\r\n\t- BMD measurement technology \r\n\t- Osteoporosis and fracture risk \r\n\t- Bone growth and remodeling
\r\n
\r\n\t \r\n\tThe submission is also open to any other original study related to these research topics.
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1. Introduction
The spleen is a unique organ with many functions, including its crosstalk with the liver in cirrhotic patients. This review aims to answer a clinical question “Should splenectomy be done in liver cirrhosis with hypersplenism and splenomegaly?”.
2. The spleen
The spleen is an organ full of mystery, as stated by Galen. From the ancient times until the Renaissance, descriptions of the gross anatomy of the spleen were relatively accurate, yet the physiology of this organ remains incomplete and inaccurate. Even until today, much of spleen’s function are still yet to be discovered [1].
Spleen comprised of two distinct compartments, both functional and morphological, namely red pulp and white pulp. The red pulp filters blood to remove foreign material and damaged erythrocytes. It also serves as iron, erythrocytes and platelets storages. With one fourth of body’s lymphocytes stores in the spleen, it is the largest secondary organ which initiate immune response to blood-borne antigens [2]. It exerts important effects on local and systemic immune responses, which have the potential to affect different tissues and organs [3]. The white pulp, composed by periarteriolar lymphoid sheath (PALS), the follicles and the marginal zones, are the one responsible for this so called immune functions [2].
In addition, the spleen also produces opsonins, a substances that bind to the foreign antigen, which in turn enhance their uptake and phagocytosis by macrophages. Furthermore, the B-lymphocytes within the germinal centers of the spleen are also sites for the production of antibody activated by foreign antigen. The realization of this important immunological function has promoted the desire for splenic preservation [4].
3. Liver cirrhosis and the spleen
The association between the liver and spleen are shown in three different categories. Both organ, anatomically important in the portal circulation. Histologically, they share similar possession of reticuloendothelial structures, participating in substance exchange and cellular migration. And immunologically, both organs plays essential roles in immune homeostasis and pathogen clearance [2].
The first recorded encounter between spleen and cirrhosis could be trace back to Carl Freiderich Quittenbaum (1793–1852) of Rostock, Germany, who removed the spleen of a woman with cirrhosis and ascites “more from the patient’s urgent entreaty rather than the surgeon’s judgment.” Unfortunately the woman lived only 6 h after the surgery [5].
The palpable spleen has long been considered as an obvious signs of liver cirrhosis, frequently occurs in parallel with hypersplenism, to be the major cause of cytopenia and thrombocytopenia. This condition are relatively sub-fatal, even in the absence of a bleeding varices. During the progression of liver cirrhosis, the spleen-derived immune cells and cytokines may travel into the injured liver via portal blood flow. Together with the portal hypertension and congestion, this will result in splenomegaly and hypersplenism. Furthermore, the chemokines, DAMPs like HMGB1, or exosomes, are also release into the circulation, which will trigger the activation and/or migration of splenocytes. This mechanism are known as the liver and spleen crosstalk pathways during liver cirrhosis [2].
Spleen size in patients with cirrhosis varies by the etiology of the disease. While in healthy adults, the size of the spleen in usually less than 12 cm, in cirrhotic patients it is relatively larger, as shown in the study by Kashani et al. This study revealed that the mean spleen size in the alcohol group (13.1 ± 2.5 cm) was significantly smaller than in the hepatitis C (15.0 ± 3.4 cm) and nonalcoholic steatohepatitis (15.2 ± 3.0 cm) groups (95% confidence intervals of the mean difference, 0.6 to 3.3 and 0.8 to 3.4 cm, respectively), sonographically [6].
4. Splenectomy effects to the liver
Cirrhotic patients are generally considered as immunocompromised, mainly due to the development of bacterial infection and community-acquired infections. Since the spleen is the largest lymphoid organs with large amount of T and B cells, macrophages, and dendritic cells, splenectomy in cirrhotic patients has produced concern over decrease immunity and elevated risk of infection, namely overwhelming post splenectomy pneumococcal sepsis.
However, a study by Hirakawa et al., showed the possibility of reducing suppressive cell fractions and enhancement of the effector cell population and functions by means of splenectomy, thus ameliorate the impaired immune status of cirrhotic patients [7].
Yamada et al. demonstrated that splenectomy improved hepatic functional reserves and nutritional metabolism, together with improvement in thrombocytopenia and leukopenia in cirrhotic patients. Splenectomy is thought to induce a decrease in platelet pooling or breakdown in the spleen of thrombocytopenic patients, and as a result, increase blood platelet counts. Bilirubinemia secondary to hypersplenism, which is caused by an increase in bilirubin production, that overloads the capacity of the liver to metabolize bilirubin, are also reduced after splenectomy [8].
In a study by Ueda et al. of rats undergoing major liver resection with or without splenectomy, early stage splenic red pulp TGF-β1 production and secretion into the portal blood exert an inhibitory effect on liver regeneration. Splenectomy reversed this inhibition and enhanced the regeneration of hepatocytes [9].
Study by Huang et al., unveiled serum cytokine profiles in HBV-related cirrhosis patients with PH and hypersplenism, indicating a potential role of the hypertensive spleen in the progression of liver disease. Furthermore, the changes in cytokine levels following splenectomy maybe potential advantageous to reduce liver fibrosis and accelerate liver regeneration as well as reduce the risk of HCC [10].
Splenectomy also enhanced the repopulation of adoptively transferred bone marrow cell in cirrhotic liver and decreased collagen deposition through the upregulation of MM9 expression in transferred bone marrow cells, as suggested by Iwamoto et al. [11], and improved the efficiency of adipose tissue-derived mesenchymal cell transplant into the liver by enhancing liver SCF-1 and HGV expressions [12].
Considering all of the above mention mechanism, targeting spleen for the treatment of liver cirrhosis can be achieved through [2]:
amelioration of cirrhosis’ fatal complications such as bleeding esophageal or gastric varices
efficiently improving liver function and the prognosis of esophageal varices
increasing the efficacy of liver transplantation and improving the prognosis of HCC
supplementary treatment for anti-HCV therapy in combination with interferons and other pharmaceuticals.
5. Technical and perioperative consideration for splenectomy in cirrhotic liver
Surgery in a patient with liver disease carries specific and higher risks, compare to those with normal populations. Perioperative care including assessment and optimalization is the key to a safe surgery. Many cirrhosis patients present themselves with a relative contraindications that preclude surgery.
The predictors for complications including Child-Pugh class B or C, ascites, etiology of cirrhosis other than PBC, elevated creatinine, preoperative infection, COPD, preoperative upper GI bleeding, invasiveness of surgical procedure, intraoperative hypotension, and ASA status 4–5. While the predictors of mortality including male gender, Child-Pugh class B or C, ascites, etiology of cirrhosis other than PBC, preoperative infection, ASA status 4–5 and respiratory surgery. The presence of 1 risk factors carries a 9.3% risk of complications, and this increase with the more numbers of risk factors. A total of 7–8 risk factors carries a 100% risk of complications [13].
Friedman proposed the following list of contraindication to elective surgery in patients with liver disease, including acute viral hepatitis, alcoholic hepatitis, acute liver failure, acute renal failure, severe coagulopathy, hypoxemia and cardiomyopathy [14].
Regarding the preferred method for splenectomy, recently laparoscopic has become technically feasible, safe and effective procedure for hypersplenism secondary to cirrhosis, and contributes to less blood loss, shorter length of stay and less impairment of liver function. However, this methods are generally more costly and might not readily available in every hospital. Thus the choice of splenectomy method must be personally selected for each patient, surgeon and hospital [15].
6. Splenectomy as a bridge to liver transplant
It is already a general consensus that liver transplantation is the preferred treatment options for patient with end stage liver disease. However, the waiting time for liver transplantation is also long due to the shortage of donor organs, even in living donor liver transplantation setting. Moreover, in some countries, liver transplantation still not a feasible option for all patients.
One among many alternatives is by doing a splenectomy prior to liver transplantation in patient with liver cirrhosis and subsequent splenomegaly-hypersplenism. A study by Kong et al., studied 833 patient patients underwent liver transplantation, of which 88 patients had splenectomy before liver transplantation. They found that postoperative infection and 90-days mortality in the splenectomy and non-splenectomy group were not statistically difference. Furthermore, the post-transplant thrombocytopenia and early allograft dysfunctions is significantly lower in splenectomy group compare to non-splenectomy group. They suggested that pre-transplantation splenectomy is recommended in cases with risky patients without appropriate source of liver for LT. Taking into consideration the possibility of more difficult operation due to adhesion when transplantation is being done. One thing to note is that as a “re-operation” the splenectomy is often as- sociated with more difficult dissection due to adhesions [16].
7. Summary
Splenectomy is beneficial in reversal of the pathologic process through live regeneration and pre-transplant splenectomy could be an alternative in patients without appropriate source of liver for liver transplantation. However, perioperative considerations should be thoroughly assessed to allow a safe surgery.
Conflict of interest
“The authors declare no conflict of interest.”
Notes/thanks/other declarations
Part of this article was presented in APASL Congress, Bali, March 2020.
