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Sample records for epidermal melanin concentration

  1. Predicting human epidermal melanin concentrations for different skin tones

    CSIR Research Space (South Africa)

    Smit, Jacoba E

    2011-07-01

    Full Text Available epidermal melanin concentrations for different skin tones JE Smit 1 , AE Karsten 2 , RW Sparrow 1 1 CSIR Biosciences, Pretoria, South Africa 2 CSIR National Laser Centre, Pretoria, South Africa Author e-mail address: KSmit...

  2. Hesperetin induces melanin production in adult human epidermal melanocytes.

    Science.gov (United States)

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Pigmented epidermal cyst with dense collection of melanin: A rare entity - Report of a case with review of the literature.

    Science.gov (United States)

    Jayalakshmy, P S; Subitha, K; Priya, P V; Johnson, Gerald

    2012-05-01

    Epidermal cyst is a very common benign cystic lesion of the skin. It is usual to find ulceration of the lining epithelium, rupture of the cyst wall with chronic inflammation and foreign body giant cell reaction. But, it is very rare to see an epidermal cyst with marked accumulation of melanin pigment. Only a few cases of pigmented epidermal cyst with dense collection of melanin pigment have been published in the literature. Here, we are reporting a case of ruptured epidermal cyst with keratin granuloma formation and showing dense collection of melanin pigment.

  4. Dynamic thermal effects of epidermal melanin and plasmonic nanoparticles during photoacoustic breast imaging

    Science.gov (United States)

    Ghassemi, Pejhman; Wang, Quanzeng; Pfefer, T. Joshua

    2016-03-01

    Photoacoustic Tomography (PAT) employs high-power near-infrared (near-IR) laser pulses to generate structural and functional information on tissue chromophores up to several centimeters below the surface. Such insights may facilitate detection of breast cancer - the most common cancer in women. PAT mammography has been the subject of extensive research, including techniques based on exogenous agents for PAT contrast enhancement and molecular specificity. However, photothermal safety risks of PAT due to strong chromophores such as epidermal melanin and plasmonic nanoparticles have not been rigorously studied. We have used computational and experimental approaches to elucidate highly dynamic optical-thermal processes during PAT. A Monte Carlo model was used to simulate light propagation at 800 and 1064 nm in a multi-layer breast tissue geometry with different epidermal pigmentation levels and a tumorsimulating inclusion incorporating nanoparticles. Energy deposition results were then used in a bioheat transfer model to simulate temperature transients. Experimental measurements involved multi-layer hydrogel phantoms with inclusions incorporating gold nanoparticles. Phantom optical properties were measured using the inverse adding-doubling technique. Thermal imaging was performed as phantoms were irradiated with 5 ns near-IR pulses. Scenarios using 10 Hz laser irradiation of breast tissue containing various nanoparticle concentrations were implemented experimentally and computationally. Laser exposure levels were based on ANSI/IEC limits. Surface temperature measurements were compared to corresponding simulation data. In general, the effect of highly pigmented skin on temperature rise was significant, whereas unexpectedly small levels of temperature rise during nanoparticle irradiation were attributed to rapid photodegradation. Results provide key initial insights into light-tissue interactions impacting the safety and effectiveness of PAT.

  5. Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation

    International Nuclear Information System (INIS)

    Cario-Andre, M.

    2000-11-01

    Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

  6. Human eccrine sweat gland cells turn into melanin-uptaking keratinocytes in dermo-epidermal skin substitutes.

    Science.gov (United States)

    Böttcher-Haberzeth, Sophie; Biedermann, Thomas; Pontiggia, Luca; Braziulis, Erik; Schiestl, Clemens; Hendriks, Bart; Eichhoff, Ossia M; Widmer, Daniel S; Meuli-Simmen, Claudia; Meuli, Martin; Reichmann, Ernst

    2013-02-01

    Recently, Biedermann et al. (2010) have demonstrated that human eccrine sweat gland cells can develop a multilayered epidermis. The question still remains whether these cells can fulfill exclusive and very specific functional properties of epidermal keratinocytes, such as the incorporation of melanin, a feature absent in sweat gland cells. We added human melanocytes to eccrine sweat gland cells to let them develop into an epidermal analog in vivo. The interaction between melanocytes and sweat gland-derived keratinocytes was investigated. The following results were gained: (1) macroscopically, a pigmentation of the substitutes was seen 2-3 weeks after transplantation; (2) we confirmed the development of a multilayered, stratified epidermis with melanocytes distributed evenly throughout the basal layer; (3) melanocytic dendrites projected to suprabasal layers; and (4) melanin was observed to be integrated into former eccrine sweat gland cells. These skin substitutes were similar or equal to skin substitutes cultured from human epidermal keratinocytes. The only differences observed were a delay in pigmentation and less melanin uptake. These data suggest that eccrine sweat gland cells can form a functional epidermal melanin unit, thereby providing striking evidence that they can assume one of the most characteristic keratinocyte properties.

  7. Photoprotective role of epidermal melanin granules against ultraviolet damage and DNA repair in guinea pig skin

    International Nuclear Information System (INIS)

    Ishikawa, T.; Kodama, K.; Matsumoto, J.; Takayama, S.

    1984-01-01

    We previously developed a quantitative autoradiographic technique with special forceps for measuring unscheduled DNA synthesis (UDS) in mouse skin after treatment with ultraviolet light in vivo. By this method, we investigated the relationship between the protective role of melanin and UV-induced DNA repair in black-and-white guinea pigs. Flat areas containing a sharp border between pigmented and unpigmented skin were selected. The skin of the selected areas was shaved and irradiated with short-wave UV (254 nm) or UV-AB (270 to 440 nm, emission peak at 312 nm) at various doses. Immediately after irradiation, the skin was clamped off with forceps, and an isotonic aqueous solution of [methyl- 3 H]thymidine was injected s.c. into the clamped off portion. UDS was clearly demonstrated as silver grains in this portion of the skin after irradiation with 254 nm UV or UV-AB. Errors due to individual differences were avoided by comparing the intensities of UDS in basal cells from pigmented skin and unpigmented skin of the same animals. Unexpectedly, in groups of animals treated with 254 nm UV or UV-AB, no difference in UDS in pigmented and unpigmented skin was seen at any UV dose. These results suggested that epidermal melanin granules do not significantly protect DNA of basal cells against 254 nm UV or UV-AB irradiation. Results of a study on the effect of the wavelength of irradiation on the UDS response of albino guinea pigs are also reported

  8. Pharmacologic induction of epidermal melanin and protection against sunburn in a humanized mouse model.

    Science.gov (United States)

    Amaro-Ortiz, Alexandra; Vanover, Jillian C; Scott, Timothy L; D'Orazio, John A

    2013-09-07

    Fairness of skin, UV sensitivity and skin cancer risk all correlate with the physiologic function of the melanocortin 1 receptor, a Gs-coupled signaling protein found on the surface of melanocytes. Mc1r stimulates adenylyl cyclase and cAMP production which, in turn, up-regulates melanocytic production of melanin in the skin. In order to study the mechanisms by which Mc1r signaling protects the skin against UV injury, this study relies on a mouse model with "humanized skin" based on epidermal expression of stem cell factor (Scf). K14-Scf transgenic mice retain melanocytes in the epidermis and therefore have the ability to deposit melanin in the epidermis. In this animal model, wild type Mc1r status results in robust deposition of black eumelanin pigment and a UV-protected phenotype. In contrast, K14-Scf animals with defective Mc1r signaling ability exhibit a red/blonde pigmentation, very little eumelanin in the skin and a UV-sensitive phenotype. Reasoning that eumelanin deposition might be enhanced by topical agents that mimic Mc1r signaling, we found that direct application of forskolin extract to the skin of Mc1r-defective fair-skinned mice resulted in robust eumelanin induction and UV protection (1). Here we describe the method for preparing and applying a forskolin-containing natural root extract to K14-Scf fair-skinned mice and report a method for measuring UV sensitivity by determining minimal erythematous dose (MED). Using this animal model, it is possible to study how epidermal cAMP induction and melanization of the skin affect physiologic responses to UV exposure.

  9. Autophagy participates in isoliquiritigenin-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling.

    Science.gov (United States)

    Yang, Zhibo; Zeng, Biyun; Pan, Yi; Huang, Pan; Wang, Chang

    2018-01-01

    Melanin is the pigment responsible for the color of human skin and hair. Melanin serves as a double-edge sword which can exert both protective and spot-causing effects on skin. Although melanin has an important role in protecting the skin against UV damage, an excessive or uneven melanin production can lead to the formation of freckles and age spots. Isoliquiritigenin (ISL) has been reported to inhibit melanin synthesis; however, its role in melanin degradation remains unclear. In the present study, we evaluated the detailed function of ISL in melanin degradation in human epidermal keratinocytes. Since autophagy has been reported to be related to melanin degradation, we also examined the activation of autophagy by ISL treatment in keratinocytes by measurement of autophagy-related proteins, ATG7, LC3 and p62. Moreover, si-ATG7-induced ATG7 knockdown and autophagy inhibitor 3-MA decreased LC3 II protein levels and increased PMEL17, p62 and melanin levels in HaCaT cells, which could be partially reversed by ISL treatment, indicating that autophagy participated in melanin degradation. The decreased p-AKT and p-mTOR proteins upon ISL treatment indicated the involvement of PI3K/AKT/mTOR signaling in ISL-induced melanin degradation. Taken together, we demonstrated that autophagy participates in ISL-induced melanin degradation in human epidermal keratinocytes through PI3K/AKT/mTOR signaling. Copyright © 2017. Published by Elsevier Masson SAS.

  10. Applying photoacoustics to quantification of melanin concentration in retinal pigment epithelium (Conference Presentation)

    Science.gov (United States)

    Shu, Xiao; Zhang, Hao F.; Liu, Wenzhong

    2016-03-01

    The melanin in the retinal pigment epithelium (RPE) protects retina and other ocular tissues by photo-screening and acting as antioxidant and free radical scavenger. It helps maintain normal visual functions since human eye is subjected to lifelong high oxygen stress and photon exposure. Loss of the RPE melanin weakens the protection mechanism and jeopardizes ocular health. Local decrease in the RPE melanin concentration is believed to be both a cause and a sign of early-stage age-related macular degeneration (AMD), the leading blinding disease in developed world. Current technology cannot quantitatively measure the RPE melanin concentration which might be a promising marker in early AMD screening. Photoacoustic ophthalmoscopy (PAOM), as an emerging optical absorption-based imaging technology, can potentially be applied to measure the RPE melanin concentration if the dependence of the detectable photoacoustic (PA) signal amplitudes on the RPE melanin concentrations is verified. In this study, we tested the feasibility of using PA signal ratio from RPE melanin and the nearby retinal blood vessels as an indicator of the RPE melanin variation. A novel whole eye optical model was designed and Monte Carlo modeling of light (MCML) was employed. We examined the influences on quantification from PAOM axial resolution, the depth and diameter of the retinal blood vessel, and the RPE thickness. The results show that the scheme is robust to individual histological and illumination variations. This study suggests that PAOM is capable of quantitatively measuring the RPE melanin concentration in vivo.

  11. Melanin-concentrating hormone: from fish skin to skinny mammals.

    Science.gov (United States)

    Pissios, Pavlos; Maratos-Flier, Eleftheria

    2003-07-01

    In recent years, the key role of melanin-concentrating hormone (MCH) in regulating mammalian energy balance has been confirmed through several lines of evidence. When administered exogenously, MCH leads to a rapid and robust feeding response and chronic infusions result in the development of mild obesity. At the physiological level, it is known that MCH expression changes in states of altered energy balance, such as fasting and obesity. Genetic studies with mice have shown that ablation of either the gene for prepro-MCH or the gene encoding the MCH receptor leads to a lean phenotype. Finally, the administration of MCH antagonists appears to inhibit both feeding and the development of diet-induced obesity. The aim of this article is to review the recent data on MCH and MCH receptors in light of their emerging roles in energy homeostasis.

  12. Melanin-concentrating hormone in peripheral circulation in the human.

    Science.gov (United States)

    Naufahu, J; Alzaid, F; Fiuza Brito, M; Doslikova, B; Valencia, T; Cunliffe, A; Murray, J F

    2017-03-01

    Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide with a well-characterised role in energy homeostasis and emergent roles in diverse physiologic functions such as arousal, mood and reproduction. Work to date has predominantly focused on its hypothalamic functions using animal models; however, little attention has been paid to its role in circulation in humans. The aims of this study were to (a) develop a radioimmunoassay for the detection of MCH in human plasma; (b) establish reference ranges for circulating MCH and (c) characterise the pattern of expression of circulating MCH in humans. A sensitive and specific RIA was developed and cross-validated by RP-HPLC and MS. The effective range was 19.5-1248 pg MCH/mL. Blood samples from 231 subjects were taken to establish a reference range of 19.5-55.4 pg/mL for fasting MCH concentrations. There were no significant differences between male and female fasting MCH concentrations; however, there were correlations between MCH concentrations and BMI in males and females with excess fat (P < 0.001 and P = 0.020) and between MCH concentrations and fat mass in females with excess fat (P = 0.038). Plasma MCH concentrations rose significantly after feeding in a group of older individuals (n = 50, males P = 0.006, females P = 0.023). There were no robust significant correlations between fasting or post-prandial MCH and resting metabolic rate, plasma glucose, insulin or leptin concentrations although there were correlations between circulating MCH and leptin concentrations in older individuals (P = 0.029). These results indicate that the role of circulating MCH may not be reflective of its regulatory hypothalamic role. © 2017 Society for Endocrinology.

  13. Melanin-concentrating hormone (MCH: a new sleep factor?

    Directory of Open Access Journals (Sweden)

    Pablo eTorterolo

    2011-03-01

    Full Text Available Neurons that utilize the neuropeptide melanin-concentrating hormone (MCH as a neuromodulator are mainly located in the lateral hypothalamus and the incerto-hypothalamic area, and have widespread projections throughout the brain. While the biological functions of this neuropeptide are exerted in humans through two metabotropic receptors, the MCHR1 and MCHR2, only the MCHR1 is present in rodents. Recently, it has been shown that the MCHergic system is involved in the control of sleep. We can summarize the experimental findings as follows:1. The areas related to the control of sleep and wakefulness have an important density of MCHergic fibers and receptors.2. MCHergic neurons are active during sleep, especially during REM sleep.3. Genetically-modified animals without MCH have less REM sleep, notably under conditions of negative energy balance. 4. Systemically administered MCHR1 antagonists reduce sleep. 5. Intraventricular microinjection of MCH increases both slow wave sleep (SWS and REM sleep; however, the increment in REM sleep is more pronounced.6. Microinjection of MCH into the dorsal raphe nucleus increases REM sleep time. REM seep is inhibited by immunoneutralization of MCH within this nucleus.7. Microinjection of MCH in the nucleus pontis oralis of the cat enhances REM sleep time and reduces REM sleep latency.All these data strongly suggest that MCH has a potent role in the promotion of sleep. Although both SWS and REM sleep are facilitated by MCH, REM sleep seems to be more sensitive to MCH modulation.

  14. Melanin concentrating hormone receptor 1 (MCHR1) antagonists - Still a viable approach for obesity treatment?

    DEFF Research Database (Denmark)

    Högberg, T.; Frimurer, T.M.; Sasmal, P.K.

    2012-01-01

    Obesity is a global epidemic associated with multiple severe diseases. Several pharmacotherapies have been investigated including the melanin concentrating hormone (MCH) and its receptor 1. The development of MCHR1 antagonists are described with a specific perspective on different chemotypes...

  15. Human hypocretin and melanin-concentrating hormone levels are linked to emotion and social interaction.

    Science.gov (United States)

    Blouin, Ashley M; Fried, Itzhak; Wilson, Charles L; Staba, Richard J; Behnke, Eric J; Lam, Hoa A; Maidment, Nigel T; Karlsson, Karl Æ; Lapierre, Jennifer L; Siegel, Jerome M

    2013-01-01

    The neurochemical changes underlying human emotions and social behaviour are largely unknown. Here we report on the changes in the levels of two hypothalamic neuropeptides, hypocretin-1 and melanin-concentrating hormone, measured in the human amygdala. We show that hypocretin-1 levels are maximal during positive emotion, social interaction and anger, behaviours that induce cataplexy in human narcoleptics. In contrast, melanin-concentrating hormone levels are minimal during social interaction, but are increased after eating. Both peptides are at minimal levels during periods of postoperative pain despite high levels of arousal. Melanin-concentrating hormone levels increase at sleep onset, consistent with a role in sleep induction, whereas hypocretin-1 levels increase at wake onset, consistent with a role in wake induction. Levels of these two peptides in humans are not simply linked to arousal, but rather to specific emotions and state transitions. Other arousal systems may be similarly emotionally specialized.

  16. Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia

    NARCIS (Netherlands)

    Unmehopa, Unga A.; van Heerikhuize, Joop J.; Spijkstra, Wenda; Woods, John W.; Howard, Andrew D.; Zycband, Emanuel; Feighner, Scott D.; Hreniuk, Donna L.; Palyha, Oksana C.; Guan, Xiao-Ming; Macneil, Douglas J.; van der Ploeg, Lex H. T.; Swaab, Dick F.

    2005-01-01

    Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R

  17. Increased melanin concentrating hormone receptor type I in the human hypothalamic infundibular nucleus in cachexia.

    NARCIS (Netherlands)

    Unmehopa, U.A.; Heerikhuize, J.J. van; Spijkstra, W.; Woods, J.W.; Howard, A.D.; Zycband, E.; Feighner, S.D.; Hreniuk, D.L.; Palyha, O.C.; Guan, X.-M.; MacNeil, D.J.; Ploeg, L.H.T.; Swaab, D.F.

    2005-01-01

    Melanin-concentrating hormone (MCH) exerts a positive regulation on appetite and binds to the G protein-coupled receptors, MCH1R and MCH2R. In rodents, MCH is produced by neurons in the lateral hypothalamus with projections to various hypothalamic and other brain sites. In the present study, MCH1R

  18. Hypocretin and melanin-concentrating hormone in patients with Huntington disease.

    NARCIS (Netherlands)

    Aziz, A.; Fronczek, R.; Maat-Schieman, M.L.; Unmehopa, U.A.; Roelandse, F.W.; Overeem, S.; Duinen, S.G. van; Lammers, G.J.; Swaab, D.F.; Roos, R.A.C.

    2008-01-01

    To evaluate whether hypocretin-1 (orexin-A) and melanin-concentrating hormone (MCH) neurotransmission are affected in patients with Huntington disease (HD), we immunohistochemically stained hypocretin and MCH neurons and estimated their total numbers in the lateral hypothalamus of both HD patients

  19. Melanin-concentrating hormone and its receptor are expressed and functional in human skin.

    Science.gov (United States)

    Hoogduijn, Martin J; Ancans, Janis; Suzuki, Itaru; Estdale, Siân; Thody, Anthony J

    2002-08-23

    In this study, we have demonstrated the presence of melanin-concentrating hormone (MCH) and melanin-concentrating hormone receptor (MCHR1) transcripts in human skin. Sequence analysis confirmed that the transcripts of both genes were identical to those previously found in human brain. In culture, endothelial cells showed pro-MCH expression whereas no signal was found in keratinocytes, melanocytes, and fibroblasts. MCHR1 expression was restricted to melanocytes and melanoma cells. Stimulation of cultured human melanocytes with MCH reduced the alpha-MSH-induced increase in cAMP production. Furthermore, the melanogenic actions of alpha-MSH were inhibited by MCH. We propose that the MCH/MCHR1 signalling system is present in human skin and may have a role with the melanocortins in regulating the melanocyte.

  20. Differences in the melanosome distribution within the epidermal melanin units and its association with the impairing background of leukoderma in vitiligo and halo nevi: a retrospective study.

    Science.gov (United States)

    Xiong, Xi-Xi; Ding, Gao-Zhong; Zhao, Wen-E; Li, Xue; Ling, Yu-Ting; Sun, Li; Gong, Qing-Li; Lu, Yan

    2017-07-01

    Skin color is determined by the number of melanin granules produced by melanocytes that are transferred to keratinocytes. Melanin synthesis and the distribution of melanosomes to keratinocytes within the epidermal melanin unit (EMU) within the skin of vitiligo patients have been poorly studied. The ultrastructure and distribution of melanosomes in melanocytes and surrounding keratinocytes in perilesional vitiligo and normal skin were investigated using transmission electron microscopy (TEM). Furthermore, we performed a quantitative analysis of melanosome distribution within the EMUs with scatter plot. Melanosome count within keratinocytes increased significantly compared with melanocytes in perilesional stable vitiligo (P vitiligo. Furthermore, melanosome counts within melanocytes and their surrounding keratinocytes in perilesional active vitiligo skin decreased significantly compared with the other groups. In addition, taking the means-standard error of melanosome count within melanocytes and keratinocytes in healthy controls as a normal lower limit, EMUs were graded into 3 stages (I-III). Perilesional active vitiligo presented a significantly different constitution in stages compared to other groups (P vitiligo. Active vitiligo varies in stages and in stage II, EMUs are slightly impaired, but can be resuscitated, providing a golden opportunity with the potential to achieve desired repigmentation with an appropriate therapeutic choice. Adverse milieu may also contribute to the low melanosome count in keratinocytes.

  1. Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation; Role des melanocytes dans l'unite epidermique de melanisation reconstruite ex-vivo apres une irradiation UV aigue

    Energy Technology Data Exchange (ETDEWEB)

    Cario-Andre, M

    2000-11-15

    Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

  2. Influence of melanocytes in the ex-vivo reconstructed epidermal melanin unit following an acute UV irradiation; Role des melanocytes dans l'unite epidermique de melanisation reconstruite ex-vivo apres une irradiation UV aigue

    Energy Technology Data Exchange (ETDEWEB)

    Cario-Andre, M

    2000-11-15

    Influence of melanocytes in skin pigmentation is well documented, however its photo-protective role has given rise to controversy. The role of melanocytes have been investigated on reconstructed epidermis with 100 % of keratinocytes or 95 % of keratinocytes and 5 % of melanocytes. In a first time, the effect of an acute UVB dose has been studied on both reconstructed epidermis, next we have investigated UVA and UVA+B effects on these epidermis. Following irradiation, the presence of melanocytes in reconstructed epidermis protects against apoptosis without protecting significantly against DNA damage formation (CPD, 6-4PP) and protects against UV-induced unbalance of the SOD/catalase ratio (antioxidants enzymes). On the contrary, the presence of melanocytes in reconstructed epidermis amplifies lipids and proteins oxidations but seems to protect against DNA oxidations. Melanocytes differ from keratinocytes by their melanin content and their more important concentration in polyunsaturated fatty acids. To evaluate what is the part of melanin and the part of polyunsaturated fatty acids in epidermal UV responses, reconstructed epidermis with keratinocytes have been supplemented with polyunsaturated fatty acid. This study indicates that polyunsaturated fatty acids are responsible for lipids and proteins oxidations and that melanin protect against DNA oxidation induced by lipid peroxidation. All these studies demonstrate that, model of reconstructed epidermis and epidermis in-vivo have the same behaviour following UV irradiation. In the last part, sunscreens and antioxidants have been tested on reconstructed epidermis and have demonstrated that model of reconstructed epidermis is suitable for photo-protective molecules screening. (author)

  3. Inhibiting roles of melanin-concentrating hormone for skin pigment dispersion in barfin flounder, Verasper moseri.

    Science.gov (United States)

    Mizusawa, Kanta; Kobayashi, Yuki; Sunuma, Toshikazu; Asahida, Takashi; Saito, Yumiko; Takahashi, Akiyoshi

    2011-03-01

    Barfin flounders change their surface color pattern to match their background. We have reported evidence of the association between hormones and body color changes in this fish. First, bolus intraperitoneal injection with melanin-concentrating hormone (MCH) immediately turned the skin color pale, while injection with melanocyte-stimulating hormone (MSH) did not change the skin color. Second, gene expression levels of MCH change in response to background color, while those of MSH do not. We also reported the expression of an MCH receptor gene (Mch-r2) in the skin of this fish. In this study, we aimed to further evaluate the roles of MCH in skin color change. First, long-term adaptation of adult barfin flounder to black or white background colors induced significantly different pigment migration patterns in both melanophores and xanthophores (Ppigment-dispersing activity of MSH in a similar manner. Finally, we identified transcripts of Mch-r2 in cells isolated from both melanophores and xanthophores. Taken together, the evidence suggests that MCH aggregates pigments via MCH-R2 in concert with the nervous system by overcoming the melanin-dispersing activities of MSH in barfin flounder. Copyright © 2010 Elsevier Inc. All rights reserved.

  4. Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

    International Nuclear Information System (INIS)

    Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

    1986-01-01

    A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake

  5. Radioanalytical methods for the measurement of melanin concentrating hormone (MCH) and detection its receptor in rat tissues

    International Nuclear Information System (INIS)

    Lelesz, B.; Szilvassy, Z.; Varga, A.; Juhasz, B.; Nemeth, J.; Toth, G.K.; Toth, A.; Enyedi, A.; Felszeghy, E.

    2016-01-01

    In the present paper the development and application of a novel melanin concentrating hormone radioimmunoassay and receptor-binding assay are described. 125 I-labeling of melanin concentrating hormone (MCH) was performed by iodogen and the mono-iodinated peptide was separated by reversed-phase high performance liquid chromatography. Detection limit of the MCH specific assay was 0.2 fmol/ml. As a practical application of the novel radioimmunoassay, we measured the MCH concentration in different rat organs. High MCH concentrations were detected in the small intestine, pancreas, kidney, liver, trachea, hypothalamus and spinal cord. 125 I-MCH was also suitable for RBA to demonstrate the presence of MCH receptors in the rat brain. (author)

  6. Deletion of Melanin Concentrating Hormone Receptor-1 disrupts overeating in the presence of food cues.

    Science.gov (United States)

    Sherwood, Andrew; Holland, Peter C; Adamantidis, Antoine; Johnson, Alexander W

    2015-12-01

    Exposure to environmental cues associated with food can evoke eating behavior in the absence of hunger. This capacity for reward cues to promote feeding behaviors under sated conditions can be examined in the laboratory using cue-potentiated feeding (CPF). The orexigenic neuropeptide Melanin Concentrating Hormone (MCH) is expressed throughout brain circuitry critical for CPF. We examined whether deletion of the MCH receptor, MCH-1R, would in KO mice disrupt overeating in the presence of a Pavlovian CS+ associated with sucrose delivery. While both wild-type controls and KO mice showed comparable food magazine approach responses during the CPF test, MCH-1R deletion significantly impaired the ability of the CS+ to evoke overeating of sucrose under satiety. Through the use of a refined analysis of meal intake, it was revealed that this disruption to overeating behavior in KO mice reflected a reduction in the capacity for the CS+ to initiate and maintain bursts of licking behavior. These findings suggest that overeating during CPF requires intact MCH-1R signaling and may be due to an influence of the CS+ on the palatability of food and on regulatory mechanisms of peripheral control. Thus, disruptions to MCH-1R signaling may be a useful pharmacological tool to inhibit this form of overeating behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. A role of melanin-concentrating hormone producing neurons in the central regulation of paradoxical sleep

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    Salin Paul

    2003-09-01

    Full Text Available Abstract Background Peptidergic neurons containing the melanin-concentrating hormone (MCH and the hypocretins (or orexins are intermingled in the zona incerta, perifornical nucleus and lateral hypothalamic area. Both types of neurons have been implicated in the integrated regulation of energy homeostasis and body weight. Hypocretin neurons have also been involved in sleep-wake regulation and narcolepsy. We therefore sought to determine whether hypocretin and MCH neurons express Fos in association with enhanced paradoxical sleep (PS or REM sleep during the rebound following PS deprivation. Next, we compared the effect of MCH and NaCl intracerebroventricular (ICV administrations on sleep stage quantities to further determine whether MCH neurons play an active role in PS regulation. Results Here we show that the MCH but not the hypocretin neurons are strongly active during PS, evidenced through combined hypocretin, MCH, and Fos immunostainings in three groups of rats (PS Control, PS Deprived and PS Recovery rats. Further, we show that ICV administration of MCH induces a dose-dependant increase in PS (up to 200% and slow wave sleep (up to 70% quantities. Conclusion These results indicate that MCH is a powerful hypnogenic factor. MCH neurons might play a key role in the state of PS via their widespread projections in the central nervous system.

  8. Neurons Containing Orexin or Melanin Concentrating Hormone Reciprocally Regulate Wake and Sleep

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    Roda Rani eKonadhode

    2015-01-01

    Full Text Available There is considerable amount of data on arousal neurons whereas there is a paucity of knowledge regarding neurons that make us fall asleep. Indeed, current network models of sleep-wake regulation list many arousal neuronal populations compared to only one sleep group located in the preoptic area. There are neurons outside the preoptic area that are active during sleep, but they have never been selectively manipulated. Indeed, none of the sleep-active neurons have been selectively stimulated. To close this knowledge gap we used optogenetics to selectively manipulate neurons containing melanin concentrating hormone (MCH. The MCH neurons are located in the posterior hypothalamus intermingled with the orexin arousal neurons. Our data indicated that optogenetic stimulation of MCH neurons in wildtype mice (J Neuroscience, 2013 robustly increased both non-REM and REM sleep. MCH neuron stimulation increased sleep during the animal’s normal active period, which is compelling evidence that stimulation of MCH neurons has a powerful effect in counteracting the strong arousal signal from all of the arousal neurons. The MCH neurons represent the only group of sleep-active neurons that when selectively stimulated induce sleep. From a translational perspective this is potentially useful in sleep disorders, such as insomnia, where sleep needs to be triggered against a strong arousal drive. Our studies indicate that the MCH neurons belong within an overall model of sleep-wake regulation.

  9. Chronic loss of melanin-concentrating hormone affects motivational aspects of feeding in the rat.

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    Joram D Mul

    2011-05-01

    Full Text Available Current epidemic obesity levels apply great medical and financial pressure to the strenuous economy of obesity-prone cultures, and neuropeptides involved in body weight regulation are regarded as attractive targets for a possible treatment of obesity in humans. The lateral hypothalamus and the nucleus accumbens shell (AcbSh form a hypothalamic-limbic neuropeptide feeding circuit mediated by Melanin-Concentrating Hormone (MCH. MCH promotes feeding behavior via MCH receptor-1 (MCH1R in the AcbSh, although this relationship has not been fully characterized. Given the AcbSh mediates reinforcing properties of food, we hypothesized that MCH modulates motivational aspects of feeding.Here we show that chronic loss of the rat MCH-precursor Pmch decreased food intake predominantly via a reduction in meal size during rat development and reduced high-fat food-reinforced operant responding in adult rats. Moreover, acute AcbSh administration of Neuropeptide-GE and Neuropeptide-EI (NEI, both additional neuropeptides derived from Pmch, or chronic intracerebroventricular infusion of NEI, did not affect feeding behavior in adult pmch(+/+ or pmch(-/- rats. However, acute administration of MCH to the AcbSh of adult pmch(-/- rats elevated feeding behavior towards wild type levels. Finally, adult pmch(-/- rats showed increased ex vivo electrically evoked dopamine release and increased limbic dopamine transporter levels, indicating that chronic loss of Pmch in the rat affects the limbic dopamine system.Our findings support the MCH-MCH1R system as an amplifier of consummatory behavior, confirming this system as a possible target for the treatment of obesity. We propose that MCH-mediated signaling in the AcbSh positively mediates motivational aspects of feeding behavior. Thereby it provides a crucial signal by which hypothalamic neural circuits control energy balance and guide limbic brain areas to enhance motivational or incentive-related aspects of food consumption.

