Constellation of symptoms for each common trigger site [36].
\r\n\tThis book will be very useful for a wide variety of readers, such as Chemists, Pharmaceuticals, Biochemists, Biotechnologists, Industrialists, Engineers, Researchers, Teachers and Students.
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Adj. of Instituto de Física Aplicada – CONICET – UNSL and Associate Professor-UNSL, San Luis, Argentina. He holds a master’s degree and a PhD and Master thesis in Membrane Technology from National University of San Luis (UNSL). He is Director of Physics Chemistry Service Laboratory, UNSL. He is expert in polysaccharides and physics chemistry of macromolecules. He is author or co-author of more than 26 peer-reviewed international publications, six book chapters, 70 communications in national and international congresses, editor of five books. He is a member of the Sociedad Argentina de Ciencia y Tecnología Ambiental and Asociación Argentina de Fisicoquímica y Química Inorgánica. He is Editor in Chief and Founder, in July 2013, of Journal of Polymer and Biopolymers Physics Chemistry, Science and Education Publishing. He is editorial board of numerous Journals.",institutionString:"Universidad Nacional de San Luis",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"National University of San Luis",institutionURL:null,country:{name:"Argentina"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"5",title:"Agricultural and Biological Sciences",slug:"agricultural-and-biological-sciences"}],chapters:[{id:"69850",title:"Extraction and Characterization of Pectins From Peels of Criolla Oranges (Citrus sinensis): Experimental Reviews",slug:"extraction-and-characterization-of-pectins-from-peels-of-criolla-oranges-citrus-sinensis-experimenta",totalDownloads:52,totalCrossrefCites:0,authors:[{id:"99994",title:"Dr.",name:"Martin",surname:"Masuelli",slug:"martin-masuelli",fullName:"Martin Masuelli"}]},{id:"65638",title:"Pectins as Emulsifying Agent on the Preparation, Characterization, and Photocatalysis of Nano-LaCrO3",slug:"pectins-as-emulsifying-agent-on-the-preparation-characterization-and-photocatalysis-of-nano-lacro3",totalDownloads:115,totalCrossrefCites:1,authors:[null]},{id:"66671",title:"Extraction and Purification of Pectin from Agro-Industrial Wastes",slug:"extraction-and-purification-of-pectin-from-agro-industrial-wastes",totalDownloads:651,totalCrossrefCites:0,authors:[null]},{id:"65895",title:"Flavonoids and Pectins",slug:"flavonoids-and-pectins",totalDownloads:157,totalCrossrefCites:0,authors:[null]},{id:"66458",title:"Pectin - Extraction, Purification, Characterization and Applications",slug:"pectin-extraction-purification-characterization-and-applications",totalDownloads:3,totalCrossrefCites:0,authors:[null]},{id:"65793",title:"Role of Pectin in Food Processing and Food Packaging",slug:"role-of-pectin-in-food-processing-and-food-packaging",totalDownloads:834,totalCrossrefCites:1,authors:[null]},{id:"66396",title:"Properties of Wine Polysaccharides",slug:"properties-of-wine-polysaccharides",totalDownloads:192,totalCrossrefCites:0,authors:[{id:"207851",title:"Dr.",name:"Zenaida",surname:"Guadalupe",slug:"zenaida-guadalupe",fullName:"Zenaida Guadalupe"},{id:"207853",title:"Dr.",name:"Belén",surname:"Ayestarán",slug:"belen-ayestaran",fullName:"Belén Ayestarán"},{id:"207854",title:"Dr.",name:"Leticia",surname:"Martínez-Lapuente",slug:"leticia-martinez-lapuente",fullName:"Leticia Martínez-Lapuente"}]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. 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Chan and Manoj Kumar Tiwari",coverURL:"https://cdn.intechopen.com/books/images_new/3794.jpg",editedByType:"Edited by",editors:[{id:"252210",title:"Dr.",name:"Felix",surname:"Chan",slug:"felix-chan",fullName:"Felix Chan"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"53202",title:"Surgical Management of Migraine Headaches",doi:"10.5772/66229",slug:"surgical-management-of-migraine-headaches",body:'\nMigraine headaches (MH) affect over 37 million people in the United States [1]. One in four households will have at least one person experienced migraines, as the prevalence for females reaches as high as 18%, and males 6% [2]. Sufferers can develop severe disability that takes away their ability to do even the most routine daily activities. Many do not seek treatment, and even if they do, traditional medications often fail to completely treat patients, leaving them with significant residual disability. It is estimated that one-third of migraine patients are refractory to preventative and pharmacological treatments [3]. A common and effective option for these patients is surgical decompression, which may be the only treatment that can provide permanent relief.
Because migraine headache development seems to be complex and multifactorial, its exact pathophysiology is complicated and incompletely understood. Classically, migraine headaches were described as a central nervous system event, but recent publications have stressed the role of peripheral nerves [4, 5]. As the evidence for a peripheral explanation of migraine development continues to increase, so does the evidence for surgical decompression as an effective treatment [6–11].
\nThere are four commonly accepted and experimentally substantiated theories that incorporate both central and peripheral nervous system activity. These include: periaqueductal gray matter dysfunction, interictal cortical derangement, cortical spreading depression, and trigeminal nerve irritation. The combined effect of these neural derangements is a cycle of nerve irritation, inflammation, and sensory hypersensitivity in the peripheral nerve [12–14]. In migraine headaches, these derangements occur in the areas of trigeminal innervation. A recent microscopic and proteomic analysis indicated that there are indeed biostructural differences in myelin between some peripheral nerves excised from migraine patients and peripheral nerves excised from patients without migraines [15].
\nOne theory that explains the cycle of trigeminal irritation and hypersensitization is the anatomical relationship between peripheral nerves and surrounding musculature. Trigger points for nerve irritation are located at points of intersection between nerve and muscle. One specific example is the interaction between the supratrochlear and supraorbital nerve branches of the ophthalmic division of the trigeminal nerve and the corrugator and depressor supercilii muscle [16]. The observation that many patients with frontal migraines have supercilii hypertrophy supports the theory that muscle impaction on the nerve at least plays a role in inducing migraine pain [17]. Furthermore, the beneficial effect of onabotulinumtoxinA injection into this muscle group reinforces this notion [18, 19]. Other trigger sites of nerve and muscle interaction include the zygomaticotemporal branch of the maxillary division of the trigeminal nerve as it pierces the temporal muscle and the greater occipital nerve (GON) as it passes through the splenius capitus muscle.
