Liver Organ Injury Scale.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\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:"451",leadTitle:null,fullTitle:"Implant Dentistry - The Most Promising Discipline of Dentistry",title:"Implant Dentistry",subtitle:"The Most Promising Discipline of Dentistry",reviewType:"peer-reviewed",abstract:"Since Dr. Branemark presented the osseointegration concept with dental implants, implant dentistry has changed and improved dramatically. The use of dental implants has skyrocketed in the past thirty years. As the benefits of therapy became apparent, implant treatment earned a widespread acceptance. The need for dental implants has resulted in a rapid expansion of the market worldwide. To date, general dentists and a variety of specialists offer implants as a solution to partial and complete edentulism. Implant dentistry continues to advance with the development of new surgical and prosthodontic techniques. \nThe purpose of Implant Dentistry - The Most Promising Discipline of Dentistry is to present a comtemporary resource for dentists who want to replace missing teeth with dental implants. It is a text that integrates common threads among basic science, clinical experience and future concepts. This book consists of twenty-one chapters divided into four sections.",isbn:null,printIsbn:"978-953-307-481-8",pdfIsbn:"978-953-51-6508-8",doi:"10.5772/964",price:139,priceEur:155,priceUsd:179,slug:"implant-dentistry-the-most-promising-discipline-of-dentistry",numberOfPages:490,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"af264376cc47bfd447ff2a0c2cf1bdc7",bookSignature:"Ilser Turkyilmaz",publishedDate:"October 3rd 2011",coverURL:"https://cdn.intechopen.com/books/images_new/451.jpg",numberOfDownloads:148230,numberOfWosCitations:42,numberOfCrossrefCitations:31,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:65,numberOfDimensionsCitationsByBook:6,hasAltmetrics:0,numberOfTotalCitations:138,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 12th 2010",dateEndSecondStepPublish:"November 9th 2010",dateEndThirdStepPublish:"March 16th 2011",dateEndFourthStepPublish:"April 15th 2011",dateEndFifthStepPublish:"June 14th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"26024",title:"Prof.",name:"Ilser",middleName:null,surname:"Turkyilmaz",slug:"ilser-turkyilmaz",fullName:"Ilser Turkyilmaz",profilePictureURL:"https://mts.intechopen.com/storage/users/26024/images/1852_n.jpg",biography:"Dr. Ilser Turkyilmaz obtained his dental degree from Hacettepe University, Ankara, Turkey in 1998. Immediately after graduation, he started his PhD program in the Department of Prosthodontics, Hacettepe University. He completed that program in 2004 and kept working as an instructor in the same department. Dr. Turkyilmaz then was invited by Goteborg University, Goteborg, Sweden for research collaborations. He worked in the Department of Biomaterials, Institute of Clinical Sciences, Sahlgrenska Academy, Goteborg University, Goteborg, Sweden in 2005. He returned to Hacettepe University in the end of 2005 and then worked in private practice in Ankara from February 2006 to May 2007. He was accepted for an implant prosthodontic fellowship program in the Department of Restorative and Prosthetic Dentistry, The Ohio State University, Columbus, Ohio, and worked in that university as an implant prosthodontic fellow from June 2007 to October 2008. He took up a full-time position as an assistant professor in the Department of Prosthodontics at the University of Texas Health Science Center in San Antonio, Texas, USA on November 1, 2008. Dr. Turkyilmaz maintains a private practice in the school’s faculty practice. He treats patients with esthetic and reconstructive needs using implants, veneers, crowns, fixed partial dentures, complete dentures, and partial dentures. Dr. Turkyilmaz is particularly interested in dental implant studies regarding early/immediate loading protocols, implant stability measurements using resonance frequency analysis, bone density evaluations using computerized tomography (CT), flapless implant surgeries using CT-generated surgical guides, and the biomechanical aspects of implants. He has currently 50 scientific articles published in well-known international journals. He has also given lectures including dental implants at local, national and international meetings. He is currently serving as an editorial board member or reviewer for several international dental journals. 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",isbn:"978-1-80356-588-0",printIsbn:"978-1-80356-587-3",pdfIsbn:"978-1-80356-589-7",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"3731c009f474c6ed4293f348ca7b27ac",bookSignature:"Dr. Asghar Ali Kamboh",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11578.jpg",keywords:"Beneficial Microorganisms, Probiotic Role in Health and Immunity, Supplementation of Probiotics in Poultry, Dietary Supplementation of Yeast in Farm Animals, Gut Health, Probiotic and Mucosal Immunity, Probiotics and Intestinal Architecture, Probiotics and Nutrient Absorption, Ban of Antibiotics in Food Animals, Regulatory Issues of Antibiotic Use in Farm Animals, Alternatives to Antibiotic in Animal Production, Consequences of Antimicrobials Use in Animals",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 15th 2022",dateEndSecondStepPublish:"June 3rd 2022",dateEndThirdStepPublish:"August 2nd 2022",dateEndFourthStepPublish:"October 21st 2022",dateEndFifthStepPublish:"December 20th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"a month",secondStepPassed:!0,areRegistrationsClosed:!1,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"A well-known researcher in the area of Veterinary Sciences with a key interest in Veterinary Microbiology and immunology. 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Treatment of traumatic liver injuries is based on patient physiology, mechanism and degree of injury, associated abdominal and extra-abdominal injuries and local expertise. Non-operative management has evolved into the treatment of choice for most patients with blunt liver injuries who are hemodynamically stable and success rates for non-operative management commonly are greater than 95%. With the sweeping shift towards the non-operative management, most hepatic injuries can be treated conservatively [3, 4, 5].
\n\t\t\tMore recently several authors have highlighted an excessive use of non-operative management (NOM), which for some high grade liver injuries is pushed far beyond the reasonable limits, carrying increased morbidity at short and long term, such as bilomas, biliary fistula, early or late haemorrhage, false aneurysm, arterio-venous fistulae, haemobilia, liver abscess, and liver necrosis [5]. Incidence of complications attributed to NOM increases in concert with the grade of injury. In a series of 337 patients with liver injury grades III-V treated non-operatively, those with grade III had a complication rate of 1%, grade IV 21%, and grade V 63% [6].
\n\t\tRoad traffic accident, antisocial violent behaviours, industrial and farming accidents are the commonest mode of injury to the liver. Though the liver is protected by the rib cage, as the largest solid organ in the abdomen, the liver is particularly vulnerable to the ability of compressive abdominal blows to rupture its relatively thin capsule. The vasculature consists of wide-bore, thin-walled vessels with a high blood flow, and injury is usually associated with significant blood loss. Blunt trauma in a road traffic accident, or fall from a height, may result in a deceleration injury as the liver continues to move on impact. This leads to tears at sites of fixation to the diaphragm and abdominal wall. A well-recognised deceleration injury involves a fracture between the posterior sector (segments VI and VII) and the anterior sector (segments V and VIII) of the right lobe. This type of injury can lead to rupture of right hepatic vein and significant bleeding. In contrast, direct blow on right upper abdomen during vehicular accident or direct blow by a weapon or fist can lead to stellate type of injury to the central liver (segment IV, V and VIII). This type of injury can lead to massive bleeding from portal vein or hepatic vein and can also lead to bile duct injury.
\n\t\t\tPenetrating injuries may be associated with a significant vascular injury. For example, a stab injury may cause major bleeding from one of the three hepatic veins or the vena cava and also from the portal vein or hepatic artery if it involves the hilum. Gunshots may similarly disrupt these major vessels; this disruption may be much more marked than with stab wounds due to the cavitation effect, particularly with bullets from high-velocity weapons.
\n\t\t\tThe connection between the thin-walled hepatic veins and the inferior vena cava (IVC), at the site where the ligamentous mechanism anchors the liver to the diaphragm and posterior abdominal wall, represents a vulnerable area, particularly to shearing forces during blunt injury. Disruption here leads to the ‘‘juxtahepatic’’ venous injuries, which are usually associated with major blood loss and present a particularly challenging management problem.
\n\t\tThe severity of liver injuries ranges from the relatively inconsequential minor capsular tear to extensive disruption of both lobes with associated hepatic vein, portal vein, or vena caval injury. Several classifications have been advised to grade the liver injury and management accordingly. Following table shows the grade of liver injury. Grade I & II are successfully managed non-operatively in most cases. Grade IV and onward injuries will eventually require emergency exploration. Grade III injuries require observation and if such patients are hemodynamically stable will recover with conservative treatment. Such patients should be closely followed in ICU with serial monitoring of hemoglobin and hematocrit level along with cardio-respiratory monitoring. Any fall in hematocrit or hemodynamic instability not responding to fluid resuscitation warrants urgent exploration.
\n\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t||
\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t|
I | \n\t\t\t\t\t\tHematoma | \n\t\t\t\t\t\tSubcapsular, <10% surface area | \n\t\t\t\t\t
Laceration | \n\t\t\t\t\t\tCapsular tear, < 1 cm parenchymal depth | \n\t\t\t\t\t|
II | \n\t\t\t\t\t\tHematoma | \n\t\t\t\t\t\tSubcapsular, <10%-50% surface area; intraparenchymal, <10 cm in diameter | \n\t\t\t\t\t
Laceration | \n\t\t\t\t\t\t1-3 cm parenchymal depth, <10 in Length | \n\t\t\t\t\t|
III | \n\t\t\t\t\t\tHematoma | \n\t\t\t\t\t\tSubcapsular,>50% surface area or expanding; ruptured subcapsular or parenchymal hematoma | \n\t\t\t\t\t
Laceration | \n\t\t\t\t\t\t>3cm parenchymal depth | \n\t\t\t\t\t|
IV | \n\t\t\t\t\t\tHematoma | \n\t\t\t\t\t\tParenchymal disruption involving 25%-75% of hepatic lobe or 1-3 Couinaud segments within a single lobe | \n\t\t\t\t\t
V | \n\t\t\t\t\t\tLaceration | \n\t\t\t\t\t\tParenchymal disruption involving >75% of hepatic lobe >3 Couinaud segments within a single lobe | \n\t\t\t\t\t
Vascular | \n\t\t\t\t\t\tJuxtahepatic venous injuries; ie, retrohepatic vena cava/central major hepatic vein | \n\t\t\t\t\t|
VI | \n\t\t\t\t\t\tHepatic avulsion | \n\t\t\t\t\t
Liver Organ Injury Scale.
It is generally accepted that initial resuscitation and management is the same as for any patient with major trauma and should follow the Advanced Trauma Life Support (ATLS) principles of aggressive fluid resuscitation, guided by monitoring of central venous pressure and urinary output [7]. Management should also be directed toward avoidance of any of the sinister triad of hypothermia, coagulopathy, and acidosis, which are associated with significantly increased mortality. Mechanisms to avoid hypothermia are standard now in major centres and include the use of rewarming blankets and heat exchanger pumps for rapid infusion of resuscitation fluids and blood [8].
