Physicochemical properties of selected veterinary drugs from different classes.
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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This book emphasizes the general biological processes of neurodegeneration in different neurodegenerative diseases. Although the primary etiology for different neurodegenerative diseases is different, there is a high level of similarity in the disease processes. The first three sections introduce how toxic proteins, intracellular calcium and oxidative stress affect different biological signaling pathways or molecular machineries to inform neurons to undergo degeneration. A section discusses how neighboring glial cells modulate or promote neurodegeneration. In the next section an evaluation is given of how hormonal and metabolic control modulate disease progression, which is followed by a section exploring some preventive methods using natural products and new pharmacological targets. We also explore how medical devices facilitate patient monitoring. This book is suitable for different readers: college students can use it as a textbook; researchers in academic institutions and pharmaceutical companies can take it as updated research information; health care professionals can take it as a reference book, even patients' families, relatives and friends can take it as a good basis to understand neurodegenerative diseases.",isbn:null,printIsbn:"978-953-307-485-6",pdfIsbn:"978-953-51-4391-8",doi:"10.5772/1252",price:159,priceEur:175,priceUsd:205,slug:"neurodegenerative-diseases-processes-prevention-protection-and-monitoring",numberOfPages:572,isOpenForSubmission:!1,isInWos:1,isInBkci:!0,hash:"3d5795dad33257368f0b7848c22d5dd4",bookSignature:"Raymond Chuen-Chung Chang",publishedDate:"December 9th 2011",coverURL:"https://cdn.intechopen.com/books/images_new/745.jpg",numberOfDownloads:63366,numberOfWosCitations:85,numberOfCrossrefCitations:23,numberOfCrossrefCitationsByBook:3,numberOfDimensionsCitations:80,numberOfDimensionsCitationsByBook:4,hasAltmetrics:1,numberOfTotalCitations:188,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 23rd 2011",dateEndSecondStepPublish:"March 23rd 2011",dateEndThirdStepPublish:"July 28th 2011",dateEndFourthStepPublish:"August 27th 2011",dateEndFifthStepPublish:"December 25th 2011",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,8,9",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"33396",title:"Dr.",name:"Raymond Chuen-Chung",middleName:null,surname:"Chang",slug:"raymond-chuen-chung-chang",fullName:"Raymond Chuen-Chung Chang",profilePictureURL:"https://mts.intechopen.com/storage/users/33396/images/system/33396.jpeg",biography:"Dr. Chang is the Lab Chief for the Laboratory of Neurodegenerative Diseases in the School of Biomedical Sciences, member in The State Key Laboratory of Brain and Cognitive Sciences. He is also the Founder and Secretary of HKU Alzheimer’s Disease Research Network, organising International Alzheimer’s Disease Conference every year since 2000.\nDr. Chang’s research interest is pathophysiological changes of Alzheimer’s disease (AD) and the risk factors leading to AD. He has published over 120 peer-reviewed papers and 14 book chapters in these areas. His h-index is 34 by Scopus, 43 by Google Scholar. He is a member in the Scientific Advisory Board of International AD/PD Symposium, Scientific Review Committee in Alzheimer Association, Senior Editor for Journal of Neuroimmune Pharmacology, and Editor-in-Chief for ‘American Journal of Alzheimer’s Disease and Other Dementias. 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However, food safety is an important issue regarding residues of veterinary drugs in foods from food producing animals. Veterinary drugs are used to prevent and treat bacterial infections as well as improve feed efficiency and to promote animal growth worldwide [2]. The use of veterinary drugs in food producing animals may result in residues of the drugs or their metabolites being present in food samples, and this might be due to the inappropriate or excessive use of these drugs [3]. Various veterinary drugs have been reported to be retained in meat and milk of food producing animals [4, 5, 6] and this might be a health problem to humans who consume these food products.
Various pre-treatment methods have been described for the extraction of veterinary drug residues in food samples, such as liquid-liquid extraction (LLE) [7, 8, 9], solid-phase extraction (SPE) [10], solid-phase micro extraction [11, 12, 13, 14]. Pre-concentration is necessary because veterinary drug residues often occur in trace amounts. However, some of these methods are laborious and time consuming, like LLE and SPE. It is very important to develop simple, rapid and efficient methods for the determination of veterinary drug residues in foods samples. In recent years, extraction and pre-concentration techniques that are compliant to the green chemistry methods have been developed and they will be discussed in Section 6. Moreover, several countries and different international organizations such as the World Health Organization (WHO), the Food Agriculture Organization (FAO) and the European Union (EU) have set maximum residue limits (MRLs) of veterinary drug residues in food to ensure food safety.
Physicochemical properties and uses of different veterinary drug classes are described below. A few examples of the physicochemical properties of selected veterinary drugs are shown on Table 1. Sulfonamides (SAs) show impartially low sorption capacity to solids compared to other veterinary drugs. These are used for the treatment of bacterial infections in animal husbandry and also act as growth promotants. Sulphonamides are also used in farm animal feeds and fish cultures [15]. Examples include sulfadiazine, sulfamethazine, sulfamethoxazole and sulfaquinoxaline.
Tetracyclines (TCs), including tetracycline, oxytetracycline, chlortetracycline and doxycycline are broad-spectrum veterinary drugs with broad use in animal husbandry. They are amphoteric compounds. Generally, TCs are more stable in acidic conditions.
Quinolones (QNs) are synthetic veterinary drugs with broad-spectrum antibacterial effects. This veterinary drug class consists of plain quinolones, such as oxolinic acid and nalidixic acid and fluorinated quinolones, known as fluoroquinolones (FQs), such as ciprofloxacin, flumequine and sarafloxacin.
Amphenicols are a broad-spectrum veterinary drug group that include chloramphenicol and its metabolites, thiamphenicol and florfenicol. Florfenicol has its own metabolite, florfenicol amine. The most common member of this veterinary drug class is chloramphenicol which is effective against many bacterial strains. Its toxicity and unwanted effects have restricted its use over the past years [16, 17].
Macrolides are a class of semi-synthetic medium-spectrum veterinary drugs. The most commonly used macrolides have 12–16 membered structures. Erythromycin is the most common veterinary drug in this class. Generally, macrolides have weak characteristics and thus are unstable under acidic conditions. Examples include erythromycin, tylosin, spiramycin, tilmicosin and tulathromycin.
Beta lactam veterinary drugs consist of several groups of compounds with cephalosporins and penicillins among the most important. Penicillins are commonly used for their microbial activity against both gram-positive and gram-negative organisms. The main clean-up method of penicillins for their analysis is pre- and post-column derivatization and the commonly used detection methods are LC-MS and LC-UV. Examples of penicillins are amoxicillin, ampicillin, oxacillin and cloxacillin, and examples of cephalosporins are cephapyin, ceftiofur and cefadroxil.
Aminoglycosides are broad spectrum veterinary drugs with antibacterial and antifungal activities produced by
Nitrofurans are synthetic chemotherapeutic agents used in the treatment and prevention of gastrointestinal infections caused by
In summary of this section, generally, veterinary drugs are compounds characterized by a complex chemical structure that have very variable water solubilities, low volatilization potential, several ionizable functional groups (amphoteric molecules) and different pKa values hence they have a low bioaccumulation potential [18]. Veterinary drugs may have different functionalities within the same molecule, making them either neutral, cationic, anionic, or zwitterionic under different pH conditions. Different functionalities within a single molecule may result in its physicochemical and biological characteristics such as, sorption behavior, photo reactivity and toxicity changing with pH. Solubility and hydrophobicity are also are pH dependent. The pH dependency of antibiotic solubility can affect the extraction and quantification by analytical techniques [19].
