Selected studies based on the thermal conductivity of graphite composites.
\\n\\n
IntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\\n\\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\\n\\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\\n\\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\\n\\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\\n\\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\\n\\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\\n\\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\\n\\nFeel free to share this news on social media and help us mark this memorable moment!
\\n\\n\\n"}]',published:!0,mainMedia:{caption:"",originalUrl:"/media/original/237"}},components:[{type:"htmlEditorComponent",content:'
After years of being acknowledged as the world's leading publisher of Open Access books, today, we are proud to announce we’ve successfully launched a portfolio of Open Science journals covering rapidly expanding areas of interdisciplinary research.
\n\n\n\nIntechOpen was founded by scientists, for scientists, in order to make book publishing accessible around the globe. Over the last two decades, this has driven Open Access (OA) book publishing whilst levelling the playing field for global academics. Through our innovative publishing model and the support of the research community, we have now published over 5,700 Open Access books and are visited online by over three million academics every month. These researchers are increasingly working in broad technology-based subjects, driving multidisciplinary academic endeavours into human health, environment, and technology.
\n\nBy listening to our community, and in order to serve these rapidly growing areas which lie at the core of IntechOpen's expertise, we are launching a portfolio of Open Science journals:
\n\nAll three journals will publish under an Open Access model and embrace Open Science policies to help support the changing needs of academics in these fast-moving research areas. There will be direct links to preprint servers and data repositories, allowing full reproducibility and rapid dissemination of published papers to help accelerate the pace of research. Each journal has renowned Editors in Chief who will work alongside a global Editorial Board, delivering robust single-blind peer review. Supported by our internal editorial teams, this will ensure our authors will receive a quick, user-friendly, and personalised publishing experience.
\n\n"By launching our journals portfolio we are introducing new, dedicated homes for interdisciplinary technology-focused researchers to publish their work, whilst embracing Open Science and creating a unique global home for academics to disseminate their work. We are taking a leap toward Open Science continuing and expanding our fundamental commitment to openly sharing scientific research across the world, making it available for the benefit of all." Dr. Sara Uhac, IntechOpen CEO
\n\n"Our aim is to promote and create better science for a better world by increasing access to information and the latest scientific developments to all scientists, innovators, entrepreneurs and students and give them the opportunity to learn, observe and contribute to knowledge creation. Open Science promotes a swifter path from research to innovation to produce new products and services." Alex Lazinica, IntechOpen founder
\n\nIn conclusion, Natalia Reinic Babic, Head of Journal Publishing and Open Science at IntechOpen adds:
\n\n“On behalf of the journal team I’d like to thank all our Editors in Chief, Editorial Boards, internal supporting teams, and our scientific community for their continuous support in making this portfolio a reality - we couldn’t have done it without you! With your support in place, we are confident these journals will become as impactful and successful as our book publishing program and bring us closer to a more open (science) future.”
\n\nWe invite you to visit the journals homepage and learn more about the journal’s Editorial Boards, scope and vision as all three journals are now open for submissions.
\n\nFeel free to share this news on social media and help us mark this memorable moment!
\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"3076",leadTitle:null,fullTitle:"Advances in Wind Power",title:"Advances in Wind Power",subtitle:null,reviewType:"peer-reviewed",abstract:"Today's wind energy industry is at a crossroads. Global economic instability has threatened or eliminated many financial incentives that have been important to the development of specific markets. Now more than ever, this essential element of the world energy mosaic will require innovative research and strategic collaborations to bolster the industry as it moves forward. This text details topics fundamental to the efficient operation of modern commercial farms and highlights advanced research that will enable next-generation wind energy technologies. The book is organized into three sections, Inflow and Wake Influences on Turbine Performance, Turbine Structural Response, and Power Conversion, Control and Integration. In addition to fundamental concepts, the reader will be exposed to comprehensive treatments of topics like wake dynamics, analysis of complex turbine blades, and power electronics in small-scale wind turbine systems.",isbn:null,printIsbn:"978-953-51-0863-4",pdfIsbn:"978-953-51-6270-4",doi:"10.5772/3376",price:139,priceEur:155,priceUsd:179,slug:"advances-in-wind-power",numberOfPages:376,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"7fd7c5d70cbc111f7a84a512c2189d48",bookSignature:"Rupp Carriveau",publishedDate:"November 21st 2012",coverURL:"https://cdn.intechopen.com/books/images_new/3076.jpg",numberOfDownloads:63717,numberOfWosCitations:43,numberOfCrossrefCitations:51,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:69,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:163,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 7th 2012",dateEndSecondStepPublish:"March 28th 2012",dateEndThirdStepPublish:"June 24th 2012",dateEndFourthStepPublish:"July 24th 2012",dateEndFifthStepPublish:"October 23rd 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"22234",title:"Dr.",name:"Rupp",middleName:null,surname:"Carriveau",slug:"rupp-carriveau",fullName:"Rupp Carriveau",profilePictureURL:"https://mts.intechopen.com/storage/users/22234/images/1816_n.jpg",biography:"Dr. Rupp Carriveau has an undergraduate degree in Structural Engineering from the University of Windsor. After several years working with expert systems in industry, he completed a Master’s degree in Environmental Hydraulics and a Doctoral Degree in Fluid Dynamics from the Boundary Layer Wind Tunnel Laboratory at the University of Western Ontario. Now an Associate Professor at the University of Windsor, Dr. Carriveau heads the Entelligence Research Group focused on energy efficiency, renewable energy generation and storage. Having spent several years collaborating with large wind park developers, Dr. Carriveau has published a number of peer reviewed articles relating to surface engineering, structural health monitoring, and group dynamics of wind parks. 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Polymers can be moulded into various shapes and forms which afford their application in different fields [1, 2, 3]. This is owing to their unique properties such as lightweight, durability and low production cost. Polymers have substituted natural materials (e.g. steel and glass) in most of their former uses [1, 2, 3]. Besides these unique features, their success in certain applications is hindered by their poor electrical, thermal and mechanical properties. The incorporation of different fillers has been subject to researchers and scientists as a suitable solution to overcome these limitations. However, the resulting composite properties were found to be directly dependent on several aspects such as matrix-type, filler-type, interaction between the filler and polymer as well as the distribution of the filler within the polymeric matrix [4].
Research has escalated on the use of conductive fillers to improve not only the electrical and thermal conductivities but also the overall physical properties of the resulting composite product. Different conductive fillers such as metal powder, carbon black, carbon nanotubes (CNTs) and natural graphite were employed as reinforcing fillers of various polymeric materials [5, 6]. Amongst all these fillers, graphite garnered in much interest owing to its unique properties such as abundant availability, low cost and easy functionalization [7].
The polymer/graphite composites exhibited a high thermal conductivity and an electrical conductivity at a fairly low concentration. Polymer/graphite composites have been used in many applications including structural, aerospace and sporting goods. Most recently, researchers have focused their attention on the development of polymer/graphite composites for applications whereby thermal conductivity is needed [8, 9]. It is documented [7] in the study that the significance of thermal conductivity and/or thermal diffusivity in polymer composites is related to the need for considerable levels of thermal conductivity in circuit boards and heat exchangers. According to the studies [10], conductive composites are frequently used in wide applications such as heating elements, temperature-dependent sensors, self-limiting electrical heaters, switching devices, antistatic materials for electromagnetic interferences and shielding of electronic devices. This chapter reviews recent development on the thermal conductivity of polymer/graphite composites.