\n',keywords:"splenectomy, liver cirrhosis, hypersplenism, splenomegaly, liver transplantation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/73679.pdf",chapterXML:"https://mts.intechopen.com/source/xml/73679.xml",downloadPdfUrl:"/chapter/pdf-download/73679",previewPdfUrl:"/chapter/pdf-preview/73679",totalDownloads:471,totalViews:0,totalCrossrefCites:0,totalDimensionsCites:0,totalAltmetricsMentions:0,introChapter:null,impactScore:0,impactScorePercentile:34,impactScoreQuartile:2,hasAltmetrics:0,dateSubmitted:"June 12th 2020",dateReviewed:"October 5th 2020",datePrePublished:"October 20th 2020",datePublished:"March 10th 2021",dateFinished:"October 20th 2020",readingETA:"0",abstract:"Spleen is a “mysterious” organ since with unique functions, and might be related to other pathology in the human body. Splenomegaly and hypersplenism can manifest following the development of portal hypertension in liver cirrhosis through fibrogenesis, immune and microenvironment dysregulation. Cirrhotic patients are generally considered as immunocompromised and prone to infections. Splenectomy in cirrhotic patients has produced concern over decrease immunity and elevated risk of infection, namely overwhelming post splenectomy pneumococcal sepsis. This review discus the splenectomy effect to the liver and how it can play a role in cirrhotic patients with portal hypertension without readily available access to liver transplantation.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/73679",risUrl:"/chapter/ris/73679",book:{id:"7031",slug:"liver-pathology"},signatures:"Adianto Nugroho",authors:[{id:"278555",title:"Dr.",name:"Adianto",middleName:null,surname:"Nugroho",fullName:"Adianto Nugroho",slug:"adianto-nugroho",email:"adiyusuf97@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. The spleen",level:"1"},{id:"sec_3",title:"3. Liver cirrhosis and the spleen",level:"1"},{id:"sec_4",title:"4. Splenectomy effects to the liver",level:"1"},{id:"sec_5",title:"5. Technical and perioperative consideration for splenectomy in cirrhotic liver",level:"1"},{id:"sec_6",title:"6. Splenectomy as a bridge to liver transplant",level:"1"},{id:"sec_7",title:"7. Summary",level:"1"},{id:"sec_11",title:"Conflict of interest",level:"1"},{id:"sec_8",title:"Notes/thanks/other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Paraskevas, G.K., Koutsouflianiotis, K.N., Nitsa, Z. et al. Knowledge of the anatomy and physiology of the spleen throughout Antiquity and the Early Middle Ages. Anat Sci Int 2016; 91, 43-55'},{id:"B2",body:'Cesta MF. Normal structure, function, and histology of the spleen. Toxicol Pathol. 2006;34(5):455-465'},{id:"B3",body:'Li, L, Duan, M, Chen, W et al. The spleen in liver cirrhosis: revisiting an old enemy with novel targets. J Transl Med 2017;15, 111'},{id:"B4",body:'Stricland A, Lloyd D. The spleen and indications for splenectomy. Surgery 2007;25(2): 98-101'},{id:"B5",body:'Morgenstern L. A history of splenectomy. In: Hiat JR, Phillips EH, Morgenstern L, ed. Surgical disease of the spleen. Springer, 1997'},{id:"B6",body:'Kashani A, Salehi B, Anghesom D, Kawayeh AM, Rouse GA, Runyon BA. Spleen size in cirrhosis of different etiologies. J Ultrasound Med. 2015;34(2):233-238'},{id:"B7",body:'Hirakawa Y, Ogata T, Sasada T, Yamashita T, Itoh K, Tanaka H and Okuda K: Immunological consequences following splenectomy in patients with liver cirrhosis. Exp Ther Med 18: 848-856, 2019'},{id:"B8",body:'Yamada S, Morine Y, Imura S, et al. Liver regeneration after splenectomy in patients with liver cirrhosis. Hepatol Res. 2016;46(5):443-449'},{id:"B9",body:'Ueda S, Yamanoi A, Hishikawa Y, et al. Transforming growth factor-b1 released from the spleen exerts a growth inhibitory effect on liver regen- eration in rats. Lab Invest. 2003;83(11):1595-603'},{id:"B10",body:'Huang N, Ji F, Zhang S, et al. Effect of Splenectomy on Serum Cytokine Profiles in Hepatitis B Virus-Related Cirrhosis Patients with Portal Hypertension. Viral Immunol. 2018;31(5):371-378'},{id:"B11",body:'Iwamoto T, Terai S, Mizunaga Y, et al. Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients. J Gastroenterol. 2012;47(3):300-312'},{id:"B12",body:'Tang WP, Akahoshi T, Piao JS, et al. Splenectomy enhances the therapeutic effect of adipose tissue-derived mesenchymal stem cell infusion on cirrhosis rats. Liver Int. 2016;36(8):1151-1159'},{id:"B13",body:'Rai R, Nagral S, Nagral A. Surgery in a patient with liver disease. J Clin Exp Hepatol. 2012;2(3):238-246'},{id:"B14",body:'Friedman L.S. Surgery in the patient with liver disease. Trans Am Clin Climatol Assoc. 2010;121:192-205'},{id:"B15",body:'Zhan XL, Ji Y, Wang YD. Laparoscopic splenectomy for hyper- splenism secondary to liver cirrhosis and portal hypertension. World J Gastroenterol 2014; 20(19): 5794-5800'},{id:"B16",body:'Kong, L., Li, M., Li, L. et al. Splenectomy before adult liver transplantation: a retrospective study. BMC Surg 2017;17, 44'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Adianto Nugroho",address:"adiyusuf97@gmail.com",affiliation:'
Department of Surgery, HPB Section, Digestive Division, Fatmawati Central General Hospital, Jakarta, Indonesia
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1. Introduction
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Research shows that certain molecules identified in the cannabis plant are able to improve aspects of cognition. Cognition encompasses multiple aspects of thought processing including decision-making, processing speed, attention span, learning and memory. Cognitive dysfunction can occur in a range of illnesses and disease states, for example Alzheimer’s disease, dementia, Parkinson’s disease, schizophrenia, hypoxic ischemia, stroke and meningitis. There is particularly strong evidence in the existing literature to support the pro-cognitive effects of the cannabinoid, cannabidiol (CBD) in disease states. There is also evidence that other phytochemicals in cannabis provide benefits for brain health and cognitive function. Furthermore, the suggested presence of an ‘entourage effect’ may mean that the therapeutic potential of CBD could be boosted through synergistic interactions with other phytochemicals. Therefore, certain cannabis strains may confer greater benefits for particular clinical indications, presenting unique opportunities for the discovery of novel personalised therapeutics. Identifying specific beneficial compounds could underpin selective breeding of plant cultivars with phytochemical profiles optimised towards restoring brain function in diseases associated with cognitive dysfunction.
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2. Cannabidiol (CBD) and the brain
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CBD is a major cannabinoid of C. sativa, considered a metabolic by-product rather than a biosynthetic product of the plant [1]. There has been a recent burst of studies showing beneficial effects of CBD in the brain, with evidence pointing to CBD as a promising novel therapy for a range of disorders. Based on its ability to change brain function and behaviour, it is, by definition ‘psychoactive’, but CBD is non-intoxicating and there is currently no evidence that it causes the deleterious hallucinogenic, paranoia and anxiety-inducing effects of the delta-tetrahydrocannabinol (Δ-THC) type chemicals, particularly Δ9-THC that is primarily responsible for the ‘high’ induced by recreational cannabis [2]. Instead, CBD has a broad spectrum of therapeutic properties, including antipsychotic, anxiolytic, immunomodulatory, anti-inflammatory, neuroprotective and pro-cognitive benefits in humans and preclinical disease models. Although its mechanisms of action are currently unclear, studies show that CBD is a cannabinoid 1 receptor (CB1) negative allosteric modulator [3], is a partial agonist of the dopamine D2 high receptor sub-type [4] and increases anandamide (AEA) signalling [5], possibly through inhibition of the AEA catabolic enzyme, fatty acid amide hydrolase (FAAH) [6].
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2.1. Cannabidiol protects against cognitive harms of high-THC Cannabis
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In terms of cognition, our recent systematic review by Osborne et al. [7] revealed a body of clinical and pre-clinical evidence supporting the pro-cognitive effects of CBD. We identified reports demonstrating that CBD can protect against cognitive harms of cannabis. For example, recreational users of cannabis containing higher (>0.75%) CBD performed better in verbal memory testing during acute intoxication compared to users of cannabis with the same Δ9-THC levels but low (<0.14%) CBD [reviewed in 7]. CBD pre-treatment (600 mg oral) also protected against deficits in verbal learning and memory, and aspects of working memory during a Δ9-THC (1.5 mg/kg intravenous (i.v.)) challenge in healthy participants (n = 22) [reviewed in 7].
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Imaging studies over the past decade have revealed altered brain morphology in key regions of the brain implicated in cognition in cannabis users. For example, chronic heavy cannabis users (n = 15) exhibit reduced brain volume in the hippocampus and amygdala compared to matched non-using controls (n = 16) [8], and hippocampal shape aberrations were detected in cannabis users (n = 15 male chronic heavy users) that were exacerbated in people with co-morbid schizophrenia (n = 8 males) compared to healthy controls [9]. Interestingly, regular users of low CBD cannabis had reduced hippocampal volumes compared to non-users; a reduction that was not observed in the participants either using cannabis containing CBD or in former users [10]. The authors of that study concluded that CBD could reduce harm to brain health caused by cannabis use, while periods of abstinence could recover damage in the parameters examined [10]. Recently, it was reported that 10-weeks of oral CBD treatment (200 mg) increased the volume of discrete hippocampal regions in cannabis users (n = 18), with higher growth observed in heavy compared to light cannabis users [11]. Overall, these studies point to a protective effect of CBD on cognitive regions of the brain during cananbis use in humans; however, larger scale placebo-controlled trials are required. A potential mechanism for these benefits may relate to the neuroprotective characteristics of CBD, particularly its ability to stimulate neurogenesis, synaptic formation and neurite outgrowth (reveiwed in [12]).
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Similar results supporting a protective role of CBD have been reported in pre-clinical studies. For example, CBD (0.5 mg/kg) increased visual learning and memory, and procedural learning in Rhesus monkeys co-administered Δ9-THC (0.2 or 0.5 mg/kg) compared to those administered Δ9-THC alone; however, spatial working memory was further impaired by combined treatment (reviewed in [7]). Chronic Δ9-THC exposure in adolescent mice (3 mg/kg daily) reduced recognition memory that persisted into adulthood, but this was not apparent in the group receiving CBD (3 mg/kg CBD) co-treatment during Δ9-THC exposure [13]. On the other hand, research shows that there are no beneficial effects of CBD on cognition, including verbal learning and memory, social recognition, executive function, spatial memory or conditioned learning, when administered to healthy subjects (humans or rodents) (reviewed in [7, 13]).
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2.2. Cannabidiol treatment for neurological disorders and inflammatory disease states
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2.2.1. Alzheimer’s disease
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Alzheimer’s disease is the most common form of dementia. It is a progressive neurological disorder characterised by the presence of plaques and neurofibrillary tangles in the brain. Amyloid β peptides form densely packed extracellular filaments (plaques) that block cell signalling and trigger neuroinflammation. Neurofibrillary tangles are caused by transport-associated proteins called tau that form twisted structures during oxidative stress and block transport of nutrients and other essentials for neuronal function [14]. The progressive disruption and destruction of synapses results in memory loss and cognitive dysfunction. A role for cannabinoids as a therapy for Alzheimer’s disease has been proposed, in part due to the neuroprotective, anti-inflammatory and anti-oxidant properties of cannabinoids, as well as the role of the endocannabinoid system in memory and Alzheimer’s disease pathology (reviewed in [15]). One study found that Sativex®, containing Δ9-THC and CBD, reduced tau and amyloid deposition in the hippocampus and cortex in a mouse model of tauopathy [16]. In addition, Δ9-THC and CBD administration improved memory deficits in AβPP/PS1 transgenic mice with an Alzheimer-like phenotype, but not in mice with cognitive decline associated with healthy ageing [17]. Another study attributed CBD treatment (20 mg/kg oral, daily for 8 months) of social recognition deficits in AβPP/PS1 mice with the prevention of neuroinflammation and cholesterol homeostasis rather than a reduction in amyloid load [18]. Clinical studies are required to confirm whether CBD/Δ9-THC therapies can improve brain health and function in people with Alzheimer’s disease or dementia.
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2.2.2. Huntington’s disease
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Huntington’s disease is a progressive neurodegenerative disease of genetic origins, manifesting in motor impairment, cognitive decline and behavioural symptoms. In a double-blinded, placebo-controlled, cross-over clinical trial, Sativex® (orally administered in 12 sprays/day) was unable to improve cognitive, motor or behavioural scores in a cohort of patients with Huntington’s disease (n = 24) compared to placebo-treated controls after 12-weeks of treatment [19]. In a smaller double-blinded, randomised cross-over study, CBD alone (10 mg/kg/day, oral) also yielded no symptom efficacy, including recall memory, in 15 patients Huntington’s disease after 6-weeks of treatment [20]. However, large cohort studies of CBD administration in people with Huntington’s disease are required.
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2.2.3. Parkinson’s disease
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Parkinson’s disease occurs through the progressive degeneration of dopaminergic neurons in the midbrain, resulting in severe motor impairment and loss of motor control. CBD is a prime novel therapeutic candidate for the treatment of Parkinson’s disease due to its neuroprotective properties. However, one clinical study reported no improvement in motor or general symptoms scores in patients treated with CBD (75 or 300 mg/day) compared to placebo-treated controls (n = 7/group), although, overall quality of life was significantly improved in the 300 mg CBD treatment group compared to placebo-treated controls [21]. Another clinical study (open-label pilot study, n = 6) of Parkinson’s disease patients with psychosis revealed significant improvements to psychiatric scores, but not motor function following CBD (>150 mg/day oral CBD) administration for 4-weeks in combination with existing L-dopa medication [22]. On the other hand, CBD (0.5 or 5 mg/kg CBD administered in four injections) prevented cognition and motor dysfunction when administered prior to reserpine treatment in a rodent model of Parkinson’s disease [23].
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2.2.4. Ischemic brain injury
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Brain injury due to blood flow impediment and hypoxic damage can result in immediate and progressive cognitive decline. Ischemic brain injury can occur following events such as a stroke, cardiac arrest, near drowning or birth complications resulting in perinatal asphyxia. Rats exposed to hypoxic ischemia at birth exhibited recognition memory deficits that were attenuated by CBD (1 mg/kg) administered subcutaneously 10 min post-ischemia, while CBD treatment (3, 10 or 30 mg/kg 30 min pre- and 3, 24 and 48 h post-ischemic insult) increased spatial memory compared to placebo-treated ischemic rats (reviewed in [7]). In a subsequent study, acute CBD treatment (5 mg/kg, intraperitoneal (i.p.)) reduced apoptosis, neuronal loss and neuroinflammation in ischemic in neonatal rats [24], providing mechanistic clues about the behavioural restorative effects of CBD during hypoxic brain damage. A clinical trial investigating THC:CBD efficacy on spasticity following a stroke has been registered [25]; however, cognitive testing has not been proposed as a treatment outcome.