  10. Electrophysiological Properties of Melanin-Concentrating Hormone and Orexin Neurons in Adolescent Rats

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    Victoria Linehan

    2018-03-01

    Full Text Available Orexin and melanin-concentrating hormone (MCH neurons have complementary roles in various physiological functions including energy balance and the sleep/wake cycle. in vitro electrophysiological studies investigating these cells typically use post-weaning rodents, corresponding to adolescence. However, it is unclear whether these neurons are functionally mature at this period and whether these studies can be generalized to adult cells. Therefore, we examined the electrophysiological properties of orexin and MCH neurons in brain slices from post-weaning rats and found that MCH neurons undergo an age-dependent reduction in excitability, but not orexin neurons. Specifically, MCH neurons displayed an age-dependent hyperpolarization of the resting membrane potential (RMP, depolarizing shift of the threshold, and decrease in excitatory transmission, which reach the adult level by 7 weeks of age. In contrast, basic properties of orexin neurons were stable from 4 weeks to 14 weeks of age. Furthermore, a robust short-term facilitation of excitatory synapses was found in MCH neurons, which showed age-dependent changes during the post-weaning period. On the other hand, a strong short-term depression was observed in orexin neurons, which was similar throughout the same period. These differences in synaptic responses and age dependence likely differentially affect the network activity within the lateral hypothalamus where these cells co-exist. In summary, our study suggests that orexin neurons are electrophysiologically mature before adolescence whereas MCH neurons continue to develop until late adolescence. These changes in MCH neurons may contribute to growth spurts or consolidation of adult sleep patterns associated with adolescence. Furthermore, these results highlight the importance of considering the age of animals in studies involving MCH neurons.

  11. The Melanin-Concentrating Hormone as an Integrative Peptide Driving Motivated Behaviors.

    Science.gov (United States)

    Diniz, Giovanne B; Bittencourt, Jackson C

    2017-01-01

    The melanin-concentrating hormone (MCH) is an important peptide implicated in the control of motivated behaviors. History, however, made this peptide first known for its participation in the control of skin pigmentation, from which its name derives. In addition to this peripheral role, MCH is strongly implicated in motivated behaviors, such as feeding, drinking, mating and, more recently, maternal behavior. It is suggested that MCH acts as an integrative peptide, converging sensory information and contributing to a general arousal of the organism. In this review, we will discuss the various aspects of energy homeostasis to which MCH has been associated to, focusing on the different inputs that feed the MCH peptidergic system with information regarding the homeostatic status of the organism and the exogenous sensory information that drives this system, as well as the outputs that allow MCH to act over a wide range of homeostatic and behavioral controls, highlighting the available morphological and hodological aspects that underlie these integrative actions. Besides the well-described role of MCH in feeding behavior, a prime example of hypothalamic-mediated integration, we will also examine those functions in which the participation of MCH has not yet been extensively characterized, including sexual, maternal, and defensive behaviors. We also evaluated the available data on the distribution of MCH and its function in the context of animals in their natural environment. Finally, we briefly comment on the evidence for MCH acting as a coordinator between different modalities of motivated behaviors, highlighting the most pressing open questions that are open for investigations and that could provide us with important insights about hypothalamic-dependent homeostatic integration.

  12. Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.

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    Brenda M Geiger

    Full Text Available BACKGROUND: Melanin-concentrating hormone (MCH, an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD. Expression of MCH is upregulated in inflamed intestinal mucosa in humans with colitis and MCH-deficient mice treated with trinitrobenzene-sulfonic acid (TNBS develop an attenuated form of colitis compared to wild type animals. Zebrafish have emerged as a new animal model of IBD, although the majority of the reported studies concern zebrafish larvae. Regulation MCH expression in the adult zebrafish intestine remains unknown. METHODS: In the present study we induced enterocolitis in adult zebrafish by intrarectal administration of TNBS. Follow-up included survival analysis, histological assessment of changes in intestinal architecture, and assessment of intestinal infiltration by myeloperoxidase positive cells and cytokine transcript levels. RESULTS: Treatment with TNBS dose-dependently reduced fish survival. This response required the presence of an intact microbiome, since fish pre-treated with vancomycin developed less severe enterocolitis. At 6 hours post-challenge, we detected a significant influx of myeloperoxidase positive cells in the intestine and upregulation of both proinflammatory and anti-inflammatory cytokines. Most importantly, and in analogy to human IBD and TNBS-induced mouse experimental colitis, we found increased intestinal expression of MCH and its receptor in TNBS-treated zebrafish. CONCLUSIONS: Taken together these findings not only establish a model of chemically-induced experimental enterocolitis in adult zebrafish, but point to effects of MCH in intestinal inflammation that are conserved across species.

  13. Melanin-concentrating hormone (MCH: role in REM sleep and depression

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    Pablo eTorterolo

    2015-12-01

    Full Text Available The melanin-concentrating hormone (MCH is a peptidergic neuromodulator synthesized by neurons of the lateral hypothalamus and incerto-hypothalamic area. MCHergic neurons project throughout the central nervous system, including areas such as the dorsal (DR and median (MR raphe nuclei, which are involved in the control of sleep and mood.Major Depression (MD is a prevalent psychiatric disease diagnosed on the basis of symptomatic criteria such as sadness or melancholia, guilt, irritability and anhedonia. A short REM sleep latency (i.e. the interval between sleep onset and the first REM sleep period, as well as an increase in the duration of REM sleep and the density of rapid-eye movements during this state, are considered important biological markers of depression. The fact that the greatest firing rate of MCHergic neurons occurs during REM sleep and that optogenetic stimulation of these neurons induces sleep, tends to indicate that MCH plays a critical role in the generation and maintenance of sleep, especially REM sleep. In addition, the acute microinjection of MCH into the DR promotes REM sleep, while immunoneutralization of this peptide within the DR decreases the time spent in this state. Moreover, microinjections of MCH into either the DR or MR promote a depressive-like behavior. In the DR, this effect is prevented by the systemic administration of antidepressant drugs (either fluoxetine or nortriptyline and blocked by the intra-DR microinjection of a specific MCH receptor antagonist. Using electrophysiological and microdialysis techniques we demonstrated also that MCH decreases the activity of serotonergic DR neurons.Therefore, there are substantive experimental data suggesting that the MCHergic system plays a role in the control of REM sleep and, in addition, in the pathophysiology of depression. Consequently, in the present report, we summarize and evaluate the current data and hypotheses related to the role of MCH in REM sleep and MD.

  14. The gene encoding the melanin-concentrating hormone receptor 1 is associated with schizophrenia in a Danish case-control sample

    DEFF Research Database (Denmark)

    Demontis, Ditte; Nyegaard, Mette; Christensen, Jane H

    2012-01-01

    OBJECTIVE: The MCHR1 gene encoding the melanin-concentrating hormone receptor 1 is located on chromosome 22q13.2 and has previously been associated with schizophrenia in a study of cases and controls from the Faroe Islands and Scotland. Herein we report an association between variations in the MCHR...

  15. Melanin distribution in human epidermis affords localized protection against DNA photodamage and concurs with skin cancer incidence difference in extreme phototypes.

    Science.gov (United States)

    Fajuyigbe, Damilola; Lwin, Su M; Diffey, Brian L; Baker, Richard; Tobin, Desmond J; Sarkany, Robert P E; Young, Antony R

    2018-02-02

    Epidermal DNA damage, especially to the basal layer, is an established cause of keratinocyte cancers (KCs). Large differences in KC incidence (20- to 60-fold) between white and black populations are largely attributable to epidermal melanin photoprotection in the latter. The cyclobutane pyrimidine dimer (CPD) is the most mutagenic DNA photolesion; however, most studies suggest that melanin photoprotection against CPD is modest and cannot explain the considerable skin color-based differences in KC incidence. Along with melanin quantity, solar-simulated radiation-induced CPD assessed immediately postexposure in the overall epidermis and within 3 epidermal zones was compared in black West Africans and fair Europeans. Melanin in black skin protected against CPD by 8.0-fold in the overall epidermis and by 59.0-, 16.5-, and 5.0-fold in the basal, middle, and upper epidermis, respectively. Protection was related to the distribution of melanin, which was most concentrated in the basal layer of black skin. These results may explain, at least in part, the considerable skin color differences in KC incidence. These data suggest that a DNA protection factor of at least 60 is necessary in sunscreens to reduce white skin KC incidence to a level that is comparable with that of black skin.-Fajuyigbe, D., Lwin, S. M., Diffey, B. L., Baker, R., Tobin, D. J., Sarkany, R. P. E., Young, A. R. Melanin distribution in human epidermis affords localized protection against DNA photodamage and concurs with skin cancer incidence difference in extreme phototypes.

  16. Effects of intracerebroventricular and intra-accumbens melanin-concentrating hormone agonism on food intake and energy expenditure.

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    Guesdon, Benjamin; Paradis, Eric; Samson, Pierre; Richard, Denis

    2009-03-01

    The brain melanin-concentrating hormone (MCH) system represents an anabolic system involved in energy balance regulation through influences exerted on the homeostatic and nonhomeostatic controls of food intake and energy expenditure. The present study was designed to further delineate the effect of the MCH system on energy balance regulation by assessing the actions of the MCH receptor 1 (MCHR1) agonism on both food intake and energy expenditure after intracerebroventricular (third ventricle) and intra-nucleus-accumbens-shell (intraNAcSH) injections of a MCHR1 agonist. Total energy expenditure and substrate oxidation were assessed following injections in male Wistar rats using indirect calorimetry. Food intake was also measured. Pair-fed groups were added to evaluate changes in thermogenesis that would occur regardless of the meal size and its thermogenic response. Using such experimental conditions, we were able to demonstrate that acute MCH agonism in the brain, besides its orexigenic effect, induced a noticeable change in the utilization of the main metabolic fuels. In pair-fed animals, MCH significantly reduced lipid oxidation when it was injected in the third ventricle. Such an effect was not observed following the injection of MCH in the NAcSH, where MCH nonetheless strongly stimulated appetite. The present results further delineate the influence of MCH on energy expenditure and substrate oxidation while confirming the key role of the NAcSH in the effects of the MCH system on food intake.

  17. Enhanced excitatory input to melanin concentrating hormone neurons during developmental period of high food intake is mediated by GABA.

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    Li, Ying; van den Pol, Anthony N

    2009-12-02

    In contrast to the local axons of GABA neurons of the cortex and hippocampus, lateral hypothalamic neurons containing melanin concentrating hormone (MCH) and GABA send long axons throughout the brain and play key roles in energy homeostasis and mental status. In adults, MCH neurons maintain a hyperpolarized membrane potential and most of the synaptic input is inhibitory. In contrast, we found that developing MCH neurons received substantially more excitatory synaptic input. Based on gramicidin-perforated patch recordings in hypothalamic slices from MCH-green fluorescent protein transgenic mice, we found that GABA was the primary excitatory synaptic transmitter in embryonic and neonatal ages up to postnatal day 10. Surprisingly, glutamate assumed only a minor excitatory role, if any. GABA plays a complex role in developing MCH neurons, with its actions conditionally dependent on a number of factors. GABA depolarization could lead to an increase in spikes either independently or in summation with other depolarizing stimuli, or alternately, depending on the relative timing of other depolarizing events, could lead to shunting inhibition. The developmental shift from depolarizing to hyperpolarizing occurred later in the dendrites than in the cell body. Early GABA depolarization was based on a Cl(-)-dependent inward current. An interesting secondary depolarization in mature neurons that followed an initial hyperpolarization was based on a bicarbonate mechanism. Thus during the early developmental period when food consumption is high, MCH neurons are more depolarized than in the adult, and an increased level of excitatory synaptic input to these orexigenic cells is mediated by GABA.

  18. Molecular characterization of melanin-concentrating hormone (MCH) in Schizothorax prenanti: cloning, tissue distribution and role in food intake regulation.

    Science.gov (United States)

    Wang, Tao; Yuan, Dengyue; Zhou, Chaowei; Lin, Fangjun; Wei, Rongbin; Chen, Hu; Wu, Hongwei; Xin, Zhiming; Liu, Ju; Gao, Yundi; Chen, Defang; Yang, Shiyong; Wang, Yan; Pu, Yundan; Li, Zhiqiong

    2016-06-01

    Melanin-concentrating hormone (MCH) is a crucial neuropeptide involved in various biological functions in both mammals and fish. In this study, the full-length MCH cDNA was obtained from Schizothorax prenanti by rapid amplification of cDNA ends polymerase chain reaction. The full-length MCH cDNA contained 589 nucleotides including an open reading frame of 375 nucleotides encoding 256 amino acids. MCH mRNA was highly expressed in the brain by real-time quantitative PCR analysis. Within the brain, expression of MCH mRNA was preponderantly detected in the hypothalamus. In addition, the MCH mRNA expression in the S. prenanti hypothalamus of fed group was significantly decreased compared with the fasted group at 1 and 3 h post-feeding, respectively. Furthermore, the MCH gene expression presented significant increase in the hypothalamus of fasted group compared with the fed group during long-term fasting. After re-feeding, there was a dramatic decrease in MCH mRNA expression in the hypothalamus of S. prenanti. The results indicate that the expression of MCH is affected by feeding status. Taken together, our results suggest that MCH may be involved in food intake regulation in S. prenanti.

  19. Ablation of neurons expressing melanin-concentrating hormone (MCH) in adult mice improves glucose tolerance independent of MCH signaling.

    Science.gov (United States)

    Whiddon, Benjamin B; Palmiter, Richard D

    2013-01-30

    Melanin-concentrating hormone (MCH)-expressing neurons have been ascribed many roles based on studies of MCH-deficient mice. However, MCH neurons express other neurotransmitters, including GABA, nesfatin, and cocaine-amphetamine-regulated transcript. The importance of these other signaling molecules made by MCH neurons remains incompletely characterized. To determine the roles of MCH neurons in vivo, we targeted expression of the human diphtheria toxin receptor (DTR) to the gene for MCH (Pmch). Within 2 weeks of diphtheria toxin injection, heterozygous Pmch(DTR/+) mice lost 98% of their MCH neurons. These mice became lean but ate normally and were hyperactive, especially during a fast. They also responded abnormally to psychostimulants. For these phenotypes, ablation of MCH neurons recapitulated knock-out of MCH, so MCH appears to be the critical neuromodulator released by these neurons. In contrast, MCH-neuron-ablated mice showed improved glucose tolerance when compared with MCH-deficient mutant mice and wild-type mice. We conclude that MCH neurons regulate glucose tolerance through signaling molecules other than MCH.

  20. Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

    OpenAIRE

    Imbernon, Monica; Beiroa, Daniel; Vázquez, María J.; Morgan, Donald A.; Veyrat–Durebex, Christelle; Porteiro, Begoña; Díaz–Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A.; Al–Massadi, Omar; Varela, Luis; Gándara, Marina; López–Soriano, Francisco–Javier; Gallego, Rosalía

    2013-01-01

    BACKGROUND AIMS Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin concentrating hormone (MCH) deficient mice are hypophagic lean and do not develop hepatosteatosis when fed a high fat diet. Herein we sought to investigate the role of MCH an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area on hepatic and adipocyte metabolism. METHODS Chronic central administration of MCH and adenoviral vectors increasing MCH sign...

  1. Mice lacking melanin-concentrating hormone receptor 1 demonstrate increased heart rate associated with altered autonomic activity.

    Science.gov (United States)

    Astrand, Annika; Bohlooly-Y, Mohammad; Larsdotter, Sara; Mahlapuu, Margit; Andersén, Harriet; Tornell, Jan; Ohlsson, Claes; Snaith, Mike; Morgan, David G A

    2004-10-01

    Melanin-concentrating hormone (MCH) plays an important role in energy balance. The current studies were carried out on a new line of mice lacking the rodent MCH receptor (MCHR1(-/-) mice). These mice confirmed the previously reported lean phenotype characterized by increased energy expenditure and modestly increased caloric intake. Because MCH is expressed in the lateral hypothalamic area, which also has an important role in the regulation of the autonomic nervous system, heart rate and blood pressure were measured by a telemetric method to investigate whether the increased energy expenditure in these mice might be due to altered autonomic nervous system activity. Male MCHR1(-/-) mice demonstrated a significantly increased heart rate [24-h period: wild type 495 +/- 4 vs. MCHR1(-/-) 561 +/- 8 beats/min (P dark phase: wild type 506 +/- 8 vs. MCHR1(-/-) 582 +/- 9 beats/min (P light phase: wild type 484 +/- 13 vs. MCHR1(-/-) 539 +/- 9 beats/min (P vs. MCHR1(-/-) 113 +/- 0.4 mmHg (P > 0.05)]. Locomotor activity and core body temperature were higher in the MCHR1(-/-) mice during the dark phase only and thus temporally dissociated from heart rate differences. On fasting, wild-type animals rapidly downregulated body temperature and heart rate. MCHR1(-/-) mice displayed a distinct delay in the onset of this downregulation. To investigate the mechanism underlying these differences, autonomic blockade experiments were carried out. Administration of the adrenergic antagonist metoprolol completely reversed the tachycardia seen in MCHR1(-/-) mice, suggesting an increased sympathetic tone.

  2. Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

    Science.gov (United States)

    Pace, Marta; Adamantidis, Antoine; Facchin, Laura; Bassetti, Claudio

    2017-01-01

    Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD) before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH) and orexin/hypocretin (OX) systems. This study aims to 1) assess the relationship between sleep and recovery; 2) test the association between MCH and OX systems with the pathological mechanisms of stroke. Sprague-Dawley rats were assigned to four experimental groups: (i) SD_IS: SD performed before ischemia; (ii) IS: ischemia; (iii) SD_Sham: SD performed before sham surgery; (iv) Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR. A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group. Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

  3. Melanin-concentrating hormone directly inhibits GnRH neurons and blocks kisspeptin activation, linking energy balance to reproduction.

    Science.gov (United States)

    Wu, Min; Dumalska, Iryna; Morozova, Elena; van den Pol, Anthony; Alreja, Meenakshi

    2009-10-06

    A link between energy balance and reproduction is critical for the survival of all species. Energy-consuming reproductive processes need to be aborted in the face of a negative energy balance, yet knowledge of the pathways mediating this link remains limited. Fasting and food restriction that inhibit fertility also upregulate the hypothalamic melanin-concentrating hormone (MCH) system that promotes feeding and decreases energy expenditure; MCH knockout mice are lean and have a higher metabolism but remain fertile. MCH also modulates sleep, drug abuse behavior, and mood, and MCH receptor antagonists are currently being developed as antiobesity and antidepressant drugs. Despite the clinical implications of MCH, the direct postsynaptic effects of MCH have never been reported in CNS neurons. Using patch-clamp recordings in brain slices from multiple lines of transgenic GFP mice, we demonstrate a strong inhibitory effect of MCH on an exclusive population of septal vGluT2-GnRH neurons that is activated by the puberty-triggering and preovulatory luteinizing hormone surge-mediating peptide, kisspeptin. MCH has no effect on kisspeptin-insensitive GnRH, vGluT2, cholinergic, or GABAergic neurons located within the same nucleus. The inhibitory effects of MCH are reproducible and nondesensitizing and are mediated via a direct postsynaptic Ba(2+)-sensitive K(+) channel mechanism involving the MCHR1 receptor. MCH immunoreactive fibers are in close proximity to vGluT2-GFP and GnRH-GFP neurons. Importantly, MCH blocks the excitatory effect of kisspeptin on vGluT2-GnRH neurons. Considering the role of MCH in regulating energy balance and of GnRH and kisspeptin in triggering puberty and maintaining fertility, MCH may provide a critical link between energy balance and reproduction directly at the level of the kisspeptin-activated vGluT2-GnRH neuron.

  4. Role of REM Sleep, Melanin Concentrating Hormone and Orexin/Hypocretin Systems in the Sleep Deprivation Pre-Ischemia.

    Directory of Open Access Journals (Sweden)

    Marta Pace

    Full Text Available Sleep reduction after stroke is linked to poor recovery in patients. Conversely, a neuroprotective effect is observed in animals subjected to acute sleep deprivation (SD before ischemia. This neuroprotection is associated with an increase of the sleep, melanin concentrating hormone (MCH and orexin/hypocretin (OX systems. This study aims to 1 assess the relationship between sleep and recovery; 2 test the association between MCH and OX systems with the pathological mechanisms of stroke.Sprague-Dawley rats were assigned to four experimental groups: (i SD_IS: SD performed before ischemia; (ii IS: ischemia; (iii SD_Sham: SD performed before sham surgery; (iv Sham: sham surgery. EEG and EMG were recorded. The time-course of the MCH and OX gene expression was measured at 4, 12, 24 hours and 3, 4, 7 days following ischemic surgery by qRT-PCR.A reduction of infarct volume was observed in the SD_IS group, which correlated with an increase of REM sleep observed during the acute phase of stroke. Conversely, the IS group showed a reduction of REM sleep. Furthermore, ischemia induces an increase of MCH and OX systems during the acute phase of stroke, although, both systems were still increased for a long period of time only in the SD_IS group.Our data indicates that REM sleep may be involved in the neuroprotective effect of SD pre-ischemia, and that both MCH and OX systems were increased during the acute phase of stroke. Future studies should assess the role of REM sleep as a prognostic marker, and test MCH and OXA agonists as new treatment options in the acute phase of stroke.

  5. Cerebrospinal fluid melanin-concentrating hormone (MCH and hypocretin-1 (HCRT-1, orexin-A in Alzheimer's disease.

    Directory of Open Access Journals (Sweden)

    Frank M Schmidt

    Full Text Available Ancillary to decline in cognitive abilities, patients with Alzheimer's disease (AD frequently suffer from behavioural and psychological symptoms of dementia (BPSD. Hypothalamic polypeptides such as melanin-concentrating hormone (MCH and hypocretin-1 (HCRT-1, orexin-A are promoters of sleep-wake regulation and energy homeostasis and are found to impact on cognitive performance. To investigate the role of MCH and HCRT-1 in AD, cerebrospinal fluid (CSF levels were measured in 33 patients with AD and 33 healthy subjects (HS using a fluorescence immunoassay (FIA. A significant main effect of diagnosis (F(1,62 = 8.490, p<0.01 on MCH levels was found between AD (93.76±13.47 pg/mL and HS (84.65±11.40 pg/mL. MCH correlated with T-tau (r = 0.47; p<0.01 and P-tau (r = 0.404; p<0.05 in the AD but not in the HS. CSF-MCH correlated negatively with MMSE scores in the AD (r = -0.362, p<0.05 and was increased in more severely affected patients (MMSE≤20 compared to HS (p<0.001 and BPSD-positive patients compared to HS (p<0.05. In CSF-HCRT-1, a significant main effect of sex (F(1,31 = 4.400, p<0.05 with elevated levels in females (90.93±17.37 pg/mL vs. 82.73±15.39 pg/mL was found whereas diagnosis and the sex*diagnosis interaction were not significant. Elevated levels of MCH in patients suffering from AD and correlation with Tau and severity of cognitive impairment point towards an impact of MCH in AD. Gender differences of CSF-HCRT-1 controversially portend a previously reported gender dependence of HCRT-1-regulation. Histochemical and actigraphic explorations are warranted to further elucidate alterations of hypothalamic transmitter regulation in AD.

  6. Meta-analysis of melanin-concentrating hormone signaling-deficient mice on behavioral and metabolic phenotypes.

    Directory of Open Access Journals (Sweden)

    Kenkichi Takase

    Full Text Available The demand for meta-analyses in basic biomedical research has been increasing because the phenotyping of genetically modified mice does not always produce consistent results. Melanin-concentrating hormone (MCH has been reported to be involved in a variety of behaviors that include feeding, body-weight regulation, anxiety, sleep, and reward behavior. However, the reported behavioral and metabolic characteristics of MCH signaling-deficient mice, such as MCH-deficient mice and MCH receptor 1 (MCHR1-deficient mice, are not consistent with each other. In the present study, we performed a meta-analysis of the published data related to MCH-deficient and MCHR1-deficient mice to obtain robust conclusions about the role of MCH signaling. Overall, the meta-analysis revealed that the deletion of MCH signaling enhanced wakefulness, locomotor activity, aggression, and male sexual behavior and that MCH signaling deficiency suppressed non-REM sleep, anxiety, responses to novelty, startle responses, and conditioned place preferences. In contrast to the acute orexigenic effect of MCH, MCH signaling deficiency significantly increased food intake. Overall, the meta-analysis also revealed that the deletion of MCH signaling suppressed the body weight, fat mass, and plasma leptin, while MCH signaling deficiency increased the body temperature, oxygen consumption, heart rate, and mean arterial pressure. The lean phenotype of the MCH signaling-deficient mice was also confirmed in separate meta-analyses that were specific to sex and background strain (i.e., C57BL/6 and 129Sv. MCH signaling deficiency caused a weak anxiolytic effect as assessed with the elevated plus maze and the open field test but also caused a weak anxiogenic effect as assessed with the emergence test. MCH signaling-deficient mice also exhibited increased plasma corticosterone under non-stressed conditions, which suggests enhanced activity of the hypothalamic-pituitary-adrenal axis. To the best of our

  7. EPR studies of melanin from Cladosporium cladosporioides

    International Nuclear Information System (INIS)

    Pilawa, B.; Buszman, E.; Latocha, M.; Wilczok, T.

    1996-01-01

    Free radical properties of Cladosporium cladosporioides mycelium and melanin, and synthetic eumelanin and pheomelanin were studied by electron paramagnetic resonance method. Single EPR line and complex EPR spectrum with hyperfine splitting were measured for model DOPA-melanin and cysteinyldopa-melanin, respectively. EPR spectra of Cladosporium cladosporioides samples and pheomelanin show the same character. The concentration of paramagnetic centers in melanins isolated from Cladosporium cladosporioides is considerably higher than that of crude mycelium, whereas the EPR line widths are lower for mycelium than for melanin samples. For all analyzed samples the increase of EPR signals intensity with the increase of microwave power, and the decrease of intensities after saturation were observed the low values of microwave power sufficient for EPR lines saturation demonstrate that the spin-lattice relaxation times of unpaired electrons in melanins are long. (author)

  8. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Directory of Open Access Journals (Sweden)

    Béatrice Marquèze-Pouey

    Full Text Available Signaling mediated by the epidermal growth factor (EGF is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer. In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  9. Physiological epidermal growth factor concentrations activate high affinity receptors to elicit calcium oscillations.

    Science.gov (United States)

    Marquèze-Pouey, Béatrice; Mailfert, Sébastien; Rouger, Vincent; Goaillard, Jean-Marc; Marguet, Didier

    2014-01-01

    Signaling mediated by the epidermal growth factor (EGF) is crucial in tissue development, homeostasis and tumorigenesis. EGF is mitogenic at picomolar concentrations and is known to bind its receptor on high affinity binding sites depending of the oligomerization state of the receptor (monomer or dimer). In spite of these observations, the cellular response induced by EGF has been mainly characterized for nanomolar concentrations of the growth factor, and a clear definition of the cellular response to circulating (picomolar) concentrations is still lacking. We investigated Ca2+ signaling, an early event in EGF responses, in response to picomolar doses in COS-7 cells where the monomer/dimer equilibrium is unaltered by the synthesis of exogenous EGFR. Using the fluo5F Ca2+ indicator, we found that picomolar concentrations of EGF induced in 50% of the cells a robust oscillatory Ca2+ signal quantitatively similar to the Ca2+ signal induced by nanomolar concentrations. However, responses to nanomolar and picomolar concentrations differed in their underlying mechanisms as the picomolar EGF response involved essentially plasma membrane Ca2+ channels that are not activated by internal Ca2+ store depletion, while the nanomolar EGF response involved internal Ca2+ release. Moreover, while the picomolar EGF response was modulated by charybdotoxin-sensitive K+ channels, the nanomolar response was insensitive to the blockade of these ion channels.

  10. Characterization of melanin-concentrating hormone (MCH) and its receptor in chickens: Tissue expression, functional analysis, and fasting-induced up-regulation of hypothalamic MCH expression.

    Science.gov (United States)

    Cui, Lin; Lv, Can; Zhang, Jiannan; Mo, Chunheng; Lin, Dongliang; Li, Juan; Wang, Yajun

    2017-06-05

    Melanin-concentrating hormone (MCH) is a neuropeptide expressed in the brain and exerts its actions through interaction with the two known G protein-coupled receptors, namely melanin-concentrating hormone receptor 1 and 2 (MCHR1 and MCHR2) in mammals. However, the information regarding the expression and functionality of MCH and MCHR(s) remains largely unknown in birds. In this study, using RT-PCR and RACE PCR, we amplified and cloned a MCHR1-like receptor, which is named cMCHR4 according to its evolutionary origin, and a MCHR2 from chicken brain. The cloned cMCHR4 was predicted to encode a receptor of 367 amino acids, which shares high amino acid identities with MCHR4 of ducks (90%), western painted turtles (85%), and coelacanths (77%), and a comparatively low identity to human MCHR1 (58%) and MCHR2 (38%), whereas chicken MCHR2 encodes a putative C-terminally truncated receptor and is likely a pseudogene. Using cell-based luciferase reporter assays or Western blot, we further demonstrated that chicken (and duck) MCHR4 could be potently activated by chicken MCH 1-19 , and its activation can elevate calcium concentration and activate MAPK/ERK and cAMP/PKA signaling pathways, indicating an important role of MCHR4 in mediating MCH actions in birds. Quantitative real-time PCR revealed that both cMCH and cMCHR4 mRNA are expressed in various brain regions including the hypothalamus, and cMCH expression in the hypothalamus of 3-week-old chicks could be induced by 36-h fasting, indicating that cMCH expression is correlated with energy balance. Taken together, characterization of chicken MCH and MCHR4 will aid to uncover the conserved roles of MCH across vertebrates. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. [18F]FE@SNAP—A new PET tracer for the melanin concentrating hormone receptor 1 (MCHR1): Microfluidic and vessel-based approaches

    Science.gov (United States)

    Philippe, Cécile; Ungersboeck, Johanna; Schirmer, Eva; Zdravkovic, Milica; Nics, Lukas; Zeilinger, Markus; Shanab, Karem; Lanzenberger, Rupert; Karanikas, Georgios; Spreitzer, Helmut; Viernstein, Helmut; Mitterhauser, Markus; Wadsak, Wolfgang

    2012-01-01

    Changes in the expression of the melanin concentrating hormone receptor 1 (MCHR1) are involved in a variety of pathologies, especially obesity and anxiety disorders. To monitor these pathologies in-vivo positron emission tomography (PET) is a suitable method. After the successful radiosynthesis of [11C]SNAP-7941—the first PET-Tracer for the MCHR1, we aimed to synthesize its [18F]fluoroethylated analogue: [18F]FE@SNAP. Therefore, microfluidic and vessel-based approaches were tested. [18F]fluoroethylation was conducted via various [18F]fluoroalkylated synthons and direct [18F]fluorination. Only the direct [18F]fluorination of a tosylated precursor using a flow-through microreactor was successful, affording [18F]FE@SNAP in 44.3 ± 2.6%. PMID:22921745

  12. Hypothalamic kappa opioid receptor mediates both diet-induced and melanin concentrating hormone-induced liver damage through inflammation and endoplasmic reticulum stress.

