"Russia"}}},{id:"210551",title:"Dr.",name:"Arbab",middleName:null,surname:"Sikandar",slug:"arbab-sikandar",fullName:"Arbab Sikandar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210551/images/system/210551.jpg",biography:"Dr. Arbab Sikandar, PhD, M. Phil, DVM was born on April 05, 1981. He is currently working at the College of Veterinary & Animal Sciences as an Assistant Professor. He previously worked as a lecturer at the same University. \nHe is a Member/Secretory of Ethics committee (No. CVAS-9377 dated 18-04-18), Member of the QEC committee CVAS, Jhang (Regr/Gen/69/873, dated 26-10-2017), Member, Board of studies of Department of Basic Sciences (No. CVAS. 2851 Dated. 12-04-13, and No. CVAS, 9024 dated 20/11/17), Member of Academic Committee, CVAS, Jhang (No. CVAS/2004, Dated, 25-08-12), Member of the technical committee (No. CVAS/ 4085, dated 20,03, 2010 till 2016).\n\nDr. Arbab Sikandar contributed in five days hands-on-training on Histopathology at the Department of Pathology, UVAS from 12-16 June 2017. He received a Certificate of appreciation for contributions for Popularization of Science and Technology in the Society on 17-11-15. He was the resource person in the lecture series- ‘scientific writing’ at the Department of Anatomy and Histology, UVAS, Lahore on 29th October 2015. He won a full fellowship as a principal candidate for the year 2015 in the field of Agriculture, EICA, Egypt with ref. to the Notification No. 12(11) ACS/Egypt/2014 from 10 July 2015 to 25th September 2015.; he received a grant of Rs. 55000/- as research incentives from Director, Advanced Studies and Research, UVAS, Lahore upon publications of research papers in IF Journals (DR/215, dated 19-5-2014.. He obtained his PhD by winning a HEC Pakistan indigenous Scholarship, ‘Ph.D. fellowship for 5000 scholars – Phase II’ (2av1-147), 17-6/HEC/HRD/IS-II/12, November 15, 2012. \n\nDr. Sikandar is a member of numerous societies: Registered Veterinary Medical Practitioner (life member) and Registered Veterinary Medical Faculty of Pakistan Veterinary Medical Council. The Registration code of PVMC is RVMP/4298 and RVMF/ 0102.; Life member of the University of Veterinary and Animal Sciences, Lahore, Alumni Association with S# 664, dated: 6-4-12. ; Member 'Vets Care Organization Pakistan” with Reference No. VCO-605-149, dated 05-04-06. :Member 'Vet Crescent” (Society of Animal Health and Production), UVAS, Lahore.",institutionString:"University of Veterinary & Animal Science",institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}},{id:"311663",title:"Dr.",name:"Prasanna",middleName:null,surname:"Pal",slug:"prasanna-pal",fullName:"Prasanna Pal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311663/images/13261_n.jpg",biography:null,institutionString:null,institution:{name:"National Dairy Research Institute",country:{name:"India"}}},{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202192/images/system/202192.png",biography:"Catrin Rutland is an Associate Professor of Anatomy and Developmental Genetics at the University of Nottingham, UK. She obtained a BSc from the University of Derby, England, a master’s degree from Technische Universität München, Germany, and a Ph.D. from the University of Nottingham. She undertook a post-doctoral research fellowship in the School of Medicine before accepting tenure in Veterinary Medicine and Science. Dr. Rutland also obtained an MMedSci (Medical Education) and a Postgraduate Certificate in Higher Education (PGCHE). She is the author of more than sixty peer-reviewed journal articles, twelve books/book chapters, and more than 100 research abstracts in cardiovascular biology and oncology. She is a board member of the European Association of Veterinary Anatomists, Fellow of the Anatomical Society, and Senior Fellow of the Higher Education Academy. Dr. Rutland has also written popular science books for the public. https://orcid.org/0000-0002-2009-4898. www.nottingham.ac.uk/vet/people/catrin.rutland",institutionString:null,institution:{name:"University of Nottingham",country:{name:"United Kingdom"}}},{id:"283315",title:"Prof.",name:"Samir",middleName:null,surname:"El-Gendy",slug:"samir-el-gendy",fullName:"Samir El-Gendy",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRduYQAS/Profile_Picture_1606215849748",biography:"Samir El-Gendy is a Professor of anatomy and embryology at the faculty of veterinary medicine, Alexandria University, Egypt. Samir obtained his PhD in veterinary science in 2007 from the faculty of veterinary medicine, Alexandria University and has been a professor since 2017. Samir is an author on 24 articles at Scopus and 12 articles within local journals and 2 books/book chapters. His research focuses on applied anatomy, imaging techniques and computed tomography. Samir worked as a member of different local projects on E-learning and he is a board member of the African Association of Veterinary Anatomists and of anatomy societies and as an associated author at local and international journals. Orcid: https://orcid.org/0000-0002-6180-389X",institutionString:null,institution:{name:"Alexandria University",country:{name:"Egypt"}}},{id:"246149",title:"Dr.",name:"Valentina",middleName:null,surname:"Kubale",slug:"valentina-kubale",fullName:"Valentina Kubale",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246149/images/system/246149.jpg",biography:"Valentina Kubale is Associate Professor of Veterinary Medicine at the Veterinary Faculty, University of Ljubljana, Slovenia. Since graduating from the Veterinary faculty she obtained her PhD in 2007, performed collaboration with the Department of Pharmacology, University of