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2.2.5. Sepsis-induced encephalopathy
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Sepsis is a potentially life-threatening systemic inflammatory state that occurs as the body attempts to eliminate a pathogen. It can cause rapid cognitive impairment, particularly memory decline that was initially considered a transient state restored through the destruction of the pathogen and attenuation of the inflammatory response. However, sepsis is also associated with encephalopathy, a disease state of the brain that can manifest symptoms ranging from mild personality changes to cognitive and motor impairment, lethargy and coma. Sepsis-induced encephalopathy can be caused by increased permeability of the blood brain barrier and neuroinflammation that can lead to permanent functional impairment and enhance susceptibility to subsequent neurodegenerative disorders post-recovery [26]. Sub-chronic CBD treatment improved associative learning in a rodent model of sepsis (CBD administered either 2.5, 5 or 10 mg/kg daily for 9 days) compared to vehicle-treated controls (reviewed in [7]). CBD (single acute dose 3 mg/kg, i.v.) treatment also preserved blood–brain barrier integrity, restored normal vascular endothelial function and reduced inflammation in the mouse brain during endotoxic shock induced by administration of lipopolysaccharide (LPS) [27], a cell wall component of Gram-negative bacteria that can be used to model an excessive pro-inflammatory response in the host.
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2.2.6. Schizophrenia
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Schizophrenia is a chronic neurodevelopmental disorder characterised by three main symptom domains: positive (e.g., hallucinations, delusions and paranoia), negative (e.g., social withdrawal, flattened emotional expression, lack of motivation) and cognitive deficits. Existing antipsychotic medications confer minimal to no cognitive benefits (in some instances can further impair cognition) [28], and can cause serious weight gain and diabetes side-effects [29, 30]. We recently discovered that chronic CBD (10 mg/kg CBD, i.p., twice daily (b.i.d.)) treated cognitive impairment (learning, working and recognition memory) and social interaction deficits in a rat prenatal infection (poly I:C) model of schizophrenia-like phenotypes [31]. No behavioural changes were observed in healthy rats administered CBD and CBD did not cause weight gain side-effects [31]. An earlier clinical study (phase II, single-centred, double-blinded, randomised parallel-group controlled clinical trial of CBD vs. amisulpride) had reported improved positive and negative symptoms in people with schizophrenia following 4 weeks of CBD treatment, with therapeutic efficacy similar to the commercial antipsychotic, amisulpride; however, cognitive function was not examined [5]. More recently, a multi-centre double-blinded parallel-group clinical trial examined the efficacy of CBD co-treatment with the patient’s existing antipsychotic medication on a range of endpoints, including positive, negative and cognitive scores and Clinical Global Impression scales (CGI, measuring illness severity, improvement and response to treatment) [32]. Results showed significant improvements in positive (not negative) symptoms and CGI scores, as well as some improvement in cognitive performance (did not reach statistical significance, p = 0.068 CBD vs. placebo) when CBD was combined with the patient’s existing antipsychotic medications [32].
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2.3. Conclusions on the use of CBD in neurological disease
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There is substantial scientific evidence to show the beneficial effects of CBD in the brain, with protection and treatment efficacy for various cognitive behaviours conferred in multiple disease states. Overall, there seems to be a general requirement for further placebo-controlled clinical trials, as well as investigation of long-term efficacy and safety in different populations of people. Evidence for illness-specific optimal dosing regimens (dose, route of administration, timing and number of daily doses, effect of concurrent medications, etc.) is also required. In addition, similar to our rodent study of CBD effects on cognition in schizophrenia [31], most studies use either isolated CBD or combined THC and CBD. While this methodology enables investigators to attribute results to a specific compound, it may not be the optimal therapeutic approach as cannabis-derived plant molecules are thought to interact and produce a synergy that enhances therapeutic effects—termed the ‘entourage effect’.
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3. The entourage effect
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The entourage effect is defined as the act by which compounds (both cannabis phytochemicals and compounds from the endogenous cannabinoid system) augment or support the effects of major cannabinoids, for example, Δ9-THC, CBD, 2-arachidonoyl-glycerol (2-AG) [33, 34]. This phenomenon has been likened to an orchestra where ‘many musicians support and harmonise the melody provided by the soloists’ [34]. Compounds can exert synergistic effects through several mechanisms, for example by interacting with each other to improve bioavailability of beneficial compounds, or through combined actions on different therapeutic targets [35].
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The concept of a cannabis entourage effect is largely based on anecdotal evidence from medicinal and recreational users attesting to the notion that cannabis ‘works better’ as a whole plant extract and its existence has been argued back and forth over time. However, there is evidence to suggest that the cannabis plant contains active ingredients as well as ‘synergists’ that boost drug effects above that of the isolated compound. Indeed, early description of a potential synergy between molecules in the cannabis plant came from a study in the 1970s that reported a 2–4 times greater deficits in parameters such as processing tasks and motor function in subjects administered Brazilian cannabis samples compared to Δ9-THC [36]. The phrase ‘entourage effect’ was first described in 1998 in response to the finding that certain endogenous molecules (2-linoleoyl-glycerol (2-LG) and 2-palmitoyl-glycerol (2-PG)) potentiated the effects of the endocannabinoid, 2-AG [33]. Interestingly, cultured hippocampal neurons exposed to CBD-rich plant extracts exhibit a significantly greater intracellular signalling response compared to CBD alone [37]. This provides preliminary (in-vitro) evidence that CBD-rich plant extracts exert greater effects on cells of the hippocampus (a region of the brain highly implicated in learning and memory) than isolated CBD. Overall, it may be possible to boost the pro-cognitive therapeutic efficacy of CBD through a synergistic approach. Studies show that cannabinoids other than CBD could confer beneficial effects on the brain through synergistic mechanisms, for example, the parent phytocannabinoid cannabigerol (CBG) exerted greater analgesic effects on mice than Δ9-THC alone, while CBG and cannabichromene (CBC) both have anti-depressant effects in rodents (reviewed in [38]) and CBG is neuroprotective in a mouse model of Huntington’s Disease [39]. However, section 4 will focus on several key non-cannabinoid cannabis phytochemicals with promising evidence of positive effects on brain function.
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4. Non-cannabinoid phytochemicals of Cannabis: terpenes, flavonoids and anthocyanins
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The cannabis plant contains hundreds of phytochemicals, with new compounds and metabolites frequently identified. The concentration of chemicals in a cannabis plant can be influenced by multiple factors including nutrition, humidity, temperature, age of plant, strain, harvest time, plant stress, organ and storage conditions [1, 40]. Therefore, plant phytochemical composition is highly variable. Variability identified even within the same strain has led some authors to conclude that the name of a plant strain does not necessarily indicate potency or chemical composition [41]. However, others found that when grown under standardised conditions, certain cannabis strains can provide reproducible terpene and phytocannabinoid profiles that have been considered chemotaxonomic markers [42]. Furthermore, cannabinoid content can be used to classify plants into chemovars (plants with distinct photochemical profiles): Type I Δ9-THC-dominant, Type II Δ9-THC and CBD, Type III CBD-dominant and distinctions can be made outside these classes based on specific terpene profiles [43]. Therefore, it is possible to optimise plants to reproduce a distinct chemical composition and, potentially, specific medicinal characteristics.
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4.1. Terpenes: linalool, alpha-pinene and beta-caryophyllene
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Terpenes have been described as the most abundant class of small natural molecules by mass on Earth, undertaking innumerable structural and functional roles in most life forms on the planet (e.g., cholesterols for structural and signalling components of cell membranes, retinal in the eye for vision, carotenoids in photosynthesis) [44]. In cannabis, they create fragrances and flavours, but are also found in other plants and commonly used as safe food additives [38]. Terpenes can cross the blood brain barrier due to their lipophilic nature and studies have demonstrated a range of health benefits for some terpenes found in cannabis.
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4.1.1. Linalool
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Linalool is a monoterpene abundant in aromatic plants, such as lavender and purple basil [45]. Evidence shows that chronic administration of linalool reverses deficits in spatial memory and learning, with reduced amyloid plaque deposition and tau dysfunction in the hippocampus in rodent models of Alzheimer’s disease [46, 47], using 25 mg/kg and 100 mg/kg linalool, respectively. Linalool also prevented deficits in spatial memory, motor function, neuroinflammation and post-ischemic neurodegeneration in a rat model of global cerebral ischemia, following oral daily administration (25 mg/kg) for 1 month [48]. However, reduced short and long-term recognition memory (50 and 100 mg/kg linalool, i.p.) [49] and memory acquisition (3% preparation for inhalation) [50] were found when linalool was administered as a single dose to healthy rats. This apparent contradiction in findings could be attributed to the administration of linalool to healthy vs. cognitively impaired rats, suggesting that the compound exerts benefits in a disease state but is detrimental when not patho physiologically required; however, further investigation is necessary to confirm.
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4.1.2. Alpha-pinene
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Alpha-pinene (α-pinene) is a highly abundant monoterpene found in coniferous trees (e.g., pine and fir) and cannabis [51] that, according to cannabis culture, provides pine-needle fragrances and tastes to cannabis. In mice with cognitive deficits caused by scopolamine-induced blockade of acetylcholine neurotransmission (apparent in advanced stages of Alzheimer’s disease [52]), α-pinene (10 mg/kg, i.p.) improved working and spatial memory, and increased markers of acetylcholine synthesis in the cortex [53]. Inhalation of α-pinene can also influence major neurotransmitter signalling in the brain, for example it improved quality and duration of sleep in mice by modulating the major inhibitory neurotransmitter signalling system, gamma-aminobutyric acid (γ-aminobutyric acid, GABA)) [54], and decreased anxiety-like behaviour that was associated with increased tyrosine hydroxylase (the rate limiting enzyme for dopamine synthesis) in the midbrain [55]. Another study reported significant improvements in avoidance memory of cognitively impaired mice following administration of an essential oil obtained from a Korean fir tree containing α-pinene [56]; however, the results cannot be entirely attributed to this terpene due to the use of whole-plant extract containing other constituents.
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4.1.3. Beta-caryophyllene
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Beta-caryophyllene (β-caryophyllene) is a sesquiterpene that has a weak woody-spicy characteristic, abundant in cloves, black pepper, cinnamon and thyme [57, 58]. In a mouse model of Alzheimer’s disease, β-caryophyllene reversed spatial memory deficits, reduced β-amyloid deposition in the hippocampus and cortex, and reduced neuroinflammation when administered for 10 weeks (48 mg/kg, oral) [59]. In rats with chronic cerebral ischemia resembling vascular dementia, β-caryophyllene (administered in a hydroxypropyl-β-cyclodextrin inclusion complex delivery system to enhance its bioavailability) attenuated cognitive deficits and increased cerebral blood flow [60]. β-caryophyllene also prevented oxidative stress in the cortex of rats following transient global cerebral hypoperfusion/reperfusion [61]. Neurological scores were improved in mice administered β-caryophyllene (24 and 72 mg/kg, i.p.) following an induced stroke [62] and anti-depressant-like behaviour was reported in healthy mice following β-caryophyllene, through mechanisms involving catecholamine (adrenergic) neurotransmission [63]. Overall, the studies provide some evidence to support the role of β-caryophyllene as pro-cognitive, with anti-inflammatory, neuroprotective and anti-depressant effects.
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4.2. Phenolic acids: flavonoids and anthocyanins
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In addition to terpenes, cannabis plants contain phenolic compounds, including flavonoids and anthocyanins [40, 64, 65, 66]. Flavonoids are commonly consumed by humans through dietary fruit, vegetable, tea and wine intake. Anthocyanins are a group of flavonoids responsible for the blue-violet and red-orange colours of plant organs. Certain strains of cannabis plants exhibit a purple phenotype (Figure 1), which is widely attributed to anthocyanin content in recreational cannabis culture; however, experimental data showing anthocyanin levels of purple compared to non-purple strains appear to be lacking.
