Actions of β-adrenergic receptors.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2115",leadTitle:null,fullTitle:"Biotechnology - Molecular Studies and Novel Applications for Improved Quality of Human Life",title:"Biotechnology",subtitle:"Molecular Studies and Novel Applications for Improved Quality of Human Life",reviewType:"peer-reviewed",abstract:"This book deals with the importance of application of molecular biology as an approach of biotechnology for improvement of the quality of human life. One of the interesting topics in this field, is the identification of the organisms that produce bioactive secondary metabolites. It also discusses how to structure a plan for use and preservation of those species that represent a potential source for new drug development, especially those obtained from bacteria. 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In 1995 he promoted to professor of molecular systematic. \nSammour published more than sixty research papers. His PhD thesis and re-searches have made use of molecular techniques for solving problems in plant diversity for yield enhancement in many food crops. For participation in the study of genetic diversity of plants, producing genetically modified plants have more of essential amino acids he was awarded encouragement award of Tanta University. 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Healthcare safety is among the most important considerations when designing, building, and managing modern patient care facilities and systems. Among many reasons why healthcare systems have not inherently “evolved into safety” were the combination of provider individualism and the lack of early recognition of the importance of effective communication and coordination as the primary method of ensuring maintenance of safety standards throughout the entire patient care continuum [1]. The first two volumes of the
As our clinics, hospitals, and more recently growing networks of facilities began to aggregate providers from diverse disciplines and training backgrounds, the need for better coordination and communication to ensure safe and seamless patient care became apparent [3, 4]. Growing teams of highly trained individuals who work together, yet may not know each other, became the reality of healthcare systems that require the performance of multistep tasks of great complexity [5, 6]. In this introductory chapter, we will discuss how team communication and appropriate coordination of care are instrumental to ensuring and improving patient safety, as well as to the overall functioning of the patient safety matrix across healthcare organizations (Figure 1).
\nIdealized diagram summarizing key components of patient safety matrix in health care. Only selected components are listed, emphasizing the importance of good leadership, communication, and team coordination, in addition to other domains previously discussed in the
The Institute of Medicine (IOM) defined six key measures to improve the overall quality of our healthcare system, including safety, effectiveness, timeliness, efficiency, equity, and focus on the patient [7]. The concept of patient safety has been an active area of opportunity for hospitals [8] and clinicians, especially with the advent of objective scorecards and pay-for-performance measures [3, 7]. Patient safety began to transform into its current, more structured format in the early 1990s as it became increasingly apparent that hospitals were not as safe as previously thought and patients undergoing treatment at our healthcare facilities were shown to be at substantial risk of adverse events [4, 9]. The field of healthcare quality and safety encompasses numerous factors, most of which have been discussed in previous volumes of this series, including topics like leadership and organizational culture [3]. In this volume we will explore in greater detail key patient safety concepts in the context of team communication and coordination. It is only through appropriately coordinated work as a team, using proven communication techniques, that we can bring tangible benefits to new and existing healthcare platforms, making care delivery safer, and establishing greater trust in the current system [10, 11, 12, 13]. Our exploration will emphasize the importance of teamwork in achieving the goals of the IOM and ultimately creating a universal and standardized environment and a culture safety (Figure 2).
\nKey components necessary for the creation of institutional culture of safety.
Historically, the practice of medicine has revolved around a personal interaction between the patient and his or her healthcare provider [14]. This viewpoint has permeated the cultural and organizational perceptions within medicine, thus heavily influencing and shaping the delivery (and effectiveness) of care [15, 16]. Even with the changing institutional and work dynamics within the healthcare system, this individualistic paradigm continued to prevail, with physicians treating patients at the point of care, characterized by only limited collaboration and coordination with other healthcare professionals [17, 18]. The transition from a physician-centered system to a more patient-centered system required a paradigm shift that inherently led to increased care complexity and the need for better coordination and communication across multidisciplinary teams [7, 19, 20]. There is ample evidence linking adverse healthcare events with inadequate team communication and/or coordination, highlighting the critical nature of “teamwork” as opposed to the more traditional and flawed “individual blame” culture [4, 5, 21, 22]. Patient safety literature also indicates that teamwork is key to establishing and maintaining patient safety, and issues related to lack of collaborative approaches and/or communication often contribute to poor quality and safety record [21, 23, 24]. Support for constructive and collaborative thinking must permeate all levels of the organization [3, 4]. At the same time, we must recognize that effective teamwork and collaboration are not going to be inherently easy within a dynamic, complex, and unpredictable environment of modern healthcare systems. However, the above limitation should not serve as a perpetual excuse for failing to improve the current status quo, as proven by other high performance or high-stakes industries that have successfully adopted effective quality, safety, and reliability models [4, 25, 26].
\nThroughout the
Patient safety can be defined as a discipline or characteristic of a healthcare system that focuses on the application of safety science methodologies to minimize the incidence and impact of adverse events, with the ultimate goal of creating a trustworthy and highly reliable healthcare delivery environment [9]. The critical importance of patient safety has been well established across the full spectrum of modern healthcare settings, including the more recent introduction of patient-centered care and quality-based reimbursement paradigms [3, 27, 28]. As the care delivery paradigm continues to evolve, we must strive to learn, grow, and make sustained improvements across all domains of practice, from the most mundane to the most complex ones. Because the focus on patient safety has its genesis in the combined desire and duty to “do the right thing” in conjunction with the realization that there is an unacceptably high prevalence of avoidable adverse events, we must all join forces and make the effort to meaningfully contribute at the personal, team, and institutional levels [3, 29, 30].
\nFor any meaningful change in practice (and thus organizational culture) to occur, a shift in mindset must be embraced at both individual and institutional levels [31]. In the past, there was a widely held belief that “well-trained and conscientious” providers generally do not commit errors and that most errors occurred because of “carelessness and incompetence” [9, 32]. Consequently, punitive approaches to error identification and correction prevailed, creating an environment of “fear, secrecy, and nondisclosure” [4, 9]. The resultant “culture of blame” gradually gave way to a more in-depth understanding of medical errors, with increasing realization that only a minority of errors are clearly attributable to a single individual or factor [3, 4, 5].
\nResearch into human factors provides evidence that in great majority of cases it is not “the individual” who is to be blamed, but rather the error results from imperfections within the organization’s systems, training, equipment, and/or management [9, 33, 34]. This sparked a transition toward system-based thinking and adoption of error management, an effective method used in aviation, into health care as a way of introducing a more sustainable paradigm change [3, 4, 35]. Subsequent identification and improved understanding of various “failure modes” such as “latent failures” that may be “hidden” within an otherwise highly efficient and safe environment [35] gave us further insight into phenomena “we did not know that we did not know.” Among various areas of scrutiny, it became apparent that the largest number of opportunities for improvement resided within the general domains of “team communication” and “team coordination” [36, 37].
\nFor the purposes of our discussion, a team is described as one or more individuals working together toward a specific, shared aim [21]. This highlights the importance of any verbal or written communication between providers and caretakers where at least two individuals are involved, regardless of how trivial such communication may seem at the time. Also, integral to the team context, each individual has a special role to play within their own area of knowledge and expertise [21]. Inherent to effective teamwork, individuals should be willing to share their resources, communicate and coordinate closely in order to provide the very best care and experience for the patient from every conceivable standpoint, including clinical outcomes, quality, and safety [21]. Of note, the above statements describe nearly every team-based microsystem within the modern healthcare construct.
\nIt seems that coordination and collaboration should be occurring intuitively in a high-performing medical system. However, breakdowns in communication, an essential element in care coordination, were found by The Joint Commission to contribute to 70% of adverse events [32], with a large proportion of these events resulting in mortality [38]. Teamwork is paramount not only to the development of a safe patient environment but also to improved patient outcomes, enhanced quality of care, and greater provider satisfaction [32, 38]. Inefficient team structure and poor functioning have been implicated in inferior quality of care and worse safety performance [21]. Given the complexities of modern healthcare environment, including the diversity of roles and increasing degree of specialization within essentially every area of practice/expertise, the above considerations become even more urgent [39, 40]. Consequently, the concurrent presence of well-choreographed coordination, communication, and teamwork is no longer optional in the interprofessional environment of modern health care, at all levels of every organization [40].
\nWhen people work together toward a common goal, remarkable achievements are possible. There are, however, important team-specific considerations. With the growth of team size and complexity, so does the potential for errors. Essential to reducing the number of errors is the presence of robust, often redundant feedback mechanisms [4, 41, 42]. In addition to improving safety and effectiveness of teams, properly structured teamwork may also help improve staff well-being and morale [21]. Consequently, targeted restructuring of microsystems and processes toward a more team-based approach can bring about important benefits and synergies [21]. Finally, thoughtful implementation of interventions that foster shared decision-making, planning, and problem-solving can also be effective in improving both clinical outcomes and patient safety [32].
\nAlthough healthcare professionals tend to be aware of the importance of teamwork, communication, and coordination, this awareness does not universally translate into appropriate or optimal behavioral manifestations [21]. As a result, breakdowns in teamwork—rather than lack of knowledge or clinical skills—continue to contribute to a significant proportion of adverse healthcare events [21]. Thus, the importance of working effectively within a complex team-based environment cannot be overstated, with evidence from one observational study conducted in the pediatric surgical setting demonstrating that “…effective teamwork was associated with fewer minor problems per operation, higher intraoperative performance and shorter operating times” [21]. If coordinated teamwork and communication are so important to ensuring patient safety, what are some of the more common failure modes and more importantly the associated barriers?
\nWithout effective communication between care providers, healthcare teams, and their patients, considerations given to safety measures are more likely to be insufficient, often creating adverse outcomes in both unexpected and unpredictable ways [6]. There are several important barriers to collaboration, coordination, and communication, as outlined in the current section. Within the highly complex and dynamic modern healthcare organizations, each individual must organize and coordinate the necessary care in accordance to their unique, specialized, and highly valued training, expertise, and patterns of practice [43]. Consequently, this inherent systemic heterogeneity is a strong determinant of breakdowns in team function, beginning with differences in the level and type of training and ending with vast and often non-overlapping skill sets that are neither universally understood nor well communicated across the involved group. For example, nurses and doctors are trained to communicate very differently. Nurses tend to be more detailed and emphasize gathering, collecting, and communicating highly granular facts [44, 45]. On the other hand, physicians are taught to interpret these facts, make a diagnosis, and communicate their conclusions without necessarily relating all of the details that led to the formulation of associated clinical plans [44, 45]. An important consideration in this general context is the potential difference in perceptions related to communication among different group members [45, 46].
\nAnother barrier to effective collaboration and communication is the persistence of hierarchical systems that place various team members at different levels of the team decision-making process, often based on specialty, expertise, politics, and other arbitrary factors [47]. Instead, approaches that embrace the fact that each individual brings a unique perspective and breadth of knowledge to the team should be encouraged and appear to be of great importance to improving patient outcomes and promoting a culture of safety [3, 4]. Inviting input and open discourse from the entire team can both improve the delivery of care and reduce the possibility of critical safety steps being missed. Mutual respect, appreciation, acknowledgement, and constructive reflection within the team must be encouraged and should constitute the foundation of sound organizational culture [48, 49]. Great emphasis also needs to be placed on valuing different perspectives, regardless of how divergent individual views may be, through respectful discourse and acknowledgment of key differences. In health care, each member of the team inherently believes that he or she is doing what is truly best for the patient. Respect for differing opinions is an important part of avoiding unnecessary “ego contests” that may be detrimental not only to the team dynamic but also to patient safety and outcomes.