Graphite is a carbon-based layered material whose structure is composed of successive layers of graphene sheets (carbon) and received much interest owing to its exceptional thermal, mechanical and electrical properties [5, 11, 12]. It is thermodynamically stable and soft with the successive layers being parallel to the base plane. The layers are bonded together by van der Waals forces. Graphite consists of carbons that are hexagonally bound to each other by covalent bonds with an interatomic separation of 0.142 nm and an interlayer separation of 0.335 nm. It is sp2-hybridized with three of four valence electrons of hexagonally attached carbons that are linked to the valence electrons of the neighbouring carbon by σ-bonding. Therefore, the fourth electron resonates freely within the graphene layer but it is no longer interacting with a specific carbon atom. Van der Waals forces acting between adjacent graphene layers result from the delocalization of π-electrons. Thus, the interatomic interaction within the single graphene layer is stronger, that is, 75 times when compared to the interaction between the adjacent layers [11]. Hence, there has been much graphite modification that takes place in between the layers in order to improve its dispersion in different polymeric materials. Graphite can be classified into two types: natural and synthetic graphite as shown in Figure 1.
Schematic representation of graphite classification.
Naturally occurring abundant graphite is classified into three categories depending on the geological environment, that is, amorphous, flake and highly crystalline [11]. Amorphous graphite has a content of graphite ranging from 25 to 85% depending on the geological conditions. It is usually derived from mesomorphic environment such as shale, slate and coal. Amorphous graphite is regarded as the less pure form of graphite with lack of considerable ordering and presence of microcrystalline structure. It has been applied in different applications where graphite is often utilized; however, its utilization depends on the degree of purity. Flake graphite is formed in either metamorphic or igneous geologic environments. It is obtained through froth floatation which results in 80–90% graphite. Flake graphite is less abundant as compared to amorphous graphite and has good electrical properties. It has been employed in various applications of graphite such as secondary steel manufacture, lubricants, pencils, powder metallurgy and coatings. Despite being found almost all over the world, crystalline (Vein/lump) graphite is commercially mined in Sri Lanka. It originates from crude oil deposits that through time, temperature and pressure were converted to graphite. As reflected by its name, it has a higher degree of crystallinity due to its direct deposition from a high-temperature fluid phase and its purity is more than 90%. Thus, it has good electrical and thermal conductivity. Vein graphite enjoyed its success in different applications such as batteries, lubricants, grinding wheels and powder metallurgy.
Synthetic graphite is produced by treating carbonaceous precursors such as coal, petroleum and synthetic or natural organic chemicals in inert atmosphere to temperatures above 2400°C as well as thermal treatment of nongraphitic carbons, graphitization or chemical vapour deposition (CVD) from hydrocarbons under temperatures of 1883°C [11]. High temperatures are often employed to facilitate solid-state phase transition effect in order to produce graphite crystals. The production method is the primary factor that influences the resulting graphite properties. Synthetic graphite can also be categorized into two, that is, electro-graphite and artificial graphite. Electro-graphite is a pure carbon-shaped graphite produced from coal tar pitch and calcined petroleum pitch in the electric furnace, while artificial graphite results from the thermal treatment of calcined petroleum pitch at 2800°C. In general, the synthetic graphite has a low density, a high electrical resistance and porosity. Synthetic graphite is employed in different applications such as energy storage, carbon brushes and aerospace. Further modifications are often not required for its application in various fields. To avoid confusion, graphite will be used in this document without discriminate, whether it is synthetic or natural-based.
Modification of graphite has been subject of research in order to afford interaction with large polymer molecules and to achieve a better graphite dispersion [5, 11]. Many efforts have been done to overcome the absence of functional groups on the surface of graphite (or graphene sheets) and space between the sheets. There are three classic forms of modified graphite, that is, graphite-intercalated compounds (GICs), graphene oxide (graphite oxide (GO)) and expanded graphite (EG).
Schematic presentation of the preparation of expanded graphite (EG).
In order to broaden the applications of polymers, the incorporation of a suitable filler with required functionality is the most cost-effective and reliable method [17]. Some of the polymers fall short when it comes to electrical, thermal and mechanical as compared to ceramics and steel. However, the unique properties of polymers such as lightweight and mouldability into different shapes make them suitable candidates for various applications. Amongst other fillers, graphite features unique properties such as a high thermal and electrical conductivity, a low coefficient of thermal expansion, an exceptional thermal resistance, a high thermal shock resistance, improved stiffness and an increased strength. It is abundantly available and easily functionalized to afford various applications. The thermal conductivity of the graphite and/or its composites is of significant importance considering the demands as thermal conductance in heat exchangers, circuit boards, machinery, electronic appliances and many other applications as explained in Section 1.
Beside the modification of graphite, the major contributor to the distribution of graphite in the polymeric matrix relies on the selected preparation method. Classic preparation methods for graphite/polymer composites are
Different types of composites arising from and interaction between the host polymer and graphite layers obtained from different preparation methods.
In situ polymerization involves the polymerization of monomer (or/and oligomer) in the presence of the filler [6, 21, 24, 25, 26]. This method is one of the most effective processes to facilitate the dispersion of the filler in the polymeric material. Moreover, it enhances strong interaction between the composite component; hence, the mechanical properties of the resulting composite are superior to the composite prepared by either solution casting or melt intercalation [25]. This technique, however, is associated with some limitations such as polymer and filler selection and limited to laboratory scale. Moreover, it is environmentally unfriendly process which makes it not feasible for composite preparation.
In solution casting, the polymer is dissolved in suitable solvents and then the filler is added into the polymer solution [22, 27]. In order to improve the dispersion of the fillers, the sonication step is usually adopted [27, 28]. Some polymers are, however, not soluble in most available solvents which then limit the choice of a polymer for this technique. This process is not environmentally friendly due to the fact that the solvent has to be evaporated from the system which can be harmful except if the solvent is water. For industrial production, this technique will be expensive with regard to the recovery of the solvent used. Nevertheless, the mechanical properties of the resulting composites are superior to melt intercalation due to the sufficient time given for the filler to interact with each other as well as the polymeric matrix. A comparison between solution casting as well as solution casting followed by melt pressing was conducted by Bai et al. [22]. It was reported that solution-casted samples had high ability to form the percolated filler network as compared to solution casting followed by melt pressing. The percolation network is essential for the conduction paths within the composite material. However, the appropriate solvent can be chosen to avoid the formation of micro-voids within the composite [29]. The solution casting followed by hot pressing serves as a good procedure to eradicate the voids within the composite material [29].
Melt intercalation is the most favourable process with regard to industrial and environmental perspectives [23, 30, 31]. Polymer and filler are mixed together in the melt-compounding technique which leads to exposure to high shear and heat. The mixture is heated to a temperature above the melting temperature of the polymer for certain period to allow homogeneity. Classic compounding techniques include a single-screw extruder, a twin-screw extruder and an internal mixer. All these techniques can be utilized alone or in combination to afford better dispersion of the fillers. Injection moulding and/or melt pressing are usually used to mould the composite for characterization. In general, the percolation threshold is little bit higher than the other processing techniques, that is, solution casting and in situ polymerization [30]. Interestingly, the balance between the mechanical properties and other properties such as electrical conductivity can be achieved through this method which is of significance towards the commercialization of the resulting composite products. Its limitations involve the choice of polymer/filler, limited filler distribution and thermal degradation of the host polymer [23]. The properties of the polymer such as molecular weight, viscosity and chain length play a major role on the properties of the resulting composite product, hence influencing conclusions reached by different authors [11].