In the last century, several surgeons demonstrated the effects of operating on nerves to treat migraine headaches. From these studies, they noticed some beneficial results, but the morbidity and adverse sequelae were unacceptable to further this practice. The first attempt to treat MH was conducted by Walter Dandy in 1931, who removed the inferior cervical and first thoracic sympathetic ganglions [20]. In 1946, Gardner resected the greater superficial petrosal nerve in 26 patients [21]. Despite having some reduction in symptoms, he reported complications such as nasal dryness, decreased tear production, and corneal ulceration. A few decades later, temporal neurovascular bundle resection and greater occipital nerve resection were reported by Murillo [22] and Murphy [23]. While innovative, these surgeries were radical and led to numerous side effects like numbness and muscle weakness. Despite the unwanted effects from surgery, these studies showed potential and provided the groundwork for modern surgical treatment of migraine headaches.
\nWith better understanding of migraine pathophysiology and advancements in technology and surgical techniques within the last two decades, surgical methods of treating migraine headaches have been demonstrated to indeed be significantly useful [4]. As the pioneer of modern surgical decompression for migraine headaches, Guyuron observed that among his patients who underwent cosmetic forehead rejuvenation, a number of those with preoperative migraine headaches received complete elimination or significant reduction in headache symptoms [16]. In this forehead rejuvenation surgery, the glabellar muscle group (corrugator, depressor supercilii, and procerus) is resected. As anatomical studies show that the supraorbital and supratrochlear nerves are intimately associated with this muscle group. Therefore, if nerve irritation from this relationship contributes significantly to the pathophysiology of migraine headaches, resection of the muscle group at this site theoretically should resolve symptoms [24]. This led to a retrospective report, and eventually a prospective double-blinded sham-controlled study, as a protocol for surgical migraine treatment was developed [16, 24]. A five-year retrospective follow-up study confirmed that 88% of these patients, who underwent this prospective trial, experienced a positive response to the surgery. Specifically, 29% reported complete elimination of all migraine symptoms [9]. In time, the recognition of additional extracranial trigger sites and several retrospective studies demonstrated significant efficacy in reducing migraine symptoms [6, 8–11, 16, 24, 25]. The combination of numerous studies shows that on average success from decompression surgery, meaning at least 50% reduction in symptoms, nears 90% [4]. As many as 63% of patients report complete elimination of migraine symptoms [9, 26–28]. As mentioned earlier, there are structural differences in the myelin sheath of some of the nerves excised from migraine patients versus those without migraines [15]. This biostructural difference suggests a peripheral mechanism in migraine pathology and thus further supports the rationale for surgical removal or decompression of these nerves. Finally, the sham controlled study conducted by Guyuron provides evidence against the placebo effect explanation [9, 25].
Following the first successful report by Guyuron in 2002, migraine trigger site deactivation surgery has been received with some controversy in neurology. Our understanding of migraine headache’s complex pathophysiology and how interactions between central and peripheral mechanisms influence the development of migraine headaches is an ongoing investigation. The unclear mechanism of action in the context of current migraine pathophysiology models, and the potential for serious irreversible adverse events, causes uncertainty and hesitation among certain headache care providers. It is possible that procedures involving nerve avulsions or possible damage to nerves may result in numbness, paresthesias, dysesthesias, and exacerbated pain postoperatively [29, 30]. However, studies have shown few nonserious complications, often limited locally to the surgical site, and no complications requiring a return to the operating room [4]. Criticisms against surgical treatments also point to possible weaknesses and design flaws in early key studies that show significant efficacy from surgical deactivation [31]. Due to the nature of long-term surgical trials, it is very difficult to design studies that can both satisfy the biggest skeptics and also remain ethical in what patients are required to undergo through the course of the trial. Even so, evidence supporting the migraine decompression surgery is accumulating at a rapid pace. In addition to over 30 anatomical studies to date, there are 17 clinical studies, including a sham control prospective trial, showing the positive effect of decompression surgery and its long-term efficacy [4]. Nevertheless, migraine pathophysiology is complex and dynamic. It is unclear the role of surgical decompression in chronic migraine patients with triggers that may be predominantly central. In each study, certified neurologists were intimately involved throughout every step of each trial [32]. Therefore, it is critical that every patient being evaluated for migraine surgical decompression is also concurrently evaluated by a neurologist to ensure the best understanding of the unique mechanistic picture of their headaches. The cooperation between neurologists and plastic surgeons in each step of treatment for migraine patients is essential: from diagnosis to medication management to postoperative management.
A recent systematic review compiled the clinical results of all studies on migraine decompression across multiple institutions [4]. In all but one study in this review, follow-up of surgical decompression patients exceeded 1 year, with every study demonstrating sustained long-term benefits from surgery. In his review, Janis reported the average success rate of, meaning at least 50% reduction in migraine symptoms, about 90%. A five-year outcomes report on the Guyuron randomized-placebo-controlled study demonstrated both sustained benefits from surgery and a lack of serious long-term adverse complications [9]. While the placebo effect for migraine surgery is possible, it is unlikely that it is so significant 5 years after intervention. This five-year study, and the other studies reviewed by Janis, provides evidence for the sustained, long-term benefits of migraine decompression surgery, with minimal risk for serious complications [4, 9, 25, 28, 33].
Before taking a migraine patient to undergo surgical intervention, there are several considerations that the headache care provider should use to identify the ideal candidate. It is of upmost importance for the patient to see a neurologist to confirm the diagnosis. A headache questionnaire and patient headache log can be very useful in identifying the migraine patient. Equally as important, the neurologist can help manage the numerous migraine medications that patients often take. It is important to control the use of narcotics to prevent medication overuse headache or even a reduced response to surgery. Narcotic users showed significantly less improvement in frequency, duration, and severity of migraines in a 2014 study [26]. On physical exam and history, there should be evidence of nerve irritation as evidenced by tenderness in the specific topographic compression sites. Additionally, there should be no other medical or neurological conditions that may likely explain another cause for their headache symptoms. Assess for any unacceptable surgical risk. Pregnant and nursing women are typically not considered for surgical intervention.