\nThere are several other potential barriers to communication and collaboration that are worth mentioning. Intimidation and disruptive behavior both can interfere with effective coordination of care. There should be “zero tolerance” for these phenomena because they can lead to the development of a hostile work environment and result in fear of communicating or reporting medical errors (e.g., unwillingness to speak up). Any evidence of intimidation or retribution should be a basis for disciplinary action, up to and including termination of employment. Disruptive behavior has been associated with preventable adverse events and adverse patient outcomes [50], and it can distract team members from focusing on effective communication and the performance of essential functions of their job [32, 51]. In summary, it is critical that these two major, yet uncomfortably under-recognized barriers to effective team collaboration and communication be identified and aggressively addressed at all levels of healthcare institutions.
\nMuch like effective communication, highly structured coordination is important to ensuring that established patient safety mechanisms continue to function properly. All team members should be “on the same page” in terms of their understanding of the group’s function and purpose. Yet, as we discussed in previous sections, this can be challenging at times due to the abovementioned barriers. In this context, resistance to change may be responsible for the reluctance of both people and institutions to embrace better ways of doing things. Such resistance can persist within clearly dysfunctional teams despite unequivocal evidence demonstrating successful culture shift within other high-stakes industries such as aviation and banking [52]. Identification of problems in the current patient safety paradigm must begin with clear and unambiguous definitions. For example, there are different categories of suboptimal communication, including poorly timed, misdirected, incomplete or inaccurate information exchanges, as well as ineffective communication due to lack of follow-through [32]. The latter type is thought to be a leading cause of medical error and patient harm in the acute care setting [32]. As outlined throughout the
Standardized team training is important to ensuring a sustained ability of our institutions to function at high-performance levels. Such training programs increasingly take into consideration the human performance science and are designed to mitigate errors and patterns of errors that commonly occur when human beings operate under high levels of stress [54]. Targeted training in leadership, decision-making, briefings, and cross-checking, as well as monitoring, reviewing, and modifying plans under stress, is integrated into the curricula [54]. Simulation constitutes another important aspect of team training. It provides an opportunity to practice various techniques and scenarios in a controlled, highly structured environment. It facilitates real-time feedback and thus creates an opportunity to proactively improve team attitudes and behaviors.
\nGood leadership is paramount to organizational success. Rapidly evolving modern healthcare environment requires leaders to be highly flexible and well-versed in change management skills, with focus on the delivery of high-quality, safe patient care. The establishment of a culture of safety is critical to the leadership’s ability to bring about institutional change, enhanced quality of care, and ultimately better patient outcomes [3, 4, 8]. Moreover, healthcare leaders must make patient safety a top organizational priority [8], and through such prioritization, a positive “trickle-down” effect will help gradually facilitate the desired institutional transformation. High-reliability organizations (HRO) can be defined as being able to successfully implement changes required to make them more efficient, safer, and cost-effective. This, in turn, exemplifies the “big picture” view of value-driven health care.
\nOrganizational culture defines the parameters of the work environment. For each healthcare institution and system, poorly managed variability within and between individuals, teams, departments, etc. has the potential to create a dangerous mix of both active and latent systemic contributors to patient safety events. In order to reconfigure the culture of an organization, not only does it takes broad-based staff buy-in but also effective leaders who are able to inspire individuals and teams to pursue both personal and operational excellence.
\nPatient safety is a dynamically evolving discipline, with many challenges and opportunities along the journey to operational excellence, just culture, and sustained “zero defect” performance record. The overarching theme of this chapter and this book is that effective teamwork requires the investment of significant amounts of time, effort, and energy by all stakeholders. Modern healthcare requires safe and efficient teamwork, which in turn requires intensive training and education. Most people find it challenging to work with large, complex teams and are often unaware of the various barriers to effective communication and coordination required to thrive in such environment. The creation of team-based healthcare systems must begin with breaking “old habits” and proactive advocacy for the adoption of modern, evidence-based approaches. Beginning with institutional leadership’s vision and strategy, trust and respect are fostered to help encourage positive behaviors and implement just culture. The ultimate goal of “zero harm” must always remain the top priority within the safer and more efficient healthcare systems of tomorrow.
\nThe 7 transmembrane receptors (7TMRs) also known as G-protein coupled receptors (GPCRs) constitute the largest family of plasma membrane receptors. The superfamily of 7TMRs includes receptors for hormones, neurotransmitters and ion channels, and is critical to mediate physiological and cellular processes [1, 2].
Composed of seven transmembrane hydrophobic alpha (α) helices joined by three intracellular and three extracellular loop structures, a cytoplasmic carboxyl terminus and an extracellular amino terminus (Figure 1), 7TMRs signal by stimulating heterotrimeric G proteins following the presentation of an agonist to the receptor [3]. Agonist binding at the 7TMR extracellular region initiates the formation of a G protein. Guanosine diphosphate (GDP) is released from the G protein in exchange for guanosine triphosphate (GTP). The GTP bound α subunit disassociates from the βγ dimer, both of which activate several effectors such as adenylyl cyclase, phospholipases and ion channels [3]. The Gα subunit can be categorised in to sub groups Gαs, Gαi, Gαq/11 and Gα12/13 [3]. The Gα subunits and the Gβγ dimer deriving from the heterotrimeric G protein can combine with downstream effector molecules such as adenylyl cyclase or phospholipase C to control cellular signalling pathways involving secondary messengers [3]. Examples of secondary messengers include cyclic adenosine monophosphate (cAMP), inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) which elicit cellular and physiological responses [4].
General structure of a seven transmembrane receptor (7TMR)/G protein coupled receptor (GPCR). Extracellular loops 1–3 (EL1–3) and intracellular loops (IL1–3) connecting the 7 transmembrane helices (TM1–7). NH2▬N-terminal chain and COOH▬C-terminal chain.
7TMRs are the target for a large proportion of therapeutic drugs, currently encompassing more than 30% of prescription medications [5] which directly or indirectly alter cellular signalling mechanisms.
Adrenergic receptors (ARs; also known as adrenoreceptors) are a class of 7TMRs located in the heart and vasculature and are responsible for relaying sympathetic nervous system (SNS) messages into cardiovascular reactions [1]. The neurotransmitters norepinephrine (NE) and epinephrine (Epi), which originate from the SNS, exert their effects on cardiac cells and tissues by binding to adrenoreceptors [6]. A number of adrenoreceptor subgroups are present in the mammalian heart, including three α1-ARs, three α2-ARs and three β-ARs (β1, β2 and β3) [6].
β-Adrenergic receptors (β-ARs) are the most important and one of the most frequently studied receptors belonging to the family of G-protein coupled receptors [7]. There are three subtypes of β-ARs: β1, β2 and β3, activation of which regulates important cardiovascular functions [7, 8]. The β1-ARs are characterised mainly for the heart, β2-ARs for blood vessels and β3-ARs for adipose tissue [9]. Within the vasculature the predominant subtype is β2-AR, which is 65–70% homologous to β1- and β3-ARs [8]. The agonists that bind with all three subtypes of β-ARs are the hormones adrenaline and noradrenaline, which help regulate cardiovascular and pulmonary function [10, 11].
Human genes encoding the β2-ARs are without introns and have been mapped to chromosome 5q31–32 [12]. The β-ARs consist of 413 amino acid residues, approximately 46.5 kDa [8]. There are three domains of β2-ARs: The extracellular domain, the transmembrane domain responsible for the ligands binding and the intracellular domain, which interacts with G protein and kinases such as β-ARK [13]. β2-ARs occur mainly in the lungs, where their presence has been shown in airway smooth muscle (30,000–40,000 per cell), epithelial and endothelial cells, type II cells and mast cells [8]. Moreover β2-ARs are in heart, kidney and blood vessels—mainly arterioles [8, 14].
As in the other G-receptors the signalling pathway of β2-ARs, which bind with a hormone ligand includes three basic steps: Receptor binding, G protein activation and effector system activation. β2-ARs may occur in two forms, activated and inactivated [6]. The binding of β-ARs agonist with β2-receptor activates the pathway in which Gs coupled proteins are involved. The stimulation of G proteins causes guanosine triphosphate (GTP) to bind to the α-subunit (Gsα) that activates it. The G-subunits dissociate, and α-subunits stimulate adenylate cyclase (AC) to formation of cyclic adenosine 3′,5′-monophosphate (cAMP). It is stated that cAMP acts as a catalyst for the process of activation of protein kinase A (PKA) and due to that it is involved in control of muscle tone. On the other hand cAMP inhibits the release of cytosolic calcium ion (Ca2+) in the smooth muscle cells, which leads to vascular relaxation (vasodilation) [8, 15].
Although the β2-ARs activated by β2-ARs agonists mostly influence the blood vessels (mainly arterioles and coronary arteries), they can also act in the heart and kidney. In the atrial and ventricular myocardium, stimulation of β2-ARs leads to increase in cardiac muscle contractility or relaxation, whilst in the kidneys it stimulates the release of renin, what it turn influences activation of the renin-angiotensin-aldosterone system [1, 8].
The primary role of the β-ARs in the heart is to coordinate the heart rate and contractility in response to the SNS neurotransmitters [6]. β1-AR is the most abundant subtype accounting for 75–80% in a healthy myocardium [6]. Around 15–18% of cardiomyocyte β-ARs are β2-AR whilst the remaining 2–3% of β-AR density is composed of β3-ARs [6]. Activation of β1-ARs and to a smaller degree β2-ARs, leads to an increase in cardiac contractility and an accelerated cardiac rate. Stimulation of the two predominate β-ARs also increases impulse transmission via the atrioventricular node [6]. The activation of cardiomyocyte β1- and β2-ARs also leads to a significant increase in free intracellular Ca2+ concentration [6]. Calcium is a secondary messenger in many biological systems. In cardiomyocytes, calcium affects ion channels which regulate ionic currents, impacting upon action potentials and muscle contractility [16]. Β3-AR appears to illicit an opposite effect on cardiac function to that induced by β1- and β2-ARs in that it acts to prevent cardiac hyperstimulation from NE and Epi (Table 1) [6].
Action | β1-AR | β2-AR | Β3-AR |
---|---|---|---|
Heart muscle contraction | Yes | Yes | |
Increases cardiac output | Yes | Yes | |
Increases heart rate in SA node | Yes | Yes | |
Increases atrial contractility | Yes | Yes | |
Increases contractility and automaticity of ventricular muscle | Yes | Yes | |
Dilates muscular blood vessels | Yes | Yes | |
Increases perfusion in blood vessels | Yes | ||
Metabolism/lipolysis/thermogenesis | Yes | ||
Prevent cardiac hyperstimulation | Yes |
Actions of β-adrenergic receptors.
Constant elevation of catecholamines leading to β-AR signalling changes results in overstimulation of cardiac function [1]. Reducing the β-AR activity is vital to alleviate the risk of long-term cardiac tissue damage such as cardiomyopathy. Propanolol was discovered to be a β-AR antagonist in 1964, a so called β-blocker. Alprenolol and Practolol β-blockers have also been used for the management of heart failure [1]. β-Blockers function to overcome the harmful effects of norepinephrine which overstimulate the β1-AR, leading to a reduction in cardiac workload [1]. The most recently used β-blockers bisoprolol and carvedilol target both β1- and β2-ARs produce a survival benefit for heart failure patients [1]. In rats β2-AR agonists (fenoterol and zinterol) were shown to reduce progression of left ventricular modelling in dilated cardiomyopathy in addition to decreasing myocardial cell death [17]. In a later study the same group determined that in a rat model of dilated ischemic cardiomyopathy, Metoprolol, a β1-AR blocker, action is enhanced when given in combination with the β2-AR agonist fenoterol [18].
