\r\n\tThere are a variety of approaches to reversing biodiversity loss, ranging from economic, to ecological and ethical. The utilitarian approach to conservation, bolstered by the concept of ecosystem services, can be utilized to improve the conservation case by supplementing the burgeoning biodiversity rhetoric. To address this issue, a pluralistic approach to biodiversity is required for conservation and sustainability.
",isbn:"978-1-80356-339-8",printIsbn:"978-1-80356-338-1",pdfIsbn:"978-1-80356-340-4",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,hash:"ab014f8ed1669757335225786833e9a9",bookSignature:"Dr. Gopal Shukla, Dr. Jahangeer Bhat and Dr. Sumit Chakravarty",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11460.jpg",keywords:"Ecosystem Services, Intrinsic Value, Global Trends in Biodiversity Loss, Convention on Biological Diversity, Utilitarian Value, Biodiversity Conservation, Perception, In Situ and Ex Situ Conservation, Nature Conservation, Sustainable Development Goals, Drivers of Degradation, Prioritizing Biodiversity",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 17th 2022",dateEndSecondStepPublish:"April 22nd 2022",dateEndThirdStepPublish:"June 21st 2022",dateEndFourthStepPublish:"September 9th 2022",dateEndFifthStepPublish:"November 8th 2022",remainingDaysToSecondStep:"a month",secondStepPassed:!0,currentStepOfPublishingProcess:3,editedByType:null,kuFlag:!1,biosketch:"Dr. Gopal Shukla, prior to becoming an assistant professor, has worked under NAIP (National Agricultural Innovation Project), NICRA ( National Innovations on Climate Resilient Agriculture), and SERB (Science and Engineering Research Board) projects. 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He has been instrumental in developing HE and TVET streams of forestry and allied programmes and worked closely in accreditation with the Fiji Higher Education Commission and forestry stakeholders. Before joining Fiji National University, he worked for HNB Garhwal University, Srinagar, India, and has 11 years of research and 8 years of teaching experience with a publication record of more than 60, including research articles, review papers, conference papers, and books of national and international repute. Dr. Jahangeer reviews research articles for several scientific journals and has handled research projects in his capacity as Principal Investigator and Co-Principal Investigator. His major interests lie in emerging issues in forestry including conservation of biodiversity, traditional knowledge of plants, and sustainable management of forest resources. His focus of research is vegetation ecology, ethnobotany, and evaluation of ecosystem services, forest plant biodiversity, climate change, and socio-cultural issues in forestry. Dr. Jahangeer is currently working at the College of Horticulture and Forestry, Rani Lakshmi Bai Central Agricultural University, Jhansi, India.",institutionString:"Central Agricultural University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"0",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Central Agricultural University",institutionURL:null,country:{name:"India"}}},coeditorTwo:{id:"94999",title:"Dr.",name:"Sumit",middleName:null,surname:"Chakravarty",slug:"sumit-chakravarty",fullName:"Sumit Chakravarty",profilePictureURL:"https://mts.intechopen.com/storage/users/94999/images/system/94999.jpg",biography:"Dr. Sumit Chakravarty, Ph.D., has wide experience in forestry training, research, and development. 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AM is located in the innermost layer of the fetal membranes [2]. It is 0.02–0.05 mm thick, lightweight, elastic, almost transparent, and avascular membrane classically composed of three layers: the epithelium, the basement membrane and the stroma layer [2]. There are two types of cells with stemness properties in AM: amniotic epithelial cells (AECs) and amniotic mesenchymal cells (AMSCs) [3], which are responsible for its unique biological properties including anti-inflammatory, anti-scarring, anti-microbial, angio-modulating, immunomodulatory, and anti-cancer effects [4, 5, 6, 7, 8, 9, 10]. Due to these properties, AM has become an ideal material for ocular reconstruction including the treatment of persistent epithelial defects and non-healing corneal ulcers, corneal perforations and descemetoceles, bullous keratopathy, as well as corneal disorders with associated limbal stem cell deficiency, pterygium, conjunctival reconstruction, corneoscleral melts and perforations, and glaucoma surgeries. However, its use span is short and many viruses (such as HIV-1/2, hepatitis B, hepatitis C, human T-cell lymphotropic virus, syphilis, and cytomegalovirus) can be in their “window period” and escape detection, further limiting the use of fresh AM. To overcome these concerns, different preservation methods have emerged, such as freezing, lyophilization, and cryopreservation. However, most methods result in the destruction of endogenous cells and cause varying degrees of extracellular matrix (ECM) damage, which can affect the functionality of AM and its clinical benefits for wound treatment [11, 12]. Cryopreservation was first introduced by Lee and Tseng and has been proven to achieve high success rate in AM transplantation, which has been distinguished from many methods for its attractive advantages of prolonging use span, optimally retaining tissue structure, and minimizing infection risk [13, 14].
Amniotic membrane (AM).
In this part, we classify the cryopreservation methods applied to amnion by commonly used cryoprotectant and analyze the influence of cryopreservation on AM combined with specific clinical trials.
The AM is normally washed using balanced saline solution containing antibiotics such as streptomycin, penicillin, neomycin, and amphotericin prior to storage. Pieces of AM resting on a carrier are placed in a vial containing cryoprotectant solution at a controlled cooling rate. Storage temperatures of −80°C are often utilized, with the maximum storage times ranging between 1 and 2 years [1, 11, 12].
The main disadvantage of cryopreservation is the requirement of a deep-freezing facility, which is expensive, cumbersome, and frequently unavailable, especially in underdeveloped countries. In addition, maintaining stable storage temperatures during transportation is also relatively difficult.
Glycerol storage was first introduced in the Netherlands in 1984 to preserve donor skin for transplantation [13]. Positive results over subsequent decades have led to its clinical acceptance, including in the preservation of AM. Glycerol has led to higher cell viability and higher bFGF secretion for up to three months of AM storage [14]. After strict preservation and sterilization processes, pieces of AM resting on a carrier are placed in a vial containing storage solution. Tseng’s laboratory introduced a methodology of glycerol (86%) in Dulbecco’s Modified Eagle Medium at a ratio of 1:1 [15, 16]. The most common cryopreservation protocol reported in the literature involves the use of 50% glycerol and storage at −80°C [17, 18, 19, 20, 21]. Undiluted and 98% glycerol have also been reported to be clinically effective [15].
In 2011, Thomasen et al. [21] showed that long-term storage of 50% glycerol cryopreserved AM for durations up to 24 months at −80°C did not significantly impair the histology of AM. Wagner et al. [14] used 85% glycerol for cryopreserved AM, and their histological examinations had no significant alterations following cryopreservation, either for straight cryopreservation or with glycerol. They also demonstrated that neither tensile strength nor Young’s modulus was significantly influenced by the storage method. In addition, they also detected a significant increase in tensile strength over storage time, independent of the storage method.
Some groups have found that storage of AM in 50% glycerol at −80°C decellularizes the AM and results in low viability [17, 18, 19, 20]. Interestingly, the results from Wagner et al. [14] research showed that epithelial cells were not significantly reduced during freezing in comparison to stromal cells, possibly indicating a higher sensitivity of stromal AM cells to freezing damage than epithelial cells (Figure 2). Through repeated measurement analysis, storage time showed a significant effect on cell viability. Prabhasawat et al. [22, 23] reported that the use of a highly concentrated glycerol solution abolishes AM cell viability. The possible toxic effect of glycerol is responsible for that.
Pathways of cellular injury during freeing.
To summarize, glycerol-cryopreserved AM retains the histological characteristics of fresh AM independent of an increase in glycerol concentration. Tensile strength and elasticity can also be better preserved, with tensile strength increasing with storage time. However, the cell viability of cryopreserved AM was significantly affected by storage time and glycerol concentration. In particular, the stromal cells were more sensitive. A previous study [24] showed that this method had little effect on the growth factors of AM. More research is needed to confirm the effect of glycerol cryopreservation on AMs.
DMSO has been used as an alternative for AM in glycerol-cryopreservation. An increasing concentration of DMSO is used instead of washing the AM with an antibiotic-saline solution after placenta collection [12]. Azuara-Blanco et al. [25] used 4%, 8%, and 10% DMSO, while Kubo et al. [26] used 0.5 M, 0.1 M, and 0.15 M DMSO for washing. AMs can be stored in 10% or 0.15 M DMSO at −80°C for several months without significant damage. In general, solutions containing DMSO are used less often for AM cryopreservation compared to glycerol, due to high toxicity [12]. However, AM storage solutions containing DMSO have been studied a lot regarding its ability to increase cell viability in AM under experimental conditions [2].
A cryopreservation method with DMSO from Duan-Arnold’s group [24] showed a retained cell viability of over 80%. Cryopreserved AM tested after three months of storage showed no changes in the tissue architecture and collagen IV, which exists in the basement membrane, compared with fresh AM. However, in 2015, Yazdanpanah et al. [8] showed that the viability of epithelial cells in fresh AMs was estimated at 97% after staining with trypan blue, decreasing to about 50% in DMSO cryopreserved tissues after six months. They evaluated the effects of cryopreservation on AM angiogenesis modulation activity compared to fresh tissue in an animal model, showing that cryopreserved AM has the same effect on angiogenesis as fresh AM. The epithelial surface of cryopreserved AM inhibited angiogenesis, and the mesenchymal surface augmented vessel sprouting and length. In 2013, Tehrani et al. [27] used 10% DMSO as a cryoprotectant to evaluate the antibacterial properties of AM after preservation in vitro. The results of this study showed that the antibacterial property of AM was maintained after cryopreservation, but was dependent on bacterial genus and strain.