\nThe headache care provider is led to suspect various trigger sites for the cause of the patient’s pain by considering the constellation of symptoms. This is outlined in Table 1. The patient can usually give an idea of where the pain originates and where it spreads to. On palpation, tender areas often correspond with anatomically studied nerve compression sites. For intranasal sources of pain, the nose can be examined in office by a direct or indirect endoscopic approach to identify septal deviations or masses such as turbinate hypertrophy and concha bullosa. These findings can be confirmed by X-ray computed tomography. Typically, after confirmation of migraine by a neurologist, patients undergo BOTOX injections in each of the identified sites to temporarily relieve symptoms. Targeted chemodenervation by this toxin is also used to confirm the sites suspected to benefit from surgical excision [17, 34]. An alternative method is chemical nerve block. Local anesthesia is often used by surgeons to identify which sites will respond to decompression. Although chemodenervation is a useful prognostic indicator for surgical success, the constellation of symptoms based on physical exam and history is just as effective at predicting which sites will benefit [35].
Site I—Frontal headache | Site II—Temporal headache |
---|---|
Frontal pain Stress Robust muscles for frowning Eyebrow/eyelid ptosis Tenderness Corrugator contraction triggered by intense and bright lights (sunglasses often needed) | Temporal pain Morning peak Stress Clenching/grinding Trigger point tenderness TMJ pain |
Site III—Rhinogenic headache | Site IV—Occipital headache |
Retroorbital pain Early morning peak Change in weather related Allergy related Hormone related Rhinorrhea Cyclic | Occipital pain No specific time when pain is worst Stress Related to heavy exercise Muscle tightness Trigger point tenderness Radiation of pain to retroorbital area or area above the posterior superior part of the ear |
Constellation of symptoms for each common trigger site [36].
There are six major trigger sites identified by careful anatomical studies and experience with migraine surgery. Site I refers to the frontal area migraines, where the glabellar muscles, fascial bands, supraorbital and supratrochlear vessels, and at times supraorbital foraminal anatomy (foramen versus notch) compress the supraorbital and supratrochlear nerves (Figure 1). Site II refers to headaches originating in the temple areas of the zygomaticotemporal branch of the trigeminal nerve (ZTBTN) (Figure 2). The zygomaticotemporal branch of the trigeminal nerve is irritated by the temporalis muscle and accompanying fascial elements. Site III refers to an intranasal origin. Septal deviation with boney spurs, turbinate pathology, or bullosa anomalies causes contact with the septum. This paranasal and retrobulbar type pain is caused by irritation of terminal branches of the trigeminal nerve via the sphenopalatine, anterior ethmoidal, and posterior ethmoidal nerves (Figure 3). Site IV refers to headaches originating around the greater occipital nerve in the occipital area of the neck. In this area, the semispinalis capitis muscle, accompanying fascia, trapezius fascia, and occipital vessels can irritate and compress the greater occipital nerve. Site V refers to auriculotemporal nerve irritation in the temple above the temporomandibular joint (TMJ) by fascial bands, and higher in the temple by the temporal artery. Site VI refers to pain originating lower in the neck from the lesser occipital nerve (LON) as it is compressed by fascial and vascular elements. Each of these sites is well understood, and multiple locations of potential compression have been elucidated. In addition to the six common sites, neurologists and plastic surgeons often encounter migraines originating from other less common sites, such as the third occipital nerve and distal tail ends of the greater and lesser occipital nerves.
\nSite I trigger site. The supraorbital and supratrochlear nerves are found here along with the glabellar muscles, fascial bands, supraorbital and supratrochlear vessels, and possible supraorbital foramen.
Site II trigger site. The zygomaticotemporal branch of the trigeminal nerve travels through the temporal muscle before piercing the deep temporal fascia 17 mm lateral and 0.6 mm superior to the lateral canthus.
Site III trigger site, intranasal trigger site. The sphenopalatine, anterior ethmoidal, and/or posterior ethmoidal nerves can become irritated by structures such as a deviated septum with contact points, boney spurs with contact points to hypertrophied turbinates, or concha bullosa that lead to paranasal and retrobulbar pain.
Site I decompression can be approached endoscopically through multiple hairline incisions or directly through transpalpebral incision. Decompression at this site involves release of the corrugator myofascial unit by partial resection of the corrugator supercilii muscle (CSM) group. Alternatively, the entire glabellar muscle group can be excised, including the corrugator supercilii, depressor supercilii, and procerus muscles. Compressing fascial bands are lysed. Foraminotomy and vascular lysis are performed if necessary.
\nAfter initiation of anesthesia, the upper tarsal crease is marked on each eyelid. An incision of 1-inch length is made and extended through the orbicularis muscle. As the dissection plane is extended, several muscles come into view. Careful exposure of the depressor supercilii and corrugator supercilii muscles allow for thorough removal. The supraorbital nerve is encountered laterally and the supratrochlear nerve more medially. A branch of the supratrochlear artery is removed, as well as the procerus muscle. To fill the empty space, autologous fat is grafted and sutured in place.
\nComplications from this procedure include forehead and frontoparietal paresthesia. Although this is common, it will almost always resolve in time if the nerves are preserved in place. Even in cases of traction avulsion of the Supratrochlear nerve (STN), with the Supraorbital nerve (SON) preserved, incidents of painful neuroma are extremely rare.
Five total incisions are made: one midline and two on either side of the temple. This approach allows for multiple procedures to be combined: frontal decompression and temporal ZTBTN avulsion. Therefore, this endoscopic approach is often preferred and in fact has a higher success rate, which is likely due to increased visualization and the ability to address accessory nerves. Similar to the transpalpebral approach, dissection is extended to expose the SON, STN, and surrounding musculature. The corrugator should be adequately removed and fat grafted into the area.
\nComplications of this approach include alopecia at port sites, which is very rare. Paresthesia of the temporal and scalp region can occur, but most resolve over time. In this area, the temporal branch of the facial nerve can theoretically be injured, resulting in paralysis of the frontalis. However, there have been no reports of this potential complication among the endoscopic surgeons. Therefore, it is important that only a well-trained and seasoned endoscopic plastic surgeon attempt this operation.