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Figure 1.
Inflorescence of purple cannabidiol (CBD)-rich, low Δ9-tetrahydrocannabinol (Δ9-THC) medicinal cannabis cultivar, GHM Genetic Development, Amsterdam, The Netherlands (2018).
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Flavonoids and anthocyanins are extensively researched due to their neuroprotective, anti-inflammatory and pro-cognitive characteristics and can pass the blood brain barrier [67]. For example, one study found that anthocyanin pre-treatment (200 mg/kg orally for 7 days) prevented cognitive deficits in a rat model of dementia [68]. Flavonoids improve working memory, processing speed, executive function and episodic memory in humans (reviewed in [69, 70]) and stimulate neurogenesis, synaptic plasticity and reduced neuroinflammation in the hippocampus (reviewed in [71]). Anthocyanin-rich cherry juice improved verbal fluency and short- and long-term memory performance in people with mild-to-moderate dementia during a 12 week randomised, controlled clinical trial of older people (+70 years) with mild to moderate dementia (200 ml/day cherry juice vs. control juice lacking anthocyanin) [72]. Interestingly, both cherries and cannabis plants contain phenolic acids related to flavonoid and anthocyanin biosynthesis pathways [65, 73]. Indeed, hemp seed extract can contain phenolic compound levels that are comparable to Japanese plums [74, 75]. Japanese plums are an important source of anthocyanins, with particularly high levels in darker purple, blue and black coloured fruits [75]. Similar to cannabis plants, the phytochemical profile of Japanese plum varieties is influenced by horticultural practices, processing and storage conditions [75]. Other commercial plants, such as violet cauliflower and Thai purple basil, gain their unusual purple colouring through modifications to anthocyanin regulatory genes [76, 77]. Therefore, it is possible that plants can be manipulated naturally and artificially (i.e., genetically) to maximise anthocyanin content.
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\n
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4.3. Conclusions on the effects of terpenes and flavonoids on the brain
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The terpenes linalool, α-pinene and β-caryophyllene, as well as flavonoids and anthocyanins confer pro-cognitive, neuroprotective and anti-inflammatory effects in models of cerebral ischemia and Alzheimer’s disease, as well as some anxiolytic effects. Most studies have been conducted in pre-clinical (rodent) models; however, pro-cognitive effects of flavonoids and anthocyanins have been shown in human clinical studies of dementia. Overall, combinations of CBD with other key phytochemicals found in cannabis could confer benefits on brain health through a multi-target synergy (entourage effect); however, further research is required.
\n
\n
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5. Overall conclusion
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This chapter has identified a consensus in the scientific literature that specific phytochemicals (CBD, linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanins) found in cannabis plants are beneficial for cognition and brain health in a number of disease states. These compounds are psychoactive as they alter the brain to effect behaviour, and there is some evidence that they can differentially affect healthy individuals (e.g., CBD has no cognitive benefits and linalool has detrimental effects on cognition in healthy subjects). Therefore, societal consideration of ‘medicinal cannabis’ as a true medicine is necessary, that is, prescribed for patients who require treatment of a clinically diagnosed illness. Further research is needed to inform optimal prescription for treating specific illnesses, including dose, route of administration, long-term clinical efficacy, safety and side effects. There is some evidence to support the existence of an ‘entourage effect’—such synergism could arise from a multi-target approach. The united benefits of specific terpenes and flavonoids could boost the therapeutic potential of CBD to improve cognition in disease states that manifest impairment; we are currently investigating these synergies in my laboratory. An other exciting future area of investigation is the identification of select cannabis phytochemical profiles that will treat specific illnesses with optimal efficacy. Following this, efforts towards standardising horticultural and cannabis plant processing practices to ensure optimal and reproducible medicines can be directed towards a proven goal—a translational interface between medical science and horticulture.
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Acknowledgments
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I wish to acknowledge the work of Ashleigh L. Osborne, Professor Nadia Solowij and Distinguished Professor Xu-Feng Huang as co-investigators on our project examining the pro-cognitive effects of CBD in a rodent model of schizophrenia. Thanks to Mr. Heiko Hampsink, GHM Genetic Development, The Netherlands, for supplying the purple cannabis photo. I extend gratitude to Mr. Thomas Forrest (Indicated Technology, Australia) and Mr. Heiko Hampsink for generously sharing their knowledge of cannabis horticulture.
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Conflict of interest
There are no conflicts of interest to declare.
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Notes/Thanks/Other declarations
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I dedicate this book chapter to my husband, M. Green, for his tireless support.
\n
\n',keywords:"medicinal cannabis, entourage effect, synergy, cannabidiol, CBD, terpenes, linalool, alpha-pinene, beta-caryophyllene, phenol, flavonoid, anthocyanins, purple cannabis, marijuana, cognition, learning, memory, brain, therapeutics, neuroprotection, inflammation",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/62431.pdf",chapterXML:"https://mts.intechopen.com/source/xml/62431.xml",downloadPdfUrl:"/chapter/pdf-download/62431",previewPdfUrl:"/chapter/pdf-preview/62431",totalDownloads:1850,totalViews:592,totalCrossrefCites:4,dateSubmitted:"March 14th 2018",dateReviewed:"June 3rd 2018",datePrePublished:"November 5th 2018",datePublished:"May 10th 2019",dateFinished:"July 3rd 2018",readingETA:"0",abstract:"‘Medicinal cannabis’ can be defined as pharmaceutical grade cannabis-based products used for the treatment of illness. Beneficial treatment effects of cannabidiol (CBD), a major non-intoxicating compound isolated from the cannabis plant, have been shown in multiple states of cognitive impairment, including neurodegenerative (Alzheimer’s, Huntington’s and Parkinson’s disease), neuroinflammatory (sepsis-induced encephalopathy) and neurological disorders (ischemic brain injury). CBD can also treat some of the symptoms of schizophrenia, including cognitive deficits (impairments in learning and memory), which is a major symptom domain of the illness that is largely resistant to existing antipsychotic medications. However, empirical evidence suggests the presence of an ‘entourage effect’ in cannabis; that is, observations that medicinal cannabis seems to work better in some instances when administered as a whole-plant extract. While scientific evidence highlights isolated CBD as a strong candidate for treating cognitive impairment, the entourage effect suggests that the co-operation of other plant molecules could provide further benefits. This chapter explores the scientific evidence surrounding the benefits of CBD and other specific key phytochemicals in cannabis: linalool, α-pinene, β-caryophyllene, flavonoids and anthocyanin, on brain health and cognition.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/62431",risUrl:"/chapter/ris/62431",signatures:"Katrina Weston-Green",book:{id:"7040",type:"book",title:"Recent Advances in Cannabinoid Research",subtitle:null,fullTitle:"Recent Advances in Cannabinoid Research",slug:"recent-advances-in-cannabinoid-research",publishedDate:"May 10th 2019",bookSignature:"Willard J Costain and Robert B Laprairie",coverURL:"https://cdn.intechopen.com/books/images_new/7040.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-152-6",printIsbn:"978-1-83880-151-9",pdfIsbn:"978-1-83880-641-5",isAvailableForWebshopOrdering:!0,editors:[{id:"89884",title:"Dr.",name:"Willard James",middleName:null,surname:"Costain",slug:"willard-james-costain",fullName:"Willard James Costain"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Cannabidiol (CBD) and the brain",level:"1"},{id:"sec_2_2",title:"2.1. Cannabidiol protects against cognitive harms of high-THC Cannabis",level:"2"},{id:"sec_3_2",title:"2.2. Cannabidiol treatment for neurological disorders and inflammatory disease states",level:"2"},{id:"sec_3_3",title:"2.2.1. Alzheimer’s disease",level:"3"},{id:"sec_4_3",title:"2.2.2. Huntington’s disease",level:"3"},{id:"sec_5_3",title:"2.2.3. Parkinson’s disease",level:"3"},{id:"sec_6_3",title:"2.2.4. Ischemic brain injury",level:"3"},{id:"sec_7_3",title:"2.2.5. Sepsis-induced encephalopathy",level:"3"},{id:"sec_8_3",title:"2.2.6. Schizophrenia",level:"3"},{id:"sec_10_2",title:"2.3. Conclusions on the use of CBD in neurological disease",level:"2"},{id:"sec_12",title:"3. The entourage effect",level:"1"},{id:"sec_13",title:"4. Non-cannabinoid phytochemicals of Cannabis: terpenes, flavonoids and anthocyanins",level:"1"},{id:"sec_13_2",title:"4.1. Terpenes: linalool, alpha-pinene and beta-caryophyllene",level:"2"},{id:"sec_13_3",title:"4.1.1. Linalool",level:"3"},{id:"sec_14_3",title:"4.1.2. Alpha-pinene",level:"3"},{id:"sec_15_3",title:"4.1.3. Beta-caryophyllene",level:"3"},{id:"sec_17_2",title:"4.2. Phenolic acids: flavonoids and anthocyanins",level:"2"},{id:"sec_18_2",title:"4.3. Conclusions on the effects of terpenes and flavonoids on the brain",level:"2"},{id:"sec_20",title:"5. Overall conclusion",level:"1"},{id:"sec_21",title:"Acknowledgments",level:"1"},{id:"sec_24",title:"Conflict of interest",level:"1"},{id:"sec_21",title:"Notes/Thanks/Other declarations",level:"1"}],chapterReferences:[{id:"B1",body:'Citti C, Pacchetti B, Vandelli MA, Forni F, Cannazza G. Analysis of cannabinoids in commercial hemp seed oil and decarboxylation kinetics studies of cannabidiolic acid (CBDA). Journal of Pharmaceutical and Biomedical Analysis. 2018;149:532-540. DOI: 10.1016/j.jpba.2017.11.044\n'},{id:"B2",body:'ElSohly MA, Gul W. 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Amelioration of scopolamine-induced learning and memory impairment by alpha-Pinene in C57BL/6 mice. Evidence-based Complementary and Alternative Medicine. 2017;2017:4926815. DOI: 10.1155/2017/4926815\n'},{id:"B54",body:'Yang H, Woo J, Pae AN, Um MY, Cho NC, Park KD, Yoon M, Kim J, Lee CJ, Cho S. Alpha-Pinene, a major constituent of pine tree oils, enhances non-rapid eye movement sleep in mice through GABAA-benzodiazepine receptors. Molecular Pharmacology. 2016;90(5):530-539. DOI: 10.1124/mol.116.105080\n'},{id:"B55",body:'Kasuya H, Okada N, Kubohara M, Satou T, Masuo Y, Koike K. Expression of BDNF and TH mRNA in the brain following inhaled administration of alpha-pinene. Phytotherapy Research. 2015;29(1):43-47. DOI: 10.1002/ptr.5224\n'},{id:"B56",body:'Kim K, Bu Y, Jeong S, Lim J, Kwon Y, Cha DS, Kim J, Jeon S, Eun J, Jeon H. Memory-enhancing effect of a supercritical carbon dioxide fluid extract of the needles of Abies koreana on scopolamine-induced amnesia in mice. Bioscience, Biotechnology, and Biochemistry. 2006;70(8):1821-1826. DOI: 10.1271/bbb.50608\n'},{id:"B57",body:'Gertsch J, Leonti M, Raduner S, Racz I, Chen J-Z, Xie X-Q, Altmann K-H, Karsak M, Zimmer A. Beta-caryophyllene is a dietary cannabinoid. Proceedings of the National Academy of Sciences of the United States of America. 2008;105(26):9099-9104. DOI: 10.1073/pnas.0803601105\n'},{id:"B58",body:'Nurdjannah N, Bermawie N, 11 - Cloves A2. In: Peter KV, editor. Handbook of Herbs and Spices. 2 ed. Cambridge, UK: Woodhead Publishing; 2012. pp. 197-215. DOI: 10.1533/9780857095671.197\n'},{id:"B59",body:'Cheng Y, Dong Z, Liu S. Beta-Caryophyllene ameliorates the Alzheimer-like phenotype in APP/PS1 mice through CB2 receptor activation and the PPARgamma pathway. Pharmacology. 2014;94(1-2):1-12. DOI: 10.1159/000362689\n'},{id:"B60",body:'Lou J, Teng Z, Zhang L, Yang J, Ma L, Wang F, Tian X, An R, Yang M, Zhang Q, Xu L, Dong Z. beta-Caryophyllene/hydroxypropyl-beta-cyclodextrin inclusion complex improves cognitive deficits in rats with vascular dementia through the cannabinoid receptor type 2-mediated pathway. Frontiers in Pharmacology. 2017;8:2. DOI: 10.3389/fphar.2017.00002\n'},{id:"B61",body:'Poddighe L, Carta G, Serra MP, Melis T, Boi M, Lisai S, Murru E, Muredda L, Collu M, Banni S, Quartu M. Acute administration of beta-caryophyllene prevents endocannabinoid system activation during transient common carotid artery occlusion and reperfusion. Lipids in Health and Disease. 