The β2-ARs have also been directed implicated in patients with ischaemic cardiomyopathy. A Gln27Glu polymorphism of β2-AR was discovered in a study investigating 155 people with heart failure of ischaemic aetiology with impaired Left Ventricular Ejection Fraction ≤35% [19]. Three allele categories were discovered, the most common genotype in heart failure was Gln27Gln, and the least common was Glu27Glu, whilst Gln27Glu was not significantly different between heart failure and control subjects. The study concluded that the Glu allele was associated with lower myocardial infarction rate and highlighted that patient response to β-blockade therapy may be altered [19]. Likewise β1-AR (Ser49Gly, Arg389Gly) and β2-AR (Arg16Gly, Gln27Glu, Thr164Ile) polymorphisms did not alter in a Polish cohort study of patients with idiopathic dilated cardiomyopathy [20]. It is of interest that in patients with Takotsubo cardiomyopathy, β-AR polymorphisms (β1-AR (Gly389Arg) and β2-AR (Arg16Gly and Gln27Glu)) were significantly different to controls but similar to patients with ST-elevation myocardial infarction [21]. Work combining beta-blockers with ACE-inhibitors/angiotensin receptor blockers over the years using meta-analysis data has shown reduced recurrence of the disorder [22].
A murine model depleting levels of β2-ARs also resulted in diabetic cardiomyopathy in vivo and reduced β2-ARs in cardiomyocytes grown under in hyperglycemic conditions [23]. Conversely, overexpression of β2-ARs (by 300 fold) in mice showed that over time severe cardiomyopathy was observed, resulting in interstitial fibrosis, loss of myocytes and myocyte hypertrophy. In the majority of the 81% of mice that died within 15 months, heart failure was observed [24]. These results were similar to other transgenic overexpression mouse lines. The authors hypothesised that a number of mechanisms from activation of growth or transcriptional factors, cross-talk with other pathways, necrosis or apoptosis of cardiac myocytes and/or high heart rates limiting energy supply.
The human heart also possesses α1 adrenoreceptors (α1-AR) although in a smaller quantity to the β-ARs [25]. The α1-ARs are expressed in the heart, both the α1A-and α1B-AR subtypes are expressed in human myocytes, and have been shown to regulate contractility [26, 27]. The α1-ARs combine with the Gq/11 family of G proteins, in turn activating phospholipase C. The secondary messenger IP3 binds to receptors on the membrane of the sarcoplasmic reticulum, triggering the release of intracellular Ca2+ [6]. The raised Ca2+ level leads an increase in vasoconstriction [6]. The coupling of α1-ARs to the Gq/11 family of G proteins also produces DAG and subsequent protein kinase C [6].
In heart failure the α1-ARs may offer a protective benefit to maintain cardiac inotropy, preventing cardiomyocyte apoptosis and maladaptive cardiac remodelling [6]. Although a small study, loss of β1-AR and no change in β2-AR levels in end-stage dilated cardiomyopathy patients was observed alongside a loss of α1A-ARs [28]. Although the role of β1-AR in heart failure has long been described, this interaction between the α-ARs was novel as the few previous studies had shown no change or increases in α-ARs binding but these were different types of heart failure. In addition a total of 26 proteins of interest were also identified in the cardiomyopathy patients, some of which have been linked to G-protein coupled receptor signalling and desensitisation [28]. Prostatic binding protein levels decreased whereas increases in ANP32A and clathrin were noted. Also of interest are Takotsubo cardiomyopathy (also known as stress cardiomyopathy) patients. This condition is often reversible, and two studies have shown that several β1-AR and α2c-AR polymorphisms were not implicated in Takotsubo cardiomyopathy [29, 30].
Angiotensin II (AngII) is an important protein in the renin-angiotensin system (RAS). In the bloodstream renin converts angiotensinogen (derived from liver) into angiotensin I, which in turn is transformed into AngII by angiotensin converting enzyme (ACE) [14, 31, 32]. AngII can be also secreted in some local tissues including within the brain, heart, arteries and kidney [32].
The Angiotensin II type 1 and 2 receptors (AT1 and AT2 receptors) belong to the wide family of G-protein coupled receptors (GPCRs), members of which have seven transmembrane spanning domains and is the biggest member of the human genome [31, 33]. The distinction and classification of AT1 and AT2 receptors is based on their varied affinity for different non-peptide antagonists [34]. Moreover the AT1 and AT2 receptors differ between each other in their number of amino acids, tissue-specific expression and mechanisms of signal transferring [13]. Both of these receptors occur in all mammals and bind a peptide hormone angiotensin II (AngII), which is the most important effector in the RAS [32].
The main role of angiotensin becomes apparent in the cardiovascular and endocrine systems where it regulates blood pressure and hydro-electrolytic homeostasis [32, 33]. It is stated that the main physiological functions of AngII (vasoconstriction, aldosterone secretion, renal regulations cellular dedifferentiation and proliferation) are mediated mostly by the AT1 subtype of angiotensin receptor [14, 31, 33, 34, 35, 36]. In humans, the genes encoding AT1 receptors are mapped on chromosome 3q21–3q25 [37]. The AT1 receptors consist of 359 amino acids, with a molecular weight of 41 kDa, and their amino sequence reveals 20–35% homology with other GPCRs [31].
In adult mammals, AT1 receptors are mainly expressed in kidney (glomeruli, proximal tubules, vasculature, medullary interstitial cells), adrenal glands (cortex, medulla), heart (myocardium, ganglia, conduction system), brain (circumventricular organs, thalamus, basal ganglia, cerebellar cortex, medulla oblongata) and vasculature (smooth muscles, adventitia) [32, 38]. Rats and mice can have two isoforms of the Angiotensin II 1 receptor: AT1A and AT1B with amino acid sequence convergence seen at 94% [14, 31, 33, 34]. AT1A receptors are present predominantly in vascular smooth muscle, liver, lung and kidney whilst AT1B receptors occur mainly in the adrenal gland and anterior pituitary [31, 34, 38]. The rodent AT1A and AT1B receptor genes are situated on chromosomes 17 and 2 respectively [38].
The activity of angiotensin II through AT1 receptors should be considered in physiological and pathophysiological conditions. The physiological signalling pathway involves the renin-angiotensin-aldosteron system and leads to changes in blood pressure primarily through vasoconstriction of arteries and arterioles, secretion of aldosterone from adrenal gland and sodium reabsorption by via the kidney tubules [32]. Ang II mediates vasoconstriction through the IP3/DAG pathway, which uses Gq/11 protein-coupled receptors. Gq/11 activates phospholipase C (PLC), which hydrolyses phosphatidylinositol 4,5-bisphosphate (PIP2) and produces diacyl glycerol (DAG) and inositol trisphosphate (IP3). IP3 causes an increase in intracellular calcium whilst DAG activates protein kinases C [31]. The increased concentration of calcium (Ca2+ ions) within vascular smooth muscle cells leads to vasoconstriction which results in an increase in blood pressure or may causing a localised reduction in blood flow in some specific tissues [32, 36]. AngII acting through the AT1 receptors located in the zona glomerulosa of the adrenal gland stimulates the release of aldosterone [32]. Aldosterone then acts on the distal convoluted tubules and the cortical collecting ducts in kidney, firstly causing sodium (Na+) retention, leading to increased peripheral resistance and secondly causing resorption of water from urine which also increases extracellular fluid volume. Both of these mechanisms lead to an elevation in arterial pressure [32].
Considering the pathological conditions, the activity of AngII through AT1 receptors may induce the proliferation of vascular smooth muscle cells which in turn promotes myocyte hypertrophy and causes vascular fibrosis. Proliferation of smooth muscle cells is also involved in the initial stages of atherosclerotic plaques formation in arteries [32]. AngII binding to AT1 receptors also activate the multiple intracellular signalling pathway that promotes atherosclerosis. The pathway includes oxidative stress, inflammation, endothelial dysfunction, tissue remodelling, proliferation fibrosis, thrombosis and autostimulation. Moreover AngII may participate in the process of atherosclerosis lesion formation as it stimulates the release of endothelin-1 (ET-1) from the endothelial cells [32]. In addition to inducing proliferation and atherosclerotic plaques formation, AngII may have an effect on the developing/developed plaques. Atherosclerotic plaque stability and disruption is in turn associated with matrix metalloproteinase (MMP) enzymes, the production of which can be stimulated by AngII [32]. The MMPs are inhibited by tissue inhibitors of metalloproteinases (TIMPs) and disruption of the balance between MMPs and TIMPs may lead to cardiovascular diseases [37, 39]. Moreover, in pathological states, the activation of AT1 receptor by AngII may cause vascular remodelling and growth by expression of autocrine growth factors (including fibroblast growth factor and platelet-derived growth factor) in vascular smooth muscle cells [32, 40].
The activation of AT2 receptors by AngII has an opposite effect to AT1 receptors. It means that the functions of AngII mediated by AT2 receptors are vasodilation, natriuresis and inhibition of cellular growth and proliferation [14]. Genes encoding AT2 receptors are localised on chromosome Xq22-q2 [13, 31]. The molecular weight of AT2 receptors is approximately 41 kDa and they consist of 363 amino acids [13, 41].
AT2 receptor expression has been localised in both foetal and adult tissues. In foetuses, expression of AT2 receptors is intense, especially in a cardiovascular system [13]. In adult mammals the expression of AT2 receptor is still observed in heart (mainly in myocardium) and renal blood vessels but is significantly lower than before birth [13, 38]. Expression of AT2 receptors has been also noted in the adrenal gland (cortex and medulla), brain (thalamus, cerebellar cortex), mesenteric and uterine arteries [38, 42].
It is stated that the AT2 receptor acts to stabilise blood pressure by controlling vascular tone by vasodilation [13]. In this action the AT2 receptor together with other GPCR family B2 receptors for bradykinin form a stable functional heterodimer, which causes the increase of nitric oxide (NO) and stimulating cyclic guanosine monophosphate (cGMP) synthesis. The cGMP contributes to relaxation of smooth muscles, which in large veins, large arteries, and smaller arterioles leads to vasodilation and causes decreased blood pressure. It has also been suggested that activation of AT2 receptors by AngII may inhibit arterial and myocardial hypertrophy and fibrosis in the ageing heart and vasculature.
Therefore AngII exerts its influence via the activation of the Angiotensin II type I receptor (AT1R), a 7TMR located in vascular smooth muscle as well as in the kidneys, brain and adrenal glands in an effort to maintain sodium/water homeostasis and moderate vasoconstriction [1]. AT1R acts to control arterial pressure, blood volume and to encourage growth and proliferation through the activation of cellular signalling mechanisms [15]. The AT1R is a Gq/11 coupled receptor [25]. Stimulation by AngII leads to the activation of phospholipase C-β and the release of DAG and IP3, followed by the activation of protein kinase C and movement of intracellular calcium [3]. AT1Rs are upregulated in cardiac tissue in response to hypertrophic triggers, encouraging unfavourable cardiac remodelling in heart failure [9]. These complex roles have resulted in a number of angiotensin receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors to be developed and used as cardiovascular treatments. ARBs and ACE inhibitors have demonstrated a reduction in deleterious left ventricular remodelling, such as hypertrophy and myocardial stiffness which as associated with heart failure [6]. ACE inhibitors alongside antagonists of the AT1R, the -sartans, have become one of the main pharmaceutical treatments for hypertension and cardiovascular disease [1]. Commonly used ARBs include Losartan, Valsartan and Candesartan [43]. ARBs function to interfere with the renin-angiotensin system by preventing the binding of AngII to AT1R. This inhibition of AngII result in vascular smooth muscle relaxation, a reduction in cellular hypertrophy, and a decrease in plasma volume resulting from an increase in salt and water excretion [43].