    Science.gov (United States)

    Imbernon, Monica; Sanchez-Rebordelo, Estrella; Romero-Picó, Amparo; Kalló, Imre; Chee, Melissa J; Porteiro, Begoña; Al-Massadi, Omar; Contreras, Cristina; Fernø, Johan; Senra, Ana; Gallego, Rosalia; Folgueira, Cintia; Seoane, Luisa M; van Gestel, Margriet; Adan, Roger A; Liposits, Zsolt; Dieguez, Carlos; López, Miguel; Nogueiras, Ruben

    2016-10-01

    The opioid system is widely known to modulate the brain reward system and thus affect the behavior of humans and other animals, including feeding. We hypothesized that the hypothalamic opioid system might also control energy metabolism in peripheral tissues. Mice lacking the kappa opioid receptor (κOR) and adenoviral vectors overexpressing or silencing κOR were stereotaxically delivered in the lateral hypothalamic area (LHA) of rats. Vagal denervation was performed to assess its effect on liver metabolism. Endoplasmic reticulum (ER) stress was inhibited by pharmacological (tauroursodeoxycholic acid) and genetic (overexpression of the chaperone glucose-regulated protein 78 kDa) approaches. The peripheral effects on lipid metabolism were assessed by histological techniques and western blot. We show that in the LHA κOR directly controls hepatic lipid metabolism through the parasympathetic nervous system, independent of changes in food intake and body weight. κOR colocalizes with melanin concentrating hormone receptor 1 (MCH-R1) in the LHA, and genetic disruption of κOR reduced melanin concentrating hormone-induced liver steatosis. The functional relevance of these findings was given by the fact that silencing of κOR in the LHA attenuated both methionine choline-deficient, diet-induced and choline-deficient, high-fat diet-induced ER stress, inflammation, steatohepatitis, and fibrosis, whereas overexpression of κOR in this area promoted liver steatosis. Overexpression of glucose-regulated protein 78 kDa in the liver abolished hypothalamic κOR-induced steatosis by reducing hepatic ER stress. This study reveals a novel hypothalamic-parasympathetic circuit modulating hepatic function through inflammation and ER stress independent of changes in food intake or body weight; these findings might have implications for the clinical use of opioid receptor antagonists. (Hepatology 2016;64:1086-1104). © 2016 The Authors. (Hepatology published by Wiley Periodicals, Inc., on

  13. Fluorescent quantification of melanin.

    Science.gov (United States)

    Fernandes, Bruno; Matamá, Teresa; Guimarães, Diana; Gomes, Andreia; Cavaco-Paulo, Artur

    2016-11-01

    Melanin quantification is reportedly performed by absorption spectroscopy, commonly at 405 nm. Here, we propose the implementation of fluorescence spectroscopy for melanin assessment. In a typical in vitro assay to assess melanin production in response to an external stimulus, absorption spectroscopy clearly overvalues melanin content. This method is also incapable of distinguishing non-melanotic/amelanotic control cells from those that are actually capable of performing melanogenesis. Therefore, fluorescence spectroscopy is the best method for melanin quantification as it proved to be highly specific and accurate, detecting even small variations in the synthesis of melanin. This method can also be applied to the quantification of melanin in more complex biological matrices like zebrafish embryos and human hair. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Fungal melanins and their interactions with metals.

    Science.gov (United States)

    Fogarty, R V; Tobin, J M

    1996-09-01

    Fungal melanins are dark brown or black pigments located in cell walls. They also exist as extracellular polymers. Melanized fungi possess increased virulence and resistance to microbial attack as well as enhanced survival while under environmental stress. Melanins contain various functional groups which provide an array of multiple nonequivalent binding sites for metal ions. Pigmented Cladosporium cladosporoides was shown to biosorb 2.5- to four-fold more Ni, Cu, Zn, Cd, and Pb than albino Penicillium digitatum and at four- to six-fold higher rates. Metal desorption was significantly lower for extracellular melanin than from pigmented or albino biomass which indicated the strength of the melanin-metal bond. At equilibrium, tributyltin chloride (TBTC) concentrations of 2.5 mM, pigmented and albino Aureobasidium pullulans absorbed approximately 0.9 and 0.7 mumol TBTC mg -1 dry wt, respectively, whereas purified extracellular melanin exhibited uptake levels of approximately 22 mumol TBTC mg-1 dry wt at an equilibrium concentration of only 0.4 mM. Addition of melanin to the growth medium reduced the toxic effect of CuSO4 and TBTC due to melanin metal binding and sequestration.

  15. Antibodies Against Melanin

    African Journals Online (AJOL)

    1973-01-06

    Jan 6, 1973 ... against the exposed protein moiety of incompletely mel- anized melanosomes. When fully melanized the antigenic protein moiety and tyrosinase may be occluded by the non-antigenic melanin. We have no further data to support this suggestion, because we did not, at the time, examine the melanin by ...

  16. Melanin-binding radiopharmaceuticals

    International Nuclear Information System (INIS)

    Packer, S.; Fairchild, R.G.; Watts, K.P.; Greenberg, D.; Hannon, S.J.

    1980-01-01

    The scope of this paper is limited to an analysis of the factors that are important to the relationship of radiopharmaceuticals to melanin. While the authors do not attempt to deal with differences between melanin-binding vs. melanoma-binding, a notable variance is assumed

  17. UVA phototransduction drives early melanin synthesis in human melanocytes.

    Science.gov (United States)

    Wicks, Nadine L; Chan, Jason W; Najera, Julia A; Ciriello, Jonathan M; Oancea, Elena

    2011-11-22

    Exposure of human skin to solar ultraviolet radiation (UVR), a powerful carcinogen [1] comprising ~95% ultraviolet A (UVA) and ~5% ultraviolet B (UVB) at the Earth's surface, promotes melanin synthesis in epidermal melanocytes [2, 3], which protects skin from DNA damage [4, 5]. UVB causes DNA lesions [6] that lead to transcriptional activation of melanin-producing enzymes, resulting in delayed skin pigmentation within days [7]. In contrast, UVA causes primarily oxidative damage [8] and leads to immediate pigment darkening (IPD) within minutes, via an unknown mechanism [9, 10]. No receptor protein directly mediating phototransduction in skin has been identified. Here we demonstrate that exposure of primary human epidermal melanocytes (HEMs) to UVA causes calcium mobilization and early melanin synthesis. Calcium responses were abolished by treatment with G protein or phospholipase C (PLC) inhibitors or by depletion of intracellular calcium stores. We show that the visual photopigment rhodopsin [11] is expressed in HEMs and contributes to UVR phototransduction. Upon UVR exposure, significant melanin production was measured within one hour; cellular melanin continued to increase in a retinal- and calcium-dependent manner up to 5-fold after 24 hr. Our findings identify a novel UVA-sensitive signaling pathway in melanocytes that leads to calcium mobilization and melanin synthesis and may underlie the mechanism of IPD in human skin. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Central melanin-concentrating hormone influences liver and adipose metabolism via specific hypothalamic nuclei and efferent autonomic/JNK1 pathways.

    Science.gov (United States)

    Imbernon, Monica; Beiroa, Daniel; Vázquez, María J; Morgan, Donald A; Veyrat-Durebex, Christelle; Porteiro, Begoña; Díaz-Arteaga, Adenis; Senra, Ana; Busquets, Silvia; Velásquez, Douglas A; Al-Massadi, Omar; Varela, Luis; Gándara, Marina; López-Soriano, Francisco-Javier; Gallego, Rosalía; Seoane, Luisa M; Argiles, Josep M; López, Miguel; Davis, Roger J; Sabio, Guadalupe; Rohner-Jeanrenaud, Françoise; Rahmouni, Kamal; Dieguez, Carlos; Nogueiras, Ruben

    2013-03-01

    Specific neuronal circuits modulate autonomic outflow to liver and white adipose tissue. Melanin-concentrating hormone (MCH)-deficient mice are hypophagic, lean, and do not develop hepatosteatosis when fed a high-fat diet. Herein, we sought to investigate the role of MCH, an orexigenic neuropeptide specifically expressed in the lateral hypothalamic area, on hepatic and adipocyte metabolism. Chronic central administration of MCH and adenoviral vectors increasing MCH signaling were performed in rats and mice. Vagal denervation was performed to assess its effect on liver metabolism. The peripheral effects on lipid metabolism were assessed by real-time polymerase chain reaction and Western blot. We showed that the activation of MCH receptors promotes nonalcoholic fatty liver disease through the parasympathetic nervous system, whereas it increases fat deposition in white adipose tissue via the suppression of sympathetic traffic. These metabolic actions are independent of parallel changes in food intake and energy expenditure. In the liver, MCH triggers lipid accumulation and lipid uptake, with c-Jun N-terminal kinase being an essential player, whereas in adipocytes MCH induces metabolic pathways that promote lipid storage and decreases lipid mobilization. Genetic activation of MCH receptors or infusion of MCH specifically in the lateral hypothalamic area modulated hepatic lipid metabolism, whereas the specific activation of this receptor in the arcuate nucleus affected adipocyte metabolism. Our findings show that central MCH directly controls hepatic and adipocyte metabolism through different pathways. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  19. Control of ventricular ciliary beating by the Melanin Concentrating Hormone-expressing neurons of the lateral hypothalamus : a functional imaging survey.

    Directory of Open Access Journals (Sweden)

    Gregory eConductier

    2013-11-01

    Full Text Available The cyclic peptide Melanin-Concentrating Hormone (MCH is known to control a large number of brain functions in mammals such as food intake and metabolism, stress response, anxiety, sleep/wake cycle, memory and reward. Based on neuroanatomical and electrophysiological studies these functions were attributed to neuronal circuits expressing MCHR1, the single MCH receptor in rodents. In complement to our recently published work (Conductier et al. 2013 we provided here new data regarding the action of MCH on ependymocytes in the mouse brain. First, we establish that MCHR1 mRNA is expressed in the ependymal cells of the third ventricle epithelium. Second, we demonstated a tonic control of MCH-expressing neurons on ependymal cilia beat frequency using in vitro optogenics. Finally, we performed in vivo measurements of CSF flow using fluorescent micro-beads in wild-type and MCHR1 knockout mice. Collectively, our results demonstrated that MCH-expressing neurons modulate ciliary beating of ependymal cells at the third ventricle and could contribute to maintain cerebro-spinal fluid homeostasis.

  20. Translational Modeling to Guide Study Design and Dose Choice in Obesity Exemplified by AZD1979, a Melanin-concentrating Hormone Receptor 1 Antagonist.

    Science.gov (United States)

    Gennemark, P; Trägårdh, M; Lindén, D; Ploj, K; Johansson, A; Turnbull, A; Carlsson, B; Antonsson, M

    2017-07-01

    In this study, we present the translational modeling used in the discovery of AZD1979, a melanin-concentrating hormone receptor 1 (MCHr1) antagonist aimed for treatment of obesity. The model quantitatively connects the relevant biomarkers and thereby closes the scaling path from rodent to man, as well as from dose to effect level. The complexity of individual modeling steps depends on the quality and quantity of data as well as the prior information; from semimechanistic body-composition models to standard linear regression. Key predictions are obtained by standard forward simulation (e.g., predicting effect from exposure), as well as non-parametric input estimation (e.g., predicting energy intake from longitudinal body-weight data), across species. The work illustrates how modeling integrates data from several species, fills critical gaps between biomarkers, and supports experimental design and human dose-prediction. We believe this approach can be of general interest for translation in the obesity field, and might inspire translational reasoning more broadly. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  1. Preclinical in vitro and in vivo evaluation of [11C]SNAP-7941 – the first PET tracer for the melanin concentrating hormone receptor 1

    International Nuclear Information System (INIS)

    Philippe, Cécile; Nics, Lukas; Zeilinger, Markus; Kuntner, Claudia; Wanek, Thomas; Mairinger, Severin; Shanab, Karem; Spreitzer, Helmut; Viernstein, Helmut; Wadsak, Wolfgang; Mitterhauser, Markus

    2013-01-01

    Introduction: Due to its involvement in a variety of pathologies (obesity, diabetes, gut inflammation and depression), the melanin concentrating hormone receptor 1 (MCHR1) is a new target for the treatment of these lifestyle diseases. We previously presented the radiosynthesis of [ 11 C]SNAP-7941, the first potential PET tracer for the MCHR1. Methods: We herein present its in vitro and in vivo evaluation, including binding affinity, plasma stability, stability against liver mircrosomes and carboxylesterase, lipohilicity, biodistribution, in vivo metabolism and small-animal PET. Results: [ 11 C]SNAP-7941 evinced high stability against liver microsomes, carboxylesterase and in human plasma. The first small-animal PET experiments revealed a 5 fold increased brain uptake after Pgp/BCRP inhibition. Therefore, it can be assumed that [ 11 C]SNAP-7941 is a Pgp/BCRP substrate. No metabolites were found in brain. Conclusion: On the basis of these experiments with healthy rats, the suitability of [ 11 C]SNAP-7941 for the visualisation of central and peripheral MCHR1 remains speculative

  2. Role of Melanin in Oncogenesis

    Science.gov (United States)

    2011-08-01

    and validating the role of melanin in human melanoma pathobiology. Conclusions  Chronic production of excess melanin caused unique gene...vitro effects in a small sample size.  A long-term study with animal models and human patient specimens is needed to determine if excess melanin ...AD_________________ Award Number: W81XWH-10-1-0066 TITLE: Role of Melanin in Oncogenesis

  3. Antiradiation properties of melanin

    Directory of Open Access Journals (Sweden)

    Bushmanov A.Ju.

    2014-12-01

    Full Text Available Aim: to examine the therapeutic efficiency of melanin administered to mice after irradiation at lethal and sublethal doses. Material and methods: Survival and hematological states were studied on CD-1 mice receiving on acute or fractionated whole-body doses on X-rays or gamma-irradiation. Melanin soluble was given with water ad libitum from the first to the 30th-day after irradiation. Results. It was shown that melanin produced a significant therapeutic and protective-therapeutic action against acute radiation injury in the dose range 6,5-7,5 Gy (LD80-LD under our conditions. Cumulative survival melanin treated mice was increased to 14,4%, in control group — 1,9%. After fractionated injury (1 Gy daily, total dose 10 Gy all mice which consumed melanin remained alive, versus 43,7% in control. Melanin decreased radiation-induced damage and stimulated the hematopoiesis recovery after sublethal exposure (5Gy. Conclusion. The results permit to regard melanin as a therapeutic agent for treatment of radiation injuries.

  4. Demonstration of tyrosinase in the vitiligo skin of human beings by a sensitive fluorometric method as well as by 14C(U)-L-tyrosine incorporation into melanin

    International Nuclear Information System (INIS)

    Husain, I.; Vijayan, E.; Ramaiah, A.; Pasricha, J.S.; Madan, N.C.

    1982-01-01

    Tyrosinase activity (Monophenol, dihydroxyphenylalanine: oxygen oxidoreductase EC 1.14.18.1) in vitiligo and normal epidermal homogenates of skin from human beings was measured by estimating beta 3,4-dihydroxyphenylalanine (dopa) by a highly sensitive fluorometric method described in this paper. The tyrosine activity in the vitiligo skin was about 4 to 37% of corresponding normal skin. The activity of tyrosinase in normal human skin from different individuals and from different regions of the body was in the range of 4 to 140 picomoles of beta 3,4-dihydroxyphenylalanine formed per min/mg protein of epidermal homogenate. The enzyme from vitiligo and normal skin was severely inhibited by substance(s) of low molecular weight. The enzyme exhibits a lag of about 4 hr in the absence of added beta 3,4-dihydroxyphenylalanine and 1 hr in presence of 5 microM dopa. Tyrosinase from the normal and vitiligo skin was inhibited by excess concentration of tyrosine. The homogenates from vitiligo skin could synthesize melanin from C14(U)-L-Tyrosine. The rate of tyrosine incorporation into melanin by the epidermal homogenates is increased by 3,4-dihydroxyphenylalanine (dopa) disproportionate to its effect on tyrosinase activity. Based on the data presented in this paper it is concluded that melanocytes are present in the vitiligo skin. A tentative hypothesis is put forward to explain the lack of melanin synthesis by the vitiligo skin under in vivo conditions, although melanocytes are present

  5. Genetic deletion of melanin-concentrating hormone neurons impairs hippocampal short-term synaptic plasticity and hippocampal-dependent forms of short-term memory.

    Science.gov (United States)

    Le Barillier, Léa; Léger, Lucienne; Luppi, Pierre-Hervé; Fort, Patrice; Malleret, Gaël; Salin, Paul-Antoine

    2015-11-01

    The cognitive role of melanin-concentrating hormone (MCH) neurons, a neuronal population located in the mammalian postero-lateral hypothalamus sending projections to all cortical areas, remains poorly understood. Mainly activated during paradoxical sleep (PS), MCH neurons have been implicated in sleep regulation. The genetic deletion of the only known MCH receptor in rodent leads to an impairment of hippocampal dependent forms of memory and to an alteration of hippocampal long-term synaptic plasticity. By using MCH/ataxin3 mice, a genetic model characterized by a selective deletion of MCH neurons in the adult, we investigated the role of MCH neurons in hippocampal synaptic plasticity and hippocampal-dependent forms of memory. MCH/ataxin3 mice exhibited a deficit in the early part of both long-term potentiation and depression in the CA1 area of the hippocampus. Post-tetanic potentiation (PTP) was diminished while synaptic depression induced by repetitive stimulation was enhanced suggesting an alteration of pre-synaptic forms of short-term plasticity in these mice. Behaviorally, MCH/ataxin3 mice spent more time and showed a higher level of hesitation as compared to their controls in performing a short-term memory T-maze task, displayed retardation in acquiring a reference memory task in a Morris water maze, and showed a habituation deficit in an open field task. Deletion of MCH neurons could thus alter spatial short-term memory by impairing short-term plasticity in the hippocampus. Altogether, these findings could provide a cellular mechanism by which PS may facilitate memory encoding. Via MCH neuron activation, PS could prepare the day's learning by increasing and modulating short-term synaptic plasticity in the hippocampus. © 2015 Wiley Periodicals, Inc.

  6. Antidepressant effects of exercise are produced via suppression of hypocretin/orexin and melanin-concentrating hormone in the basolateral amygdala.

    Science.gov (United States)

    Kim, Tae-Kyung; Kim, Ji-Eun; Park, Jin-Young; Lee, Jung-Eun; Choi, Juli; Kim, Hannah; Lee, Eun-Hwa; Kim, Seung-Woo; Lee, Ja-Kyeong; Kang, Hyun-Sik; Han, Pyung-Lim

    2015-07-01

    Physical exercise is considered beneficial in the treatment of depression, but the underlying mechanism is not clearly understood. In the present study, we investigated the mechanism regulating antidepressant effects of exercise by focusing on the role of the amygdala using a well-defined animal model of depression. C57BL/6 mice treated with repeated restraint showed depression-like behaviors, which was counteracted by post-stress treatment with physical exercise. The two neuropeptides hypocretin/orexin (Hcrt/Orx) and melanin-concentrating hormone (MCH) were transcriptionally upregulated in the BLA after repeated stress, and their enhanced expression was downregulated by treatment with exercise, mirroring stress-induced depression-like behaviors and their reversal by exercise. Stereotaxic injection of either Hcrt/Orx peptide or MCH peptide within the BLA commonly increased phospho-CaMKIIα level and produced depression-like behaviors, mimicking the neural states in the BLA of mice subjected to repeated stress. In contrast, siRNA-mediated suppression of Hcrt/Orx or MCH in the BLA blocked stress-induced depression-like behaviors. Furthermore, siRNA-mediated inhibition of CaMKIIα in the BLA also counteracted stress-induced depression-like behaviors. Local injection of Hcrt/Orx peptide or MCH peptide within the BLA in exercise-treated animals blocked antidepressant-like effects of exercise. Together these results suggest that exercise produces antidepressant effects via suppression of Hcrt/Orx and MCH neural systems in the BLA. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Photothermal imaging of melanin

    Science.gov (United States)

    Kerimo, Josef; DiMarzio, Charles A.

    2013-02-01

    We present photothermal images of melanin using modulation with two laser beams. Strong melanin absorption followed by efficient nonradiative relaxation caused heating and an increase in temperature. This temperature effect was used as an imaging contrast to detect melanin. Melanin from several samples including Sepia officinalis, black human hair, and live zebra fish, were imaged with a high signal-to-noise ratio. For the imaging, we focused two near infrared laser beams (pump and probe) collinearly with different wavelengths and the pump was modulated in amplitude. The thermally induced variations in the refractive index, at the modulation frequency, were detected by the scattering of the probe beam. The Photothermal method brings several imaging benefits including the lack of background interference and the possibility of imaging for an extended period of time without photodamage to the melanin. The dependence of the photothermal signal on the laser power, modulation frequency, and spatial offset of the probe is discussed. The new photothermal imaging method is promising and provides background-free and label-free imaging of melanin and can be implemented with low-cost CW lasers.

  8. Melanin: A scavenger in gingival inflammation

    Directory of Open Access Journals (Sweden)

    S Nilima

    2011-01-01

    Full Text Available Background: One of the major direct or indirect targets of ultraviolet exposure of skin is the melanocyte or the melanin -forming cell. Epidermal melanocytes act as a trap for free radicals. Based on the protective role of melanocytes in medical literature, the role of melanin pigmentation in gingiva needs to be elucidated. Periodontal pathogens and their products demonstrate the ability to induce the generation of reactive oxygen species. Hence purpose of this study was to unravel the protective role of melanin (if any against the gingival inflammation. Materials and Methods: A total of 80 subjects; 20 in each group were selected. The selection of subjects regarding gingival pigmentation was based on Dummett′s scoring criteria 0, 3. A complete medical, dental history and an informed consent were obtained from the patients. After evaluation of clinical parameters the GCF was collected using microcapillary pipettes at the selected sites. IL-1β levels were quantitated using ELISA. Results: In non-pigmented healthy and gingivitis groups, there was a positive correlation between plaque index, gingival index and bleeding index versus IL-1β level: indicating an increase in the biochemical mediator of inflammation corresponding to an increase in the clinical parameters of inflammation. Also a positive correlation was found between the gingival index and bleeding index versus the IL-1β levels in the pigmented healthy group. The pigmented gingivitis groups showed a negative correlation between the plaque index, gingival index and bleeding index. Conclusions: The clinical markers of inflammation such as gingival index, bleeding index was of low numerical value in pigmented group than in the non-pigmented group, supposedly due to the protective action of melanin. The negative correlation of clinical markers of inflammation to the IL-1β levels in the pigmented gingivitis group could possibly be attributed to the protective role of melanins.

  9. Melanin determination by high performance liquid chromatography (HPLC) for K. marxianus

    Science.gov (United States)

    Ultraviolet light (UV) mutated K. marxianus was found to turn dark brown during a growth assay. This brown color was hypothesized to be melanin overproduction influenced by the UV exposure. Cell cultures were oxidized and HPLC analyzed to determine melanin concentrations. The resulting melanin con...

  10. Paradoxical (REM) sleep deprivation in mice using the small-platforms-over-water method: polysomnographic analyses and melanin-concentrating hormone and hypocretin/orexin neuronal activation before, during and after deprivation.

    Science.gov (United States)

    Arthaud, Sebastien; Varin, Christophe; Gay, Nadine; Libourel, Paul-Antoine; Chauveau, Frederic; Fort, Patrice; Luppi, Pierre-Herve; Peyron, Christelle

    2015-06-01

    Studying paradoxical sleep homeostasis requires the specific and efficient deprivation of paradoxical sleep and the evaluation of the subsequent recovery period. With this aim, the small-platforms-over-water technique has been used extensively in rats, but only rare studies were conducted in mice, with no sleep data reported during deprivation. Mice are used increasingly with the emergence of transgenic mice and technologies such as optogenetics, raising the need for a reliable method to manipulate paradoxical sleep. To fulfil this need, we refined this deprivation method and analysed vigilance states thoroughly during the entire protocol. We also studied activation of hypocretin/orexin and melanin-concentrating hormone neurones using Fos immunohistochemistry to verify whether mechanisms regulating paradoxical sleep in mice are similar to those in rats. We showed that 48 h of deprivation was highly efficient, with a residual amount of paradoxical sleep of only 2.2%. Slow wave sleep and wake quantities were similar to baseline, except during the first 4 h of deprivation, where slow wave sleep was strongly reduced. After deprivation, we observed a 124% increase in paradoxical sleep quantities during the first hour of rebound. In addition, 34% of hypocretin/orexin neurones were activated during deprivation, whereas melanin-concentrated hormone neurones were activated only during paradoxical sleep rebound. Corticosterone level showed a twofold increase after deprivation and returned to baseline level after 4 h of recovery. In summary, a fairly selective deprivation and a significant rebound of paradoxical sleep can be obtained in mice using the small-platforms-over-water method. As in rats, rebound is accompanied by a selective activation of melanin-concentrating hormone neurones. © 2014 European Sleep Research Society.

  11. Antibacterial Activity of Melanin from Cuttlefish and Squid Ink

    Directory of Open Access Journals (Sweden)

    Yuspihana Fitrial

    2017-08-01

    Full Text Available Marine environment comprises of many organism which are known to posses bioactive compound as a common means of self-defense or for the protection of eggs and embryos. Class Cephalopods (such as squidand cuttlefish are notable for their defences, such as jetting escape movements, changes in colouration, toxic venom and inking.This study aims to compare the antibacterial activity of melanin from cuttlefish ink (Sepia sp. with squid ink (Loligo sp. against E. coli. Extraction and purification studies were carried out on Sepia and Loligo melanin using a hydrochloric acid 0,5M treatment under mechanical.The melanins were obtained and further evaluated their activity by direct contact methods between melanin and E. coli in nutrient broth.Total microbes was counted by total plate count.Both inks also was tested their activity against E. coli. The results showed that melanin from cuttlefish and squid inks had inhibitory activity at concentrations of 10 mg / ml and 20 mg / mL, respectively reaching 99.99% against E. coli.The inks of both Cephalopods at the same concentration as melanin, did not show any inhibitory activity against E. coli.  The melanin of Sepia sp. have a higher antibacterial activity than the melanin of Loligo sp.

  12. The effects of Sophora angustifolia and other natural plant extracts on melanogenesis and melanin transfer in human skin cells.

    Science.gov (United States)

    Singh, Suman K; Baker, Richard; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond J

    2013-01-01

    Skin pigmentation is a multistep process of melanin synthesis by melanocytes, its transfer to recipient keratinocytes and its degradation. As dyspigmentation is a prominent marker of skin ageing, novel effective agents that modulate pigmentation safely are being sought for both clinical and cosmetic use. Here, a number of plant extracts were examined for their effect on melanogenesis (by melanin assay and Western blotting) and melanin transfer (by confocal immunomicroscopy of gp100-positive melanin granules in cocultures and by SEM analysis of filopodia), in human melanocytes and in cocultures with phototype-matched normal adult epidermal keratinocytes. Mulberry, Kiwi and Sophora extracts were assessed against isobutylmethylxanthine, hydroquinone, vitamin C and niacinamide. Compared with unstimulated control, all extracts significantly reduced melanogenesis in human melanoma cells and normal adult epidermal melanocytes. These extracts also reduced melanin transfer and reduced filopodia expression on melanocytes, similar to hydroquinone and niacinamide, indicating their effectiveness as multimode pigmentation actives. © 2013 John Wiley & Sons A/S.

  13. Ultraviolet B, melanin and mitochondrial DNA: Photo-damage in human epidermal keratinocytes and melanocytes modulated by alpha-melanocyte-stimulating hormone [version 1; referees: 2 approved

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    Markus Böhm

    2016-05-01

    Full Text Available Alpha-melanocyte-stimulating hormone (alpha-MSH increases melanogenesis and protects from UV-induced DNA damage. However, its effect on mitochondrial DNA (mtDNA damage is unknown. We have addressed this issue in a pilot study using human epidermal keratinocytes and melanocytes incubated with alpha-MSH and irradiated with UVB. Real-time touchdown PCR was used to quantify total and deleted mtDNA. The deletion detected encompassed the common deletion but was more sensitive to detection. There were 4.4 times more mtDNA copies in keratinocytes than in melanocytes. Irradiation alone did not affect copy numbers. Alpha-MSH slightly increased copy numbers in both cell types in the absence of UVB and caused a similar small decrease in copy number with dose in both cell types. Deleted copies were nearly twice as frequent in keratinocytes as in melanocytes. Alpha-MSH reduced the frequency of deleted copies by half in keratinocytes but not in melanocytes. UVB dose dependently led to an increase in the deleted copy number in alpha-MSH-treated melanocytes. UVB irradiation had little effect on deleted copy number in alpha-MSH-treated keratinocytes. In summary, alpha-MSH enhances mtDNA damage in melanocytes presumably by increased melanogenesis, while α-MSH is protective in keratinocytes, the more so in the absence of irradiation.

  14. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

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    Néstor Correa

    2017-07-01

    Full Text Available Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an important virulence factor. To evaluate if cryptococcal and human melanins have antifungal activity against Cryptococcus species they both were assayed for their antifungal properties and physico-chemical characters. Melanin extracts from human hair and different strains of C. neoformans (n = 4 and C. gattii (n = 4 were investigated. The following minimum inhibitory concentrations were found for different melanins against C. neoformans and C. gattii were (average/range: 13.7/(7.8–15.6 and 19.5/(15.6–31.2 μg/mL, respectively, for human melanin; 273.4/(125–>500 and 367.2/(125.5–>500 μg/mL for C. neoformans melanin and 125/(62.5–250 and 156.2/(62–250 μg/mL for C. gattii melanin. Using Scanning Electron Microscopy we observed that human melanin showed a compact conformation and cryptococcal melanins exposed an amorphous conformation. Infrared spectroscopy (FTIR showed some differences in the signals related to C-C bonds of the aromatic ring of the melanin monomers. High Performance Liquid Chromatography established differences in the chromatograms of fungal melanins extracts in comparison with human and synthetic melanin, particularly in the retention time of the main compound of fungal melanin extracts and also in the presence of minor unknown compounds. On the other hand, MALDI-TOF-MS analysis showed slight differences in the spectra, specifically the presence of a minor intensity ion in synthetic and human melanin, as well as in some fungal

  15. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies.

    Science.gov (United States)

    Correa, Néstor; Covarrubias, Cristian; Rodas, Paula I; Hermosilla, Germán; Olate, Verónica R; Valdés, Cristián; Meyer, Wieland; Magne, Fabien; Tapia, Cecilia V

    2017-01-01

    Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an important virulence factor. To evaluate if cryptococcal and human melanins have antifungal activity against Cryptococcus species they both were assayed for their antifungal properties and physico-chemical characters. Melanin extracts from human hair and different strains of C. neoformans ( n = 4) and C. gattii ( n = 4) were investigated. The following minimum inhibitory concentrations were found for different melanins against C. neoformans and C. gattii were (average/range): 13.7/(7.8-15.6) and 19.5/(15.6-31.2) μg/mL, respectively, for human melanin; 273.4/(125->500) and 367.2/(125.5->500) μg/mL for C. neoformans melanin and 125/(62.5-250) and 156.2/(62-250) μg/mL for C. gattii melanin. Using Scanning Electron Microscopy we observed that human melanin showed a compact conformation and cryptococcal melanins exposed an amorphous conformation. Infrared spectroscopy (FTIR) showed some differences in the signals related to C-C bonds of the aromatic ring of the melanin monomers. High Performance Liquid Chromatography established differences in the chromatograms of fungal melanins extracts in comparison with human and synthetic melanin, particularly in the retention time of the main compound of fungal melanin extracts and also in the presence of minor unknown compounds. On the other hand, MALDI-TOF-MS analysis showed slight differences in the spectra, specifically the presence of a minor intensity ion in synthetic and human melanin, as well as in some fungal melanin extracts. We

  16. Melanin fate in the human epidermis: a reassessment of how best to detect and analyse histologically.

    Science.gov (United States)

    Joly-Tonetti, Nicolas; Wibawa, Judata I D; Bell, Mike; Tobin, Desmond

    2016-07-01

    Melanin is the predominant pigment responsible for skin colour and is synthesized by the melanocyte in the basal layer of the epidermis and then transferred to surrounding keratinocytes. Despite its optical properties, melanin is barely detectable in unstained sections of human epidermis. However, identification and localization of melanin is of importance for the study of skin pigmentation in health and disease. Current methods for the histologic quantification of melanin are suboptimal and are associated with significant risk of misinterpretation. The aim of this study was to reassess the existing literature and to develop a more effective histological method of melanin quantification in human skin. Moreover, we confirm that Warthin-Starry (WS) stain provides a much more sensitive and more specific melanin detection method than the commonplace Fontana-Masson (FM) stain. For example, WS staining sensitivity allowed the visualization of melanin even in very pale Caucasian skin that was missed by FM or Von Kossa (VK) stains. From our reassessment of the histology-related literature, we conclude that so-called melanin dust is most likely an artifact of discoloration due to non-specific silver deposition in the stratum corneum. Unlike FM and VK, WS was not associated with this non-specific stratum corneum darkening, misinterpreted previously as 'degraded' melanin. Finally, WS melanin particle counts were largely similar to previously reported manual counts by transmission electron microscopy, in contrast to both FM and VK. Together these findings allow us to propose a new histology/Image J-informed method for the accurate and precise quantification of epidermal melanin in skin. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs.