2018;17(1):23. DOI: 10.1186/s12944-018-0661-4\n'},{id:"B62",body:'Yang M, Lv Y, Tian X, Lou J, An R, Zhang Q, Li M, Xu L, Dong Z. Neuroprotective effect of beta-caryophyllene on cerebral ischemia-reperfusion injury via regulation of necroptotic neuronal death and inflammation: In vivo and in vitro. Frontiers in Neuroscience. 2017;11:583. DOI: 10.3389/fnins.2017.00583\n'},{id:"B63",body:'Oliveira DR, Silva DM, Florentino IF, de Brito A, Fajemiroye JO, Silva DPB, da Rocha F, Costa EA, De Carvalho PG. Monoamine involvement in the antidepressant-like effect of beta-caryophyllene. CNS & Neurological Disorders Drug Targets. 2018. DOI: 10.2174/1871527317666180420150249\n'},{id:"B64",body:'Flores-Sanchez IJ, Verpoorte R. Secondary metabolism in Cannabis. Phytochemistry Reviews. 2008;7(3):615-639. DOI: 10.1007/s11101-008-9094-4\n'},{id:"B65",body:'Docimo T, Consonni R, Coraggio I, Mattana M. Early Phenylpropanoid biosynthetic steps in Cannabis sativa: Link between genes and metabolites. International Journal of Molecular Sciences. 2013;14(7):13626-13644. DOI: 10.3390/ijms140713626\n'},{id:"B66",body:'Lesma G, Consonni R, Gambaro V, Remuzzi C, Roda G, Silvani A, Vece V, Visconti GL. Cannabinoid-free Cannabis sativa L. grown in the Po valley: Evaluation of fatty acid profile, antioxidant capacity and metabolic content. Natural Product Research. 2014;28(21):1801-1807. DOI: 10.1080/14786419.2014.926354\n'},{id:"B67",body:'Youdim KA, Dobbie MS, Kuhnle G, Proteggente AR, Abbott NJ, Rice-Evans C. Interaction between flavonoids and the blood-brain barrier: In vitro studies. Journal of Neurochemistry. 2003;85(1):180-192\n'},{id:"B68",body:'Gutierres JM, Carvalho FB, Schetinger MRC, Marisco P, Agostinho P, Rodrigues M, Rubin MA, Schmatz R, da Silva CR, de Cognato PG, Farias JG, Signor C, Morsch VM, Mazzanti CM, Bogo M, Bonan CD, Spanevello R. Anthocyanins restore behavioral and biochemical changes caused by streptozotocin-induced sporadic dementia of Alzheimer’s type. Life Sciences. 2014;96(1):7-17. DOI: 10.1016/j.lfs.2013.11.014\n'},{id:"B69",body:'Bell L, Lamport JD, Butler TL, Williams MC. A review of the cognitive effects observed in humans following acute supplementation with flavonoids, and their associated mechanisms of action. Nutrients. 2015;7(12):10290-10306. DOI: 10.3390/nu7125538\n'},{id:"B70",body:'Spencer JP. The impact of fruit flavonoids on memory and cognition. The British Journal of Nutrition. 2010;104(Suppl 3):S40-S47. DOI: 10.1017/s0007114510003934\n'},{id:"B71",body:'Vauzour D. Effect of flavonoids on learning, memory and neurocognitive performance: Relevance and potential implications for Alzheimer’s disease pathophysiology. Journal of the Science of Food and Agriculture. 2014;94(6):1042-1056. DOI: 10.1002/jsfa.6473\n'},{id:"B72",body:'Kent K, Charlton K, Roodenrys S, Batterham M, Potter J, Traynor V, Gilbert H, Morgan O, Richards R. Consumption of anthocyanin-rich cherry juice for 12 weeks improves memory and cognition in older adults with mild-to-moderate dementia. European Journal of Nutrition. 2017;56(1):333-341. DOI: 10.1007/s00394-015-1083-y\n'},{id:"B73",body:'Kent K, Charlton KE, Jenner A, Roodenrys S. Acute reduction in blood pressure following consumption of anthocyanin-rich cherry juice may be dose-interval dependant: A pilot cross-over study. International Journal of Food Sciences and Nutrition. 2016;67(1):47-52. DOI: 10.3109/09637486.2015.1121472\n'},{id:"B74",body:'Smeriglio A, Galati EM, Monforte MT, Lanuzza F, D’Angelo V, Circosta C. Polyphenolic compounds and antioxidant activity of cold-pressed seed oil from Finola cultivar of Cannabis sativa L. Phytotherapy Research. 2016;30(8):1298-1307. DOI: 10.1002/ptr.5623\n'},{id:"B75",body:'Fanning KJ, Topp B, Russell D, Stanley R, Netzel M. Japanese plums (Prunus salicina Lindl.) and phytochemicals—Breeding, horticultural practice, postharvest storage, processing and bioactivity. Journal of the Science of Food and Agriculture. 2014;94(11):2137-2147. DOI: 10.1002/jsfa.6591\n'},{id:"B76",body:'Chiu L-W, Zhou X, Burke S, Wu X, Prior RL, Li L. The purple cauliflower arises from activation of a MYB transcription factor. Plant Physiology. 2010;154(3):1470-1480. DOI: 10.1104/pp.110.164160\n'},{id:"B77",body:'Phippen WB, Simon JE. Anthocyanin inheritance and instability in purple basil (Ocimum basilicum L.). Journal of Heredity. 2000;91(4):289-296\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Katrina Weston-Green",address:"katrina_green@uow.edu.au",affiliation:'
Neuropharmacology and Molecular Psychiatry Research Laboratory, School of Medicine, Faculty of Science, Medicine and Health, University of Wollongong, Australia
Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Australia
Illawarra Health and Medical Research Institute, Australia
Australian Centre for Cannabinoid Clinical and Research Excellence, Australia
'}],corrections:null},book:{id:"7040",type:"book",title:"Recent Advances in Cannabinoid Research",subtitle:null,fullTitle:"Recent Advances in Cannabinoid Research",slug:"recent-advances-in-cannabinoid-research",publishedDate:"May 10th 2019",bookSignature:"Willard J Costain and Robert B Laprairie",coverURL:"https://cdn.intechopen.com/books/images_new/7040.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83880-152-6",printIsbn:"978-1-83880-151-9",pdfIsbn:"978-1-83880-641-5",isAvailableForWebshopOrdering:!0,editors:[{id:"89884",title:"Dr.",name:"Willard James",middleName:null,surname:"Costain",slug:"willard-james-costain",fullName:"Willard James Costain"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"177829",title:"MSc.",name:"Jesus A.",middleName:null,surname:"Díaz-Real",email:"jdiaz@cideteq.mx",fullName:"Jesus A. 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LOC devices exhibit advantages related to the use of microfluidic channels such as small sample and reagent consumption, portability, low-power consumption, laminar flow, and higher surface area/volume ratio that enhances both thermal dissipation and electrochemical kinetics. Fuel cells are electrochemical devices that convert chemical energy to electrical energy. These are considered as one of the greener ways to generate electricity because typical fuel cells produce water and heat as the main reaction byproducts. The technical challenges to develop systems at the microscale and the advantages of microfluidics exhibited an important impact on fuel cells for several reasons, mainly related to avoid inherent problems of gaseous-based fuel cells. As a result, the birth of a new type of fuel cells as microfluidic fuel cells (MFCs) took place. The first microfluidic fuel cell was reported in 2002. This MFC was operated with liquid fuel/oxidant and had the advantage of the low laminar flow generated using a “Y” microfluidic channel to separate the anodic and cathodic streams, resulting in an energy conversion device that did not require a physical barrier to separate both streams. This electrochemical system originated a specific type of MFCs categorized as membraneless also called colaminar microfluidic fuel cells. Since that year, numerous works focused on the nature of fuels, oxidants and anodic/cathodic electrocatalysts, and cell designs have been reported. The limiting parameters of this kind of devices toward their use in portable applications are related to their low cell performances, small mass activity, and partial selectivity/durability of electrocatalysts. On the other hand, it has been observed that the cell design has a high effect on the cell performance due to internal cell resistances and the crossover effect. Furthermore, current technology is growing faster than last centuries and new microfabrication technologies are always emerging, allowing the development of smaller and more powerful microfluidic energy devices. In this chapter, the application of microfluidics in membraneless fuel cells is addressed in terms of evolution of cell designs of miniaturized microfluidic fuel cells as a result of new discoveries in microfabrication technology and the use of several fuels and electrocatalysts for specific and selective applications.",signatures:"Jesus A. Diaz-Real, Minerva Guerra-Balcázar, Noe Arjona, Francisco\nCuevas-Muñiz, Luis Gerardo Arriaga and Janet Ledesma-García",authors:[{id:"23083",title:"Dr.",name:"Luis Gerardo",surname:"Arriaga",fullName:"Luis Gerardo Arriaga",slug:"luis-gerardo-arriaga",email:"larriaga@cideteq.mx"},{id:"176367",title:"Dr.",name:"Janet",surname:"Ledesma-García",fullName:"Janet Ledesma-García",slug:"janet-ledesma-garcia",email:"janet.ledesma@uaq.mx"},{id:"177828",title:"Dr.",name:"Noe",surname:"Arjona",fullName:"Noe Arjona",slug:"noe-arjona",email:"wvelazquez@cideteq.mx"},{id:"177829",title:"MSc.",name:"Jesus A.",surname:"Díaz-Real",fullName:"Jesus A. Díaz-Real",slug:"jesus-a.-diaz-real",email:"jdiaz@cideteq.mx"},{id:"177830",title:"Dr.",name:"Francisco",surname:"Cuevas-Muñiz",fullName:"Francisco Cuevas-Muñiz",slug:"francisco-cuevas-muniz",email:"fcuevas@cideteq.mx"},{id:"177831",title:"Dr.",name:"Minerva",surname:"Guerra-Balcázar",fullName:"Minerva Guerra-Balcázar",slug:"minerva-guerra-balcazar",email:"minbalca@yahoo.com.mx"}],book:{id:"5099",title:"Advances in Microfluidics",slug:"advances-in-microfluidics-new-applications-in-biology-energy-and-materials-sciences",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"176954",title:"Ph.D. Student",name:"Babak",surname:"Taghavi",slug:"babak-taghavi",fullName:"Babak Taghavi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Royal Institute of Technology",institutionURL:null,country:{name:"Sweden"}}},{id:"176973",title:"Ph.D. Student",name:"Natalia",surname:"Bakhtina",slug:"natalia-bakhtina",fullName:"Natalia Bakhtina",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Karlsruhe Institute of Technology",institutionURL:null,country:{name:"Germany"}}},{id:"176994",title:"Prof.",name:"Lin",surname:"Gui",slug:"lin-gui",fullName:"Lin Gui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Chinese Academy of Sciences",institutionURL:null,country:{name:"China"}}},{id:"177016",title:"Dr.",name:"Adrien",surname:"Chauvet",slug:"adrien-chauvet",fullName:"Adrien Chauvet",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"More Than 10 years of experience in developing and applying ultrafast spectroscopy to molecular complexes:\r\n- PhD in BioPhysics from Purdue University (USA)\r\n- 2.5y postdoc in Physical Chemistry at EPFL (CH)\r\n- 1y postodc in BioPhysics at the University of Geneva (CH)\r\n- Lecturer of Physical Chemistry since 2016",institutionString:null,institution:{name:"University of Sheffield",institutionURL:null,country:{name:"United Kingdom"}}},{id:"177026",title:"Dr.",name:"Neil",surname:"MacKinnon",slug:"neil-mackinnon",fullName:"Neil MacKinnon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Karlsruhe Institute of Technology",institutionURL:null,country:{name:"Germany"}}},{id:"177027",title:"Prof.",name:"Jan",surname:"Korvink",slug:"jan-korvink",fullName:"Jan Korvink",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Karlsruhe Institute of Technology",institutionURL:null,country:{name:"Germany"}}},{id:"177061",title:"Dr.",name:"Jiantong",surname:"Li",slug:"jiantong-li",fullName:"Jiantong Li",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Royal Institute of Technology",institutionURL:null,country:{name:"Sweden"}}},{id:"177064",title:"Ph.D.",name:"Meng",surname:"Gao",slug:"meng-gao",fullName:"Meng Gao",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Technical Institute of Physics and Chemistry",institutionURL:null,country:{name:"China"}}},{id:"177065",title:"Associate Prof.",name:"Taotao",surname:"Fu",slug:"taotao-fu",fullName:"Taotao Fu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Tianjin University",institutionURL:null,country:{name:"China"}}},{id:"177071",title:"Dr.",name:"Victor",surname:"Sebastian",slug:"victor-sebastian",fullName:"Victor Sebastian",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Zaragoza",institutionURL:null,country:{name:"Spain"}}}]},generic:{page:{slug:"copyright-policy",title:"Copyright Policy",intro:"
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Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
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IntechOpen only publishes manuscripts for which it has publishing rights. This is governed by a publication agreement between the Author and IntechOpen. This agreement is accepted by the Author when the manuscript is submitted and deals with both the rights of the publisher and Author, as well as any obligations concerning a particular manuscript. However, in accepting this agreement, Authors continue to retain significant rights to use and share their publications.