A number of advances in terms of cardiomyopathy and ANGII and its receptors have been made in the last few years. In terms of cardiomyopathy, the AngII receptor inhibitor LCZ696 has been shown to inhibit extracellular signal-regulated kinase (ERK), resulting in increased survival in pregnancy-associated cardiomyopathy mice. The authors indicated that by reducing cardiac hypertrophy, fibrosis and apoptosis it could act as a potential treatment for this cardiomyopathy [44]. Another study showed that this angiotensin receptor-neprilysin inhibitor reduced inflammation, oxidative stress and apoptosis in vitro and in vivo [45]. It has also been stated that in end-stage hypertrophic cardiomyopathy, the modern Angiotensin receptor neprilysin inhibitor treatments are both safe and effective [46]. Angiotensin-converting enzyme 2 (ACE2) has also showed therapeutic potential when looking at doxorubicin-induced cardiomyopathy rat models [47]. The enzyme reduced apoptosis, inflammatory responses, and oxidative stress and reduced mortality and myocardial fibrosis whilst improving ventricular remodelling and cardiac function. They also showed activation of the AMPK and PI3K-AKT pathways, inhibition of the ERK pathway, and decreased TGF-β1 [47]. Sulforaphane, which activates nuclear factor erythroid 2-related factor 2 (Nrf2), has also been shown to present angiotensin II-induced cardiomyopathy via Akt/GSK-3ß/Fyn -mediated Nrf2 activation [48].
Aldehyde dehydrogenase 2 (ALDH2) has also been shown to protect against alcoholic cardiomyopathy [49]. By decreasing angiotensinogen and AngII this cardioprotective enzyme inhibited local RAS in mice by inhibiting the p38 MAPK/CREB pathway. In another form of cardiomyopathy, hypertrophic, ACE inhibitors angiotensin-receptor blockers have been used to try and regulate the renin-angiotensin-aldosterone system [50]. This has resulted in patients having a lower risk of developing atrial fibrillation which is associated with hypertrophic cardiomyopathy.
Much work has looked into polymorphisms in the angiotensin-converting enzyme gene itself in relation to hypertrophic cardiomyopathy risk; however, the studies have sometimes shown conflicting results. A systematic review and meta-analysis indicated that the ACE insertion/deletion (I/D of 287 base pairs in intron 16) polymorphism was probably a risk for hypertrophic cardiomyopathy [51]. People with the DD genotype have increased levels of ACE and angiotensin II and therefore more hypertrophy and fibrosis, as seen in other situations where their levels increase. Although many of the 1 in 500 people affected by hypertrophic cardiomyopathy have mutations in the genes coding for sarcomeric proteins, polymorphisms in the components of the RAS are implicated. ACE DD has also been associated with dilated cardiomyopathy patients, angiotensin receptor type 11166CC genotypes with both hypertrophic and dilated cardiomyopathy and the 235TT genotype of angiotensinogen (M235T) is associated with hypertrophic, dilated and restrictive cardiomyopathy [52].
Overstimulation of AngII has also been reported in dilated cardiomyopathy [53] and AT1R overexpression resulted in female mice being more affected (especially in terms of heart failure and increased mortality) than males [53]. In particular, ventricular hypertrophy and dilation and changes in Ca2+ activity and homeostasis were observed, and these reflect that clinical observations that dilated cardiomyopathy can be exacerbated in women in comparison to men. This can also be linked to oestrogen which increases angiotensinogen and decreased renin, ACE and AT1R expression but of course following menopause these effects are lost [54].
Much has been investigated in relation to the use of ACE inhibitors in patients with ischemic cardiomyopathy. Much work has been carried out in patients with an ejection fraction of less than 40% with these enzymes working well. More recently attention has turned to those with an ejection fraction of more than 40% who were studied less. In patients with 40–50% ejection fraction, the ACE inhibitors were seen to reduce the risk of mortality, nonfatal myocardial infarction and stroke by 21% [55].
There are three different forms of 21-amino acid peptides, which belong to the endothelin peptide family: ET-1, ET-2, and ET-3 [56]. They vary in biological function and may affect blood vessels as well as other tissues both within and outside of the cardiovascular system [56]. The predominant form of endothelin peptide is an isopeptide ET-1 with potent vasoconstrictor and proliferative properties [57]. ET-1 is synthetized by endothelial cells, airway smooth muscles cells, cardiomyocytes, macrophages, leukocytes and mesangial cells [57].
There are two subtypes of receptors which are mediated by endothelin, known as Endothelin Type A receptor (ETA) and type B (ETB) [57]. Although mediated by the same peptide agonist, activity of these two subtypes is usually opposite, as the ETA receptor promotes vasoconstriction, growth, and inflammation whilst ETB receptors may cause both vasoconstriction and vasodilation and also increases in sodium excretion and inhibition of growth and inflammation [57, 58, 59].
The potential to bind with ETA receptors is the same for ET-1 and ET-2 endothelin but lower for ET-3 endothelin, whilst the potential binding rate with ETB receptors is equal for every form of endothelin [57, 58]. In people the genes responsible for expression of the ETA receptors are situated on chromosome 4q31.22-q31.23, whilst genes encoding ETB receptors are mapped onto chromosome 13q22.3 [60]. The molecular weight of the ETA and ETB receptors are 48 and 50 kDa respectively [61, 62]. The human 427 amino acid long ETA receptors and 442 amino acid long ETB receptors are approximately 64% homologous [58]. The homology of ETA and ETB receptors in humans and other mammalian species is between 88% and 97% [58].
ETA receptors are expressed predominantly in the heart (coronary vasculature and cardiomyocytes), lungs (pulmonary artery), kidney (renal artery, afferent and efferent arteriole, cortical vasculature, mesangial cells), brain (cerebral vasculature) and adrenal gland. ETB receptors also occur in the heart (coronary vasculature and cardiomyocytes), lungs (pulmonary artery), kidney (renal artery, afferent and efferent arteriole, medullar vasculature), brain (cerebral vasculature) and adrenal gland [63].
The ETA receptors mediated by ET-1 endothelin in vascular smooth muscle cells promoting vasoconstriction, hypertension, hypertrophy, fibrosis and inflammatory changes, including atherosclerosis and due to that has activity similar to the AT1 receptors mediated by AngII [63]. The vasoconstrictive pathway of ETA receptors includes: Coupling to phospholipase C (PLC) via GTP-binding protein, phospholipase C activation, phosphatidyl inositol hydrolysis, inositol 1,4,5 triphosphate (IP3) generation and 1,2-diacylglycerol (DCG) accumulation. Inositol triphosphate is a signalling molecule that leads to mobilisation of Ca2+ from intra- and extra-cellular sources resulting in long-lasting vasoconstriction [56, 64].
The ETB receptors mediated by ET-1 endothelin in the vascular endothelium are involved in the clearance of ET-1 and stimulate vasodilation due to the nitric oxide and cyclooxygenase metabolites production, which also exert vasorelaxant effects on the underlying smooth muscle. Moreover, the ETB receptors have a natriuretic action causing sodium and water resorption from the distal tubules and collecting ducts in the kidney. The ETB receptors, which occur in smooth muscle cells, additionally act as vasoconstrictors [57, 63, 64].
In the last few years research into endothelin has progressed the information known about links to cardiomyopathies. Some of the early published studies showed that ET-1 and its receptor either played a causative role in hypertrophic cardiomyopathy, idiopathic dilated cardiomyopathy and uremic cardiomyopathy or could be a marker [65, 66, 67, 68]. Indeed work in cats has even reflected the increased ET-1 levels in cases of hypertrophic, dilated, restrictive and unclassified cardiomyopathy [69]. More work has now been carried out into other cardiomyopathies and the potential mechanisms of action. Much like ACE2, the endothelin receptor blocker bosentan has been shown to inhibit doxorubicin-induced cardiomyopathy in a rodent model [70]. This study looked at the receptor blocker as elevated levels of ET-1 were discovered in doxorubicin treated patients. The in vitro studies indicated that activation of the epidermal growth factor (EGF) receptor and the MEK1/2-ERK1/2 cascade were possible mechanisms of action [70]. A good review looking at endothelin-1 and atrial cardiomyopathy, published in 2019 brings together the information in this area. The work over the years has indicated that endothlin-1 plays an active role affecting Ca2+ levels, via the ET-1-superoxide-MMP9 cascade and via apoptosis, resulting in both electrical and anatomical remodelling [71].
Not only is endothelin-1 a potential therapeutic route but it also shows promise in predicting patient outcomes. A recent study investigating new-onset atrial fibrillation in patients with obstructive hypertrophic cardiomyopathy has shown that elevated pre-operative levels may indicate increased likelihood of atrial fibrillation [72]. Big endothelin-1, the precursor of endothelin-1 has also been shown to be useful when predicting prognosis for hypertrophic cardiomyopathy patients and the authors have suggested that it should be added to marker panels [73, 74]. Endothelin 1 has also been implicated as a modifier in dilated cardiomyopathy. With variations including the rare G > A and a C > T at c.90 seen in dilated cardiomyopathy patients and
Cardiac function is controlled by the SNS and parasympathetic nervous system (PNS). Parasympathetic vagal nerves are distributed throughout all areas of the heart, particularly in the ventricles [77]. Cardiac muscarinic receptors are activated by acetylcholine, having been stimulated by vagal nerve activation. The muscarinic acetylcholine receptors (M-ChR) are glycoproteins belonging to the 7TMR superfamily [77]. The M2 subtype of M-ChR are the most prevalent group within the mammalian heart and their function is opposed to the β-ARs in that they cause a reduction in myocardium contractility and a lower cardiac rate [10]. M-ChR exert their influence on the myocardium via the Gα1-coupled receptors which inhibit adenylyl cyclase whilst the Gβγ dimer impedes the activity of potassium channels in the sinoatrial node [1]. M-ChR can also exert an effect over Ca2+ channels [77] affecting cardiac contractility.
Heart failure patients demonstrate an increase in M2 muscarinic receptor density, with activated M2 receptors encouraging an inotropic response [9]. One study using serum from a patient showed that when autoantibodies to the muscarinic receptors and β-ARs were activated it resulted in cardiomyopathy and atrial tachyarrhythmias [78]. Along a similar line, autoantibodies against β1-ARs have been shown to cause sudden death in idiopathic dilated cardiomyopathy patients [79]. Antibodies to β-ARs have been discovered in people with idiopathic dilated cardiomyopathy, even leading to the suggestion of a form of ‘adrenergic cardiomyopathy’ [80]. In addition autoantibodies against muscarinic receptors have also been noted in cases of peripartum cardiomyopathy [81], dilated cardiomyopathy [82, 83, 84, 85], and M2-muscarinic acetylcholine receptor autoantibodies have been implicated in playing a role in atrial fibrillation in dilated cardiomyopathy patients [86] Similar increases were not observed in patients with Takotsubo cardiomyopathy [87] or in rats with cirrhotic cardiomyopathy [88]. Autoantibodies against cardiomyocytes, β1- or β2-ARs or M2 muscarinic receptors were not noted in 20 people with Takotsubo cardiomyopathy in comparison to healthy controls, or in rats with cirrhotic cardiomyopathy.
The superfamily of 7TMRs includes receptors for hormones, neurotransmitters and ion channels, and are critical to mediate physiological and cellular processes [1, 2]. This chapter has investigated adrenoreceptors (both α- and β-adrenergic receptors) and the components of the renin-angiotensin system (RAS) especially AngII, ACE and the AT1 and AT2 receptors. The chapter has also looked at endothelin-1 (ET-1) and its receptor, and precursor Big endothelin-1 and finally the muscarinic receptors. By looking at their numerous effects in both healthy and diseased vasculature and cardiac disorders, especially cardiomyopathies, it can be seen that there are wide ranging effects. Developing these 7TMRs as markers of disease, for prognosis, diagnosis and therapeutic treatments is becoming more important as their many roles as being uncovered in the cardiovascular system.