Copenhagen, Denmark. She continued as a post-doctoral fellow at the University of Copenhagen with a Lundbeck foundation fellowship. She is the editor of three books and author/coauthor of 23 articles in peer-reviewed scientific journals, 16 book chapters, and 68 communications at scientific congresses. Since 2008 she has been the Editor Assistant for the Slovenian Veterinary Research journal. She is a member of Slovenian Biochemical Society, The Endocrine Society, European Association of Veterinary Anatomists and Society for Laboratory Animals, where she is board member.",institutionString:"University of Ljubljana",institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"258334",title:"Dr.",name:"Carlos Eduardo",middleName:null,surname:"Fonseca-Alves",slug:"carlos-eduardo-fonseca-alves",fullName:"Carlos Eduardo Fonseca-Alves",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/258334/images/system/258334.jpg",biography:"Dr. Fonseca-Alves earned his DVM from Federal University of Goias – UFG in 2008. He completed an internship in small animal internal medicine at UPIS university in 2011, earned his MSc in 2013 and PhD in 2015 both in Veterinary Medicine at Sao Paulo State University – UNESP. Dr. Fonseca-Alves currently serves as an Assistant Professor at Paulista University – UNIP teaching small animal internal medicine.",institutionString:null,institution:{name:"Universidade Paulista",country:{name:"Brazil"}}},{id:"245306",title:"Dr.",name:"María Luz",middleName:null,surname:"Garcia Pardo",slug:"maria-luz-garcia-pardo",fullName:"María Luz Garcia Pardo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/245306/images/system/245306.png",biography:"María de la Luz García Pardo is an agricultural engineer from Universitat Politècnica de València, Spain. She has a Ph.D. in Animal Genetics. Currently, she is a lecturer at the Agrofood Technology Department of Miguel Hernández University, Spain. Her research is focused on genetics and reproduction in rabbits. The major goal of her research is the genetics of litter size through novel methods such as selection by the environmental sensibility of litter size, with forays into the field of animal welfare by analysing the impact on the susceptibility to diseases and stress of the does. Details of her publications can be found at https://orcid.org/0000-0001-9504-8290.",institutionString:null,institution:{name:"Miguel Hernandez University",country:{name:"Spain"}}},{id:"350704",title:"M.Sc.",name:"Camila",middleName:"Silva Costa",surname:"Ferreira",slug:"camila-ferreira",fullName:"Camila Ferreira",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/350704/images/17280_n.jpg",biography:"Graduated in Veterinary Medicine at the Fluminense Federal University, specialist in Equine Reproduction at the Brazilian Veterinary Institute (IBVET) and Master in Clinical Veterinary Medicine and Animal Reproduction at the Fluminense Federal University. She has experience in analyzing zootechnical indices in dairy cattle and organizing events related to Veterinary Medicine through extension grants. I have experience in the field of diagnostic imaging and animal reproduction in veterinary medicine through monitoring and scientific initiation scholarships. I worked at the Equus Central Reproduction Equine located in Santo Antônio de Jesus – BA in the 2016/2017 breeding season. I am currently a doctoral student with a scholarship from CAPES of the Postgraduate Program in Veterinary Medicine (Pathology and Clinical Sciences) at the Federal Rural University of Rio de Janeiro (UFRRJ) with a research project with an emphasis on equine endometritis.",institutionString:null,institution:null},{id:"41319",title:"Prof.",name:"Lung-Kwang",middleName:null,surname:"Pan",slug:"lung-kwang-pan",fullName:"Lung-Kwang Pan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41319/images/84_n.jpg",biography:null,institutionString:null,institution:null},{id:"125292",title:"Dr.",name:"Katy",middleName:null,surname:"Satué Ambrojo",slug:"katy-satue-ambrojo",fullName:"Katy Satué Ambrojo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/125292/images/system/125292.jpeg",biography:"Katy Satué Ambrojo received her Veterinary Medicine degree, Master degree in Equine Technology and doctorate in Veterinary Medicine from the Faculty of Veterinary, CEU-Cardenal Herrera University in Valencia, Spain.Dr. Satué is accredited as a Private University Doctor Professor, Doctor Assistant, and Contracted Doctor by AVAP (Agència Valenciana d'Avaluació i Prospectiva) and currently, as a full professor by ANECA (since January 2022). To date, Katy has taught 22 years in the Department of Animal Medicine and Surgery at the CEU-Cardenal Herrera University in undergraduate courses in Veterinary Medicine (General Pathology, integrated into the Applied Basis of Veterinary Medicine module of the 2nd year, Clinical Equine I of 3rd year, and Equine Clinic II of 4th year). Dr. Satué research activity is in the field of Endocrinology, Hematology, Biochemistry, and Immunology in the Spanish Purebred mare. She has directed 5 Doctoral Theses and 5 Diplomas of Advanced Studies, and participated in 11 research projects as a collaborating researcher. She has written 2 books and 14 book chapters in international publishers related to the area, and 68 scientific publications in international journals. Dr. Satué has attended 63 congresses, participating with 132 communications in international congresses and 19 in national congresses related to the area. 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We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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