\n\t\t\t\tThe next management phase depends largely on the response to resuscitation and the stability of the patient. Liver injury should be suspected in all patients with blunt or penetrating thoracoabdominal trauma but particularly in shocked patients with blunt or penetrating trauma to the right side. There are two major determinants to consider when making decisions in suspected liver trauma: hemodynamic stability and mechanism of injury. In general, hemodynamic instability or peritonism makes decision-making in trauma more straightforward, although ultimately, the surgical procedure required may be complex. Management decisions are more challenging when patients are hemodynamically stable as the array of potential therapeutic modalities are substantial and the patient’s future clinical course is unknown [9].
\n\t\t\tThe appropriate evaluation and management of liver injuries results from an organized approach to abdominal trauma. Experience and technical developments over the past several decades make the current approach both logical and effective. It is generally accepted that initial resuscitation and management is the same as for any patient with major trauma and should follow the Advanced Trauma Life Support (ATLS) principles of aggressive fluid resuscitation, guided by monitoring of central venous pressure and urinary output [7]. Management should also be directed toward avoidance of any of the sinister triad of hypothermia, coagulopathy, and acidosis, which are associated with significantly increased mortality.
\n\t\t\tUltrasonography (USG) is the most important and readily available investigation for any patient with blunt or sharp abdominal injury. It is particularly useful for detecting injury to parenchymal organs and the presence of free intraperitoneal fluid or blood. USG is a quick, non-invasive, inexpensive, and transportable tool, used with increasing frequency in the initial workup of patients with abdominal trauma [10].
\n\t\t\t\tThe particular relevance to major liver injury is the focused assessment by ultrasound for trauma (FAST), often performed in the emergency department, which involves a rapid examination of several areas, namely, the pericardial region, right upper quadrant (including Morrison’s pouch), left upper quadrant, and the pelvis, specifically looking for free fluid. One of the main limitations of USG is that parenchymal injuries, sometimes relevant and requiring surgical or embolization therapy, may be present without combined peritoneal fluid [11,12].
\n\t\t\t\tOn the basis of detection of free fluid or parenchymal injury, the sensitivity of USG has been found to be 72% to 95% for abdominal organ injuries, 51% to 92% for liver lesions, and 98% for grade III or higher liver injuries [13]. Richards et al reported 56% and 68% sensitivity of FAST and complete USG, respectively, in detecting childhood abdominal trauma [11].
\n\t\t\t\tDetection of peritoneal fluid is the first step in FAST. Fluid in the right upper quadrant or in the right upper quadrant and pelvic recess suggests hepatic injury, as opposed to splenic, renal, or enteric injury [14]. Fluid limited to the left upper quadrant or to both upper quadrants is not seen in patients with isolated liver trauma [14]. Hemoperitoneum recognition must prompt further imaging, but its absence does not definitely exclude parenchymal injury. Clinical assessment and observation are also relevant in combination with USG. With special reference to liver trauma, it has been noted that patients with negative USG results but with an aspartate aminotransferase level of greater than 360 IU/L should undergo CT imaging because of potentially overlooked hepatic injury, whereas patients with normal levels can be effectively discharged [15].
\n\t\t\t\tAlthough FAST provides a rapid assessment of liver disruption and intraperitoneal bleeding, it is a limited scan that is highly operator dependent. It is very important to note that a negative FAST scan does not safely rule out injury [12, 16]. Due to the operator dependence of the modality, different end points, and inconsistent comparative gold standards in the studies, the reported specificities, sensitivities, and overall accuracies are variable [17]. It has been demonstrated that up to a quarter of hepatic and splenic injuries, as well as renal, bladder, pancreatic, mesenteric, and gut injuries, can be missed if ultrasound is used as the primary investigative modality in the stable patient. However, while the possibility of false negatives is ever present, the combination of a negative ultrasound scan and normal clinical examination and observations almost excludes liver injury in the event of significant blunt trauma [12, 18].
\n\t\t\tThe wide availability of high-resolution CT has changed the manner in which blunt abdominal trauma is diagnosed and managed (figure 1). Currently, multi-detector computed tomography (MDCT) scanning with intravenous contrast is the gold standard diagnostic modality in hemodynamically stable patients with intra-abdominal fluid detected with FAST.
\n\t\t\t\tCT has a sensitivity of 92% to 97% and a specificity of 98.7% for detection of liver injury. The type and grade of liver injury, the volume of hemoperitoneum, and differentiation between clotted blood and active bleeding can be identified. In addition to increasing the rate of detection of liver lesions following trauma, CT has also helped to improve the understanding of the course of liver injuries [19]. CT scan also allows diagnosis of associated intraperitoneal and retroperitoneal injuries, including splenic, renal, bowel, and chest trauma, and pelvic fractures.
\n\t\t\t\tEven though NOM has proven to be of tremendous benefit, a couple of controversies regarding the current management of trauma patients should be discussed. Advances in CT technology have improved the practitioner’s ability to determine the degree of injury and to identify patients who are more likely to fail NOM. However, until now, MDCT scanning has not been able to differentiate, in a precise manner, among which patients should be treated conservatively, which would benefit from angio-embolization and which would respond best to a surgical response.
\n\t\t\t\tCT scan images of blunt abdominal trauma patients. (A) CT scan of liver showing intraparenchymal hematoma in segment VI. (B) CT scan of liver showing intraparenchymal hematoma in segment VI and extending to segment VII and V.
Although CT is the investigative gold standard, it is important to remember that it involves exposure to high levels of ionising radiation and the use of intravenous contrast may compromise renal function. In the majority of hospitals the use of CT requires movement of the patient away from adequate resuscitation facilities to the X-ray department, highlighting the importance of hemodynamic stability in patients with abdominal trauma being considered for CT examination [16].
\n\t\t\tThe use of laparoscopy for trauma patients has been slower to evolve partly due to factors inherent in the trauma population and some limitations of the laparoscopic technique. Initially, the evaluation of peritoneal violation in hemodynamically stable patients was seen as the greatest benefit of laparoscopy for trauma [20]. Improvements in laparoscopic training and technology have enabled an increase in the use of diagnostic and therapeutic procedures in trauma patients.
\n\t\t\t\tAlgorithm - Advanced trauma life support, FAST- focused assessment by ultrasound for trauma. ATLS for managing liver trauma patients.
There are a number of series describing the successful haemostasis of minor liver injuries, in both the civilian [21] and military setting [22], although it is likely that these were self-limiting injuries anyway.
\n\t\t\tThere are two major determinants to consider when making decisions in suspected liver trauma: hemodynamic stability and mechanism of injury. In general, hemodynamic instability or peritonism makes decision-making in trauma more straightforward, although ultimately, the surgical procedure required may be complex (figure 2). Management decisions are more challenging when patients are hemodynamically stable as the array of potential therapeutic modalities are substantial and the patient’s future clinical course is unknown [9].
\n\t\t\t\n\t\t\tHogarth Pringle, in 1908, provided the first description of operative management of liver trauma. Unfortunately, all eight patients died and Pringle recommended conservative non-operative management of these patients. In the modern surgical literature, non-operative management was first reported in 1972 and has been one of the most significant changes in the treatment of liver injuries over the last two decades [23, 24].
\n\t\t\t\tInitiated in pediatric trauma patients [25], nonsurgical management of blunt liver trauma has become recognized as an appropriate treatment option for hemodynamically stable adult patients with blunt hepatic injury [26, 27].
\n\t\t\t\tWith the wide availability and improved quality of CT scanning, and the more modern, less invasive intervention options, such as angio-embolization, NOM has evolved into the treatment of choice for hemodynamically stable patients. Although angio-embolization has been defined the logical augmentation of damage control techniques for controlling hemorrhage, the overall liver-related complication rate can be as high as 60.6% with 42.2% incidence of major hepatic necrosis [28]. Non-operative management (NOM) consists of close observation of the patient completed with angio-embolization, if necessary. Observational management involves admission to a unit and the monitoring of vital signs, with strict bed rest, frequent monitoring of hemoglobin concentration and serial abdominal examinations [29].
\n\t\t\t\tFollowing factors contribute to conservative management of liver trauma:
\n\t\t\t\tRealization that more than 50% of liver injuries stop bleeding spontaneously at the time of exploration
Availability of CT scan imaging for better assessment of grade of liver injury and associated injuries
The success of non-operative management in paediatric patients
Knowledge that the liver has tremendous capacity of healing after injury,
Improved critical care management in specialized unit
The introduction of angio-embolization which allows patients with specific CT findings to potentially be treated in a minimally invasive manner.
Given the availability of angio-embolization, trauma surgeons are more likely to initiate non-operative treatment, even in higher grade injuries, because, in the event of failure, intervention in the form of angio-embolization is possible and, in the event of angio-embolization failure, surgical intervention is possible. Criteria for non-operative management include foremost, hemodynamic stability, absence of other abdominal injuries that require laparotomy, immediate availability of resources including a fully staffed operating room, and a vigilant surgeon. While non-operative management was initially introduced for minor injuries, it was soon in vogue for more severe injuries (grades III–V) [6, 30]. Close observation and repeated scans are usually recommended to document non-expansion of hematoma and healing of the injuries over time. The shift towards non-operative management of liver injuries has resulted in a lower mortality rate, but still a significant percentage of complications [31]. The current reported success rate of non-operative management of hepatic trauma ranges from 82% to 100%. Twenty-five percent of patients with blunt hepatic injury managed non-operatively, 92% of whom have grade IV or V injury will require an intervention for complications [5].
\n\t\t\t\tDespite the reduction of mortality that has been achieved using angio-embolization, some studies describe a rise in severe but treatable complications such as hepatic necrosis, abscesses or bile leakage [6, 28]. Gallbladder ischemia, hepatic parenchymal necrosis and biloma may also occur, and in patients with a high grade liver injury (grade 4 and 5) the incidence of complications can be high [32].
\n\t\t\t\tA determinant of the success of NOM is the level of cooperation between different specialists in the hospital. Good teamwork among the trauma surgeon, the anaesthesiologist and the interventional radiologist leads to a quicker understanding of the underlying injuries and thus shortens the time between entering the hospital and the initiation of therapeutic interventions. This seems obvious in level 1 trauma centers, but can be a matter of concern, especially in level II or III trauma centers.
\n\t\t\t\tWhile there has been considerable debate about the grade of liver injury and the acceptable volume of hemoperitoneum, it is now generally accepted that the ultimate decisive factor in favour of non-operative management is the hemodynamic stability of the patient, irrespective of the grade of injury or the volume of hemoperitoneum. It is also essential that appropriate clinical and radiological follow-up is arranged [33].