Decompression at the temporal site can be part of the endoscopic approach. The dissection is extended in the plane of the periosteum and carried to the lateral part of the supraorbital rim, lateral orbital rim, and over the deep layer of temporal fascia to the zygomatic arch, and malar arch. The ZTBTN emerges from the temporalis muscle approximately 17 mm lateral and 6 mm superior to the lateral canthus. It is found superficial to the deep temporal fascia [37]. The ZTBTN can be avulsed or decompressed, each with similar rates of surgical success [33]. As mentioned, there are no reports of neuroma with traction avulsion.
\nRarely, complications from this procedure include temporary paresthesia and anesthesia. Alopecia can occur at port sites and sites of local anesthetic injection. Facial nerve injury, as mentioned above, is a theoretical complication.
\nThe auriculotemporal nerve (AT) is addressed by decompression with a small 1 cm incision in the high temple over the compression site of the temporal artery, with or without traction avulsion of the nerve in the periauricular area and ligation of the temporal artery (Amirlak’s approach) [38]. Similarly, low rates of temporary paresthesia and minor anesthesia have been reported, without reports of facial nerve injury. However, this incision in the periauricular area possesses a higher likelihood of inadvertent injury to the temporal branch of the facial nerve. Therefore, a nerve stimulator is used during surgery confirm the identities of encountered nerves.
In the preoperative waiting room, markings are made at the midline, at the hairline, and at points of maximum tenderness. After initiation of anesthesia, the patient’s hair is shaved to expose the surgical area. A midline incision is made. At this point, efforts should be made to keep the incision within hair-bearing areas to prevent visible scarring. As the dissection is extended, fibers of the trapezius and semispinalis capitus muscles are differentiated. In most cases, the third occipital nerve is encountered during dissection. Although this nerve is usually avulsed when encountered, evidence has shown that there is no difference in surgical success whether or not the nerve is taken [39]. The semispinalis is further exposed by retraction. The trunk of the greater occipital nerve (GON) is located roughly 3 cm below the occipital protuberance and 1.5 cm lateral from the midline. After the nerve and surrounding musculature are identified and exposed, a full thickness section of the semispinalis is resected medial to the path of the GON. This excision is complete when the nerve is completely released, and no muscle tissue remains medial to the nerve. Superiorly, a portion of the trapezius fascia and muscle are removed, along with any fascial bands encountered on the nerve. The trapezium tunnel is opened and decompressed. An endoscopic modification of the Guyuron technique was described by the senior author (BA), which further elucidates the dynamic compression of the occipital vessels on the nerve (manuscript in preparation). Most of these vessels are lysed with no complications. Finally, a subcutaneous fat flap is passed underneath the nerve and sutured in place to protect the nerve from further compression. Figure 4 shows the greater occipital nerve after partial decompression (opening of the trapezius fascia proximally and removal of the medial portion of the semispinalis muscle to expose the body of the nerve show that the right GON is more flat and compressed than the left).
Intraoperative view of the greater occipital nerve (GON). The trapezius fascia has been opened proximally, and a minimal amount of the medial portion of the semispinalis muscle has been removed to expose the body of the nerve. In this patient, the right greater occipital nerve (GON) looks flatter and more compressed than the left.
The lesser occipital nerve (LON) is addressed similarly, but it possesses a more complicated and ill-defined anatomy. However, several approaches, including traction neurectomy, the decompression and crush technique, and the cut and burying in the muscle technique, have been described with no clear benefit of one over the other.
\nTemporary paresthesia and anesthesia have been reported, which improve over time.
In patients with weather-related migraines, and incomplete results from Botox injections, septonasal triggers should be considered. This pain is often described as behind the eye and can be unmasked after other primary sites are relieved either with surgery, BOTOX, or nerve blocks. A CT scan and nasal endoscopy are required to confirm diagnoses and will show any contact points and any complicated nasal pathology. Intranasal injection or spray of lidocaine may be used to further enhance the diagnostic power. At the time of surgery, local lidocaine and epinephrine are injected into the nose. Aroutine open or endoscopic septoplasty is used to address any contact points. In the cases of concha bullosa or significant enlargement of turbinates, full or partial resection of the turbinates is required. In cases of superior turbinate contact, outfracture or shaving is done and should only be performed by an expert plastic surgeon or ear-nose-throat surgeon experienced in this area.
\nComplications of this procedure include temporary or long-term nasal dryness. Synechiae and sinus infections are rare. Cerebrospinal fluid (CSF) leaks or more serious complications have not been reported in plastic surgery literature.
\nRoutine activity within 1 week, and heavy activity within 3 weeks, is routine for all migraine surgery patients. Paresthesia and itching should improve with frequent massage and use of special brushes.
Select migraine headache patients, occipital neuralgia patients, and NDPH (New Daily Persistent Headache) patients can be successfully treated by surgical intervention. However, they should also be simultaneously seen by a neurologist, who can manage medications and rule out other diagnoses apart from migraine headache. Typically, these patients also have failed multiple classes of traditional conservative treatments. Careful documentation, such as patient migraine diaries, should be kept to track changes. Upon confirmation of migraine headache, various trigger sites can be identified by a constellation of symptoms and chemical denervation. Patients with severe anxiety and depression, medication overuse, and narcotic use respond poorly to surgery. Therefore, maximizing medical treatment by neurology following surgery is essential. Surgical decompression for treatment of migraine pain has proven significantly useful by multiple studies, both controlled prospective and retrospective [7].
\nCurrently, surgical intervention becomes a viable option after complete exhaustion of other treatment methods. Rates of complication are low and potential benefits are life-changing. This small group of patients who do not respond to the available preventative and abortive treatments are often left with a very low quality of life. As a result, surgery is often the last resort for an effective treatment and potential permanent relief from their symptoms. In the future, further multicenter randomized prospective trials can elucidate which patients maybe better candidates and improve the response rate.
In today’s engineering world, light-weight materials have gained much attention because of demand in low-cost production and increasing efficiency through weight reduction. Correspondingly, Magnesium is one of the materials which attributed in the lightweight material category after aluminum and its alloys. Magnesium and its alloys have some unique application in aerospace and other engineering sectors. But due to some characteristics regarding the manufacturing process such as complex in forming the components and other cold working processes [1]. Particularly in Biomedical application, magnesium has some restriction since Mg dissolves in the body fluid during the restorative process, so degradation of magnesium has to be controlled [2]. One is the low mechanical properties comparing with the bioinert titanium alloys, which makes their application limited in load-bearing implants. Another one is the fast degradation behavior, which involves the gas cavity and high alkaline microenvironment around the implants leading to a poor osteointegration. The mechanical processing of magnesium alloy at elevated temperature influences the grain distribution.