To sum up, the literature we collected on DMSO-cryopreserved AM showed no significant differences in tissue integrity and biological properties (antibacterial and angiogenesis modulation) compared with fresh AM. However, although many research groups use DMSO as a cryoprotectant, the data related to cell viability vary. These conflicting results can be attributed to several factors, including differing cryopreservation procedures and storage times.
In 2000, Kruse et al. [18] believed that devitalized AM exhibited therapeutic effects, and their data showed that the preservation of viable cells in AM provided no additional benefits. This conclusion led to the development of cryopreservation methods including AM devitalization steps. One of them, known as the CRYOTEK® process, includes a freezing step before cryopreservation, resulting in devitalized tissue [28]. However, Yan et al. [29] demonstrated that the combination of exogenous cells and acellular AM resulted in faster wound closure compared with acellular AM alone. Duan-Arnold et al. [24] demonstrated that endogenous viable cells allow cryopreserved AM with higher angiogenic, anti-inflammatory, antioxidant, fibroblast, and keratinocyte chemo-attractive activities when compared with AM in devitalization. Before 2001, most studies reported that cell viability of 50% or less at cryopreserved post-thaw with cells failing to survive after 18 months of storage at −80°C [26, 30]. Since then, scientists have been attempting to improve the cryopreservation method, for improved cell viability retention. For example, the cryopreservation protocol invented by the group of Duan Arnold et al. [24] can maintain 70% or greater cell viability after 24 months of storage at −80°C. AM storage solutions containing dimethyl sulfoxide (DMSO) have been studied, mostly under experimental conditions, and shown the ability to increase AM cell viability [2]. Although the survival of amniotic cells is related to storage time, different cryopreservation steps can also affect cell viability, thus exerting different clinical effects.
The best storage temperature (−196°C or − 80°C) is also a controversial issue for cryopreservation. AMs stored at −196°C have showed morphology similar to fresh AM in both preservation media, and AM stored at −80°C showed disruption of the stromal matrix [2, 31]. However, −80°C is still widely used by international scientists.
To sum up, cryopreservation protocols are not standardized. Preparation and sterilization before cryopreservation, as well as the selection of cryoprotectant during cryopreservation, will lead to high variability in cell viability [2, 32]. Different storage temperature and storage time also affects the structure and function of amniotic membrane. It is important to establish adaptable protocols for the clinical banking of AM that include verification of graft quality and viability before its release for transplantation, whether in the trial or clinical stage.
PROKERA®Slim (PKS) (Bio-Tissue, Inc., Miami, FL, USA) is a Class II medical device approved by the Food and Drug Administration in 2003 to be used as a temporary AM patch for delivering the biological actions of AM to a corneal surface without using sutures. It contains a piece of cryopreserved AM clipped into a concave poly-carbonate dual-ring system, like a symblepharon ring, that conforms to the corneal and limbal surface like a contact lens. The ring system has an inner diameter of 15 or 16 mm.
It has become the most common commercially available cryopreserved AM product in ophthalmology and is applied to various ocular surface and orbital disorders. It is a safe and effective method that makes AM transplantation sutureless and adhesiveless, contributing to healing and reconstruction of the ocular surface and orbit with minimal side effects [33]. However, PROKERA is not recommended for eyes with functioning blebs or glaucoma drainage implants because of the oppositional positioning of the retaining ring [34].
Corneal disease is one of the world’s leading causes of blindness. Corneal scarring and haze due to various factors can affect vision, making corneal transplantation an important means of treatment for corneal diseases [35, 36, 37]. Advances in corneal preservation techniques have improved the survival rate of corneal grafts [38] and have largely contributed to the development of modern corneal transplant surgery [39]. With the flourishing of corneal preservation technology, breakthroughs have been made in preservation times and corneal activity. Nevertheless, cryopreservation is the only current method that can virtually preserve tissue structure for a long time.
Meanwhile, the development of modern eye banks have been accompanied by the advancement of corneal preservation technology. The establishment of an eye bank provides favorable conditions for corneal transplantation [40, 41].
The idea of replacing the turbid cornea with transparent tissue was first proposed by Pellier de Quengsy in 1789 [42, 43]. In 1824, Reisinger exploited animal corneas in surgery [44], which was named keratoplasty. Later in the nineteenth century, a large number of animal experiments helped doctors realize that inter-species transplantation was a necessary condition to avoid corneal opacity after transplantation [45, 46, 47]. In view of this, researchers began to experiment with human corneal transplantation. Early corneal transplantation relied on living donor tissues due to fears relating to transplanting dead tissue. The first successful full-thickness corneal transplantation (including all corneal layers) was completed in 1905 [48]. It was not until the 1930s that the cornea of the deceased donor was used and the entire eye was kept in a glass jug (wet room) for several days [49].
In 1912, Magitot reported that excised corneal grafts could be preserved in red blood cells at 5°C for eight days [50, 51, 52]. The grafts were successfully used for corneal lamellar transplantation [53]. At first, the freshness of the cornea was considered key to corneal transplantation [54, 55]. However, Ukrainian doctor Filatov systematically reported the application of corpus corneal tissue to clinical practice [56], which possessed an inter-generational meaning. It opened a new era of corneal preservation and transplantation [57, 58, 59]. These developments led to the establishment of the world’s first ophthalmology bank in New York in the 1940s. The preservation technique of the original eye bank was very simple [60, 61]: eyeballs were kept in a small glass bottle in a humid and cool environment [62]. Immediate removal of the eyeball after donor death was the only way to ensure the quality of the corneal grafts [63, 64, 65]. Eye banks were established in major cities, such as London, to guarantee that eyeballs were promptly forwarded [66, 67]. In the early 1950s, the activity of CECs was first considered as an important factor affecting transplantation [68, 69, 70]. The emphasis on preservation techniques was transferred to maintain the activity and integrity of CECs [71, 72]. Since then, corneal preservation techniques have been increasingly successful, resulting in approximately 40,000 corneal transplants per year in the United States, 20,000 per year in Europe, and thousands per year in other countries, such as India.
Corneal preservation is divided into two categories according to the survival of CECs: inactive and active preservation [73, 74, 75]. The former method includes dry preservation and cryopreservation [76, 77, 78] and operates under the principle of removing corneal moisture while inhibiting enzyme activity and autolysis in cells for long-term preservation [79, 80]. Common preservatives are glycerin, molecular sieves, and silica gel [81, 82, 83], which can preserve intact lamellar collagen structure [84]. Active preservation comprises short-term (hours to two days), medium-long term (7 to 30 days) and long-term (months to years) preservation. In terms of storage conditions, it utilizes normal (34~37°C), low (usually 4°C) and deep low (subzero) temperatures [85, 86, 87, 88].
Short-term corneal storage mainly refers to the preservation of wet rooms, the simplest and most convenient of all corneal storage technologies. For this reason, it is still the basic technology for preserving cornea in the eye banks of developing countries. As for medium-term corneal preservation, corneal preservation solution is stored at 4°C for 4 to 14 days [89].
The prolongation of corneal preservation allows more preparation for patients and flexible adjusting of operation times, while also satisfying blood test and corneal transportation times. With the improvement of preservation techniques, the composition of the corneal preservation solution has been constantly changing. A certain concentration of chondroitin sulfate is added to modify M-K solution, which can alleviate the swelling state during preservation. Optisol corneal medium preservation solution was proposed by Lindstrom and has become the most common preservation solution in US eye banks, which is mainly a mixture of K-liquid and Dexsol solution [90]. Long-term corneal preservation refers to organ culture storage and cryopreservation. Organ culture is to simulate the presence of a normal human cornea environment with medium at 30–37°C [91].
At present, there are several corneal preservation methods applied in global eye banks, but none of those is perfect. Each preservation method has its own advantages and disadvantages, which differ from the preservation temperature, the composition of the preservation solution, and the penetrant preventing matrix edema.
After donor death, the sudden stop of the aqueous humor causes nutrient and oxygen shortages, leading to final depletion at room temperature, which can, in turn, lead to autolysis of the corneal cells and initial damage to the cornea [92]. During the period from donor death to corneal removal and storage, the donor’s corpse is exposed to room temperatures, necessitating minimal time delays to ensure that the initial donor cornea is healthy and intact along with functional endothelial cells.
The acceptable short storage time, as well as organ damage, poses a logistical challenge to organ storage and ultimately affects grafts and patient survival. Prolonged storage times can cause many transplantable organs, further exacerbating the growing imbalance between organ supply and demand. Organ cryopreservation is used to preserve long-lived cells and tissues. Theoretically, the storage of biological materials, including cells, tissues, and organs for transplantation at a low temperature (i.e., in liquid nitrogen at −160°C) is uncertain [93, 94]. Such a technique would have the potential to alter the way in which organs are recovered, distributed, and utilized for transplantation. However, ice is the biggest enemy in the cryopreservation of organs and tissues. Ice crystals, especially intracellular ice, can cause significant cellular damage and destroy the complex macroscopic tissues of intact organs. In this field, current developments are used to avoid the formation of ice, or mitigate it, during cryogenic storage. Any successful organ cryopreservation strategy requires a delicate balance between the relative needs of cryopreservation and toxicity in these situations.