\n\t\t\t\tThe rate of liver-related complications is low, and generally ranges from 0% to 7% [31]. Liver-related complication rates in high-grade liver injury patients are 11-13% and can be predicted by the grade of liver injury and the volume of packed red blood cells transfused at 24 hours post-injury [6, 34]. Incidence of complications attributed to NOM increases in concert with the grade of injury. In a series of 337 patients with liver injury grades III-V treated non-operatively, those with grade III had a complication rate of 1%, grade IV 21%, and grade V 63% [6]. Patients with grades IV and V injuries are more likely to require operation, and to have complications of non-operative treatment. Therefore, although it is not essential to perform liver resection at the first laparotomy, if bleeding has been effectively controlled, increasing evidence suggests that liver resection should be considered as a surgical option in patients with complex liver injury, as an initial or delayed strategy, which can be accomplished with low mortality and liver related morbidity in experienced hands [3].
\n\t\t\t\tSome of the complications related to conservative management of liver injuries are bile leaks, liver abscess, delayed haemorrhage, false aneurysm, arterio-venous fistulae, haemobilia, liver and gall bladder necrosis. Carrillo described complications in up to 85% of patients with a high (≥4) Abbreviated Injury Score (AIS) in a series of 32 patients who were treated non-operatively [27].
\n\t\t\t\tHigh grade liver injury (>3) treated with NOM and angio-embolization may be associated with severe complications like liver necrosis, bile leaks and severe sepsis. Mortality has been noted in up to 11% of patients in high grade liver injury treated conservatively [35]. Although angio-embolization has been defined the logical augmentation of damage control techniques for controlling hemorrhage, the overall liver-related complication rate can be as high as 60.6% with 42.2% incidence of major hepatic necrosis [28]. Early liver lobectomy in such cases required lesser number of procedures and achieved lower complication rate and lower mortality compared to less aggressive approaches such as serial operative debridements and/or percutaneous drainage [36].
\n\t\t\tTAE of blunt hepatic injury was first recognized as a safe and effective treatment for the control of recurrent postoperative hemorrhage, hemobilia and hepatic artery-portal vein fistulas in the late 1970s [37]. Hashimoto et al. [38] also showed the efficacy of emergency TAE in four patients with severe complex hepatic injury and suggested that this method may be useful in nonsurgical management of unstable patients with severe hepatic injury. This multidisciplinary approach to the management of complex hepatic injuries is becoming much more important as the role of interventional radiology expands. Denton et al. [39] reported successful use of a combination of arterial embolization and transhepatic venous stenting in the management of a grade V injury involving the retrohepatic vena cava in a patient whose injury had been temporarily controlled by perihepatic packing. Recent more extensive series of angiography for control of hepatic haemorrhage have reported increasing success, with identification and control of bleeding rates ranging from 68 to 87%. [40] Angiography and embolization or stenting is a very useful adjunctive technique in the stable patient who is being managed non-operatively or in the patient who either has been stabilised by perihepatic packing or has re-bled after a period of initial stability.
\n\t\t\t\tThe recent literature reveals that the increased use of angio-embolization and decreased mortality rates result in increased frequencies of severe complications, such as liver necrosis, bile leakage and intra-abdominal abscesses [28, 32, 41]. Indications of angiography in hemodynamically stable patients are high grade liver injury in CT scan, evidence of arterial vascular injury, and the presence of hepatic venous injury [41]. Angio-embolization can be used immediately after a damage control laparotomy as part of the primary haemorrhage control strategy [42]. Alternatively, angio-embolization can be used in post-operative patients to manage ongoing bleeding not associated with hemodynamic compromise [32]. This can involve not only angio-embolization, but also the placement of stents to reconstruct vasculature [39].
\n\t\t\tBile leaks are a frequent complication in the non-operative management of liver injuries, occurring in 6% to 20% of cases. Bile leaks present either as trauma, drainage of bile through surgically placed drain, or percutaneously placed catheter to drain biloma. The time of presentation of biliary leaks is variable. Ultrasound and CT scan are used to diagnose a biloma, whereas a hepatobiliary iminodiacetic acid scan is used to show an active bile leak.
\n\t\t\t\t\tMajority of bile leaks can be treated by ultrasound or CT-guided percutaneous drainage or ERCP and stenting.
\n\t\t\t\tThe prevalence of delayed haemorrhage following non-operative management of blunt liver injury ranges from 1.7 to 5.9% [27, 43]. The mechanism of delayed hemorrhage may be related to an expanding injury or to a pseudoaneurysm induced by a biloma which eventually causes an expanding hematoma and free rupture into the peritoneal cavity. Early bleeding episodes are attributed directly to the traumatic insult, while late hemorrhage is probably related to infectious hepatic complications. Angio-embolization may prove an useful technique to deal with such complications.
\n\t\t\t\tPatients with associated liver and spleen injuries are twice as likely to fail non-operative therapy as those with only a single organ injured [44]. Missing associated intra-abdominal injury and delayed treatment, significantly affects the outcome. This occurs more often in conjunction with liver than with splenic injury, especially pancreas and bowel injury are significantly associated with liver injury in blunt trauma.
\n\t\t\t\tPatients with high grade liver injury who are hemodynamically unstable require surgical management. Failure of NOM also requires urgent exploration and appropriate surgical management.
\n\t\t\t\tAnesthesia must ensure that blood products are already in the room. The massive transfusion protocol should be activated so that the blood bank is always ahead of the patient’s needs for packed red blood cells, fresh frozen plasma, platelets, and cryoprecipitate. Adequate vascular access and arterial blood pressure monitoring are essential. It is important to preferentially have venous access above the diaphragm. Resuscitation fluids infused under pressure through femoral access will exacerbate hepatic venous bleeding, at times dramatically so. Massive transfusion protocols should be activated early to prevent any delay in resuscitation with blood products.
\n\t\t\t\tThe most widely adopted incision for the patient with liver trauma is a long midline laparotomy, which can be extended to the right chest if a posterior right lobe injury, major hepatic venous injury, or vena caval injury is encountered. An effective alternative, which gives good exposure and avoids a thoracotomy, is a right subcostal extension. A bilateral subcostal incision is sometimes favoured by hepatobiliary surgeons if there is an obvious penetrating through-and-through liver injury. This allows excellent exposure of the right lobe of the liver, the hepatic veins, and vena cava without having to open the chest or diaphragm; however, it does compromise access to the lower abdomen.
\n\t\t\t\tIf a major liver injury is encountered, immediate control of bleeding is an absolute priority because the greatest threat to the patient’s life at this juncture is exsanguination. Liver should immediately be manually closed and compressed. Patients with massive hemoperitoneum are at risk of coagulopathy, hypothermia and acidosis. Measures should be taken to prevent and treat all these consequences of massive bleeding. If this still does not control the bleeding, pedicle occlusion (Pringle manoeuvre) should be applied using an atraumatic vascular clamp or non-crushing bowel clamp. If bleeding stops after Pringle manoeuvre, the bleeding is from branches of portal vein or hepatic artery. If bleeding continuous after this manoeuvre, the bleeding is likely to be from hepatic vein or IVC. The time of Pringle manoeuvre is controversial, but it can be applied up to 1 hour without compromising the blood supply to the liver.
\n\t\t\t\tThe concept of damage control was introduced by Stone et al [45] in the 1980s and promulgated by the group at Ben Taub in 1992 [46]. This came after the report by Denver General in patients sustaining fatal hepatic hemorrhage.
\n\t\t\t\t\tAfter trauma, hemostasis was not possible as patients were hypothermic, acidotic, and receiving large volumes of packed red cells before blood component or fresh blood [47]. This led to the concept of the “bloody vicious cycle.” The term “damage control” was popularized by the group at the University of Pennsylvania in the 1993 [48]. They described initial control of haemorrhage and contamination followed by packing and temporary abdominal closure, ICU restoration of normal physiology, and delayed definitive repair of intra-abdominal injuries. The decision for damage control should be made very early in the operation before the onset of severe coagulopathy, acidosis, and hypothermia. Early institution of packing as a damage control technique has been shown to lessen mortality [49].
\n\t\t\t\t\tThe damage control concept is very appropriate for the management of major liver injuries. The three key factors that interact to produce a deteriorating metabolic situation are hypothermia, coagulopathy, and acidosis. Patients in this condition are at the limit of their physiological reserve and persistence with prolonged and complex surgical repair attempts will cause exceptionally high mortality [50]. Early recognition of hypo-thermia, coagulopathy, and acidosis is the key to the damage control approach. It is recommended that definitive surgery should cease and a damage control approach be adopted when hypothermia is deteriorating or a temperature of 34oC is reached, when coagulopathy has developed (nonsurgical oozing or prothrombin time greater than 50% above normal), or when acidosis exists (pH<7.2 despite adequate volume resuscitation).
\n\t\t\t\t\tOnce the patient is stabilized, patient is returned to the operation theatre and definitive surgery is undertaken if needed.
\n\t\t\t\tTamponade which is achieved by manual compression that can then be maintained by packs, which can also be manually compressed if bleeding continues. Packs placed in an anterio-posterior axis will often distract the injured liver further and worsen the bleeding. The lobes of the liver must be compressed back to normal position, essentially back toward midline. Simultaneously, the liver is pushed toward the diaphragm. Maintenance of this anatomic compression by the first or second assistant is critical to reduce bleeding as the surgeon assesses the liver injury or mobilizes the liver. Perihepatic packing can help to maintain this tamponade. Most minor venous bleeding and small lacerations to the parenchyma can be temporized by this manoeuvre. Haemostatic agents such as surgicell, thrombin-soaked gel foam, or fibrin glue are useful adjuncts.
\n\t\t\t\t\tPacking is not as effective for the injuries to the left hemiliver, because with the abdomen open, there is insufficient abdominal and thoracic wall anterior to the left hemiliver to provide adequate compression. Fortunately, haemorrhage from the left hemiliver can be controlled by dividing the left triangular and left coronary ligaments and compressing the left hemiliver between the hands.
\n\t\t\t\t\tPacks must be placed around the liver to reconstitute its anatomical shape. Packs should never be inserted into the hepatic wound, as it will tear the vessels and will increase the bleeding. It is also important to avoid excessive packing, as compression of IVC can lead to resultant decreased venous return, and reduces left ventricular filling. Excessive packing can also lead to compartment syndrome and multi-organ failure [51]. Conversely under-packing is associated with increased transfusion requirements and unplanned re-look laparotomies [52]. To reduce the risk of abdominal compartment syndrome, some advocate closing the upper part of the wound to enhance the tamponade effect but leaving the lower two-thirds open and temporarily covered with a silastic sheet sutured to the skin edges [53, 54].
\n\t\t\t\t\tPerihepatic packing will control profuse haemorrhage in up to 80% of patients undergoing laparotomy and will allow intraoperative resuscitation (resuscitative packing) [50, 55]. In the management of severe injuries of the liver, packing has emerged as the key to effective damage control [56]. However, more definitive ‘‘therapeutic’’ packing is also a very effective technique, particularly when used judiciously to prevent the cascade of hypothermia, coagulopathy, and acidosis [57].