    Science.gov (United States)

    Fernandes, Chantal; Prados-Rosales, Rafael; Silva, Branca M A; Nakouzi-Naranjo, Antonio; Zuzarte, Mónica; Chatterjee, Subhasish; Stark, Ruth E; Casadevall, Arturo; Gonçalves, Teresa

    2015-12-28

    The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Normal Morning Melanin-Concentrating Hormone Levels and No Association with Rapid Eye Movement or Non-Rapid Eye Movement Sleep Parameters in Narcolepsy Type 1 and Type 2

    DEFF Research Database (Denmark)

    Schrölkamp, Maren; Jennum, Poul J; Gammeltoft, Steen

    2017-01-01

    in rapid eye movement (REM) and non-rapid eye movement (NREM) sleep regulation. Hypocretin neurons reciprocally interact with MCH neurons. We hypothesized that altered MCH secretion contributes to the symptoms and sleep abnormalities of narcolepsy and that this is reflected in morning cerebrospinal fluid...... MCH levels. CONCLUSIONS: Our study shows that MCH levels in CSF collected in the morning are normal in narcolepsy and not associated with the clinical symptoms, REM sleep abnormalities, nor number of muscle movements during REM or NREM sleep of the patients. We conclude that morning lumbar CSF MCH......STUDY OBJECTIVES: Other than hypocretin-1 (HCRT-1) deficiency in narcolepsy type 1 (NT1), the neurochemical imbalance of NT1 and narcolepsy type 2 (NT2) with normal HCRT-1 levels is largely unknown. The neuropeptide melanin-concentrating hormone (MCH) is mainly secreted during sleep and is involved...

  19. Quantitative variation of melanins in alpaca (Lama pacos L.

    Directory of Open Access Journals (Sweden)

    Marco Antonini

    2011-07-01

    Full Text Available The amount of melanin pigments was investigated in 95 Peruvian alpaca, representative of six different fleece colours, by means of spectrophotometric assays: SpEM (Spectrophoto­metric Eumelanin, SpPM (Spectrophotometric Pheomelanin, SpASM (Spectrophotometric Alkali Soluble Melanin, and SpTM (Spectro­photometric Total Melanin. It was found that these melanin pigments were suitable for identifying three homogeneous groups, each consisting of two closely related colours. A low, an intermediate, and a high amount of SpASM, SpTM, and SpPM characterize pinkish grey and light reddish brown, brown and reddish brown, dark reddish brown and black fleeces, respectively. SpEM and SpTM provide a further split within this latter group; higher concentrations of these pigments distinguish black fleece from dark reddish brown.

  20. Ebselen is a new skin depigmenting agent that inhibits melanin biosynthesis and melanosomal transfer.

    Science.gov (United States)

    Kasraee, Behrooz; Nikolic, Damjan S; Salomon, Denis; Carraux, Pierre; Fontao, Lionel; Piguet, Vincent; Omrani, Gholamhossein R; Sorg, Olivier; Saurat, Jean-Hilaire

    2012-01-01

    We assessed the ability of ebselen, a glutathione peroxidase mimic, to reduce pigmentation in various models. In murine B16 melanocytes, 25 μm ebselen inhibited melanogenesis and induced a depolymerisation of actin filaments. In co-cultures of B16 melanocytes with BDVII keratinocytes, a pretreatment of melanocytes with ebselen resulted in a strong inhibition of melanosome transfer to keratinocytes, as shown under optical and electron microscopy. In reconstructed epidermis, topical 0.5% ebselen led to a twofold decrease of melanin without affecting the density of active melanocytes. A similar result was obtained with topical 0.5% ebselen in black guinea pig ears. Ebselen induced a decrease of epidermal melanin parallel to a localisation of melanin and melanosomes in the basal layer. Ebselen appears as a new depigmenting compound that inhibits melanin synthesis and melanosome transfer to keratinocytes. © 2011 John Wiley & Sons A/S.

  1. Syndecan-2 regulates melanin synthesis via protein kinase C βII-mediated tyrosinase activation.

    Science.gov (United States)

    Jung, Hyejung; Chung, Heesung; Chang, Sung Eun; Choi, Sora; Han, Inn-Oc; Kang, Duk-Hee; Oh, Eok-Soo

    2014-05-01

    Syndecan-2, a transmembrane heparan sulfate proteoglycan that is highly expressed in melanoma cells, regulates melanoma cell functions (e.g. migration). Since melanoma is a malignant tumor of melanocytes, which largely function to synthesize melanin, we investigated the possible involvement of syndecan-2 in melanogenesis. Syndecan-2 expression was increased in human skin melanoma tissues compared with normal skin. In both mouse and human melanoma cells, siRNA-mediated knockdown of syndecan-2 was associated with reduced melanin synthesis, whereas overexpression of syndecan-2 increased melanin synthesis. Similar effects were also detected in human primary epidermal melanocytes. Syndecan-2 expression did not affect the expression of tyrosinase, a key enzyme in melanin synthesis, but instead enhanced the enzymatic activity of tyrosinase by increasing the membrane and melanosome localization of its regulator, protein kinase CβII. Furthermore, UVB caused increased syndecan-2 expression, and this up-regulation of syndecan-2 was required for UVB-induced melanin synthesis. Taken together, these data suggest that syndecan-2 regulates melanin synthesis and could be a potential therapeutic target for treating melanin-associated diseases. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Melanin-Based Functional Materials

    Directory of Open Access Journals (Sweden)

    Marco d’Ischia

    2018-01-01

    Full Text Available Melanin biopolymers are currently the focus of growing interest for a broad range of applications at the cutting edge of biomedical research and technology. This Special Issue presents a collection of papers dealing with melanin-type materials, e.g., polydopamine, for classic and innovative applications, offering a stimulating perspective of current trends in the field. Besides basic scientists, the Special Issue is directed to researchers from industries and companies that are willing to invest in melanin research for innovative and inspiring solutions.

  3. Sponge-Associated Bacteria Produce Non-cytotoxic Melanin Which Protects Animal Cells from Photo-Toxicity.

    Science.gov (United States)

    Vijayan, Vijitha; Jasmin, Chekidhenkuzhiyil; Anas, Abdulaziz; Parakkaparambil Kuttan, Sreelakshmi; Vinothkumar, Saradavey; Perunninakulath Subrayan, Parameswaran; Nair, Shanta

    2017-09-01

    Melanin is a photo-protective polymer found in many organisms. Our research shows that the bacteria associated with darkly pigmented sponges (Haliclona pigmentifera, Sigmadocia pumila, Fasciospongia cavernosa, Spongia officinalis, and Callyspongia diffusa) secrete non-cytotoxic melanin, with antioxidant activity that protects animal cells from photo-toxicity. Out of 156 bacterial strains screened, 22 produced melanin and these melanin-producing bacteria (MPB) were identified as Vibrio spp., Providencia sp., Bacillus sp., Shewanella sp., Staphylococcus sp., Planococcus sp., Salinococcus sp., and Glutamicibacter sp. Maximum melanin production was exhibited by Vibrio alginolyticus Marine Microbial Reference Facility (MMRF) 534 (50 mg ml -1 ), followed by two isolates of Vibrio harveyi MMRF 535 (40 mg ml -1 ) and MMRF 546 (30 mg ml -1 ). Using pathway inhibition assay and FT-IR spectral analysis, we identified the melanin secreted into the culture medium of MPB as 1,8-dihydroxynaphthalene-melanin. The bacterial melanin was non-cytotoxic to mouse fibroblast L929 cells and brine shrimps up to a concentration of 200 and 500 ppm, respectively. Bacterial melanin showed antioxidant activity at very low concentration (IC 50 -9.0 ppm) and at 50 ppm, melanin protected L929 cells from UV-induced intracellular reactive oxygen stress. Our study proposes sponge-associated bacteria as a potential source of non-cytotoxic melanin with antioxidant potentials.

  4. B16F1 melanoma cells upregulate melanin synthesis after photodynamic therapy

    International Nuclear Information System (INIS)

    Moder, A.; Gassner, F.; Krammer, B.; Thalhamer, J.; Hammerl, P.

    2003-01-01

    Full text: The success of photodynamic therapy (PDT) of melanotic tumors is severely limited by insufficient penetration of light into deeper tissue layers. In this study, we analyzed the effect of PDT on the melanin production of the melanoma cell line B16F1. In vitro, these cells produce only little melanin. However, after PDT we found a dramatic elevation in intracellular melanin. Melanin production increased with, both, the concentration of the sensitizing agent and the light dose, and was found to continue for several hours after cell death. PDT-induced melanin synthesis was not prevented by the addition of cycloheximide or actinomycin D prior to irradiation, indicating that de-novo protein synthesis and transcriptional activity are not required for this effect. We also analyzed tyrosinase activity, a key enzyme in melanin biosynthesis, in PDT-treated B16 cells. Tyrosinase activity was found in PDT-treated as well as untreated cells. Cell fractionation experiments showed that tyrosinase was present in the cytosolic as well as the melanosomal fractions of, both, PDT-treated (melanin-high) as well as untreated (melanin-low) cells. These data indicate that PDT-induced production of melanin is not controlled at the transcriptional or translational level and that tyrosinase is not likely an essential regulator in this process. (author)

  5. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

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    Rodrigo Almeida-Paes

    Full Text Available Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC and minimal fungicidal concentrations (MFC of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  6. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies. PMID:27031728

  7. Melanins Protect Sporothrix brasiliensis and Sporothrix schenckii from the Antifungal Effects of Terbinafine.

    Science.gov (United States)

    Almeida-Paes, Rodrigo; Figueiredo-Carvalho, Maria Helena Galdino; Brito-Santos, Fábio; Almeida-Silva, Fernando; Oliveira, Manoel Marques Evangelista; Zancopé-Oliveira, Rosely Maria

    2016-01-01

    Terbinafine is a recommended therapeutic alternative for patients with sporotrichosis who cannot use itraconazole due to drug interactions or side effects. Melanins are involved in resistance to antifungal drugs and Sporothrix species produce three different types of melanin. Therefore, in this study we evaluated whether Sporothrix melanins impact the efficacy of antifungal drugs. Minimal inhibitory concentrations (MIC) and minimal fungicidal concentrations (MFC) of two Sporothrix brasiliensis and four Sporothrix schenckii strains grown in the presence of the melanin precursors L-DOPA and L-tyrosine were similar to the MIC determined by the CLSI standard protocol for S. schenckii susceptibility to amphotericin B, ketoconazole, itraconazole or terbinafine. When MICs were determined in the presence of inhibitors to three pathways of melanin synthesis, we observed, in four strains, an increase in terbinafine susceptibility in the presence of tricyclazole, a DHN-melanin inhibitor. In addition, one S. schenckii strain grown in the presence of L-DOPA had a higher MFC value when compared to the control. Growth curves in presence of 2×MIC concentrations of terbinafine showed that pyomelanin and, to a lesser extent, eumelanin were able to protect the fungi against the fungicidal effect of this antifungal drug. Our results suggest that melanin protects the major pathogenic species of the Sporothrix complex from the effects of terbinafine and that the development of new antifungal drugs targeting melanin synthesis may improve sporotrichosis therapies.

  8. EFFECT OF CADMIUM(II) ON FREE RADICALS IN DOPA-MELANIN TESTED BY EPR SPECTROSCOPY.

    Science.gov (United States)

    Zdybel, Magdalena; Pilawa, Barbara; Chodurek, Ewa

    2015-01-01

    Electron paramagnetic resonance (EPR) spectroscopy may be applied to examine interactions of melanin with metal ions and drugs. In this work EPR method was used to examination of changes in free radical system of DOPA-melanin--the model eumelanin after complexing with diamagnetic cadmium(II) ions. Cadmium(II) may affect free radicals in melanin and drugs binding by this polymer, so the knowledge of modification of properties and free radical concentration in melanin is important to pharmacy. The effect of cadmium(II) in different concentrations on free radicals in DOPA-melanin was determined. EPR spectra of DOPA-melanin, and DOPA-melanin complexes with cadmium(II) were measured by an X-band (9.3 GHz) EPR spectrometer produced by Radiopan (Poznań, Poland) and the Rapid Scan Unit from Jagmar (Krak6w, Poland). The DOPA (3,4-dihydroxyphenylalanine) to metal ions molar ratios in the reaction mixtures were 2:1, 1:1, and 1: 2. High concentrations of o-semiquinone (g ~2.0040) free radicals (~10(21)-10(22) spin/g) characterize DOPA-melanin and its complexes with cadmium(II). Formation of melanin complexes with cadmium(II) increase free radical concentration in DOPA-melanin. The highest free radical concentration was obtained for DOPA-melanin-cadmium(II) (1:1) complexes. Broad EPR lines with linewidths: 0.37-0.73 mT, were measured. Linewidths increase after binding of cadmium(II) to melanin. Changes of integral intensities and linewidths with increasing microwave power indicate the homogeneous broadening of EPR lines, independently on the metal ion concentration. Slow spin-lattice relaxation processes existed in all the tested samples, their EPR lines saturated at low microwave powers. Cadmium(II) causes fastening of spin-lattice relaxation processes in DOPA-melanin. The EPR results bring to light the effect of cadmium(II) on free radicals in melanin, and probably as the consequence on drug binding to eumelanin.

  9. [Progress in epidermal stem cells].

    Science.gov (United States)

    Wang, Li-Juan; Wang, You-Liang; Yang, Xiao

    2010-03-01

    Mammalian skin epidermis contains different epidermal stem cell pools which contribute to the homeostasis and repair of skin epithelium. Epidermal stem cells possess two essential features common to all stem cells: self-renewal and differentiation. Disturbing the balance between self-renewal and differentiation of epidermal stem cell often causes tumors or other skin diseases. Epidermal stem cell niches provide a special microenvironment that maintains a balance of stem cell quiescence and activity. This review primarily concentrates on the following points of the epidermal stem cells: the existing evidences, the self-renewal and differentiation, the division pattern, the signal pathways regulating self-renewal and differentiation, and the microenvironment (niche) and macroenvironment maintaining the homeostasis of stem cells.

  10. New Poly(lactic acid Active Packaging Composite Films Incorporated with Fungal Melanin

    Directory of Open Access Journals (Sweden)

    Łukasz Łopusiewicz

    2018-04-01

    Full Text Available In this work, fungal melanin was used for the first time to prepare poly(lactic acid-based composites. The films of various melanin concentrations (0.025%, 0.05% and 0.2% w/w were prepared using an extrusion method. The mechanical, antioxidant, antimicrobial, water vapor and UV-Vis barrier properties, as well as available polyphenolics on the surface, were studied. FT-IR and Raman spectroscopy studies were carried out to analyze the chemical composition of the resulting films. The hydrophobicity, color response, thermal, optical properties, and opacity values were also determined. The results of this study show that the addition of fungal melanin to poly(lactic acid (PLA as a modifier influenced mechanical and water vapor barrier properties depending on melanin concentration. In low concentration, melanin enhanced the mechanical and barrier properties of the modified films, but in larger amounts, the properties were decreased. The UV-Vis barrier properties of PLA/melanin composites were marginally improved. Differential Scanning Calorimetry (DSC analysis indicated that crystallinity of PLA increased by the addition of melanin, but this did not affect the thermal stability of the films. Modified PLA/melanin films showed good antioxidant activity and were active against Enterococcus faecalis, Pseudomonas aeruginosa and Pseudomonas putida. The addition of melanin caused changes in color values, decreasing lightness and increasing the redness and yellowness of films. Based on the results of this study, fungal melanin has good potential to be exploited as a value-added modifier that can improve the overall properties of PLA.

  11. Effects of melanin on the accumulation of exopolysaccharides by Aureobasidium pullulans grown on nitrate.

    Science.gov (United States)

    Zheng, Weifa; Campbell, Bradley S; McDougall, Barbara M; Seviour, Robert J

    2008-11-01

    Aureobasidium pullulans produced pullulan and melanin when grown in medium containing low nitrate levels. With high nitrate concentrations, however, this fungus produced a mixture of exopolysaccharides (EPS) without melanin synthesis. At 0.78 g l(-1) N as nitrate, where no melanin synthesis occurred, maximum EPS yields reached 6.92 g l(-1) and then decreased to the final yield of 2.36 g l(-1). Following melanin addition (0.1 g l(-1)), yields reached 7.02 g l(-1) at 48 h and fell to a final yield of 5.21 g l(-1). The EPS produced in high nitrate medium contained both pullulan and (1-->3)-beta-glucan, but only pullulan was produced with melanin-supplementation. With melanin addition a doubling of (1-->3)-beta-glucanase activity was observed in high nitrate medium compared to that without supplementation. On the other hand amylolytic activities disappeared in medium with melanin production or addition. Culture filtrates sustained a higher reducing capacity (RC) when melanin was present. Low RC appeared to reduce (1-->3)-beta-glucanase activity and increase amylolytic activities. Thus, higher RC appears to inhibit production/activity of amylose-degrading enzymes capable of degrading pullulan, and stimulates (1-->3)-beta-glucanase synthesis/activity, leading to a preferential accumulation of pullulan.

  12. Amine-free melanin-concentrating hormone receptor 1 antagonists: Novel 1-(1H-benzimidazol-6-yl)pyridin-2(1H)-one derivatives and design to avoid CYP3A4 time-dependent inhibition.

    Science.gov (United States)

    Igawa, Hideyuki; Takahashi, Masashi; Shirasaki, Mikio; Kakegawa, Keiko; Kina, Asato; Ikoma, Minoru; Aida, Jumpei; Yasuma, Tsuneo; Okuda, Shoki; Kawata, Yayoi; Noguchi, Toshihiro; Yamamoto, Syunsuke; Fujioka, Yasushi; Kundu, Mrinalkanti; Khamrai, Uttam; Nakayama, Masaharu; Nagisa, Yasutaka; Kasai, Shizuo; Maekawa, Tsuyoshi

    2016-06-01

    Melanin-concentrating hormone (MCH) is an attractive target for antiobesity agents, and numerous drug discovery programs are dedicated to finding small-molecule MCH receptor 1 (MCHR1) antagonists. We recently reported novel pyridine-2(1H)-ones as aliphatic amine-free MCHR1 antagonists that structurally featured an imidazo[1,2-a]pyridine-based bicyclic motif. To investigate imidazopyridine variants with lower basicity and less potential to inhibit cytochrome P450 3A4 (CYP3A4), we designed pyridine-2(1H)-ones bearing various less basic bicyclic motifs. Among these, a lead compound 6a bearing a 1H-benzimidazole motif showed comparable binding affinity to MCHR1 to the corresponding imidazopyridine derivative 1. Optimization of 6a afforded a series of potent thiophene derivatives (6q-u); however, most of these were found to cause time-dependent inhibition (TDI) of CYP3A4. As bioactivation of thiophenes to form sulfoxide or epoxide species was considered to be a major cause of CYP3A4 TDI, we introduced electron withdrawing groups on the thiophene and found that a CF3 group on the ring or a Cl adjacent to the sulfur atom helped prevent CYP3A4 TDI. Consequently, 4-[(5-chlorothiophen-2-yl)methoxy]-1-(2-cyclopropyl-1-methyl-1H-benzimidazol-6-yl)pyridin-2(1H)-one (6s) was identified as a potent MCHR1 antagonist without the risk of CYP3A4 TDI, which exhibited a promising safety profile including low CYP3A4 inhibition and exerted significant antiobesity effects in diet-induced obese F344 rats. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Real-time visualization of melanin granules in normal human skin using combined multiphoton and reflectance confocal microscopy.

    Science.gov (United States)

    Majdzadeh, Ali; Lee, Anthony M D; Wang, Hequn; Lui, Harvey; McLean, David I; Crawford, Richard I; Zloty, David; Zeng, Haishan

    2015-05-01

    Recent advances in biomedical optics have enabled dermal and epidermal components to be visualized at subcellular resolution and assessed noninvasively. Multiphoton microscopy (MPM) and reflectance confocal microscopy (RCM) are noninvasive imaging modalities that have demonstrated promising results in imaging skin micromorphology, and which provide complementary information regarding skin components. This study assesses whether combined MPM/RCM can visualize intracellular and extracellular melanin granules in the epidermis and dermis of normal human skin. We perform MPM and RCM imaging of in vivo and ex vivo skin in the infrared domain. The inherent three-dimensional optical sectioning capability of MPM/RCM is used to image high-contrast granular features across skin depths ranging from 50 to 90 μm. The optical images thus obtained were correlated with conventional histologic examination including melanin-specific staining of ex vivo specimens. MPM revealed highly fluorescent granular structures below the dermal-epidermal junction (DEJ) region. Histochemical staining also demonstrated melanin-containing granules that correlate well in size and location with the granular fluorescent structures observed in MPM. Furthermore, the MPM fluorescence excitation wavelength and RCM reflectance of cell culture-derived melanin were equivalent to those of the granules. This study suggests that MPM can noninvasively visualize and quantify subepidermal melanin in situ. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Sexual dimorphism in melanin pigmentation, feather coloration and its heritability in the barn swallow (Hirundo rustica.

    Directory of Open Access Journals (Sweden)

    Nicola Saino

    Full Text Available Melanin is the main pigment in animal coloration and considerable variation in the concentrations of the two melanin forms (pheo- and eumlanin in pigmented tissues exists among populations and individuals. Melanin-based coloration is receiving increasing attention particularly in socio-sexual communication contexts because the melanocortin system has been hypothesized to provide a mechanistic basis for covariation between coloration and fitness traits. However, with few notable exceptions, little detailed information is available on inter-individual and inter-population variation in melanin pigmentation and on its environmental, genetic and ontogenetic components. Here, we investigate melanin-based coloration in an Italian population of a passerine bird, the barn swallow (Hirundo rustica rustica, its sex- and age-related variation, and heritability. The concentrations of eu- and pheomelanin in the throat (brown and belly (white-to-brownish feathers differed between sexes but not according to age. The relative concentration of either melanin (Pheo:Eu differed between sexes in throat but not in belly feathers, and the concentrations in males compared to females were larger in belly than in throat feathers. There were weak correlations between the concentrations of melanins within as well as among plumage regions. Coloration of belly feathers was predicted by the concentration of both melanins whereas coloration of throat feathers was only predicted by pheomelanin in females. In addition, Pheo:Eu predicted coloration of throat feathers in females and that of belly feathers in males. Finally, we found high heritability of color of throat feathers. Melanization was found to differ from that recorded in Hirundo rustica rustica from Scotland or from H. r. erythrogaster from North America. Hence, present results show that pigmentation strategies vary in a complex manner according to sex and plumage region, and also among geographical populations

  15. Molecular mechanisms involved in the inhibition of tumor cells proliferation exposed to elevated concentrations of the epidermal growth factor

    International Nuclear Information System (INIS)

    Guillen, Isabel A; Berlanga, Jorge; Camacho, Hanlet

    2013-01-01

    The EGF promotes inhibition of cell proliferation in vitro and in vivo models depending on its concentration, application schema and the type of tumor cells on which it acts. Our research hypothesis was based on the fact that the EGF varies the expression of genes involved in a negative regulation of tumor cell lines proliferation carrying high levels of its receptor (EGFR). Our objectives were, to obtain information about the effect of EGF on tumor cell proliferation in vitro and in vivo models and, know the gene expression patterns of a group of genes involved in cancer signaling pathways and EGFR. The results showed that EGF at nanomolar concentrations inhibits the tumor cells proliferation bearing high levels of EGFR and, promotes the survival of treated animals, establishing a direct relationship between the inhibition of cell proliferation, high concentrations of EGF and, high amount of EGFR in the cells. The differential gene expression profile showed a variation in a group of genes which exert a powerful control over the cell cycle progression, gene transcription and apoptosis. It was concluded that the inhibition of tumor cell proliferation by the action of EGF is due to activation of molecular mechanisms controlling cell cycle progression. This work won the Annual Award of the Cuban Academy of Sciences in 2012

  16. Variation of Human Hairiness: A Possible Adaptation to Solar Radiation and Melanin

    Directory of Open Access Journals (Sweden)

    Dhugga Amrita

    2014-07-01

    Full Text Available Many theories have been advanced to explain human hairlessness, however, there is no consensus. This study of 76 males observed that skin reflectance measuring skin colouration and melanin pigmentation correlated with hair size and follicle density. Individuals with a greater concentration of melanin within the superficial layer of the skin had a lower follicle density and smaller sizes of hairs. In contrast, individuals with a lower melanin concentration and lighter skin colour had a full range of hairiness. This leads to the suggestion that over the course of human evolution, high concentrations of melanin in consistently exposed to ultraviolet radiation areas developed first and that hair loss was a consequence of competition in the skin between melanin production and hair growth. Darker pigmented skin and lower follicle density are significantly correlated (R2=0.283; p<0.05. Individuals with darker skin had a mean of 4.91 follicles per cm2 whereas those with lighter skin reflectance had 11.20 follicles per cm2. This suggests that increased concentrations of melanin in the basal layer of the epidermis may limit hairiness by negatively influencing the skin's ability to produce hair.

  17. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

    Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

  18. Characterization and biological activities of extracellular melanin produced by Schizophyllum commune (Fries).

    Science.gov (United States)

    Arun, G; Eyini, M; Gunasekaran, P

    2015-06-01

    Melanins are enigmatic pigments produced by a wide variety of microorganisms including bacteria and fungi. Here, we have isolated and characterized extracellular melanin from mushroom fungus, Schizophyllum commune. The extracellular dark pigment produced by the broth culture of S. commune, after 21 days of incubation was recovered by hot acid-alkali treatment. The melanin nature of the pigment was characterized by biochemical tests and further, confirmed by UV, IR, EPR, NMR and MALDI-TOF Mass Spectra. Extracellular melanin, at 100 μg/ml, showed significant antibacterial activity against Escherichia coli, Bacillus subtilis, Klebsiella pneumoniae and Pseudomonas fluorescens and antifungal activity against Trichophyton simii and T. rubrum. At a concentration of 50 μg/ml, melanin showed high free radical scavenging activity of DPPH (2,2-diphenyl-1-picrylhydrazyl) indicating its antioxidant potential. It showed concentration dependent inhibition of cell proliferation of Human Epidermoid Larynx Carcinoma Cell Line (HEP-2). This study has demonstrated characterization of melanin from basidiomycetes mushroom fungus, Schizophyllum commune and its applications.

  19. Spiders do have melanin after all.

    Science.gov (United States)

    Hsiung, Bor-Kai; Blackledge, Todd A; Shawkey, Matthew D

    2015-11-01

    Melanin pigments are broadly distributed in nature - from bacteria to fungi to plants and animals. However, many previous attempts to identify melanins in spiders were unsuccessful, suggesting that these otherwise ubiquitous pigments were lost during spider evolution. Yet, spiders exhibit many dark colours similar to those produced by melanins in other organisms, and the low solubility of melanins makes isolation and characterization difficult. Therefore, whether melanins are truly absent or have simply not yet been detected is an open question. Raman spectroscopy provides a reliable way to detect melanins in situ, without the need for isolation. In this study, we document the presence of eumelanin in diverse species of spiders using confocal Raman microspectroscopy. Comparisons of spectra with theoretically calculated data falsify the previous hypothesis that dark colours are produced solely by ommochromes in spiders. Our data indicate that melanins are present in spiders and further supporting that they are present in most living organisms. © 2015. Published by The Company of Biologists Ltd.

  20. Evaluation of melanin production by Sporothrix luriei

    Directory of Open Access Journals (Sweden)

    Ingrid Ludmilla Rodrigues Cruz

    Full Text Available There is a paucity of studies on the cell biology of Sporothrix luriei, the less common of the pathogenic Sporothrix species worldwide. The production of DHN-melanin, eumelanin, and pyomelanin were evaluated on the mycelial and yeast forms of the S. luriei ATCC 18616 strain. The mycelial form of this species produced only pyomelanin, which protected the fungus against environmental stressors such as ultraviolet light, heat, and cold. The yeast form was unable to produce any of the tested melanin types. The lack of melanin in the parasitic form of S. luriei may be an explanation for its low frequency in human infections.

  1. Evaluation of melanin production by Sporothrix luriei.

    Science.gov (United States)

    Cruz, Ingrid Ludmilla Rodrigues; Figueiredo-Carvalho, Maria Helena Galdino; Zancopé-Oliveira, Rosely Maria; Almeida-Paes, Rodrigo

    2018-01-01

    There is a paucity of studies on the cell biology of Sporothrix luriei, the less common of the pathogenic Sporothrix species worldwide. The production of DHN-melanin, eumelanin, and pyomelanin were evaluated on the mycelial and yeast forms of the S. luriei ATCC 18616 strain. The mycelial form of this species produced only pyomelanin, which protected the fungus against environmental stressors such as ultraviolet light, heat, and cold. The yeast form was unable to produce any of the tested melanin types. The lack of melanin in the parasitic form of S. luriei may be an explanation for its low frequency in human infections.

  2. Andrographolide suppresses melanin synthesis through Akt/GSK3β/β-catenin signal pathway.

    Science.gov (United States)

    Zhu, Ping-Ya; Yin, Wei-Han; Wang, Meng-Ran; Dang, Yong-Yan; Ye, Xi-Yun

    2015-07-01

    Tyrosinase (TYR) is the key enzyme controlling the production of melanin. Very few papers have reported that andrographolide can inhibit melanin content. To investigate the effects of andrographolide on melanin synthesis. Cell viability, melanin content, TYR activity, transcriptional and protein expression levels of TYR family and other kinds of proteins involved in melanogenesis were measured after the treatments of andrographolide. It was found that andrographolide decreased melanin content, TYR activity and transcriptional and protein expression of TYR family and microphthalmia-associated transcription factor (MITF) in B16F10 melanoma cells. Data showed andrographolide also decreased melanin content and TYR content in ultraviolet B (UVB) irradiation induced brown guinea pigs. Moreover, we found that melanin content and TYR activity were effectively inhibited in Human Epidermis Melanocyte (HEM) treated with andrographolide at the medium concentrations without apparent effect on cell viability. Results in experiments treated with MG-132 or cycloheximide (CHX) showed that andrographolide lowered the content of β-catenin in cell nucleus resulting from accelerating the degradation of β-catenin. Phosphorylation of glycogen synthase kinase 3β (GSK3β) and Akt decreased simultaneously. 6-Bromoindirubin-3'-oxime (BIO, inhibitor of GSK3β) and insulin-like growth factors-1 (IGF-1, activator of Akt) could reverse the decline of β-catenin in B16F10 cells induced by andrographolide. These results demonstrate that andrographolide can effectively suppress melanin content and TYR activity in B16F10 cells, HEM cells and UVB-induced brown guinea pig skin by decreasing phosphorylation of GSK3β dependent on Akt, promoting the degradation of β-catenin, inhibiting β-catenin into the nucleus and decreasing the expression of MITF and TYR family. Data indicate that andrographolide may be a potential whiting agent which can have great market in cosmetics and in clinical such as

  3. Nitroxides as redox probes of melanins: dark-induced and photoinduced changes in redox equilibria

    International Nuclear Information System (INIS)

    Sarna, T.; Korytowski, W.; Sealy, R.C.