The combination of solution casting followed by melt intercalation/pressing has also been reported [28, 32, 33]. The main was to ensure the interaction between the fillers in order to promote the conductance path network within the host matrix. On the other hand, electrospun graphite composites were also reported in the study [34]. Despite the advantages associated with these techniques,
Numerous researchers studied the thermal conductivity of polymer composites with regard to their importance to reach appreciable levels of thermal conductance in circuit boards, heat exchangers, appliances and machinery as summarized in Table 1 [7, 17, 39]. Amongst all thermal conductive fillers, graphite merits special interest not only due to its high thermal conductivity, that is, 25–470 W m−1 K−1, but high thermal stability, exceptional chemical resistance and mechanical properties [40]. A comparative study of the thermal conductivity between graphite and other conductive fillers (
System | Maximum particle content | Preparation method | Thermal conductivity (W m−1 K−1) | Refs. |
---|---|---|---|---|
LDPE/graphite | 10 vol.% | Melt mixing | 6.5 | [39] |
HDPE/graphite | 7% | Melt mixing | 1.59 | [40] |
LDPE/low-temperature expandable graphite | 50 wt% | Melt mixing followed by pan milling and dilution with neat LDPE | 5.04 | [51] |
LDPE/untreated low-temperature expandable graphite | 50 wt% | Melt mixing | 7.02 | [51] |
LDPE/low-temperature expandable graphite (LTEG) | 37 vol% (60 wt%) | Melt mixing | 11.24 | [36] |
Ethylene vinyl acetate/natural graphite | 7.5 | Melt mixing | ~0.29 | [52] |
Ethylene vinyl acetate/expanded graphite (EG) | 7.5 | Melt mixing | ~0.31 | [52] |
Ethylene vinyl acetate/expanded graphite (EG) | 4 phr | Solution casting followed by melt pressing | 0.87 | [33] |
Ethylene vinyl acetate/natural graphite (NG) | 4 phr | Solution casting followed by melt pressing | 0.48 | [33] |
Epoxy resin/graphite | 44.3 wt% | Oven curing | 1.68 | [37] |
Epoxy resin/graphite | 4.5 wt% | Oven curing | 1.0 | [38] |
Epoxy resin/graphite | 2 wt% | Oven curing | 1.0 | [50] |
Selected studies based on the thermal conductivity of graphite composites.
Mu and Feng [41] prepared graphite/silicone rubber composites using solution-casting and melt-mixing processing techniques. They reported that the thermal conductivity increased with an increase in graphite content; however, solution-casted composites had a high conductivity as compared to melt-mixed ones. The authors reported that the thermal conductivity of solution-casted composites reached a value of 0.32 W m−1 K−1 at 9 per hundred rubber (phr) of graphite, whereas for melt-mixed it was only 0.24 W m−1 K−1, which is the conductivity level similar to solution-casted composite at 4 phr. This was attributed to the conducting path networks created by contact between the graphite layers at a fairly low content in the case of solution casting compared to the reduction of surface-to-volume ratio in the case of melt mixing as shown in Figure 4. The latter resulted in a higher content of graphite required so that they can abut or contact in order to form the conducting paths. A comparison between two commercial graphite (EG-10, synthetic graphite, SGL Carbon, UK, and KS-15, synthetic graphite, Lonza, Switzerland) in two different polymeric matrices (high-density polyethylene (HDPE) and polystyrene (PS)) was conducted by Krupa and Chodák [7]. They reported a nonlinear increase of thermal conductivity with an increase in graphite content regardless of matrix and graphite type. It was, however, reported that the graphite KS displayed higher thermal conductivities than the thermal conductivities of EG-filled material especially for PS composites at a higher graphite content. The graphite KS had smaller particles with a narrow particle size distribution as well as a higher specific surface than graphite EG which corroborate the fact that the size of the particles did not influence the thermal conductivity, however, the contact between the graphite particles even if they are agglomerated. In another study, it was reported that the crystallinity of the polymer also plays a major role on the thermal conductivity of the resulting composite product [44]. It was reported that high-density polyethylene (HDPE)-based composites displayed high thermal conductivities over the whole graphite composition as compared to less crystalline low-density polyethylene (LDPE). Similarly, Deng et al. investigated the effect of chain structure on the thermal conductivity of expanded graphite/polymer composites [45]. Expanded graphite (EG) was blended with three different polymers, that is, polyphenylene sulphide (PPS), syndiotactic polystyrene (sPS) and amorphous polystyrene (aPS). The thermal conductivities of the neat aPS, sPS and PPS samples were reported as 0.18, 0.23 and 0.24, respectively. This was ascribed to the crystallinity of polymers. Similar result of observation was reported elsewhere in the study [46, 47]. The EG/PPS composites showed the highest thermal conductivity throughout the whole range in comparison to the two counterpart composites (Figure 5). The observed behaviour was attributed to the difference in polymer matrices with varied chain structures which may result in different crystallizations and interactions of composites.
Schematic presentation of the proposed mechanism for thermal conductive paths for (a) solution-casted and (b) melt-mixed samples.
The thermal conductivity of EG/polymer composites as a function of EG volume contents (the error bar is marked). The inset shows the thermal conductivity at a low content [
Sefadi et al. [48] studied the influence of graphite treatment with sodium dodecyl sulphate (SDS) in water on the thermal conductivity. Moreover, the authors exposed the samples to 50-KGy electron beam irradiation to improve the interaction between graphite and ethylene vinyl acetate (EVA), as host matrix. They reported an increase in thermal conductivity with an increase in filler content due to high conductivity of graphite, regardless of the treatment. However, the thermal conductivity of the irradiated samples was slightly lower than unirradiated samples. This was attributed to the restriction of the polymer chains
There has been an ever-increasing interest in incorporating additional conductive filler into a graphite composite product to overcome the limitation of these materials [22, 31, 53, 54, 55]. It can be argued that the maximum thermal conductivity value achieved in graphite composites is 11.24 W m−1 K−1 (see Table 1). It is envisaged that the incorporation of the second filler can further enhance the thermal conductivity of the resulting composite products [31, 53, 56]. Lebedev et al. [53] reported that the inclusion of 1 wt% of carbon nanotubes (CNT) into polylactic acid (PLA)/natural graphite composites improved thermal conductivity by more than 40% of magnitude. The thermal conductivity was increased from 0.93 W m−1 K−1 for neat polymer to 2.73 W m−1 K−1 after the addition of 30 wt% graphite, whereas after the inclusion of 1 wt% CNT, the thermal conductivity value reached 3.8 W m−1 K−1. This is ascribed to the additional CNT bridges which closely adjoin the surface of graphite. A similar study using HDPE as the polymeric matrix was recent conducted by Che et al. [31]. The authors reported that the thermal conductivity further increased with the addition of CNT compared to that with EG composites. In another study, it was demonstrated that a small content of a second filler, that is, below 2 wt%, has no significant influence on the thermal conductivity when compared to EG composites due to the fillers being wrapped in between the graphite layers [57]. A maximum increase of 38.5% compared to single filler-based composite was achieved at 5 wt% of the second filler. Self-hybrid composites of EG by crushing EG using a high-speed crusher to obtain different particle sizes were recently studied by Kim et al. [54]. The composites were prepared by mixing the crushed EG and raw EG with polycarbonate (PC) using melt extrusion. Hybrid composites (10 wt% crushed EG and raw EG) displayed a higher thermal conductivity by 12 and 20.7% compared to 20 wt% raw EG and crushed EG composites. The thermal conductivity value reached 2.62 W m−1 K−1 compared to 2.34 and 2.17 W m−1 K−1 for raw-EG and crushed EG-based composites due to synergistic effect. Various thermal conductive particles rather than carbon-based ones can also be used to enhance the thermal conductivity. Kostagiannakopoulou et al. [58] also reported that the thermal conductivity of the epoxy system increased significantly by increasing the filler content. However, the inclusion of the second filler, that is, multiwalled carbon nanotubes (MWCNTs) did improve the thermal conductivity at a higher graphite content (5, 10 and 15%). The highest enhancement percentage was 48 at 15% of graphite. The highest increase of ~176 was achieved in the case of 15% wt of the filler. A combination of graphite and aluminium nitride (AIN) was reported by Yuan et al. [59] and the thermal conductivity reached a value of 2.77 W m−1 K−1 that was 14.6 times that of neat polymeric matrix by combining only 50 wt% AIN and 6 wt% graphite.