In 1954, Eastcott first adopted a cryopreserved human cornea for transplantation successfully [95, 96], pretreating the keratin tissue in glycerol before freezing it in a mixture of alcohol and carbon dioxide for cryopreservation of the full-thickness cornea [97]. This method generally removes the cornea under the protection of a cryogen to −80°C, and stores it in liquid nitrogen at −196°C. Therefore, the CECs are in a dormant state. The state can completely inhibit the metabolism of cells, eliminate the toxic effects caused by the accumulation of metabolites, and avoid the need to change the liquid during organ culture. In addition, it also restrains microorganisms during cryopreservation, protecting the cornea from microbial invasion.
The components currently contained in corneal cryoprotectants include DMSO, propylene glycol, ChS, and sucrose. DMSO is a relatively stable protective agent to maintain the integrity of corneal cells, while sucrose molecules act as buffers in corneal protection, and ChS improves CEC activity in cryopreservation [98]. DMSO began to be treated as a tissue preservative to preserve cultured rabbit CECs by Smith [99]. Shortly thereafter, Mueller injected a preservation solution containing DMSO into the anterior chamber of an eyeball, placing the eyeball in a preservation solution containing glycerol. The cornea was removed before surgery for full-thickness transplantation [100, 101]. In 1965, Capella [102] used DMSO as an antifreeze to improve a cryopreservation method, ensuring corneal graft activity. According to another report [103], the clinical application of cryopreservation techniques has little differences in techniques. The corneal tissue must be preserved eight hours after death. By increasing the level of DMSO, it eventually reaches a concentration of 7.5%. The classic four-step cooling is to initiate a cooling rate at 1.5~2°C/min, drop the temperature to −30°C, change to 5–7°C/min, and ultimately maintain −80°C [104, 105].
It is still essential to further explore the rate of cooling to keep CEC activity and reduce cell loss [106, 107]. Temperature-controlled thawing before transplantation is a key step in protecting the corneal endothelium. At present, the prevalent view is that rapid rewarming could decrease the contact of cells with high concentrations of electrolytes and reduce cell damage [108]. The thawing process of the cryopreserved cornea must be strictly controlled, as the solute containing DMSO has endotoxicity once the temperature exceeds 37°C [109]. Cryopreservation would impair the morphology and function of the corneal endothelium. During the thawing process, an ascending solute concentration, the formation of crystals, changes in pH, and osmotic pressure will reduce the survival rate of CECs [110]. Glycerol, polyvinylpyrrolidone, and DMSO can all be used as cryopreservatives, but DMSO is currently the most widely used [111, 112].
The ultra-low temperature preservation method overcomes the drawbacks of most other corneal preservation methods, significantly prolonging corneal preservation time, reducing pollution, and avoiding the toxic effects of its own metabolic substances. Electron microscopy can observe changes in the subcellular morphology of CECs caused by cryopreservation, some of which are considered irreversible [113]. Studies have shown that, after cryopreservation, the barrier function of endothelial cells is impaired. Compared with wet room preservation and MK solution preservation, cryopreserved corneal grafts have been completely transparent for a long time after surgery. For one-year cryopreservation, 55% of endothelial cells were deactivated, while the rate of CECs preserved by MK solution was only 21–22% [114]. There are barely significant structural differences in microbiological, histological, and ultrastructural features when comparing long-term cryopreservation of tissue (>7 years) and short-term cryopreserved cat corneal sclera (<1 year) [115]. As such, tissues cryopreserved for up to 10 years could be used for tectonic support without structural or microbial barriers.
Under suitable conditions, no crystal solidification occurs during the freezing process, called vitrification [116]. Vitrification requires a high concentration of cryoprotectant, yet theoretically, tissue could be stored in a very low temperature environment without forming intracellular or extracellular crystals, and corneal endothelium damage could be avoided significantly [117]. Glycerol, 1,2-propanetriol, and 2,3-butanediol are all considered as eligible cryopreservation agents for corneal vitrification [118, 119].
Studies have found that an effective concentration of a single cryopreservative is toxic to CECs, yet the mixture of preservatives or the addition of preservatives at low temperatures seems to reduce toxicity [120]. As a means of corneal preservation, further study is warranted to investigate whether vitrification would achieve good results. In 1981, Sperling used corneal grafts in a corneal preservation solution at the early stage and carried out a cryopreservation operation later. After rewarming, the cornea was transferred to a preservation solution, identifying corneal activity. The following studies indicated that the corneal grafts maintained transparency 71% of the time after 1 year and 58% of the time after 12 years [121].
In our previous study, we performed lamellar keratoplasty combined with keratopigmentation in 22 corneal leukoma eyes using glycerol-cryopreserved corneal tissues, and no graft-rejection occurred during the 3 years of follow-up. Moreover, the outcome of a low graft rejection rate in glycerol-cryopreserved corneal tissues was also confirmed by our preceding study in treating Terrien marginal degeneration. In the subsequent study, for patients with refractive herpes simplex keratitis, 3 eyes of 27 eyes (11.1%) suffered allograft stromal rejection, all eyes reversed after prompt medication. Meanwhile, only 2 eyes (7.41%) exhibited refractive herpes simplex keratitis recurrence and the main site was located at the margin of the graft and the recipient bed. This result is consistent with the theory that grafts survive better when compared with reports clarifying that up to 33% of patients have suffered recurrence using fresh grafts. The recurrence rate in fresh grafts may be partially related to the long-term usage of topical steroid eye drops; however, it may be much more closely correlated with fewer keratocytes in the cryopreserved donor tissue to reactivate immune-inflammatory responses [122, 123, 124]. Based on the above information, glycerol-cryopreserved corneal tissues can be effectively and biosafely used with a low rejection and recurrence rate in corneal transplantation, especially in developing countries where good donor corneas are difficult to get.
The cryopreservation method can preserve the activity of the AM and cornea for extended periods up to several years, solving the problem of preservation time and activity deterioration. However, equipment complications, expensive technical support, and transport difficulties have become impediments to widespread use. The functional status of AM, endothelial cells, and corneal transparency have been of vital importance in the development of cryopreservation. As researchers become more aware of the function and properties of CECs, attempts to find a more conducive method and media for the preservation of AMs and corneas will continue.
We declare that we have no conflicts of interest.
The National Nature Science Foundation of China (81470028).
The Municipal Human Resources Development Program for Outstanding Leaders in Medical Disciplines in Shanghai (2017BR060).
Shanghai Shenkang Hospital Development Project: A Three- Year Action Plan (16CR3027A).
Calorie intake that exceeds body requirements results in storage of the excess calories in the body. Although proteins are highly versatile in function, they cannot be used to store excess energy. The amount of glycogen that can be stored in adult liver is 100–120 grams, the skeletal muscle can store about 400 gram glycogen in a 70 kg adult. Small amounts are also present in other cells. The triacylglycerols (TAGs) are the best suited for energy storage purpose: they are energy-dense, hydrophobic (therefore do not associate with space-filling calorie empty water molecules), and can be stored in huge amounts. However, excess storage of the TAGs is often associated with ailments and early mortality. The Obesity Medicine Association has defined obesity as a ‘chronic, relapsing, multi-factorial, neurobehavioral disease, wherein an increase in body fat promotes adipose tissue dysfunction and abnormal fat mass physical forces, resulting in adverse metabolic, biomechanical, and psychosocial health consequences’ [1]. Since measurement of body fat content is tedious and requires sophisticated instruments, it is easier to define overweight and obesity on the basis of the Body Mass Index (BMI). BMI is calculated easily by dividing the weight of the person in kilograms by the square of height in meters. According to the World Health Organization, persons with BMI < 18.5 kg/m2 are underweight, those with BMI 18.5 to < 25 kg/m2 fare of normal weight, those with BMI 25 to < 30 kg/m2 are overweight, and those with BMI > 30 kg/m2 are obese [2]. Besides affecting the patient on the individual level (posing increased risk of obesity-related diseases), obesity affects families and nations in terms of healthcare requirements, reduced working capacity, and economic burden. Annual healthcare costs for obesity exceed $700 billion [3]. With the global increase in the incidence of obesity and obesity-related diseases, healthcare costs for obesity have exceeded those for smoking [4].
Thermodynamics can explain the excess storage of TAGs in a simple, succinct manner: storage of calories occurs when calorie intake exceeds calorie expenditure. Decreasing the intake and increasing the expenditure should melt away the excess fat. Research conducted in the past 70 years reveals that adipose tissue that has grown out of size wants more of itself and persuades the body to devise ways to hoard calories. Thus, obesity is not merely a case of poor self-control. Also, all persons with obesity do not develop obesity-related diseases, as the type of adipose tissue and the site of deposition influence the risks to health.
The fact that weight is related to longevity of the person was realized by life insurance companies [5]. A higher health risk was predicted for weight more than 20% the ideal weight for that height. This is equivalent to a BMI of 27.8 kg/m2. BMI cannot differentiate muscle from fat, or inform about the distribution of fat. It cannot detect changes in body composition due to sarcopenia or osteopenia. It has been observed that some races are at a higher risk of type 2 diabetes mellitus and cardiovascular diseases at BMI values lower than what are normal for persons of European descent. Distribution of body fat is different in different races, Asians tend to have more central adiposity compared to the Caucasians [6]. Males have higher lean mass and bone mineral mass compared to females, however, females have more peripheral distribution of fat [7]. Pregnancy, age, and menopause cause redistribution of body fat, promoting central obesity [8]. It is important to determine the fat content of the body as well as the distribution of the body fat. The best method for determining fat content and fat distribution is cadaver analysis, as no in vivo technique can be that accurate [9].