    1985-01-01

    The interaction of nitroxide free radicals and their reduced products (hydroxylamines) with synthetic and natural melanins has been studied. Electron spin resonance spectroscopy was used to measure changes in radical concentration in the dark and during irradiation with visible or uv light. Some reduction of nitroxide occurs in the dark, and is reversible: the nitroxide can be completely regenerated by the one-electron oxidant ferricyanide. The kinetics of the process depend strongly on radical charge and pH. For positively charged nitroxides the rate is much faster than for either neutral or anionic radicals. At pH 10 the rate is about 20 times faster than at pH 5. Oxidation of hydroxylamine also can occur so that a redox equilibrium is established. The equilibrium constant has been estimated for the reaction between a nitroxide and melanin from autoxidation of 3,4-dihydroxyphenylalanine. Results are also dependent upon the type of melanin used and chemical modification (oxidation or reduction) of the melanin. Redox equilibria are altered during irradiation with either visible or uv light. Rapid oxidation of hydroxylamine to nitroxide is apparent, together with a slower reduction of nitroxide. Action spectra for these processes are related to those for melanin radical production and oxygen consumption in nitroxide-free melanin systems. Reduction of nitroxide is inhibited by oxygen, suggesting a competition between nitroxide and oxygen for photoinduced reducing equivalents

  4. Does melanin matter in the dark?

    Science.gov (United States)

    Płonka, Przemysław M; Picardo, Mauro; Slominski, Andrzej T

    2017-07-01

    In living cells, melanin pigment is formed within melanosomes, which not only protect the cells from autodestruction, but also serve as second messenger organelles regulating important skin functions, with melanocytes acting as primary sensory and regulatory cells of the epidermis. Yet, one can argue that skin melanin, which may negatively affect cellular homeostasis in melanoma, really exerts protective functions. Consequently, the actual functions of melanin and the melanogenic pathway in skin biology remains enigmatic. Yet, the solution of this riddle seems simple - to check the actual influence of natural melanin on skin cells in the dark. Since many interesting hypotheses and theories put forward in this respect did not survive confrontation with the experiment, a leading pigment research group from Naples was brave to "jump off the cliff" by confronting theory with experimental reality. They showed that, in the dark, human hair-derived melanin promotes inflammatory responses in keratinocytes, lowers their viability, promotes oxidative stress, and that pheomelanin does so more strongly than eumelanin. Thus, pheomelanin hardly protects red-haired individuals, even when avoiding the sun. Black hairs do not do much better either, unless they undergo graying. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Loss of Melanin by Eye Retinal Pigment Epithelium Cells Is Associated with Its Oxidative Destruction in Melanolipofuscin Granules.

    Science.gov (United States)

    Dontsov, A E; Sakina, N L; Ostrovsky, M A

    2017-08-01

    The effect of superoxide radicals on melanin destruction and degradation of melanosomes isolated from cells of retinal pigment epithelium (RPE) of the human eye was studied. We found that potassium superoxide causes destruction of melanin in melanosomes of human and bovine RPE, as well as destruction of melanin from the ink bag of squid, with the formation of fluorescent decay products having an emission maximum at 520-525 nm. The initial kinetics of the accumulation of the fluorescent decay products is linear. Superoxide radicals lead simultaneously to a decrease in the number of melanosomes and to a decrease in concentration of paramagnetic centers in them. Complete degradation of melanosomes leads to the formation of a transparent solution containing dissolved proteins and melanin degradation products that do not exhibit paramagnetic properties. To completely degrade one melanosome of human RPE, 650 ± 100 fmol of superoxide are sufficient. The concentration of paramagnetic centers in a melanolipofuscin granule of human RPE is on average 32.5 ± 10.4% (p melanin undergoing a destruction process in these granules. RPE cells also contain intermediate granules that have an EPR signal with a lower intensity than that of melanolipofuscin granules, but higher than that of lipofuscin granules. This signal is due to the presence of residual melanin in these granules. Irradiation of a mixture of melanosomes with lipofuscin granules with blue light (450 nm), in contrast to irradiation of only melanosomes, results in the appearance of fluorescent melanin degradation products. We suggest that one of the main mechanisms of age-related decrease in melanin concentration in human RPE cells is its destruction in melanolipofuscin granules under the action of superoxide radicals formed during photoinduced oxygen reduction by lipofuscin fluorophores.

  6. Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Gledhill, Karl; Guo, Zongyou; Umegaki-Arao, Noriko; Higgins, Claire A; Itoh, Munenari; Christiano, Angela M

    2015-01-01

    The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs) present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

  7. Melanin Transfer in Human 3D Skin Equivalents Generated Exclusively from Induced Pluripotent Stem Cells.

    Directory of Open Access Journals (Sweden)

    Karl Gledhill

    Full Text Available The current utility of 3D skin equivalents is limited by the fact that existing models fail to recapitulate the cellular complexity of human skin. They often contain few cell types and no appendages, in part because many cells found in the skin are difficult to isolate from intact tissue and cannot be expanded in culture. Induced pluripotent stem cells (iPSCs present an avenue by which we can overcome this issue due to their ability to be differentiated into multiple cell types in the body and their unlimited growth potential. We previously reported generation of the first human 3D skin equivalents from iPSC-derived fibroblasts and iPSC-derived keratinocytes, demonstrating that iPSCs can provide a foundation for modeling a complex human organ such as skin. Here, we have increased the complexity of this model by including additional iPSC-derived melanocytes. Epidermal melanocytes, which are largely responsible for skin pigmentation, represent the second most numerous cell type found in normal human epidermis and as such represent a logical next addition. We report efficient melanin production from iPSC-derived melanocytes and transfer within an entirely iPSC-derived epidermal-melanin unit and generation of the first functional human 3D skin equivalents made from iPSC-derived fibroblasts, keratinocytes and melanocytes.

  8. New Poly(lactic acid) Active Packaging Composite Films Incorporated with Fungal Melanin

    OpenAIRE

    Łukasz Łopusiewicz; Filip Jędra; Małgorzata Mizielińska

    2018-01-01

    In this work, fungal melanin was used for the first time to prepare poly(lactic acid)-based composites. The films of various melanin concentrations (0.025%, 0.05% and 0.2% w/w) were prepared using an extrusion method. The mechanical, antioxidant, antimicrobial, water vapor and UV-Vis barrier properties, as well as available polyphenolics on the surface, were studied. FT-IR and Raman spectroscopy studies were carried out to analyze the chemical composition of the resulting films. The hydrophob...

  9. Methyl gallate from Acer barbinerve decreases melanin synthesis in Mel-Ab cells.

    Science.gov (United States)

    Kim, In Wook; jeong, Hyo-Soon; Kim, Jin Kyu; Lee, Jin-Koo; Kim, Hak Rim; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2015-01-01

    Methyl gallate (MG) was isolated from the bark of Acer barbinerve, which has traditionally been used in Oriental medicine. In the present study, we examined the effects of MG on melanin synthesis in Mel-Ab melanocyte cells. MG decreased melanin pigmentation in a concentration-dependent manner, but did not directly inhibit tyrosinase activity. Further analysis showed that MG had no effect on extracellular signal-regulated kinase (ERK) activation, but induced phosphorylation of glycogen synthase kinase (GSK)3β, which is known to increase β-catenin accumulation. Accordingly, the β-catenin level was increased by MG. However, a specific GSK3β inhibitor did not rescue the MG-induced inhibition of melanogenesis. Additionally, MG decreased the protein expression of microphthalmia-associated transcription factor (MITF) and tyrosinase, which regulate melanin synthesis. Based on these results, we conclude that MG inhibits melanogenesis by decreasing the expression of MITF and tyrosinase.

  10. Melanin as an active layer in biosensors

    Energy Technology Data Exchange (ETDEWEB)

    Piacenti da Silva, Marina, E-mail: marinaness@yahoo.com; Congiu, Mirko, E-mail: congiumat@gmail.com; Oliveira Graeff, Carlos Frederico de, E-mail: graeff@fc.unesp.br [Department of Physics, Faculty of Sciences - UNESP, Bauru, SP (Brazil); Fernandes, Jéssica Colnaghi, E-mail: jeziga-cf@yahoo.com.br; Biziak de Figueiredo, Natália, E-mail: natbiziak@yahoo.com.br; Mulato, Marcelo, E-mail: mmulato@ffclrp.usp.br [Department of Physics, Faculty of Philosophy, Science and Letters at Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP (Brazil)

    2014-03-15

    The development of pH sensors is of great interest due to its extensive application in several areas such as industrial processes, biochemistry and particularly medical diagnostics. In this study, the pH sensing properties of an extended gate field effect transistor (EGFET) based on melanin thin films as active layer are investigated and the physical mechanisms related to the device operation are discussed. Thin films were produced from different melanin precursors on indium tin oxide (ITO) and gold substrates and were investigated by Atomic Force Microscopy and Electrochemical Impedance Spectroscopy. Experiments were performed in the pH range from 2 to 12. EGFETs with melanin deposited on ITO and on gold substrates showed sensitivities ranging from 31.3 mV/pH to 48.9 mV/pH, depending on the melanin precursor and the substrate used. The pH detection is associated with specific binding sites in its structure, hydroxyl groups and quinone imine.

  11. Melanin as an active layer in biosensors

    International Nuclear Information System (INIS)

    Piacenti da Silva, Marina; Congiu, Mirko; Oliveira Graeff, Carlos Frederico de; Fernandes, Jéssica Colnaghi; Biziak de Figueiredo, Natália; Mulato, Marcelo

    2014-01-01

    The development of pH sensors is of great interest due to its extensive application in several areas such as industrial processes, biochemistry and particularly medical diagnostics. In this study, the pH sensing properties of an extended gate field effect transistor (EGFET) based on melanin thin films as active layer are investigated and the physical mechanisms related to the device operation are discussed. Thin films were produced from different melanin precursors on indium tin oxide (ITO) and gold substrates and were investigated by Atomic Force Microscopy and Electrochemical Impedance Spectroscopy. Experiments were performed in the pH range from 2 to 12. EGFETs with melanin deposited on ITO and on gold substrates showed sensitivities ranging from 31.3 mV/pH to 48.9 mV/pH, depending on the melanin precursor and the substrate used. The pH detection is associated with specific binding sites in its structure, hydroxyl groups and quinone imine

  12. Neural stem cells inhibit melanin production by activation of Wnt inhibitors.

    Science.gov (United States)

    Hwang, Insik; Park, Ju-Hwang; Park, Hang-Soo; Choi, Kyung-Ah; Seol, Ki-Cheon; Oh, Seung-Ick; Kang, Seongman; Hong, Sunghoi

    2013-12-01

    Melanin for skin pigmentation is synthesized from tyrosine via an enzymatic cascade that is controlled by tyrosinase (TYR), tyrosinase-related protein 1 (TRP1), and dopachrome tautomerase/tyrosinase related protein 2 (Dct/TRP2), which are the targets of microphthalmia-associated transcription factor (MITF). MITF is a master regulator of pigmentation and a target of β-catenin in Wnt/β-catenin signaling during melanocyte differentiation. Stem cells have been used in skin pigmentation studies, but the mechanisms were not determined for the conditioned medium (CM)-mediated effects. In this study, the inhibition and mechanisms of melanin synthesis were elucidated in B16 melanoma cells and UV-B irradiated C57/BL-6 mice that were treated with human neural stem cell-conditioned medium (NSC-CM). B16-F10 melanoma cells (1.5×10(4)cells/well) and the shaved dorsal skin of mice were pretreated with various amount (5, 10, 20, 50, and 100%) of NSC-CM. Melanin contents and TYR activity were measured by a Spectramax spectrophotometer. The expression of TYR, TRP1, Dct/TRP2, MITF, β-catenin and Wnt inhibitors were evaluated by RT-PCR and western blot. The dorsal skin samples were analyzed by immunofluorescence with various antibodies and compared with that control of tissues. Marked decreases were evident in melanin content and TYR, TRP1, DCT/TRP2, MITF, and β-catenin expression in B16 cells and C57/BL-6 mice. NSC-CM negatively regulated Wnt/β-catenin signaling by decreasing the expression of β-catenin protein, which resulted from robust expression of Wnt inhibitors Dickkopf-1 (DKK1) and secreted frizzled-related protein 2 (sFRP2). These results demonstrate that NSC-CM suppresses melanin production in vitro and in vivo, suggesting that factors in NSC-CM may play an important role in deregulation of epidermal melanogenesis. Copyright © 2013 Japanese Society for Investigative Dermatology. All rights reserved.

  13. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    Science.gov (United States)

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content. PMID:23781272

  14. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    Directory of Open Access Journals (Sweden)

    Hwayong Park

    2013-01-01

    Full Text Available To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in α-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

  15. Microneedling dilates the follicular infundibulum and increases transfollicular absorption of liposomal sepia melanin

    Directory of Open Access Journals (Sweden)

    Serrano G

    2015-06-01

    Full Text Available Gabriel Serrano,1 Patricia Almudéver,2 Juan M Serrano,3 Julio Cortijo,2 Carmen Faus,1 Magda Reyes,1 Inmaculada Expósito,3 Ana Torrens,3 Fernando Millán1 1Clínica Dermatológica Serrano, 2Department of Pharmacology, University of Valencia, 3Research and Development Department, Sesderma Laboratories, Valencia, Spain Abstract: Encapsulation of chemicals in liposomes and microneedling are currently used techniques to enhance the penetration of several substances through skin and hair. In this study, we apply a liposomal melanin–fluorescein compound to an ex vivo model of human skin, using a new electrical microneedling device (Nanopore turbo roller. The product was applied by hand massage (A or with the assistance of the electrical roller for 2 minutes (B. An additional test was performed free of product and with only the E-roller (C. Histological changes and product absorption were evaluated by optical and fluorescent microscopy 60 and 90 minutes after the treatment. Site B showed larger deposits of melanin–fluorescein at superficial and deep levels of hair structures in comparison to site A. Light, epidermal deposits of the melanin–fluorescein complex were also observed. Sites B and C showed a significant widening (47% of the follicular infundibulum which could explain the increased penetration of the formulation. Microneedling also removed the scales and sebum residues in the neighborhood of the infundibulum. Targeting hair follicles with melanin may be useful to dye poorly pigmented hairs, improving laser hair removal. The procedure accelerates the delivery of melanin into hair structures allowing an even absorption, larger pigment deposits, and deeper penetration of the formulation into the hair. Keywords: liposomes, melanin, microneedling, follicular infundibulum, hair removal

  16. In vivo stepwise multi-photon activation fluorescence imaging of melanin in human skin

    Science.gov (United States)

    Lai, Zhenhua; Gu, Zetong; Abbas, Saleh; Lowe, Jared; Sierra, Heidy; Rajadhyaksha, Milind; DiMarzio, Charles

    2014-03-01

    The stepwise multi-photon activated fluorescence (SMPAF) of melanin is a low cost and reliable method of detecting melanin because the activation and excitation can be a continuous-wave (CW) mode near infrared (NIR) laser. Our previous work has demonstrated the melanin SMPAF images in sepia melanin, mouse hair, and mouse skin. In this study, we show the feasibility of using SMPAF to detect melanin in vivo. in vivo melanin SMPAF images of normal skin and benign nevus are demonstrated. SMPAF images add specificity for melanin detection than MPFM images and CRM images. Melanin SMPAF is a promising technology to enable early detection of melanoma for dermatologists.

  17. Parkinson's disease-associated melanin steal.

    Science.gov (United States)

    Hinz, Marty; Stein, Alvin; Cole, Ted

    2014-01-01

    Urinary dopamine fluctuations in the competitive inhibition state were first documented in 2009. At that time, it was noted that progressively higher daily dosing values of L-tyrosine decreased the magnitude of these fluctuations. While extensive statistical analysis has been performed by the authors since 2004, it was not until 2012 that a plausible explanation was formulated. In the process, correlations with L-tyrosine administration and the on/off effect of Parkinson's disease were defined. This paper documents the current knowledge with regard to the management of retrograde phase 1 dopamine fluctuations and investigates the hypothesis that they are caused by a melanin steal phenomenon.

  18. Biocompatibility of biodegradable semiconducting melanin films for nerve tissue engineering.

    Science.gov (United States)

    Bettinger, Christopher J; Bruggeman, Joost P; Misra, Asish; Borenstein, Jeffrey T; Langer, Robert

    2009-06-01

    The advancement of tissue engineering is contingent upon the development and implementation of advanced biomaterials. Conductive polymers have demonstrated potential for use as a medium for electrical stimulation, which has shown to be beneficial in many regenerative medicine strategies including neural and cardiac tissue engineering. Melanins are naturally occurring pigments that have previously been shown to exhibit unique electrical properties. This study evaluates the potential use of melanin films as a semiconducting material for tissue engineering applications. Melanin thin films were produced by solution processing and the physical properties were characterized. Films were molecularly smooth with a roughness (R(ms)) of 0.341 nm and a conductivity of 7.00+/-1.10 x 10(-5)S cm(-1) in the hydrated state. In vitro biocompatibility was evaluated by Schwann cell attachment and growth as well as neurite extension in PC12 cells. In vivo histology was evaluated by examining the biomaterial-tissue response of melanin implants placed in close proximity to peripheral nerve tissue. Melanin thin films enhanced Schwann cell growth and neurite extension compared to collagen films in vitro. Melanin films induced an inflammation response that was comparable to silicone implants in vivo. Furthermore, melanin implants were significantly resorbed after 8 weeks. These results suggest that solution-processed melanin thin films have the potential for use as a biodegradable semiconducting biomaterial for use in tissue engineering applications.

  19. Expression of melanin and insecticidal protein from Rhodotorula ...

    African Journals Online (AJOL)

    Both the salmon/red melanin and the insecticidal producing genes of Rhodotorula glutinis was successfully expressed in Escherichia coli using plasmid pZErO-1. This work suggests that in Rhodotorula species melanin and insecticidal toxin are co-expressed and therefore possibly co-evolved. Keywords: Rhodotorula ...

  20. Aspergillus fumigatus conidial melanin modulates host cytokine response

    NARCIS (Netherlands)

    L.Y.A. Chai (Louis); M.G. Netea (Mihai); J. Sugui (Janyce); A.G. Vonk (Alieke); W.W.J. van de Sande (Wendy); A. Warris (Adilia); K.J. Kwon-Chung (Kyung); B. Jan Kullberg (Bart)

    2010-01-01

    textabstractMelanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced

  1. Aspergillus fumigatus conidial melanin modulates host cytokine response.

    NARCIS (Netherlands)

    Chai, L.; Netea, M.G.; Sugui, J.; Vonk, A.G.; Sande, W.W. van de; Warris, A.; Kwon-Chung, K.J.; Kullberg, B.J.

    2010-01-01

    Melanin biopigments have been linked to fungal virulence. Aspergillus fumigatus conidia are melanised and are weakly immunogenic. We show that melanin pigments on the surface of resting Aspergillus fumigatus conidia may serve to mask pathogen-associated molecular patterns (PAMPs)-induced cytokine

  2. Interocular agreement in melanin and macular pigment optical density.

    NARCIS (Netherlands)

    Kanis, M.J.; Berendschot, T.T.J.M.; van Norren, D.

    2007-01-01

    Macular pigment (MP) and melanin possibly protect the macular area by absorbing blue light and acting as antioxidants. Because little is known about the interocular correlation of melanin, we determined its optical density (MOD) in both eyes of healthy subjects using fundus reflectometry. The

  3. Protective role of Aspergillus fumigatus melanin against ultraviolet ...

    African Journals Online (AJOL)

    Melanin protects pigmented cells from physical and biological stresses which are associated with virulence in several important human pathogens, but little is known about the immune response to this ubiquitous biologic compound. Melanin content increased in Aspergillus fumigatus mycelium exposed to ultraviolet for 10 ...

  4. Natural melanin composites by layer-by-layer assembly

    Science.gov (United States)

    Eom, Taesik; Shim, Bong Sub

    2015-04-01

    Melanin is an electrically conductive and biocompatible material, because their conjugated backbone structures provide conducting pathways from human skin, eyes, brain, and beyond. So there is a potential of using as materials for the neural interfaces and the implantable devices. Extracted from Sepia officinalis ink, our natural melanin was uniformly dispersed in mostly polar solvents such as water and alcohols. Then, the dispersed melanin was further fabricated to nano-thin layered composites by the layer-by-layer (LBL) assembly technique. Combined with polyvinyl alcohol (PVA), the melanin nanoparticles behave as an LBL counterpart to from finely tuned nanostructured films. The LBL process can adjust the smart performances of the composites by varying the layering conditions and sandwich thickness. We further demonstrated the melanin loading degree of stacked layers, combination nanostructures, electrical properties, and biocompatibility of the resulting composites by UV-vis spectrophotometer, scanning electron microscope (SEM), multimeter, and in-vitro cell test of PC12, respectively.

  5. Influence of epidermal growth factor on liver regeneration after partial hepatectomy in rats

    DEFF Research Database (Denmark)

    Olsen, Peter Skov; Boesby, S.; Kirkegaard, P.

    2013-01-01

    The role of epidermal growth factor on liver regeneration after partial hepatectomy in rats was investigated. After a 70% hepatectomy in rats, the concentration of epidermal growth factor in portal venous blood was unchanged compared with unoperated controls. However, small amounts of epidermal...... growth factor could be identified in portal venous blood after intestinal instillation of epidermal growth factor. Brunner's glands and the submandibular glands secrete epidermal growth factor. Extirpation of Brunner's glands decreased liver regeneration, whereas removal of the submandibular glands had...... no effect on liver regeneration. Epidermal growth factor antiserum reduced liver regeneration significantly. Oral or s.c. administration of epidermal growth factor had no effect on liver regeneration, whereas epidermal growth factor enhanced the effect of insulin and glucagon on liver regeneration...

  6. Simultaneous estimation of transcutaneous bilirubin, hemoglobin, and melanin based on diffuse reflectance spectroscopy

    Science.gov (United States)

    Nishidate, Izumi; Abdul, Wares MD.; Ohtsu, Mizuki; Nakano, Kazuya; Haneishi, Hideaki

    2018-02-01

    We propose a method to estimate transcutaneous bilirubin, hemoglobin, and melanin based on the diffuse reflectance spectroscopy. In the proposed method, the Monte Carlo simulation-based multiple regression analysis for an absorbance spectrum in the visible wavelength region (460-590 nm) is used to specify the concentrations of bilirubin (Cbil), oxygenated hemoglobin (Coh), deoxygenated hemoglobin (Cdh), and melanin (Cm). Using the absorbance spectrum calculated from the measured diffuse reflectance spectrum as a response variable and the extinction coefficients of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of bilirubin, oxygenated hemoglobin, deoxygenated hemoglobin, and melanin, are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Total hemoglobin concentration (Cth) and tissue oxygen saturation (StO2) are simply calculated from the oxygenated hemoglobin and deoxygenated hemoglobin. In vivo animal experiments with bile duct ligation in rats demonstrated that the estimated Cbil is increased after ligation of bile duct and reaches to around 20 mg/dl at 72 h after the onset of the ligation, which corresponds to the reference value of Cbil measured by a commercially available transcutaneous bilirubin meter. We also performed in vivo experiments with rats while varying the fraction of inspired oxygen (FiO2). Coh and Cdh decreased and increased, respectively, as FiO2 decreased. Consequently, StO2 was dramatically decreased. The results in this study indicate potential of the method for simultaneous evaluation of multiple chromophores in skin tissue.

  7. Melanin photosensitizes ultraviolet light (UVC) DNA damage in pigmented cells

    International Nuclear Information System (INIS)

    Huselton, C.A.; Hill, H.Z.

    1990-01-01

    Melanins, pigments of photoprotection and camouflage, are very photoreactive and can both absorb and emit active oxygen species. Nevertheless, black skinned individuals rarely develop skin cancer and melanin is assumed to act as a solar screen. Since DNA is the target for solar carcinogenesis, the effect of melanin on Ultraviolet (UV)-induced thymine lesions was examined in mouse melanoma and carcinoma cells that varied in melanin content. Cells prelabeled with 14C-dThd were irradiated with UVC; DNA was isolated, purified, degraded to bases by acid hydrolysis and analyzed by HPLC. Thymine dimers were detected in all of the extracts of irradiated cells. Melanotic and hypomelanotic but not mammary carcinoma cell DNA from irradiated cells contained hydrophilic thymine derivatives. The quantity of these damaged bases was a function of both the UVC dose and the cellular melanin content. One such derivative was identified by gas chromatography-mass spectroscopy as thymine glycol. The other appears to be derived from thymine glycol by further oxidation during acid hydrolysis of the DNA. The finding of oxidative DNA damage in melanin-containing cells suggests that melanin may be implicated in the etiology of caucasian skin cancer, particularly melanoma. Furthermore, the projected decrease in stratospheric ozone could impact in an unanticipated deleterious manner on dark-skinned individuals

  8. Fungal melanin: what do we know about structure?

    Directory of Open Access Journals (Sweden)

    Joshua D Nosanchuk

    2015-12-01

    Full Text Available The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositional and organizational insights could further our ability to develop novel therapeutic approaches to combat fungal disease and enhance our understanding of how melanin is inserted into the cell wall.

  9. Modelling and verification of melanin concentration on human skin type

    CSIR Research Space (South Africa)

    Karsten, AE

    2012-03-01

    Full Text Available exposure to long-wave ultraviolet and visible light. J. Invest. Dermatol. 39, 13 435-443. 14 30. Lavker, R. M. and K. H. Kaidbey (1982) Redistribution of melanosomal complexes 15 within keratinocytes following UV-A irradiation: A possible mechanism..., 1146-1154. 10 20. Salomatina, E., B. Jiang, J. Novak, and A. N. Yaroslavsky (2006) Optical properties of 11 normal and cancerous human skin in the visible and near-infrared spectral range. J. 12 Biomed. Opt. 11. 13 21. Young, A. R. (1997...

  10. Microstructure of Cell Wall-Associated Melanin in the Human Pathogenic Fungus cryptococcus neoformans

    OpenAIRE

    Eisenman, H.C.; Nosanchuk, J.D.; Webber, J. Beau W.; Emerson, T.A.; Casadevall, A.

    2005-01-01

    Melanin is a virulence factor for many pathogenic fungal species,including Cryptococcus neoformans. Melanin is deposited in the cell wall, and melanin isolated from this fungus retains the shape of the cells, resulting in hollow spheres called ``ghosts''. In this study, atomic force, scanning electron, and transmission electron microscopy revealed that melanin ghosts are covered with roughly spherical granular particles approximately 40-130 nm in diameter, and that the melanin is arranged in ...

  11. Melanin as a virulence factor of Paracoccidioides brasiliensis and other dimorphic pathogenic fungi: a minireview

    OpenAIRE

    Taborda, Carlos P.; da Silva, Marcelo B.; Nosanchuk, Joshua D.; Travassos, Luiz R.

    2008-01-01

    Melanin pigments are substances produced by a broad variety of pathogenic microorganisms, including bacteria, fungi, and helminths. Microbes predominantly produce melanin pigment via tyrosinases, laccases, catecholases, and the polyketide synthase pathway. In fungi, melanin is deposited in the cell wall and cytoplasm, and melanin particles (“ghosts”) can be isolated from these fungi that have the same size and shape of the original cells. Melanin has been reported in several human pathogenic ...

  12. Melanins as biomarkers of ovarian follicular atresia in the catfish Heteropneustes fossilis: biochemical and histochemical characterization, seasonal variation and hormone effects.

    Science.gov (United States)

    Kumar, Ravi; Joy, Keerikkattil P

    2015-06-01

    Follicular atresia is a common feature of the vertebrate ovary that occurs at different stages of folliculogenesis and ovarian regression. It has physiological significance to maintain homeostasis and control fecundity, and ensure removal of post-ovulatory follicular remnants for preparing the ovary for the next cycle. Pigments appear late in the atretic process as indigestible waste formed out of the degradation of the oocytes, follicle wall and granulocytes. In the present study, pigment accumulation was demonstrated by Schmorl's and Perls' staining methods in the atretic ovarian follicles of Heteropneustes fossilis during follicular development and regression. Melanins were characterized spectrophotometrically for the first time in fish ovary. The predominant form is eumelanin, followed by pheomelanin and alkali-soluble melanin. Melanins showed significant seasonal variations with levels low in gonad resting phase, increasing to the peak in the post-spawning phase. The concentration of melanins increased time-dependently in post-ovulated ovary after human chorionic gonadotropin treatment. In the spawning phase, in vitro incubation of ovary slices with estradiol-17β or dexamethasone for 8 or 16 h decreased both eumelanin and pheomelanin levels time-dependently. The alkali-soluble melanin showed a significant decrease only in the dexamethasone group at 16 h. The results show that melanin assay can be used as a biomarker of follicular atresia in fish ovary, natural or induced by environmental toxicants.

  13. Low-melanin containing pullulan production from sugarcane bagasse hydrolysate by Aureobasidium pullulans in fermentations assisted by light-emitting diode.

    Science.gov (United States)

    Terán Hilares, Ruly; Orsi, Camila Ayres; Ahmed, Muhammad Ajaz; Marcelino, Paulo Franco; Menegatti, Carlos Renato; da Silva, Silvio Silvério; Dos Santos, Júlio César

    2017-04-01

    Pullulan is a polymer produced by Aureobasidium pullulans and the main bottleneck for its industrial production is the presence of melanin pigment. In this study, light-emitting diodes (LEDs) of different wavelengths were used to assist the fermentation process aiming to produce low-melanin containing pullulan by wild strain of A. pullulans LB83 with different carbon sources. Under white light using glucose-based medium, 11.75g.L -1 of pullulan with high melanin content (45.70UA 540nm .g -1 ) was obtained, this production improved in process assisted by blue LED light, that resulted in 15.77g.L -1 of pullulan with reduced content of melanin (4.46UA 540nm .g -1 ). By using sugarcane bagasse (SCB) hydrolysate as carbon source, similar concentration of pullulan (about 20g.L -1 ) was achieved using white and blue LED lights, with lower melanin contents in last. Use of LED light was found as a promising approach to assist biotechnological process for low-melanin containing pullulan production. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Melanin fluorescence spectra by step-wise three photon excitation

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; DiMarzio, Charles A.

    2012-03-01

    Melanin is the characteristic chromophore of human skin with various potential biological functions. Kerimo discovered enhanced melanin fluorescence by stepwise three-photon excitation in 2011. In this article, step-wise three-photon excited fluorescence (STPEF) spectrum between 450 nm -700 nm of melanin is reported. The melanin STPEF spectrum exhibited an exponential increase with wavelength. However, there was a probability of about 33% that another kind of step-wise multi-photon excited fluorescence (SMPEF) that peaks at 525 nm, shown by previous research, could also be generated using the same process. Using an excitation source at 920 nm as opposed to 830 nm increased the potential for generating SMPEF peaks at 525 nm. The SMPEF spectrum peaks at 525 nm photo-bleached faster than STPEF spectrum.

  15. Diversion of the melanin synthetic pathway by dopamine product

    African Journals Online (AJOL)

    acetylcysteine adducts of dopamine studied using quantum chemical ... cyclization reaction of dopaminoquinone which leads to the synthesis of melanin. ..... a hydrogen bond with the carbonyl oxygen (−O−H---O=C− and the second one points ...

  16. Low temperature specific heat anomalies in melanins and tumor melanosomes

    Energy Technology Data Exchange (ETDEWEB)

    Mizutani, U [Carnegie--Mellon Univ., Pittsburgh; Massalski, T B; McGinness, J E; Corry, P M

    1976-02-12

    Human malignant melanoma cells obtained at autopsy were used. Data indicate that melanins exhibit a large linear term (50-200 erg g/sup -1/K/sup -2/) and that they seem to undergo a phase transition as indicated by the heat capacity near 1.9/sup 0/K. A table is presented to show low temperature specific heat data for melanin samples. The measurements include two anomalies, a transition and an unusually high linear contribution. (HLW)

  17. Fungal Melanin: What do We Know About Structure?

    OpenAIRE

    Nosanchuk, Joshua D.; Stark, Ruth E.; Casadevall, Arturo

    2015-01-01

    The production of melanin significantly enhances the virulence of many important human pathogenic fungi. Despite fungal melanin’s importance in human disease, as well as melanin’s contribution to the ability of fungi to survive in diverse hostile environments, the structure of melanin remains unsolved. Nevertheless, ongoing research efforts have progressively revealed several notable structural characteristics of this enigmatic pigment, which will be the focus of this review. These compositio...

  18. Two-photon excited fluorescence spectroscopy and imaging of melanin in vitro and in vivo

    Science.gov (United States)

    Krasieva, Tatiana B.; Liu, Feng; Sun, Chung-Ho; Kong, Yu; Balu, Mihaela; Meyskens, Frank L.; Tromberg, Bruce J.