Class of veterinary antibiotic drugs | Name of antibiotic | Solubility in water (mg L−1) | pKa |
---|---|---|---|
Tetracyclines | Tetracycline | 231 | 3.3 |
Chlortetracycline | ~8600 | 3.3 | |
Doxycycline | 50,000 | — | |
Oxytetracycline | 1 × 106 | 3.27 | |
Sulphonamides | Sulfadiazine | 77 | 6.5 |
Sulfamethoxazole | 500 | 8.8 | |
Sulfaquinoxaline | 7.5 | — | |
Sulfamethazine | 1500 | 8.43 | |
Macrolides | Erythromycin | 2000 | 8.8 |
Tylosin | 5000 | — | |
Azithromycin | <1000 | — | |
Quinolones | Ciprofloxacin | Insoluble | — |
Enrofloxacin | 146 | — | |
Oxolinic acid | Insoluble | 6.87 |
Physicochemical properties of selected veterinary drugs from different classes.
–, Not available.
The use of veterinary drugs in food producing animals can result in the presence of residues in animal derived products such meat, milk, eggs and honey. This poses a health hazard to the consumers [3]. Veterinary drugs such as macrolides, tetracyclines, sulfonamides and penicillins are also used as antibiotics in humans [20, 21]. Physicochemical properties of drugs, pharmacokinetic characteristics or biological processes of animals are factors that affect the presence of drug residues in food of animal origin. Improper drug usage and failure to observe withdrawal periods may be a reason for the occurrence of veterinary drug residues in foods derived from animals.
The threat of food contamination by veterinary drug residues is one of the major challenges to public health worldwide [3]. The presence of low levels of veterinary drug residues may not have a negative impact on public health. However, the substantial use of drugs may increase the risk of adverse effects of these residues to humans [3, 22, 23]. Continuous ingestion of veterinary drug residues can promote the development of drug resistance bacterial strains in an individual, resulting in resistance to treatment with the same antibiotics when need arises [24, 25, 26]. Veterinary drug traces also have harmful effects on humans, such as allergic reactions, liver damage, yellowing of teeth and gastrointestinal disturbance [27]. Sulphonamides can cause drug intoxication and hypersensitivity. Signs of hypersensitivity and intoxication are fever and anemia respectively.
Manuring, treatment of animals and disposal of carcasses, offals, urine, feces and unused products can contaminate the environment with veterinary drugs [28]. An excessive use of antibiotics in commercially reared animals does not only affect humans, it can also affect the food chain leading to ecological imbalances. For example, a deficient management of the livestock carcasses can lead to antibiotic resistance in the scavengers that ingest them, like vultures [24, 25, 26]. The disposal of medicated animals should be regulated to minimize the risk in scavenger birds.
The MRL values for food products result from calculations based upon the acceptable daily intake. MRL values depend on chronic toxicity of the antibiotic in question. More toxic drugs have lower MRL values compared to moderately toxic drugs. Prohibited substances are pharmacologically active substances for which an MRL cannot be established because of their toxicity and these include substances such as chloramphenicol, nitrofurans and nitroimidazoles. The kidney is the most important organ of drug excretion and that might be the reason why for most drugs it is allocated a higher MRL. For example, in the European Union (EU), countries have established a MRL of 200, 100, and 300 μg kg−1 for liver, muscle and kidney tissues, respectively for enrofloxacin and ciprofloxacin. The MRL set by the EU Committee for veterinary medicinal products is 200 μg kg−1 in muscles, liver and kidneys of animal origin, 40 μg kg−1 in milk, and 150 μg kg−1 in eggs for the macrolide drugs. Table 2 shows some MRL values for different foods of animal origin.
Class of veterinary drugs | Target veterinary drug | Matrix | MRL (μg kg−1) |
---|---|---|---|
Sulphonamides | Sulphonamides | Milk, fish and other seafood | 100 |
Sulphonamides | Eggs | Not allowed | |
Quinolones | Danofloxacin, enrofloxacin-ciprofloxacin and oxolinic acid | Muscle | 100 |
Enrofloxacin and ciprofloxacin | Eggs | Not allowed | |
Enrofloxacin and ciprofloxacin | Liver | 200 | |
Enrofloxacin and ciprofloxacin | Kidney | 300 | |
Macrolides | Macrolides | Muscle, liver and kidneys | 200 |
Macrolides | Milk | 40 | |
Macrolides | Eggs | 150 | |
Tetracyclines (single/total) | Tetracycline, oxytetracycline, chlortetracycline and doxycycline | Muscle, milk | 100 |
Tetracyclines (single/total) | Tetracycline, oxytetracycline, chlortetracycline and doxycycline | Eggs | 200 |
Maximum residue limit for veterinary drug residues in food samples according to European Community, Commission Regulation (EU) No. 37/2010.
Veterinary drug residues in food of animal origin are of great concern to regulatory agencies and consumers, hence reliable extraction methods for rapid, selective and sensitive detection of these residues are necessary to ensure food safety [29]. There are various extraction methods that have been used in veterinary drug residues analysis in food samples, such as liquid-liquid extraction (LLE) [30, 31, 32] and solid phase extraction (SPE) [33, 34]. These methods suffer a number of drawbacks even though they perform their tasks adequately. Both LLE and SPE are environmentally unfriendly due to the large amounts of organic solvents they use, they are time consuming and labor intensive. Another disadvantage of SPE is that cartridges are costly.
Promising extraction and pre-concentration techniques for veterinary drug residues that have been explored recently by many researchers include dispersive liquid-liquid microextraction (DLLME) [5, 6, 35, 36], hollow fiber based liquid-phase microextraction (HFLPME) [37, 38, 39, 40] and quick, easy, cheap, effective, rugged and safe (QuEChERS) [4, 41, 42, 43] where the general trend is compliance with green chemistry principles. Veterinary drug residues occur at trace levels as low nanogram per gram [4, 37] hence the need to pre-concentrate. The application of QuEChERS, DLLME, HFLPME and molecularly imprinted polymers (MIPs) for the extraction and pre-concentration of veterinary drug residues in food samples will be discussed below and summarized in Table 3.