\nNormally a combination of fine grain structure and coarse grain structure are formed through the various forming operation of wrought materials, and homogeneous grain structures obtained by the cast formed materials [3]. During cold working, the fine grain formed along with the boundaries in the magnesium wrought materials which through the dynamic recrystallization and the distribution is multi-modal [4]. Normally area of the cross section has been reduced through the total plastic deformation method at certain temperature range. Consequently, the methods mentioned above are not having enough capacity to form homogeneous grain refinement at the initial structure and make the grain structure distribution the multimodal phase [5].
\nFor the last few years, the development of plastic deformation technology, which includes the equal channel angular pressing (ECAP) is emerging [6]. The limitation in the plastic deformation of magnesium alloys will neglect through the SPD technique, so severe plastic deformation of magnesium and its alloys initiate the probability for manufacturing the ultrafine grain materials along with the increased mechanical properties and additionally the superplastic capabilities also experienced by the formed material [7].
\nTowards the application, ECAP paved a path for refinement of grains in the lightweight materials, particularly in concern aluminum and magnesium alloys. In concern with f.c.c metals, misorientation in the low angles boundaries and alignment of the elongated subgrains in parallel to the primary slip will occur when the sample subjected to severe plastic deformation [8, 9]. Followed by the first pass, the upcoming passes designed to induce further refinement of grains and rearrangement consistent with the dislocation theory for low energy structure [10, 11] after the multiple passes in the ECAP, a set of equiaxial grains which in different angles. The structure changes have been accounted in many metals having f.c.c arrangement, which also constitutes aluminum [12]. On the contrary, by using the ECAP process, UFG can be obtained from the magnesium alloys, and grains get refined by the subsequent passes [13].
\nDuring the ECAP process of the magnesium and its alloys, grain refinement depends on the number of passes, channel angle, die angle, and the initial grain structure before to the ECAP. By varying the various parameters of the ECAP process, including the temperature, Mg will exhibit diverse morphology such as grain orientation, distribution, size in multimodal type after SPD [12, 13]. Many studies focused on analyzing the microstructure and the mechanical properties after ECAP processing.
\nAs explained, the pattern specified for the grain refinement channels towards a usual perception of the several articles resembling in the research literature and lead to understanding the ability for the further structure of grain formed under the various condition during SPD of magnesium alloys. In magnesium alloys, grain refinement defined in a simple way [14]. This statement is crucial for highlighting, though, that exact grain refinement mechanism elaborated which authorizes various structure formations based on the experimental circumstances including those primary inferences towards maximum processing steps in SPD of magnesium alloys. Different methods regarding severe plastic deformation consistently engage in developing the process and regarding the nanostructure formation in the samples [15].
\nUnder the certain experimental circumstance getting the ultrafine-grained structure along with predominating boundaries oriented in the high degree of angle and it will be varied according to materials. Furthermore, the nanostructure formation in the alloy during the ECAP process is stable in the entire uni, which required for providing durable characteristics for the metals [7, 13]. Followed by, ensuring the ECAP processed samples for mechanical damages or any penetrated cracks in the material. The other methods of SPD will not meet the requirements as above, such as drawing, hot extrusion, and rolling. Nanostructure formation in the samples is only possible with the mechanical deformations at relatively low temperature as well as optimal parameters for material processing [16].
\nTo make a competent design, it is essential to analyze different grain structures of magnesium and its alloys, which processed through the ECAP [17]. An initial documented reports organized, and general review presented in Table 1 for pure magnesium and magnesium alloys, which processed through ECAP.
\nAlloy | \nInitial grain size (μm) | \nFinal grain size (μm) | \nInter-mediate structure | \nStructure after multiple passes | \nAdditional information | \nReferences | \n
---|---|---|---|---|---|---|
AZ31 | \n48.3 | \n2.5 | \nA | \nB | \n_ | \n[18] | \n
AZ31 | \n48.1 | \n1.4 | \nB | \nB | \nU = 100 L | \n[19] | \n
AZ31 | \n2.5 | \n0.7 | \n— | \nB | \nU = 110 L | \n[20] | \n
AZ31 | \n15–22 | \n1 | \nA | \nB | \nBP-ECAP (423 K) | \n[21] | \n
AZ31 | \n5–30 | \n1.9 | \nA | \nB | \nPre-deformed by extrusion | \n[22] | \n
AZ31 | \n5–30 | \n2.2 | \nA | \nB | \nU = 110 L | \n[23] | \n
AZ31 | \n450 | \n1–3 | \nA | \nA | \n\n | [24] | \n
AZ31 | \n20 | \n1–2 | \n— | \nB | \nPre-deformed by hot-rolling | \n[25] | \n
AZ31 | \n10–20 | \n3.0 | \nA | \nB | \n\n | [26] | \n
AZ31 | \n10 | \n3.2 | \n— | \nB | \nPre-deformed by rolling | \n[27] | \n
AZ31 | \n7–20 | \n2 | \nA | \nB | \nRoute A | \n[28] | \n
AZ31 | \n15–22 | \n0.9 | \nA | \nB | \nBP-ECAP | \n[29] | \n
AZ31 | \n28 | \n8 | \nA | \n— | \nOne pass of BP-ECAP | \n[30] | \n
AZ61 | \n16 | \n0.62 | \nB | \nB | \nPre-deformed by extrusion | \n[31] | \n
AZ91 | \n\n | 0.5 | \n— | \nB | \nPre-deformed by extrusion | \n[32] | \n
AZ91 | \n40 | \n1.2 | \nA | \nB | \nRoute C | \n[33] | \n
Mg (pure) | \n400 | \n120 | \n— | \nB | \n— | \n[34] | \n
Mg (pure) | \n200 | \n20 | \nA | \nA | \n— | \n[35] | \n
Mg (pure) | \n900 | \n70 | \nA | \nB | \n— | \n[36] | \n
Mg–0.9% Al | \n100 | \n17 | \n— | \nB | \n— | \n[34] | \n
Comparison of experiments conducted on pure magnesium and a range of magnesium alloy.