    2012-03-01

    The ability to detect early melanoma non-invasively would improve clinical outcome and reduce mortality. Recent advances in two-photon excited fluorescence (TPEF) in vivo microscopy offer a powerful tool in early malignant melanoma diagnostics. The goal of this work was to develop a TPEF optical index for measuring relative concentrations of eumelanin and pheomelanin since ex vivo studies show that changes in this ratio have been associated with malignant transformation. We acquired TPEF emission spectra (λex=1000 nm) of melanin from several specimens, including human hair, malignant melanoma cell lines, and normal melanocytes and keratinocytes in different skin layers (epidermis, papillary dermis) in five healthy volunteers in vivo. We found that the pheomelanin emission peaks at around 620 nm and is blue-shifted from the eumelanin with broad maximum at 640-680nm. We defined "optical melanin index" (OMI) as a ratio of fluorescence signal intensities measured at 645 nm and 615nm. The measured OMI for a melanoma cell line MNT-1 was 1.6+/-0.2. The MNT-46 and MNT-62 lines (Mc1R gene knockdown) showed an anticipated change in melanins production ratio and had OMI of 0.55+/-0.05 and 0.17+/-0.02, respectively, which strongly correlated with HPLC data obtained for these lines. Average OMI measured for basal cells layers (melanocytes and keratinocytes) in normal human skin type I, II-III (not tanned and tanned) in vivo was 0.5, 1.05 and 1.16 respectively. We could not dependably detect the presence of pheomelanin in highly pigmented skin type V-VI. These data suggest that a non-invasive TPEF index could potentially be used for rapid melanin ratio characterization both in vitro and in vivo, including pigmented lesions.

  19. Bird Integumentary Melanins: Biosynthesis, Forms, Function and Evolution

    Science.gov (United States)

    Galván, Ismael; Solano, Francisco

    2016-01-01

    Melanins are the ubiquitous pigments distributed in nature. They are one of the main pigments responsible for colors in living cells. Birds are among the most diverse animals regarding melanin-based coloration, especially in the plumage, although they also pigment bare parts of the integument. This review is devoted to the main characteristics of bird melanins, including updated views of the formation and nature of melanin granules, whose interest has been raised in the last years for inferring the color of extinct birds and non-avian theropod dinosaurs using resistant fossil feathers. The molecular structure of the two main types of melanin, eumelanin and pheomelanin, and the environmental and genetic factors that regulate avian melanogenesis are also presented, establishing the main relationship between them. Finally, the special functions of melanin in bird feathers are also discussed, emphasizing the aspects more closely related to these animals, such as honest signaling, and the factors that may drive the evolution of pheomelanin and pheomelanin-based color traits, an issue for which birds have been pioneer study models. PMID:27070583

  20. Bird Integumentary Melanins: Biosynthesis, Forms, Function and Evolution

    Directory of Open Access Journals (Sweden)

    Ismael Galván

    2016-04-01

    Full Text Available Melanins are the ubiquitous pigments distributed in nature. They are one of the main pigments responsible for colors in living cells. Birds are among the most diverse animals regarding melanin-based coloration, especially in the plumage, although they also pigment bare parts of the integument. This review is devoted to the main characteristics of bird melanins, including updated views of the formation and nature of melanin granules, whose interest has been raised in the last years for inferring the color of extinct birds and non-avian theropod dinosaurs using resistant fossil feathers. The molecular structure of the two main types of melanin, eumelanin and pheomelanin, and the environmental and genetic factors that regulate avian melanogenesis are also presented, establishing the main relationship between them. Finally, the special functions of melanin in bird feathers are also discussed, emphasizing the aspects more closely related to these animals, such as honest signaling, and the factors that may drive the evolution of pheomelanin and pheomelanin-based color traits, an issue for which birds have been pioneer study models.

  1. Enzymatic synthesis of arbutin undecylenic acid ester and its inhibitory effect on melanin synthesis.

    Science.gov (United States)

    Tokiwa, Yutaka; Kitagawa, Masaru; Raku, Takao; Yanagitani, Shusaku; Yoshino, Kenji

    2007-06-01

    Transesterification of arbutin and undecylenic acid vinyl ester was catalyzed by alkaline protease, Bioprase, in dimethylformamide to get arbutin derivative having undecylenic acid at 6-position of glucose moiety, 6-O-undecylenoyl p-hydroxyphenyl beta-D-glucopyranoside. The reaction rate increased with increase of arbutin concentration, and when its concentration was 0.9 M, the conversion rate was more than 90% under addition of 2 M undecylenic acid vinyl ester. The obtained arbutin ester significantly suppressed melanin production in murine B16 melanoma cells.

  2. UVB-induced epidermal hyperproliferation is modified by a single, topical treatment with a mitosis inhibitory epidermal pentapeptide

    International Nuclear Information System (INIS)

    Olsen, W.M.; Elgjo, K.

    1990-01-01

    A single application of a water-miscible cream base containing the recently identified mitosis inhibitory epidermal pentapeptide pyroGlu-Glu-Asp-Ser-GlyOH (EPP) to hairless mouse skin is followed by a long-lasting period of reduced epidermal cell proliferation. To examine if a similar growth inhibition could be achieved in stimulated and rapidly proliferating epidermis, EPP was applied at two different concentrations, 0.005 or 0.02%, to hairless mouse skin immediately after exposure of the left flank to an erythemic dose of ultraviolet B light (UVB). This dose of UVB alone induces a sustained period of rapid epidermal cell proliferation, starting at about 18 h after the irradiation. Epidermal cell proliferation was followed from 18 to 54 h (0.005% cream) or from 18 to 30 h (0.02% cream) after the treatment by estimating the rate of G2-M cell flux (the mitotic rate) by means of Colcemid, and epidermal DNA synthesis by counting labeled cells after pulse-labeling with 3H-thymidine. The unirradiated side of the mice was used as reference. The results showed that topical treatment with a 0.02% EPP cream partially inhibited UVB-induced epidermal hyperproliferation, while the 0.005% EPP cream inhibited as well as stimulated the UVB-induced hyperproliferation. Thus, EPP is effective even in rapidly proliferating epidermal cell populations, but the outcome is obviously dose-dependent in this test system

  3. Optical properties of cells with melanin

    Science.gov (United States)

    Rohde, Barukh; Coats, Israel; Krueger, James; Gareau, Dan

    2014-02-01

    The optical properties of pigmented lesions have been studied using diffuse reflectance spectroscopy in a noninvasive configuration on optically thick samples such as skin in vivo. However, it is difficult to un-mix the effects of absorption and scattering with diffuse reflectance spectroscopy techniques due to the complex anatomical distributions of absorbing and scattering biomolecules. We present a device and technique that enables absorption and scattering measurements of tissue volumes much smaller than the optical mean-free path. Because these measurements are taken on fresh-frozen sections, they are direct measurements of the optical properties of tissue, albeit in a different hydration state than in vivo tissue. Our results on lesions from 20 patients including melanomas and nevi show the absorption spectrum of melanin in melanocytes and basal keratinocytes. Our samples consisted of fresh frozen sections that were unstained. Fitting the spectrum as an exponential decay between 500 and 1100 nm [mua = A*exp(-B*(lambda-C)) + D], we report on the fit parameters of and their variation due to biological heterogeneity as A = 4.20e4 +/- 1.57e5 [1/cm], B = 4.57e-3 +/- 1.62e-3 [1/nm], C = 210 +/- 510 [nm] , D = 613 +/- 534 [1/cm]. The variability in these results is likely due to highly heterogeneous distributions of eumelanin and pheomelanin.

  4. Melanin targeting for intracellular drug delivery: Quantification of bound and free drug in retinal pigment epithelial cells.

    Science.gov (United States)

    Rimpelä, Anna-Kaisa; Hagström, Marja; Kidron, Heidi; Urtti, Arto

    2018-05-31

    Melanin binding affects drug distribution and retention in pigmented ocular tissues, thereby affecting drug response, duration of activity and toxicity. Therefore, it is a promising possibility for drug targeting and controlled release in the pigmented cells and tissues. Intracellular unbound drug concentrations determine pharmacological and toxicological actions, but analyses of unbound vs. total drug concentrations in pigmented cells are lacking. We studied intracellular binding and cellular drug uptake in pigmented retinal pigment epithelial cells and in non-pigmented ARPE-19 cells with five model drugs (chloroquine, propranolol, timolol, diclofenac, methotrexate). The unbound drug fractions in pigmented cells were 0.00016-0.73 and in non-pigmented cells 0.017-1.0. Cellular uptake (i.e. distribution ratio Kp), ranged from 1.3 to 6300 in pigmented cells and from 1.0 to 25 in non-pigmented cells. Values for intracellular bioavailability, F ic , were similar in both cells types (although larger variation in pigmented cells). In vitro melanin binding parameters were used to predict intracellular unbound drug fraction and cell uptake. Comparison of predictions with experimental data indicates that other factors (e.g. ion-trapping, lipophilicity-related binding to other cell components) also play a role. Melanin binding is a major factor that leads to cellular uptake and unbound drug fractions of a range of 3-4 orders of magnitude indicating that large reservoirs of melanin bound drug can be generated in the cells. Understanding melanin binding has important implications on retinal drug targeting, efficacy and toxicity. Copyright © 2017. Published by Elsevier B.V.

  5. Hyperosmotic stress reduces melanin production by altering melanosome formation.

    Science.gov (United States)

    Bin, Bum-Ho; Bhin, Jinhyuk; Yang, Seung Ha; Choi, Dong-Hwa; Park, Kyuhee; Shin, Dong Wook; Lee, Ai-Young; Hwang, Daehee; Cho, Eun-Gyung; Lee, Tae Ryong

    2014-01-01

    Many tissues of the human body encounter hyperosmotic stress. The effect of extracellular osmotic changes on melanin production has not yet been elucidated. In this study, we determined that hyperosmotic stress induced by organic osmolytes results in reduced melanin production in human melanoma MNT-1 cells. Under hyperosmotic stress, few pigmented mature melanosomes were detected, but there was an increase in swollen vacuoles. These vacuoles were stained with an anti-M6PR antibody that recognizes late endosomal components and with anti-TA99 and anti-HMB45 antibodies, implying that melanosome formation was affected by hyperosmotic stress. Electron microscopic analysis revealed that the M6PR-positive swollen vacuoles were multi-layered and contained melanized granules, and they produced melanin when L-DOPA was applied, indicating that these vacuoles were still capable of producing melanin, but the inner conditions were not compatible with melanin production. The vacuolation phenomenon induced by hyperosmotic conditions disappeared with treatment with the PI3K activator 740 Y-P, indicating that the PI3K pathway is affected by hyperosmotic conditions and is responsible for the proper formation and maturation of melanosomes. The microarray analysis showed alterations of the vesicle organization and transport under hyperosmotic stress. Our findings suggest that melanogenesis could be regulated by physiological conditions, such as osmotic pressure.

  6. Genetic validation and spectroscopic detailing of DHN-melanin extracted from an environmental fungus

    Directory of Open Access Journals (Sweden)

    Nitya Meenakshi Raman

    2017-12-01

    Full Text Available Accurate characterization of melanin using analytical methodologies has proved to be difficult due to its heterogeneity, insolubility in wide pH and broad range of solvents. The present study was undertaken to characterize melanin extracted from an environmental Aspergillus fumigatus AFGRD105 by studying its genes, chemical properties and spectral data. A gene based approach to confirm the type of melanin carried out indicated the extracted melanin to be of the dihydroxynaphthalene type. On comparison with synthetic melanin, UV–Vis and IR spectra of the extracted melanin revealed characteristic peaks that can be further used for confirmation of DHN-melanin extracted from any source. Solid state 13C NMR spectroscopy established the presence of the hydroxyl-naphthalene moiety and validated the results obtained by genetic analysis. The correct assignment of the observed spectral frequency characteristic of functional groups can be further adapted in future works that deal with binding capacities and biomolecule systems involving melanin.

  7. Pharmacological Properties of Melanin and its Function in Health.

    Science.gov (United States)

    ElObeid, Adila Salih; Kamal-Eldin, Afaf; Abdelhalim, Mohamed Anwar K; Haseeb, Adil M

    2017-06-01

    The biological pigment melanin is present in most of the biological systems. It manifests a host of biological and pharmacological properties. Its role as a molecule with special properties and functions affecting general health, including photoprotective and immunological action, are well recognized. Its antioxidant, anti-inflammatory, immunomodulatory, radioprotective, hepatic, gastrointestinal and hypoglycaemic benefits have only recently been recognized and studied. It is also associated with certain disorders of the nervous system. In this MiniReview, we consider the steadily increasing literature on the bioavailability and functional activity of melanin. Published literature shows that melanin may play a number of possible pharmacological effects such as protective, stimulatory, diagnostic and curative roles in human health. In this MiniReview, possible health roles and pharmacological effects are considered. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

  8. MMS 1001 inhibits melanin synthesis via ERK activation.

    Science.gov (United States)

    Lee, Hyun-E; Song, Jiho; Kim, Su Yeon; Park, Kyoung-Chan; Min, Kyung Hoon; Kim, Dong-Seok

    2013-03-01

    Melanin plays major a role in pigmentation of hair, eyes, and skin in mammals. In this study, the inhibitory effects of MMS 1001 on alpha-MSH-stimulated melanogenesis were investigated in B16F10 melanoma cells. MMS 1001 did not show cytotoxic effects up to 10 microM. Melanin content and intracellular tyrosinase activity were inhibited by MMS 1001 treatment in a dose-dependent manner. In Western blot analysis, MITF expression was decreased by MMS 1001. In addition, tyrosinase expressions were also reduced after MMS 1001 treatment. Further results showed that the phosphorylation of ERK was induced by MMS 1001. Moreover, a specific MEK inhibitor, PD98059, abrogated the inhibitory effects of MMS 1001 on melanin production and tyrosinase expression. These results indicate that the hypopigmentary effects of MMS 1001 resulted from the inhibition of MITF and tyrosinase expression via phosphorylation of ERK. Thus, MMS 1001 could be developed as a new effective skin-whitening agent.

  9. Epidermal cell death in frogs with chytridiomycosis

    Directory of Open Access Journals (Sweden)

    Laura A. Brannelly

    2017-02-01

    Full Text Available Background Amphibians are declining at an alarming rate, and one of the major causes of decline is the infectious disease chytridiomycosis. Parasitic fungal sporangia occur within epidermal cells causing epidermal disruption, but these changes have not been well characterised. Apoptosis (planned cell death can be a damaging response to the host but may alternatively be a mechanism of pathogen removal for some intracellular infections. Methods In this study we experimentally infected two endangered amphibian species Pseudophryne corroboree and Litoria verreauxii alpina with the causal agent of chytridiomycosis. We quantified cell death in the epidermis through two assays: terminal transferase-mediated dUTP nick end-labelling (TUNEL and caspase 3/7. Results Cell death was positively associated with infection load and morbidity of clinically infected animals. In infected amphibians, TUNEL positive cells were concentrated in epidermal layers, correlating to the localisation of infection within the skin. Caspase activity was stable and low in early infection, where pathogen loads were light but increasing. In animals that recovered from infection, caspase activity gradually returned to normal as the infection cleared. Whereas, in amphibians that did not recover, caspase activity increased dramatically when infection loads peaked. Discussion Increased cell death may be a pathology of the fungal parasite, likely contributing to loss of skin homeostatic functions, but it is also possible that apoptosis suppression may be used initially by the pathogen to help establish infection. Further research should explore the specific mechanisms of cell death and more specifically apoptosis regulation during fungal infection.

  10. Melanin binding study of clinical drugs with cassette dosing and rapid equilibrium dialysis inserts

    OpenAIRE

    Pelkonen L; Tengvall-Unadike U; Ruponen M; Kidron H; del Amo EM; Reinisalo M; Urtti A

    2017-01-01

    Melanin pigment is a negatively charged polymer found in pigmented human tissues. In the eye, iris, ciliary body, choroid and retinal pigment epithelium (RPE) are heavily pigmented. Several drug molecules are known to bind to melanin, but larger sets of drugs have not been compared often in similar test conditions. In this study, we introduce a powerful tool for screening of melanin binding. The binding of a set of 34 compounds to isolated porcine RPE melanin was determined by cassette (n-in-...

  11. Differential Antifungal Activity of Human and Cryptococcal Melanins with Structural Discrepancies

    OpenAIRE

    Néstor Correa; Néstor Correa; Néstor Correa; Cristian Covarrubias; Paula I. Rodas; Germán Hermosilla; Verónica R. Olate; Verónica R. Olate; Cristián Valdés; Wieland Meyer; Fabien Magne; Cecilia V. Tapia; Cecilia V. Tapia

    2017-01-01

    Melanin is a pigment found in all biological kingdoms, and plays a key role in protection against ultraviolet radiation, oxidizing agents, and ionizing radiation damage. Melanin exerts an antimicrobial activity against bacteria, fungi, and parasites. We demonstrated an antifungal activity of synthetic and human melanin against Candida sp. The members of the Cryptococcus neoformans and C. gattii species complexes are capsulated yeasts, which cause cryptococcosis. For both species melanin is an...

  12. Functional Role of Cyclin-Dependent Kinase 5 in the Regulation of Melanogenesis and Epidermal Structure.

    Science.gov (United States)

    Dong, Changsheng; Yang, Shanshan; Fan, Ruiwen; Ji, Kaiyuan; Zhang, Junzhen; Liu, Xuexian; Hu, Shuaipeng; Xie, Jianshan; Liu, Yu; Gao, Wenjun; Wang, Haidong; Yao, Jianbo; Smith, George W; Herrid, Muren

    2017-10-23

    The mammalian integumentary system plays important roles in body homeostasis, and dysfunction of melanogenesis or epidermal development may lead to a variety of skin diseases, including melanoma. Skin pigmentation in humans and coat color in fleece-producing animals are regulated by many genes. Among them, microphthalmia-associated transcription factor (MITF) and paired-box 3 (PAX3) are at the top of the cascade and regulate activities of many important melanogenic enzymes. Here, we report for the first time that cyclin-dependent kinase 5 (Cdk5) is an essential regulator of MITF and PAX3. Cdk5 knockdown in mice causes a lightened coat color, a polarized distribution of melanin and hyperproliferation of basal keratinocytes. Reduced expression of Keratin 10 (K10) resulting from Cdk5 knockdown may be responsible for an abnormal epidermal structure. In contrast, overexpression of Cdk5 in sheep (Ovis aries) only produces brown patches on a white background, with no other observable abnormalities. Collectively, our findings show that Cdk5 has an important functional role in the regulation of melanin production and transportation and in normal development of the integumentary system.

  13. Toxic epidermal necrolysis.

    Science.gov (United States)

    Pereira, Frederick A; Mudgil, Adarsh Vijay; Rosmarin, David M

    2007-02-01

    Toxic epidermal necrolysis (TEN) is an unpredictable, life-threatening drug reaction associated with a 30% mortality. Massive keratinocyte apoptosis is the hallmark of TEN. Cytotoxic T lymphocytes appear to be the main effector cells and there is experimental evidence for involvement of both the Fas-Fas ligand and perforin/granzyme pathways. Optimal treatment for these patients remains to be clarified. Discontinuation of the offending drug and prompt referral to a burn unit are generally agreed upon steps. Beyond that, however, considerable controversy exists. Evidence both pro and con exists for the use of IVIG, systemic corticosteroid, and other measures. There is also evidence suggesting that combination therapies may be of value. All the clinical data, however, is anecdotal or based on observational or retrospective studies. Definitive answers are not yet available. Given the rarity of TEN and the large number of patients required for a study to be statistically meaningful, placebo controlled trials are logistically difficult to accomplish. The absence of an animal model further hampers research into this condition. This article reviews recent data concerning clinical presentation, pathogenesis and treatment of TEN. At the conclusion of this learning activity, participants should have acquired a more comprehensive knowledge of our current understanding of the classification, clinical presentation, etiology, pathophysiology, prognosis, and treatment of TEN.

  14. Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells

    International Nuclear Information System (INIS)

    Ranadive, N.S.; Shirwadkar, S.; Persad, S.; Menon, I.A.

    1986-01-01

    Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of 51 Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker 51 Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H 2 O 2 or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells

  15. Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ranadive, N.S.; Shirwadkar, S.; Persad, S.; Menon, I.A.

    1986-03-01

    Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of /sup 51/Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker /sup 51/Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H/sub 2/O/sub 2/ or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.

  16. Estimation of Melanin and Hemoglobin Using Spectral Reflectance Images Reconstructed from a Digital RGB Image by the Wiener Estimation Method

    Directory of Open Access Journals (Sweden)

    Yoshihisa Aizu

    2013-06-01

    Full Text Available A multi-spectral diffuse reflectance imaging method based on a single snap shot of Red-Green-Blue images acquired with the exposure time of 65 ms (15 fps was investigated for estimating melanin concentration, blood concentration, and oxygen saturation in human skin tissue. The technique utilizes the Wiener estimation method to deduce spectral reflectance images instantaneously from an RGB image. Using the resultant absorbance spectrum as a response variable and the extinction coefficients of melanin, oxygenated hemoglobin and deoxygenated hemoglobin as predictor variables, multiple regression analysis provides regression coefficients. Concentrations of melanin and total blood are then determined from the regression coefficients using conversion vectors that are numerically deduced in advance by the Monte Carlo simulations for light transport in skin. Oxygen saturation is obtained directly from the regression coefficients. Experiments with a tissue-like agar gel phantom validated the method. In vivo experiments on fingers during upper limb occlusion demonstrated the ability of the method to evaluate physiological reactions of human skin.

  17. Increased epidermal laser fluence through simultaneous ultrasonic microporation

    Science.gov (United States)

    Whiteside, Paul J. D.; Chininis, Jeff A.; Schellenberg, Mason W.; Qian, Chenxi; Hunt, Heather K.

    2016-03-01

    Lasers have demonstrated widespread applicability in clinical dermatology as minimally invasive instruments that achieve photogenerated responses within tissue. However, before reaching its target, the incident light must first transmit through the surface layer of tissue, which is interspersed with chromophores (e.g. melanin) that preferentially absorb the light and may also generate negative tissue responses. These optical absorbers decrease the efficacy of the procedures. In order to ensure that the target receives a clinically relevant dose, most procedures simply increase the incident energy; however, this tends to exacerbate the negative complications of melanin absorption. Here, we present an alternative solution aimed at increasing epidermal energy uence while mitigating excess absorption by unintended targets. Our technique involves the combination of a waveguide-based contact transmission modality with simultaneous high-frequency ultrasonic pulsation, which alters the optical properties of the tissue through the agglomeration of dissolved gasses into micro-bubbles within the tissue. Doing so effectively creates optically transparent pathways for the light to transmit unobstructed through the tissue, resulting in an increase in forward scattering and a decrease in absorption. To demonstrate this, Q-switched nanosecond-pulsed laser light at 532nm was delivered into pig skin samples using custom glass waveguides clad in titanium and silver. Light transmission through the tissue was measured with a photodiode and integrating sphere for tissue with and without continuous ultrasonic pulsation at 510 kHz. The combination of these techniques has the potential to improve the efficiency of laser procedures while mitigating negative tissue effects caused by undesirable absorption.

  18. Morphological and chemical composition characterization of commercial sepia melanin

    CSIR Research Space (South Africa)

    Mbonyiryivuze, A

    2015-06-01

    Full Text Available granules with different size distributions that have been determined using image-J software. The small granule diameter obtained from different TEM and SEM micrographs were 100-200nm. EDS reveals that C and O were the most abundant in sepia melanin...

  19. Genetic monitoring of irradiated Drosophila populations treated with antimutagen melanine

    International Nuclear Information System (INIS)

    Mosseh, I.B.; Savchenko, V.K.; Lyakh, I.P.

    1986-01-01

    A nonspecific increase was noted in the resistance of Drosophila populations to toxic and mutagenic effects of ionizing radiation and the chemical mutagen ethylmethansulphonate during long-term exposure. It was established that under the effect of melanine, less resistant genotypes retained, and the resistance of the populations to damaging factors did not increase

  20. Genetic monitoring of irradiated Drosophila populations treated with antimutagen melanine

    International Nuclear Information System (INIS)

    Mosseh, I.B.; Savchenko, V.K.; Lyakh, I.P.

    1986-01-01

    It was shown that viability of irradiated Drosophila is, on an average, lower than in intact populations. The fertility first decreases then increases exceeding the control level. Melanine added to the diet increases fertility and viability of both exposed and intact Drosophila populations

  1. Uncovering of melanin fluorescence in human skin tissue

    Science.gov (United States)

    Scholz, Matthias; Stankovic, Goran; Seewald, Gunter; Leupold, Dieter

    2007-07-01

    Due to its extremely low fluorescence quantum yield, in the conventionally (one-photon) excited autofluorescence of skin tissue, melanin fluorescence is masked by several other endogenous and possibly also exogenous fluorophores (e.g. NADH, FAD, Porphyrins). A first step to enhance the melanin contribution had been realized by two-photon fs-pulse excitation in the red/near IR, based on the fact that melanin can be excited by stepwise two-photon absorption, whereas all other fluorophores in this spectral region allow only simultaneous two-photon excitation. Now, the next and decisive step has been realized: Using an extremely sensitive detection system, for the first time twophoton fluorescence of skin tissue excited with pulses in the ns-range could be measured. The motivation for this step was based on the fact that the population density of the fluorescent level resulting from a stepwise excitation has a different dependence of the pulse duration than that from a simultaneous excitation (Δt2 vs. Δt). Due to this strong discrimination between the fluorophores, practically pure melanin fluorescence can be obtained. Examples for in-vivo, ex-vivo as well as paraffin embedded skin tissue will be shown. The content of information with respect to early diagnosis of skin deseases will be discussed.

  2. Red blood cell membrane-camouflaged melanin nanoparticles for enhanced photothermal therapy.

    Science.gov (United States)

    Jiang, Qin; Luo, Zimiao; Men, Yongzhi; Yang, Peng; Peng, Haibao; Guo, Ranran; Tian, Ye; Pang, Zhiqing; Yang, Wuli

    2017-10-01

    Photothermal therapy (PTT) has represented a promising noninvasive approach for cancer treatment in recent years. However, there still remain challenges in developing non-toxic and biodegradable biomaterials with high photothermal efficiency in vivo. Herein, we explored natural melanin nanoparticles extracted from living cuttlefish as effective photothermal agents and developed red blood cell (RBC) membrane-camouflaged melanin (Melanin@RBC) nanoparticles as a platform for in vivo antitumor PTT. The as-obtained natural melanin nanoparticles demonstrated strong absorption at NIR region, higher photothermal conversion efficiency (∼40%) than synthesized melanin-like polydopamine nanoparticles (∼29%), as well as favorable biocompatibility and biodegradability. It was shown that RBC membrane coating on melanin nanoparticles retained their excellent photothermal property, enhanced their blood retention and effectively improved their accumulation at tumor sites. With the guidance of their inherited photoacoustic imaging capability, optimal accumulation of Melanin@RBC at tumors was achieved around 4 h post intravenous injection. Upon irradiation by an 808-nm laser, the developed Melanin@RBC nanoparticles exhibited significantly higher PTT efficacy than that of bare melanin nanoparticles in A549 tumor-bearing mice. Given that both melanin nanoparticles and RBC membrane are native biomaterials, the developed Melanin@RBC platform could have great potential in clinics for anticancer PTT. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Melanin: spin behaviour and implications for bioelectronic devices (Presentation Recording)

    Science.gov (United States)

    Meredith, Paul; Sheliakina, Margarita; Mostert, Bernard

    2015-10-01

    The melanins are a broad class of pigmentary macromolecules found through nature that perform a wide range of functions including photo-protection [1]. The most common melanin - the brown, black pigment eumelanin, has been much studied because of its role in melanoma and also for its functional material properties [2]. Synthetic eumelanin has been shown to be photoconductive in the solid state and also possess a water content dependent dark conductivity [3]. It is now well established that these electrical properties arise from hybrid ionic-electronic behaviour, leading to the proposition that melanins could be model biocompatible systems for ion-to-electron transduction in bioelectronics. In my talk, I will discuss the basic science behind these bioelectronics properties - electrical and optical. In this context I will also describe recent electron paramagnetic spin studies which isolate the role of the various chemical moieties responsible for the hybrid ionic-electronic behaviour. I will also highlight preliminary results on prototype melanin-based bioelectronics devices and discuss possible architectures to realise elements such as solid-state switches and transducers. [1] "The physical and chemical properties of eumelanin", P. Meredith and T. Sarna, Pigment Cell Research, 19(6), pp572-594 (2006). [2] "Electronic and optoelectronic materials and devices inspired by nature", P Meredith, C.J. Bettinger, M. Irimia-Vladu, A.B. Mostert and P.E. Schwenn, Reports on Progress in Physics, 76, 034501 (2013). [3] "Is melanin a semiconductor: humidity induced self doping and the electrical conductivity of a biopolymer", A.B. Mostert, B.J. Powell, F.L. Pratt, G.R. Hanson, T. Sarna, I.R. Gentle and P. Meredith, Proceedings of the National Academy of Sciences of the USA, 109(23), 8943-8947 (2012).

  4. Epidermal protection with cryogen spray cooling during high fluence pulsed dye laser irradiation: an ex vivo study.

    Science.gov (United States)

    Tunnell, J W; Nelson, J S; Torres, J H; Anvari, B

    2000-01-01

    Higher laser fluences than currently used in therapy (5-10 J/cm(2)) are expected to result in more effective treatment of port wine stain (PWS) birthmarks. However, higher incident fluences increase the risk of epidermal damage caused by absorption of light by melanin. Cryogen spray cooling offers an effective method to reduce epidermal injury during laser irradiation. The objective of this study was to determine whether high laser incident fluences (15-30 J/cm(2)) could be used while still protecting the epidermis in ex vivo human skin samples. Non-PWS skin from a human cadaver was irradiated with a Candela ScleroPlus Laser (lambda = 585 nm; pulse duration = 1.5 msec) by using various incident fluences (8-30 J/cm(2)) without and with cryogen spray cooling (refrigerant R-134a; spurt durations: 40-250 msec). Assessment of epidermal damage was based on histologic analysis. Relatively short spurt durations (40-100 msec) protected the epidermis for laser incident fluences comparable to current therapeutic levels (8-10 J/cm(2)). However, longer spurt durations (100-250 msec) increased the fluence threshold for epidermal damage by a factor of three (up to 30 J/cm(2)) in these ex vivo samples. Results of this ex vivo study show that epidermal protection from high laser incident fluences can be achieved by increasing the cryogen spurt duration immediately before pulsed laser exposure. Copyright 2000 Wiley-Liss, Inc.

  5. Effects of ultraviolet-visible irradiation in the presence of melanin isolated from human black or red hair upon Ehrlich ascites carcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Menon, I.A.; Persad, S.; Ranadive, N.S.; Haberman, H.F.

    1983-07-01

    The present study is an attempt to investigate the possibility that ultraviolet irradiation in the presence of pheomelanin may be more harmful to cells than the irradiation in the presence of eumelanin. The effects of UV-visible irradiation upon Ehrlich ascites carcinoma cells in the presence of the melanin isolated from human black hair (eumelanin) or from red hair (pheomelanin) were investigated. Irradiation of these cells was found to produce cell lysis, as observed by leakage of 51Cr from labeled cells and intracellular lactic dehydrogenase from the cells and decrease in cell viability demonstrated by the trypan blue exclusion test. The three parameters were quantitatively parallel to one another under various experimental conditions, namely different periods of irradiation and irradiation in the presence of different concentrations of melanin. The above effects were more pronounced when the irradiation was carried out in the presence of melanin from red hair than in the presence of black-hair melanin. In the absence of either melanin, the irradiation did not produce any significant effect in cell viability or cell lysis. Irradiation of the cells in the presence of red-hair melanin also decreased the transplantability of these cells. These observations clearly show that irradiation of cells in the presence of pheomelanin could produce cytotoxic effects. The present experimental design may have application in the development of in vitro models for the study of UV radiation-induced cutaneous carcinogenesis. The reactions of pheomelanin may be related to the susceptibility of ''Celtic'' skin to UV radiation-induced skin damage and carcinogenesis.