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By accepting the agreement terms Authors retain their copyright on their Work but grant broad publishing and distribution rights to the publisher.
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Depending on the type of publication (Chapter or Long Form Monograph/Compacts; see definitions below), IntechOpen applies a Creative Commons license to the publication, allowing readers to use and share it freely.
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Although this chapter cannot provide a comprehensive account of the state of knowledge regarding plant saponins, we hope that it will help make saponins the focus of ongoing international cooperation.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Dorota Kregiel, Joanna Berlowska, Izabela Witonska, Hubert\nAntolak, Charalampos Proestos, Mirko Babic, Ljiljana Babic and\nBolin Zhang",authors:[{id:"179443",title:"Associate Prof.",name:"Dorota",middleName:null,surname:"Kregiel",slug:"dorota-kregiel",fullName:"Dorota Kregiel"},{id:"197451",title:"MSc.",name:"Hubert",middleName:null,surname:"Antolak",slug:"hubert-antolak",fullName:"Hubert Antolak"},{id:"198329",title:"Dr.",name:"Joanna",middleName:null,surname:"Berlowska",slug:"joanna-berlowska",fullName:"Joanna Berlowska"},{id:"198330",title:"Prof.",name:"Izabela",middleName:null,surname:"Witonska",slug:"izabela-witonska",fullName:"Izabela Witonska"},{id:"198333",title:"Dr.",name:"Charalampos",middleName:null,surname:"Proestos",slug:"charalampos-proestos",fullName:"Charalampos Proestos"},{id:"198334",title:"Prof.",name:"Mirko",middleName:null,surname:"Babic",slug:"mirko-babic",fullName:"Mirko Babic"},{id:"198335",title:"Prof.",name:"Bolin",middleName:null,surname:"Zhang",slug:"bolin-zhang",fullName:"Bolin Zhang"},{id:"204881",title:"Prof.",name:"Ljiljana",middleName:null,surname:"Babic",slug:"ljiljana-babic",fullName:"Ljiljana Babic"}]},{id:"55368",doi:"10.5772/intechopen.68755",title:"Multifunctional Gemini Surfactants: Structure, Synthesis, Properties and Applications",slug:"multifunctional-gemini-surfactants-structure-synthesis-properties-and-applications",totalDownloads:4501,totalCrossrefCites:23,totalDimensionsCites:46,abstract:"Gemini cationic surfactants are compounds which are composed of two hydrophilic head groups and two hydrophobic tails linked by a spacer at the head groups or closed to them. The spacer can be either hydrophobic or hydrophilic. It can be rigid or flexible. The neutral charge of the molecule is retained by the presence of organic or inorganic counterions. Critical micelle concentrations (CMCs), surface tension (γ) and minimal inhibitory concentration (MIC) are dozen times lower than corresponding parameters of monomeric surfactants. The unique properties of gemini surfactants with a wide range of hydrophilic-lipophilic balance (HLB) make them a very useful, innovative material in detergents, cosmetics, personal care products, additives for paints and coatings, biocides, material science, organic synthesis, pharmacy, textiles, enhanced oil recovery, nanotechnology, petroleum and many other branches of life. A large number of papers concerning gemini surfactants have been published so far. This review presents a synthetic look at current work devoted to structure, synthesis and applications of gemini surfactants.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Bogumil E. Brycki, Iwona H. Kowalczyk, Adrianna Szulc, Olga\nKaczerewska and Marta Pakiet",authors:[{id:"197271",title:"Dr.",name:"Bogumil E.",middleName:null,surname:"Brycki",slug:"bogumil-e.-brycki",fullName:"Bogumil E. Brycki"},{id:"207547",title:"Dr.",name:"Iwona",middleName:null,surname:"Kowalczyk",slug:"iwona-kowalczyk",fullName:"Iwona Kowalczyk"},{id:"207548",title:"Dr.",name:"Adrianna",middleName:null,surname:"Szulc",slug:"adrianna-szulc",fullName:"Adrianna Szulc"},{id:"207549",title:"Dr.",name:"Olga",middleName:null,surname:"Kaczerewska",slug:"olga-kaczerewska",fullName:"Olga Kaczerewska"},{id:"207550",title:"Dr.",name:"Marta",middleName:null,surname:"Pakiet",slug:"marta-pakiet",fullName:"Marta Pakiet"}]},{id:"54704",doi:"10.5772/67977",title:"Amino Acid-Based Surfactants for Biomedical Applications",slug:"amino-acid-based-surfactants-for-biomedical-applications",totalDownloads:3189,totalCrossrefCites:9,totalDimensionsCites:21,abstract:"The growing demand for surfactants worldwide has a profound impact on the environment and public health. The quest for environmentally friendly “green” surfactants has driven research toward bio-based surfactants from renewable sources with improved performances and low toxicity. Amino acid-based surfactants (AAS) are a promising class of biocompatible and biodegradable surfactants for biomedical applications due to their improved safety profiles that meet the requirements of both physiological and ecological compatibility. Natural amino acids are chiral compounds and important raw materials for production of AAS. The amino acid pool allows the synthesis of multifunctional surfactants with chiral properties that can be tailored for specific technological and/or biomedical applications. The nature of the amino acid residue, the chirality, and the ability for hydrogen bond formation strongly influences the surface active properties and self-assembly behavior of AAS. This review summarizes recent developments in AAS structure-property relationships providing valuable information for modulation of the surface active and biological properties of AAS to meet specific biomedical applications. The interaction of AAS with biointerfaces and biological molecules is also addressed concerning cellular toxicity and potential therapeutic applications of AAS as antimicrobial agents, drug delivery vehicles, and a promising alternative to viral vectors in gene therapy.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Lídia Pinheiro and Célia Faustino",authors:[{id:"199931",title:"Dr.",name:"Lidia",middleName:null,surname:"Pinheiro",slug:"lidia-pinheiro",fullName:"Lidia Pinheiro"},{id:"201447",title:"Dr.",name:"Celia",middleName:null,surname:"Faustino",slug:"celia-faustino",fullName:"Celia Faustino"}]},{id:"54753",doi:"10.5772/67998",title:"Recent Advances in Catanionic Mixtures",slug:"recent-advances-in-catanionic-mixtures",totalDownloads:1973,totalCrossrefCites:8,totalDimensionsCites:18,abstract:"Most surfactant mixtures display synergistic physicochemical properties, which have led to their extensive application in various technologies. Aqueous mixtures of two oppositely charged surfactants, so‐called catanionic surfactant mixtures, exhibit the strongest synergistic effect, which is manifested as high surface activity, enhanced adsorption and a low critical aggregation concentration. In addition, catanionic systems display rich phase behavior and a range of nano and microstructures, including small spherical micelles, rod‐like micelles as well as open and closed bilayers (vesicles). The spontaneous formation of catanionic vesicles is of special interest due to their various applications in nanotechnology and pharmaceutical formulations. In this chapter, the properties of catanionic mixtures of amphiphilic molecules with advantageous properties are discussed. Since numerous papers dealing with catanionic mixtures of monomeric surfactants already exist, the aim of this chapter is to summarize recent progress in mixtures of structurally different surfactants. At the end of the chapter, special emphasis is placed on applications of catanionic mixtures.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Darija Domazet Jurašin, Suzana Šegota, Vida Čadež, Atiđa Selmani\nand Maja Dutour Sikirć",authors:[{id:"30822",title:"Dr.",name:"Maja",middleName:null,surname:"Dutour Sikiric",slug:"maja-dutour-sikiric",fullName:"Maja Dutour Sikiric"},{id:"169636",title:"Dr.",name:"Darija",middleName:null,surname:"Domazet Jurašin",slug:"darija-domazet-jurasin",fullName:"Darija Domazet Jurašin"},{id:"199044",title:"Dr.",name:"Suzana",middleName:null,surname:"Šegota",slug:"suzana-segota",fullName:"Suzana Šegota"},{id:"199045",title:"Dr.",name:"Vida",middleName:null,surname:"Čadež",slug:"vida-cadez",fullName:"Vida Čadež"},{id:"199046",title:"Dr.",name:"Atiđa",middleName:null,surname:"Selmani",slug:"atidja-selmani",fullName:"Atiđa Selmani"}]},{id:"54922",doi:"10.5772/68020",title:"The Versatile Dioctadecyldimethylammonium Bromide",slug:"the-versatile-dioctadecyldimethylammonium-bromide",totalDownloads:1557,totalCrossrefCites:2,totalDimensionsCites:12,abstract:"Dioctadecyldimethylammonium bromide (DODAB) is a quaternary ammonium surfactant (Quat) with interesting properties and applications. In this chapter, DODAB characteristics as compared to other Quats emphasize its self-assembly in aqueous solutions and the novel applications involving this useful cationic lipid so easily combined with biomolecules and interfaces to yield a wide range of novel uses in many fields such as delivery of drugs, vaccines and genes, design of nanoparticles, modification of interfaces, and many others yet to come.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Ana Maria Carmona-Ribeiro",authors:[{id:"5978",title:"Prof.",name:"Ana Maria",middleName:null,surname:"Carmona-Ribeiro",slug:"ana-maria-carmona-ribeiro",fullName:"Ana Maria Carmona-Ribeiro"}]}],mostDownloadedChaptersLast30Days:[{id:"54735",title:"Saponin-Based, Biological-Active Surfactants from Plants",slug:"saponin-based-biological-active-surfactants-from-plants",totalDownloads:6756,totalCrossrefCites:29,totalDimensionsCites:74,abstract:"Plants have the ability to synthesize almost unlimited number of substances. In many cases, these chemicals serve in plant defense mechanisms against microorganisms, insects, and herbivores. Generally, any part of the plant may contain the various active ingredients. Among the plant, active compounds are saponins, which are traditionally used as natural detergents. The name ‘saponin’ comes from the Latin word ‘sapo,’ which means ‘soap’ as saponins show the unique properties of foaming and emulsifying agents. Steroidal and triterpenoid saponins can be used in many industrial applications, from the preparation of steroid hormones in the pharmaceutical industry to utilization as food additives that exploit their non‐ionic surfactant properties. Saponins also exhibit different biological activities. This chapter has been prepared by participants of the Marie Sklodowska‐Curie Action—Research and Innovation Staff Exchange (RISE) in the framework of the proposal ‘ECOSAPONIN.’ Interactions between the participants, including chemists, physicists, technologists, microbiologists and botanists from four countries, will contribute to the development of collaborative ties and further promote research and development in the area of saponins in Europe and China. Although this chapter cannot provide a comprehensive account of the state of knowledge regarding plant saponins, we hope that it will help make saponins the focus of ongoing international cooperation.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Dorota Kregiel, Joanna Berlowska, Izabela Witonska, Hubert\nAntolak, Charalampos Proestos, Mirko Babic, Ljiljana Babic and\nBolin Zhang",authors:[{id:"179443",title:"Associate Prof.",name:"Dorota",middleName:null,surname:"Kregiel",slug:"dorota-kregiel",fullName:"Dorota Kregiel"},{id:"197451",title:"MSc.",name:"Hubert",middleName:null,surname:"Antolak",slug:"hubert-antolak",fullName:"Hubert Antolak"},{id:"198329",title:"Dr.",name:"Joanna",middleName:null,surname:"Berlowska",slug:"joanna-berlowska",fullName:"Joanna Berlowska"},{id:"198330",title:"Prof.",name:"Izabela",middleName:null,surname:"Witonska",slug:"izabela-witonska",fullName:"Izabela Witonska"},{id:"198333",title:"Dr.",name:"Charalampos",middleName:null,surname:"Proestos",slug:"charalampos-proestos",fullName:"Charalampos Proestos"},{id:"198334",title:"Prof.",name:"Mirko",middleName:null,surname:"Babic",slug:"mirko-babic",fullName:"Mirko Babic"},{id:"198335",title:"Prof.",name:"Bolin",middleName:null,surname:"Zhang",slug:"bolin-zhang",fullName:"Bolin Zhang"},{id:"204881",title:"Prof.",name:"Ljiljana",middleName:null,surname:"Babic",slug:"ljiljana-babic",fullName:"Ljiljana Babic"}]},{id:"55124",title:"Environmental Impact of the Use of Surfactants and Oxygenates in the Petroleum Industry",slug:"environmental-impact-of-the-use-of-surfactants-and-oxygenates-in-the-petroleum-industry",totalDownloads:2209,totalCrossrefCites:2,totalDimensionsCites:3,abstract:"The role of surfactants and hydrophilic additives in gasoline fuel was demonstrated. The impact of anionic surfactant sodium bis‐(2‐ethylhexyl)sulfosuccinate (AOT) and hydrophilic oxygen containing additives, such as alcohols (methanol, ethanol, propan‐2‐ol, butanol, 2‐methylpropanol) and methyl t‐butyl ether (MTBE) on solubility of water, electrolytic conductivity in gasoline and interfacial tension in the water/gasoline system was studied. Small amounts of amphiphilic components improve the solubility of water in gasoline as a result of the occurrence of association phenomena with the formation of reverse micelles. The formation of surfactant aggregates and droplet clusters results in an increase in the solubility of water in gasoline, electrolytic conductivity, and a decrease in interfacial tension. The changes depend on concentration of the surfactant and type of applied biocomponents. Gasoline fuel in the form of microemulsion has a positive impact on the natural environment. The presence of water causes the almost complete combustion of hydrocarbons to the low toxic gases and the absence of carbon black among combustion products reduces fuel consumption, enhances engine power and decreases its temperature, reduces emissions of volatile organic compounds (VOCs), NOx, SO2, CO, and particulate matter. The alternative fuel may have a potential use in spark‐ignition engines in the future.