Target antibiotic | Food matrix | Analytical technique | Extraction technique | Concentration of antibiotic detected | LOD | LOQ | Recovery (%) | References |
---|---|---|---|---|---|---|---|---|
Seven macrolides | Milk | LC-MS/MS | QuEChERS based on acetonitrile extraction + a mixture of salts (sodium sulfate, sodium chloride and potassium carbonate) | — | 0.84 μg kg−1 | 2.79 μg kg−1 | 89–97 | [41] |
Six multi-residues | Bovine milk | LC-MS/MS | QuEChERS based on acetonitrile followed by a cleanup with d-SPE based C18, PSA and sodium acetate | — | — | — | 84.18–115.99 | [42] |
Sixteen multi-residues | Preserved eggs | UHPLC-MS/MS | QuEChERS based on water, acetonitrile with 1% acetic acid followed by a cleanup using d-SPE with C18 and PSA as sorbents | — | 0.1–0.9 μg kg−1 | 0.3–3.0 μg kg−1 | 73.8–127.4 | [43] |
Three SAs | Chicken breast | HPLC-DAD | QuEChERS based on acetonitrile and water with 1% CH3CO2H followed by a cleanup using d-SPE Oasis HLB as a sorbent. | — | 10 and 13 μg kg−1 | 25–30 μg kg−1 | 75.4–98.7 | [46] |
Seven TCs | Beef | LC-MS/MS | DLLME, methanol was a disperser solvent and dichloromethane was an extracting solvent | 38.4 and 82.3 μg kg−1 | 2.2–3.6 μg kg−1 | 7.4–11.5 μg kg−1 | 80–105 | [5] |
Several SAs | Milk | HPLC-FD | Traditional DLLME (extraction solvent (1 mL chloroform) and dispersive solvent (1.9 mL acetonitrile) | — | 0.73–1.21 μg L−1 | — | 92.9–104.7 | [36] |
Six FQs | Milk | HPLC-UV | DLLME was coupled to QuEChERS | — | — | 2.5–15 μg kg−1 | 74.1–101.4 | [35] |
Four TCs | Milk and eggs | HPLC-UV | IL-DLLME ([C6MIM][PF6] as an extraction solvent, FIL-NOSM a disperser solvent) | — | 0.08–1.12 μg kg−1 | — | 94.1–102.1 | [6] |
Florfenicol and Chloramphenicol | Pasteurized Milk | HPLC-UV | Traditional DLLME (chloroform as an extracting solvent and water as a dispenser solvent) | 62.4 μg kg−1 florfenicol | 12.2 and 12.5 μg kg−1 | 36.6 and 37.5 μg kg−1 | — | [53] |
Five QNs and four TCs | Milk, honey, fish, liver and muscles of lamb | HPLC-DAD | HFLPME (0.1 mol L−1 nitric acid and sodium chloride was the acceptor phase, 10% w/v Aliquat-336 in 1-octanol | 24. 8 ng g−1 danofloxacin 37.5 ng g−1 tetracycline | 0.5–20 ng g−1 | 1.25–40 ng g−1 | — | [37] |
Four TCs | Milk | HPLC-UV | HF-DLLME (chloroform as an extracting solvent and water as a dispenser solvent) | — | 0.95–3.6 μg L−1 | 5–15 μg L−1 | 92.38–107.3 | [38] |
Three TCs | Bovine milk | HPLC-UV | Carrier mediated three phase HFLPME (0.1 M phosphoric acid, 1.0 M sodium chloride with pH = 1.6 as an acceptor phase, 0.05 M disodium hydrogen phosphate (pH between 9.1 and 9.5) as donor phase and 10% (w/v) of Aliquat-336 in octanol as an SLM. | 6.0–27.4 μg L−1 | 0.5–1.0 μg L−1 | 0.5–1.0 μg L−1 | - | [39] |
Tylosin | Milk | UV/Vis | HFLPME-TiO2 (TiO2 was dispersed in 1-octanol) | — | 0.21 μg L−1 | — | 89–99 | [40] |
Eight FQs, eight SAs and four TCs | Pork | UPLC-PDA | Mixed template MIP-MSPD (0.15 g MMIP, methanol/water (2:8, v/v) as a washing solvent, methanol/acetic acid (9:1, v/v) as an eluting solvent) | — | 0.5–3.0 ng g−1 | 1.5–6.0 ng g−1 | 92–99 | [57] |
Four TCs | Pork, milk and eggs | HPLC-PDA | MIP-SPE (30 mg MIP particles, 0.01 mol L−1 trifluoroacetic acid, pH 3.0 as the loading solvent, methanol/acetic acid (9:1, v/v) as the elution solvent) | 52 ng mL−1: TC 87 ng mL−1: oxytetracycline in milk only | 20–40 ng mL−1 | 50–80 ng mL−1 | 74–93 | [58] |
Ten macrolides | Swine, cattle and chicken muscles | LC-MS/MS | MIP-SPE (20 mg MIP particles, 10% methanol in water as the washing solvent, 5% ammonia in methanol as the elution solvent) | — | 0.1–0.4 μg kg−1 | 0.3–1.0 μg kg−1 | 60.7–100.3 | [56] |
Ten FQs | Fish | HPLC-FLD | DMIP-MSPD (50 mg MIP particles, 20% methanol in water as the washing solvent, 1% trifluoroacetic acid in acetonitrile as the elution solvent) | — | 0.06–0.22 ng g−1 | — | 64.4–102.7 | [59] |
Three FQs | Milk | HPLC-UV | Mini-MISPE (40 mg MIP particles, water as the washing solvent, methanol-acetic acid (19:1, v/v) as the elution solvent) | Ciprofloxacin: 0.21 and 0.25 g mL−1 | 1.5–2.3 ng mL−1 | 5.0–7.5 ng mL−1 | 87.2–106.1 | [60] |
TCs | Milk | Fluorescent sensing | CDs@MIPs (40 mg MIP particles, 1% (v/v) trichloroacetic acid solution was a solvent) | ND | 5.48 nM | — | 97.3–105.3 | [61] |
Modern analytical techniques in the analysis of antibiotic residues in food samples.
–, Not mentioned; ND, not detected.
The food industry also needs the development of new methods that are fast, easy and cheap for routine analysis of residues in food samples. The latest trend in drug residue analysis is the development of generic methods that are capable of monitoring a wide variety of compounds, belonging to different veterinary drug classes. This has proven to be challenge due to the varying chemistries and physicochemical properties of veterinary drugs from different classes, as a result, multi-class methods for veterinary drugs are still not so widespread although they are strongly required.
The quick easy cheap effective rugged safe (QuEChERS) method is an extraction technique that employs an organic solvent and phase separation using high salt content, in some cases followed by dispersive solid phase extraction (d-SPE) for sample clean up. The QuEChERS method, which was originally developed for pesticide analysis in fruits and vegetables [44, 45], has recently been proposed for the analysis of veterinary drugs in different food matrices [4, 41, 43, 46]. Recent applications of this method are discussed below.
da Costa et al. [41] developed a modified QuEChERS extraction technique using acetonitrile, followed by the addition of a mixture of salts (sodium sulfate, sodium chloride and potassium carbonate) for the extraction of seven macrolide drugs in milk followed by analysis on liquid chromatography and tandem mass spectrometry (LC-MS/MS). Sodium sulfate and sodium chloride removed water from samples promoting the salting out effect while acetonitrile was used for deproteination. Potassium carbonate salt was included to elevate the extraction pH to around 9.5 promoting an increase in the recovery, since macrolides have a pKa between 6.6 and 9.2. The limit of detection (LOD) and limit of quantification (LOQ) were 0.84 and 2.79 μg kg−1 respectively and recoveries were ranging between 89 and 97%. No further clean-up step such as an additional d-SPE step was required, hence reducing time, cost and labor.
In another study by Wang et al. [42], a modified QuEChERS extraction technique based on octadecylsilane (C18), primary secondary amine (PSA) and sodium acetate for six multi-residue veterinary drugs in bovine milk followed by analysis using LC-MS/MS. The QuEChERS method was optimized for use in the determination of multi-class veterinary drug residues in fatty foods (milk) using response surface methodology. The amounts of C18, PSA, and sodium acetate used in this study were determined by the response surface methodology variables. PSA, C18 and sodium acetate have a dissolving effect on milk-fat globules and hence, resulting in higher recoveries (84.18–115.99%) compared to da Costa et al. [41]. Organic solvents, such as acetonitrile, methanol and ethanol, are commonly employed in the precipitation of proteins in biological matrices. For all residues, the LOQs were low enough to quantify the analytes below their MRLs.
Li et al. [43] employed the QuEChERS method followed by d-SPE coupled to ultrahigh-performance liquid chromatography tandem mass spectrometry for the multi-residue analysis of 16 veterinary drugs belonging to three classes (macrolides, quinolones, and sulfonamides) in preserved eggs. Graphitized carbon black was used as a comparative d-SPE sorbent. The recoveries of all veterinary drugs decreased with the addition of graphitized carbon black, while purification with a conjugation of PSA and C18 in the presence of magnesium sulfate resulted in better results. The results demonstrated good linearity, accuracy, precision, LOD (0.1–0.9 μg kg−1) and LOQ (0.3–3.0 μg kg−1) which indicated that the proposed method was highly sensitive and could efficiently determine trace amounts.
