Comparison of results obtained by Raman spectroscopy and LC/MS/MS of liquid milk from the first test.
\r\n\tFrequently, bullous diseases are misdiagnosed, and the precise diagnosis requires a skilled dermatologist. Nowadays, histopathology is the standard method which requires supplemented methods including direct immunofluorescence (DIF) confirming the origin and location of autoantibody. Indirect immunofluorescence (IIF) is filled up with ELISA allowing the precise type of autoantibody playing the mainstay role in the pathogenesis of a disease. Follow up of serum titer of autoantibody is important in the management of disease, especially in pemphigus group. Established time of free clinical appearance and negative detection of autoantibody using ELISA or IIF allow confirming a loss of production of autoantibody using DIF. Negative results in these examinations allow discontinuing the immunosuppressive therapy in patients with pemphigus and bullous pemphigoid groups. In dermatitis herpetiformis, the pathogenesis differs, and the immunosuppressive therapy and/or gluten-free diet should be used for the whole lifetime. The book will provide a comprehensive overview of the current diagnostic skills and methods, management of immunosuppressive therapy and topical therapy, which may allow decreasing the systemic administration of immunosuppressive medications.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:null,priceUsd:null,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"f91d25ba59038b77804ec2af35ef8447",bookSignature:"Dr. Danka Svecova",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/8703.jpg",keywords:" Pemphigus Vulgaris, Paraneoplastic Pemphigus, Pemphigus Foliaceus, Pemphigoid Gestationis, Bullous Pemphigoid, Iga Pemphigus, Mucous Membrane Pemphigoid, Linear Iga Dermatosis, Epidemiology, Etiology and Pathophysiology, Histopathology, Immunopathology",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 29th 2018",dateEndSecondStepPublish:"December 20th 2018",dateEndThirdStepPublish:"February 18th 2019",dateEndFourthStepPublish:"May 9th 2019",dateEndFifthStepPublish:"July 8th 2019",remainingDaysToSecondStep:"2 years",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"209275",title:"Dr.",name:"Danka",middleName:null,surname:"Svecova",slug:"danka-svecova",fullName:"Danka Svecova",profilePictureURL:"https://mts.intechopen.com/storage/users/209275/images/system/209275.jpg",biography:"Dr.Danka Svecova, Medicine Doctor (PhD., dermatology), is a professor of Dermato-venerology, Head of Bullous Disorders Unit at Dept. of Dermatovenerology, University Hospital and Faculty of Medicine, Comenius University in Bratislava, Slovakia. \r\nShe is a board member of the Division Committee for Dermatovenerology Dissertation for Ph.D. She is a member of a committee for Probation of Specialization for Dermatovenerology. \r\nShe participated in research on Skin Allergology and Immunology under the supervision of Professor Akira Ohkawara, at Hokkaido University in Sapporo, Japan. She held several grant projects on fungal infection, therapy of psoriasis, borreliosis, immunomodulatory and anti-inflammatory efficacy of normal polyphenols, immunogenetic determination to psoriasis Vulgaris and pemphigus Vulgaris, GWAS (Genome-Wide Association Study) on pemphigus vulgaris in cooperation Harvard Medical School in USA and Anhui Medical University in China under supervision of Professor Liangdan Sun.",institutionString:"Comenius University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Comenius University",institutionURL:null,country:{name:"Slovakia"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"175",title:"Dermatology",slug:"dermatology"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"225753",firstName:"Marina",lastName:"Dusevic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/225753/images/7224_n.png",email:"marina.d@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. 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Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"43589",title:"Surface-Enhanced Raman Scattering Liquid Sensor for Quantitative Detection of Trace Melamine in Dairy Products",doi:"10.5772/52485",slug:"surface-enhanced-raman-scattering-liquid-sensor-for-quantitative-detection-of-trace-melamine-in-dair",body:'\n\t\tRaman spectroscopy has emerged as a fast, non-invasive, analytical method for the detection and quantification of adulterants in many fields (Wong et al., 2007; Weng et al., 2003; Muik et al., 2003; Micklander et al., 2002; Peica et al., 2005; Rubayiza et al., 2005; Ellis et al., 2005; Paradkar et al., 2001; Abalde-Cela et al., 2009; Mulvihill et al., 2008; Zhou et al., 