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Tomasz Kalak",authors:[{id:"197816",title:"Dr.",name:"Tomasz",middleName:null,surname:"Kalak",slug:"tomasz-kalak",fullName:"Tomasz Kalak"}]},{id:"55368",title:"Multifunctional Gemini Surfactants: Structure, Synthesis, Properties and Applications",slug:"multifunctional-gemini-surfactants-structure-synthesis-properties-and-applications",totalDownloads:4498,totalCrossrefCites:23,totalDimensionsCites:46,abstract:"Gemini cationic surfactants are compounds which are composed of two hydrophilic head groups and two hydrophobic tails linked by a spacer at the head groups or closed to them. The spacer can be either hydrophobic or hydrophilic. It can be rigid or flexible. The neutral charge of the molecule is retained by the presence of organic or inorganic counterions. Critical micelle concentrations (CMCs), surface tension (γ) and minimal inhibitory concentration (MIC) are dozen times lower than corresponding parameters of monomeric surfactants. The unique properties of gemini surfactants with a wide range of hydrophilic-lipophilic balance (HLB) make them a very useful, innovative material in detergents, cosmetics, personal care products, additives for paints and coatings, biocides, material science, organic synthesis, pharmacy, textiles, enhanced oil recovery, nanotechnology, petroleum and many other branches of life. A large number of papers concerning gemini surfactants have been published so far. This review presents a synthetic look at current work devoted to structure, synthesis and applications of gemini surfactants.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Bogumil E. Brycki, Iwona H. Kowalczyk, Adrianna Szulc, Olga\nKaczerewska and Marta Pakiet",authors:[{id:"197271",title:"Dr.",name:"Bogumil E.",middleName:null,surname:"Brycki",slug:"bogumil-e.-brycki",fullName:"Bogumil E. Brycki"},{id:"207547",title:"Dr.",name:"Iwona",middleName:null,surname:"Kowalczyk",slug:"iwona-kowalczyk",fullName:"Iwona Kowalczyk"},{id:"207548",title:"Dr.",name:"Adrianna",middleName:null,surname:"Szulc",slug:"adrianna-szulc",fullName:"Adrianna Szulc"},{id:"207549",title:"Dr.",name:"Olga",middleName:null,surname:"Kaczerewska",slug:"olga-kaczerewska",fullName:"Olga Kaczerewska"},{id:"207550",title:"Dr.",name:"Marta",middleName:null,surname:"Pakiet",slug:"marta-pakiet",fullName:"Marta Pakiet"}]},{id:"55934",title:"SAXS and SANS Techniques for Surfactant Characterization: Application in Corrosion Science",slug:"saxs-and-sans-techniques-for-surfactant-characterization-application-in-corrosion-science",totalDownloads:2004,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"This chapter presents advances in the characterization of surfactants and detergents using small angle X‐ray scattering (SAXS) and small angle neutron scattering (SANS) techniques. Surfactant molecules have been extensively used for corrosion prevention as part of commercial corrosion‐inhibitor formulations. It is generally established that the interactions between surfactant molecule and metallic substrate play a key role in the formation of a corrosion‐protective film. It is therefore essential to develop understanding about the nature of surfactant and detergent molecules in bulk solutions prior to formation of a surface film, as well as the mechanisms of their interactions with metallic substrates. These properties and interactions determine the properties of the surface film, including its persistency, and in turn define its protectiveness against corrosion. X‐ray and neutron reflectivity methods are important investigating tools that could be used to characterize surfactant interactions with metallic substrates. These techniques have recently been utilized to investigate adsorption energies and contact angles between molecules or particles and variable substrates. This chapter addresses basic principles of these techniques and discusses their application for surfactant and detergent studies in corrosion science. Several case studies are presented and provide outlook for future prospects in this field of science.",book:{id:"5840",slug:"application-and-characterization-of-surfactants",title:"Application and Characterization of Surfactants",fullTitle:"Application and Characterization of Surfactants"},signatures:"Deepak Dwivedi and Kateřina Lepková",authors:[{id:"197497",title:"Ph.D.",name:"Katerina",middleName:null,surname:"Lepkova",slug:"katerina-lepkova",fullName:"Katerina Lepkova"},{id:"207546",title:"Dr.",name:"Deepak",middleName:null,surname:"Dwivedi",slug:"deepak-dwivedi",fullName:"Deepak Dwivedi"}]},{id:"56940",title:"Phase Transition effect on the Parametric Instability of Liquid Crystals",slug:"phase-transition-effect-on-the-parametric-instability-of-liquid-crystals",totalDownloads:1140,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"We review advances in the last few years on the study of the Faraday instability onset on thermotropic liquid crystals of nematic and smectic A types under external magnetic fields which have been investigated with a linear stability theory. Especially, we show that thermal phase transition effects on nematics of finite thickness samples produce an enhanced response to the instability as a function of the frequency of Shaker’s movement. The linear stability theory has successfully been used before to study dynamical processes on surfaces of complex fluids. Consequently, in Section 1, we show its extension to the study of the instability in the nematics, which set the theoretical framework for its further application to smectics or other anisotropic fluids such as lyotropic liquid crystals. We present the dispersion relationships of both liquids and its dependence on interfacial elastic parameters governing the surface elastic responses to external perturbations, to the sample size and their bulk viscosities. Finally, we point out the importance of following both experimental and theoretical analysis of various effects that needs to be incorporated into this model for the quantitative understanding of the hydrodynamics behavior of surface phenomena in liquid crystals.",book:{id:"6070",slug:"liquid-crystals-recent-advancements-in-fundamental-and-device-technologies",title:"Liquid Crystals",fullTitle:"Liquid Crystals - Recent Advancements in Fundamental and Device Technologies"},signatures:"Martin Hernández Contreras",authors:[{id:"207318",title:"Dr.",name:"Martin",middleName:null,surname:"Hernandez Contreras",slug:"martin-hernandez-contreras",fullName:"Martin Hernandez Contreras"}]}],onlineFirstChaptersFilter:{topicId:"514",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"81713",title:"Transition Metals-Based Metal-Organic Frameworks, Synthesis, and Environmental Applications",slug:"transition-metals-based-metal-organic-frameworks-synthesis-and-environmental-applications",totalDownloads:41,totalDimensionsCites:0,doi:"10.5772/intechopen.104294",abstract:"This work illustrates examples of metal-organic frameworks (MOFs) derived from transition metals and their environmental applications in areas of catalysis, sorption, and hydrogen evolution. Explanation of some of the techniques employed for their synthesis has been discussed. On the other hand, the advantages of the use of hybrid materials such as the metal-organic frameworks are exposed in this book as well a detailed description of the different linkers and metals used for the synthesis of this kind of porous materials going through the methodologies and techniques utilized by different authors to obtain good-quality crystalline applicable materials. Adjustments of linker geometry, length, ratio, and the functional group can tune the size, shape, and internal surface property of an MOF for a targeted application. The uses of MOFs are exploring new different areas of chemistry such as catalysis, adsorption, carrier systems, hydrogen evolution, photocatalysis, and more. Different examples of MOFs from Scandium to Zinc are well described in this book, and finally, a brief description of some common environmental applications such as metals and azo dyes sorption, hydrogen evolution, and catalyst in the transesterification process of vegetable oils to produce biodiesel is explored and commented.",book:{id:"11216",title:"Sorption - From Fundamentals to Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11216.jpg"},signatures:"Lidia E. Chiñas-Rojas, Guadalupe Vivar-Vera, Yafeth F. Cruz-Martínez, Seth Limón Colohua, José María Rivera and Eric Houbron"},{id:"81332",title:"Adsorption of Chromium from an Aqueous Solution onto Chitosan Beads Modified with Sodium Dodecyl Sulfate (SDS)",slug:"adsorption-of-chromium-from-an-aqueous-solution-onto-chitosan-beads-modified-with-sodium-dodecyl-sul",totalDownloads:25,totalDimensionsCites:0,doi:"10.5772/intechopen.104093",abstract:"The goal of this research is to make chitosan beads that have been treated with sodium dodecyl sulfate (SDS) to remove chromium (Cr) from an aqueous solution effectively. The successful synthesis of the SDS-chitosan was proven through characterization, which were carried out using by scanning electron microscopy–energy dispersive X–ray spectroscopy (SEM-EDS), Fourier transform-infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS). The adsorption of Cr on the SDS material was investigated by varying experimental conditions such as pH, contact time and adsorbent dosage. The maximum adsorption capacity of SDS-chitosan for Cr(III) was estimated to be 3.42 mg·g−1 and 3.23 mg·g−1 for Cr(VI). Based on the results of adsorption kinetics and isothermal models, the adsorption process conform to the pseudo-second-order and Langmuir isotherm models. This indicates that the adsorption of Cr on SDS-chitosan is mainly dominated by chemical adsorption and monolayer reaction. In addition, according to thermodynamic analyses, the adsorption of Cr is an endothermic reaction. These results show that the new adsorbent has obvious application prospect for removing Cr.",book:{id:"11216",title:"Sorption - From Fundamentals to Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11216.jpg"},signatures:"Naoki Kano, Zou Ming, David Eva Vanessa Anak and Muhammad Nabil Md Sari"},{id:"81111",title:"Coconut Shell Charcoal Adsorption to Remove Methyl Orange in Aqueous Solutions",slug:"coconut-shell-charcoal-adsorption-to-remove-methyl-orange-in-aqueous-solutions",totalDownloads:34,totalDimensionsCites:0,doi:"10.5772/intechopen.102898",abstract:"Activated charcoal was prepared and characterized from residues of coconut peel (CACC) to remove by adsorption the Methyl Orange (AM) dye in aqueous solution. The charcoal was activated with phosphoric acid. The morphology and structure of the pores of the carbon obtained were analyzed by Scanning Electron Microscopy (SEM) and a surface analyzer. The adsorption data were evaluated by the BET, Langmuir and Freundlich isotherms, finding the Langmuir type I model. The surface area of the activated carbon was 526 m2/g with a pore volume of 0.234 cm3/g and an average pore diameter of 1.78 nm, according to BET, which indicates the presence of micropores. The calculated thermodynamic parameters showed that the adsorption of the AM dye in CACC is a spontaneous process at room temperature and that physisorption and chemisorption are probably involved. The adsorption tests were followed by UV–visible spectrophotometry. The effects of the adsorbate concentration (AM) and the heat treatment (450–500°C) with an air atmosphere were investigated, keeping constant the stirring time and the