  6. Melanin-Associated Synthesis of SERS-Active Nanostructures and the Application for Monitoring of Intracellular Melanogenesis

    OpenAIRE

    Haixin Dong; Zhiming Liu; Huiqing Zhong; Hui Yang; Yan Zhou; Yuqing Hou; Jia Long; Jin Lin; Zhouyi Guo

    2017-01-01

    Melanin plays an indispensable role in the human body. It serves as a biological reducer for the green synthesis of precious metal nanoparticles. Melanin?Ag nanocomposites were successfully produced which exhibited very strong surface-enhanced Raman scattering (SERS) effect because of the reducibility property of melanin. A melanin?Ag composite structure was synthesized in situ in melanin cells, and SERS technique was performed for the rapid imaging and quantitative assay of intracellular mel...

  7. AUTOIMMUNE EPIDERMAL BLISTERING DISEASES

    Directory of Open Access Journals (Sweden)

    Ana Maria Abreu Velez

    2013-11-01

    Full Text Available Autoimmune bullous skin diseases (ABDs are uncommon, potentially fatal diseases of skin and mucous membranes which are associated with deposits of autoantibodies and complement against distinct molecules of the epidermis and dermal/epidermal basement membrane zone (BMZ. These autoantibodies lead to a loss in skin molecular integrity, which manifests clinically as formation of blisters or erosions. In pemphigus vulgaris, loss of adhesion occurs within the epidermis. The pioneering work of Ernst H. Beutner, Ph.D. and Robert E. Jordon, M.D. confirmed the autoimmune nature of these diseases. Walter F. Lever, M.D. contributed significantly to our understanding of the histopathologic features of these diseases. Walter Lever, M.D. and Ken Hashimoto, M.D. contributed electron microscopic studies of these diseases, especially in pemphigus vulgaris and bullous pemphigoid. In bullous pemphigoid (BP, linear IgA bullous dermatosis, epidermolysis bullosa acquisita (EBA and dermatitis herpetiformis (DH, loss of adhesion takes place within or underneath the BMZ. Classic EBA demonstrates extensive skin fragility; DH is commonly associated with gluten-sensitive enteropathy, and manifests clinically with pruritic papulovesicles on the extensor surfaces of the extremities and the lumbosacral area. The clinical spectrum of bullous pemphigoid includes tense blisters, urticarial plaques, and prurigo-like eczematous lesions. Pemphigoid gestationis mostly occurs during the last trimester of pregnancy, and mucous membrane pemphigoid primarily involves the oral mucosa and conjunctivae and leads to scarring. Linear IgA bullous dermatosis manifests with tense blisters in a „cluster of jewels”-like pattern in childhood (chronic bullous disease of childhood and is more clinically heterogeneous in adulthood. Many of the autoantigens in these disorders are known and have been well characterized. ABDs may be influenced by both genetic and exogenous factors. The diagnoses of

  8. Effect of norfloxacin and moxifloxacin on melanin synthesis and antioxidant enzymes activity in normal human melanocytes.

    Science.gov (United States)

    Beberok, Artur; Wrześniok, Dorota; Otręba, Michał; Miliński, Maciej; Rok, Jakub; Buszman, Ewa

    2015-03-01

    Fluoroquinolone antibiotics provide broad-spectrum coverage for a number of infectious diseases, including respiratory as well as urinary tract infections. One of the important adverse effects of these drugs is phototoxicity which introduces a serious limitation to their use. To gain insight the molecular mechanisms underlying the fluoroquinolones-induced phototoxic side effects, the impact of two fluoroquinolone derivatives with different phototoxic potential, norfloxacin and moxifloxacin, on melanogenesis and antioxidant enzymes activity in normal human melanocytes HEMa-LP was determined. Both drugs induced concentration-dependent loss in melanocytes viability. The value of EC50 for these drugs was found to be 0.5 mM. Norfloxacin and moxifloxacin suppressed melanin biosynthesis; antibiotics were shown to inhibit cellular tyrosinase activity and to reduce melanin content in melanocytes. When comparing the both analyzed fluoroquinolones, it was observed that norfloxacin possesses greater inhibitory effect on tyrosinase activity in melanocytes than moxifloxacin. The extent of oxidative stress in cells was assessed by measuring the activity of antioxidant enzymes: SOD, CAT, and GPx. It was observed that norfloxacin caused higher depletion of antioxidant status in melanocytes when compared with moxifloxacin. The obtained results give a new insight into the mechanisms of fluoroquinolones toxicity directed to pigmented tissues. Moreover, the presented differences in modulation of biochemical processes in melanocytes may be an explanation for various phototoxic activities of the analyzed fluoroquinolone derivatives in vivo.

  9. Kinetic and thermodynamic studies on the adsorption of heavy metals from aqueous solution by melanin nanopigment obtained from marine source: Pseudomonas stutzeri.

    Science.gov (United States)

    Manirethan, Vishnu; Raval, Keyur; Rajan, Reju; Thaira, Harsha; Balakrishnan, Raj Mohan

    2018-05-15

    The difficulty in removal of heavy metals at concentrations below 10 mg/L has led to the exploration of efficient adsorbents for removal of heavy metals. The adsorption capacity of biosynthesized melanin for Mercury (Hg(II)), Chromium (Cr(VI)), Lead (Pb(II)) and Copper (Cu(II)) was investigated at different operating conditions like pH, time, initial concentration and temperature. The heavy metals adsorption process was well illustrated by the Lagergren's pseudo-second-order kinetic model and the equilibrium data fitted excellently to Langmuir isotherm. Maximum adsorption capacity obtained from Langmuir isotherm for Hg(II) was 82.4 mg/g, Cr(VI) was 126.9 mg/g, Pb(II) was 147.5 mg/g and Cu(II) was 167.8 mg/g. The thermodynamic parameters revealed that the adsorption of heavy metals on melanin is favorable, spontaneous and endothermic in nature. Binding of heavy metals on melanin surface was proved by Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Spectroscopy (XPS). Contemplating the results, biosynthesized melanin can be a potential adsorbent for efficient removal of Hg(II), Cr(VI), Pb(II) and Cu(II) ions from aqueous solution. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. The effect of melanin on the bystander effect in human keratinocytes

    Energy Technology Data Exchange (ETDEWEB)

    Mosse, I. [Institute of Genetics and Cytology of the National Academy of Sciences, Academicheskaya Str. 27, Minsk (Belarus)]. E-mail: i.mosse@igc.bas-net.by; Marozik, P. [Institute of Genetics and Cytology of the National Academy of Sciences, Academicheskaya Str. 27, Minsk (Belarus); Radiation and Environmental Science Centre, DIT, Dublin 8 (Ireland); Seymour, C. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ont. (Canada); Mothersill, C. [Department of Medical Physics and Applied Radiation Sciences, McMaster University, Hamilton, Ont. (Canada)

    2006-05-11

    The influence of melanin on radiation-induced bystander effects has been studied. Melanin is known to be a natural substance with proved radioprotective properties in different organisms and cell lines. It is non-toxic and is effective against acute and chronic irradiation. The lower the radiation dose, the higher the relative impact of melanin protection. In this study influence of melanin on human keratinocytes (HPV-G cells) has been studied using the colony-forming assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells when transferred to unirradiated cells, caused almost the same effect as direct irradiation. Melanin increased the colony-forming ability of bystander recipient cells when it was added into culture medium before irradiation. The effect of melanin added after irradiation was to produce less protection in both the directly irradiated and bystander medium treated groups. The absorption spectrum of the filtered medium is identical to one of the intact culture medium showing that melanin was not present in filtered medium. Thus, it cannot protect recipient cells but reduces the amount of the bystander effect. It is concluded that melanin added before irradiation effectively decreased the radiation dose. The reduction of the impact of the bystander signal on recipient cells when melanin was added to the donor medium after harvest but before filtration, may mean that the bystander signal has a physical component as melanin can absorb all types of physical energy.

  11. The effect of melanin on the bystander effect in human keratinocytes

    International Nuclear Information System (INIS)

    Mosse, I.; Marozik, P.; Seymour, C.; Mothersill, C.

    2006-01-01

    The influence of melanin on radiation-induced bystander effects has been studied. Melanin is known to be a natural substance with proved radioprotective properties in different organisms and cell lines. It is non-toxic and is effective against acute and chronic irradiation. The lower the radiation dose, the higher the relative impact of melanin protection. In this study influence of melanin on human keratinocytes (HPV-G cells) has been studied using the colony-forming assay. We have shown that bystander donor medium from 0.5 Gy irradiated cells when transferred to unirradiated cells, caused almost the same effect as direct irradiation. Melanin increased the colony-forming ability of bystander recipient cells when it was added into culture medium before irradiation. The effect of melanin added after irradiation was to produce less protection in both the directly irradiated and bystander medium treated groups. The absorption spectrum of the filtered medium is identical to one of the intact culture medium showing that melanin was not present in filtered medium. Thus, it cannot protect recipient cells but reduces the amount of the bystander effect. It is concluded that melanin added before irradiation effectively decreased the radiation dose. The reduction of the impact of the bystander signal on recipient cells when melanin was added to the donor medium after harvest but before filtration, may mean that the bystander signal has a physical component as melanin can absorb all types of physical energy

  12. Melanin and Melanin-Related Polymers as Materials with Biomedical and Biotechnological Applications-Cuttlefish Ink and Mussel Foot Proteins as Inspired Biomolecules.

    Science.gov (United States)

    Solano, Francisco

    2017-07-18

    The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules. Melanin has a controversial molecular structure, dependent on the conditions of polymerization, and therefore tunable. It is found in animal hair and skin, although one of the common sources is cuttlefish (Sepia officinalis) ink. On the other hand, mussels synthesize adhesive proteins to anchor these marine animals to wet surfaces. Both melanin and mussel foot proteins contain a high number of catecholic residues, and their properties are related to these groups. Dopamine (DA) can easily polymerize to get polydopamine melanin (PDAM), that somehow shares properties with melanin and mussel proteins. Furthermore, PDAM can easily be conjugated with other components. This review accounts for the main aspects of melanin, as well as DA-based melanin-like materials, related to their biomedical and biotechnological applications.

  13. Melanin and Melanin-Related Polymers as Materials with Biomedical and Biotechnological Applications—Cuttlefish Ink and Mussel Foot Proteins as Inspired Biomolecules

    Science.gov (United States)

    2017-01-01

    The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules. Melanin has a controversial molecular structure, dependent on the conditions of polymerization, and therefore tunable. It is found in animal hair and skin, although one of the common sources is cuttlefish (Sepia officinalis) ink. On the other hand, mussels synthesize adhesive proteins to anchor these marine animals to wet surfaces. Both melanin and mussel foot proteins contain a high number of catecholic residues, and their properties are related to these groups. Dopamine (DA) can easily polymerize to get polydopamine melanin (PDAM), that somehow shares properties with melanin and mussel proteins. Furthermore, PDAM can easily be conjugated with other components. This review accounts for the main aspects of melanin, as well as DA-based melanin-like materials, related to their biomedical and biotechnological applications. PMID:28718807

  14. Melanin and Melanin-Related Polymers as Materials with Biomedical and Biotechnological Applications—Cuttlefish Ink and Mussel Foot Proteins as Inspired Biomolecules

    Directory of Open Access Journals (Sweden)

    Francisco Solano

    2017-07-01

    Full Text Available The huge development of bioengineering during the last years has boosted the search for new bioinspired materials, with tunable chemical, mechanical, and optoelectronic properties for the design of semiconductors, batteries, biosensors, imaging and therapy probes, adhesive hydrogels, tissue restoration, photoprotectors, etc. These new materials should complement or replace metallic or organic polymers that cause cytotoxicity and some adverse health effects. One of the most interesting biomaterials is melanin and synthetic melanin-related molecules. Melanin has a controversial molecular structure, dependent on the conditions of polymerization, and therefore tunable. It is found in animal hair and skin, although one of the common sources is cuttlefish (Sepia officinalis ink. On the other hand, mussels synthesize adhesive proteins to anchor these marine animals to wet surfaces. Both melanin and mussel foot proteins contain a high number of catecholic residues, and their properties are related to these groups. Dopamine (DA can easily polymerize to get polydopamine melanin (PDAM, that somehow shares properties with melanin and mussel proteins. Furthermore, PDAM can easily be conjugated with other components. This review accounts for the main aspects of melanin, as well as DA-based melanin-like materials, related to their biomedical and biotechnological applications.

  15. Detection of antibodies against Paracoccidioides brasiliensis melanin in in vitro and in vivo studies during infection.

    Science.gov (United States)

    Urán, Martha E; Nosanchuk, Joshua D; Restrepo, Angela; Hamilton, Andrew J; Gómez, Beatriz L; Cano, Luz E

    2011-10-01

    Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice.

  16. Inhibitory effect of artocarpanone from Artocarpus heterophyllus on melanin biosynthesis.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2006-09-01

    In our previous efforts to find new tyrosinase inhibitory materials, we investigated 44 Indonesian medicinal plants belonging to 24 families. Among those plants, the extract of Artocarpus heterophyllus was one of the strongest inhibitors of tyrosinase activity. By activity-guided fractionation of A. heterophyllus wood extract, we isolated artocarpanone, which inhibited both mushroom tyrosinase activity and melanin production in B16 melanoma cells. This compound is a strong candidate as a remedy for hyperpigmentation in human skin.

  17. Antibacterial Activity of Melanin from Cuttlefish and Squid Ink

    OpenAIRE

    Yuspihana Fitrial; Iin Khusnul Khotimah

    2017-01-01

    Marine environment comprises of many organism which are known to posses bioactive compound as a common means of self-defense or for the protection of eggs and embryos. Class Cephalopods (such as squidand cuttlefish) are notable for their defences, such as jetting escape movements, changes in colouration, toxic venom and inking.This study aims to compare the antibacterial activity of melanin from cuttlefish ink (Sepia sp.) with squid ink (Loligo sp.) against E. coli. Extraction and purificatio...

  18. Turnover of pigment granules: cyclic catabolism and anabolism of ommochromes within epidermal cells.

    Science.gov (United States)

    Insausti, T C; Casas, J

    2009-12-01

    Ommochromes are end products of the tryptophan metabolism in arthropods. While the anabolism of ommochromes has been well studied, the catabolism is totally unknown. In order to study it, we used the crab-spider Misumena vatia, which is able to change color reversibly in a few days, from yellow to white and back. Ommochromes is the only pigment class responsible for the body coloration in this animal. The aim of this study was to analyze the fine structure of the epidermal cells in bleaching spiders, in an attempt to correlate morphological changes with the fate of the pigment granules. Central to the process of bleaching is the lysis of the ommochrome granules. In the same cell, intact granules and granules in different degradation stages are found. The degradation begins with granule autolysis. Some components are extruded in the extracellular space and others are recycled via autophagy. Abundant glycogen appears associated to granulolysis. In a later stage of bleaching, ommochrome progranules, typical of white spiders, appear in the distal zone of the same epidermal cell. Catabolism and anabolism of pigment granules thus take place simultaneously in spider epidermal cells. A cyclic pathway of pigment granules formation and degradation, throughout a complete cycle of color change is proposed, together with an explanation for this turnover, involving photoprotection against UV by ommochromes metabolites. The presence of this turnover for melanins is discussed.

  19. Flavonoids and Melanins: a common strategy across two kingdoms.

    Science.gov (United States)

    Carletti, Giorgia; Nervo, Giuseppe; Cattivelli, Luigi

    2014-01-01

    Ultraviolet (UV) radiations alter a number of metabolic functions in vivant. They produce damages to lipids, nucleic acids and proteins, generating reactive oxygen species such as singlet oxygen (O2), hydroxyl radical (HO) and superoxide anion (O2 (-)). Plants and animals, after their water emersion, have developed biochemical mechanisms to protect themselves from that environmental threat through a common strategy. Melanins in animals and flavonoids in plants are antioxidant pigments acting as free radical scavenging mechanisms. Both are phenol compounds constitutively synthesized and enhanced after exposure to UV rays, often conferring a red-brown-dark tissue pigmentation. Noteworthy, beside anti-oxidant scavenging activity, melanins and flavonoids have acquired secondary functions that, both in plants and animals, concern reproductions and fitness. Plants highly pigmented are more resistant to biotic and abiotic stresses. Darker wild vertebrates are generally more aggressive, sexually active and resistant to stress than lighter individuals. Flavonoids have been associated with signal attraction between flowers and insects and with plant-plant interaction. Melanin pigmentation has been proposed as trait in bird communication, acting as honest signals of quality. This review shows how the molecular mechanisms leading to tissue pigmentation have many functional analogies between plants and animals and how their origin lies in simpler organisms such as Cyanobacteria. Comparative studies between plant and animal kingdoms can reveal new insight of the antioxidant strategies in vivant.

  20. Genetic Basis of Melanin Pigmentation in Butterfly Wings.

    Science.gov (United States)

    Zhang, Linlin; Martin, Arnaud; Perry, Michael W; van der Burg, Karin R L; Matsuoka, Yuji; Monteiro, Antónia; Reed, Robert D

    2017-04-01

    Despite the variety, prominence, and adaptive significance of butterfly wing patterns, surprisingly little is known about the genetic basis of wing color diversity. Even though there is intense interest in wing pattern evolution and development, the technical challenge of genetically manipulating butterflies has slowed efforts to functionally characterize color pattern development genes. To identify candidate wing pigmentation genes, we used RNA sequencing to characterize transcription across multiple stages of butterfly wing development, and between different color pattern elements, in the painted lady butterfly Vanessa cardui This allowed us to pinpoint genes specifically associated with red and black pigment patterns. To test the functions of a subset of genes associated with presumptive melanin pigmentation, we used clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing in four different butterfly genera. pale , Ddc , and yellow knockouts displayed reduction of melanin pigmentation, consistent with previous findings in other insects. Interestingly, however, yellow-d , ebony , and black knockouts revealed that these genes have localized effects on tuning the color of red, brown, and ochre pattern elements. These results point to previously undescribed mechanisms for modulating the color of specific wing pattern elements in butterflies, and provide an expanded portrait of the insect melanin pathway. Copyright © 2017 by the Genetics Society of America.

  1. Sub-nm 3D observation of human hair melanin by high-voltage STEM.

    Science.gov (United States)

    Imai, Takehito; Higuchi, Kimitaka; Yamamoto, Yuta; Arai, Shigeo; Nakano, Takashi; Tanaka, Nobuo

    2016-04-01

    The ultrastructure of melanin granules in human hair was studied using 1,000 kV high-voltage scanning transmission electron microscopy to successfully reconstruct three-dimensional images of the whole melanin granule. It was revealed that the melanin granule was composed of a membrane-like outer structure that included many spherical vesicles, and an inner matrix containing a sheet-like structure in the elongated direction of the melanin granule and a sheet-like arrays structure in the cross direction. The outer structure of the melanin granule was maintained even after exposure to hair-bleaching agents to decompose the melanin granule, suggesting that the outer structure was a highly robust structure and composition compared with the inner matrix . © The Author 2015. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Ionizing radiation changes the electronic properties of melanin and enhances the growth of melanized fungi.

    Science.gov (United States)

    Dadachova, Ekaterina; Bryan, Ruth A; Huang, Xianchun; Moadel, Tiffany; Schweitzer, Andrew D; Aisen, Philip; Nosanchuk, Joshua D; Casadevall, Arturo

    2007-05-23

    Melanin pigments are ubiquitous in nature. Melanized microorganisms are often the dominating species in certain extreme environments, such as soils contaminated with radionuclides, suggesting that the presence of melanin is beneficial in their life cycle. We hypothesized that ionizing radiation could change the electronic properties of melanin and might enhance the growth of melanized microorganisms. Ionizing irradiation changed the electron spin resonance (ESR) signal of melanin, consistent with changes in electronic structure. Irradiated melanin manifested a 4-fold increase in its capacity to reduce NADH relative to non-irradiated melanin. HPLC analysis of melanin from fungi grown on different substrates revealed chemical complexity, dependence of melanin composition on the growth substrate and possible influence of melanin composition on its interaction with ionizing radiation. XTT/MTT assays showed increased metabolic activity of melanized C. neoformans cells relative to non-melanized cells, and exposure to ionizing radiation enhanced the electron-transfer properties of melanin in melanized cells. Melanized Wangiella dermatitidis and Cryptococcus neoformans cells exposed to ionizing radiation approximately 500 times higher than background grew significantly faster as indicated by higher CFUs, more dry weight biomass and 3-fold greater incorporation of (14)C-acetate than non-irradiated melanized cells or irradiated albino mutants. In addition, radiation enhanced the growth of melanized Cladosporium sphaerospermum cells under limited nutrients conditions. Exposure of melanin to ionizing radiation, and possibly other forms of electromagnetic radiation, changes its electronic properties. Melanized fungal cells manifested increased growth relative to non-melanized cells after exposure to ionizing radiation, raising intriguing questions about a potential role for melanin in energy capture and utilization.

  3. The Analgesic Acetaminophen and the Antipsychotic Clozapine Can Each Redox-Cycle with Melanin.

    Science.gov (United States)

    Temoçin, Zülfikar; Kim, Eunkyoung; Li, Jinyang; Panzella, Lucia; Alfieri, Maria Laura; Napolitano, Alessandra; Kelly, Deanna L; Bentley, William E; Payne, Gregory F

    2017-12-20

    Melanins are ubiquitous but their complexity and insolubility has hindered characterization of their structures and functions. We are developing electrochemical reverse engineering methodologies that focus on properties and especially on redox properties. Previous studies have shown that melanins (i) are redox-active and can rapidly and repeatedly exchange electrons with diffusible oxidants and reductants, and (ii) have redox potentials in midregion of the physiological range. These properties suggest the functional activities of melanins will depend on their redox context. The brain has a complex redox context with steep local gradients in O 2 that can promote redox-cycling between melanin and diffusible redox-active chemical species. Here, we performed in vitro reverse engineering studies and report that melanins can redox-cycle with two common redox-active drugs. Experimentally, we used two melanin models: a convenient natural melanin derived from cuttlefish (Sepia melanin) and a synthetic cysteinyldopamine-dopamine core-shell model of neuromelanin. One drug, acetaminophen (APAP), has been used clinically for over a century, and recent studies suggest that low doses of APAP can protect the brain from oxidative-stress-induced toxicity and neurodegeneration, while higher doses can have toxic effects in the brain. The second drug, clozapine (CLZ), is a second generation antipsychotic with polypharmacological activities that remain incompletely understood. These in vitro observations suggest that the redox activities of drugs may be relevant to their modes-of-action, and that melanins may interact with drugs in ways that affect their activities, metabolism, and toxicities.

  4. Different culture media containing methyldopa for melanin production by Cryptococcus species

    Directory of Open Access Journals (Sweden)

    Ralciane de Paula Menezes

    2011-10-01

    Full Text Available INTRODUCTION: Melanin production by species of Cryptococcus is widely used to characterize C. neoformans complex in mycology laboratories. This study aims to test the efficacy of methyldopa from pharmaceutical tablet as a substrate for melanin production, to compare the production of melanin using different agar base added with methyldopa, and to compare the melanin produced in those media with that produced in Niger seed agar and sunflower seed agar by C. neoformans, C. laurentii, and C. albidus. Two isolates of each species, C. neoformans, C. laurentii, and C. albidus, and one of Candida albicans were used to experimentally detect conditions for melanin production. METHODS: The following media were tested: Mueller-Hinton agar (MHA, brain and heart infusion agar (BHIA, blood agar base (BAB, and minimal medium agar (MMA, all added with methyldopa, and the media Niger seed agar (NSA and sunflower seed agar (SSA. RESULTS: All isolates grew in most of the culture media after 24h. Strains planted on media BAB and BHIA showed growth only after 48h. All isolates produced melanin in MMA, MHA, SSA, and NSA media. CONCLUSIONS: Methyldopa in the form pharmaceutical tablet can be used as a substrate for melanin production by Cryptococcus species; minimal medium plus methyldopa was more efficient than the BAB, MHA, and BHIA in the melanin production; and NSA and SSA, followed by MMA added with methyldopa, were more efficient than other media studied for melanin production by all strains studied.

  5. Evolution of dinosaur epidermal structures.

    Science.gov (United States)

    Barrett, Paul M; Evans, David C; Campione, Nicolás E

    2015-06-01

    Spectacularly preserved non-avian dinosaurs with integumentary filaments/feathers have revolutionized dinosaur studies and fostered the suggestion that the dinosaur common ancestor possessed complex integumentary structures homologous to feathers. This hypothesis has major implications for interpreting dinosaur biology, but has not been tested rigorously. Using a comprehensive database of dinosaur skin traces, we apply maximum-likelihood methods to reconstruct the phylogenetic distribution of epidermal structures and interpret their evolutionary history. Most of these analyses find no compelling evidence for the appearance of protofeathers in the dinosaur common ancestor and scales are usually recovered as the plesiomorphic state, but results are sensitive to the outgroup condition in pterosaurs. Rare occurrences of ornithischian filamentous integument might represent independent acquisitions of novel epidermal structures that are not homologous with theropod feathers. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. Metabolic epidermal necrosis in two dogs with different underlying diseases.

    Science.gov (United States)

    Bond, R; McNeil, P E; Evans, H; Srebernik, N

    1995-05-06

    Two dogs with metabolic epidermal necrosis had hyperkeratosis of the footpads accompanied by erythematous, erosive and crusting lesions affecting the muzzle, external genitalia, perineum and periocular regions. Histopathological examination of skin biopsies revealed a superficial hydropic dermatitis with marked parakeratosis. Both dogs had high plasma activities of alkaline phosphatase and alanine aminotransferase and high concentrations of glucose, and also a marked hypoaminoacidaemia. Despite these similarities, the cutaneous eruptions were associated with different underlying diseases. One dog had a pancreatic carcinoma which had metastasised widely; the primary tumour and the metastases showed glucagon immunoreactivity on immunocytochemical staining, and the dog's plasma glucagon concentration was markedly greater than that of control dogs. The other dog had diffuse hepatic disease; its plasma glucagon concentration was similar to that of control samples and cirrhosis was identified post mortem. Metabolic epidermal necrosis in dogs is a distinct cutaneous reaction pattern which may be associated with different underlying systemic diseases; however, the pathogenesis of the skin lesions remains unclear.

  7. The prospect of using the chitin-melanin-glukancontaining materials in measures of radiating protection

    International Nuclear Information System (INIS)

    Senyuk, O.F.; Myshkovskij, N.M.; Ivchenko, V.G.; Kovalev, V.A.; Gorovoj, L.F.; Kosyakov, V.N.; Kurchenko, V.P.; Sushinskaya, N.V.; Gavrilenko, N.V.

    2004-01-01

    An installation for testing the efficiency of Petryanov fabrics in conditions of the maximal humidity is created. It was shown in research, that chitin-melanin-glukan-containing materials (ChMGM) from higher bazidial fungi has high sorptive ability in relation to isotopes of strontium, uranium, transuranic elements, in particular to americium, and also salts of heavy metals (copper, silver, lead, chromium). Main part of metal ions are quickly absorbed by these materials. The technique of processing them by ChMGM is developed with the purpose to estimate amplification the detaining ability of these filters. High concentration of salts of alkaline and alkaline-earth metals do not essentially influence the absorption level of ChMGM heavy metals and transuranic elements

  8. EPR persistence measurements of UV-induced melanin free radicals in whole skin

    International Nuclear Information System (INIS)

    Collins, B.; Poehler, T.O.; Bryden, W.A.

    1995-01-01

    Electron paramagnetic resonance is used to detect the formation of free radicals caused by exposure to ultraviolet radiation in chemically untreated rabbit skin. A fast jump in EPR signal level, occurring over a few seconds, is observed immediately after a skin sample is exposed to UV. This is followed by a slower increase toward an elevated steady-state signal over a period of hours as the skin is continuously exposed to a UV light source. Upon cessation of UV light exposure, EPR signal levels undergo an abrupt drop followed by a slower decay toward natural levels. Elevated free radical concentrations following UV exposure are found to persist for several hours in whole skin. These results are consistent with time resolved EPR measurements of photoinduced radicals in various natural melanins. (Author)

  9. Biochemistry of epidermal stem cells.

    Science.gov (United States)

    Eckert, Richard L; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A; Vemuri, Mohan C; Boucher, Shayne E; Bickenbach, Jackie R; Kerr, Candace

    2013-02-01

    The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Biochemistry of epidermal stem cells☆

    Science.gov (United States)

    Eckert, Richard L.; Adhikary, Gautam; Balasubramanian, Sivaprakasam; Rorke, Ellen A.; Vemuri, Mohan C.; Boucher, Shayne E.; Bickenbach, Jackie R.; Kerr, Candace

    2014-01-01

    Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells. PMID:22820019

  11. Melanin, a promising radioprotector: Mechanisms of actions in a mice model

    Energy Technology Data Exchange (ETDEWEB)

    Kunwar, A., E-mail: amitbio@rediffmail.com [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Adhikary, B. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Jayakumar, S. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Barik, A. [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Chattopadhyay, S. [Bio-Organic Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Raghukumar, S. [Myko Tech Private Limited, Dona Paula, Goa‐403004 (India); Priyadarsini, K.I., E-mail: kindira@barc.gov.in [Radiation and Photochemistry Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2012-10-15

    The radioprotective effect of extracellular melanin, a naturally occurring pigment, isolated from the fungus Gliocephalotrichum simplex was examined in BALB/C mice, and the probable mechanism of action was established. At an effective dose of 50 mg/kg body weight, melanin exhibited both prophylactic and mitigative activities, increasing the 30-day survival of mice by 100% and 60%, respectively, after exposure to radiation (7 Gy, whole body irradiation (WBI)). The protective activity of melanin was primarily due to inhibition of radiation-induced hematopoietic damages as evidenced by improvement in spleen parameters such as index, total cellularity, endogenous colony forming units, and maintenance of circulatory white blood cells and platelet counts. Melanin also reversed the radiation-induced decrease in ERK phosphorylation in splenic tissue, which may be the key feature in its radioprotective action. Additionally, our results indicated that the sustained activation of AKT, JNK and P38 proteins in splenic tissue of melanin pre-treated group may also play a secondary role. This was also supported by the fact that melanin could prevent apoptosis in splenic tissue by decreasing BAX/Bcl-XL ratio, and increasing the expressions of the proliferation markers (PCNA and Cyclin D1), compared to the radiation control group. Melanin also reduced the oxidative stress in hepatic tissue and abrogated immune imbalance by reducing the production of pro-inflammatory cytokines (IL6 and TNFα). In conclusion, our results confirmed that fungal melanin is a very effective radioprotector against WBI and the probable mechanisms of radioprotection are due to modulation in pro-survival (ERK) signaling, prevention of oxidative stress and immunomodulation. -- Highlights: ► Melanin showed promising radioprotection under pre and post irradiation condition. ► Melanin protects the hematopoietic system from radiation induced damage. ► Melanin modulates pro-survival pathways, immune system

  12. From tyrosine to melanin: Signaling pathways and factors regulating melanogenesis

    Directory of Open Access Journals (Sweden)

    Zuzanna Rzepka

    2016-06-01

    Full Text Available Melanins are natural pigments of skin, hair and eyes and can be classified into two main types: brown to black eumelanin and yellow to reddish-brown pheomelanin. Biosynthesis of melanins takes place in melanosomes, which are specialized cytoplasmic organelles of melanocytes - dendritic cells located in the basal layer of the epidermis, uveal tract of the eye, hair follicles, as well as in the inner ear, central nervous system and heart. Melanogenesis is a multistep process and begins with the conversion of amino acid L-tyrosine to DOPAquinone. The addition of cysteine or glutathione to DOPAquinone leads to the intermediates formation, followed by subsequent transformations and polymerization to the final product, pheomelanin. In the absence of thiol compounds DOPAquinone undergoes an intramolecular cyclization and oxidation to form DOPAchrome, which is then converted to 5,6-dihydroksyindole (DHI or 5,6-dihydroxyindole-2-carboxylic acid (DHICA. Eumelanin is formed by polymerization of DHI and DHICA and their quinones. Regulation of melanogenesis is achieved by physical and biochemical factors. The article presents the intracellular signaling pathways: cAMP/PKA/CREB/MITF cascade, MAP kinases cascade, PLC/DAG/PKCβ cascade and NO/cGMP/PKG cascade, which are involved in the regulation of expression and activity of the melanogenesis-related proteins by ultraviolet radiation and endogenous agents (cytokines, hormones. Activity of the key melanogenic enzyme, tyrosinase, is also affected by pH and temperature. Many pharmacologically active substances are able to inhibit or stimulate melanin biosynthesis, as evidenced by in vitro studies on cultured pigment cells.