The design of composites from graphite is inexpensive and available in abundance. This has initiated new ideas in the field of science for the development of a wide range of novel functional materials. Generally, the addition of graphite improved the thermal conductivity of the host polymer matrix irrespective of filler functionalization, the type of polymer and the method of preparation. Various processing techniques such as solvent casting melt blending and pan milling and masterbatch melt mixing have been used for the preparation of graphite composites. The type of mixing method seemed to have had an effect on the resultant thermal conductivity of the graphite/polymer composites. For instance, solution-casted composites had a high thermal conductivity as compared to melt-mixed system. It is understood that during solution casting, the EG particles will have a sufficient surface-to-volume ratio; as a result, they can contact easily and form conducting path networks at low EG contents. However, for melt mixing, one is of the idea that the EG particles’ shape is changed during the melt-mixing process, resulting in a decrease of surface-to-volume ratio. Therefore, only a higher content of EG can contact and form conductive paths. Furthermore, the type of polymer had an influence on the thermal conductivity of the polymer/graphite composites, with the crystalline polymers having a higher thermal in the composites. It was further observed that the type of treatment on the graphite or its polymer composites also played a significant role in the improvement or non-improvement of the thermal conductivity of the polymer graphite composites. For example, the silane-treated graphite composites showed a higher thermal conductivity than the non-silane-treated graphite composites. In some cases, the treatment of the graphite with UV/O3 did not have an influence on thermal conductivity of the resulting composite materials. Lately, the incorporation of the second filler with graphite can further enhance the thermal conductivity of the resulting composite products and widen the application of graphite composites.
The rotation of the Earth on its axis is the root of the 24-h light-dark cycle and all of the astronomical phenomena that are measured concerning the plane of the horizon—the sunrise and sunset, twilight periods, photoperiod, solar eclipses, movement of the tides, and the lunar perigee and apogee. These phenomena all have the common denominator that they cause variations in the periods of light versus darkness. This light-dark cycle and its variations directly influence the myriad of activities of living organisms, including sleep and wakefulness, rest and activity, feeding, and body temperature changes [1].
The timing and pattern of mammalian behavioral activities are regulated by an evolutionarily optimized interplay between the genetically based biological (circadian) clock and superimposed environmental factors and thus mask the effects mediated by the clock. The main regulator in endogenous circadian rhythms is the suprachiasmatic nucleus, which sits above the optic chiasm and, in humans, is composed of approximately 20,000 neurons. The most important external synchronizing factors, or “Zeitgebers,” is the light-induced phase-setting of the circadian rhythmicity to the 24-h solar day. This influence results in a roughly 24-h activity-rest cycle in diurnal organisms and the converse rest-activity cycle in nocturnal organisms.
Although the 24-h light-dark cycle is the most important Zeitgeber, there are many other modulators that further synchronize or mask circadian rhythms, including social stimuli, sounds, smells, or physical contact, which generate behavioral states that impact endogenous clocks [2]. Regarding the light-dark cycle as a Zeitgeber, the production of melatonin (5-methoxitriptamine), an indolamine secreted by the pineal gland, is dependent on the photoperiod. This hormone is released at night by the pineal gland and collected by the internal recess, the third ventricle. From this location, melatonin is distributed by the cerebrospinal fluid to the brain tissue acting as a synchronizing signal of the internal media with the environmental light [3]. The circadian production of melatonin by the pineal gland is controlled by the circadian clock through a multi-synaptic pathway and released melatonin carries the timing information to the peripheral oscillating structures to couple the oscillating functions (Figure 1).
Regulation pattern of melatonin synthesis. In the scheme is showed the principal structures involved in the circadian rhythm of melatonin synthesis, the suprachiasmatic nucleus and the pineal gland as well as the neuronal and the endocrine pathways to transmit the circadian information, the autonomous nervous system and the variation of circulating melatonin.
The role of melatonin as circadian messenger, as well as the organization of the circadian system, has been described mainly using confined animals; however, studying biological rhythms under natural conditions allows us to understand how geophysical variables impact endogenous clocks. In this regard, initially, chronobiologists conducted their studies under experimental laboratory conditions, while behavioral ecologists have focused their research on observing the behavior of free-living organisms. In the year 2000, in their book “Activity patterns in small mammals” Halle and Stenth of the University of Jena in Germany proposed the integration of behavioral ecology and chronobiology under natural and semi-natural conditions, founding the new discipline of “behavioral chrono ecology,” that is, the study of rhythms under natural conditions and the synchronization of rhythms with nature [4].
In behavioral field studies of primates’ activity rhythms and their modulation by environmental variables, the possible dual, synchronizing and/or masking effects of variables other than light-dark cycles are often ignored. However, there are some studies that addressed these issues. One of these was studied in the Mexican spider monkeys (
Circadian rhythm of motor activity in the Mexican spider monkeys
In other study, additional environmental variables such as the effect of housing conditions and season were incorporated to the daily timing and pattern of activity in this species. Thus, the activity patterns between monkeys living under natural lighting and climatic conditions in either a large wire netting cage or a 0.25-ha forest enclosure in the primatological field station of Veracruz State University near Catemaco, Mexico, were studied. Also, a pregnant female was followed in the forest enclosure, which gave us insight into the effect of late pregnancy and parturition on the monkey’s activity rhythm. Spider moneys are strictly diurnal, with 90% of their total activity occurring during daylight. Monkeys that lived in the forest enclosure had a higher second activity peak in the late afternoon compared to those living in the caged area, resulting in a more pronounced bimodal activity pattern. The spider monkeys kept there had an earlier activity onset and morning activity peak than their conspecifics in the cage; however, no differences were found in the phase-setting parameters of the circadian system to the environmental 24-h periodicity, either by comparison or correlation with the sunrise and sunset. The late pregnancy, parturition, and lactation induced a reduction on the activity level during the week of parturition and the following week. The long days of the summer season and the short days of the winter season were decisive in the expression of the activity time of the morning and evening peaks. Together, data suggest that in Mexican spider monkeys, a weak circadian component and strong direct masking effects of multiple environmental factors are involved in the regulation of the daily activity rhythm [6].