Machado et al. [46] developed a QuEChERS method followed by analysis on the high performance liquid chromatography (HPLC) with a diode array detector (DAD) for the simultaneous determination of sulfadiazine, sulfamethoxazole and sulfamethoxypyridazine in chicken breast samples. The LODs ranged between 10 and 13 μg kg−1 and the LOQs ranged between 25 and 30 μg kg−1 while recoveries ranged between 75.4 and 98.7%. SPE was done for comparison and recoveries lower than 70% were obtained. However, SPE, proved to reduce the matrix effect compared to the QuEChERS method.
Traditional sample preparation techniques such as liquid-liquid extraction (LLE) have drawbacks in spite of the substantial use of this method over the years. The LLE method is tedious, time consuming and uses large amounts of toxic organic solvents which are non-compliant to the green analytical chemistry (GAC) principles. In order to overcome these drawbacks, new extraction techniques that are simple, rapid and inexpensive, miniaturized and have the ability of automation have been developed in recent years [47]. The efforts of various researchers in this area have resulted in the development of a new extraction technique known as liquid-phase microextraction (LPME). LPME offers an alternative to SPME [48]. LPME can be divided into three main modes which are single-drop microextraction (SD-LPME), hollow fiber liquid phase microextraction (HFLPME) and dispersive liquid-liquid microextraction (DLLME). Among these modes of LPME, HFLPME and DLLME have been the most used because of the advantages that they offer [47]. SD-LPME is the least used mode because excessive stirring tends to break up the droplet, extraction is time consuming and reaching equilibrium can be a challenge. This disadvantage overrides the advantage that this method has, which is the enormous reduction of volumes of organic solvent it uses [49].
These methods are cheap and do not have sample carryover problems that are associated with SPME [48]. LPME offers advantages such as high recovery and high enrichment factors, simplicity of operation, rapidity and they are also environment friendly [50]. Below is a summary of some studies that have used DLLME and HFLPME for the extraction of veterinary drug residues from food samples.
Rezaee and co-workers [51] introduced DLLME as a new LLE technique for the determination of polyaromatic hydrocarbons and pesticides. The application of DLLME in the extraction of veterinary drugs in literature has increased over the years [5, 6, 35, 36]. This technique is based on a ternary component solvent system including an extraction solvent, disperser solvent and an aqueous sample and is known as traditional DLLME. The advantages of traditional DLLME are the microliter-level volumes required for extraction and dispersive solvents and short extraction times. However, the disadvantage of traditional DLLME is the use of organic solvents as the extraction and dispersive solvents.
Modified modes of DLLME have been invented recently and they include, low-density solvent based DLLME (LDS-DLLME), solidified floating organic drop DLLME (SFO-DLLME), effervescence assisted DLLME, air assisted dispersive liquid-liquid microextraction (AA-DLLME), surfactant assisted DLLME (SA-DLLME) and cloud point DLLME (CP-DLLME), ionic liquid DLLME (IL-DLLME) [6] to address the disadvantages associated with traditional DLLME. Despite these disadvantages, DLLME is more advantageous in terms of short total time, low cost and feasibility compared with other liquid-phase microextraction techniques [52]. Below is research that has been done recently on veterinary drugs in food samples using DLLME.
Mookantsa et al. [5] employed traditional DLLME for the extraction of seven tetracyclines from beef where methanol was a disperser solvent and dichloromethane was an extracting solvent followed by LC-MS/MS. Recoveries of spiked blank muscle samples at three levels (50, 100 and 150 μg kg−1) ranged from 80–105%. LODs and LOQs ranged from 2.2 to 3.6 μg kg−1 and from 7.4 to 11.5 μg kg−1 respectively. Concentrations of chlortetracycline and oxytetracycline were detected in bovine muscle samples to be between 38.4 and 82.3 μg kg−1 which is lower than the stipulated European Union MRL of 100 μg kg−1. DLLME was compared to a South African National Accreditation System accredited d-SPE method and the t-test showed that the results obtained by the methods had no significant difference. However, DLLME was simple, fast, inexpensive and uses very low volumes of organic solvents hence more greener compared to d-SPE.
In a study done by Karami-Osboo et al. [35], DLLME was coupled to QuEChERS for the determination of six fluoroquinolones using HPLC with ultra-violet (UV) detection. The dried supernatant from the QuEChERS method was resuspended in 1.0 mL of a 10% acetic acid-acetonitrile mixture, combined with 200 μL of chloroform and rapidly injected into 4 mL of deionized water. The cloudy solution was centrifuged for 5 minutes at 4500 rpm. By coupling QuEChERS to DLLME, the authors removed matrix interference, which is a common problem with the detection of fluoroquinolones. The method showed good recoveries (74.1–101.4% for all analytes) and low LOQs (below 2.5 μg kg−1 for danofloxacin and below 15 μg kg−1 for all other FQs).
Arroyo-Manzanares et al. [36] used traditional DLLME for the determination of several sulfonamides in milk. The analytes were detected by HPLC with fluorescence detection. The authors also compared their optimized DLLME procedure to QuEChERS. Proteins were precipitated using trichloroacetic acid and then filtered. The DLLME extraction procedure was optimized using a central composite design. The optimum volumes for chloroform as an extraction solvent and acetonitrile as a dispersive solvent were 1 and 1.9 mL, respectively. DLLME resulted in lower LODs (0.73–1.21 μg L−1) than QuEChERS (1.15–2.73 μg L−1) and higher recoveries (92.9–104.7% compared to 83.6–97.1%, when samples were spiked with sulfonamides at 150 μg L−1. However, QuEChERS proved to be more reproducible than DLLME with lower relative standard deviation values of 2.9–7.1 and 3.0–9.7%, respectively.
In another study by Karami-Osboo et al. [53], traditional DLLME coupled to HPLC- UV was used for the determination of chloramphenicol and florfenicol residues in milk samples where chloroform was used as extraction solvent and the deproteinized milk as a disperser solvent. The blank milk samples were spiked at three levels, 150, 300 and 600 μg of each chloramphenicol and florfenicol per kg of milk and recoveries were between 69.1 and 79.4%. The LODs for chloramphenicol and florfenicol were 12.5 and 12.2 μg kg−1 respectively whereas the LOQs were 37.5 and 36.6 μg kg−1 respectively. Despite the use of florfenicol not being permitted for milk producing animals from which milk is produced for human consumption, it was detected in one of the samples at a concentration of 62.4 μg kg−1.
Ionic liquids (ILs), consisting of organic cations and inorganic or organic anions with melting points at or below 100°C, have been widely applied as green solvents to improve extraction and enrichment performance as compared to the traditional use of organic solvents. A significant advantage of this method is that the metathesis reaction and extraction are accomplished in one step making it rapid and suitable for high-throughput analysis. Gao et al. [6] used functionalized ionic liquid-based non-organic solvent microextraction (FIL-NOSM) based on 1-butyl-3-methylimidazolium naphthoic acid salt ([C4MIM][NPA]) with strong acidity for the determination of TCs in milk and eggs. The use of [C4MIM][NPA] in the FIL-NOSM method eliminated the pH adjustment step because of its strong acidity which saves as a pH regulator. This proposed method provided high extraction efficiency, less pretreatment time and requires non-organic solvents for determination of trace TC concentrations in complex animal-based food matrices. Moreover, no organic solvent was utilized in this IL-based DLLME procedure making this method more environmentally friendly. The LODs were between 0.08 and 1.12 μg kg−1 in milk and egg samples. The recoveries ranged from 94.1 to 102.1%.