The authors would like to thank their institutions for funding them. Ewelina Prozorowska, Kristýna Glocová, and Lucy Slater were undertaking research internships with Catrin Sian Rutland at The University of Nottingham, UK. Kristýna Glocová had her internship funded by The European Association of Veterinary Anatomists (EAVA), Young Research Career Development Award; therefore, Kristýna and Catrin would like to thank the EAVA. The ORCID ID of Catrin Rutland is https://orcid.org/0000-0002-2009-4898.
The authors declare no conflicts of interest.
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Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"64851",doi:"10.5772/intechopen.80348",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14206,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"54028",doi:"10.5772/67291",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]},{id:"58270",doi:"10.5772/intechopen.72437",title:"Toxicity and Safety Implications of Herbal Medicines Used in Africa",slug:"toxicity-and-safety-implications-of-herbal-medicines-used-in-africa",totalDownloads:3376,totalCrossrefCites:16,totalDimensionsCites:39,abstract:"The use of herbal medicines has seen a great upsurge globally. In developing countries, many patronize them largely due to cultural acceptability, availability and cost. In developed countries, they are used because they are natural and therefore assumed to be safer than allopathic medicines. In recent times, however, there has been a growing concern about their safety. This has created a situation of ambivalence in discussions regarding their use. Some medicinal plants are intrinsically toxic by virtue of their constituents and can cause adverse reactions if inappropriately used. Other factors such as herb-drug interactions, lack of adherence to good manufacturing practice (GMP), poor regulatory measures and adulteration may also lead to adverse events in their use. Many in vivo tests on aqueous extracts largely support the safety of herbal medicines, whereas most in vitro tests on isolated single cells mostly with extracts other than aqueous ones show contrary results and thus continue the debate on herbal medicine safety. It is expected that toxicity studies concerning herbal medicine should reflect their traditional use to allow for rational discussions regarding their safety for their beneficial use. While various attempts continue to establish the safety of various herbal medicines in man, their cautious and responsible use is required.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Merlin L.K. Mensah, Gustav Komlaga, Arnold D. Forkuo, Caleb\nFirempong, Alexander K. Anning and Rita A. Dickson",authors:[{id:"190435",title:"Dr.",name:"Caleb",middleName:null,surname:"Firempong",slug:"caleb-firempong",fullName:"Caleb Firempong"},{id:"212111",title:"Dr.",name:"Gustav",middleName:null,surname:"Komlaga",slug:"gustav-komlaga",fullName:"Gustav Komlaga"},{id:"217045",title:"Dr.",name:"Arnold Forkuo",middleName:null,surname:"Donkor",slug:"arnold-forkuo-donkor",fullName:"Arnold Forkuo Donkor"},{id:"217049",title:"Prof.",name:"Merlin Lincoln Kwao",middleName:null,surname:"Mensah",slug:"merlin-lincoln-kwao-mensah",fullName:"Merlin Lincoln Kwao Mensah"},{id:"217488",title:"Dr.",name:"Alexander K.",middleName:null,surname:"Anning",slug:"alexander-k.-anning",fullName:"Alexander K. Anning"},{id:"223959",title:"Prof.",name:"Akosua Rita",middleName:null,surname:"Dickson",slug:"akosua-rita-dickson",fullName:"Akosua Rita Dickson"}]},{id:"26489",doi:"10.5772/28224",title:"Alternative and Traditional Medicines Systems in Pakistan: History, Regulation, Trends, Usefulness, Challenges, Prospects and Limitations",slug:"alternative-and-traditional-medicines-systems-in-pakistan-history-regulation-trends-usefulness-chall",totalDownloads:9199,totalCrossrefCites:9,totalDimensionsCites:21,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Shahzad Hussain, Farnaz Malik, Nadeem Khalid, Muhammad Abdul Qayyum and Humayun Riaz",authors:[{id:"73162",title:"Dr.",name:"Shahzad",middleName:null,surname:"Hussain",slug:"shahzad-hussain",fullName:"Shahzad Hussain"},{id:"82266",title:"Dr.",name:"Farnaz",middleName:null,surname:"Malik",slug:"farnaz-malik",fullName:"Farnaz Malik"},{id:"124185",title:"Dr.",name:"Humayun",middleName:null,surname:"Riaz",slug:"humayun-riaz",fullName:"Humayun Riaz"},{id:"124186",title:"Mr.",name:"Muhammad Abdul",middleName:null,surname:"Qayyum",slug:"muhammad-abdul-qayyum",fullName:"Muhammad Abdul Qayyum"},{id:"125340",title:"Mr.",name:"Nadeem",middleName:null,surname:"Khalid",slug:"nadeem-khalid",fullName:"Nadeem Khalid"}]}],mostDownloadedChaptersLast30Days:[{id:"64851",title:"Herbal Medicines in African Traditional Medicine",slug:"herbal-medicines-in-african-traditional-medicine",totalDownloads:14207,totalCrossrefCites:30,totalDimensionsCites:52,abstract:"African traditional medicine is a form of holistic health care system organized into three levels of specialty, namely divination, spiritualism, and herbalism. The traditional healer provides health care services based on culture, religious background, knowledge, attitudes, and beliefs that are prevalent in his community. Illness is regarded as having both natural and supernatural causes and thus must be treated by both physical and spiritual means, using divination, incantations, animal sacrifice, exorcism, and herbs. Herbal medicine is the cornerstone of traditional medicine but may include minerals and animal parts. The adjustment is ok, but may be replaced with –‘ Herbal medicine was once termed primitive by western medicine but through scientific investigations there is a better understanding of its therapeutic activities such that many pharmaceuticals have been modeled on phytochemicals derived from it. Major obstacles to the use of African medicinal plants are their poor quality control and safety. Traditional medical practices are still shrouded with much secrecy, with few reports or documentations of adverse reactions. However, the future of African traditional medicine is bright if viewed in the context of service provision, increase of health care coverage, economic potential, and poverty reduction. Formal recognition and integration of traditional medicine into conventional medicine will hold much promise for the future.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Ezekwesili-Ofili Josephine Ozioma and Okaka Antoinette Nwamaka\nChinwe",authors:[{id:"191264",title:"Prof.",name:"Josephine",middleName:"Ozioma",surname:"Ezekwesili-Ofili",slug:"josephine-ezekwesili-ofili",fullName:"Josephine Ezekwesili-Ofili"},{id:"211585",title:"Prof.",name:"Antoinette",middleName:null,surname:"Okaka",slug:"antoinette-okaka",fullName:"Antoinette Okaka"}]},{id:"61866",title:"Plants Secondary Metabolites: The Key Drivers of the Pharmacological Actions of Medicinal Plants",slug:"plants-secondary-metabolites-the-key-drivers-of-the-pharmacological-actions-of-medicinal-plants",totalDownloads:8875,totalCrossrefCites:56,totalDimensionsCites:140,abstract:"The vast and versatile pharmacological effects of medicinal plants are basically dependent on their phytochemical constituents. Generally, the phytochemical constituents of plants fall into two categories based on their role in basic metabolic processes, namely primary and secondary metabolites. Primary plant metabolites are involved in basic life functions; therefore, they are more or less similar in all living cells. On the other hand, secondary plant metabolites are products of subsidiary pathways as the shikimic acid pathway. In the course of studying, the medicinal effect of herbals is oriented towards the secondary plant metabolites. Secondary plant metabolites played an important role in alleviating several aliments in the traditional medicine and folk uses. In modern medicine, they provided lead compounds for the production of medications for treating various diseases from migraine up to cancer. Secondary plant metabolites are classified according to their chemical structures into various classes. In this chapter, we will be presenting various classes of secondary plant metabolites, their distribution in different plant families and their important medicinal uses.",book:{id:"6302",slug:"herbal-medicine",title:"Herbal Medicine",fullTitle:"Herbal Medicine"},signatures:"Rehab A. Hussein and Amira A. El-Anssary",authors:[{id:"212117",title:"Dr.",name:"Rehab",middleName:null,surname:"Hussein",slug:"rehab-hussein",fullName:"Rehab Hussein"},{id:"221140",title:"Dr.",name:"Amira",middleName:null,surname:"El-Anssary",slug:"amira-el-anssary",fullName:"Amira El-Anssary"}]},{id:"77433",title:"Extraction of Bioactive Compounds from Medicinal Plants and Herbs",slug:"extraction-of-bioactive-compounds-from-medicinal-plants-and-herbs",totalDownloads:1266,totalCrossrefCites:2,totalDimensionsCites:5,abstract:"Human beings have relied on herbs and medicinal plants as sources of food and remedy from time immemorial. Bioactive compounds from plants are currently the subject of much research interest, but their extraction as part of phytochemical and/or biological investigations present specific challenges. Herbalists or scientists have developed many protocols of extraction of bioactive ingredients to ensure the effectiveness and the efficacy of crude drugs that were used to get relief from sickness. With the advent of new leads from plants such as morphine, quinine, taxol, artemisinin, and alkaloids from Voacanga species, a lot of attention is paid to the mode of extraction of active phytochemicals to limit the cost linked to the synthesis and isolation. Thus, the extraction of active compounds from plants needs appropriate extraction methods and techniques that provide bioactive ingredients-rich extracts and fractions. The extraction procedures, therefore, play a critical role in the yield, the nature of phytochemical content, etc. This chapter aims to present, describe, and compare extraction procedures of bioactive compounds from herbs and medicinal plants.",book:{id:"10356",slug:"natural-medicinal-plants",title:"Natural Medicinal Plants",fullTitle:"Natural Medicinal Plants"},signatures:"Fongang Fotsing Yannick Stéphane, Bankeu Kezetas Jean Jules, Gaber El-Saber Batiha, Iftikhar Ali and Lenta Ndjakou Bruno",authors:[{id:"224515",title:"Dr.",name:"Fongang Fotsing",middleName:null,surname:"Yannick Stéphane",slug:"fongang-fotsing-yannick-stephane",fullName:"Fongang Fotsing Yannick Stéphane"},{id:"227816",title:"Dr.",name:"Bankeu Kezetas",middleName:null,surname:"Jean Jules",slug:"bankeu-kezetas-jean-jules",fullName:"Bankeu Kezetas Jean Jules"},{id:"227817",title:"Prof.",name:"Lenta Ndjakou",middleName:null,surname:"Bruno",slug:"lenta-ndjakou-bruno",fullName:"Lenta Ndjakou Bruno"},{id:"349790",title:"Prof.",name:"Gaber",middleName:null,surname:"El-Saber Batiha",slug:"gaber-el-saber-batiha",fullName:"Gaber El-Saber Batiha"},{id:"357350",title:"Dr.",name:"Iftikhar",middleName:null,surname:"Ali",slug:"iftikhar-ali",fullName:"Iftikhar Ali"}]},{id:"26491",title:"Homeopathy: Treatment of Cancer with the Banerji Protocols",slug:"homeopathy-treatment-of-cancer-with-the-banerji-protocols",totalDownloads:54048,totalCrossrefCites:1,totalDimensionsCites:2,abstract:null,book:{id:"542",slug:"a-compendium-of-essays-on-alternative-therapy",title:"A Compendium of Essays on Alternative Therapy",fullTitle:"A Compendium of Essays on Alternative Therapy"},signatures:"Prasanta Banerji and Pratip Banerji",authors:[{id:"79939",title:"Dr",name:"Prasanta",middleName:null,surname:"Banerji",slug:"prasanta-banerji",fullName:"Prasanta Banerji"},{id:"79943",title:"Dr.",name:"Pratip",middleName:null,surname:"Banerji",slug:"pratip-banerji",fullName:"Pratip Banerji"}]},{id:"54028",title:"Chemical Composition and Biological Activities of Mentha Species",slug:"chemical-composition-and-biological-activities-of-mentha-species",totalDownloads:7474,totalCrossrefCites:13,totalDimensionsCites:46,abstract:"The genus Mentha L. (Lamiaceae) is distributed all over the world and can be found in many environments. Mentha species, one of the world’s oldest and most popular herbs, are widely used in cooking, in cosmetics, and as alternative or complementary therapy, mainly for the treatment of gastrointestinal disorders like flatulence, indigestion, nausea, vomiting, anorexia, and ulcerative colitis. Furthermore, it is well documented that the essential oil and extracts of Mentha species possess