2006). Although signals from conventional Raman spectroscopy are very weak, great progress has been made with the development of surface-enhanced Raman spectroscopy (SERS) as a sensing method. SERS is a powerful spectroscopy technique that can provide ultra-sensitive characterization of adsorbate molecules on roughened metal (e.g., Ag, Au, and Cu) surfaces that produce a large enhancement to the Raman scattering signal (Lin et al., 2008; Lee et al., 1982; Wei et al., 2009; Küstner et al., 2009; Koglin et al., 1996; House et al., 2008; Leopold et al., 2003; Yaffe et al., 2008; Yu et al., 2007; Tiwari et al., 2007; Guingab et al., 2007; Tian et al., 2002; Wang et al., 2005; Chen et al., 2012; Betz et al., 2012). Generally, solid/liquid substrates are necessary to enhance the SERS spectrum to obtain adequate sensitivity.Solid substrates, generally prepared as gold or silver nanoparticles with a silica or alumina shell, have a wide application range. However, only a few examples of liquid substrates have been reported, though they are easily prepared and enhance the analysis some analytes.For example, using a silver colloid, at least a 105-fold enhancement of the Raman signal is achieved for the measurement of melamine (Zou et al., 2010).
Presently, there are two commonly accepted sensing mechanisms(Chu et al., Phys. Rev; Campion et al., 1998; Knoll, 1998; Kneipp et al., 1999; Moskovits et al., 1998; Otto et al. 2005): the electro-magnetic enhancement mechanism, which involves enhancement in the field intensity by plasmon resonance excitation; and the chemical enhancement mechanism, which involves enhancement of the polarizability by chemical effects such as a charge-transfer excited states.The efficiency of the generation of the SERS signal is high enough to observe the Raman spectrum of even a single molecule. With the rapid development of nanofabrication technology, SERS has grown to become a very active field of research in several areas of materials and analytical sciences, such as medicine, the environment, food, gems, cultural relics, and archaeology (Fan et al., 2011; Jun et al., 2010; Deiss et al., 2011).
In the following section, liquid milk melamine detection using a SERS liquid sensor is described as an example of this technique. In the example, liquid milk samples preparation process is very easy, i.e. only diluted with double-distilled water and centrifugation is required. With the aid of silver colloid, at least a 105-fold enhancement of the Raman signal was achieved for the measurement of melamine. The limit of detection by this method was 0.01 g mL-1 for melamine standard samples. Based on the intensity of the Raman spectroscopy with vibration bands normalized by the band at 928 cm-1 (CH2), external standard method was employed for the quantitative analysis. The linear regression square (R2) of curve was 0.9998, the limit of quantitation using this approach was 0.5 g mL-1 of melamine in liquid milk, the relative standard deviation was ≤ 10% and recoveries were from 93 to 109%. The test results for SERS were very precise and as good as those obtained by LC/MS/MS.
\n\t\tSince 2008, there has been mounting concern about the intentional adulteration of protein ingredients in milk powder with melamine, because milk powder blended with melamine can lead to kidney disease and even death in babies. Thisfear of milk powder tainted with melamine has an important influence on the dairy production of milk powder and cow breeding, as well as an important impact on the food market and industry. Currently, new methods such as high-performance liquid chromatography (HPLC) (Ehling et al., 2007; Muniz-Valencia et al., 2008), liquid chromatography coupled with mass spectroscopy (LC-MS)(Varelis et al., 2008), LC-MS/MS (http://www.cfsan.fda.gov/∼frf/lib4421.htm), thin-layer chromatography (TLC) (Broszat et al., 2008), commercial enzyme-linked immunosorbent assay technology (Eric et al., 2008), matrix-assisted laser desorption/ionization mass spectrometry (Tang et al., 2009), and surface desorption atmospheric pressure chemical ionization mass spectrometry (Yang et al.,2009) are the principal analysis techniques used for the detection and quantification of melamine in food. However, these methods are time consuming and cannot satisfy the need for melamine detection in practice because raw milk spoils and must be assayed within 4 h. Moreover, these methods require access to complicated and expensive laboratory facilities, especially in terms of sample preparation and clean-up steps. Therefore, it is of particular importance to develop a simple, quick, cost-effective, and sensitive method for detection of melamine in food.