Hollow fiber liquid phase microextraction is a mode of LPME that uses a porous polypropylene hollow fiber for immobilization of organic solvent in its pores. The development of HFLPME provides a way to stabilize the extraction droplet in SD-LPME by placing it in a hollow fiber [54]. The main consumable material is the hollow fiber membrane, which is lower than other methods in cost and sample consumption [38]. The different modes of HFLPME are static, dynamic, two and three phase. The advantages of HFLPME are high enrichment, high degree of sample clean-up and low solvent consumption. The disadvantage of HFLPME procedure is that it is slow with extraction times ranging from 15 to 45 minutes and target analytes may partly be trapped in the supporting liquid membrane (SLM) [39]. Another disadvantage is that there is no complete setup commercially available for this method although hollow fibers are commercially available [55]. Below are some recent studies on veterinary drug residues that have been carried out using HFLPME.
Tajabadi et al. [37] used a carrier mediated three phase HLFPME prior to analysis on the HPLC-DAD for the simultaneous determination of the veterinary drug residues of four TCs and five QNs in a wide range of animal source food samples such as fish, milk and honey as well as the liver and muscles of lamb and chicken. Multivariate curve resolution-alternative least squares was used for resolving some overlapped peaks in multivariate data of HPLC-DAD and made possible the simultaneous analysis of nine TCs and QNs in minimum time. LODs and LOQs for the different veterinary drugs ranged between 0.5–20 and 1.25–40 ng g−1. Danofloxacin was detected at a concentration of 24.8 ng g−1 in chicken liver, tetracycline was detected at 37.5 ng g−1 in lamb liver which are less than the stipulated MRLs according to EU 37/2010 and the rest of the veterinary drugs were not detected.
Xu et al. [38] employed a carrier mediated three phase hollow fiber membrane based dynamic liquid-liquid microextraction coupled with HPLC-UV detection for the residue analysis of TCs in milk samples without deproteinization and defatting, but the milk samples were diluted five folds. A peristaltic pump was used to promote mass transfer between the carrier and the operated solution. The standard addition method was used to eliminate the matrix effect. Octanol containing 20% (w/w) Aliquat-336 was used as a SLM, 0.05 M disodium hydrogen phosphate, pH 9.0 containing the sample was a donor phase and solutions of 1.0 mol L−1 sodium chloride and phosphoric acid (pH = 1.0) were used as the acceptor solvent. The LOD and LOQ were in the range of 0.95–3.6 and 5–15 μg L−1 respectively. The recoveries in spiked samples ranged from 92.38 to 107.3%.
A similar study was carried out by Shariati et al. [39] where tetracycline, oxytetracycline and doxycycline were extracted from bovine milk, human plasma and water samples using a carrier mediated three phase HFLPME prior analysis on the HPLC-UV. The acceptor solvent was 0.1 M phosphoric acid, 1.0 M sodium chloride with pH = 1.6, 0.05 M disodium hydrogen phosphate (pH between 9.1 and 9.5) containing the sample as the donor phase and 10% (w/v) of Aliquat-336 in octanol as a SLM. The LOD and LOQ were 0.5–1.0 and 0.5–1.0 μg L−1 respectively which are lower compared to the ones obtained by Xu et al. [38] proving that fiber membrane-based dynamic liquid-liquid microextraction is a more efficient extraction method. All the milk samples contained TCs in the range of 6.0–27.4 μg L−1 that was below the MRL as set by the EU.
From the two studies that are above it can be concluded that passive transport of TCs in the absence of the carrier is difficult because of existence of TCs as zwitterionic forms (at the studied conditions) in solution and hence they have a very small tendency to pass through the impregnated organic solvent. A unique advantage of the carrier mediator Aliquat-336 is that it stays in a cationic form in all pH ranges.
Sehati et al. [40] coupled HFLPME to nanomaterials, where TiO2 nanomaterials were dispersed in 1-octanol and used it to fill the lumen of a HF. Then, they sealed the two ends of the HF with orthodontic stainless steel wires. The LPME took place by putting the HF into the milk samples for the extraction of tylosin. This method allowed obtaining recovery percentages in the range 89–99% and despite using an ultraviolet- visible spectrophotometer for the determination of tylosin, an LOD of 0.21 mg L−1 was achieved which proves the efficiency of the extraction method that was used.
Molecularly imprinted polymers (MIPs) are synthesized using a template, functional monomer, cross-linker and an initiator. MIPs are selective towards the target molecules, allowing them to be eluted from the SPE cartridge almost free of co-extracted compounds compared to classical sorbents used for clean-up procedures [56]. SPE sorbents such as C18, hydrophilic lipophilic balanced (HLB) material, diatomite, N-propylethylenediamine, alumina and Florisil are susceptible to interferences by impurities in biological samples and the cartridges can only be used once [57]. Therefore, it is important to develop simple, rapid and environmentally friendly methods. MIPs overcome the above-mentioned drawbacks of traditional SPE sorbents. MIPs are stable under different harsh conditions (extreme pH, high pressures and high temperatures) and can be reused several times [58]. Below are a few studies where MIPs were applied in the solid phase extraction of veterinary drug residues in food samples.
In a study conducted by Song et al. [56], a MIP-SPE method combining LC-MS/MS was developed to determine the residues of macrolide drugs in animal derived foods. Tylosin was used as a virtual template and the synthesized MIPs were used as the selective sorbent for packing SPE cartridge. A system of sodium borate buffer solution (pH = 10.0) and ethyl acetate was selected for the extraction of the residues of macrolides from muscle samples. Mean recoveries of 10 target analytes were in the range of 60.7–100.3%. Compared with the conventional SPE cartridges (approximately 60–90%), the MISPE cartridge was highly selective and obtained higher recoveries for the 10 macrolides drugs. The LOD and LOQ values ranged between 0.1–0.4 and 0.3–1.0 μg kg−1 respectively. The results indicated that the sensitivity of the proposed method for the determination of 10 macrolide drugs residues in animal muscle samples was acceptable.
Wang et al. [57] used a mixed-template molecularly imprinted polymer (MMIP) coupled with matrix solid phase dispersion (MSPD) to recognize eight FQs, eight SAs and four TCs from pork samples following analysis with ultraperformance liquid chromatography with a photo diode array detector. The LOD and LOQ were 0.5–3.0 and 1.5–6.0 ng g−1 respectively. The recoveries ranged between 92 and 99%. MMIPs were compared to C18 and diatomaceous earth dispersing sorbents. The obtained chromatograms showed that the two sorbents were able to achieve the satisfactory purification effects, but the recoveries of the 20 drugs from the two sorbents (70–95%) were lower than that from MMIP.
In another study by Feng et al. [58], a MIP-SPE method combining HPLC was developed to determine the residues of TC drugs in animal derived foods. A template for MIP synthesis was selected among doxycycline, oxytetracycline and chlortetracycline for enhanced enrichment factors. Results showed that one milk sample contained TC residue (52 ng mL−1) and another milk sample contained oxytetracycline residue (87 ng mL−1), but the residue levels were lower than their MRLs in milk (100 ng mL−1). Results of other samples were negative. In order to compare the purification effect of MIP-SPE with conventional SPE, the extracts of TCs fortified blank milk (100 ng mL−1) were purified with three commercial SPE cartridges containing different sorbents (strong cation exchange phase, HLB and C18) and there were different interfering peaks around TCs peaks in the chromatograms, revealing inferior purification performances of these sorbents. MIP-SPE proved to be specific, sensitive and accurate for the extraction of TCs residues.