The outcome in the given Table 1 indicates the utilization of an ECAP die set up with the 90 internal channel angle, operating with and without back pressure, and the expected outcomes notified in the column number six of Table 1. From the table, A and B represent the heterogeneous and homogeneous grain structure, respectively. BP indicates the back pressure, and U is for the channel angle within the die. Then ECAP routes defined by route A indicate that ECAP processed without any specimen rotation in-between the two passes, BA indicates the specimen rotation of 90° in the alternative direction in-between the passes and C denotes the rotation of 180° in-between the passes.
\nFrom Table 1, we can observe that materials represented in the first column, the grain sizes of the material before and after ECAP provided in the following columns. Then followed by that intermediate stage in the ECAP process is given in the fourth column and the fifth column provided with the additional information regarding the total number of passes. Finally, the references provided in the last column. Additionally, the structure of the grain after processing with the ECAP have given in the notation of Bi-m and Trim to indicate the grain distribution, whether it is tri-modal or Bimodal correspondingly.
\nFrom the interference of Table 1 observation of the distribution of the heterogeneous grain size has done after many passes, particularly while the grain size is large at the initial stage. Certainly, grains were heterogeneous at the initial stage in which the size of the grain ranges from the minimum 45.5 μm for magnesium alloy ZK60 to a higher grain size range of 640 μm magnesium alloy AZ31. From the observation made from the existing investigation, with the minimum number of ECAP passes, the homogeneous grain arrays can obtain with the average grain size of ~40 μm. The high-temperature ECAP processed help to form the homogenization: for instance, the grain size with bi-modal configuration with homogeneity attained with six ECAP passes at the temperature of 423 K in the magnesium AZ31 alloy. In Magnesium-Zn alloy bi-modal distribution is obtained in grain size in which initially the fine and coarse grains have found.
\nFrom Table 1, there were two significant limitations found; one is the results illustrated that by considering the process limitations, the initial structure might exhibit the homogenous distribution, tri-modal or bi-modal grain size distribution. And another observed one is when the grain size is larger, or it formed in coarse then the bi-modal distribution in the grain size is preferred. These were the two important consideration which made based on the grain structure.
\nFrom Figure 1, which shows the patterned design model which created based on the grain structure formation of ECAP processed of magnesium alloys. The design raised based on the assumption of grain size and distribution on the initial stage and mechanism which proposed earlier regarding the grain structure.
\nPatterned design on the refinement of grain of the ECAP processed Mg alloys. (a), (d), (g), (j) are the initial grain structure whose grain size can be termed as d>>dc, d>dc, d>dc and dc respectively. (b), (e) and (h) are the intermediate structure at the shear zone during the ECAP. (c), (f), (i) and (k) are the final structure after the pass [8].
The various grain structure at the initial stage, which is before the ECAP is shown in Figure 1a,d,g, and j. In which dc, the critical grain size integrates with the concept which effectively reduced the size, which initiates the nucleation with proper homogenization during the processing of the materials. The structure of the grain and its refinement process is given below.
\nParticularly, the initial structure of the coarse grain at the initial stage with the size, d and the grain size, d, is larger than dc (d >> dc), which is the critical grain size which shown in Figure 1a, d, and g. From Figure 1j, d < dc, which means the initial grain structure is granular than the critical size. In certain, the grains which attained homogenous nucleation in which entire grain structure is non-basal slips. Furthermore a complete has been yet to be considered to improve the standard of the processing parameters, and it is important to expect that it will rely on kind of alloy and temperature for processing of ECAP and present investigations show that back pressure also a dependent factor for the grain structure.
\nFrom the second column of Figure 1, which illustrates the grain structure formed after one pass. Followed by that third column indicated the grain structure formed after more than one number of passes. Where the structure of the initial size of the grain is comparably larger than critical diameter dc, as shown in the first column of Figure 1, the grain structure develops in the initial pass, such as the bimodal or multimodal distribution of the grain as shown in the second column of Figure 1. Subsequently, the region occupied by the extended cores of the grains at the initial stage and by the grains which newly formed after refinement have significantly relied on the initial size of the grains which observed during the analysis of Figure 1. For a better explanation, differentiation among the cores of the initial grains which are usually larger which exist even after one pass of ECAP, the core regions mentioned above illustrated in the second column and the third column of Figure 1, in particular recently refined grains which indicated in the dotted region.
\nIn Figure 1, the first row illustrates the condition of the grain structure at initial stage which is particularly coarse, because of that even after the one pass of ECAP the initial grains last and hold an extended region which shown in Figure 1b and the same grains may get unrefined until multiple passes which are shown in Figure 1c. From Figure 1b, it can be observed that twinning takes place across the larger grains, so it leads to refinement of grain accompanying with the twinning features. The condition where the critical size of the grain is very smaller than the initial grain size which made bi-modal or multi-modal grain distribution possible which continues even after the multiple passes of ECAP which shown in Figure 1c.
\nIn defining the features of the newly developed grains, it is important to explain whether the grain size distribution is multimodal or homogeneous. The dc grain size variations observed from the first two rows in Figure 1 were the result of variation in the processing parameters particularly the temperature through the initial structure is similar which illustrated in Figure 1a and d. The fractional volume of the newly developed grains after one pass is small when compared to the initial structure because it is too coarse which observed from the first row of Figure 1 and this will be the cause for the formation of bimodal and multimodal distribution among the grain size after the multi passes of ECAP. Subsequently, the same initial structure subjected to the one pass of ECAP with different processing conditions such as lower strain rate and elevated temperature which resulted in the formation of new grains and occupy the extended region which illustrated in Figure 1e and also after multiple passes of ECAP the sample exhibits uniform grain structure as illustrated in Figure 1f.
\nAfter a single pass of ECAP, the grain size distribution becomes bimodal or multimodal by forming reasonably fine structures grains. But the existing grains or grain which not affected by the pass occupied lesser fraction area that the newly formed ones which illustrated in Figure 1g. Figure 1i shows, by multiple ECAP, passes, the grains get refined and resulted in the homogeneous distribution.
\nBy having the initial grain size as smaller than the critical grain diameter as shown in Figure 1j, the homogeneous array distribution achieved through the single pass of ECAP as illustrated in Figure 1i and subsequently after many passes homogeneity remains the same.