We demonstrate an approach to detect melamine in liquid milk using surface-enhanced Raman spectroscopy in a silver colloid, which can be used for the rapid and online detection of melamine in dairy products.
\n\t\t\tIn recent years, gold nanoparticles (Au NPs) and silver nanoparticles (Ag NPs) have been widely used as colorimetric probes for chemical sensing and biosensing of various substances (Zhao, et al., 2008), such as viruses (Niikura et al., 2009), protein (Wang et al., 2008), DNA (Cho, et al., 2008), cancerous cells (Medley et al., 2008), and small molecules (Chen, et al., 2010; Li et al., 2009; Zhang et al., 2008), relying on their unique size-dependent and/or interparticle distance-dependent absorption spectra and solution color. For example, triple hydrogenbonding recognition between melamine and a cyanuric acid derivative grafted on the surfaced of Au NPs can be used for reliable detection of melamine (Ai et al., 2009).
Currently, much attention has been paid to the study of the optical absorption spectra of nanoscale colloidal silver in the quest for SERS enhancement factors. Compared to Au NPs, Ag NPs have some advantages, for example, lower cost of preparation and higher extinction coefficients relative to Au NPs of the same size (Lee, et al, 2007). Therefore, Ag NPs are also good candidates for melamine sensing (Han, et al., 2010; Ping et al., 2012).
Upon considering the influence of temperature, ionic strength, and aggregation behavior of colloids on the SERS spectra band intensity in the presence of adsorbates and the wavelength at which maximum enhancement occurs, the latter shift to higher values with time. In particular, the adsorption of the colloid is strongly influenced by chloride ions (Koglin et al., 1996) and pH (House et al., 2008). Scanning electron microscopy images of a silver colloid before and after addition of reagent A (Sodium chloride aqueous solution or aqueous potassium chloride solutions) and reagent B (Aqueous sodium hydroxide or potassium hydroxide solution) are presented in Figure 1. As shown in Figure 1a, the colloidal silver particles mainly displayed a spherical morphology with a uniform size of ~70-100 nm. After added reagent A (Fig. 1b) or reagent B (Fig. 1c), the silver colloid became aggregated and inhomogeneous. When reagents A and B were added to the colloidal silver at the same time, the morphology of the silver colloid became more dense and uniform (Fig. 1d), which is the best form for SERS enhancement. Thus, this system was chosen as the surfaced-enhancing substrate for further study. Figure 1e shows the SERS spectra of 1 μg mL-1 melamine on the corresponding enhancing substrates from (a), (b), (c) and (d) in Figure 1. There are no evident Raman bands of melamine on silver colloid (curve ⅰin Fig. 1e) or on silver colloid with reagent A (curve ⅱin Fig. 1e). However, when reagent B was added to the silver colloid (curveⅲin Fig. 1e), a weak characteristic peak of melamine was observed at 698 cm-1, i.e., the SERS spectra band intensity was affected by pH. After reagents A and B were added to the silver colloid (Curve IV in Fig. 1e), the characteristic peak of melamine was strongly enhanced, with the intensity of the peak at 698 cm-1being the greatest.
\n\t\t\t\ta-d) Scanning electron microscopy images of colloids and(e)SERS spectra of 1 μg mL-1 melamine with the corresponding enhancing substrates.Scanning electron microscopy images of silver colloids (a)before and(b) after addition of reagent A, (c) reagent B, and (d) reagents A and B together.(e) Curves ⅰ, ⅱ, ⅲ, and ⅳare SERS spectra of 1 μg mL-1 melamine from the corresponding enhancing substrates from (a), (b), (c), and (d), respectively.