Dummy molecularly imprinted polymers (DMIPs) based on the matrix solid phase dispersion method for the extraction of FQs from fish prior to analysis on the HPLC with fluorescence detection were used by Sun et al. [59]. The use of DMIPs was to prevent any possible template leakage which could still happen even after thorough washing steps. Template leakage could have a serious impact on the accuracy of the analytical method or made it not suitable for simultaneous analysis of the whole class of FQs. This problem has become one of the major area of concern in sample pre-treatment methods of MIPs. Good recoveries, low LODs and excellent accuracy demonstrated the suitability of the DMIP sorbent for pre-treatment of FQs in fish samples. The use of DMIP resulted in less matrix interferences compared to directly extracted samples and no co-eluted peaks were observed in the chromatogram. The LOD was 0.06–0.22 ng g−1 and recoveries ranged between 64.4 and 102.7%.
Wang et al. [60] used an inorganic-organic co-functional monomer, methacrylic acid-vinyltriethoxysilane (MAA-VTES) for the synthesis of molecularly imprinted microspheres (MIMs). The obtained MAA-VTES based MIMs exhibited good recognition and selectivity to FQs and were successfully applied as selective sorbents of a miniaturized home-made solid phase extraction device for the determination of ofloxacin, lomefloxacin and ciprofloxacin in milk samples. The LODs and the LOQs of FQs were 1.5–2.3 and 5.0–7.5 ng mL−1, respectively. The average recoveries for the analyte were in the range of 87.2–106.1%. Ciprofloxacin was detected in two samples as 0.21 and 0.25 ng mL−1 which were below the MRL established by EU (100 g kg−1). Due to the efficiency of the developed co-functional monomer based mini-MISPE-HPLC method, it was possible to analyze the target compounds in milk samples at ng mL−1 level.
A selective and eco-friendly sensor for the detection of tetracycline by grafting imprinted polymers onto the surface of carbon quantum dots was used by Hou et al. [61]. A simple microwave-assisted approach was utilized to fabricate the fluorescent imprinted composites rapidly for the first time, which could shorten the polymerization time which normally takes 8–24 hours and simplify the experimental procedure. In this study polymerization took about 1 hour. The development of fluorescent molecularly imprinted composites might be a promising method for rapid analysis in complex samples in future. TCs were not detected in milk samples. Recoveries ranged from 97.3 to 105.3%.
In high-fat foods like milk and meat, veterinary drug residues may bind to lipoproteins and extraction solvents forming emulsions and foam, especially polar veterinary drugs which may decrease recoveries and hence, affecting separation and analysis [56, 62]. Extracting analytes from biological samples using modern extraction techniques like DLLME has some challenges. In traditional DLLME, prior to a DLLME procedure on a complex matrix such as milk, lipids and proteins must be eliminated since they can act like surfactants and disrupt the interfacial tension at the droplet surface, constraining phase separation [63]. During the sample pre-treatment step, salts are added for analyte partitioning, phase separation, buffering and for reducing the amounts of co-extracted matrix that could hinder the transfer of analytes from the aqueous phase to the organic phase [5].
TCs are challenging drugs for analytical analysis because they are hydrophilic compounds with high solubility in aqueous media. They have both acidic and basic functionalities, and therefore exist in various forms at different pH conditions [39]. Moreover, they can form complexes with divalent metal ions and silanolic groups on the HPLC column which may result in severe peak tailing [64]. Reverse phase-HPLC with mobile phases containing acids such as phosphoric, acetic and tartaric acids can be used to reduce peak tailing or an RP-amide column can be used. The ability of the RP-amide column to separate TCs might be explained by the hydrogen bonding between the amide functionality of the column and the hydroxyl functionality of TCs. Another challenge is that TCs are prone to photo-degradation.
Overlapping peaks during multi-residual analysis when using HPLC-DAD is a challenge. Multivariate curve-resolution coupled to alternating least squares to calculate the exact peak area of overlapping compounds was used by Tajabadi et al. [37], hence more sensitive analytical instruments such as the LC-MS/MS are required for multi-residual analysis. Moreover, the solubilization procedure of veterinary drug residues is a rate-limiting step in multi-residual analysis.
The matrix effect still remains an issue when extracting veterinary drug residues using the QuEChERS method from complex samples such as meat, and hence reducing the sensitivity of chromatographic instruments [46].
The world is moving towards the use of greener solvents and hence promoting the principles of GAC, therefore, it can be envisioned that most extraction methods still making use of organic solvents may be completely eliminated in future. Currently greener solvents such ionic liquids are widely used in microextraction procedures as dispersive or extraction solvents according to their different solubilities in DLLME.
Electrochemical sensors and their relative detection strategies, with the advantages of high sensitivity, simplicity and rapid response, have attracted considerable attention in recent years. Among them, aptasensors are considered as one of the most promising research directions owing to the employment of an aptamer. Aptamers, with the advantage of high affinity and specificity to targets, low price and easy to be synthetic in vitro, have provided a broad prospect for developing electrochemical sensing system.
Expanding agriculture, aquaculture and apiculture practices have resulted in increased levels of infections among species. Various classes of veterinary drugs including QNs, TCs, β-lactams, SAs and others exhibit activity against both gram-positive and gram-negative bacteria, hence they are widely used to treat or prevent diseases. However, extended use of these veterinary drugs has led to food safety issues worldwide and hence a need for developing sensitive methods for their determination. The focus of this chapter has been to present the trends in modern extraction and clean-up techniques of veterinary drug residues from food samples of animal origin, with milk being the most studied matrix because of its importance on the diet of humans and one of the most consumed foods in the world. Even though some of these veterinary drugs such as chloramphenicols have been banned in some countries due to their dangerous side effects on humans they are still detected in food samples because farmers are not adhering to EU regulations. Generally, in most studies these veterinary drug residues are below stipulated MRLs. Although most extraction methods that are emerging are promising, multi-residual analysis is still a challenge.
Loose connective tissue disorders include lipedema, Dercum’s disease (DD), familial multiple lipomatosis (FML) and multiple symmetric lipomatosis (MSL). All these disorders share many similarities with lipedema including painful lipomas, obesity, fibrosis, a risk of developing lymphedema and difficulty in losing the abnormal fat through diet and exercise. There are clinical characteristics specific for lipedema, including the onset of the disease, fat location and associated health issues (\nTable 1\n) [1, 2].
\nCharacteristic | \nLipedema | \nDD | \nMSL | \nFML | \nMSL | \n
---|---|---|---|---|---|
Abnormal fat location | \nLegs, arms, abdomen | \nGlobal | \nUpper; can be global | \nArms, thighs, trunk, abdomen | \nUpper; can be global | \n
Diet-resistant fat | \nYes | \nYes | \nYes | \nYes | \nYes | \n
Lipomas | \nYes | \nCommon | \nCommon in men | \nCommon | \nCommon in men | \n
Time fat change | \nPuberty; 3rd decade | \nChild-adult | \nAdult; child rare | \nChild-adult | \nAdult; child rare | \n
Painful fat | \nYes | \nYes | \nNot usually | \nLipoma | \nNot usually | \n
Sex predominance | \nFemale | \nFemale | \nMale | \nMale = female | \nMale | \n
Lymphatic dysfunction | \nYes | \nYes | \nYes | \nYes | \nYes | \n
Prevalence | \nPossibly common | \nPossibly common | \nRare | \nRare | \nRare | \n
Associated conditions | \nLymphedema | \nAutoimmune; diabetes | \nNeuropathy | \nMoles; neuropathy | \nNeuropathy | \n
Inheritance pattern | \nAutosomal dominant; incomplete penetrance | \nAutosomal dominant; sex-specific influence | \nAutosomal dominant or recessive | \nAutosomal dominant | \nAutosomal dominant or recessive | \n
Lipedema is often misdiagnosed as lifestyle-induced obesity that affects ~10% of women of European descent as well as other populations [3, 4]. Although both disorders are considered inflammatory diseases due to the presence of increased macrophages and hypertrophic adipocytes, there are significant differences between the two disorders. Among these is the location of the fat, primarily abdominal or spread widely over the body in obesity compared to the symmetric distribution in the lower extremities in lipedema, the texture of the skin (thin and soft in lipedema and thicker in obesity), easy bruising and pain upon the introduction of pressure in lipedema [5, 6].