The study of the monkeys under their natural environment may allow us to obtain evidence to highlight the importance of melatonin to modulate diverse oscillating functions and behavioral activities controlled by the circadian clock that can repercuss on mental health. Hence, the main goal of this chapter is to review and discuss the evidence that supports the influence of melatonin on circadian physiology focusing on its modulatory effects on neurodevelopment and brain plasticity as well as on the importance of this indole for the treatment of neuropsychiatric diseases.
Melatonin (
Synthesis pathway of melatonin. The metabolic pathway for melatonin biosynthesis begins necessarily with tryptophan This synthesis consists of several enzymatic reactions; among them the hydroxylation by tryptophan hydroxylase (TPH) produces 5-hydroxytryptophan; in addition, serotonin is formed by the aromatic amino acid decarboxylase (AADC); at the end,
As mentioned previously, circulating melatonin concentration oscillates following a circadian rhythm with a nocturnal peak in almost all studied species (Figure 4). This oscillation is regulated by light implying that the rhythm could be synchronized by the photoperiod, in the same manner as other functions [11]. The most ancient function of melatonin apparently is the protection against oxidative stress. Still, in animals, this indole regulates even complex behaviors such as daily activity and seasonal reproduction, some sleep properties, as well as retinal, hormonal, metabolic, and immune functions [12]. In contrast to non-mammalian vertebrates, pinealectomy in rat or mouse does not disrupt the circadian rhythmicity; instead, these animals retain most of their circadian rhythms, including the oscillating locomotor activity; however, a subtle uncoupling of several physiological functions occurs [13]. In mammals, the melatonergic system has only a secondary rank in the circadian system [14]. Apparently, the temporal signal produced by SCN is distributed to peripheral clocks by both neural pathways through the hypothalamic nucleus and the autonomous nervous system [15, 16], and endocrine pathways mediated mainly through melatonin from the pineal gland. An example of the latter is the requirement of melatonin signal in the maintenance of circadian activity in the
Circadian rhythm of melatonin release. The hormone melatonin is released from the pineal gland in mammals at night. This molecule has been considered the signal of darkness to adjust the circadian system.
To address the role of melatonin as a synchronizer molecule, several experimental strategies have been developed. For example, the organisms are maintained under constant environmental conditions in which the circadian rhythms present a free-running period that could be shorter or longer than 24 h. In this condition, one stimulation with exogenous melatonin applied at different circadian times can induce a phase shift in the oscillation; this change can be a delay or an advance of the rhythm phase. Also, under the same constant environmental condition, a daily melatonin stimulus is applied at a specific external time, so the rhythm becomes adjusted with respect to the periodic stimulation. Both the period and the phase of the rhythms change and are synchronized by melatonin. In both cases, the conclusion is that melatonin is a synchronizer acting on the circadian pacemaker.
In all vertebrates, melatonin membrane receptors seem to be involved in both the phase shifts induced in the circadian oscillations and in the synchronization of the rhythms by injected or infused melatonin [18, 19, 20]. It has been proposed that the pathway activated by melatonin is dependent on the subtype of membrane receptors distributed in the SCN or in the pineal gland itself. In many non-mammalian vertebrates, melatonin receptors distributed in different tissues, including the SCN, seem to be involved in the transduction of the timing of circadian rhythms, but also in phase shifts and synchronization [20].
Melatonin shifts the phase of the locomotor activity rhythm and the firing rate of the mammalian SCN neurons. These actions can be mediated by MT2 receptors. The mammalian circadian pacemaker is sensitive to exogenous melatonin at the hours around day-night and night-day transitions [21, 22]. When melatonin is applied to male C3H/HeN mice at CT10, that is, two circadian hours before the onset of activity, the hormone induces dose-dependent phase advances [23]. This effect is significantly reduced by application of the selective MT2 antagonist 4P-PDOT. This antagonist also diminishes the melatonin-induced phase advances of the SCN neuronal firing rhythm in male Long-Evans rats [24]. In MT1 receptor-deficient mice, the application of melatonin at CT10 still produced phase advances [25]. A common example of circadian rhythms phase shift is the so-called jet lag induced by traveling across several time zones. Melatonergic agonists such as ramelteon and tasimelteon (nonselective MT1/MT2 agonists) have been used as therapeutic options for alleviating the sleep disturbances associated with this transient perturbation in the temporal organization of the circadian system [26].
Melatonin synchronizes the locomotor circadian rhythm in Long-Evans rats, Wistar rats, and the diurnal rodent
Even though pinealectomy does not induce apparent changes in the properties of most of the circadian rhythms in mammals, it has been observed that the decrease in melatonin levels affects some important circadian functions such as the sleep-wake cycle and triggers depressive-like symptoms; these disturbances have been improved with the administration of melatonin receptor agonists [31], suggesting that the role of this pleiotropic hormone in physiology might be underestimated. One important function of melatonin that can repercuss in the brain physiology is the modulation of neurogenic processes and circuit functioning as explained below.
Similarly, to the behavioral studies of primates’ activity rhythms and their modulation by environmental variables, there are also studies about the regulation of molecular and cellular processes influenced by Zeitgebers that participate in the behavior. One example is the neurodevelopment in the hippocampus, which is the brain region where learning and memory are integrated [32]. This function plays a key role in the adaptation of the organism to the environment. Neurodevelopment implicates the formation of new neurons, cell migration, cell differentiation, and the formation of neuronal projections dendrites and axons as well as the formation of synaptic contacts that culminate in the establishment of neuronal connections that together constitute the structural network that underlies brain function.
In 1966, Altman found that new neuron formations occur in the adult brain, making a breakthrough in the concept of that times that new neuron formation occurred only at embryonic stages [33]. However, Altman, for the first time, demonstrated by immunohistology and autoradiographic technique the incorporation of 3H-thymidine into the DNA of cerebellar cells of rats at postnatal age [33]. In the last decade of the past century, further contributions to this field emerged, and it was clear that neurogenesis continues throughout the entire life at various locations in the brain such as the subventricular zone, the olfactory bulb, and the dentate gyrus of the hippocampus [34]. In an analogous manner to neurogenesis, dendrite and axonal formation as well as synaptic contact, establishment occurs during the entire life, making the brain a highly neuroplastic an adaptative organ.
Adult neurogenesis as well as neuroplasticity is conserved processes in all mammalian species studied so far including non-human primates and humans [35]. Both processes are mechanisms that allow the survival and the well adaptation of the organisms to environmental conditions. In this regard, melatonin, a phylogenetically conserved molecule, allows survival and adaptation acting as a free radical scavenger and enhancing the levels of antioxidant enzymes protecting the brain against stressful stimuli. Moreover, because the indolamine stimulates neurogenesis and new neuronal contact formation in the hippocampus, it makes the organism more competent for survival.