It is believed that melamine (2,4,6-triamino-1,3,5-triazine) is sometimes intentionally added to food ingredients to make the products appear to contain higher protein levels due to the high nitrogen content of melamine. A safety limit for melamine ingestion is officially set at 2.5 ppm for adult food and 1 ppm infant formula by the US Food and Drug Administration (Zhao et al., 2009; http://www.fda.gov/NewsEvents/ Newsroom-/ PressAnnouncements/ 2008/ ucm116960.htm.). The maximum residue level of melamine in infant formula is now legally regulated at 1 ppm by the Chinese government after the recent melamine accident (Guo et al., 2010). To achieve this lower limit of detection (LOD), silver colloids are ideal candidates to be used as surfaced-enhancing substrate liquid sensors due to their strong Raman-enhancing effect. Thus, we chose silver colloid as a surfaced-enhancing substrate for the detection of melamine in this study, and the detection process is diagrammed in Figure 2.First, liquid milk was diluted with double-distilled water (Fig. 2a) toobtain a diluted milk sample. Next, the diluted sample was placed into a 1.5-mL conical centrifuge tube and centrifuged for 4 min at 14,000 rpm, and then it was delaminated (Fig. 2b). Next, the supernatant was removed from the centrifuge tube and was added to the silver colloid, which was previously prepared with drop-wise addition of reagents A andB, and uniformly mixed (Fig. 2c).Finally, the SERS spectra were recorded using a portable Raman spectrometer (Fig. 2d) to collect analytical results.
\n\t\t\t\tSchematic diagram of the on-line and rapid method for measuring melamine in liquid milk using surface-enhanced Raman spectroscopy.(a) Liquid milk was first diluted with double-distilled water.(b) The diluted sample was then centrifuged and delaminated.(c) The supernatant was addedto the silver colloid.(d) SERS spectra were recorded using a portable Raman spectrometer.
Based on these experimental results, the spectra of different concentrations of melamine in solution were investigated from 500–1200 cm-1, as shown in Figure 3.Typical Raman peaks of solid melamine at 382, 584, 678, and 983 cm-1 were observed (Fig. 3a).The most intense peak at 678 cm-1 is assigned to the ring breathing II mode, which involves in-plane deformation of the triazine ring. And the second most intense peak at 983 cm-1 arises from the ring breathing mode I of the triazine ring (Koglin et al., 1996). The peaks at 698 and 1005 cm-1, visible in the SERS spectra of Figure 3b–d, were obtained from melamine samples at concentrations of 5×10-1, 10-1, and 10-2 μg mL-1. The Raman spectra of the enhanced substrate, i.e., silver colloid treated with reagents A and B,is shown in Figure 3e.In the absence of melamine, small peaks at 698 and 1005 cm-1 were observed, and the other peaks disappeared. Only a small peak at 678 cm-1 was observed in the Raman spectra of melamine dissolved in water (Fig. 3f), and no peaks were evident in the spectra obtained from the 103 μg mL-1 melamine sample in the absence of the enhancing substrate (Fig. 3g).
Clearly, in the SERS spectra, the relative intensities of the peaks at 698 and 1005 cm-1 were enhanced with increasing melamine concentration. Furthermore, the spectra markedly changed in the presence of the silver colloid enhancing substrate. The specific melamine peaks at 698 and 1005 cm-1 were shifted by 20 cm-1, which is a large Raman shift compared to the peaks for the Raman spectroscopy of solid melamine. This may be due to the effect of the enhancement system (Haynes et al., 2005). In addition, due to “electromagnetic field enhancement” and “chemical or electronic enhancement” (He et al., 2008; Kneipp et al., 2002), Raman signals can be significantly enhanced, by up to six orders of magnitude, in the highly localized optical fields of such structures. Therefore, this specific approach is reasonable and promising for the field detection of melamine in various liquid milk products, such as raw milk, pure milk, and yoghurt.