Anthropometric methods are the most convenient and most popular for estimating the extent of fatness. Besides BMI, these include waist and hip circumferences, waist-to-hip ratio (WHR), skin fold thickness, and waist-to stature ratio (WSR). Since shorter individuals usually weigh less, weight alone cannot be used as a criterion to determine the amount of fat stores. WSR and waist circumference are easy and relatively accurate techniques to estimate visceral fat [10]. The body adiposity index (BAI) does not require weight measurement; it is the ratio of hip circumference to height. It is a fairly accurate measure of adiposity and can be easily used in remote areas without accessibility to reliable scales [11].
According to the two compartment (2C) model, the mass of the human body can be categorized into anhydrous Fat Mass (FM) and Fat Free Mass (FFM). The FFM includes water, minerals, and proteins. FM is assumed to have a density of 0.9007 g/cm3 while the FFM is assumed to have a density of 1.1000 g/cm3. Water content of the body is assumed to be 73.72% [12]. Techniques based on two-component model are bioelectric impedance analysis, whole body counting of total body potassium, densitometry methods (hydrostatic underwater weighing and air displacement plethysmography), and hydrometry using isotope dilution technique. The water content (hydration fraction), bone mineral content, and density of the FFM vary with age, pubertal status, and pregnancy. These values are altered in patients with deranged hydration and in those who have recently lost weight. Differences related to ethnicities have also been observed.
In the 3 compartment (3C) model of body composition assessment, the FFM is sub-divided into lean tissue mass (LTM) and bone mineral content (BMC). This method requires densitometry as well as hydrometry measurements and includes dual energy X-ray absorptiometry (DEXA), a rapid non-invasive method for regional as well as whole body measurement in which high- and low-energy X-rays are transmitted through the body.
The 4 compartment model further categorizes LTM into total body water (TBW) and protein. It requires a combination of several measurement techniques: hydrodensitometry like under-water weighing or air-displacement plethysmography (to measure fat), DEXA (to measure mineral), isotope dilution (to measure water), and residual techniques (to measure protein) [13, 14]. It is an expensive, elaborate, and time requiring technique.
Multi-component models have also been used that incorporate results from many techniques, and are therefore more accurate. Simple methods can be used in the field, while lab-based methods or CT, MRI, X-ray techniques can be used only in clinical settings.
Anthropometric methods and bioelectric impedance analysis are considered indirect methods of assessment. Direct methods include measurement of total body water by isotope dilution technique, total body counting to measure radioactive potassium, and neutron activation techniques with a body scan to measure different elements. Criterion methods include underwater weighing, air-displacement plethysmography, DEXA, computed tomography (CT) scan, and magnetic resonance imaging (MRI) [15].
Vague in 1947 [16] noted that pear-shaped body with higher fat distribution in hips and thigh regions is associated with protection against metabolic diseases. Deposition of fat in the abdominal region (usually seen in males) is associated with development of metabolic diseases [17, 18]. Most of the adipose tissue in the adult human is white adipose tissue (WAT), the main function of which is to store excess calories as triacylglycerols. The brown adipose tissue (BAT), present in small quantities in the interscapular region, is responsible for non-shivering thermogenesis. WAT present in visceral regions is called visceral adipose tissue (VAT), and that present below the skin for insulation is called subcutaneous adipose tissue (SAT). Excess VAT is associated with the metabolic complications of obesity, like metabolic syndrome, type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. TAGs may deposit in tissues other than the adipose; this is called ectopic fat. Ectopic fat in viscera, heart, and vasculature can be seen in lipodystrophy, characterized by little subcutaneous fat and high amounts of ectopic fat. Deposition of thoracic periaortic fat and peripheral artery disease is considered local toxic effect of the ectopic fat. The renal sinus fat has been associated with hypertension and chronic kidney disease [19]. Although BMI is the most common method to identify overweight and obesity, it is unable to differentiate VAT and SAT, and central and global obesity. CT and MRI can be used to quantify the amount of visceral fat accurately. DEXA can also be used, however, it tends to underestimate VAT in people with normal BMI, and overestimates VAT in people with severe obesity [20].
It has been noted that some individuals classified as overweight or obese according to their BMI do not show insulin resistance or increased risk of metabolic diseases. Such people are said to have metabolically healthy obesity (MHO), which can be a transient stage of variable duration that progresses towards metabolically unhealthy obesity (MUO) [21]. A person with obesity can be classified as metabolically healthy if blood pressure, blood glucose, TAG, and high density lipoprotein cholesterol levels are normal without medication [22]. Metabolically unhealthy obesity results when adipocytes of SAT are unable to proliferate and differentiate. Such tissue shows hypertrophy instead of hyperplasia, leading to ectopic and visceral deposition of fat.
The imbalance between energy intake and expenditure can result from various causes that can be broadly classified into endogenous and exogeneous. In his paper on obesity, Pennington has described how the concept of endogenous obesity originated in 1907 [23].
Genetic and epigenetic disorders, hormonal imbalances, maternal and birth-related factors, microbiome, and infections are included in the endogenous causes of obesity. In case of children, pathologic cause can be suspected if the patient shows hyperphagia with absence of satiety signals, shows food-seeking behavior, hides or steals food, has neuroendocrine abnormalities, has skin and hair that are lighter than those of siblings, or is gaining weight rapidly before the age of 5 years.
Ethnic differences in obesity have been observed; admixture mapping studies show that obesity correlates with percentage of ancestry derived from ethnic groups [24]. Studies on individual families and animal models revealed rare obesity causing genes like leptin and leptin receptor genes, melanocortin 4 receptor gene, and the proopiomelanocortin genes, etc. Studies on obesity concordant monozygotic twins show BMI and other anthropometric measures like WHR are 40–60% heritable in children and adults [25]. The genome-wide association studies (GWAS) using massive study populations identified 119 independent loci associated with BMI [26]. The human obesity gene map discussed by Rankinen et al. [27] lists single-gene mutations in 11 different genes, 50 loci related to Mendelian syndromic obesity, 253 quantitative trace loci (QTL) for obesity-related phenotypes. On the basis of clinical presentations, genetic obesity can be classified into monogenic non-syndromic, monogenic syndromic, and polygenic obesity.
Mutations in leptin gene are very rare, lead to hyperphagia and obesity, and can be ameliorated by leptin administration [29]. Administration of exogenous leptin reduces hyperphagia that is spontaneous or induced by fasting [30]; chronic administration causes weight loss by reducing food intake [31, 32]. In most persons with obesity, circulating leptin levels are high, indicating that leptin resistance rather than leptin deficiency is the underlying reason for weight gain.
Obesity-related leptin-resistance may be due to overexpression of the SOCS-3. This has been supported by the fact that
The secretory isoform of the leptin receptor binds circulating leptin and modulates its biologic availability, while the short isoform of the leptin receptor is involved in the transport of leptin across the blood–brain barrier [43]. Leptin resistance may be due to defect in leptin receptor, or in the transport of leptin across the blood–brain barrier. Such persons have early-onset obesity and hypogonadism, however, the obesity is not as severe as in the case of persons lacking plasma leptin [42]. In rodents, a high-fat diet produces leptin resistance, prior to the weight gain [43].
Mutations in leptin receptor gene (
Mutations in the
Mutations in
Only a few patients with
The MC4R plays a key role in weight regulation. It is activated by α-MSH, and cocaine- and amphetamine-regulated transcript (CART) to decrease food intake and increase energy expenditure. The orexigenic peptides neuropeptide Y (NPY) and AgRP are the natural antagonists of MC4R, and increase appetite and reduce energy expenditure by binding to MC4R [54]. Leptin stimulates the secretion of POMC, and inhibits that of AgRP and NPY.
Heterozygous mutations in
Receptors for BDNF include TrkB, encoded by the
WAGR syndrome involves disorders of many body systems and is named for its main features: Wilms tumor (a childhood kidney cancer), aniridia, genitourinary anomalies, and intellectual disability (formerly referred to as mental retardation). A subtype of the WAGR syndrome called WAGRO (characterized by childhood onset obesity) has been reported to be strongly associated with haploinsufficiency for BDNF [60]. Nineteen patients with deletions in any portion of the
Targeted deletion of
The SH2B1 is a product of the
Several
Administration of adiponectin to rodents, and transgenic mice with increased adiponectin showed increased energy expenditure and oxygen consumption without affecting food intake [69, 70]. Adiponectin has been shown to suppress obesity [71], insulin resistance, type 2 diabetes [72, 73], atherosclerosis, and non-alcoholic fatty liver disease [74].
Adiponectin receptor AdipoR1 is more in the skeletal muscle, and AdipoR2 is more in the liver. Expression of receptors is proportional to insulin levels, and in case of receptors on the muscle cells, the number is increased with exercise [75]. AdipoR1 has a higher affinity for globular adiponectin while AdipoR2 has higher affinity for full length adiponectin. The T-cadherin receptor for adiponectin recognizes hexameric and HMW forms of adiponectin. It is present in the vasculature and is involved in the cardioprotective action of adiponectin. Action of adiponectin on receptor requires adaptor proteins APPL1 or its isoform APPL2.