The evidence about circadian regulation of neurodevelopment in the adult brain was aroused by the observation that melatonin stimulates different stages of neurodevelopment and because the indolamine is synthesized according to the photoperiod and synchronized the internal activity with the environmental light. In this regard, melatonin synchronizes the sleep-wake cycle, the body temperature, the cortisol release, among other functions.
The adult brain presents neuroplastic changes that follows a circadian rhythm; for instance, the maximal amplitude of neuroplasticity occurs during the scotophase regardless of the activity pattern of the species (diurnal or nocturnal). In the hippocampal subgranular zone of murine adult, proliferation of immature neurons increases at the middle of the scotophase (
In diurnal zebrafish, and in nocturnal mice, the stages of the cell cycle in stem cells of neurogenic niches show a circadian rhythm with nocturnal peak [37]. These rhythms correlate with the expression of Clock1 and Per1 in zebrafish [37] and with Per2 and Bmal1 in mice [38]. These results suggest that cell proliferation is controlled by the clock genes in most mammalian species [39, 40, 41]; interestingly, melatonin can influence the level of clock gene expression [42] and the half-life of clock proteins by timing their degradation in the proteasome [43].
Neuroplastic changes in dendrites also follow a circadian pattern. In Siberian hamsters, the hippocampal dendritic structure of basilar dendrites of CA1pyramidal neurons revealed dendrite length increase that occurs during the dark phase [44]. Moreover, the number of branch points significantly increases during short days (8 h L: 16 h D), indicating a more complex dendritic arbor, while during long days (16 h L: 8 h D), the dendrites are longer. Administration of melatonin at the end of the light phase induces the nocturnal dendritic morphology in CA1 neurons within 4 h. In addition, in organotypic cultures of hippocampus incubated with melatonin 100 nM, dendrite formation in the hilar zone is evident after 6 h of incubation and increased formation of secondary and tertiary dendrites [45] (Figure 5). The changes in dendrite size and complexity are correlated with the increase in the expression of Per1 and Bmal1 in the hippocampus [46]. Hence, in short or long photoperiod schemes, the duration of endogenous melatonin release would change respecting the length of the dark phase, providing seasonal information to neurogenic niches [47].
Neurogenesis in hippocampus and neuronal precursor cells. The neurogenesis process has been studied in organotypic cultures and in isolated precursors obtained from the olfactory epithelium to determine the stimulatory effect of melatonin.
Synaptogenesis, the main event by which neurons are connected, is also regulated by the circadian rhythms. Two approaches have been used to study synaptic formation: (1) structural studies in which immunostaining of synaptic proteins by specific antibodies was used to label dendrite spines the site where synaptogenesis takes place and electrophysiological approaches where long-term potentiation is studied (LTP). The former showed a circadian pattern reaching a maximum number or size of dendritic spines during the dark phase in the hippocampus and somatosensory cortex in mice [48, 49]. Moreover, increased synapses formation is observed in hippocampal organotypic cultures incubated with 100 nM melatonin and by staining with an anti-synapsin antibody, which labels synapsin a protein localized in the presynapsis [45]. Despite this information, studies in Siberian hamsters indicate a decrease in dendritic spine density during the dark phase in the dentate gyrus [44, 46]. Thus, it is necessary to study more deeply the rhythmicity of synapses formation and the factors that influence it.
On the other hand, electrophysiological studies have shown that synaptic strength measured through hippocampal LTP was more significant in magnitude and stability in slices obtained during the dark phase [50]. This pattern persisted even in constant darkness or in slices obtained at daytime and recording LTP at night; these results suggest an endogenous rhythm in synaptic plasticity that could persist
Current studies indicate that olfactory neuronal precursors are a subrogate model of the central nervous system to study neurotransmitter receptors expression, enzymes involved in neurotransmitter synthesis as well as the neurodevelopment in the adulthood.
Olfactory neurons have a common ectodermal embryonic origin with the CNS neurons and are derived from embryonic placodes and the neural crest, which are structures analogous to the neural tube [53, 54].
Gene expression profiles of olfactory neuronal precursors are similar to mesenchymal stem cells and can be differentiated into mature olfactory neurons and other types of neurons such as dopaminergic neurons [55, 56]. The expression of hundreds of genes such as CNS neurons has been shown in olfactory neuroepithelial cells. Some of these are the pituitary adenylate cyclase-activating peptide and the glutamate receptor, among others [57, 58, 59]. Moreover, in postmortem samples obtained from Alzheimer’s disease patients, paired helical filaments of tau protein and amyloid-β plaques similar to those found in cortical and subcortical neurons have been described in olfactory neuroepithelial cells characterized by cytokeratin-18 expression reflecting its stromal epithelial cell nature, as well as in olfactory neurons characterized by III β-tubulin expression [60, 61]. Recently, neuronal precursors were obtained from alive patients with Alzheimer’s disease diagnosis and demonstrated the paired helical filaments, as well as increased levels of tau total and phospho-tau supporting that olfactory neuroepithelial cells are a mirror model that reflects molecular changes produced in the CNS and useful to study different stages of neurodevelopment in samples obtained from alive patients [62].
In this regard, it was demonstrated that spontaneous axogenesis occurs in olfactory neuronal precursors derived from a clone obtained by unlimited dilution from a female of 55 years with no psychiatric history. Twelve percent of these cells maintained in primary culture the ability to form axons. In the presence of melatonin, axonal formation augmented by 15% in the primary cultures of olfactory neuronal precursors [63].
In addition to these observations, spine and new neuron formation in a clone of human olfactory neuronal precursors stimulated by melatonin was demonstrated. Spines were labeled with Phalloidin-Rhodamine and an anti-spinophilin antibody and counted. The prelaminar results showed that melatonin increases spine formation in primary cultures of human olfactory neuronal precursors. Moreover, neurogenesis measured as clusters of proliferating neuronal precursors has been observed in the presence of 100 nM melatonin (manuscript in preparation). Altogether, evidence supports that melatonin stimulates three important stages of neurodevelopment, neurogenesis, spine formation, and axogenesis.
In addition to natural
In human subjects, the pattern of motor activity in unmedicated schizophrenia patients and healthy subjects had been study to disclose whether the pattern was affected by treatment with typical and atypical antipsychotics (haloperidol and risperidone). Twenty unmedicated schizophrenic patients wore a wrist actigraph that recorded activity at 1-min intervals for five days. The activity pattern of patients and healthy subjects was compared; then, the patients were randomly assigned to treatment with low-dose haloperidol or risperidone, and the effect of treatment on the activity was tested. Untreated patients were less active during morning, evening, and late-night periods compared with controls. Both haloperidol and risperidone induce significant effects on activity level (this effect was more prominent with haloperidol). The results suggest that unmedicated schizophrenic patients exhibit abnormally low levels of motor activity, which persists with antipsychotic treatment, even though symptoms improve. Future studies should clarify whether motor disturbances are a primary effect of the illness or related to the lifestyle effects [64].
In addition, some antidepressants flatten the amplitude of melatonin secretion, contributing to the alterations of biological rhythms inherent to major depression. Thus, it can be suggested the use of melatonin as a therapeutical adjuvant to regulate biological rhythms such as the sleep/wake cycle.