\n\t\t\t\tRaman spectra and SERS spectra of melamine at different concentrations.(a) Raman spectra of solid melamine.SERS spectra of melamine solution at (b) 5×10-1 μg mL-1, (c) 1×10-1 μg mL-1, and (d) 1×10-2 μg mL-1.Raman spectra of silver colloid treated with reagents A and B (e) and melamine at different concentrations: (f) ~3.3×103 μg mL-1; and (g) 1×103 μg mL-1.
To demonstrate the practical application of melamine in liquid milk, we used melamine in raw liquid milk as an example. Various concentrations of melamine in liquid milk were extracted and analyzed by their SERS spectra (Fig. 4). As shown in Figure 4a, seven concentrations (0.5, 1, 2, 2.5, 5, 8, and 10 μg mL-1) of melamine in liquid milk were studied, and the intensity of the melamine peak at 698 cm-1 was enhanced with increasing melamine concentration. To eliminate the effects of the matrix and other factors (e.g., temperature, humidity, and focal distance), the intensity of the peak at 928 cm-1 was set at 100 for milk, and the Raman peak at 698 cm-1 in the absence of melamine had a fixed value. Accordingly, a melamine standard curve was obtained by establishing a plot correlating the melamine concentrations in liquid milk to the intensity of the intense SERS spectral peak of melamine at ~698 cm-1. A linear regression (R2 = 0.9996) was found between the Raman intensity and melamine concentration (Fig. 4b). The limit of quantification (LOQ) using this approach to detect melamine in liquid milk was also investigated, as shown in Figure 5. We found that this specific approach is reasonable for the detection of melamine in liquid milk because only one prominent peak was present in the melamine SERS spectra, which can be applied to field detection of various liquid milk products.
Moreover, the tests were performed and assessed by the Ministry of Science and Technology of the P. R. China, complying with the general administration quality supervision inspection quarantine of the P. R. China, the Ministry of Agriculture of the P. R. China, the Ministry of Health of the P. R. China, and the National Institute of Metrology P. R. China. The SERS test results were very precise and as good as those obtained by the LC/MS/MS method (Table 1). Forty-nine of 50 test samples results were correct, i.e., melamine was correctly detected in 98% of the test samples (Table 2).The concentration error in the samples was 0.2 ppm, which exceeds the limit of quantification using Raman spectra. The relative standard deviations (RSDs) were ≤ 10%, and the relative measurement deviations (RMD) were ≤ 10%.Therefore, the SERS method is an effective approach for measuring liquid milk melamine, which provides on-line, rapid, and reliable screening.
\n\t\t\t\t\n\t\t\t\t\t\t\t\t\tSample #\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tLC/MS/MS (μg mL-1)\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tQuantity\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tQuality\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t
No.1 | \n\t\t\t\t\t\t\t2.37 | \n\t\t\t\t\t\t\t2.6 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
No.2 | \n\t\t\t\t\t\t\t2.37 | \n\t\t\t\t\t\t\t2.5 | \n\t\t\t\t\t\t\tNegative | \n\t\t\t\t\t\t
No.3 | \n\t\t\t\t\t\t\t0.48 | \n\t\t\t\t\t\t\t1.1 | \n\t\t\t\t\t\t\tNegative | \n\t\t\t\t\t\t
No.4 | \n\t\t\t\t\t\t\t7.20 | \n\t\t\t\t\t\t\t7.5 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
No.5 | \n\t\t\t\t\t\t\t2.37 | \n\t\t\t\t\t\t\t2.8 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
No.6 | \n\t\t\t\t\t\t\t2.37 | \n\t\t\t\t\t\t\t2.7 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
No.7 | \n\t\t\t\t\t\t\t≤0.1 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\tNegative | \n\t\t\t\t\t\t
No.8 | \n\t\t\t\t\t\t\t2.37 | \n\t\t\t\t\t\t\t2.6 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
No.9 | \n\t\t\t\t\t\t\t1.91 | \n\t\t\t\t\t\t\t2.05 | \n\t\t\t\t\t\t\tPositive | \n\t\t\t\t\t\t
Comparison of results obtained by Raman spectroscopy and LC/MS/MS of liquid milk from the first test.
SERS spectra and standard curve of melamine in milk.(a) SERS spectra of different concentrations of melamine in milk. (b) Standard curve of melamine in milk.