\n\t\t\t\t\tOnce the patient is stabilized, temporary closure of the abdomen is done and patient is shifted to the ICU. Packs can be removed after 36-48 hours. Broad spectrum antibiotics should be started to prevent sepsis. The exact timing of the removal of packs is controversial, but they should not be removed before 24 hours as this is related to re-bleeding and leaving them in place for 24 hours or more does improve outcome [58]. Even delayed removal (up to 1 week) has been reported without increasing the morbidity [59]. During removal, the packs should gently be removed after soaking with saline. Liver should be checked for re- bleeding and if adequate hemostasis is achieved, closure of the abdomen can be done after putting a drain.
\n\t\t\t\tThis is an older technique which involves passing deep parenchymal sutures to bring disrupted tissue together compressing bleeding vessels and reducing dead space. The major drawback of this procedure is ischemic necrosis and infection of the liver parenchyma. However, some advocate hepatorrhaphy for “hard-to-reach” areas such as the dome and posterior portion of the right lobe.
\n\t\t\t\t\tMesh-wrapping is a quick and technically feasible method to achieve definitive hemostasis in severe liver trauma. It can be combined ideally with conventional procedures. Mesh-wrapping technique provides a highly selective, tight compression confined to the liver and does not produce an increased intra-abdominal pressure. Emphasis should be given in two important technical aspects while mesh wrapping. First, the traumatized liver has to be slung with the mesh under enough tension to create a tamponade effect. In addition the mesh should be attached into two anchoring stable points. The diaphragmatic crus and the falciform ligament provide the best options to stabilize the mesh. The mesh is resorbable and therefore reoperation for removal is not necessary. Furthermore, the resulting product of mesh hydrolysis has a bacteriostatic effect, minimizing the risk of infection [60].
\n\t\t\t\t\tCombined hepatotomy and selective vascular ligation has emerged as the preferred method of management for major hepatic venous, portal venous, and arterial injuries in many centres [61]. For control of major vascular injuries, Pachter et al. recommend a rapid and extensive finger fracture, often through normal parenchyma, to reach the site of injury. However, it is important to emphasise that with a major hepatic venous injury, significant haemorrhage may occur while attempting to extend a deep liver laceration and that this bleeding will not be controlled by a Pringle clamp and increased morbidity may be incurred. Hepatotomy is done under Pringle manoeuvre and finger fracture method is used to divide the parenchyma to ligate the bleeding vessels. Pringle clamp is released intermittently to identify bleeding vessels.
\n\t\t\t\tThis refers to removal of devitalised parenchyma using the line of injury as the boundary of the resection rather than standard anatomical planes [62]. Resectional debridement is indicated for peripheral portion of nonviable hepatic parenchyma. Debridement is rarely a technique practised in isolation and is frequently used in conjunction with inflow control and hepatotomy. This allows for haemorrhage control prior to resection of all devitalised tissue while usually involves crossing traditional anatomical boundaries hence the term “non-anatomical resection”. All devitalized tissues should be removed without making any attempt to resect normal parenchyma. Operative time should be as short as possible.
\n\t\t\t\t\tExcept in rare circumstances, the amount of tissue removed should not be more than 25% of the liver. In some cases simple completion of an extensive parenchymal avulsion may suffice, e.g., when there has been an avulsion of the posterior sector of the right lobe (segments VI and VII). This type of injury is often associated with a right hepatic vein laceration and completion of the ‘‘resection’’ will allow control and suture of this. In such situations, vascular stapling devices are extremely useful for rapid and secure division of major veins.
\n\t\t\t\tThe final alternative for patients with extensive injury to one hemiliver is anatomic hepatic resection. In elective circumstances, anatomic hemi-hepatectomies can be performed with excellent results; however, in the setting of trauma, the mortality associated with this procedure exceeds 50% in most series [63, 64]. This, plus the fact that the time and magnitude of the surgery goes against the later principles of conservative surgery and damage control, has resulted in anatomical resection being practised rarely and it is now performed in only approximately 2–4% major liver trauma cases [51].
\n\t\t\t\t\tHepatic resection for an injured segment of the liver definitively controls bleeding, potential bile leak, and removes devitalized tissue. However, the role of hepatic resection in the management of liver injury remains controversial. The traditional poor results and lack of enthusiasm for this technique have been contradicted by the results of some recent series particularly that from Strong et al. who achieved excellent results in a series of 37 patients, 11 of whom (33%) had grade V juxtahepatic venous injuries [61]. These results probably reflect the fact that this procedure was performed in a specialist liver resection and transplantation unit, and while the majority of liver injuries continue to be managed initially in trauma centres or district hospitals, it is likely that more conservative and damage control procedures will remain the most widely practised techniques.
\n\t\t\t\tIntrahepatic balloon tamponade is useful for transhepatic penetrating injury. A device can either be fashioned from a Foley catheter and Penrose drain [65] or a Sengstaken-Blakemore tube. The device is gently delivered into the length of the tract and then inflated, often with a radio-opaque contrast fluid so integrity and position can be later confirmed radiologically if required. Once the patient is stabilized and coagulation and acidosis is corrected, the balloon can be deflated and removed during re-laparotomy.
\n\t\t\t\tTotal vascular exclusion of liver is sometimes used for extensive retrohepatic venous injuries. The technique involves clamping of the portal triad and infra- and supra-hepatic IVC and therefore requires experience with mobilisation of the liver as done in liver resection and transplantation. Excellent results were reported for this technique by Khaneja et al. [66] who used it to manage grade V penetrating injuries with 90% of patients surviving the operation and an overall survival rate of 70%.
\n\t\t\t\t\tThe major drawback of this technique is decreased venous return due to clamping of IVC. This will lead to further hypotension in patient who is already in hypothermia and hypotension. This procedure can only be feasible in experienced hand in high volume centres.
\n\t\t\t\tThis remains a therapy of last resort limited to specialist centres with the literature limited to occasional case reports and series [67]. While liver transplantation may be life-saving for major liver trauma, the logistical problems will mean that it remains a limited option, available only in specialist centres.
\n\t\t\t\tOverall mortality for patients with hepatic injuries is approximately 10%. The most common cause of death is exsanguination, followed by MODS and intracranial haemorrhage. Liver trauma is a morbid injury with complication rates from recent series ranges from between 8.1% to 30% [68].
\n\t\t\tPrimary exsanguinating haemorrhage is a major source of mortality, but most studies report secondary haemorrhage occurring in 3- 6% of survivors with no significant difference between blunt and penetrating mechanisms [69]. Surgical haemorrhage (ie discrete bleeding) and disseminated intravascular coagulation account for the majority of causes in even proportions. In patients managed by peri-hepatic packing, patients who had packs removed at <36hrs had more episodes of haemorrhage requiring re-packing than those with removal between 36 hours and 72 hours.
\n\t\t\t\tIn most instances of persistent postoperative haemorrhage, the patient is best served by being returned to the operation room. Angiography with embolization may be considered in selected patients. If the reason for haemorrhage is coagulopathy, it should be corrected first and then patients should be reassessed.
\n\t\t\tPost-operative sepsis occurs in 12-32% of patients. Minor morbidity occurs with urinary tract, surgical wound and respiratory tract sepsis. More serious are intra-abdominal abscesses which occur in up 24% of patients and are associated with concomitant bowel injury, higher grades of liver injury (IV and V) and massive transfusion [70].
\n\t\t\t\tAn abdominal CT with intravenous and oral contrast should be performed to diagnose the cause of sepsis. Majority of the abscesses can be drained percutaneously under USG or CT-guidance; however, infected hematoma and infected necrotic liver tissue cannot be expected to respond to percutaneous drainage. Operative drainage may be a better option in such type of patients.
\n\t\t\tBilomas are loculated collection of bile, which is with or without infection. CT-guided percutaneous drainage is the best option for infected bilomas. If the biloma is sterile, it will eventually be resorbed. Biliary ascites is caused by disruption of major bile duct. Reoperation after the establishment of appropriate drainage is the prudent course.
\n\t\t\t\tBiliary fistulas occur in approximately 3% of the patients with major liver injury [71]. They are usually of little consequences and generally close without specific treatment.
\n\t\t\tExtrahepatic bile ducts are rarely injured during blunt or penetrating abdominal injuries [72, 73]. Diagnosis is usually made during surgery or sometimes postoperatively. Management of bile duct injury detected postoperatively has already been described. If laparotomy is performed for patient with trauma, collection of bile in to the right upper quadrant suggest major bile duct injury. Sometimes it is very difficult to detect the site of bile duct injury, as associated disruption of liver parenchyma and haemorrhage makes detection a challenging task.
\n\t\t\tManagement of bile duct injury is further complicated by small calibre and thin wall of the bile duct. Bile duct injury ranges from small laceration to tissue loss or complete disruption. Primary repair may be attempted when there is small laceration and no tissue loss. When there is a tissue loss or the laceration is larger than 25% to 50% of the diameter of the duct, the treatment option is a Roux-en-Y choledocho-jejunostomy [74, 75]. Isolated injury to left or right hepatic duct is even more challenging and should only be managed by experienced hepatobiliary surgeon. If expertise is not available, large bore tube should be kept and patient should be transferred to higher centre. If both the ducts are injured, both the ducts should be intubated by separate tubes and brought out. Elective repair should be undertaken once the patient is stable and after adequate assessment of injury by cholangiogram.
\n\t\t\tInjury to the gall bladder is treated either by repair or cholecystectomy.
\n\t\tThe management of injuries of the liver has evolved significantly throughout the last two decades. Non-operative techniques for the management of grade IV–V injuries in stable patients have been established, although there is a higher failure rate for these injuries compared with grade I–III injuries. Because of the progress that has been made in the quality and wide availability of the MDCT scan combined with minimally invasive intervention options like angio-embolization, NOM has evolved to be the treatment of choice for hemodynamically stable patients. In terms of surgical management there has been a definite move away from major, time-consuming procedures toward conservative surgery and damage control. The preferred surgical technique for inaccessible bleeding within a laceration is rapid finger fracture hepatotomy, Kelly –crush hepatic transection and direct suture or ligation. Prolonged attempts at surgical control and repair should be avoided, and definitive perihepatic packing should be employed at an early stage in the persistently unstable patient or at the first signs of coagulopathy. Formal anatomical resection carries a high morbidity when used for haemorrhage control, although in an experienced centre this may be appropriate. Hepatorrhaphy has become discouraged due to complications of sepsis and bleeding, but may be a useful technique in penetrating trauma where the liver is difficult to access.
\n\t\tUnlike animals, plants do not have the ability to move, making them vulnerable to attack by pests and sometimes animals. To overcome this problem, plant tissues synthesize enormous compounds, such as terpenes, polyphenols, cardenolides, steroids, alkaloids, and glycosides, and use them as defense strategies [1]. These defense compounds are called secondary metabolites and are not necessary for essential plant functions, such as growth, photosynthesis, and reproduction. These compounds are accumulated in the plant body to use by man as pharmaceutical, agrochemicals, aromatics, and food additives [1, 2]. Despite the progress in synthetic chemistry, plants are considered the most successful sources of drugs due to their bioactive compounds produced through secondary metabolism pathways [2].