antimicrobial, fungicidal, antiviral, insecticidal, and antioxidant properties. The economic importance of mints is also evident; mint oil and its constituents and derivatives are used as flavoring agents throughout the world in food, pharmaceutical, herbal, perfumery, and flavoring industry. To provide a scientific basis for their traditional uses, several studies have been conducted to determine the chemical composition of mints and assess their biological activities. This chapter describes the therapeutic effects and uses of Mentha species and their constituents, particularly essential oils and phenolic compounds; some additional biological activities will also be considered.",book:{id:"5612",slug:"aromatic-and-medicinal-plants-back-to-nature",title:"Aromatic and Medicinal Plants",fullTitle:"Aromatic and Medicinal Plants - Back to Nature"},signatures:"Fatiha Brahmi, Madani Khodir, Chibane Mohamed and Duez Pierre",authors:[{id:"193281",title:"Dr.",name:"Fatiha",middleName:null,surname:"Brahmi",slug:"fatiha-brahmi",fullName:"Fatiha Brahmi"},{id:"199693",title:"Prof.",name:"Khodir",middleName:null,surname:"Madani",slug:"khodir-madani",fullName:"Khodir Madani"},{id:"199694",title:"Prof.",name:"Pierre",middleName:null,surname:"Duez",slug:"pierre-duez",fullName:"Pierre Duez"},{id:"203738",title:"Prof.",name:"Mohamed",middleName:null,surname:"Chibane",slug:"mohamed-chibane",fullName:"Mohamed Chibane"}]}],onlineFirstChaptersFilter:{topicId:"991",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:31,numberOfPublishedChapters:314,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:11,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:105,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:19,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:14,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,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:"10",title:"Physiology",doi:"10.5772/intechopen.72796",issn:"2631-8261",scope:"Modern physiology requires a comprehensive understanding of the integration of tissues and organs throughout the mammalian body, including the cooperation between structure and function at the cellular and molecular levels governed by gene and protein expression. While a daunting task, learning is facilitated by identifying common and effective signaling pathways mediated by a variety of factors employed by nature to preserve and sustain homeostatic life. \r\nAs a leading example, the cellular interaction between intracellular concentration of Ca+2 increases, and changes in plasma membrane potential is integral for coordinating blood flow, governing the exocytosis of neurotransmitters, and modulating gene expression and cell effector secretory functions. Furthermore, in this manner, understanding the systemic interaction between the cardiovascular and nervous systems has become more important than ever as human populations' life prolongation, aging and mechanisms of cellular oxidative signaling are utilised for sustaining life. \r\nAltogether, physiological research enables our identification of distinct and precise points of transition from health to the development of multimorbidity throughout the inevitable aging disorders (e.g., diabetes, hypertension, chronic kidney disease, heart failure, peptic ulcer, inflammatory bowel disease, age-related macular degeneration, cancer). With consideration of all organ systems (e.g., brain, heart, lung, gut, skeletal and smooth muscle, liver, pancreas, kidney, eye) and the interactions thereof, this Physiology Series will address the goals of resolving (1) Aging physiology and chronic disease progression (2) Examination of key cellular pathways as they relate to calcium, oxidative stress, and electrical signaling, and (3) how changes in plasma membrane produced by lipid peroxidation products can affect aging physiology, covering new research in the area of cell, human, plant and animal physiology.",coverUrl:"https://cdn.intechopen.com/series/covers/10.jpg",latestPublicationDate:"June 20th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:11,editor:{id:"35854",title:"Prof.",name:"Tomasz",middleName:null,surname:"Brzozowski",slug:"tomasz-brzozowski",fullName:"Tomasz Brzozowski",profilePictureURL:"https://mts.intechopen.com/storage/users/35854/images/system/35854.jpg",biography:"Prof. Dr. Thomas Brzozowski works as a professor of Human Physiology and is currently Chairman at the Department of Physiology and is V-Dean of the Medical Faculty at Jagiellonian University Medical College, Cracow, Poland. His primary area of interest is physiology and pathophysiology of the gastrointestinal (GI) tract, with the major focus on the mechanism of GI mucosal defense, protection, and ulcer healing. He was a postdoctoral NIH fellow at the University of California and the Gastroenterology VA Medical Center, Irvine, Long Beach, CA, USA, and at the Gastroenterology Clinics Erlangen-Nuremberg and Munster in Germany. He has published 290 original articles in some of the most prestigious scientific journals and seven book chapters on the pathophysiology of the GI tract, gastroprotection, ulcer healing, drug therapy of peptic ulcers, hormonal regulation of the gut, and inflammatory bowel disease.",institutionString:null,institution:{name:"Jagiellonian University",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"10",title:"Animal Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/10.jpg",isOpenForSubmission:!0,editor:{id:"202192",title:"Dr.",name:"Catrin",middleName:null,surname:"Rutland",slug:"catrin-rutland",fullName:"Catrin Rutland",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",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},{id:"11",title:"Cell Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/11.jpg",isOpenForSubmission:!0,editor:{id:"133493",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/133493/images/3091_n.jpg",biography:"Prof. Dr. Angel Catalá \r\nShort Biography Angel Catalá was born in Rodeo (San Juan, Argentina). He studied \r\nchemistry at the Universidad Nacional de La Plata, Argentina, where received aPh.D. degree in chemistry (Biological Branch) in 1965. From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). W inner of the Bimbo PanAmerican Nutrition, Food Science and Technology Award 2006 and 2012, South AmericaHuman Nutrition, Professional Category. 2006 award in pharmacology, Bernardo\r\nHoussay, in recognition of his meritorious works of research. Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. He is a physiologist working in the field of skeletal muscle. He was awarded his sports science diploma in 1995 by the University of Tsukuba and began his scientific work at the Department of Physiology, Aichi Human Service Center, focusing on the molecular mechanism of congenital muscular dystrophy and normal muscle regeneration. His interest later turned to the molecular mechanism and attenuating strategy of sarcopenia (age-related muscle atrophy). His opinion is to attenuate sarcopenia by improving autophagic defects using nutrient- and pharmaceutical-based treatments.",institutionString:null,institution:{name:"Tokyo Institute of Technology",institutionURL:null,country:{name:"Japan"}}},editorTwo:{id:"331519",title:"Dr.",name:"Kotomi",middleName:null,surname:"Sakai",slug:"kotomi-sakai",fullName:"Kotomi Sakai",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000031QtFXQA0/Profile_Picture_1637053227318",biography:"Senior researcher Kotomi Sakai, Ph.D., MPH, works at the Research Organization of Science and Technology in Ritsumeikan University. She is a researcher in the geriatric rehabilitation and public health field. She received Ph.D. from Nihon University and MPH from St.Luke’s International University. Her main research interest is sarcopenia in older adults, especially its association with nutritional status. Additionally, to understand how to maintain and improve physical function in older adults, to conduct studies about the mechanism of sarcopenia and determine when possible interventions are needed.",institutionString:null,institution:{name:"Ritsumeikan University",institutionURL:null,country:{name:"Japan"}}},editorThree:null},{id:"13",title:"Plant Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/13.jpg",isOpenForSubmission:!0,editor:{id:"332229",title:"Prof.",name:"Jen-Tsung",middleName:null,surname:"Chen",slug:"jen-tsung-chen",fullName:"Jen-Tsung Chen",profilePictureURL:"https://mts.intechopen.com/storage/users/332229/images/system/332229.png",biography:"Dr. Jen-Tsung Chen is currently a professor at the National University of Kaohsiung, Taiwan. He teaches cell biology, genomics, proteomics, medicinal plant biotechnology, and plant tissue culture. Dr. Chen\\'s research interests include bioactive compounds, chromatography techniques, in vitro culture, medicinal plants, phytochemicals, and plant biotechnology. He has published more than ninety scientific papers and serves as an editorial board member for Plant Methods, Biomolecules, and International Journal of Molecular Sciences.",institutionString:"National University of Kaohsiung",institution:{name:"National University of Kaohsiung",institutionURL:null,country:{name:"Taiwan"}}},editorTwo:null,editorThree:null}]},overviewPageOFChapters:{paginationCount:45,paginationItems:[{id:"82135",title:"Carotenoids in Cassava (Manihot esculenta Crantz)",doi:"10.5772/intechopen.105210",signatures:"Lovina I. Udoh, Josephine U. Agogbua, Eberechi R. Keyagha and Itorobong I. Nkanga",slug:"carotenoids-in-cassava-manihot-esculenta-crantz",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Carotenoids - New Perspectives and Application",coverURL:"https://cdn.intechopen.com/books/images_new/10836.jpg",subseries:{id:"13",title:"Plant Physiology"}}},{id:"82112",title:"Comparative Senescence and Lifespan",doi:"10.5772/intechopen.105137",signatures:"Hassan M. Heshmati",slug:"comparative-senescence-and-lifespan",totalDownloads:7,totalCrossrefCites:0,totalDimensionsCites:0,authors:[{name:"Hassan M.",surname:"Heshmati"}],book:{title:"Mechanisms and Management of Senescence",coverURL:"https://cdn.intechopen.com/books/images_new/10935.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81796",title:"Apoptosis-Related Diseases and Peroxisomes",doi:"10.5772/intechopen.105052",signatures:"Meimei Wang, Yakun Liu, Ni Chen, Juan Wang and Ye Zhao",slug:"apoptosis-related-diseases-and-peroxisomes",totalDownloads:11,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}},{id:"81723",title:"Peroxisomal Modulation as Therapeutic Alternative for Tackling Multiple Cancers",doi:"10.5772/intechopen.104873",signatures:"Shazia Usmani, Shadma Wahab, Abdul Hafeez, Shabana Khatoon and Syed Misbahul Hasan",slug:"peroxisomal-modulation-as-therapeutic-alternative-for-tackling-multiple-cancers",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"The Metabolic Role of Peroxisome in Health and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/10837.jpg",subseries:{id:"11",title:"Cell Physiology"}}}]},overviewPagePublishedBooks:{paginationCount:11,paginationItems:[{type:"book",id:"7264",title:"Calcium and Signal Transduction",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7264.jpg",slug:"calcium-and-signal-transduction",publishedDate:"October 24th 2018",editedByType:"Edited by",bookSignature:"John N. Buchholz and Erik J. Behringer",hash:"e373a3d1123dbd45fddf75d90e3e7c38",volumeInSeries:1,fullTitle:"Calcium and Signal Transduction",editors:[{id:"89438",title:"Dr.",name:"John N.",middleName:null,surname:"Buchholz",slug:"john-n.