\nFrom the mode, it concluded that bi- and multi-modal grain size distributions which formed through the ECAP were transitional and the distribution of the grains gets altered as ECAP passes the increase.
\nSpitale et al. processed ECAP in minimal temperature, which is about 250°C with the channel angle of 90° and with 45°of the radius of curvature. The plunger speed for the process is 0.1 mm/s. They observed the evolution of grain structure at different location of the deformation zone. Figure 2 shows the appearance of the structure entering the deformation zone [37].
\nThe grain structure in the region of deformation [37].
The initial structure of the grain exists with the witness of twinning action. Grain boundaries observed with the serration like features. Grains with fine size within the range of 20 μm have witnessed within the region of grain boundaries and twins, which is developed from the initial grain structure, as shown in Figure 3. Apart from the certain limits from the grain boundaries and twins, fine grains were not witnessed with then fine grains.
\nStructure of the grain inside the region of deformation [37].
From Figure 4, it witnessed that a large area occupied by the fine grains. The fine grains average size is around ~15 μm, which observed from the deformation zone. The fine grain distribution followed the necklace pattern which exists around the area of unrefined grain (>100 μm).
\nGrain structure at the end of the deformation zone [37].
The processing routes influenced the final structure of the grain, failure of billet, and shear localization effect through the grain structure size distribution and refinement mechanism of the magnesium and its alloys. The formation of the shear bands is due to the concentration of the thin layer which belongs to the newly formed grains along with the existing grain boundaries. This shear concentration occurs in a layer due to the nearby regions shear, and it develops damage pile; thus, the failure in the billet takes place. The rise in the initial grain coarse volume leads to the rise in the shear amount, which is in the shear band. The possibilities of the localization of the shear are higher, which is shown in the first row of Figure 1 successively the growth shown in below rows. This decision is in Correspond with the failure of the coarse grain structure in the magnesium and its alloys.
\nTo rectify the issues in the ECAP process of the magnesium and its alloys, some measures have been improvised and designed such as the processing route along with temperature, die angle and the back pressure range and its usage. To bring down the tenor for shear localization the grain cores along with the boundary extents have to reduce. Thus a primary step of extrusion is made to refine the microstructure which can change the initial grain structure as illustrated as Figure 1 an into refined grain structure like Figure 1g or j. As shown in the second row of Figure 1a, the grain refinement sequence of the newly formed grains can alter through the rise in the processing temperature. This alteration in the ECAP process can provide a huge volume of formed grains and reduced tenor for localization of shear [14, 24, 25, 26, 27, 29]. The accumulation of the damage and the shear bands strain have reduced through the increase in the die angel during the ECAP process. The billet cracking which normally caused by the damage accumulation and the additional grain refinement can achieve by using the back-pressure during the ECAP process of the magnesium alloys.
\nAn alternate method is by subjecting the magnesium alloys to the multiple ECAP as initial pas in the elevated temperature, and the sequent passes in lower temperature can help to achieve a fine-grain structure with the homogeneous distribution. This process resembles the technique which follows the extrusion process before the ECAP [31].
\nThe customizing of the grain size distribution in the magnesium alloys is associated with the grain structure refinement mechanism of the alloys, which processed through the ECAP process. By changing the ECAP process, it is desirable to alter or control the grain structure and its fine or coarse refinement structure. To increase the certain mechanical properties of the material such as ductility and strength concept of manipulating the material grain boundary and grain refinement was introduced many years ago in the basis of the grain boundary engineering, the same concept have been followed and approached in the process of ECAP. The recent investigations showed that through the ECAP process, the alteration of the grains structure and its distribution achieved in the selected materials. This merit region in the process mentioned above is, for instance, developing a grain distribution in the bimodal configuration in nanostructured Cu, a combination of enhanced ductility and sufficient strength showed up during the tensile testing at ambient temperature which presented in research work. To obtain the sufficient strength and altered elongated grains to increase the stability during the tensile deformation, ECAP method paves the way for these through the forming ultrafine grains and altering the grain size distribution. Among the Grain size distribution, the bimodal configuration considered as the efficient thing for rising the ductility characteristics during the cyclic loading and deformation which assure mechanical properties can improve through the grain size engineering [23, 24, 25, 26, 27].
\nThe influence of texture is not straightly integrated with any developed model for the refinement of the grain structure. Unless the developed modal is expected to be effective for ECAP processing route and initial texture. This typical thing supposed due to the forming mechanism of the grain structure along with the grain boundaries has witnessed in the magnesium and its alloys which are having the distinctive initial structures while processing in the various temperature range where ECAP is typically carried out [17]. With the uniform procedure, a recent research work analyzed the texture of magnesium AZ31 which processed through the rolling process and ECAP process and they concluded that texture did not influence the size of the grain which formed after the process meanwhile texture influences the chance of formation of new grains and deformation amount which needed to achieve the deformation.
\nWith the recent proposed modal of ECAP, the progression in the structure of the grain refinement mechanism is witnessed [29]. The bimodal distribution of grain structure observed due to the fine grain refinement and grain nucleate around the boundaries of the groan and twins in the presence of area which does not get affected by the process. A research work [8] provides a technique in which grain which subjected to the recrystallization is nucleate throughout the existing grains in the materials and progress until the structure reaches the homogenous structure equiaxial. The variation among the grain structure refinement modal relies upon the region of nucleation, which tends to form the new grain and feasibility of forming the heterogeneous distribution of grains. Some research delivered that heterogeneous grain size distribution in the magnesium and its alloys.
\nBecause of the coarse grains at the initial stage, the predicted criteria from the developed grain refinement model is getting disapproved with the homogeneous distribution of grain sizes. Possibly grain growth and altered grain structure had observed in the material after subjecting it to the complete ECAP process. In the different stages of the grain refinement, fine grains get nucleated throughout the existing grains and in the region of twin boundaries which happened as expected by the grain structure refinement modal which leads to the distribution of grain size in a heterogeneous manner. The temperature for the intermediate process is likely to prevent the growth of grain and influenced the grain structure to form the bimodal distribution, which witnessed after the ECAP process.
\nThe maximum tensile strength is recorded through the compressive tests and in various ways as possible for the material which subjected for three passes of ECAP process which given in Figure 5. The data of the received material included for better understanding [30]. It witnessed that the ECAP processed specimen shows elevated flow stress in multiple directions when compared with processed ones.