In industrialized and developing countries, raw plant materials and plant-derived pharmaceuticals have naturally an essential component of present-day human healthcare systems. A known fact is that over 80% of the human beans use herbal medicines for healthy living [3]. In this respect, at present, more than 40% of the used pharmaceuticals by Western countries are derivatives of natural resources [4]. Worldwide, man uses about 35000–70000 plant species to prevent and cure diseases, most of them are reported in China (10,000–11,250), India (7500), Mexico (2237), and others [5]. Quality assurance and standardization of herbal medicines during the collection, handling, processing, and production of herbal medicine are essential prerequisites to ensure safety for the global herbal market. Wild plant materials are collected from gardens, open pasture, or forest land. In some cases, medicinal plants grow like weeds on agricultural land. While the bulk of the medicinal plant materials is still wild-harvested, a very small number of plant species are cultivated commercially [6]. However, increase populations and urban growth were associated with an over-exploitation of natural resources. Unfortunately, several medicinal plant species are disappeared due to the expansion of land for the purpose of growing crops, urban expansion, uncontrolled deforestation, and intensive collection [7]. Now, the increase in demand for these compounds encouraged the cultivation of large areas of medicinal plants and the application of new technologies, such as plant tissue culture (PTC) to preserve them from extinction and improve their productivity in quality and quantity.
Manufacturing of medicinal products from soil-grown plants faces some challenges, such as: (1) The wild-targeted plant does not exist in sufficient abundance in the local environment or is rare in general, (2) Cultivation of the target plant may need certain conditions, (3) Production of the target substance may require to grow plants for a long time, (4) The target substance may present at low concentration in cultivated or harvested plants, (5) Variations in environmental conditions may result in the production of bioactive compounds at a non-homogeneous quantity or quality, (6) Collection of plants for pharmaceuticals may be unsafe, (7) Harvest of propagated medicinal plants for drug industries is time- and money-consuming [8]. To overcome all the obstacles, PTC techniques express the great potential for bioproduction of phytoconstituents of high therapeutic value. By application of artificial techniques, regulation of the biosynthetic pathway of the certain plant to enhance the production of valuable compounds or avoidance of production of an unwanted substance become possible.
With the aid of gene technology and molecular techniques,
Application of PTC technologies in the medicinal plant does not free from problems but avoiding their problems can be precisely controlled, which makes
Through PTC techniques, a whole plant can be regenerated from an organ, small tissue, or a plant cell but it should carry out on a suitable culture medium and under a controlled environment [15]. Under these conditions, the obtained plantlets are true to type and show characteristics identical to the mother plant. On the other hand, the culture conditions can be controlled to stimulate genetic variation for plant improvement, but it requires the construction of a selection procedure to select an elite mutant. For several decades,
The application of PTC techniques in the medicinal and other plant species becomes an essential prerequisite for plant propagation and improvement [15, 17]. The application of plant tissue culture has several advantages: (1) It results in the production of thousands of plantlets in a short period from a small segment of the tested plant. (2) It is a main procedure to obtain pathogen-free plants. (3) It can be used to culture plants round the year, irrespective of weather or season. (4) It needs little space for the propagation of the southlands of plants. (5) It can be used as the main procedure to produce a new cultivar of a certain plant. (6) It can be used to understand the effect of a specific biotic or abiotic factor on a tested plant beyond the interaction of other factors. (7) It helps to understand the molecular biology of plant differentiation. (8) It is an essential prerequisite during the production of genetically engineered plants. (9) It is an effective procedure for the production of pharmaceutical compounds. (10) It is an essential procedure for the preservation of endangered plant species, genetic assets, and gene banks.
Phytotherapy becomes a complementary and important part of pharmacotherapy and modern medicine. It is a type of treatment based on natural medicinal resources (drugs) and herbal remedies for the purposes of prevention and treatment of illness. Herbal drugs mean using the whole plant or part of it, fresh or dry, to treat or prevent human disease. Any plant part (flower, leaf, root, bark, fruit, and seed), resins, balsams, rubber, plant exudates, algae, fungi, or lichen can be used as herbal drugs for its medicinal properties. Herbal drugs or herbal remedies contain active ingredients of herbal medicinal products. The aerial plant parts, such as leaves, seeds, and flowers, are often able to synthesize and accumulate secondary metabolites more than those obtained by underground parts, such as roots or rhizomes [19]. For example, in
Based on their biosynthetic origins, reports classify the bioactive secondary metabolites of the plant into major groups, including phenolic compounds, terpenoids, nitrogen-containing alkaloids, and sulfur-containing compounds [21]. Phenolic compounds were the most important group where they are largely used to enhance human health and they naturally occur in fruits, vegetables, cereals, and beverages. Phenols are classified into different groups, including phenolic acids, flavonoids, stilbenes, and lignans, and they include apigenin, diosmin, quercetin, kaempferol, eriodictyol, naringenin, hesperetin, baicalein, chrysin, catechin, morin, genistein, curcumin, colchicine, resveratrol, and emodin. For the production and extraction of hundreds of these secondary products, plant cell, tissue, or organ cultures were used [21].
As a part of complementary and alternative medicine, medicinal plant extracts are widely used in chronic diseases like diabetes, hypertension, cancer, etc. Melatonin and serotonin, as antioxidants, were detected in the field and greenhouse-grown
Screening of 346 methanol extracts of 281 native and cultivated plant species in Egypt indicated that
Plant tissue culture is the most promising savior of medicinal plants that face problems of low yield and susceptibility to biotic or abiotic stress. Also, PTC can be used for
High multiplication using seedling tissues or shoot meristems was achieved in several plant species, such as
For long-term storage of medicinal plant materials, cryopreservation is recommended where it is carried out in liquid nitrogen (−196°C). Different plant organs or parts, including seeds, corms, bulbs, rhizomes, roots, tubers, buds, and cuttings, can be stored for conservation purposes [11], especially in medicinal plants with recalcitrant seeds. The main applied techniques of cryopreservation of medicinal plants are vitrification, desiccation, and encapsulation–dehydration. Vitrification-cryopreservation of shoot tips of
PTC is more efficient than naturally grown plant materials to assess the effect of different experimental conditions on the production of secondary metabolites of medicinal plants [55]. PTC opens the way for the production of engineered molecules and produces new forms of plant secondary metabolites [56]. These new forms of compounds may have a valuable effect on biological control, food, pharmaceutical, and other strategies. Transformation techniques are widely dependent on PTC for enhancing the
Different types of PTC techniques are successfully exploited for
The synthetic capacity of secondary metabolites of the dedifferentiated tissue often differs substantially from that of differentiated one, both quantitatively and qualitatively. The differences in synthetic capacities are a direct response to differences in enzyme patterns between differentiated and undifferentiated tissues, they are mirrors for gene expression of these tissues. The culture of differentiated plant materials often shows biochemical and genetic stability, it offers a high-productivity system that does not need wide-ranging optimization. For example, the major alkaloid (vindoline) is scarcely produced by
Generally,
Under aseptic conditions, cultured plant materials can be used to generate bioactive or secondary metabolites, including flavonoids, alkaloids and other phenolics, terpenoids, saponins, steroids, tannins, glycosides, colorants, fragrances, and volatile oils [14]. Production of high-value active secondary metabolites at industrial levels, such as shikonin, berberine, and sanguinarine, was fulfilled from cell cultures of
Pharmaceutical compounds that are obtained from
The biosynthesis of secondary metabolites using unorganized cultured cells or organized organs, such as roots, can be enhanced by altering the environmental conditions or selecting an elite variant clone [66]. There are many procedures that can be controlled to increase the productivity of
To understand factors that control the biosynthesis of pharmaceutical compounds by cultured plant materials, studies on gene expression, enzyme activity, and signal transductions were carried out [12, 14]. The establishment of desired productivity of the PTC needs optimization of overall culture conditions to enhance both culture biomass and metabolites productivity. For example, while sulfate and ammonium nitrate ions increased the colchicine content of
When nodal segments of
The effect of carbon source concentration and type on culture biomass and metabolites productivity should be investigated. To enhance the biomass and biosynthesize of secondary metabolites, sucrose is widely used as a carbon source and it was better than maltose, glucose, and others [77]. During
Physical culture conditions can also affect the ability of
In a scale-up production system, modulation the composition of the culture media is an essential prerequisite to enhance the production efficiency of a selected cell line, but long-term cultivation may lead to the reduction of the yield [64] due to an increase in somaclonal variation [84]. Consequently, genetic stability of the cultured plant materials should be established using determined indicators, such as molecular markers, stability of growth parameter index over extended subculture cycles, and metabolite production.