Binding of adiponectin to its receptor leads to activation of the AMP-activated protein kinase (AMPK) and the mitogen-activated protein kinase (MAPK). This causes increased NO production, adiponectin-induced glucose uptake, degradation of ceramide by ceramidase, and fatty acid oxidation, ultimately increasing insulin sensitivity.
Adiponectin deficiency has been associated with increased atherosclerosis while increased expression of adiponectin protects against atherosclerosis in mice [76]. Thiazolidinediones (TZD) used in the treatment of type 2 diabetes mellitus, are known to activate transcription factor peroxisome proliferator-activated receptor (PPAR)-γ, which has been shown to increase adiponectin levels in plasma [77].
Adiponectin mutations have been associated with type 2 diabetes mellitus [78] and hypoadiponectinemia [79]. Recently, mutation in ADIPOQ has been associated with early-onset obesity and metabolic syndrome [80].
Insulin-sensitizing drugs thiazolidinediones are potent agonists of PPAR-γ. This can also lead to increased adiponectin levels (see above).
The BBS phenotype is less apparent in the first decade of life and the condition is usually diagnosed in late childhood or early adulthood.
Gene encoding the alpha-subunit of the stimulatory G protein (
The phenotype in Finnish patients is homogeneous: non-progressive psychomotor retardation, microcephaly, characteristic facial features, myopia, progressive retinochoroidal dystrophy, neutropenia, and cheerful disposition. Non-Finnish patients have a confusing phenotype. Affected persons have low birth weight but develop abnormal truncal fat distribution in teenage. This is an autosomal recessive condition, with mutation in the vacuolar protein sorting 13 homolog B (VPS13B, also called COH1 gene) located on chromosome 8q. This transmembrane protein is involved in vesicle-mediated intracellular protein transport.
Although the DNA in every cell of the multicellular organism is the same (exception: mosaicism [99]), the expression of genes is different in different cell types. The mechanisms that regulate the expression of genes can be heritable. Epigenetic modifications are mitotically and meiotically heritable modulation of gene function without changes in the sequence of the DNA [100]. Such modifications allow or silence the expression of specific genes. Epigenetic programming can be influenced by environmental and dietary factors as well as by the gut microbiota.
The epigenetic modifications are brought about by DNA methylation (by DNA methyltransferases, DNMTs, at distinct CpG sites), histone modification (methylation, acetylation, ubiquitination, or phosphorylation), and by short non-coding RNA species called micro-RNAs or miRNAs.
Epigenetic changes influence embryo formation and development, inactivation of X chromosome in female, genomic imprinting, cell differentiation, stable inheritance of gene expression, and immune cell function. In case of mice it was observed that pregnant animals exposed to polycyclic hydrocarbons during pregnancy gave birth to offspring with higher weight and fat mass. These offspring showed higher expression of PPAR-γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. This epigenetic change was heritable, as it was also observed in the subsequent generation [109]. Female mice born following perinatal exposure to bisphenol A showed significantly different DNA methylated regions compared to controls [110].
Certain factors related to the mother cannot be altered but are known to influence body weight or metabolic processes of the offspring. A U-shaped association between maternal age and fasting glucose concentration in adult offspring has been reported [111]. Adult offspring of younger or older mothers had blood glucose levels higher by about 0.05 mmol/L higher than the reference group. Early maternal menarche [112], maternal diabetes [113], and maternal smoking during pregnancy [114] are associated with a higher BMI in offspring. Low maternal education influences obesity, however, the relationship is different in different ethnicities [115, 116]. Maternal employment has also been found to influence children’s weight [117].
Secondary obesity (consequence of some other illness) due to endocrine causes is relatively less common.
Weight gain has been reported in thyroid insufficiency. About 54% patients with overt hypothyroidism report gain of weight compared to 13.8% control subjects [118]. Hypothyroidism is also associated with dyslipidemia with increased cholesterol levels. The thyroid gland secretes prohormone thyroxine or T4 (3,5,3′,5′-tetraiodothyronine) along with small quantities of active T3 (3,5,3′-triiodothyronine), on receiving the signal from the pituitary gland in the form of thyroid stimulating hormone (TSH) or thyrotropin. TSH is released from the pituitary under the influence of thyrotropin releasing hormone (TRH), the master regulator of thyroid function, produced in the paraventricular nucleus of the hypothalamus. Depending on the underlying cause, hypothyroidism can be primary (decreased production of thyroxine by thyroid due to various reasons), secondary (due to decreased TSH), tertiary (due to deficiency of TRH), and peripheral or consumptive hypothyroidism (due to increased activity of deiodinase 3 which degrades thyroid hormone). Secondary and tertiary hypothyroidism are together called central hypothyroidism [119].
Every organ system and cell in the body is influenced directly or indirectly by the thyroid hormones. Gut motility, heart rate, body temperature, perfusion of lungs, and muscle contraction modulate the effect of catecholamines. In females, thyroid hormones influence menstruation, ovulation, and fertility. Bone growth and brain maturation in children are also influenced by these hormones, while in adults they affect the mood [120]. Thyroid hormones regulate the basal metabolic rate (BMR) and therefore are responsible for increase/decrease/maintenance of body weight.
Decreased thyroxine levels cause accumulation of hyaluronic acid in the dermis which causes water retention and non-pitting edema [121]. Decreased blood flow to kidneys resulting in lowered glomerular filtration rate in hypothyroidism causes water retention and increase in body weight [122]. This is aided by decreased tubular resorption and secretion in thyroxine deficiency. Thyroid hormones also regulate the number of adrenergic receptors and dopaminergic activation of the tubular cells, thus affecting the renin-angiotensin-aldosterone (RAA) axis [123].
Hypothyroidism has been shown to cause decreased mitochondrial biogenesis and decreased levels of uncoupler proteins [124, 125].
Thyroid dysfunction has been associated with decreased insulin sensitivity [126]. This may be a consequence of increased adipose deposition from decreased BMR. Increased adipose tissue is known to cause insulin resistance in obese subjects.
All conditions in which cortisol level is higher than normal are classified under Cushing syndrome, while Cushing disease is pituitary dependent [133]. Cushing syndrome can be classified into ACTH-dependent, ACTH-independent, and pseudo-Cushing syndrome. Cushing disease, ectopic ACTH syndrome, ectopic CRH syndrome, macronodular adrenal hyperplasia, and iatrogenic treatment with ACTH are included in the ACTH-dependent variety of Cushing syndrome. The ACTH-independent Cushing syndrome includes adrenal adenoma and carcinoma, primary pigmented adrenal nodular hyperplasia and Carney’s syndrome, McCune-Albright syndrome, aberrant receptor expression, and iatrogenic Cushing caused by pharmacotherapy by steroids. Chronic alcoholism and depression can cause pseudo-Cushing syndrome. A rare condition with repeated episodes of cortisol excess interspersed by regular or irregular periods of normal cortisol secretion is called the cyclic Cushing syndrome.
Chronically elevated levels of cortisol in Cushing’s syndrome cause redistribution of fat and central obesity [133]. Glucocorticoids (GCs) increase hypothalamic endocannabinoids, hypothalamic AMPK activity, and gene expression of orexigenic NPY and agouti-related peptide, resulting in increased appetite. GCs promote adipocyte differentiation and sensitize preadipocytes to insulin. Visceral adipose tissue (VAT) shows differential response to GCs: increased deposition and insulin resistance occurs in VAT compared to subcutaneous adipose tissue (SAT). Excess glucocorticoids also produce hyperglycemia, dyslipidemia, and increased protein degradation.
Congenital, acquired, or idiopathic deficiency of GH may be associated with increased adipose deposition, especially in the waist region, and insulin resistance. However, reduced GH levels have been reported in some patients with obesity [135, 136]. Usually, deficiency of GH in children is due to insufficient production of growth hormone releasing hormone in the hypothalamus. Damage to the pituitary or hypothalamus (due to tumor or tumor-related surgery, stroke, bleeding, infection, etc) in adulthood may lead to decreased GH production. GH increases lipolysis in the adipose tissue, and reduces storage of TG in a non-uniform manner. Thus it promotes loss of intra-abdominal fat. Scacchi et al. [137] reported that a primary growth hormone deficiency causes centripetal adiposity, while obesity with increase in visceral adipose tissue produces secondary growth hormone deficiency.
Two distinct forms of ghrelin are present in blood: acylated ghrelin (AG) and unacylated ghrelin (UAG). About 90% of the circulating ghrelin in unacylated (UAG). The AG acts on GHSR 1a mediating growth hormone release, while UAG acts on GHSR 1a on pancreatic cells stimulating the release of insulin and glucose utilization. AG opposes the action of UAG, inhibiting the release of insulin. In obesity, UAG levels decrease while the AG levels remain unchanged.
Highest levels of ghrelin in blood are immediately before a meal, and drop to lowest levels immediately after the meal. Ghrelin administration increases appetite in both humans and rats. Ghrelin and synthetic ghrelin mimetics bind to the GHSR1a in hypothalamus, brain stem, and in the mesolimbic pathway, cause secretion of orexigenic neuropeptide Y (NPY) and agouti-related protein (AgRP). GHSR 1a is also expressed in vagal efferent neurons. Under influence of ghrelin, the gastric vagal efferents become less sensitive to gastric distension, increasing food intake.