-buchholz",fullName:"John N. Buchholz",profilePictureURL:"https://mts.intechopen.com/storage/users/89438/images/6463_n.jpg",biography:"Full Professor and Vice Chair, Division of Pharmacology, Loma Linda University, School of Medicine. He received his B.S. Degree in Biology at La Sierra University, Riverside California (1980) and a PhD in Pharmacology from Loma Linda University School of Medicine (1988). Post-Doctoral Fellow at University of California, Irvine, College of Medicine 1989-1992 with a focus on autonomic nerve function in blood vessels and the impact of aging on the function of these nerves and overall blood vessel function. Twenty years of research funding and served on NIH R01 review panels, Editor-In-Chief of Edorium Journal of Aging Research. Serves as a peer reviewer for biomedical journals. Military Reserve Officer serving with the 100 Support Command, 100 Troop Command, 40 Infantry Division, CA National Guard.",institutionString:null,institution:{name:"Loma Linda University",institutionURL:null,country:{name:"United States of America"}}}]},{type:"book",id:"6925",title:"Endoplasmic Reticulum",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6925.jpg",slug:"endoplasmic-reticulum",publishedDate:"April 17th 2019",editedByType:"Edited by",bookSignature:"Angel Català",hash:"a9e90d2dbdbc46128dfe7dac9f87c6b4",volumeInSeries:2,fullTitle:"Endoplasmic Reticulum",editors:[{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. He is the co-editor of The Open Biology Journal and associate editor for Oxidative Medicine and Cellular Longevity.",institutionString:"Universidad Nacional de La Plata",institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}}]},{type:"book",id:"6924",title:"Adenosine Triphosphate in Health and Disease",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/6924.jpg",slug:"adenosine-triphosphate-in-health-and-disease",publishedDate:"April 24th 2019",editedByType:"Edited by",bookSignature:"Gyula Mozsik",hash:"04106c232a3c68fec07ba7cf00d2522d",volumeInSeries:3,fullTitle:"Adenosine Triphosphate in Health and Disease",editors:[{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",institutionURL:null,country:{name:"Hungary"}}}]},{type:"book",id:"8008",title:"Antioxidants",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/8008.jpg",slug:"antioxidants",publishedDate:"November 6th 2019",editedByType:"Edited by",bookSignature:"Emad Shalaby",hash:"76361b4061e830906267933c1c670027",volumeInSeries:5,fullTitle:"Antioxidants",editors:[{id:"63600",title:"Prof.",name:"Emad",middleName:null,surname:"Shalaby",slug:"emad-shalaby",fullName:"Emad Shalaby",profilePictureURL:"https://mts.intechopen.com/storage/users/63600/images/system/63600.png",biography:"Dr. Emad Shalaby is a professor of biochemistry on the Biochemistry Department Faculty of Agriculture, Cairo University. He\nreceived a short-term scholarship to carry out his post-doctoral\nstudies abroad, from Japan International Cooperation Agency\n(JICA), in coordination with the Egyptian government. Dr.\nShalaby speaks fluent English and his native Arabic. He has 77\ninternationally published research papers, has attended 15 international conferences, and has contributed to 18 international books and chapters.\nDr. Shalaby works as a reviewer on over one hundred international journals and is\non the editorial board of more than twenty-five international journals. He is a member of seven international specialized scientific societies, besides his local one, and\nhe has won seven prizes.",institutionString:"Cairo University",institution:{name:"Cairo University",institutionURL:null,country:{name:"Egypt"}}}]}]},openForSubmissionBooks:{paginationCount:6,paginationItems:[{id:"11669",title:"Fatty Acids - Recent Advances",coverURL:"https://cdn.intechopen.com/books/images_new/11669.jpg",hash:"9117bd12dc904ced43404e3383b6591a",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 3rd 2022",isOpenForSubmission:!0,editors:[{id:"415310",title:"Assistant Prof.",name:"Erik",surname:"Froyen",slug:"erik-froyen",fullName:"Erik Froyen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11674",title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",hash:"5d7d49bd80f53dad3761f78de4a862c6",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 6th 2022",isOpenForSubmission:!0,editors:[{id:"238047",title:"Dr.",name:"Gaia",surname:"Favero",slug:"gaia-favero",fullName:"Gaia Favero"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11672",title:"Chemokines Updates",coverURL:"https://cdn.intechopen.com/books/images_new/11672.jpg",hash:"c00855833476a514d37abf7c846e16e9",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 6th 2022",isOpenForSubmission:!0,editors:[{id:"14794",title:"Prof.",name:"Murat",surname:"Şentürk",slug:"murat-senturk",fullName:"Murat Şentürk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11670",title:"Chitin-Chitosan - Isolation, Properties, and Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11670.jpg",hash:"69f009be08998711eecfb200adc7deca",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"May 26th 2022",isOpenForSubmission:!0,editors:[{id:"176093",title:"Dr.",name:"Brajesh",surname:"Kumar",slug:"brajesh-kumar",fullName:"Brajesh Kumar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"12215",title:"Cell Death and Disease",coverURL:"https://cdn.intechopen.com/books/images_new/12215.jpg",hash:"dfd456a29478fccf4ebd3294137eb1e3",secondStepPassed:!0,currentStepOfPublishingProcess:3,submissionDeadline:"June 24th 2022",isOpenForSubmission:!0,editors:[{id:"59529",title:"Dr.",name:"Ke",surname:"Xu",slug:"ke-xu",fullName:"Ke Xu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{id:"11673",title:"Stem Cell Research",coverURL:"https://cdn.intechopen.com/books/images_new/11673.jpg",hash:"13092df328080c762dd9157be18ca38c",secondStepPassed:!1,currentStepOfPublishingProcess:2,submissionDeadline:"July 13th 2022",isOpenForSubmission:!0,editors:[{id:"203598",title:"Ph.D.",name:"Diana",surname:"Kitala",slug:"diana-kitala",fullName:"Diana Kitala"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},onlineFirstChapters:{paginationCount:43,paginationItems:[{id:"82374",title:"The Potential of the Purinergic System as a Therapeutic Target of Natural Compounds in Cutaneous Melanoma",doi:"10.5772/intechopen.105457",signatures:"Gilnei Bruno da Silva, Daiane Manica, Marcelo Moreno and Margarete Dulce Bagatini",slug:"the-potential-of-the-purinergic-system-as-a-therapeutic-target-of-natural-compounds-in-cutaneous-mel",totalDownloads:4,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Purinergic System",coverURL:"https://cdn.intechopen.com/books/images_new/10801.jpg",subseries:{id:"17",title:"Metabolism"}}},{id:"82103",title:"The Role of Endoplasmic Reticulum Stress and Its Regulation in the Progression of Neurological and Infectious Diseases",doi:"10.5772/intechopen.105543",signatures:"Mary Dover, Michael Kishek, Miranda Eddins, Naneeta Desar, Ketema Paul and Milan Fiala",slug:"the-role-of-endoplasmic-reticulum-stress-and-its-regulation-in-the-progression-of-neurological-and-i",totalDownloads:5,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Updates on Endoplasmic Reticulum",coverURL:"https://cdn.intechopen.com/books/images_new/11674.jpg",subseries:{id:"14",title:"Cell and Molecular Biology"}}},{id:"82212",title:"Protein Prenylation and Their Applications",doi:"10.5772/intechopen.104700",signatures:"Khemchand R. 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She is now a lecturer at the University of Witwatersrand, South Africa, and a principal researcher at the Health Economics and Epidemiology Research Office (HE2RO), South Africa. Dr. Moolla holds a Ph.D. in Psychology with her research being focused on mental health and resilience. In her professional work capacity, her research has further expanded into the fields of early childhood development, mental health, the HIV and TB care cascades, as well as COVID. She is also a UNESCO-trained International Bioethics Facilitator.",institutionString:"University of the Witwatersrand",institution:{name:"University of the Witwatersrand",country:{name:"South Africa"}}},{id:"342152",title:"Dr.",name:"Santo",middleName:null,surname:"Grace Umesh",slug:"santo-grace-umesh",fullName:"Santo Grace Umesh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/342152/images/16311_n.jpg",biography:null,institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"333647",title:"Dr.",name:"Shreya",middleName:null,surname:"Kishore",slug:"shreya-kishore",fullName:"Shreya Kishore",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333647/images/14701_n.jpg",biography:"Dr. Shreya Kishore completed her Bachelor in Dental Surgery in Chettinad Dental College and Research Institute, Chennai, and her Master of Dental Surgery (Orthodontics) in Saveetha Dental College, Chennai. She is also Invisalign certified. She’s working as a Senior Lecturer in the Department of Orthodontics, SRM Dental College since November 2019. She is actively involved in teaching orthodontics to the undergraduates and the postgraduates. Her clinical research topics include new orthodontic brackets, fixed appliances and TADs. She’s published 4 articles in well renowned indexed journals and has a published patency of her own. Her private practice is currently limited to orthodontics and works as a consultant in various clinics.",institutionString:null,institution:{name:"SRM Dental College",country:{name:"India"}}},{id:"323731",title:"Prof.",name:"Deepak M.",middleName:"Macchindra",surname:"Vikhe",slug:"deepak-m.-vikhe",fullName:"Deepak M. Vikhe",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/323731/images/13613_n.jpg",biography:"Dr Deepak M.Vikhe .\n\n\t\n\tDr Deepak M.Vikhe , completed his Masters & PhD in Prosthodontics from Rural Dental College, Loni securing third rank in the Pravara Institute of Medical Sciences Deemed University. He was awarded Dr.G.C.DAS Memorial Award for Research on Implants at 39th IPS conference Dubai (U A E).He has two patents under his name. He has received Dr.Saraswati medal award for best research for implant study in 2017.He has received Fully funded scholarship to Spain ,university of Santiago de Compostela. He has completed fellowship in Implantlogy from Noble Biocare. \nHe has attended various conferences and CDE programmes and has national publications to his credit. His field of interest is in Implant supported prosthesis. Presently he is working as a associate professor in the Dept of Prosthodontics, Rural Dental College, Loni and maintains a successful private practice specialising in Implantology at Rahata.\n\nEmail: drdeepak_mvikhe@yahoo.com..................",institutionString:null,institution:{name:"Pravara Institute of Medical Sciences",country:{name:"India"}}},{id:"204110",title:"Dr.",name:"Ahmed A.",middleName:null,surname:"Madfa",slug:"ahmed-a.-madfa",fullName:"Ahmed A. Madfa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204110/images/system/204110.jpg",biography:"Dr. Madfa is currently Associate Professor of Endodontics at Thamar University and a visiting lecturer at Sana'a University and University of Sciences and Technology. He has more than 6 years of experience in teaching. His research interests include root canal morphology, functionally graded concept, dental biomaterials, epidemiology and dental education, biomimetic restoration, finite element analysis and endodontic regeneration. Dr. Madfa has numerous international publications, full articles, two patents, a book and a book chapter. Furthermore, he won 14 international scientific awards. Furthermore, he is involved in many academic activities ranging from editorial board member, reviewer for many international journals and postgraduate students' supervisor. Besides, I deliver many courses and training workshops at various scientific events. Dr. Madfa also regularly attends international conferences and holds administrative positions (Deputy Dean of the Faculty for Students’ & Academic Affairs and Deputy Head of Research Unit).",institutionString:"Thamar University",institution:null},{id:"210472",title:"Dr.",name:"Nermin",middleName:"Mohammed Ahmed",surname:"Yussif",slug:"nermin-yussif",fullName:"Nermin Yussif",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/210472/images/system/210472.jpg",biography:"Dr. Nermin Mohammed Ahmed Yussif is working at the Faculty of dentistry, University for October university for modern sciences and arts (MSA). Her areas of expertise include: periodontology, dental laserology, oral implantology, periodontal plastic surgeries, oral mesotherapy, nutrition, dental pharmacology. She is an editor and reviewer in numerous international journals.",institutionString:"MSA University",institution:null},{id:"204606",title:"Dr.",name:"Serdar",middleName:null,surname:"Gözler",slug:"serdar-gozler",fullName:"Serdar Gözler",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204606/images/system/204606.jpeg",biography:"Dr. Serdar Gözler has completed his undergraduate studies at the Marmara University Faculty of Dentistry in 1978, followed by an assistantship in the Prosthesis Department of Dicle University Faculty of Dentistry. Starting his PhD work on non-resilient overdentures with Assoc. Prof. Hüsnü Yavuzyılmaz, he continued his studies with Prof. Dr. Gürbüz Öztürk of Istanbul University Faculty of Dentistry Department of Prosthodontics, this time on Gnatology. He attended training programs on occlusion, neurology, neurophysiology, EMG, radiology and biostatistics. In 1982, he presented his PhD thesis \\Gerber and Lauritzen Occlusion Analysis Techniques: Diagnosis Values,\\ at Istanbul University School of Dentistry, Department of Prosthodontics. As he was also working with Prof. Senih Çalıkkocaoğlu on The Physiology of Chewing at the same time, Gözler has written a chapter in Çalıkkocaoğlu\\'s book \\Complete Prostheses\\ entitled \\The Place of Neuromuscular Mechanism in Prosthetic Dentistry.