Predicted melamine value (μg mL-1) compared to a spiked melamine value (μg mL-1) using (a) the external standard method and (b) the error line. The spectral region = 1000-1800 cm−1; spectral number n = 63.
\n\t\t\t\t\t\t\t\t\tSerial number\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\tRandomnumber | \n\t\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t\t\tRaman (ppm)\n\t\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t\tLC/MS(μg mL-1) | \n\t\t\t\t\t\t\t\tAveragevalue (μg mL-1) | \n\t\t\t\t\t\t\t\tRSD(%) | \n\t\t\t\t\t\t\t\tRMD(%) | \n\t\t\t\t\t\t\t
1 | \n\t\t\t\t\t\t\t754 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t\t<0.03 | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t |
2 | \n\t\t\t\t\t\t\t769 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t||||
3 | \n\t\t\t\t\t\t\t775 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t||||
4 | \n\t\t\t\t\t\t\t781 | \n\t\t\t\t\t\t\t<0.2 | \n\t\t\t\t\t\t||||
5 | \n\t\t\t\t\t\t\t788 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t||||
6 | \n\t\t\t\t\t\t\t800 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t||||
7 | \n\t\t\t\t\t\t\t695 | \n\t\t\t\t\t\t\t0.19 | \n\t\t\t\t\t\t\t0.20 | \n\t\t\t\t\t\t\t0.25 | \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\t | \n\t\t\t\t\t\t |
8 | \n\t\t\t\t\t\t\t709 | \n\t\t\t\t\t\t\t0.29 | \n\t\t\t\t\t\t||||
9 | \n\t\t\t\t\t\t\t719 | \n\t\t\t\t\t\t\t0.24 | \n\t\t\t\t\t\t||||
10 | \n\t\t\t\t\t\t\t725 | \n\t\t\t\t\t\t\t0.16 | \n\t\t\t\t\t\t||||
11 | \n\t\t\t\t\t\t\t731 | \n\t\t\t\t\t\t\t0.28 | \n\t\t\t\t\t\t||||
12 | \n\t\t\t\t\t\t\t736 | \n\t\t\t\t\t\t\t0.51 | \n\t\t\t\t\t\t||||
13 | \n\t\t\t\t\t\t\t741 | \n\t\t\t\t\t\t\t0 | \n\t\t\t\t\t\t||||
14 | \n\t\t\t\t\t\t\t751 | \n\t\t\t\t\t\t\t0.29 | \n\t\t\t\t\t\t||||
15 | \n\t\t\t\t\t\t\t658 | \n\t\t\t\t\t\t\t0.57 | \n\t\t\t\t\t\t\t0.50 | \n\t\t\t\t\t\t\t0.55 | \n\t\t\t\t\t\t\t10 | \n\t\t\t\t\t\t\t0.10 | \n\t\t\t\t\t\t
16 | \n\t\t\t\t\t\t\t669 | \n\t\t\t\t\t\t\t0.52 | \n\t\t\t\t\t\t||||
17 | \n\t\t\t\t\t\t\t676 | \n\t\t\t\t\t\t\t0.47 | \n\t\t\t\t\t\t||||
18 | \n\t\t\t\t\t\t\t684 | \n\t\t\t\t\t\t\t0.58 | \n\t\t\t\t\t\t||||
19 | \n\t\t\t\t\t\t\t692 | \n\t\t\t\t\t\t\t0.62 | \n\t\t\t\t\t\t||||
20 | \n\t\t\t\t\t\t\t700 | \n\t\t\t\t\t\t\t0.54 | \n\t\t\t\t\t\t||||
21 | \n\t\t\t\t\t\t\t711 | \n\t\t\t\t\t\t\t0.54 | \n\t\t\t\t\t\t||||