Plasma level of ghrelin is lower in persons with obesity, except in patients with Prader-Willi syndrome, where ghrelin levels are proportional to the food intake. AG and UAG levels were compared in insulin-resistant and insulin-sensitive subjects with obesity. It was found that UAG and total ghrelin was lowered in insulin-resistant subjects, while only AG levels were lowered in the insulin-sensitive subjects [142]. In patients with anorexia nervosa and with cancer-induced cachexia, ghrelin levels are high [143, 144]. Obese rodents with low levels of ghrelin in plasma have reduced levels of ghrelin-receptor mRNA as compared to the normal lean controls. Experiments on rodents showed that central ghrelin signaling activates reward centres in response to alcohol, food, high-fat diet, and psychosomatic drugs like cocaine [145, 146].
Besides being the hunger signal, the ghrelin-GHSR 1a system is related to the rewarding aspects of food intake. It is activated in anticipation of food intake, negative energy balance, and psychological stress. In times of food scarcity, the effect of the ghrelin/GHSR 1a system on the mesolimbic pathway is advantageous for the animal’s survival.
In developed countries, as well as in the rapidly developing countries, the changes in environment are favoring sedentary lifestyle, easy availability of calorie-dense tasty affordable foods, and increased stress levels are promoting increased appetite. The action of ghrelin on the mesolimbic system increases the appetite, acting as a spice to further increase food intake. In the current scenario of easy availability of food, the ghrelin/GHSR 1a system is no longer an evolutionary advantage but is in part responsible for the obesity epidemic and the associated diseases [147].
Weight gain may also be influenced by insulin, estrogen, progesterone, prolactin, and melatonin.
Certain factors that are preventable and influence the person from outside the body are classified as exogenous causes.
Type of food taken influences the population of gut biota. High fat Western diet reduces Bacteroidetes and increases in Firmicutes population, similar to what is seen in obesity. Increased ratio of Bacteroidetes to Firmicutes is linked with diminished body mass.
More than 800 EDCs have been identified [168]. Persistent organic pollutants (POPs) and certain heavy metals have been classified into EDCs, metabolism disrupting chemicals (MDCs), and mitochondrial function disrupting chemicals (MtDCs). They can interact with nuclear and mitochondrial genes and bring about epigenetic changes, decrease insulin sensitivity, promote inflammation and obesity, decrease basal metabolic rate (BMR), and narrow down the vasculature.
EDCs may be classified into obesogens and diabetogens. The obesogens (e.g. tributyltin, bisphenol A, phthalates, and metals like arsenic) can increase adipocyte differentiation and adipose tissue depots, disrupt normal lipid metabolism leading to obesity. The compound atrazine inhibits the electron transport chain in the mitochondrion. It has been shown to decrease BMR. Diabetogens either destroy beta cells of pancreas or disrupt their function leading to diabetes [169]. Bisphenol A blocks insulin receptor site causing insulin resistance.
Tricyclic agents like amitriptyline and doxepine.
Selective serotonin reuptake inhibitors (SSRIs) like paroxetine and citalopram.
Serotonin and norepinephrine uptake inhibitors (SNRIs) like venlafaxine and duloxetine.
Monoamine oxidase inhibitors (MAOIs) like moclobemide, phenelzine.
Others like mirtazapine, mianserine, and maprotiline.
Bupropion is a norepinephrine and dopamine reuptake inhibitor that reduces food cravings. In US bupropion and naltrexone combination has been approved as an anti-obesity drug.
Since many of the patients are already struggling with the problem of overweight or obesity, it is important to prescribe drugs that are weight neutral or promote weight loss.
The obesity pandemic has spread across the globe and a lot of research is being done regarding its control. If the cause of obesity is known, it is easier to cure or limit the disease. Most of the current research is related to diagnosis of the underlying causes of the condition, as removal of the cause can ameliorate the condition. Suitable lifestyle changes and pharmacotherapies are being designed to reduce weight. Different types of surgical interventions have been improvised to stop weight gain/promote weight loss in patients with severe obesity.
Obesity prevalence is increasing worldwide to assume pandemic proportions. Since many diseases are associated with obesity, it is important to identify the presence and causes behind overweight and obesity. We have attempted to list the various causes behind obesity, but we may have missed out some inadvertently or due to lack of space. The purpose behind this work is to generate awareness about how overweight and obesity are sometimes beyond the patient’s control. People with obesity of all ages have to face discrimination in the society, teaching institutes, and at the workplace. Often this discrimination leads to depression, stress, and overeating and aggravates the problem. It is important to remove this stigma and to consider people who are having to deal with this stigma as victims, rather than justifying the discrimination.
The World Health Organization has recognized obesity as a disease. It is important for physicians and healthcare workers to treat patients with obesity with compassion and empathy, to be open to endogenous and exogenous causes of obesity, and to suggest weight loss remedies if the patient is unable to achieve it himself/herself.
The authors declare no conflict of interest.
IntechOpen publishes different types of publications
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Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:302,paginationItems:[{id:"198499",title:"Dr.",name:"Daniel",middleName:null,surname:"Glossman-Mitnik",slug:"daniel-glossman-mitnik",fullName:"Daniel Glossman-Mitnik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/198499/images/system/198499.jpeg",biography:"Dr. Daniel Glossman-Mitnik is currently a Titular Researcher at the Centro de Investigación en Materiales Avanzados (CIMAV), Chihuahua, Mexico, as well as a National Researcher of Level III at the Consejo Nacional de Ciencia y Tecnología, Mexico. His research interest focuses on computational chemistry and molecular modeling of diverse systems of pharmacological, food, and alternative energy interests by resorting to DFT and Conceptual DFT. He has authored a coauthored more than 255 peer-reviewed papers, 32 book chapters, and 2 edited books. He has delivered speeches at many international and domestic conferences. He serves as a reviewer for more than eighty international journals, books, and research proposals as well as an editor for special issues of renowned scientific journals.",institutionString:"Centro de Investigación en Materiales Avanzados",institution:{name:"Centro de Investigación en Materiales Avanzados",country:{name:"Mexico"}}},{id:"76477",title:"Prof.",name:"Mirza",middleName:null,surname:"Hasanuzzaman",slug:"mirza-hasanuzzaman",fullName:"Mirza Hasanuzzaman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/76477/images/system/76477.png",biography:"Dr. Mirza Hasanuzzaman is a Professor of Agronomy at Sher-e-Bangla Agricultural University, Bangladesh. He received his Ph.D. in Plant Stress Physiology and Antioxidant Metabolism from Ehime University, Japan, with a scholarship from the Japanese Government (MEXT). Later, he completed his postdoctoral research at the Center of Molecular Biosciences, University of the Ryukyus, Japan, as a recipient of the Japan Society for the Promotion of Science (JSPS) postdoctoral fellowship. He was also the recipient of the Australian Government Endeavour Research Fellowship for postdoctoral research as an adjunct senior researcher at the University of Tasmania, Australia. Dr. Hasanuzzaman’s current work is focused on the physiological and molecular mechanisms of environmental stress tolerance. Dr. Hasanuzzaman has published more than 150 articles in peer-reviewed journals. He has edited ten books and written more than forty book chapters on important aspects of plant physiology, plant stress tolerance, and crop production. According to Scopus, Dr. Hasanuzzaman’s publications have received more than 10,500 citations with an h-index of 53. He has been named a Highly Cited Researcher by Clarivate. He is an editor and reviewer for more than fifty peer-reviewed international journals and was a recipient of the “Publons Peer Review Award” in 2017, 2018, and 2019. He has been honored by different authorities for his outstanding performance in various fields like research and education, and he has received the World Academy of Science Young Scientist Award (2014) and the University Grants Commission (UGC) Award 2018. He is a fellow of the Bangladesh Academy of Sciences (BAS) and the Royal Society of Biology.",institutionString:"Sher-e-Bangla Agricultural University",institution:{name:"Sher-e-Bangla Agricultural University",country:{name:"Bangladesh"}}},{id:"187859",title:"Prof.",name:"Kusal",middleName:"K.",surname:"Das",slug:"kusal-das",fullName:"Kusal Das",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSBDeQAO/Profile_Picture_1623411145568",biography:"Kusal K. Das is a Distinguished Chair Professor of Physiology, Shri B. M. Patil Medical College and Director, Centre for Advanced Medical Research (CAMR), BLDE (Deemed to be University), Vijayapur, Karnataka, India. Dr. Das did his M.S. and Ph.D. in Human Physiology from the University of Calcutta, Kolkata. His area of research is focused on understanding of molecular mechanisms of heavy metal activated low oxygen sensing pathways in vascular pathophysiology. He has invented a new method of estimation of serum vitamin E. His expertise in critical experimental protocols on vascular functions in experimental animals was well documented by his quality of publications. He was a Visiting Professor of Medicine at University of Leeds, United Kingdom (2014-2016) and Tulane University, New Orleans, USA (2017). For his immense contribution in medical research Ministry of Science and Technology, Government of India conferred him 'G.P. Chatterjee Memorial Research Prize-2019” and he is also the recipient of 'Dr.Raja Ramanna State Scientist Award 2015” by Government of Karnataka. He is a Fellow of the Royal Society of Biology (FRSB), London and Honorary Fellow of Karnataka Science and Technology Academy, Department of Science and Technology, Government of Karnataka.",institutionString:"BLDE (Deemed to be University), India",institution:null},{id:"243660",title:"Dr.",name:"Mallanagouda Shivanagouda",middleName:null,surname:"Biradar",slug:"mallanagouda-shivanagouda-biradar",fullName:"Mallanagouda Shivanagouda Biradar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243660/images/system/243660.jpeg",biography:"M. S. Biradar is Vice Chancellor and Professor of Medicine of\nBLDE (Deemed to be University), Vijayapura, Karnataka, India.