\nThe focus of this review will be on the disease of lipedema, different stages and types, diagnosis and treatment, pathogenesis and current research in the field.
\nLipedema also referred to as lipedema, is a painful loose connective tissue disorder first described in 1940 by Allen and Hines [7]. Lipedema is characterized by symmetric enlargement of the buttocks, hips and legs due to deposition of loose connective tissue that includes fascia, adipocytes, immune cells and other structures; arms are also affected in 80% of patients [3, 4]. Feet are typically spared, but ankle cuffs are often noted in advanced stages of lipedema where the risk of lymphedema is also high [8, 9]. Patients with lipedema experience mobility issues, psychosocial distress, anxiety, eating disorders, sleep apnea and depression [1, 10].
\nLipedema is considered a hormone-related disorder affecting almost exclusively women during puberty, childbirth or menopause. Case reports of men with lipedema have been described in literature. Men with lipedema have elevated estrogen level and low to absent testosterone levels resulting in cirrhosis, gynecomastia and hypogonadism [11, 12, 13]. While the exact etiopathogenesis of this disease is unknown [10, 14], many studies have demonstrated that inflammatory cells, hypertrophic adipocytes, abnormal blood vessels and lymphatic dysfunction are associated with tissue damage and development of a fibrotic disease [14, 15, 16, 17].
\nLipedema consists of three stages characterized by the texture of skin and tissue formation. Stage 1 involves smooth skin over pearl-sized nodules in a hypertrophic fat layer; Stage 2 has skin indentations over a hypertrophic fat structure of pearl-to-apple-size masses; and Stage 3 includes pearl-sized nodules and much larger fat masses causing lobules of skin and fat to form mainly on the hips, thighs, and around the knees. Lymphedema, causing fluid accumulation in the limbs, may develop during any stage of lipedema and is referred to as lipo-lymphedema [1, 3, 10, 18, 19].
\nHealthcare providers often misdiagnose women with lipedema as they do not take into account the disproportionate size of the legs compared to trunk especially in Stage 1 and 2 along with the inability to lose fat from areas affected by lipedema. It is possible to confuse women with Stage 3 lipedema as having lifestyle-induced obesity due to fat involving more areas of the body.
\nIn addition to stages of lipedema, lipedema is also characterized by types determined by the area of the body that is affected. There are five types of lipedema; types I, II, and III are the most common. In Type I, fat is deposited in the areas of the buttocks and hips resembling saddle bags. In Type II, fat extends to the knees from the buttocks area with the formation of folds of fat around the inside of the knee. In Type III, fat spreads all over the lower body from the hips to the ankles. In Type IV, upper arms are affected causing difficulty in lifting the arm and stress on the shoulder. In Type V, fat is restricted to the lower legs. It is worth noting that patients with lipedema can clinically present with a mixture of types [3, 10].
\nPain, tenderness, bruising easily, symmetrical swelling of the legs, heaviness of affected limbs, burning sensations in the skin and fat, soft skin, negative stemmer’s sign and hypermobile joints are among the common symptoms observed in lipedema patients [2, 3, 6, 13]. Hypermobility in women with has been reported to contribute to joint damage and increase the risk of cardiovascular disease as seen in Ehlers Danlos Syndrome-Hypermobility Type (EDS-HT) with Beighton score higher than 5 [2, 3, 20, 21]. Thus, hypermobility causes structural changes in lipedema tissue resulting in increased fibrosis, dysfunction of blood vessels and accumulation of interstitial fluid.
\nWomen with lipedema also experience emotional symptoms due to unexplained weight gain including embarrassment, anxiety and depression that impact their overall quality of life [22, 23]. Symptoms may progress in advanced stages of lipedema that might be associated with increased cardiovascular and renal diseases. A study conducted by Herbst el al. in 2015 provides a detailed list of symptoms experienced by lipedema patients [3].
\nDiagnosis of lipedema involves a comprehensive physical exam based on the criteria listed by Wold and colleagues in 1951, [4] medical and surgical history, list of medications that might affect weight or fluid retention and family history. A physical examination includes assessment of the enlarged lower extremities carefully noting the texture of the affected areas such as velvety soft skin that can be found in hypermobility, nodular fat, pain when applying pressure, tenderness upon palpation and accumulation of fluid such as pitting or non-pitting edema which may indicate lymphedema [18, 24]. Bruising caused by increased capillary fragility [6], spider veins and telangiectasia showing on the surface of the skin due to venous insufficiency are also observed in lipedema patients [4, 10].
\nAlthough, there is no cure for lipedema, treatments like liposuction (tumescent and water jet) [25], complete decongestive therapy that includes manual lymphatic drainage [26, 27], compression garments, a healthy diet, physical activity, medications and supplements (statins, selenium, diosmin, amphetamines and butcher’s broom) have been shown to reduce pain, improve lymphatic function, decrease leakage from blood vessels, lessen inflammation and fibrosis and maintain a healthy gut [24, 28, 29, 30, 31, 32, 33, 34].
\nLiposuction is by far the most effective treatment to decrease the fibrotic lipedema fat and thereby maintain mobility which is essential for the welfare of women living with lipedema [35, 36, 37]. Water jet-assisted liposuction has been proven to be as effective as tumescent liposuction. Damage to the lymph vessels has not been show as evidenced in a histological study conducted by Stutz et al. on lipoaspirates collected from lipedema patients [32]. Nevertheless, special care should be taken with lipo-lymphedema patients, where accumulated lymph and or fibrotic tissue should be removed first. Furthermore, follow-up and compression therapy are advised for successful and effective treatment.
\nDeep tissue massage has also been demonstrated to improve the quality of subcutaneous adipose tissue by decreasing pain, fibrosis and fat tissue in women with lipedema [29, 38].
\nAdditionally, a healthy non-inflammatory diet is highly recommended, even though it will not reduce the lipedema tissue, but it might slow the progression of the disease by reducing inflammation and pain, lessen the swelling and ultimately improve quality of life. No one plan works for everyone but a ketogenic diet with low processed carbohydrate and mild physical exercises like walking, swimming, Pilates, yoga and other home excise programs are suggested by lipedema specialists. These activates will help the function of lymphatic pump and maintain a normal metabolism.
\nFinally, it is very important to detect and treat lipedema at early stages thus preventing the complications that might occur due to the progression of disease. These complications comprise eating disorders, sleep apnea, diabetes mellitus, arthritis, hypertension, cellulitis, cardiac and renal disease.