H3PO4/sample weight ratio. The results obtained indicate that the activated carbon obtained could be used as an alternative low-cost adsorbent in the removal of AM from effluents in aqueous solution.",book:{id:"11216",title:"Sorption - From Fundamentals to Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11216.jpg"},signatures:"Isabel Cristina Páez-Pumar Romer, Isabella Victoria Plazola Santana, Rosa María Rodríguez Bengoechea and Miguel Manuel Pérez Hernández"},{id:"80319",title:"Sorption Isotherms and Some Functional Properties of Cowpea Varieties Flour",slug:"sorption-isotherms-and-some-functional-properties-of-cowpea-varieties-flour",totalDownloads:58,totalDimensionsCites:0,doi:"10.5772/intechopen.101902",abstract:"In sub-Sahara, preservation of processed cowpea flour remained a challenge, and there are no standard isotherm conditions for drying cowpea flour. This study aims to define the optimum isotherm conditions for cowpea flour and assess their functional properties. Adsorption isotherms of three varieties of cowpea at temperatures 30, 40, and 50°C and in each case with six different applications depending on the constant relative humidity of the medium were executed. Water and oil absorption capacities including swelling index were determined. Results show that water content at equilibrium is inversely proportional to the temperature, and at the same temperature, the water content increases when water activity augments. The adsorption isotherms are of type II according to the fitted BET and GAB models. The absorption capacities ranged from 1.06 ± 0.01, 1.08 ± 0.02, and 1.09 ± 0.01(mL/g), respectively, for CS133, CS032, and control. However, the swelling index was significantly separated (P < 0.05). The adsorption isotherm curve of the sample CS032 at 50°C shows a stronger correlation (R2 = 0.9274) than the other varieties regardless of the mathematical isotherm model used. It can be concluded that depending on some functional properties of cowpea variety flour, these varieties seemed to behave separately vis-a-vis their sorption isotherm.",book:{id:"11216",title:"Sorption - From Fundamentals to Applications",coverURL:"https://cdn.intechopen.com/books/images_new/11216.jpg"},signatures:"Issoufou Amadou"}],onlineFirstChaptersTotal:4},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:0,limit:8,total:null},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:141,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"24",title:"Sustainable Development",doi:"10.5772/intechopen.100361",issn:"2753-6580",scope:"
\r\n\tTransforming our World: the 2030 Agenda for Sustainable Development endorsed by United Nations and 193 Member States, came into effect on Jan 1, 2016, to guide decision making and actions to the year 2030 and beyond. Central to this Agenda are 17 Goals, 169 associated targets and over 230 indicators that are reviewed annually. The vision envisaged in the implementation of the SDGs is centered on the five Ps: People, Planet, Prosperity, Peace and Partnership. This call for renewed focused efforts ensure we have a safe and healthy planet for current and future generations.
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\r\n\tThis Series focuses on covering research and applied research involving the five Ps through the following topics:
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\r\n\t1. Sustainable Economy and Fair Society that relates to SDG 1 on No Poverty, SDG 2 on Zero Hunger, SDG 8 on Decent Work and Economic Growth, SDG 10 on Reduced Inequalities, SDG 12 on Responsible Consumption and Production, and SDG 17 Partnership for the Goals
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\r\n\t2. Health and Wellbeing focusing on SDG 3 on Good Health and Wellbeing and SDG 6 on Clean Water and Sanitation
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\r\n\t3. Inclusivity and Social Equality involving SDG 4 on Quality Education, SDG 5 on Gender Equality, and SDG 16 on Peace, Justice and Strong Institutions
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\r\n\t
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\r\n\t4. Climate Change and Environmental Sustainability comprising SDG 13 on Climate Action, SDG 14 on Life Below Water, and SDG 15 on Life on Land
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\r\n\t
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\r\n\t5. Urban Planning and Environmental Management embracing SDG 7 on Affordable Clean Energy, SDG 9 on Industry, Innovation and Infrastructure, and SDG 11 on Sustainable Cities and Communities.
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\r\n\tThe series also seeks to support the use of cross cutting SDGs, as many of the goals listed above, targets and indicators are all interconnected to impact our lives and the decisions we make on a daily basis, making them impossible to tie to a single topic.
",coverUrl:"https://cdn.intechopen.com/series/covers/24.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:1,editor:{id:"262440",title:"Prof.",name:"Usha",middleName:null,surname:"Iyer-Raniga",slug:"usha-iyer-raniga",fullName:"Usha Iyer-Raniga",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRYSXQA4/Profile_Picture_2022-02-28T13:55:36.jpeg",biography:"Usha Iyer-Raniga is a professor in the School of Property and Construction Management at RMIT University. Usha co-leads the One Planet Network’s Sustainable Buildings and Construction Programme (SBC), a United Nations 10 Year Framework of Programmes on Sustainable Consumption and Production (UN 10FYP SCP) aligned with Sustainable Development Goal 12. The work also directly impacts SDG 11 on Sustainable Cities and Communities. She completed her undergraduate degree as an architect before obtaining her Masters degree from Canada and her Doctorate in Australia. Usha has been a keynote speaker as well as an invited speaker at national and international conferences, seminars and workshops. Her teaching experience includes teaching in Asian countries. She has advised Austrade, APEC, national, state and local governments. She serves as a reviewer and a member of the scientific committee for national and international refereed journals and refereed conferences. She is on the editorial board for refereed journals and has worked on Special Issues. Usha has served and continues to serve on the Boards of several not-for-profit organisations and she has also served as panel judge for a number of awards including the Premiers Sustainability Award in Victoria and the International Green Gown Awards. Usha has published over 100 publications, including research and consulting reports. 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She is regularly invited as a keynote speaker at conferences. She is a guest editor for several special issues and a member of the editorial board of several scientific journals. She has published more than 200 articles and is currently working on book projects in the field of OFDL. Ossiannilsson is a visiting professor at several international universities and was recently appointed Professor and Research Fellow at Victoria University of Wellington, NZ. Ossiannilsson has been awarded the following fellowships: EDEN Fellows, EDEN Council of Fellows, and Open Education Europe. She is a ICDE OER Ambassador, Open Education Europe Ambassador, GIZ Ambassador for Quality in Digital Learning, and part of the Globe-Community of Digital Learning and Champion of SPARC Europe. On a national level, she is a quality developer at the Swedish Institute for Standards (SIS) and for ISO. She is a member of the Digital Skills and Jobs Coalition Sweden and Vice President of the Swedish Association for Distance Education. She is currently working on a government initiative on quality in distance education at the National Council for Higher Education. 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He got his Ph.D. in Animal Ecology at Umeå University in Sweden in 1998. He conducted postdoc research in stream ecology at the University of California at Santa Barbara in the USA. After that, he was a postdoc research fellow at the University of British Columbia in Canada to do research on large-scale stream experimental manipulation and watershed ecological survey in temperate rainforests of BC. He was a faculty member at the University of Hong Kong to run ecological research projects on aquatic insects, fishes, and newts in Tropical Asian streams. He also conducted research in streams, rivers, and caves in Texas, USA, to study the ecology of macroinvertebrates, big-claw river shrimp, fish, turtles, and bats. 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She is a member of the Coordination and Scientific Committees of the doctoral program “Tropical Knowledge and Management” (NOVA), Master in Biotechnology (UEM), and Master in Conservation Biology (GNP); and a national expert for Food and Nutrition Security and Sustainable Agriculture - High-Level Policy Dialogue EU-Africa. 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Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. 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:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{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:{name:"University of Agriculture Faisalabad",country:{name:"Pakistan"}}},{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:"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:"117248",title:"Dr.",name:"Andrew",middleName:null,surname:"Macnab",slug:"andrew-macnab",fullName:"Andrew Macnab",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"322007",title:"Dr.",name:"Maria Elizbeth",middleName:null,surname:"Alvarez-Sánchez",slug:"maria-elizbeth-alvarez-sanchez",fullName:"Maria Elizbeth Alvarez-Sánchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidad Autónoma de la Ciudad de México",country:{name:"Mexico"}}},{id:"337443",title:"Dr.",name:"Juan",middleName:null,surname:"A. 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Gonzalez-Sanchez",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico System",country:{name:"United States of America"}}},{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"}}}]}},subseries:{item:{id:"27",type:"subseries",title:"Multi-Agent Systems",keywords:"Collaborative Intelligence, Learning, Distributed Control System, Swarm Robotics, Decision Science, Software Engineering",scope:"Multi-agent systems are recognised as a state of the art field in Artificial Intelligence studies, which is popular due to the usefulness in facilitation capabilities to handle real-world problem-solving in a distributed fashion. The area covers many techniques that offer solutions to emerging problems in robotics and enterprise-level software systems. Collaborative intelligence is highly and effectively achieved with multi-agent systems. Areas of application include swarms of robots, flocks of UAVs, collaborative software management. Given the level of technological enhancements, the popularity of machine learning in use has opened a new chapter in multi-agent studies alongside the practical challenges and long-lasting collaboration issues in the field. It has increased the urgency and the need for further studies in this field. We welcome chapters presenting research on the many applications of multi-agent studies including, but not limited to, the following key areas: machine learning for multi-agent systems; modeling swarms robots and flocks of UAVs with multi-agent systems; decision science and multi-agent systems; software engineering for and with multi-agent systems; tools and technologies of multi-agent systems.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/27.jpg",hasOnlineFirst:!0,hasPublishedBooks:!1,annualVolume:11423,editor:{id:"148497",title:"Dr.",name:"Mehmet",middleName:"Emin",surname:"Aydin",slug:"mehmet-aydin",fullName:"Mehmet Aydin",profilePictureURL:"https://mts.intechopen.com/storage/users/148497/images/system/148497.jpg",biography:"Dr. Mehmet Emin Aydin is a Senior Lecturer with the Department of Computer Science and Creative Technology, the University of the West of England, Bristol, UK. His research interests include swarm intelligence, parallel and distributed metaheuristics, machine learning, intelligent agents and multi-agent systems, resource planning, scheduling and optimization, combinatorial optimization. Dr. Aydin is currently a Fellow of Higher Education Academy, UK, a member of EPSRC College, a senior member of IEEE and a senior member of ACM. In addition to being a member of advisory committees of many international conferences, he is an Editorial Board Member of various peer-reviewed international journals. 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