\nHe obtained his MD with a gold medal in General Medicine and\nhas devoted himself to medical teaching, research, and administrations. He has also immensely contributed to medical research\non vascular medicine, which is reflected by his numerous publications including books and book chapters. Professor Biradar was\nalso Visiting Professor at Tulane University School of Medicine, New Orleans, USA.",institutionString:"BLDE (Deemed to be University)",institution:{name:"BLDE University",country:{name:"India"}}},{id:"289796",title:"Dr.",name:"Swastika",middleName:null,surname:"Das",slug:"swastika-das",fullName:"Swastika Das",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/289796/images/system/289796.jpeg",biography:"Swastika N. Das is Professor of Chemistry at the V. P. Dr. P. G.\nHalakatti College of Engineering and Technology, BLDE (Deemed\nto be University), Vijayapura, Karnataka, India. She obtained an\nMSc, MPhil, and PhD in Chemistry from Sambalpur University,\nOdisha, India. Her areas of research interest are medicinal chemistry, chemical kinetics, and free radical chemistry. She is a member\nof the investigators who invented a new modified method of estimation of serum vitamin E. She has authored numerous publications including book\nchapters and is a mentor of doctoral curriculum at her university.",institutionString:"BLDEA’s V.P.Dr.P.G.Halakatti College of Engineering & Technology",institution:{name:"BLDE University",country:{name:"India"}}},{id:"248459",title:"Dr.",name:"Akikazu",middleName:null,surname:"Takada",slug:"akikazu-takada",fullName:"Akikazu Takada",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248459/images/system/248459.png",biography:"Akikazu Takada was born in Japan, 1935. After graduation from\nKeio University School of Medicine and finishing his post-graduate studies, he worked at Roswell Park Memorial Institute NY,\nUSA. He then took a professorship at Hamamatsu University\nSchool of Medicine. In thrombosis studies, he found the SK\npotentiator that enhances plasminogen activation by streptokinase. He is very much interested in simultaneous measurements\nof fatty acids, amino acids, and tryptophan degradation products. By using fatty\nacid analyses, he indicated that plasma levels of trans-fatty acids of old men were\nfar higher in the US than Japanese men. . He also showed that eicosapentaenoic acid\n(EPA) and docosahexaenoic acid (DHA) levels are higher, and arachidonic acid\nlevels are lower in Japanese than US people. By using simultaneous LC/MS analyses\nof plasma levels of tryptophan metabolites, he recently found that plasma levels of\nserotonin, kynurenine, or 5-HIAA were higher in patients of mono- and bipolar\ndepression, which are significantly different from observations reported before. In\nview of recent reports that plasma tryptophan metabolites are mainly produced by\nmicrobiota. He is now working on the relationships between microbiota and depression or autism.",institutionString:"Hamamatsu University School of Medicine",institution:{name:"Hamamatsu University School of Medicine",country:{name:"Japan"}}},{id:"137240",title:"Prof.",name:"Mohammed",middleName:null,surname:"Khalid",slug:"mohammed-khalid",fullName:"Mohammed Khalid",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/137240/images/system/137240.png",biography:"Mohammed Khalid received his B.S. degree in chemistry in 2000 and Ph.D. degree in physical chemistry in 2007 from the University of Khartoum, Sudan. He moved to School of Chemistry, Faculty of Science, University of Sydney, Australia in 2009 and joined Dr. Ron Clarke as a postdoctoral fellow where he worked on the interaction of ATP with the phosphoenzyme of the Na+/K+-ATPase and dual mechanisms of allosteric acceleration of the Na+/K+-ATPase by ATP; then he went back to Department of Chemistry, University of Khartoum as an assistant professor, and in 2014 he was promoted as an associate professor. In 2011, he joined the staff of Department of Chemistry at Taif University, Saudi Arabia, where he is currently an assistant professor. His research interests include the following: P-Type ATPase enzyme kinetics and mechanisms, kinetics and mechanisms of redox reactions, autocatalytic reactions, computational enzyme kinetics, allosteric acceleration of P-type ATPases by ATP, exploring of allosteric sites of ATPases, and interaction of ATP with ATPases located in cell membranes.",institutionString:"Taif University",institution:{name:"Taif University",country:{name:"Saudi Arabia"}}},{id:"63810",title:"Prof.",name:"Jorge",middleName:null,surname:"Morales-Montor",slug:"jorge-morales-montor",fullName:"Jorge Morales-Montor",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/63810/images/system/63810.png",biography:"Dr. Jorge Morales-Montor was recognized with the Lola and Igo Flisser PUIS Award for best graduate thesis at the national level in the field of parasitology. He received a fellowship from the Fogarty Foundation to perform postdoctoral research stay at the University of Georgia. He has 153 journal articles to his credit. He has also edited several books and published more than fifty-five book chapters. He is a member of the Mexican Academy of Sciences, Latin American Academy of Sciences, and the National Academy of Medicine. He has received more than thirty-five awards and has supervised numerous bachelor’s, master’s, and Ph.D. students. Dr. Morales-Montor is the past president of the Mexican Society of Parasitology.",institutionString:"National Autonomous University of Mexico",institution:{name:"National Autonomous University of Mexico",country:{name:"Mexico"}}},{id:"217215",title:"Dr.",name:"Palash",middleName:null,surname:"Mandal",slug:"palash-mandal",fullName:"Palash Mandal",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217215/images/system/217215.jpeg",biography:null,institutionString:"Charusat University",institution:null},{id:"49739",title:"Dr.",name:"Leszek",middleName:null,surname:"Szablewski",slug:"leszek-szablewski",fullName:"Leszek Szablewski",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49739/images/system/49739.jpg",biography:"Leszek Szablewski is a professor of medical sciences. He received his M.S. in the Faculty of Biology from the University of Warsaw and his PhD degree from the Institute of Experimental Biology Polish Academy of Sciences. He habilitated in the Medical University of Warsaw, and he obtained his degree of Professor from the President of Poland. Professor Szablewski is the Head of Chair and Department of General Biology and Parasitology, Medical University of Warsaw. Professor Szablewski has published over 80 peer-reviewed papers in journals such as Journal of Alzheimer’s Disease, Biochim. Biophys. Acta Reviews of Cancer, Biol. Chem., J. Biomed. Sci., and Diabetes/Metabol. Res. Rev, Endocrine. He is the author of two books and four book chapters. He has edited four books, written 15 scripts for students, is the ad hoc reviewer of over 30 peer-reviewed journals, and editorial member of peer-reviewed journals. Prof. Szablewski’s research focuses on cell physiology, genetics, and pathophysiology. He works on the damage caused by lack of glucose homeostasis and changes in the expression and/or function of glucose transporters due to various diseases. He has given lectures, seminars, and exercises for students at the Medical University.",institutionString:"Medical University of Warsaw",institution:{name:"Medical University of Warsaw",country:{name:"Poland"}}},{id:"173123",title:"Dr.",name:"Maitham",middleName:null,surname:"Khajah",slug:"maitham-khajah",fullName:"Maitham Khajah",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/173123/images/system/173123.jpeg",biography:"Dr. Maitham A. Khajah received his degree in Pharmacy from Faculty of Pharmacy, Kuwait University, in 2003 and obtained his PhD degree in December 2009 from the University of Calgary, Canada (Gastrointestinal Science and Immunology). Since January 2010 he has been assistant professor in Kuwait University, Faculty of Pharmacy, Department of Pharmacology and Therapeutics. His research interest are molecular targets for the treatment of inflammatory bowel disease (IBD) and the mechanisms responsible for immune cell chemotaxis. He cosupervised many students for the MSc Molecular Biology Program, College of Graduate Studies, Kuwait University. Ever since joining Kuwait University in 2010, he got various grants as PI and Co-I. He was awarded the Best Young Researcher Award by Kuwait University, Research Sector, for the Year 2013–2014. He was a member in the organizing committee for three conferences organized by Kuwait University, Faculty of Pharmacy, as cochair and a member in the scientific committee (the 3rd, 4th, and 5th Kuwait International Pharmacy Conference).",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"195136",title:"Dr.",name:"Aya",middleName:null,surname:"Adel",slug:"aya-adel",fullName:"Aya Adel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/195136/images/system/195136.jpg",biography:"Dr. Adel works as an Assistant Lecturer in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. Dr. Adel is especially interested in joint attention and its impairment in autism spectrum disorder",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"94911",title:"Dr.",name:"Boulenouar",middleName:null,surname:"Mesraoua",slug:"boulenouar-mesraoua",fullName:"Boulenouar Mesraoua",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/94911/images/system/94911.png",biography:"Dr Boulenouar Mesraoua is the Associate Professor of Clinical Neurology at Weill Cornell Medical College-Qatar and a Consultant Neurologist at Hamad Medical Corporation at the Neuroscience Department; He graduated as a Medical Doctor from the University of Oran, Algeria; he then moved to Belgium, the City of Liege, for a Residency in Internal Medicine and Neurology at Liege University; after getting the Belgian Board of Neurology (with high marks), he went to the National Hospital for Nervous Diseases, Queen Square, London, United Kingdom for a fellowship in Clinical Neurophysiology, under Pr Willison ; Dr Mesraoua had also further training in Epilepsy and Continuous EEG Monitoring for two years (from 2001-2003) in the Neurophysiology department of Zurich University, Switzerland, under late Pr Hans Gregor Wieser ,an internationally known epileptologist expert. \n\nDr B. Mesraoua is the Director of the Neurology Fellowship Program at the Neurology Section and an active member of the newly created Comprehensive Epilepsy Program at Hamad General Hospital, Doha, Qatar; he is also Assistant Director of the Residency Program at the Qatar Medical School. \nDr B. Mesraoua's main interests are Epilepsy, Multiple Sclerosis, and Clinical Neurology; He is the Chairman and the Organizer of the well known Qatar Epilepsy Symposium, he is running yearly for the past 14 years and which is considered a landmark in the Gulf region; He has also started last year , together with other epileptologists from Qatar, the region and elsewhere, a yearly International Epilepsy School Course, which was attended by many neurologists from the Area.