Recently, we explored if neuroplasticity is altered in schizophrenia. By using the translational experimental model of olfactory neuronal precursors, we found that these cells derived from a patient with schizophrenia were unable to form axons spontaneously. However, in the presence of melatonin, these cells formed axons with the same rate as cells derived from a healthy subject with no psychiatric history [63]. Thus, data suggest that besides the inherent disruption of biological rhythms in schizophrenia patients and drug administration, they also have impaired axonal rhythm formation during adulthood that can be restored by melatonin.
As mentioned before, human beings have a rhythmic expression in their physiology and behavior. In homeostasis states, this endogenous rhythmicity is synchronized by cyclic environmental factors. This coupling provides several advantages: anticipating cyclical changes in the background and facilitating the organism’s adaptation to its environment. This rhythmicity has systems that allow measuring the passage of time, and it is regulated by environmental signals (exogenous) that act as external synchronizers. These rhythms oscillate approximately every 24 h, and among these, the most important is the light-dark cycle or cycle circadian. This concerted, internal, and external rhythmic expression is essential to maintain a healthy state. There is strong evidence that supports the idea that the disruption or chrono-disruption of this adaptive mechanism is detrimental to health and has, among other consequences, sleep disorders, which can lead to cognitive deterioration. It has also been associated with an increased risk of cardiovascular disease, hypertension, metabolic conditions such as diabetes, cancer, obesity, and affective disorders such as anxiety and depression, increasing the prevalence of neuropsychiatric disorders such as schizophrenia and major depression.
The synchronization of circadian rhythms with pharmacotherapy is crucial for neuropsychiatric and affective disorders treatment since it is about combining the maximum benefit with the minimum time complexity of the treatments.
Adequate coordination between drug administration schedules to obtain an optimal therapeutic response has been little explored and currently represents a challenge for chrono-pharmacology.
Desynchronization between the times of administration and the potential pharmacological effects could be one of the reasons why a high percentage of patients with major and bipolar depression (MD) are resistant to treatment, as well as the chronic recurrence of depressive and seasonal disorders. Chronotherapeutic strategies that reset the internal clock may have a specific advantage for treating depression and other mental disorders.
For instance, seasonal affective disorder (SAD) is a sub-type of depression in which individuals experience depressive symptoms and show hypersomnia only in the winter months, in which the period of darkness is more extended than at other times of the year. In a pioneering study, Rosenthal and coworkers [65] found that treatment with bright environmental light suppresses the endogen melatonin secretion and reverses the winter depressive symptoms of patients with SAD. In contrast, light too dim to suppress endogen melatonin is therapeutically ineffective.
This same paper described the antidepressant effects of phototherapy in eight SAD patients by oral melatonin administration. However, in another study with 19 SAD patients, the authors did not find any therapeutic difference between the atenolol, a beta-adrenergic blocker, which inhibits melatonin secretion, and placebo. In contrast, research with seven SAD patients showed that the antidepressant effects of phototherapy were not photoperiodic and appeared to be independent of melatonin suppression. Authors conclude that melatonin can mediate the effects of shortening days on the winter symptoms of SAD and that the modification of melatonin secretion by bright light mediates its antidepressant effects and gives evidence that melatonin secretion may be abnormal in SAD [65].
Multiple factors can disrupt this chronicity because of imbalances in the sleep-wake cycle. Disruption of circadian cycles has also been associated with affective disorders.
Depression disorders are characterized by a broad range of symptoms, including altered mood, loss of cognitive functions, and recurrent thoughts of death or suicide. The relationship between chrono-disruption and the etiology of depression is not yet clear. However, evidence suggests that existing pharmacotherapies such as lithium and antidepressants such as melatonin and agomelatine act on the circadian system.
Although it is known that melatonin is a mediator of photoperiodic changes on seasonal rhythms in animals, a gradual increase in circulating levels of melatonin occurs after lights off, reaching its maximum around the middle of the dark phase. There is contradictory evidence about the antidepressant effect of melatonin itself. We found that the melatonin administration in mice at two
Agomelatine is an antidepressant that acts as an agonist on the melatonin receptors and as a 5HT2C receptor antagonist. Several studies suggest that the antidepressant effect caused by agomelatine results from the resynchronization of circadian rhythms that are disturbed in depressed patients ameliorating symptoms of depression. In contrast to other antidepressants, this has shown low relapse rates upon discontinuation and high tolerability. Furthermore, agomelatine treatment improves the amplitude of the circadian (rest/activity) sleep/wake cycle and diminishes the depression and anxiety symptoms in comparison with sertraline treatment [67].
There is strong evidence about the association between sleep disturbances and depression; in depressive disorder (MDD), the desynchronization of circadian rhythms occurs, producing disturbed sleep and insomnia, and these symptoms improve markedly with melatonergic (MT1 and MT2) and 5HT2C agonist treatment such as melatonin and agomelatine, which act as modulating the circadian rhythmicity.
The foregoing gives evidence of the disruptions of the sleep-wake cycle (sleep architecture and timing) and residual symptoms may prevent the attainment of high-quality remission and delay recovery from MDD.
Benedetti and coworkers studied the effect of morning light therapy or placebo combined with the serotonin reuptake inhibitor citalopram in treating patients affected by a major depressive episode without psychotic features. They found that the combination of this antidepressant and light treatment was more effective than citalopram alone or placebo in the treatment of major depression, administered with an optimized timing of administration, and low-intensity light treatment that significantly hastened and potentiated the effect of citalopram. This evidence provides the clinical psychiatrists with an augmenting strategy, effective and devoid of side effects [68].
Alterations in circadian rhythmicity have been little studied in patients with schizophrenia, in which sleep disorders are common, with an 80% prevalence that often responds to circadian disruption.
This study showed that the variability of sleep-wake time is notably more significant and more remarkable in the schizophrenia group than in the people without the disorder [69].
In addition, polysomnography studies have shown that these patients present a higher sleep latency, diminished total sleep time, lower efficiency, more interruptions, a shorter duration, and latency of REM dreams, as well as a lower proportion of slow-wave sleep than people without this condition. Also, deficit sleep spindles in schizophrenia people could be an endophenotype of this disorder.
In a study of rest activity, a cohort of patients with schizophrenia matched with healthy subjects, Wulff and coworkers [69] showed that there is clear evidence of sleep and circadian rhythm disruption in schizophrenia patients, over half the cohort, tested showed severe circadian misalignment, including the melatonin cycle.
Compared rest-activity patterns in a cohort of patients with schizophrenia with matched healthy unemployed controls showed significant sleep/circadian disruption in all 20 patients studied. Of these, half showed severe circadian misalignment in sleep-wake and melatonin cycles, demonstrating that abnormal entrainment of the circadian system is prevalent in schizophrenia.
Although the results are not conclusive yet and more research is needed in this regard, chronotherapy is a relatively recent proposal to optimize pharmacological treatments based on the biological clock to maximize the pharmacological response or produce adjustments when there is a desynchronization in the biological functions that are affected in illnesses, including mental disorders. Therefore, it is necessary to adequately coordinate medication administration schedules to obtain the maximum pharmacological results and increase treatment adherence.
Evidence presented in this chapter indicates that neuroplasticity is modulated by an external
Funded by Consejo Nacional de Ciencia y Tecnología (CONACyT) Grant No. 290526 to GBK. CONACyT had no further role in review design, in the collection, analysis and interpretation of data, neither in the writing of the report, nor in the decision to submit the paper for publication.