22 | \n\t\t\t\t\t\t\t606 | \n\t\t\t\t\t\t\t1.19 | \n\t\t\t\t\t\t\t1.02 | \n\t\t\t\t\t\t\t1.07 | \n\t\t\t\t\t\t\t10 | \n\t\t\t\t\t\t\t0.10 | \n\t\t\t\t\t\t
23 | \n\t\t\t\t\t\t\t617 | \n\t\t\t\t\t\t\t1.08 | \n\t\t\t\t\t\t||||
24 | \n\t\t\t\t\t\t\t685 | \n\t\t\t\t\t\t\t0.98 | \n\t\t\t\t\t\t||||
25 | \n\t\t\t\t\t\t\t694 | \n\t\t\t\t\t\t\t1.01 | \n\t\t\t\t\t\t||||
26 | \n\t\t\t\t\t\t\t703 | \n\t\t\t\t\t\t\t1.06 | \n\t\t\t\t\t\t||||
27 | \n\t\t\t\t\t\t\t708 | \n\t\t\t\t\t\t\t1 | \n\t\t\t\t\t\t||||
28 | \n\t\t\t\t\t\t\t721 | \n\t\t\t\t\t\t\t1.15 | \n\t\t\t\t\t\t||||
29 | \n\t\t\t\t\t\t\t451 | \n\t\t\t\t\t\t\t2.26 | \n\t\t\t\t\t\t\t2.02 | \n\t\t\t\t\t\t\t2.23 | \n\t\t\t\t\t\t\t2 | \n\t\t\t\t\t\t\t0.10 | \n\t\t\t\t\t\t
30 | \n\t\t\t\t\t\t\t523 | \n\t\t\t\t\t\t\t2.14 | \n\t\t\t\t\t\t||||
31 | \n\t\t\t\t\t\t\t574 | \n\t\t\t\t\t\t\t2.2 | \n\t\t\t\t\t\t||||
32 | \n\t\t\t\t\t\t\t611 | \n\t\t\t\t\t\t\t2.23 | \n\t\t\t\t\t\t||||
33 | \n\t\t\t\t\t\t\t615 | \n\t\t\t\t\t\t\t2.25 | \n\t\t\t\t\t\t||||
34 | \n\t\t\t\t\t\t\t620 | \n\t\t\t\t\t\t\t2.3 | \n\t\t\t\t\t\t||||
35 | \n\t\t\t\t\t\t\t626 | \n\t\t\t\t\t\t\t2.2 | \n\t\t\t\t\t\t||||
36 | \n\t\t\t\t\t\t\t634 | \n\t\t\t\t\t\t\t2.23 | \n\t\t\t\t\t\t||||
37 | \n\t\t\t\t\t\t\t642 | \n\t\t\t\t\t\t\t2.2 | \n\t\t\t\t\t\t||||
38 | \n\t\t\t\t\t\t\t652 | \n\t\t\t\t\t\t\t2.22 | \n\t\t\t\t\t\t||||
39 | \n\t\t\t\t\t\t\t686 | \n\t\t\t\t\t\t\t2.27 | \n\t\t\t\t\t\t||||
40 | \n\t\t\t\t\t\t\t589 | \n\t\t\t\t\t\t\t28.37 | \n\t\t\t\t\t\t\t30.25 | \n\t\t\t\t\t\t\t30.78 | \n\t\t\t\t\t\t\t6 | \n\t\t\t\t\t\t\t0.02 | \n\t\t\t\t\t\t
41 | \n\t\t\t\t\t\t\t590 | \n\t\t\t\t\t\t\t32.69 | \n\t\t\t\t\t\t||||
42 | \n\t\t\t\t\t\t\t609 | \n\t\t\t\t\t\t\t32.31 | \n\t\t\t\t\t\t||||
43 | \n\t\t\t\t\t\t\t621 | \n\t\t\t\t\t\t\t33.4 | \n\t\t\t\t\t\t||||
44 | \n\t\t\t\t\t\t\t625 | \n\t\t\t\t\t\t\t30.86 | \n\t\t\t\t\t\t||||
45 | \n\t\t\t\t\t\t\t644 | \n\t\t\t\t\t\t\t29.97 | \n\t\t\t\t\t\t||||
46 | \n\t\t\t\t\t\t\t646 | \n\t\t\t\t\t\t\t30.51 | \n\t\t\t\t\t\t||||
47 | \n\t\t\t\t\t\t\t691 | \n\t\t\t\t\t\t\t28.1 | \n\t\t\t\t\t\t||||
48 | \n\t\t\t\t\t\t\t457 | \n\t\t\t\t\t\t\t10.55 | \n\t\t\t\t\t\t\t10.07 | \n\t\t\t\t\t\t\t10.67 | \n\t\t\t\t\t\t\t3 | \n\t\t\t\t\t\t\t0.07 | \n\t\t\t\t\t\t
49 | \n\t\t\t\t\t\t\t614 | \n\t\t\t\t\t\t\t10.8 | \n\t\t\t\t\t\t||||
50 | \n\t\t\t\t\t\t\t683 | \n\t\t\t\t\t\t\t11.15 | \n\t\t\t\t\t\t
Comparison of results obtained by Raman spectroscopy and LC/MS/MS of liquid milk from the second test.