\n\nInternationally, Dr Mesraoua is an active and elected member of the Commission on Eastern Mediterranean Region (EMR ) , a regional branch of the International League Against Epilepsy (ILAE), where he represents the Middle East and North Africa(MENA ) and where he holds the position of chief of the Epilepsy Epidemiology Section; Dr Mesraoua is a member of the American Academy of Neurology, the Europeen Academy of Neurology and the American Epilepsy Society.\n\nDr Mesraoua's main objectives are to encourage frequent gathering of the epileptologists/neurologists from the MENA region and the rest of the world, promote Epilepsy Teaching in the MENA Region, and encourage multicenter studies involving neurologists and epileptologists in the MENA region, particularly epilepsy epidemiological studies. \n\nDr. Mesraoua is the recipient of two research Grants, as the Lead Principal Investigator (750.000 USD and 250.000 USD) from the Qatar National Research Fund (QNRF) and the Hamad Hospital Internal Research Grant (IRGC), on the following topics : “Continuous EEG Monitoring in the ICU “ and on “Alpha-lactoalbumin , proof of concept in the treatment of epilepsy” .Dr Mesraoua is a reviewer for the journal \"seizures\" (Europeen Epilepsy Journal ) as well as dove journals ; Dr Mesraoua is the author and co-author of many peer reviewed publications and four book chapters in the field of Epilepsy and Clinical Neurology",institutionString:"Weill Cornell Medical College in Qatar",institution:{name:"Weill Cornell Medical College in Qatar",country:{name:"Qatar"}}},{id:"282429",title:"Prof.",name:"Covanis",middleName:null,surname:"Athanasios",slug:"covanis-athanasios",fullName:"Covanis Athanasios",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/282429/images/system/282429.jpg",biography:null,institutionString:"Neurology-Neurophysiology Department of the Children Hospital Agia Sophia",institution:null},{id:"190980",title:"Prof.",name:"Marwa",middleName:null,surname:"Mahmoud Saleh",slug:"marwa-mahmoud-saleh",fullName:"Marwa Mahmoud Saleh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/190980/images/system/190980.jpg",biography:"Professor Marwa Mahmoud Saleh is a doctor of medicine and currently works in the unit of Phoniatrics, Department of Otolaryngology, Ain Shams University in Cairo, Egypt. She got her doctoral degree in 1991 and her doctoral thesis was accomplished in the University of Iowa, United States. Her publications covered a multitude of topics as videokymography, cochlear implants, stuttering, and dysphagia. She has lectured Egyptian phonology for many years. Her recent research interest is joint attention in autism.",institutionString:"Ain Shams University",institution:{name:"Ain Shams University",country:{name:"Egypt"}}},{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259190/images/system/259190.png",biography:"Dr. Naqvi is a radioanalytical chemist and is working as an associate professor of analytical chemistry in the Department of Chemistry, Government College University, Faisalabad, Pakistan. Advance separation techniques, nuclear analytical techniques and radiopharmaceutical analysis are the main courses that he is teaching to graduate and post-graduate students. In the research area, he is focusing on the development of organic- and biomolecule-based radiopharmaceuticals for diagnosis and therapy of infectious and cancerous diseases. Under the supervision of Dr. Naqvi, three students have completed their Ph.D. degrees and 41 students have completed their MS degrees. He has completed three research projects and is currently working on 2 projects entitled “Radiolabeling of fluoroquinolone derivatives for the diagnosis of deep-seated bacterial infections” and “Radiolabeled minigastrin peptides for diagnosis and therapy of NETs”. He has published about 100 research articles in international reputed journals and 7 book chapters. Pakistan Institute of Nuclear Science & Technology (PINSTECH) Islamabad, Punjab Institute of Nuclear Medicine (PINM), Faisalabad and Institute of Nuclear Medicine and Radiology (INOR) Abbottabad are the main collaborating institutes.",institutionString:"Government College University",institution:{name:"Government College University, Faisalabad",country:{name:"Pakistan"}}},{id:"58390",title:"Dr.",name:"Gyula",middleName:null,surname:"Mozsik",slug:"gyula-mozsik",fullName:"Gyula Mozsik",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/58390/images/system/58390.png",biography:"Gyula Mózsik MD, Ph.D., ScD (med), is an emeritus professor of Medicine at the First Department of Medicine, Univesity of Pécs, Hungary. He was head of this department from 1993 to 2003. His specializations are medicine, gastroenterology, clinical pharmacology, clinical nutrition, and dietetics. His research fields are biochemical pharmacological examinations in the human gastrointestinal (GI) mucosa, mechanisms of retinoids, drugs, capsaicin-sensitive afferent nerves, and innovative pharmacological, pharmaceutical, and nutritional (dietary) research in humans. He has published about 360 peer-reviewed papers, 197 book chapters, 692 abstracts, 19 monographs, and has edited 37 books. He has given about 1120 regular and review lectures. He has organized thirty-eight national and international congresses and symposia. He is the founder of the International Conference on Ulcer Research (ICUR); International Union of Pharmacology, Gastrointestinal Section (IUPHAR-GI); Brain-Gut Society symposiums, and gastrointestinal cytoprotective symposiums. He received the Andre Robert Award from IUPHAR-GI in 2014. Fifteen of his students have been appointed as full professors in Egypt, Cuba, and Hungary.",institutionString:"University of Pécs",institution:{name:"University of Pecs",country:{name:"Hungary"}}},{id:"277367",title:"M.Sc.",name:"Daniel",middleName:"Martin",surname:"Márquez López",slug:"daniel-marquez-lopez",fullName:"Daniel Márquez López",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/277367/images/7909_n.jpg",biography:"Msc Daniel Martin Márquez López has a bachelor degree in Industrial Chemical Engineering, a Master of science degree in the same área and he is a PhD candidate for the Instituto Politécnico Nacional. His Works are realted to the Green chemistry field, biolubricants, biodiesel, transesterification reactions for biodiesel production and the manipulation of oils for therapeutic purposes.",institutionString:null,institution:{name:"Instituto Politécnico Nacional",country:{name:"Mexico"}}},{id:"196544",title:"Prof.",name:"Angel",middleName:null,surname:"Catala",slug:"angel-catala",fullName:"Angel Catala",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/196544/images/system/196544.jpg",biography:"Angel Catalá studied chemistry at Universidad Nacional de La Plata, Argentina, where he received a Ph.D. in Chemistry (Biological Branch) in 1965. From 1964 to 1974, he worked as an Assistant in Biochemistry at the School of Medicine at the same university. From 1974 to 1976, he was a fellow of the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor of Biochemistry at the Universidad Nacional de La Plata. He is a member of the National Research Council (CONICET), Argentina, and the Argentine Society for Biochemistry and Molecular Biology (SAIB). His laboratory has been interested for many years in the lipid peroxidation of biological membranes from various tissues and different species. Dr. Catalá has directed twelve doctoral theses, published more than 100 papers in peer-reviewed journals, several chapters in books, and edited twelve books. He received awards at the 40th International Conference Biochemistry of Lipids 1999 in Dijon, France. He is the winner of the Bimbo Pan-American Nutrition, Food Science and Technology Award 2006 and 2012, South America, Human Nutrition, Professional Category. In 2006, he won the Bernardo Houssay award in pharmacology, in recognition of his meritorious works of research. Dr. Catalá belongs to the editorial board of several journals including Journal of Lipids; International Review of Biophysical Chemistry; Frontiers in Membrane Physiology and Biophysics; World Journal of Experimental Medicine and Biochemistry Research International; World Journal of Biological Chemistry, Diabetes, and the Pancreas; International Journal of Chronic Diseases & Therapy; and International Journal of Nutrition. 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At the National Cancer Institute (National Institute of Health, Bethesda, MD) he worked as a research associate on the molecular biology of selenium and its role in health and disease. After postdoctoral collaborations with Carlos Gutierrez-Merino (University of Extremadura, Spain) and Dario Alessi (University of Dundee, UK), he established his own laboratory in 2008. 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