The authors declare no conflict of interest.
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His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. He has authored and reviewed a number of journal articles and book chapters.",institutionString:"National Veterinary Research Institute",institution:{name:"National Veterinary Research Institute",country:{name:"Nigeria"}}},{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. He is also an international opinion leader/expert in vaccination for Japanese encephalitis by IPIC (UK).",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",country:{name:"India"}}},{id:"94928",title:"Dr.",name:"Takuo",middleName:null,surname:"Mizukami",slug:"takuo-mizukami",fullName:"Takuo Mizukami",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94928/images/6402_n.jpg",biography:null,institutionString:null,institution:{name:"National Institute of Infectious Diseases",country:{name:"Japan"}}},{id:"233433",title:"Dr.",name:"Yulia",middleName:null,surname:"Desheva",slug:"yulia-desheva",fullName:"Yulia Desheva",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/233433/images/system/233433.png",biography:"Dr. Yulia Desheva is a leading researcher at the Institute of Experimental Medicine, St. Petersburg, Russia. She is a professor in the Stomatology Faculty, St. Petersburg State University. She has expertise in the development and evaluation of a wide range of live mucosal vaccines against influenza and bacterial complications. Her research interests include immunity against influenza and COVID-19 and the development of immunization schemes for high-risk individuals.",institutionString:'Federal State Budgetary Scientific Institution "Institute of Experimental Medicine"',institution:null},{id:"238958",title:"Mr.",name:"Atamjit",middleName:null,surname:"Singh",slug:"atamjit-singh",fullName:"Atamjit Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/238958/images/6575_n.jpg",biography:null,institutionString:null,institution:null},{id:"333753",title:"Dr.",name:"Rais",middleName:null,surname:"Ahmed",slug:"rais-ahmed",fullName:"Rais Ahmed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333753/images/20168_n.jpg",biography:null,institutionString:null,institution:null},{id:"252058",title:"M.Sc.",name:"Juan",middleName:null,surname:"Sulca",slug:"juan-sulca",fullName:"Juan Sulca",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252058/images/12834_n.jpg",biography:null,institutionString:null,institution:null},{id:"191392",title:"Dr.",name:"Marimuthu",middleName:null,surname:"Govindarajan",slug:"marimuthu-govindarajan",fullName:"Marimuthu Govindarajan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/191392/images/5828_n.jpg",biography:"Dr. M. Govindarajan completed his BSc degree in Zoology at Government Arts College (Autonomous), Kumbakonam, and MSc, MPhil, and PhD degrees at Annamalai University, Annamalai Nagar, Tamil Nadu, India. He is serving as an assistant professor at the Department of Zoology, Annamalai University. His research interests include isolation, identification, and characterization of biologically active molecules from plants and microbes. He has identified more than 20 pure compounds with high mosquitocidal activity and also conducted high-quality research on photochemistry and nanosynthesis. He has published more than 150 studies in journals with impact factor and 2 books in Lambert Academic Publishing, Germany. He serves as an editorial board member in various national and international scientific journals.",institutionString:null,institution:null},{id:"274660",title:"Dr.",name:"Damodar",middleName:null,surname:"Paudel",slug:"damodar-paudel",fullName:"Damodar Paudel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/274660/images/8176_n.jpg",biography:"I am DrDamodar Paudel,currently working as consultant Physician in Nepal police Hospital.",institutionString:null,institution:null},{id:"241562",title:"Dr.",name:"Melvin",middleName:null,surname:"Sanicas",slug:"melvin-sanicas",fullName:"Melvin Sanicas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241562/images/6699_n.jpg",biography:null,institutionString:null,institution:null},{id:"337446",title:"Dr.",name:"Maria",middleName:null,surname:"Zavala-Colon",slug:"maria-zavala-colon",fullName:"Maria Zavala-Colon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Puerto Rico, Medical Sciences Campus",country:{name:"United States of America"}}},{id:"338856",title:"Mrs.",name:"Nur Alvira",middleName:null,surname:"Pascawati",slug:"nur-alvira-pascawati",fullName:"Nur Alvira Pascawati",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universitas Respati Yogyakarta",country:{name:"Indonesia"}}},{id:"441116",title:"Dr.",name:"Jovanka M.",middleName:null,surname:"Voyich",slug:"jovanka-m.-voyich",fullName:"Jovanka M. 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\r\n This topic aims to provide a comprehensive overview of the latest trends in Oral Health based on recent scientific evidence. Subjects will include an overview of oral diseases and infections, systemic diseases affecting the oral cavity, prevention, diagnosis, treatment, epidemiology, as well as current clinical recommendations for the management of oral, dental, and periodontal diseases.
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Her qualifications are: a specialist in Dental Imaging and Radiology, Master in Dentistry (Periodontics) from the University of São Paulo (FORP-USP, Ribeirão Preto, SP), and Doctor (Ph.D.) in Dentistry (Stomatology Clinic) from Hospital São Lucas of the Pontifical Catholic University of Rio Grande do Sul (HSL-PUCRS, Porto Alegre, RS). She held a postdoctoral internship at the Federal University from Jequitinhonha and Mucuri Valleys (UFVJM, Diamantina, MG). She is currently a member of the Brazilian Society for Dental Research (SBPqO) and the Brazilian Society of Stomatology and Pathology (SOBEP). Dr. Marinho's experience in Dentistry mainly covers the following subjects: oral diagnosis, oral radiology; oral medicine; lesions and oral infections; oral pathology, laser therapy and epidemiological studies.",institutionString:null,institution:{name:"State University of Paraíba",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,series:{id:"3",title:"Dentistry",doi:"10.5772/intechopen.71199",issn:"2631-6218"},editorialBoard:null},onlineFirstChapters:{paginationCount:20,paginationItems:[{id:"80964",title:"Upper Airway Expansion in Disabled Children",doi:"10.5772/intechopen.102830",signatures:"David Andrade, Joana Andrade, Maria-João Palha, Cristina Areias, Paula Macedo, Ana Norton, Miguel Palha, Lurdes Morais, Dóris Rocha Ruiz and Sônia Groisman",slug:"upper-airway-expansion-in-disabled-children",totalDownloads:35,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"80839",title:"Herbs and Oral Health",doi:"10.5772/intechopen.103715",signatures:"Zuhair S. 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Percival, Angela Wann, Sophie Taylor, Mark Edgar, Miles Gibson and Martin Grootveld",slug:"metabolomics-distinction-of-cigarette-smokers-from-non-smokers-using-non-stationary-benchtop-nuclear",totalDownloads:53,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"80295",title:"Preventive Methods and Treatments of White Spot Lesions in Orthodontics",doi:"10.5772/intechopen.102064",signatures:"Elif Nadide Akay",slug:"preventive-methods-and-treatments-of-white-spot-lesions-in-orthodontics",totalDownloads:81,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Oral Health Care - An Important Issue of the Modern Society",coverURL:"https://cdn.intechopen.com/books/images_new/10827.jpg",subseries:{id:"1",title:"Oral Health"}}},{id:"79876",title:"Management and Prevention Strategies for Treating Dentine Hypersensitivity",doi:"10.5772/intechopen.101495",signatures:"David G. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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