A method was established to detect melamine in liquid milk using surface-enhanced Raman spectroscopy with the aid of a silver colloid enhancing substrate. An enhancement factor of ≥ 105-fold was achieved in the measurement of melamine on this SERS-active substrate. In addition, the milk sample preparation process used in this technique is easy and time-saving, only requiring four steps: dilution, centrifugation, addition of samples to the enhanced base, and collection of the Raman spectra. The total detection time using SERS to measure a sample was ~3 min, which is starting from the dilution up to the final results. And the Raman spectra were acquired for only 3 s. Based on the calculations of the most intense peak in the melamine SERS spectra at approximately698 cm-1, the LOQ of the SERS spectra achieved a level of 0.01 μg mL-1 for melamine standard samples, which corresponds to 0.5 μg mL-1 melamine in liquid milk. The RSD was ≤ 10 %, and recoveries were from 93-109%.The results from actual sample analyses were very precise and as good as those results obtained by LC/MS/MS.
\n\t\t\tMelamine, a nitrogen-rich chemical, has recently caused enormous economic losses to the food industry due to instances of milk products being adulterated by melamine, which has led to an urgent need for a rapid and reliable detection method for melamine in food. Here, we used a SERS liquid sensor to detect melamine in dairy products. The preparation processfor the dairy product samples is very easy, i.e.,only dilution with double-distilled water and centrifugation is required.With the aid of a silver colloid, at least a 105-fold enhancement of the Raman signal was achieved for the measurement of melamine. The LOD by this method was 0.01 g mL-1 for melamine standard samples. Based on the intensity of the Raman spectra with vibration bands normalized by the band at 928 cm-1 (CH2),the external standard method was employed for quantitative analysis. The linear regression (R2) of the curve was 0.9998, the LOQ using this approach was 0.5 g mL-1 melamine in dairy product samples, the relative standard deviation was ≤ 10%, and the recoveries ranged from 93-109%. The test results for SERS were very precise and as good as those obtained by LC/MS/MS.
Our method is simple, quick (only requiring ~3 min), cost-effective, and sensitive for the detection of melamine in dairy product samples using a SERS liquid sensor. Therefore, Ag NPs are good candidates for melamine sensing and suitable for the detection of melamine in dairy products. We believe that liquid Au NPs and Ag NPs will be widely used as liquid sensing substrates and that SERS will be widely investigated and applied for the analysis of other molecules, including pesticides, herbicides, pharmaceutical chemicals, banned food dyes, explosives, nicotine, and organic pollutants.
\n\t\tWe are grateful for financial support by the International Science and Technology Cooperation and Exchange Foundation (No. 2008DFA40270), a Strategic Eleventh-five-year Science and Technology Supporting Grant (No. 2009BAK58B01), and Special Funded Projects of the Fundamental Research Funds from the Chinese Academy of Inspection and Quarantine of China (Grant No. 2010JK017).
\n\t\tLoose 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.
Supporting women in scientific research and encouraging more women to pursue careers in STEM fields has been an issue on the global agenda for many years. But there is still much to be done. And IntechOpen wants to help.
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