Callus culture is an undifferentiated-unorganized mass obtained by cell division on cultured plant material on an agar medium. Then, calli are subcultured either for
Callus culture itself is exploited to produce and study secondary compounds in many medicinal plant species [66]. For induction of callus formation, specific culture conditions should be established, which means that cultured cells divide and proliferate rapidly as long as the cultural environment has sufficient nutrients and suitable growth regulators. Conditions for callus induction and proliferation are not favorable for the production of secondary metabolites. For induction of secondary metabolites, calli culture conditions should be changed or transferred to a new medium with a different composition [11]. High yields of proteolytic enzymes from the callus tissue culture of
The advantages of the application of suspension-cell cultures are obvious including: (1) The biomass production is usually more rapid than that of other
Application of specific cell lines and selective culture of that cell lines lead to the production of secondary compounds more than those obtained from original tissues and normal culture conditions [87]. The addition of plant growth regulators enhances the production of target secondary metabolites in several medicinal plant species [88]. Cell immobilization [89] and genetic makeup [90] can be optimized to enhance the synthesis of secondary compounds under
Two-phase cell suspension cultures establish a growth medium for maximizing cell biomass and production of naphthoquinone pigment in the first phase, but the second phase was established at the dark condition and room temperature with alkaline pH. These two phases system enhanced biomass production six-fold and optimized metabolite production in
Most of the used biotic elicitors are either exogenous or endogenous microbial agents but abiotic is a wide range of materials, mainly heavy metals [14, 99]. Methyl jasmonate, salicylic acid, yeast extract, chitosan, inorganic salts, UV radiation, or others can be used as elicitors to improve secondary metabolites production of the cultured plant materials [97, 100]. Citric acid, L-ascorbic acid, and casein hydrolysate were also used as elicitors to enhance the total phenolic content in the callus of
In the suspension culture of
Abiotic stresses for a given period can be used as an elicitor. Temperature, light parameters (intensity, photoperiod, and wavelength), and water potential of the medium influence the fresh and dry biomass [15] as well as the concentration of active metabolites [107]. Any factor that affects the water stress of the media should affect growth and bioactive compound synthesis. The profound change in the culture water potential due to the addition of NaCl, mannitol, or polyethylene glycol can elicit the production of secondary metabolites [107]. The relationship between abiotic-nutritional deficiency stress and enhancement of the production of secondary metabolites was reported [108]. Deficiencies of nitrogen, phosphate, potassium, sulfur, or magnesium increase the production of phenolic compound accumulation in different plant species [109], which may be due to oxidative stress and modulation of the expression of some genes [110]. The combination between target gene overexpression and elicitors increased the yield of secondary metabolites. Across studied plant species, elicitors promoted the yield of secondary metabolites from 1.0 to a maximum of 2230-fold [100]. Abiotic elicitors were applied to enhance growth and ginseng saponin biosynthesis in
Specific microorganisms can be used for elicitor purposes [112]. It takes place through the co-cultivation of plant cells with microorganisms. Compared to non-elicited control tissues, coculture of
Under perfect and controlled conditions,
Feeding the culture medium with organic compounds, such as vitamins or amino acids enhanced
The yield of salidroside was improved by feeding Rhodiola genus plants with an appropriate concentration of precursors and elicitors such as precursors, phenylalanine, tyrosol, and tyrosine [123]. Tyrosol feeding (0.5 mM) expressed the most obvious effect on salidroside content in the cell suspension cultures of
Genetic diversity within medicinal plants has great importance and can be used for plant improvement and the selection of an elite line. The selection of high biomass and metabolite(s) producing cell lines plays an important role in optimizing the productivity of
To get a high yield of metabolites, Briskin [127] described the biotechnological methods for the selection of high-yielding cell lines in medicinal plants by addressing several topics, including media components, elicitation, immobilization, physical stress, and transformation. This means that the identification and establishment of high producing and fast-growing
Qualitative and quantitative estimation of active metabolites may show variability depending on the spatial and temporal changes that may happen during the process. Variation in secondary metabolites yield may be due to their repression or losses before or during the extraction processes. Consequently, the determined secondary metabolite value may not exactly indicate the actual content of secondary metabolite in a given tissue or plant species. Nevertheless, quantitative and qualitative methods can be applied to select high-yielding cell lines [14]. Selection of the high-yielding lines can be established by exposing the population of plant materials to toxic inhibitors, biosynthetic precursors, or stressful environments and followed by selecting cells that show higher production of targeted components [2]. Selection can be carried out using callus, cell suspension, or through any other
The production of secondary metabolites is a metabolic process that is influenced by several physicochemical factors. These factors can be controlled and optimized in large-scale production. Traditional mutagenesis programs have been used by the pharmaceutical industry for yield improvement of medicinal plants. Recently, the development of recombinant DNA technology has provided new and effective tools to obtain elite strains with high content of secondary metabolites through overexpression of specific enzymes involved in their biosynthetic pathways aiming to increase the production levels and speed the metabolic processes [67, 96]. Consequently, plant genetics, recombinant DNA technologies, and PTC have developed to improve the ability of several medicinal plants to biosynthesize secondary metabolites efficiently.
To control the synthesis of certain natural products, the enzymes involved in the synthesis of these reactions and how they are influenced by
Using PTC, key gene overexpression that involved in the biosynthetic of valuable biologically active compounds can be controlled leading to produce compounds in high quantity and quantity. For example, the overexpression of geranyl diphosphate synthase and geraniol synthase genes in
Bioactive secondary metabolites are under coordinated control of the biosynthetic genes, and transcription factors (TFs) play an important role in this regulation [135]. Transcriptional regulation means the change in gene expression levels by modulation of transcription rates. Studies on the regulation of the production of secondary metabolite pathways are focused on the regulation of structural genes through TFs [135]. For example, the expression of genes involved in TIAs (terpenoid indole alkaloids, such as vincristine and vinblastine) metabolic pathway is elicited by jasmonates, it is regulated biosynthesis of terpenoid indole alkaloid (TIAs) and artemisinin [135]. Jasmonate was demonstrated as a regulator of deacetylvindoline 4-O-acetyltransferase (DAT) expression [136]. Expressed DAT is involved in the biosynthesis of TIAs member-vindoline through transferring an acetyl group to deacetylvindoline for vindoline production. It was clear that most of the genes codded for TIA pathway enzymes are tightly regulated by specific TFs under the regulation of JAs but it is carried out in coordination with developmental growth stage and environmental factors [135].
TFs of TIA genes respond to JAs and/or other elicitors. In
The genetic transformation was used as a powerful tool to improve the productivity of secondary metabolites. In general,
Gene transfer using
The application of PTC in medicinal plants can be scaled up using “bioreactors,” which allow atomization and production of a high yield of medicinal secondary products [154]. Therefore, scale-up production is a bioreactor application for the cultivation of plant cells on large-scale aiming for the mass production of valuable bioactive compounds. Also, bioreactor-based micropropagation was found to increase shoot multiplication for the commercial propagation of
Cell suspension offers the wright combination of physical and chemical environments that must be used in the large-scale production of secondary metabolites in the bioreactor process [156]. Consequently, scale-up production in the bioreactor was used to expand the production of secondary metabolites from research to the industrial level. Systems of various sizes and features of bioreactors were created and applied for the mass production of secondary metabolites [157]. The application of plant tissue culture techniques in bioreactors for scale-up production facilitates obtaining some expensive pharmaceuticals that are synthesized in low quantity during
Bioreactor operating system should provide efficient oxygen and nutrient supply, homogenous distribution of cultivated plant materials, and other factors that ensure optimal biomass and metabolite production [161]. While most of these bioreactors rely on cell suspension cultures, few of which are rely on differentiated tissues such as somatic embryos and hairy roots [162]. Application of suspension culture facilitates metabolites isolation [157].
For scale-up production, automation becomes an essential prerequisite, where it controls the pH of the culture area, culture viscosity, osmolarity, temperature, redox potential, oxygen supply, production of carbon dioxide, nutrients, weight, and liquid levels, and follows the rate of cell density. This automation needs sensors and monitoring systems that ensure mass production of pharmaceuticals and monitoring of physical, chemical, and biological parameters [163].
Perfusion cultivation is a system where continuous feeding of fresh media into a bioreactor system and removal of cells-free media were carried out in a modified bioreactor. The aim of this type of bioreactor and perfusion cultivation is to scaling-up the production of pharmaceutical compounds using plant cell, tissue, and organ cultures. The perfusion system offers a great advantage where it overcomes nutrient depletion and accumulation of growth inhibitors within the cultivated system, and it resulted in the promotion of biomass and pharmaceutical compounds. Semi-continuous perfusion was established in
Advances in immobilization and scale-up production techniques increase the applications of plant cell cultures for the purpose of producing high added value secondary compounds such as compounds with chemotherapeutic or antioxidant properties. For example, cell cultures of
In general, there are many factors that may hinder the application of PTC for various purposes in the field of medicinal and other plant species. The production of medicinal compounds using PTC has two important aspects—the amount of plant materials should be sufficient for the production of the target substance, as well as the quantity and quality of the produced substance. Hence, it is necessary to identify and avoid the conditions and phenomena that may negatively affect the growth efficiency of the
Obstacles facing the production of medicinal compounds from wild or cultivated plants can be avoided by using cell and tissue cultures, but these compounds may be toxic to the
Long-term culture can be used for the accumulation of desirable metabolite(s), but it can be a problematic and limiting factor that should be avoided by the application of certain techniques, such as medium enrichment or substitution in bioreactors [167]. These strategies include accumulation of metabolites in vacuoles, and other subcellular compartments or the exudation of metabolites into the culture medium [168]. The last strategy needs the application of additional techniques to decrease the concentration of the accumulated metabolite leading to further biosynthesis. It is accomplished by changing the medium of the culture manually or mechanically. In this regard, hairy roots were recommended, but not all secondary compounds are synthesized and accumulated in the roots [66].
While successful production of a wide range of valuable secondary metabolites can be obtained using unorganized callus or suspension cultures, the differentiated organ can be used but each of them may face some problems. The most important problems are the slow growth rate and somaclonal variation [84]. Consequently, the production of secondary compounds through the application of PTC techniques becomes unstable at a specific period. Generally, the problems facing the production of secondary metabolites using PTC can be easily solved by changing the culture conditions to avoid growth retardation and somaclonal variation [11]. Also, the application of PTC techniques in combination with other approaches could be used to avoid growth retardation and genetic variation [11].
The appropriate conditions for increasing the growth of the cultured plant materials may be different from the conditions for increasing the concentration of the active substance. To overcome these dilemmas, a two-step protocol is used, one of which provides optimal conditions for growth and the other provides optimal conditions to produce the active substance [12]. For example, while growth stimulators should be used during the growth phase, elicitors should be used to stimulate the biosynthesis of active compounds [169].
Accumulation of secondary metabolites is obtained under the influence of biotic or abiotic stress, but it retards the biological mass. To ensure a high yield of secondary metabolites, producers hope to conserve conditions to stimulate high biomass and biosynthesis of the targeted metabolite. Consequently, optimization of culture conditions to increase growth parameters or application of elicitors become an essential prerequisite [169].
Despite
Production of the secondary metabolites using the cell culture technique is low during the early stage of growth where high carbon utilization exists and is associated with enhancement of primary metabolism. On the other hand, the production of secondary metabolites is high at the late stage when carbon is less needed for the production of primary metabolism [14]. Prolonged the age of the cultured plant materials is necessary but it may be associated with genetic variation [47, 84]. Therefore, the enhancement of growth criteria of the cultured plant materials is not sufficient to confirm the optimization of
Somaclonal variation results from chromosomal changes in number or structure, transposable elements, or possibly pre-existing genetic changes in the donor plant. To detect somaclonal variation, several molecular techniques such as Random Amplified Polymorphic DNA (RAPD), Inter Simple Sequence Repeat (ISSR), and Simple Sequence Repeat (SSR) were recommended [18, 47].
Sometimes, the production of secondary metabolites through some techniques such as cell suspension is not always an adequate procedure. Then, other techniques such as organ culture can be used as a supernumerary method for the production of secondary metabolites [85]. Shoot cultures as same as hairy root cultures are recommended for production of pharmaceuticals where they are genetically stable [179]. Shooty teratomas were produced for the production of secondary metabolites, such as vincristine in
Generally, tissue culture plant materials were incubated in vessels to prevent microbial contamination and retard culture desiccation but these conditions may cause restriction of gases exchange between cultures and their surrounds. Under insufficient ventilation stress, the growth of the cultured plant materials was retarded due to retardation of photosynthesis, transpiration, and uptake of water and nutrients leading to the accumulation of ethylene and the appearance of vitrification or hyperhydricity [182]. The symptoms of vitrification are slowing growth rate, necrosis of shoot tips, loss of apical dominance, disorganized cell wall, fragile leaves, reduction of shoot multiplication, poor acclimatization, impaired stomatal function, reduction of some metabolites, alteration of ion composition, inhibition of H2O2 detoxification enzymes [183, 184].