\nThere are distinctive criteria for lipedema which are absent in lymphedema including a negative Stemmer’s sign, minimal pitting edema, thin skin, easy bruising, tenderness and pain [14, 39, 40]. Although lymphatic microaneurysms might develop in the later stages of lipedema leading to secondary lymphedema, imaging techniques like high-resolution cutaneous ultrasonography and magnetic resonance imaging showed no defects in the lymphatic system in early stages [24, 41, 42, 43]. Other methods have also been successfully used to differentiate lipedema from lymphedema which includes tissue dielectric constant and dual-energy X-ray absorptiometry techniques [44, 45, 46, 47, 48].
\nDysfunction of lymphatic vessels results in accumulation of interstitial fluid (edema) in adipose tissues triggering inflammation by the recruitment of macrophages resulting in fibrosis and difficulty with weight loss. As a consequence, adipose tissue loses its elasticity suggesting that lipedema might be a connective tissue disorder [15, 49]. Studies have also indicated that edema might induce growth of lipedema fat as well as hypoxia resulting in adipocyte cell death [50].
\nFurther, morphologic changes in lymphatic vessels and accumulation of interstitial fluid are present in some women with lipedema, with no change in transport of lymphatic fluid, which suggests these individuals might have a higher risk of progressing to lipo-lymphedema especially in advanced stages of lipedema [15, 51]. Accurate diagnosis of lipedema in association with lymphedema is essential for treating and following up of lipedema patients.
\nHormones, genetic factors, leaky blood vessels, dysfunctional lymphatics system, inflammation, hypertrophic adipocytes and interstitial thickening are among the factors that contribute to the pathogenesis of lipedema [10, 12, 15].
\nHormones play an essential role in the etiology of the lipedema, but how they affect the metabolism and function of adipocytes function is still unknown. Studies have shown that hormones, like estrogen and progesterone, have a direct effect on lipogenesis, insulin levels and adipose tissue distribution in the body. Dysregulation of hormonal levels lead to fat dysregulation, impairment of the lipogenesis-lipolysis mechanism, hypertension, insulin resistance and hyperinsulinemia [13, 52, 53]. Hormones might also have an impact on the nervous system which might explain the pain experienced by lipedema patients. Szél et al. hypothesized that alteration in estrogen (or estrogen receptors) maybe involved in the pathogenesis of lipedema by suggesting a link between accumulation of adipose tissue, imbalanced estrogen levels and inflammation of the peripheral and sympathetic nerves of the disease [13].
\nLipedema fat tissue is characterized by hypertrophic adipocytes, inflammatory immune cells, dilation of subdermal blood and lymphatic vessels. We and others have shown a high number of infiltrating macrophages in lipedema adipose tissue detected by the CD68 marker and observed as around blood vessels or as crown-like structures surrounding necrotic adipocytes. In addition to macrophages, mast cells and T-lymphocytes were detected in hyper-vascular areas mainly around blood vessels in lipedema fat tissue which might contribute to capillary permeability and accumulation of interstitial fluid [15, 16, 54].
\nAn article published in 2004 by Taylor et al. showed that accumulation of mast cells in lipedema tissue contributed to increased interstitial fluid, deterioration of adipocytes and potentially elastic fiber fragmentation due to the release of elastase [55], confirming that lipedema is a connective tissue disorder. Adding to that, direct cell-cell interaction between hypertrophic adipocyte and macrophages as well as secreted paracrine factors such as vascular endothelial growth factor (VEGF), a marker of angiogenesis, previously reported in the blood of women with lipedema [56] might be associated with increase in the number of blood vessels, dilation of capillaries, hypoxia, inflammation and tissue fibrosis found in lipedema patients [15, 18, 57].
\nAdipose tissue-derived stem cells are widely studied for their immunomodulatory, anti-inflammatory, anti-fibrotic, anti-apoptotic and pro-angiogenic effects [58, 59, 60], but how ASCs contribute to the development of lipedema has not been investigated yet. Due to their high therapeutic potential, ASCs are now considered an indispensable tool in regenerative medicine [61, 62, 63, 64]. Studies have shown the successful treatment with ASCs for many disease including graft-versus-host disease [65], wound healing [66], cardiovascular [67], inflammatory bowel disease [68], diabetes mellitus [69] and several injuries including kidney and spinal cord [70], bone and craniofacial reconstruction [71, 72], liver cirrhosis [73], multiple sclerosis [74]. In addition to their self-renewal ability, ASCs have the ability to differentiate into multiple lineages, including adipocytes, osteoblasts, chondrocytes, and endothelial cells [75, 76]. Thus, ASCs might play a role in lipedema adiposity by inducing the expansion and differentiation of progenitor adipose-derived stem/progenitor cells (pre-adipocytes) into mature adipocytes (hyperplasia). Suga el at. have shown an increase in proliferation of adipose-derived stem/progenitor cell proliferation using Ki67 and CD34 markers suggesting an increase in adipogenesis, hypoxia, and adipocyte necrosis, at least in one case [16].
\nAdding to that, inflammatory cytokines secreted by hypertrophic adipocytes and factors in the interstitial fluid could stimulate ASC differentiation into mature adipocytes. Alternatively, ASCs produce a plethora of pro- and anti-inflammatory cytokines that might contribute to angiogenesis and inflammation resulting in leaky and fragile blood vessels [77, 78]. Priglinger et al. have characterized lipedema ASCs isolated from liposuction samples and showed an increasing number of endothelial/pericytic cells using CD146 marker in lipedema patients compared to healthy individuals proposing that this increase might be a marker of repair of leaky blood and lymphatic vessels in lipedema tissues [54].
\nAlthough, ASCs might induce adipogenesis in lipedema an in-depth characterization of ASCs is required to confirm this theory. Otherwise, if ASCs prove to have anti-inflammatory, anti-fibrotic or pro-angiogenic effects, then they might be used to lessen tissue damage caused by leaky vessels; hence autologous treatment might be a promising tool for lipedema patients.
\nLipedema is a painful fat disease that should be differentiated from obesity and lymphedema. It is the responsibility of the healthcare provider to determine the accurate diagnosis of the disease for successful treatment and management. Liposuction, hands-on therapy, exercise, and a healthy eating plan are recommended for lipedema patients. Although the etiology of lipedema is complicated, hypertrophic adipocytes, inflammatory cytokines, and macrophages, hypoxia, leaky vessels and accumulation of interstitial fluid contribute to the pathogenesis of the disease and may also help guide treatment.
\nThis work was funded by a grant from the Lipedema Foundation.
\nThe authors declare no conflict of interest.
This is a brief overview of the main steps involved in publishing with IntechOpen Compacts, Monographs and Edited Books. Once you submit your proposal you will be appointed a Author Service Manager who will be your single point of contact and lead you through all the described steps below.
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He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"7",type:"subseries",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11403,editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",slug:"slawomir-wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",biography:"Professor Sławomir Wilczyński, Head of the Chair of Department of Basic Biomedical Sciences, Faculty of Pharmaceutical Sciences, Medical University of Silesia in Katowice, Poland. His research interests are focused on modern imaging methods used in medicine and pharmacy, including in particular hyperspectral imaging, dynamic thermovision analysis, high-resolution ultrasound, as well as other techniques such as EPR, NMR and hemispheric directional reflectance. Author of over 100 scientific works, patents and industrial designs. Expert of the Polish National Center for Research and Development, Member of the Investment Committee in the Bridge Alfa NCBiR program, expert of the Polish Ministry of Funds and Regional Policy, Polish Medical Research Agency. Editor-in-chief of the journal in the field of aesthetic medicine and dermatology - Aesthetica.",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,series:{id:"7",title:"Biomedical Engineering",doi:"10.5772/intechopen.71985",issn:"2631-5343"},editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",slug:"alexandros-tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",slug:"lulu-wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",slug:"reda-r.-gharieb",fullName:"Reda R. 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