\nUltimate tensile strength obtained for the CP-Mg before and after ECAP processing [30].
The material which undergone the ECAP process display an improved yield and maximum yield stress along with improved behavior in the work hardening towards the different compression direction. Significantly the ECAP processed material which tested along the direction of the Y-axis which is perpendicular to the die channel of the ECAP setup shows a concave up like feature with the strain range of 0.02–0.05. Another major witness is that processed sample demonstrates a constant hardening strain range from 0.01 to 0.03 towards the direction of Z-axis and in the direction of X axis it shows 0.01–0.06 in which the hardening rate is slightly get decreased from the initial stage. The processed material showed up a rise in hardening rate in the range of 0.015–0.3045 in the direction of Y-axis.
\nFrom the above results, it is clear that ECAP processing ensures the mechanical anisotropy behavior of the commercially pure Magnesium. The appearance of twinning action in the material during the compression test leads to the anisotropy. The incident of increased hardening rate is clearly because of the twinning action which occurred in the direction of Y-axis. Furthermore, the same twinning action indicated in the ECAP processed AZ31 alloy during the compressive test along the direction of the y-axis, which ensured through the microscopic examination. Along with that observation notable amount of twins were witnessed in the magnesium alloy after subjecting it to the strain of only 0.04 (in approx.) in the compressive test along the direction of Y-axis. The twins obtained after a certain level of strain in the corresponding direction was notably lower. Finally, the outcomes represent that after ECAP processing of commercially pure magnesium, the material shows an improved anisotropic behavior and notably twinning action also takes place while the material compressed in the direction of the Y-axis which is perpendicular to the die channel angle. The tensile characteristics of the rolled magnesium are in the good range and lowered elongation when compared to the ECAP processed commercially pure magnesium. These factors indicate that ECAP processing slightly reduces the yield stress and improves the ductile characteristics of the material. And also fine grain refinement was witnessed through the microstructural study of the ECAP processed Magnesium. Thus, the decreased yield stress after the rolling process, along with ECAP contribute to the texture effect of the magnesium.
\nMagnesium has plenty of tones and choice when equaled to the other metals or nonmetals which have utilized under the category of lightweight materials in automotive, aerospace and biomedical application. Certain advancements are transpiring in magnesium development, and that will engage a fine pathway to the prospect. Among the Severe Plastic deformation (SPD), one of its type Equal Channel Angular Pressing (ECAP) emerged as the technique which can be able to extend the magnesium alloys to the vast application. Among the science group, there is mindfulness about to witness the transcendent application of magnesium and its alloys. Furthermore, enough research and the experimental establishment is needed for the unique evolution of deformation behavior of the magnesium alloys to achieve aspired microstructures which influence the mechanical properties plus fine shapes for avoiding post processes and further greater transformations of the phase which compromise to permit improvement of magnesium alloys. This very low density concerning magnesium and its alloy collectively among attractive characteristics such as castability is traversing to extended transportation business. The progressed application can begin from an expanded design along with many perceptions of the basic features of magnesium behavior and also the rise of cost-affordable magnesium alloys.
\nThis work was supported by “Research and Modernization fund, SASTRA University” grant number R&M/0035/SoME-008/2015-16. The authors thank SASTRA Deemed University for their financial assistance.
\nEdited by Jan Oxholm Gordeladze, ISBN 978-953-51-3020-8, Print ISBN 978-953-51-3019-2, 336 pages,
\nPublisher: IntechOpen
\nChapters published March 22, 2017 under CC BY 3.0 license
\nDOI: 10.5772/61430
\nEdited Volume
This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\\n\\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\\n\\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\\n\\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\\n\\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\\n\\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\\n\\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\\n\\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\\n\\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\\n\\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\\n\\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\\n\\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
\\n"}]'},components:[{type:"htmlEditorComponent",content:'This book serves as a comprehensive survey of the impact of vitamin K2 on cellular functions and organ systems, indicating that vitamin K2 plays an important role in the differentiation/preservation of various cell phenotypes and as a stimulator and/or mediator of interorgan cross talk. Vitamin K2 binds to the transcription factor SXR/PXR, thus acting like a hormone (very much in the same manner as vitamin A and vitamin D). Therefore, vitamin K2 affects a multitude of organ systems, and it is reckoned to be one positive factor in bringing about "longevity" to the human body, e.g., supporting the functions/health of different organ systems, as well as correcting the functioning or even "curing" ailments striking several organs in our body.
\n\nChapter 1 Introductory Chapter: Vitamin K2 by Jan Oxholm Gordeladze
\n\nChapter 2 Vitamin K, SXR, and GGCX by Kotaro Azuma and Satoshi Inoue
\n\nChapter 3 Vitamin K2 Rich Food Products by Muhammad Yasin, Masood Sadiq Butt and Aurang Zeb
\n\nChapter 4 Menaquinones, Bacteria, and Foods: Vitamin K2 in the Diet by Barbara Walther and Magali Chollet
\n\nChapter 5 The Impact of Vitamin K2 on Energy Metabolism by Mona Møller, Serena Tonstad, Tone Bathen and Jan Oxholm Gordeladze
\n\nChapter 6 Vitamin K2 and Bone Health by Niels Erik Frandsen and Jan Oxholm Gordeladze
\n\nChapter 7 Vitamin K2 and its Impact on Tooth Epigenetics by Jan Oxholm Gordeladze, Maria A. Landin, Gaute Floer Johnsen, Håvard Jostein Haugen and Harald Osmundsen
\n\nChapter 8 Anti-Inflammatory Actions of Vitamin K by Stephen J. Hodges, Andrew A. Pitsillides, Lars M. Ytrebø and Robin Soper
\n\nChapter 9 Vitamin K2: Implications for Cardiovascular Health in the Context of Plant-Based Diets, with Applications for Prostate Health by Michael S. Donaldson
\n\nChapter 11 Vitamin K2 Facilitating Inter-Organ Cross-Talk by Jan O. Gordeladze, Håvard J. Haugen, Gaute Floer Johnsen and Mona Møller
\n\nChapter 13 Medicinal Chemistry of Vitamin K Derivatives and Metabolites by Shinya Fujii and Hiroyuki Kagechika
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