Vitrification in medicinal and other plant species can be avoided by reducing the relative humidity and improving the aeration within culture vessels [183, 184], decreasing the concentration of free water by increasing the concentration of agar [185], and using anti-ethylene compounds including CoCl2, AgNO3 or salicylic acid [47, 183]. To confirm which anti-ethylene compounds can be used to conserve the genetic fidelity of
An increase in the world’s population imposed an important matter, which is the inevitability of leaving arable land for food production. Where modern agricultural techniques can be used to produce secondary metabolites and preserve the genetic assets of these plants, the most notable technique is PTC. In addition, different PTC techniques are used to propagate rare and endangered plant species. Changes in the physical and chemical conditions of
The use of plant tissue techniques has become dependent on it to produce pharmaceutical materials after laboratory and applied experiments have proven that
The use of PTC techniques to produce pharmaceutical compounds depends on the availability of production of sufficient-viable plant biomass to produce pharmaceutical substances with the requested quality and quantity. Therefore, it is necessary to understand all the factors that limit the production of targeted mass to avoid them such as the toxicity of secondary metabolites, low growth rate of cultured plant materials, and problems that constrain the application of transformation on a wide spectrum of plant species, somaclonal variation during cell or tissue cloning and verification of the cultured plant organs.
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Implantology",slug:"oral-implantology",parent:{id:"174",title:"Dentistry",slug:"dentistry"},numberOfBooks:5,numberOfSeries:0,numberOfAuthorsAndEditors:179,numberOfWosCitations:307,numberOfCrossrefCitations:147,numberOfDimensionsCitations:385,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicId:"998",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"7056",title:"An Update of Dental Implantology and Biomaterial",subtitle:null,isOpenForSubmission:!1,hash:"fab27916553ca6427ec1be823a6d81f2",slug:"an-update-of-dental-implantology-and-biomaterial",bookSignature:"Mazen Ahmad Almasri",coverURL:"https://cdn.intechopen.com/books/images_new/7056.jpg",editedByType:"Edited by",editors:[{id:"150413",title:"Dr.",name:"Mazen Ahmad",middleName:null,surname:"Almasri",slug:"mazen-ahmad-almasri",fullName:"Mazen Ahmad 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Osseointegration",slug:"dental-implant-surface-enhancement-and-osseointegration",totalDownloads:18676,totalCrossrefCites:38,totalDimensionsCites:99,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"S.Anil, P.S. Anand, H. Alghamdi and J.A. Jansen",authors:[{id:"25232",title:"Prof.",name:"Sukumaran",middleName:null,surname:"Anil",slug:"sukumaran-anil",fullName:"Sukumaran Anil"},{id:"28373",title:"Prof.",name:"John",middleName:null,surname:"Jansen",slug:"john-jansen",fullName:"John Jansen"},{id:"77058",title:"Dr.",name:"Seham",middleName:null,surname:"Alyafei",slug:"seham-alyafei",fullName:"Seham Alyafei"},{id:"82073",title:"Dr.",name:"Subhash",middleName:null,surname:"Narayanan",slug:"subhash-narayanan",fullName:"Subhash Narayanan"}]},{id:"18415",doi:"10.5772/16936",title:"Osseointegration and Bioscience of Implant Surfaces - Current Concepts at Bone-Implant Interface",slug:"osseointegration-and-bioscience-of-implant-surfaces-current-concepts-at-bone-implant-interface",totalDownloads:12502,totalCrossrefCites:16,totalDimensionsCites:42,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Mustafa Ramazanoglu and Yoshiki Oshida",authors:[{id:"26726",title:"Prof.",name:"Yoshiki",middleName:null,surname:"Oshida",slug:"yoshiki-oshida",fullName:"Yoshiki Oshida"},{id:"29841",title:"Prof.",name:"Mustafa",middleName:null,surname:"Ramazanoglu",slug:"mustafa-ramazanoglu",fullName:"Mustafa Ramazanoglu"}]},{id:"18426",doi:"10.5772/18746",title:"Factors Affecting the Success of Dental Implants",slug:"factors-affecting-the-success-of-dental-implants",totalDownloads:17474,totalCrossrefCites:9,totalDimensionsCites:35,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Carlos Nelson Elias",authors:[{id:"32438",title:"Prof.",name:"Carlos",middleName:null,surname:"Elias",slug:"carlos-elias",fullName:"Carlos Elias"}]},{id:"18414",doi:"10.5772/17512",title:"Dental Implant Surfaces – Physicochemical Properties, Biological Performance, and Trends",slug:"dental-implant-surfaces-physicochemical-properties-biological-performance-and-trends",totalDownloads:13080,totalCrossrefCites:5,totalDimensionsCites:30,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Ahmed M. Ballo, Omar Omar, Wei Xia and Anders Palmquist",authors:[{id:"19042",title:"Dr.",name:"Wei",middleName:null,surname:"Xia",slug:"wei-xia",fullName:"Wei Xia"},{id:"28549",title:"Dr.",name:"Ahmed",middleName:"M.",surname:"Ballo",slug:"ahmed-ballo",fullName:"Ahmed Ballo"},{id:"81291",title:"Dr.",name:"Omar",middleName:null,surname:"Omar",slug:"omar-omar",fullName:"Omar Omar"},{id:"81292",title:"Dr.",name:"Anders",middleName:null,surname:"Palmquist",slug:"anders-palmquist",fullName:"Anders Palmquist"}]},{id:"18417",doi:"10.5772/18309",title:"Implant Stability - Measuring Devices and Randomized Clinical Trial for ISQ Value Change Pattern Measured from Two Different Directions by Magnetic RFA",slug:"implant-stability-measuring-devices-and-randomized-clinical-trial-for-isq-value-change-pattern-measu",totalDownloads:13176,totalCrossrefCites:8,totalDimensionsCites:19,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Jong-Chul Park, Jung-Woo Lee, Soung-Min Kim and Jong-Ho Lee",authors:[{id:"31057",title:"Prof.",name:"Jong-Ho",middleName:null,surname:"Lee",slug:"jong-ho-lee",fullName:"Jong-Ho Lee"},{id:"48351",title:"Prof.",name:"Jong-Chul",middleName:null,surname:"Park",slug:"jong-chul-park",fullName:"Jong-Chul Park"},{id:"83313",title:"Dr.",name:"JungWoo",middleName:null,surname:"Lee",slug:"jungwoo-lee",fullName:"JungWoo Lee"}]}],mostDownloadedChaptersLast30Days:[{id:"18432",title:"Clinical Complications of Dental Implants",slug:"clinical-complications-of-dental-implants",totalDownloads:56478,totalCrossrefCites:2,totalDimensionsCites:5,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Su-Gwan Kim",authors:[{id:"27797",title:"Prof.",name:"Su-Gwan",middleName:null,surname:"Kim",slug:"su-gwan-kim",fullName:"Su-Gwan Kim"}]},{id:"47927",title:"Miniscrew Applications in Orthodontics",slug:"miniscrew-applications-in-orthodontics",totalDownloads:4697,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"4548",slug:"current-concepts-in-dental-implantology",title:"Current Concepts in Dental Implantology",fullTitle:"Current Concepts in Dental Implantology"},signatures:"Fatma Deniz Uzuner and Belma Işık Aslan",authors:[{id:"42847",title:"Dr.",name:"Belma",middleName:null,surname:"Işik Aslan",slug:"belma-isik-aslan",fullName:"Belma Işik Aslan"},{id:"172009",title:"Dr.",name:"Fatma Deniz",middleName:null,surname:"Uzuner",slug:"fatma-deniz-uzuner",fullName:"Fatma Deniz Uzuner"}]},{id:"50308",title:"Antibiotics in Implant Dentistry",slug:"antibiotics-in-implant-dentistry",totalDownloads:2369,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"Antibiotics have been recommended either as an extended treatment for several days or as a single antibiotic prophylaxis dose since the development of dental implant osseointegration technique in the 1970s. It is also performed as part of surgical protocol during the peri-operative phase in the treatment of peri-implantitis. To date, there is a lack of scientific evidence regarding the additive effect of antibiotics in the treatment of dental implant. This has thus left the clinician with inconclusive recommendations, leading to increase antibiotic prescription. With this increase, the development of antibiotic resistance is becoming a threat to modern healthcare that requires revisiting of current indications and implementation of rational treatment strategies. Therefore, more studies are needed to assess the benefit of antibiotic prescription and whether it is safe to refrain from its use.",book:{id:"5185",slug:"dental-implantology-and-biomaterial",title:"Dental Implantology and Biomaterial",fullTitle:"Dental Implantology and Biomaterial"},signatures:"Dalia Khalil, Bodil Lund and Margareta Hultin",authors:[{id:"179031",title:"Dr.",name:"Dalia",middleName:null,surname:"Khalil",slug:"dalia-khalil",fullName:"Dalia Khalil"},{id:"185113",title:"Dr.",name:"Bodil",middleName:null,surname:"Lund",slug:"bodil-lund",fullName:"Bodil Lund"},{id:"185114",title:"Dr.",name:"Margareta",middleName:null,surname:"Hultin",slug:"margareta-hultin",fullName:"Margareta Hultin"}]},{id:"47915",title:"Rationale for Dental Implants",slug:"rationale-for-dental-implants",totalDownloads:3076,totalCrossrefCites:0,totalDimensionsCites:2,abstract:null,book:{id:"4548",slug:"current-concepts-in-dental-implantology",title:"Current Concepts in Dental Implantology",fullTitle:"Current Concepts in Dental Implantology"},signatures:"Ilser Turkyilmaz and Gokce Soganci",authors:[{id:"171984",title:"Associate Prof.",name:"Ilser",middleName:null,surname:"Turkyilmaz",slug:"ilser-turkyilmaz",fullName:"Ilser Turkyilmaz"}]},{id:"18430",title:"An Important Dilemma in Treatment Planning: Implant or Endodontic Therapy?",slug:"an-important-dilemma-in-treatment-planning-implant-or-endodontic-therapy-",totalDownloads:6264,totalCrossrefCites:0,totalDimensionsCites:0,abstract:null,book:{id:"179",slug:"implant-dentistry-a-rapidly-evolving-practice",title:"Implant Dentistry",fullTitle:"Implant Dentistry - A Rapidly Evolving Practice"},signatures:"Funda Kont Cobankara and Sema Belli",authors:[{id:"28846",title:"Dr.",name:"Funda",middleName:null,surname:"Kont Çobankara",slug:"funda-kont-cobankara",fullName:"Funda Kont Çobankara"},{id:"75862",title:"Prof.",name:"Sema",middleName:null,surname:"Belli",slug:"sema-belli",fullName:"Sema Belli"}]}],onlineFirstChaptersFilter:{topicId:"998",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81595",title:"Prosthetic Concepts in Dental Implantology",slug:"prosthetic-concepts-in-dental-implantology",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.104725",abstract:"This chapter will address evidence-based prosthetic concepts in dental implantology as well as clinical evidence with focus on appropriate logic and technical skills. Those prosthetic factors are as just important as surgical factors, and long-term success can only be achieved if both of those factors are considered, respected, and strictly followed from planning to prosthetic phase of treatment. This chapter will deal with materials selection for prosthetic part, shape, size, and design of supracrestal parts of abutments and their influence on soft tissue and bone stability around dental implants. Furthermore, one of most important decisions is about choosing the proper way of retention: screw- vs. cement-retained restorations, and it will be discussed in detail. Additionally, emergence profile and its function in soft tissues adaptation and adhesion to different prosthetic materials also have important role in long-term success of dental implant restorations.