\\ The book was published five times since by the Istanbul University Publications. Having presented in various conferences about occlusion analysis until 1998, Dr. Gözler has also decided to use the T-Scan II occlusion analysis method. Having been personally trained by Dr. Robert Kerstein on this method, Dr. Gözler has been lecturing on the T-Scan Occlusion Analysis Method in conferences both in Turkey and abroad. Dr. Gözler has various articles and presentations on Digital Occlusion Analysis methods. He is now Head of the TMD Clinic at Prosthodontic Department of Faculty of Dentistry , Istanbul Aydın University , Turkey.",institutionString:"Istanbul Aydin University",institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"240870",title:"Ph.D.",name:"Alaa Eddin Omar",middleName:null,surname:"Al Ostwani",slug:"alaa-eddin-omar-al-ostwani",fullName:"Alaa Eddin Omar Al Ostwani",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/240870/images/system/240870.jpeg",biography:"Dr. Al Ostwani Alaa Eddin Omar received his Master in dentistry from Damascus University in 2010, and his Ph.D. in Pediatric Dentistry from Damascus University in 2014. Dr. Al Ostwani is an assistant professor and faculty member at IUST University since 2014. \nDuring his academic experience, he has received several awards including the scientific research award from the Union of Arab Universities, the Syrian gold medal and the international gold medal for invention and creativity. Dr. Al Ostwani is a Member of the International Association of Dental Traumatology and the Syrian Society for Research and Preventive Dentistry since 2017. He is also a Member of the Reviewer Board of International Journal of Dental Medicine (IJDM), and the Indian Journal of Conservative and Endodontics since 2016.",institutionString:"International University for Science and Technology.",institution:{name:"Islamic University of Science and Technology",country:{name:"India"}}},{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/42847/images/system/42847.jpg",biography:"Dr. Belma IşIk Aslan was born in 1976 in Ankara-TURKEY. After graduating from TED Ankara College in 1994, she attended to Gazi University, Faculty of Dentistry in Ankara. She completed her PhD in orthodontic education at Gazi University between 1999-2005. Dr. Işık Aslan stayed at the Providence Hospital Craniofacial Institude and Reconstructive Surgery in Michigan, USA for three months as an observer. She worked as a specialist doctor at Gazi University, Dentistry Faculty, Department of Orthodontics between 2005-2014. She was appointed as associate professor in January, 2014 and as professor in 2021. Dr. Işık Aslan still works as an instructor at the same faculty. She has published a total of 35 articles, 10 book chapters, 39 conference proceedings both internationally and nationally. Also she was the academic editor of the international book 'Current Advances in Orthodontics'. She is a member of the Turkish Orthodontic Society and Turkish Cleft Lip and Palate Society. She is married and has 2 children. Her knowledge of English is at an advanced level.",institutionString:"Gazi University Dentistry Faculty Department of Orthodontics",institution:null},{id:"178412",title:"Associate Prof.",name:"Guhan",middleName:null,surname:"Dergin",slug:"guhan-dergin",fullName:"Guhan Dergin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178412/images/6954_n.jpg",biography:"Assoc. Prof. Dr. Gühan Dergin was born in 1973 in Izmit. He graduated from Marmara University Faculty of Dentistry in 1999. He completed his specialty of OMFS surgery in Marmara University Faculty of Dentistry and obtained his PhD degree in 2006. In 2005, he was invited as a visiting doctor in the Oral and Maxillofacial Surgery Department of the University of North Carolina, USA, where he went on a scholarship. Dr. Dergin still continues his academic career as an associate professor in Marmara University Faculty of Dentistry. He has many articles in international and national scientific journals and chapters in books.",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"178414",title:"Prof.",name:"Yusuf",middleName:null,surname:"Emes",slug:"yusuf-emes",fullName:"Yusuf Emes",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178414/images/6953_n.jpg",biography:"Born in Istanbul in 1974, Dr. Emes graduated from Istanbul University Faculty of Dentistry in 1997 and completed his PhD degree in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery in 2005. He has papers published in international and national scientific journals, including research articles on implantology, oroantral fistulas, odontogenic cysts, and temporomandibular disorders. Dr. Emes is currently working as a full-time academic staff in Istanbul University faculty of Dentistry Department of Oral and Maxillofacial Surgery.",institutionString:null,institution:{name:"Istanbul University",country:{name:"Turkey"}}},{id:"192229",title:"Ph.D.",name:"Ana Luiza",middleName:null,surname:"De Carvalho Felippini",slug:"ana-luiza-de-carvalho-felippini",fullName:"Ana Luiza De Carvalho Felippini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192229/images/system/192229.jpg",biography:null,institutionString:"University of São Paulo",institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"256851",title:"Prof.",name:"Ayşe",middleName:null,surname:"Gülşen",slug:"ayse-gulsen",fullName:"Ayşe Gülşen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256851/images/9696_n.jpg",biography:"Dr. Ayşe Gülşen graduated in 1990 from Faculty of Dentistry, University of Ankara and did a postgraduate program at University of Gazi. \nShe worked as an observer and research assistant in Craniofacial Surgery Departments in New York, Providence Hospital in Michigan and Chang Gung Memorial Hospital in Taiwan. \nShe works as Craniofacial Orthodontist in Department of Aesthetic, Plastic and Reconstructive Surgery, Faculty of Medicine, University of Gazi, Ankara Turkey since 2004.",institutionString:"Univeristy of Gazi",institution:null},{id:"255366",title:"Prof.",name:"Tosun",middleName:null,surname:"Tosun",slug:"tosun-tosun",fullName:"Tosun Tosun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255366/images/7347_n.jpg",biography:"Graduated at the Faculty of Dentistry, University of Istanbul, Turkey in 1989;\nVisitor Assistant at the University of Padua, Italy and Branemark Osseointegration Center of Treviso, Italy between 1993-94;\nPhD thesis on oral implantology in University of Istanbul and was awarded the academic title “Dr.med.dent.”, 1997;\nHe was awarded the academic title “Doç.Dr.” (Associated Professor) in 2003;\nProficiency in Botulinum Toxin Applications, Reading-UK in 2009;\nMastership, RWTH Certificate in Laser Therapy in Dentistry, AALZ-Aachen University, Germany 2009-11;\nMaster of Science (MSc) in Laser Dentistry, University of Genoa, Italy 2013-14.\n\nDr.Tosun worked as Research Assistant in the Department of Oral Implantology, Faculty of Dentistry, University of Istanbul between 1990-2002. \nHe worked part-time as Consultant surgeon in Harvard Medical International Hospitals and John Hopkins Medicine, Istanbul between years 2007-09.\u2028He was contract Professor in the Department of Surgical and Diagnostic Sciences (DI.S.C.), Medical School, University of Genova, Italy between years 2011-16. \nSince 2015 he is visiting Professor at Medical School, University of Plovdiv, Bulgaria. \nCurrently he is Associated Prof.Dr. at the Dental School, Oral Surgery Dept., Istanbul Aydin University and since 2003 he works in his own private clinic in Istanbul, Turkey.\u2028\nDr.Tosun is reviewer in journal ‘Laser in Medical Sciences’, reviewer in journal ‘Folia Medica\\', a Fellow of the International Team for Implantology, Clinical Lecturer of DGZI German Association of Oral Implantology, Expert Lecturer of Laser&Health Academy, Country Representative of World Federation for Laser Dentistry, member of European Federation of Periodontology, member of Academy of Laser Dentistry. Dr.Tosun presents papers in international and national congresses and has scientific publications in international and national journals. He speaks english, spanish, italian and french.",institutionString:null,institution:{name:"Istanbul Aydın University",country:{name:"Turkey"}}},{id:"171887",title:"Prof.",name:"Zühre",middleName:null,surname:"Akarslan",slug:"zuhre-akarslan",fullName:"Zühre Akarslan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/171887/images/system/171887.jpg",biography:"Zühre Akarslan was born in 1977 in Cyprus. She graduated from Gazi University Faculty of Dentistry, Ankara, Turkey in 2000. \r\nLater she received her Ph.D. degree from the Oral Diagnosis and Radiology Department; which was recently renamed as Oral and Dentomaxillofacial Radiology, from the same university. \r\nShe is working as a full-time Associate Professor and is a lecturer and an academic researcher. \r\nHer expertise areas are dental caries, cancer, dental fear and anxiety, gag reflex in dentistry, oral medicine, and dentomaxillofacial radiology.",institutionString:"Gazi University",institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"256417",title:"Associate Prof.",name:"Sanaz",middleName:null,surname:"Sadry",slug:"sanaz-sadry",fullName:"Sanaz Sadry",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/256417/images/8106_n.jpg",biography:null,institutionString:null,institution:null},{id:"272237",title:"Dr.",name:"Pinar",middleName:"Kiymet",surname:"Karataban",slug:"pinar-karataban",fullName:"Pinar Karataban",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/272237/images/8911_n.png",biography:"Assist.Prof.Dr.Pınar Kıymet Karataban, DDS PhD \n\nDr.Pınar Kıymet Karataban was born in Istanbul in 1975. After her graduation from Marmara University Faculty of Dentistry in 1998 she started her PhD in Paediatric Dentistry focused on children with special needs; mainly children with Cerebral Palsy. She finished her pHD thesis entitled \\'Investigation of occlusion via cast analysis and evaluation of dental caries prevalance, periodontal status and muscle dysfunctions in children with cerebral palsy” in 2008. She got her Assist. Proffessor degree in Istanbul Aydın University Paediatric Dentistry Department in 2015-2018. ın 2019 she started her new career in Bahcesehir University, Istanbul as Head of Department of Pediatric Dentistry. In 2020 she was accepted to BAU International University, Batumi as Professor of Pediatric Dentistry. She’s a lecturer in the same university meanwhile working part-time in private practice in Ege Dental Studio (https://www.egedisklinigi.com/) a multidisciplinary dental clinic in Istanbul. Her main interests are paleodontology, ancient and contemporary dentistry, oral microbiology, cerebral palsy and special care dentistry. She has national and international publications, scientific reports and is a member of IAPO (International Association for Paleodontology), IADH (International Association of Disability and Oral Health) and EAPD (European Association of Pediatric Dentistry).",institutionString:null,institution:null},{id:"202198",title:"Dr.",name:"Buket",middleName:null,surname:"Aybar",slug:"buket-aybar",fullName:"Buket Aybar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/202198/images/6955_n.jpg",biography:"Buket Aybar, DDS, PhD, was born in 1971. She graduated from Istanbul University, Faculty of Dentistry, in 1992 and completed her PhD degree on Oral and Maxillofacial Surgery in Istanbul University in 1997.\nDr. Aybar is currently a full-time professor in Istanbul University, Faculty of Dentistry Department of Oral and Maxillofacial Surgery. She has teaching responsibilities in graduate and postgraduate programs. Her clinical practice includes mainly dentoalveolar surgery.\nHer topics of interest are biomaterials science and cell culture studies. 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