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Ivica Pelivan"},{id:"80500",title:"Novel Dental Implants with Herbal Composites: A Review",slug:"novel-dental-implants-with-herbal-composites-a-review",totalDownloads:49,totalDimensionsCites:0,doi:"10.5772/intechopen.101489",abstract:"Missing a permanent tooth is a miserable condition faced by a common man. A tooth decay, periodontitis, mechanical trauma, or any systemic complications lead to such a complication. These bone defects when left untreated lead to severe resorption of the alveolar bone. A proper dental filling with an appropriate bone substitute material could prevent such resorption and paves a way for subsequent implant placement. Dental implants are considered as the prime option by dentists to replace a single tooth or prevent bone resorption. A variety of bone substitutes are available differ in origin, consistency, particle size, porosity, and resorption characteristics. Herbal composites in dentistry fabricated using biphospho-calcium phosphate, casein, chitosan, and certain herbal extracts of Cassia occidentalis, Terminalia arjuna bark, Myristica fragans also were reported to possess a higher ossification property, osteogenic property and were able to repair bone defects. C. occidentalis was reported to stimulate mineralization of the bone and osteoblastic differentiation through the activation of the PI3K-Akt/MAPKs pathway in MC3T3-E1 cells of mice. This implant proved better osteoconductivity and bioactivity compared to pure HAP and other BCP ratios. Terminalia Arjuna was also worked in the incorporation in the graft to enhance the osteogenic property of the implant and gave good results. Another implant bone graft was synthesized containing BCP, biocompatible casein, and the extracts of Myristica fragans and subjected to in vitro investigations and the results revealed the deposition of apatite on the graft after immersing in SBF and also the ALP activity was high when treated with MG-63 cells, NIH-3 T3, and Saos 2 cell lines. This study indicates that the inclusion of plant extract enhances the osteogenic property of the graft. Thus, these novel dental implants incorporated with herbal composites evaluated by researchers revealed an enhanced bone healing, accelerates osseointegration, inhibits osteopenia, and inhibits inflammation. This application of herbal composite inclusion in dentistry and its applications has a greater potential to improve the success rate of dental implants and allows the implications of biotechnology in implant dentistry.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Gopathy Sridevi and Seshadri Srividya"},{id:"78320",title:"Implant-Retained Maxillary and Mandibular Overdentures - A Solution for Completely Edentulous Patients",slug:"implant-retained-maxillary-and-mandibular-overdentures-a-solution-for-completely-edentulous-patients",totalDownloads:66,totalDimensionsCites:0,doi:"10.5772/intechopen.99575",abstract:"The main goal of modern removable prosthodontics is to restore the normal appearance, function, esthetics and speech in each completely edentulous patient. However, if all teeth are missing in a patient, it becomes very complicated to achieve it using traditional protocols. Therefore, implants were introduced into removable prosthodontics to ensure better retention and stability of the conventional dentures. In case of a large amount of bone missing in the jaw it is necessary to ensure the functioning of the dentures constructing various additional stabilizing and retentive prosthodontic solutions on the osseointegrated implants. Numerous types of attachment systems have been used recently for relating implant-retained overdentures to underlying implants: basically splinting (various bar shape designs) and non-splinting attachments (various ball type attachment, magnet attachment, telescopic coping systems). Indications for their use depend on the surgical and prosthodontic factors such as the number and position of the implants, the amount of free intermaxillary space and the type and size of the overdentures. Different indications, types of the overdentures and the attachment systems will be discussed in this chapter.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Dubravka Knezović Zlatarić, Robert Ćelić and Hrvoje Pezo"},{id:"79724",title:"Implant Stability Quotient (ISQ): A Reliable Guide for Implant Treatment",slug:"implant-stability-quotient-isq-a-reliable-guide-for-implant-treatment",totalDownloads:60,totalDimensionsCites:0,doi:"10.5772/intechopen.101359",abstract:"Implant stability is a prerequisite for successful dental implants and osseointegration. To determine the status of implant stability, continuous monitoring in an objective and qualitative manner is important. To measure implant stability two different stages are there: Primary and secondary. Primary implant stability at placement is a mechanical phenomenon that is related to the local bone quality and quantity, the type of implant and placement technique used. Primary stability is checked from mechanical engagement with cortical bone. Secondary stability is developed from regeneration and remodeling of the bone and tissue around the implant after insertion and affected by the primary stability, bone formation and remodeling. Implant stability is essential for the time of functional loading. Classical benchmark methods to measure implant stability were radiographs or microscopic analysis, removal torque, push-through and pull-through but due to lack of feasibility, time consumption and ethical reasons other methods have been propounded over period of time like measurement of implant torque, model analysis and most important ISQ which has the ability to monitor osseointegration and the life expectancy of an implant. ISQ is a valuable diagnostic and clinical tool that has far-reaching consequences on implant dentistry and this article throws light on advanced and reliable methods of assessing ISQ.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Gaurav Gupta"},{id:"79817",title:"Peri-Implant Soft Tissue Augmentation",slug:"peri-implant-soft-tissue-augmentation",totalDownloads:128,totalDimensionsCites:0,doi:"10.5772/intechopen.101336",abstract:"The peri-implant soft tissue (PIS) augmentation procedure has become an integral part of implant-prosthetic rehabilitation. Minimal width of keratinized mucosa (KM) of 2 mm is deemed necessary to facilitate oral hygiene maintenance around the implant and provide hard and soft peri-implant tissue stability. PIS thickness of at least 2 mm is recommended to achieve the esthetic appearance and prevent recessions around implant prosthetic rehabilitation. The autogenous soft tissue grafts can be divided into two groups based on their histological composition—free gingival graft (FGG) and connective tissue graft (CTG). FGG graft is used mainly to increase the width of keratinized mucosa while CTG augment the thickness of PIS. Both grafts are harvested from the same anatomical region—the palate. Alternatively, they can be harvested from the maxillary tuberosity. Soft tissue grafts can be also harvested as pedicle grafts, in case when the soft tissue graft remains attached to the donor site by one side preserving the blood supply from the donor region. Clinically this will result in less shrinkage of the graft postoperatively, improving the outcome of the augmentation procedure. To bypass the drawback connected with FGG or CTG harvesting, substitutional soft tissue grafts have been developed.",book:{id:"10808",title:"Current Concepts in Dental Implantology - From Science to Clinical Research",coverURL:"https://cdn.intechopen.com/books/images_new/10808.jpg"},signatures:"Marko Blašković and Dorotea Blašković"},{id:"79611",title:"Growth Factors and Dental Implantology",slug:"growth-factors-and-dental-implantology",totalDownloads:103,totalDimensionsCites:0,doi:"10.5772/intechopen.101082",abstract:"Normal healing procedure of bone involves various sequential events to develop bone and bridge the bone -to- bone gap. When this healing occurs with a metal (titanium) fixture on one side, it is called as osseointegration. After extensive studies on this topic, it is found that this procedure occurs in presence of various biologic constituents that are spontaneously released at the site. 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He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. 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He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. 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She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. 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His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. Voyich",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Montana State University",country:{name:"United States of America"}}},{id:"330412",title:"Dr.",name:"Muhammad",middleName:null,surname:"Farhab",slug:"muhammad-farhab",fullName:"Muhammad Farhab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{id:"349495",title:"Dr.",name:"Muhammad",middleName:null,surname:"Ijaz",slug:"muhammad-ijaz",fullName:"Muhammad Ijaz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Veterinary and Animal Sciences",country:{name:"Pakistan"}}}]}},subseries:{item:{id:"20",type:"subseries",title:"Animal Nutrition",keywords:"Sustainable Animal Diets, Carbon Footprint, Meta Analyses",scope:"An essential part of animal production is nutrition. Animals need to receive a properly balanced diet. One of the new challenges we are now faced with is sustainable animal diets (STAND) that involve the 3 P’s (People, Planet, and Profitability). We must develop animal feed that does not compete with human food, use antibiotics, and explore new growth promoters options, such as plant extracts or compounds that promote feed efficiency (e.g., monensin, oils, enzymes, probiotics). These new feed options must also be environmentally friendly, reducing the Carbon footprint, CH4, N, and P emissions to the environment, with an adequate formulation of nutrients.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/20.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11416,editor:{id:"175967",title:"Dr.",name:"Manuel",middleName:null,surname:"Gonzalez Ronquillo",slug:"manuel-gonzalez-ronquillo",fullName:"Manuel Gonzalez Ronquillo",profilePictureURL:"https://mts.intechopen.com/storage/users/175967/images/system/175967.png",biography:"Dr. Manuel González Ronquillo obtained his doctorate degree from the University of Zaragoza, Spain, in 2001. He is a research professor at the Faculty of Veterinary Medicine and Animal Husbandry, Autonomous University of the State of Mexico. He is also a level-2 researcher. He received a Fulbright-Garcia Robles fellowship for a postdoctoral stay at the US Dairy Forage Research Center, Madison, Wisconsin, USA in 2008–2009. He received grants from Alianza del Pacifico for a stay at the University of Magallanes, Chile, in 2014, and from Consejo Nacional de Ciencia y Tecnología (CONACyT) to work in the Food and Agriculture Organization’s Animal Production and Health Division (AGA), Rome, Italy, in 2014–2015. He has collaborated with researchers from different countries and published ninety-eight journal articles. He teaches various degree courses in zootechnics, sheep production, and agricultural sciences and natural resources.\n\nDr. Ronquillo’s research focuses on the evaluation of sustainable animal diets (StAnD), using native resources of the region, decreasing carbon footprint, and applying meta-analysis and mathematical models for a better understanding of animal production.",institutionString:null,institution:{name:"Universidad Autónoma del Estado de México",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,series:{id:"13",title:"Veterinary Medicine and Science",doi:"10.5772/intechopen.73681",issn:"2632-0517"},editorialBoard:[{id:"175762",title:"Dr.",name:"Alfredo J.",middleName:null,surname:"Escribano",slug:"alfredo-j.-escribano",fullName:"Alfredo J. 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