  13. Complexation in two-component chlortetracycline-melanin solutions

    Science.gov (United States)

    Lapina, V. A.; Pershukevich, P. P.; Dontsov, A. E.; Bel'Kov, M. V.

    2008-01-01

    The spectra and kinetics of fluorescence of two-component solutions of the chlortetracycline (CHTC)-DOPA-melanin (melanin or ME) system in water have been investigated. The data obtained have been compared to similar data for solutions of CHTC-melanosome from bull eye (MB), which contains natural melanin, in K-phosphate buffer at pH 7.4. The overall results indicate the occurrence of complexation between molecules of CHTC and ME as they are being excited. The studies of complexation in the solution of CHTC-MB in the buffer are complicated by the formation of a CHTC-buffer complex. The effect of optical radiation in the range 330-750 nm on the CHTC-ME complex shows selectivity: the greatest change in the spectrum occurs when the wavelength of the exciting radiation coincides with the long-wavelength band maximum of the fluorescence excitation spectrum of the CHTC-ME complex in aqueous solution. In this range, CHTC and especially ME show high photochemical stability. The nature of the radiation effect on the studied compounds in the hard UV range (λ < 330 nm) differs greatly from that in the range 330-750 nm. It is apparently accompanied by significant photochemical transmutations of all system components. By comparing the characteristics of the CHTC-ME systems with those of the related drug doxycycline (DC-ME), the conclusion has been made that the chlorine atom plays a vital role in formation of the short-wavelength band in the fluorescence spectrum of the CHTC-ME complex.

  14. Melanin-gamma rays assistants for bismuth oxide nanoparticles synthesis at room temperature for enhancing antimicrobial, and photocatalytic activity.

    Science.gov (United States)

    El-Batal, Ahmed I; El-Sayyad, Gharieb S; El-Ghamry, Abbas; Agaypi, Kerolos M; Elsayed, Mohamed A; Gobara, Mohamed

    2017-08-01

    Melanin pigment has been deemed as a natural photoprotector with strong hydrophobicity. It allured considerable compatibility with many applications in medicine, food, and nanotechnology. Penicillium chrysogenium has been devoted to the green synthesis of melanin whereby optimizing its culture and environmental conditions. The impacts of alternative economic L-tyrosine natural sources (unprecedented alternate origins) and gamma radiation were pledged for the potential growing of the pigment. Herein, notable increases in melanin yield (6.4mg/ml; much higher than nonoptimized one by 40 folds) was obtained by optimizing the culture, and environmental requirements [potato starch (3.0%), yeast extract (5.0%), copper sulfate (0.2mM), 0.25% L-tyrosine, 0.1% L-glycine, and 0.1% Tween 20 at pH5.0, and 30°C for 7.0days using 180.0rpm shaking speed]. The addition of banana's peel (2.0%) has been led to increase the melanin production up to (8.3mg/ml; much higher than optimized one by 1.29 folds). It stimulated the induced enzymes, (i.e., tyrosinase) because it contained significant amounts of L-tyrosine, dopamine, and L-DOPA as resources for melanin biosynthesis. Then irradiated P. chrysogenium (2.5kGy) induced the pigment yield to 10.3mg/ml; much higher than optimized one by (1.61 folds). On the other hand, we tailored a methodology involved the product of melanin and gamma rays (25.0kGy) to an eco-friendly synthesis of Bismuth oxide nanoparticles (BiONPs) at the room temperature. Melanin under such alkaline condition functioning as simultaneously hydrolyzes, photoprotection of the Bi seeds, and stabilizer against the uncontrolled growth and the free radicals attack. Whereas the gamma irradiation induced the room temperature condensation reaction to occur, a novel mechanism proposal was discussed. BiONPs were characterized by UV-Vis., DLS, XRD, SEM, EDX, and FTIR. DLS and XRD calculations with TEM analysis exhibited the mean diameter of BiONPs was 29.82nm. Moreover, the as

  15. Odontogenic Cyst with Verrucous Proliferation Exhibiting Melanin Pigmentation

    Directory of Open Access Journals (Sweden)

    Nidhi Manaktala

    2017-01-01

    Full Text Available Verrucous proliferation arising from odontogenic cysts is a rare entity. We report an unusual case of an infected odontogenic cyst with verrucous proliferation and melanin pigmentation in a 13-year-old male patient who presented with an intraoral swelling in relation to impacted teeth 26 and 27. The enucleated lesion was diagnosed as an odontogenic keratocyst and the patient died within two years of presentation due to multiple recurrences. The clinical, radiological, and microscopic features of the lesion are presented with an attempt to discuss the etiopathogenesis. The case hereby reported is uncommon with only eight cases reported in the literature.

  16. ESTIMATION OF MELANIN CONTENT IN IRIS OF HUMAN EYE

    Directory of Open Access Journals (Sweden)

    E. A. Genina

    2008-12-01

    Full Text Available Based on the experimental data obtained in vivo from digital analysis of color images of human irises, the mean melanin content in human eye irises has been estimated. For registration of color images the digital camera Olympus C-5060 has been used. The images have been obtained from irises of healthy volunteers as well as from irises of patients with open-angle glaucoma. The computer program has been developed for digital analysis of the images. The result has been useful for development of novel methods and optimization of already existing ones for non-invasive glaucoma diagnostics.

  17. Physico-chemical basis of radioprotection by melanin: a fungal pigment

    International Nuclear Information System (INIS)

    Barik, A.; Kunwar, A.; Singh, B.G.; Priyadarsini, K.I.; Raghukumar, S.

    2014-01-01

    Melanin is a biopolymer with wide spread biological activity like protection from UV-radiation damage, decrease of oxidative stress, binding to metals and drugs etc. Recently it has been observed that melanized fungal species grow in areas of high-radiation background in Chernobyl, and also in cooling pool water of nuclear reactors. Some of these organisms survived even after radiation exposure up to 6400 Gy. This prompted us to evaluate the radioprotecting ability of melanin. Although there are various types of melanin available, for the present radioprotection studies, melanin isolated from the culture filtrate of a fungus Gliocephalotrichum simplex was used. Chemically this particular type of melanin is the oligomeric form of dihydroxy indole and dihydroxy indole carboxylic acid and termed as eumelanin. Due to the presence of dihydroxy group in the benzene ring, they are in equilibrium with the partially oxidized (semiquinone radical form) and fully oxidized (quinone, non-radical) form. The radical nature of melanin was detected by electron paramagnetic resonance (EPR) spectrum and quantitative estimation of radical was made, in terms of spin density i. e. as 6.62 x 1017 spins/g. The protective activity of melanin was primarily due to inhibition of radiation-induced hematopoietic damages as evidenced by improvement in spleen parameters. To further understand the physico-chemical properties associated with radioprotection, reactions radiolytically generated free radicals with melanin was studied using pulse radiolysis

  18. Transferring Biomarker into Molecular Probe: Melanin Nanoparticle as a Naturally Active Platform for Multimodality Imaging

    OpenAIRE

    Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

    2014-01-01

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (

  19. (Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

    NARCIS (Netherlands)

    Wenczl, E.; Schans, G.P. van der; Roza, L.; Kolb, R.M.; Timmerman, A.J.; Smit, N.P.M.; Pavel, S.; Schothorst, A.A.

    1998-01-01

    The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by

  20. Bio-inspired Structural Colors from Deposition of Synthetic Melanin Nanoparticles by Evaporative Self-assembly

    Science.gov (United States)

    Xiao, Ming; Li, Yiwen; Deheyn, Dimitri; Yue, Xiujun; Gianneschi, Nathan; Shawkey, Matthew; Dhinojwala, Ali

    2015-03-01

    Melanin, a ubiquitous black or brown pigment in the animal kingdom, is a unique but poorly understood biomaterial. Many bird feathers contain melanosomes (melanin-containing organelles), which pack into ordered nanostructures, like multilayer or two-dimensional photonic crystal structures, to produce structural colors. To understand the optical properties of melanin and how melanosomes assemble into certain structures to produce colors, we prepared synthetic melanin (polydopamine) particles with variable sizes and aspect ratios. We have characterized the absorption and refractive index of the synthetic melanin particles. We have also shown that we can use an evaporative process to self-assemble melanin films with a wide range of colors. The colors obtained using this technique is modeled using a thin-film interference model and the optical properties of the synthetic melanin nanoparticles. Our results on self-assembly of synthetic melanin nanoparticles provide an explanation as why the use of melanosomes to produce colors is prevalent in the animal kingdom. National science foundation, air force office of scientific research, human frontier science program.

  1. Color reduction of melanin by lysosomal and peroxisomal enzymes isolated from mammalian cells.

    Science.gov (United States)

    Park, Dong Jun; Sekhon, Simranjeet Singh; Yoon, Jihee; Kim, Yang-Hoon; Min, Jiho

    2016-02-01

    Lysosomes and peroxisomes are organelles with many functions in all eukaryotic cells. Lysosomes contain hydrolytic enzymes (lysozyme) that degrade molecules, whereas peroxisomes contain enzymes such as catalase that convert hydrogen peroxide (H2O2) to water and oxygen and neutralize toxicity. In contrast, melanin is known as a helpful element to protect the skin against harmful ultraviolet rays. However, a high quantity of melanin leads to hyperpigmentation or skin cancer in human. New materials have already been discovered to inhibit tyrosinase in melanogenesis; however, melanin reduction does not suggest their preparation. In this study, we report that the color intensity because of melanin decreased by the cellular activation of lysosomes and peroxisomes. An increase in the superficial intensity of lysosome and peroxisome activities of HeLa cells was observed. In addition, a decrease in the amount of melanin has also been observed in mammalian cells without using any other chemical, showing that the process can work in vivo for treating melanin. Therefore, the results of this study indicate that the amount of melanin decreases by the lysosome and peroxisome activity after entering the cells, and functional organelles are effective in color reduction. This mechanism can be used in vivo for treating melanin.

  2. Interactions between Melanin Enzymes and Their Atypical Recruitment to the Secretory Pathway by Palmitoylation

    Directory of Open Access Journals (Sweden)

    Srijana Upadhyay

    2016-11-01

    Full Text Available Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered “atypical” secretory proteins. In this work, we found interactions among melanin enzymes and all melanin enzymes formed protein complexes. Surprisingly, the formation of protein complexes by melanin enzymes was not critical for their trafficking to the endosomal system. By palmitoylation profiling and biochemical analyses, we discovered that all four early melanin enzymes were strongly palmitoylated during conidiation. However, only the polyketide synthase (PKS Alb1 was strongly palmitoylated during both vegetative hyphal growth and conidiation when constitutively expressed alone. This posttranslational lipid modification correlates the endosomal localization of all early melanin enzymes. Intriguingly, bioinformatic analyses predict that palmitoylation is a common mechanism for potential membrane association of polyketide synthases (PKSs and nonribosomal peptide synthetases (NRPSs in A. fumigatus. Our findings indicate that protein-protein interactions facilitate melanization by metabolic channeling, while posttranslational lipid modifications help recruit the atypical enzymes to the secretory pathway, which is critical for compartmentalization of secondary metabolism.

  3. Influence of variation in melanin content on absorbance spectra of liquid skin phantoms

    CSIR Research Space (South Africa)

    Smit, Jacoba E

    2010-09-01

    Full Text Available content on absorbance spectra of liquid skin phantoms JE Smit, AE Karsten, AF Grobler, RW Sparrow Presented by JE Smit Date: 25 September 2010 circle6 Background circle6 Why study melanin? circle6 Skin pigments, melanocytes, melanosomes, melanin...

  4. Gingival melanin depigmentation by Er:YAG laser: A literature review.

    Science.gov (United States)

    Pavlic, Verica; Brkic, Zlata; Marin, Sasa; Cicmil, Smiljka; Gojkov-Vukelic, Mirjana; Aoki, Akira

    2018-04-01

    Laser ablation is recently suggested as a most effective and reliable technique for depigmentation of melanin hyperpigmented gingiva. To date, different lasers have been used for gingival depigmentation (CO 2 , diode, Nd:YAG, Er:YAG and Er,Cr:YSGG lasers). The use of Er:YAG laser for depigmentation of melanin hyperpigmented gingiva has gained increasing importance in recent years. The purpose of this study was to report removal of gingival melanin pigmentation using an Er:YAG laser in a literature review. The main outcomes, such as improvement of signs (clinical parameters of bleeding, erythema, swelling and wound healing), symptoms (pain) and melanin recurrence/repigmentation were measured. The literature demonstrated that depigmentation of gingival melanin pigmentation can be performed safely and effectively by Er:YAG laser resulting in healing and an esthetically significant improvement of gingival discoloration. Thus, Er:YAG laser seems to be safe and useful in melanin depigmentation procedure. However, the main issue in giving the final conclusion of the optimal Er:YAG laser use in melanin depigmentation is that, to date, studies are offering completely discrepant Er:YAG laser procedure protocols (complex settings of laser parameters), and different criteria for the assessment of depigmentation and repigmentation (recurrence), thus hampering the comparison of the results. Therefore, further studies are necessary to give an optimal recommendation on the use of Er:YAG laser in gingival melanin hyperpigmentation.

  5. Detection of Antibodies against Paracoccidioides brasiliensis Melanin in In Vitro and In Vivo Studies during Infection ▿

    OpenAIRE

    Urán, Martha E.; Nosanchuk, Joshua D.; Restrepo, Angela; Hamilton, Andrew J.; Gómez, Beatriz L.; Cano, Luz E.

    2011-01-01

    Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal anti...

  6. Quercus infectoria and Terminalia chebula decrease melanin content and tyrosinase activity in B16/F10 cell lines

    Directory of Open Access Journals (Sweden)

    Akram Jamshidzadeh

    2017-10-01

    Full Text Available Context: One of the most complained skin cares in ethnic skin like Asian women is hyperpigmentation, and lightening preparations have been long-standing desired. Due to the side effects of current drugs, medicinal plants have attracted more attentions as a source of novel drugs. Mazo (Quercus infectoria galls and Terminalia chebula fruits have been suggested in Persian Traditional Medicine as a safe treatment for hyperpigmentation. Aims: To evaluate the cytotoxicity and the effect on melanin synthesis in B16/F10 melanoma of Q. infectoria and T. chebula extracts. Methods: After collection and scientific authentication, plants were extracted by maceration method with methanol and were standardized based on total phenolic content. MTT assay and colorimetric method were used for cytotoxicity and determination of melanin content and tyrosinase activity in B16/F10 cells, respectively. Kojic acid was used as a reference compound. Results: Total phenolic content of Q. infectoria and T. chebula was determined as 287.34 ± 4.21 and 172.61 ± 8.67 mg gallic acid equivalent/g dried extract, respectively. Both plants decreased cell viability at 100 µg/mL and significantly reduced intercellular melanin to 66.25% and 71.1%, respectively in comparison to kojic acid (56.63% at 50 µg/mL. In the same concentration, 65.7% and 71.2% tyrosinase activity was inhibited by Q. infectoria and T. chebula, which significantly were different from control (p<0.001. Conclusions: These findings suggest that both plants especially Q. infectoria could inhibit melanogenesis in non-toxic concentrations and would be a good candidate for further studies.

  7. Melanin targets LC3-associated phagocytosis (LAP): A novel pathogenetic mechanism in fungal disease.

    Science.gov (United States)

    Chamilos, Georgios; Akoumianaki, Tonia; Kyrmizi, Irene; Brakhage, Axel; Beauvais, Anne; Latge, Jean-Paul

    2016-05-03

    Intracellular swelling of conidia of the major human airborne fungal pathogen Aspergillus fumigatus results in surface exposure of immunostimulatory pathogen-associated molecular patterns (PAMPs) and triggers activation of a specialized autophagy pathway called LC3-associated phagocytosis (LAP) to promote fungal killing. We have recently discovered that, apart from PAMPs exposure, cell wall melanin removal during germination of A. fumigatus is a prerequisite for activation of LAP. Importantly, melanin promotes fungal pathogenicity via targeting LAP, as a melanin-deficient A. fumigatus mutant restores its virulence upon conditional inactivation of Atg5 in hematopoietic cells of mice. Mechanistically, fungal cell wall melanin selectively excludes the CYBA/p22phox subunit of NADPH oxidase from the phagosome to inhibit LAP, without interfering with signaling regulating cytokine responses. Notably, inhibition of LAP is a general property of melanin pigments, a finding with broad physiological implications.

  8. Feasibility of Ionization-Mediated Pathway for Ultraviolet-Induced Melanin Damage.

    Science.gov (United States)

    Mandal, Mukunda; Das, Tamal; Grewal, Baljinder K; Ghosh, Debashree

    2015-10-22

    Melanin is the pigment found in human skin that is responsible for both photoprotection and photodamage. Recently there have been reports that greater photodamage of DNA occurs when cells containing melanin are irradiated with ultraviolet (UV) radiation, thus suggesting that the photoproducts of melanin cause DNA damage. Photoionization processes have also been implicated in the photodegradation of melanin. However, not much is known about the oxidation potential of melanin and its monomers. In this work we calculate the ionization energies of monomers, dimers, and few oligomers of eumelanin to estimate the threshold energy required for the ionization of eumelanin. We find that this threshold is within the UV-B region for eumelanin. We also look at the charge and spin distributions of the various ionized states of the monomers that are formed to understand which of the ionization channels might favor monomerization from a covalent dimer.

  9. Madecassoside Inhibits Melanin Synthesis by Blocking Ultraviolet-Induced Inflammation

    Directory of Open Access Journals (Sweden)

    Eunsun Jung

    2013-12-01

    Full Text Available Madecassoside (MA, a pentacyclic triterpene isolated from Centella asitica (L., is used as a therapeutic agent in wound healing and also as an anti-inflammatory and anti-aging agent. However, the involvement of MA in skin-pigmentation has not been reported. This study was conducted to investigate the effects of MA on ultraviolet (UV-induced melanogenesis and mechanisms in a co-culture system of keratinocytes and melanocytes. MA significantly inhibited UVR-induced melanin synthesis and melanosome transfer in the co-culture system. These effects were further demonstrated by the MA-induced inhibition of protease-activated receptor-2 expression and its signaling pathway, cyclooxygenase-2, prostaglandin E2 and prostaglandin F2 alpha in keratinocytes. The clinical efficacy of MA was confirmed on artificially tanned human skin. MA significantly reduced UV-induced melanin index at 8 weeks after topical application. Overall, the study demonstrated significant benefits of MA use in the inhibition of hyperpigmentation caused by UV irradiation.

  10. Melanin is Effective Radioprotector against Chronic Irradiation and Low Radiation Doses

    International Nuclear Information System (INIS)

    Mosse, I.; Plotnikova, S.; Kostrova, L.; Molophei, V.; Dubovic, B.

    2001-01-01

    Full text: Earlier we found pigment melanin ability to reduce significantly genetic consequences of acute irradiation in animals (drosophila, mice) and cultured human cells and to decrease strongly 'genetic load' accumulated in irradiated populations. The influence of melanin isolated from human hair on genetic effects of chronic irradiation in mice has been investigated. Melanin suspension or distilled water were injected every day into stomach of animals during 1-3 Gy g-irradiation with dose rate 0.007Gy/h. Levels of reciprocal translocations in germ cells were analysed cytologically. Melanin influence on genetic effect of chronic irradiation was shown to be even more effective than that of acute one. Radioadaptive response was used in order to study melanin influence on low radiation dose effect. We have demonstrated adaptive response in mice germ cells and bone marrow cells frequency of chromosomal aberrations in these cells after 0.2+1.5 Gy was about half as much as 1.7 Gy effect. Melanin injection 2 hours before the conditioning dose of 0.2 Gy resulted in the same mutation level as before 1.7 Gy adaptive response was not found. If melanin was applied between the first and second doses, both adaptive reaction and protection led to 4-fold decrease in aberration level. Thus melanin is able to remove completely low radiation dose effect. Complete toxicological tests have been conducted. The pigment melanin is not toxic and does not possess a mutagenic, teratogenic or carcinogenic activity. Melanin could be used in medicine for people protection against genetic consequences of long-term irradiation at low doses. (author)

  11. Renal origin of rat urinary epidermal growth factor

    DEFF Research Database (Denmark)

    Nexø, Ebba; Poulsen, Steen Seier

    1984-01-01

    The origin of rat urinary epidermal growth factor (EGF) has been investigated. Unilateral nephrectomy decreased the concentration, total output of EGF and EGF/creatinine ratio by approximately 50%, while the output of creatinine was unchanged. Removal of the submandibular glands and duodenal...... Brunner's glands, organs known to produce EGF, had no influence on the output of EGF in urine. Renal clearance of EGF exceeded that of creatinine, and after bilateral nephrectomy or bilateral ligation of the ureters, the concentration of creatinine in serum increased, while the concentration of EGF...

  12. Multimodal microscopy and the stepwise multi-photon activation fluorescence of melanin

    Science.gov (United States)

    Lai, Zhenhua

    The author's work is divided into three aspects: multimodal microscopy, stepwise multi-photon activation fluorescence (SMPAF) of melanin, and customized-profile lenses (CPL) for on-axis laser scanners, which will be introduced respectively. A multimodal microscope provides the ability to image samples with multiple modalities on the same stage, which incorporates the benefits of all modalities. The multimodal microscopes developed in this dissertation are the Keck 3D fusion multimodal microscope 2.0 (3DFM 2.0), upgraded from the old 3DFM with improved performance and flexibility, and the multimodal microscope for targeting small particles (the "Target" system). The control systems developed for both microscopes are low-cost and easy-to-build, with all components off-the-shelf. The control system have not only significantly decreased the complexity and size of the microscope, but also increased the pixel resolution and flexibility. The SMPAF of melanin, activated by a continuous-wave (CW) mode near-infrared (NIR) laser, has potential applications for a low-cost and reliable method of detecting melanin. The photophysics of melanin SMPAF has been studied by theoretical analysis of the excitation process and investigation of the spectra, activation threshold, and photon number absorption of melanin SMPAF. SMPAF images of melanin in mouse hair and skin, mouse melanoma, and human black and white hairs are compared with images taken by conventional multi-photon fluorescence microscopy (MPFM) and confocal reflectance microscopy (CRM). SMPAF images significantly increase specificity and demonstrate the potential to increase sensitivity for melanin detection compared to MPFM images and CRM images. Employing melanin SMPAF imaging to detect melanin inside human skin in vivo has been demonstrated, which proves the effectiveness of melanin detection using SMPAF for medical purposes. Selective melanin ablation with micrometer resolution has been presented using the Target system

  13. Photoreactivity of biologically active compounds. VII. Interaction of antimalarial drugs with melanin in vitro as part of phototoxicity screening.

    Science.gov (United States)

    Kristensen, S; Orsteen, A L; Sande, S A; Tønnesen, H H

    1994-10-01

    The drugs commonly used in the treatment of malaria are photochemically unstable. Several of these compounds accumulate in melanin-rich tissues and cause toxic reactions which may be light induced. As part of the screening of the photochemical properties and phototoxic capabilities of antimalarials, the in vitro interaction of eight antimalarials with melanin was studied. The dissociation constant for the drug-melanin complex and the relative number of binding sites on melanin were estimated for six of the drugs using a curve-fitting program. The reaction rate for the formation of the melanin-drug complex was determined, and the complexes were further characterized by zeta potential measurements.

  14. Stepwise multiphoton activation fluorescence reveals a new method of melanin detection

    Science.gov (United States)

    Lai, Zhenhua; Kerimo, Josef; Mega, Yair; DiMarzio, Charles A.

    2013-06-01

    The stepwise multiphoton activated fluorescence (SMPAF) of melanin, activated by a continuous-wave mode near infrared (NIR) laser, reveals a broad spectrum extending from the visible spectra to the NIR and has potential application for a low-cost, reliable method of detecting melanin. SMPAF images of melanin in mouse hair and skin are compared with conventional multiphoton fluorescence microscopy and confocal reflectance microscopy (CRM). By combining CRM with SMPAF, we can locate melanin reliably. However, we have the added benefit of eliminating background interference from other components inside mouse hair and skin. The melanin SMPAF signal from the mouse hair is a mixture of a two-photon process and a third-order process. The melanin SMPAF emission spectrum is activated by a 1505.9-nm laser light, and the resulting spectrum has a peak at 960 nm. The discovery of the emission peak may lead to a more energy-efficient method of background-free melanin detection with less photo-bleaching.

  15. Evidence for the ectopic synthesis of melanin in human adipose tissue.

    Science.gov (United States)

    Randhawa, Manpreet; Huff, Tom; Valencia, Julio C; Younossi, Zobair; Chandhoke, Vikas; Hearing, Vincent J; Baranova, Ancha

    2009-03-01

    Melanin is a common pigment in animals. In humans, melanin is produced in melanocytes, in retinal pigment epithelium (RPE) cells, in the inner ear, and in the central nervous system. Previously, we noted that human adipose tissue expresses several melanogenesis-related genes. In the current study, we confirmed the expression of melanogenesis-related mRNAs and proteins in human adipose tissue using real-time polymerase chain reaction and immunohistochemical staining. TYR mRNA signals were also detected by in situ hybridization in visceral adipocytes. The presence of melanin in human adipose tissue was revealed both by Fontana-Masson staining and by permanganate degradation of melanin coupled with liquid chromatography/ultraviolet/mass spectrometry determination of the pyrrole-2,3,5-tricarboxylic acid (PTCA) derivative of melanin. We also compared melanogenic activities in adipose tissues and in other human tissues using the L-[U-(14)C] tyrosine assay. A marked heterogeneity in the melanogenic activities of individual adipose tissue extracts was noted. We hypothesize that the ectopic synthesis of melanin in obese adipose may serve as a compensatory mechanism that uses its anti-inflammatory and its oxidative damage-absorbing properties. In conclusion, our study demonstrates for the first time that the melanin biosynthesis pathway is functional in adipose tissue.

  16. Keratinocyte-derived laminin-332 protein promotes melanin synthesis via regulation of tyrosine uptake.

    Science.gov (United States)

    Chung, Heesung; Jung, Hyejung; Lee, Jung-Hyun; Oh, Hye Yun; Kim, Ok Bin; Han, Inn-Oc; Oh, Eok-Soo

    2014-08-01

    Melanocytes, which produce the pigment melanin, are known to be closely regulated by neighboring keratinocytes. However, how keratinocytes regulate melanin production is unclear. Here we report that melanin production in melanoma cells (B16F10 and MNT-1) was increased markedly on a keratinocyte-derived extracellular matrix compared with a melanoma cell-derived extracellular matrix. siRNA-mediated reduction of keratinocyte-derived laminin-332 expression decreased melanin synthesis in melanoma cells, and laminin-332, but not fibronectin, enhanced melanin content and α-melanocyte-stimulating hormone-regulated melanin production in melanoma cells. Similar effects were observed in human melanocytes. Interestingly, however, laminin-332 did not affect the expression or activity of tyrosinase. Instead, laminin-332 promoted the uptake of extracellular tyrosine and, subsequently, increased intracellular levels of tyrosine in both melanocytes and melanoma cells. Taken together, these data strongly suggest that keratinocyte-derived laminin-332 contributes to melanin production by regulating tyrosine uptake. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  17. A Non-canonical Melanin Biosynthesis Pathway Protects Aspergillus terreus Conidia from Environmental Stress.

    Science.gov (United States)

    Geib, Elena; Gressler, Markus; Viediernikova, Iuliia; Hillmann, Falk; Jacobsen, Ilse D; Nietzsche, Sandor; Hertweck, Christian; Brock, Matthias

    2016-05-19

    Melanins are ubiquitous pigments found in all kingdoms of life. Most organisms use them for protection from environmental stress, although some fungi employ melanins as virulence determinants. The human pathogenic fungus Aspergillus fumigatus and related Ascomycetes produce dihydroxynaphthalene- (DHN) melanin in their spores, the conidia, and use it to inhibit phagolysosome acidification. However, biosynthetic origin of melanin in a related fungus, Aspergillus terreus, has remained a mystery because A. terreus lacks genes for synthesis of DHN-melanin. Here we identify genes coding for an unusual NRPS-like enzyme (MelA) and a tyrosinase (TyrP) that A. terreus expressed under conidiation conditions. We demonstrate that MelA produces aspulvinone E, which is activated for polymerization by TyrP. Functional studies reveal that this new pigment, Asp-melanin, confers resistance against UV light and hampers phagocytosis by soil amoeba. Unexpectedly, Asp-melanin does not inhibit acidification of phagolysosomes, thus likely contributing specifically to survival of A. terreus conidia in acidic environments. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Bioinspired near-infrared-excited sensing platform for in vitro antioxidant capacity assay based on upconversion nanoparticles and a dopamine-melanin hybrid system.

    Science.gov (United States)

    Wang, Dong; Chen, Chuan; Ke, Xuebin; Kang, Ning; Shen, Yuqing; Liu, Yongliang; Zhou, Xi; Wang, Hongjun; Chen, Changqing; Ren, Lei

    2015-02-11

    A novel core-shell structure based on upconversion fluorescent nanoparticles (UCNPs) and dopamine-melanin has been developed for evaluation of the antioxidant capacity of biological fluids. In this approach, dopamine-melanin nanoshells facilely formed on the surface of UCNPs act as ultraefficient quenchers for upconversion fluorescence, contributing to a photoinduced electron-transfer mechanism. This spontaneous oxidative polymerization of the dopamine-induced quenching effect could be effectively prevented by the presence of various antioxidants (typically biothiols, ascorbic acid (Vitamin C), and Trolox). The chemical response of the UCNPs@dopamine-melanin hybrid system exhibited great selectivity and sensitivity toward antioxidants relative to other compounds at 100-fold higher concentration. A satisfactory correlation was established between the ratio of the "anti-quenching" fluorescence intensity and the concentration of antioxidants. Besides the response of the upconversion fluorescence signal, a specific evaluation process for antioxidants could be visualized by the color change from colorless to dark gray accompanied by the spontaneous oxidation of dopamine. The near-infrared (NIR)-excited UCNP-based antioxidant capacity assay platform was further used to evaluate the antioxidant capacity of cell extracts and human plasma, and satisfactory sensitivity, repeatability, and recovery rate were obtained. This approach features easy preparation, fluorescence/visual dual mode detection, high specificity to antioxidants, and enhanced sensitivity with NIR excitation, showing great potential for screening and quantitative evaluation of antioxidants in biological systems.

  19. Anti-infective properties of the melanin-glucan complex obtained from medicinal tinder bracket mushroom, Fomes fomentarius (L.: Fr.) Fr. (Aphyllophoromycetideae).

    Science.gov (United States)

    Seniuk, Olga F; Gorovoj, Leontiy F; Beketova, Galina V; Savichuk, Hatalia O; Rytik, Petr G; Kucherov, Igor I; Prilutskay, Alla B; Prilutsky, Alexandr I

    2011-01-01

    The goal of this investigation was to comparatively study the efficiency of traditionally used anti-infective drugs and biopolymer complexes originated from the medicinal mushroom Fomes fomentarius (L.:Fr.) Fr.: 1) water-soluble melanin-glucan complex (MGC; -80% melanins and -20% beta-glucans) and 2) insoluble chitin-glucan-melanin complex (ChGMC; -70% chitin, -20% beta-glucans, and -10% melanins). Infectious materials (Helicobacter pylori, Candida albicans, and Herpes vulgaris I and HIV-1(zmb) were used in pure cultures of in vitro and in vivo models on experimental animals. Comparison studies of fungal biopolymers and effective modern antifungal, antibacterial, and antiviral drugs were used in in vitro models. The comparative clinical efficiency of ChGMC and of etiotropic pharmaceuticals in models of H. pylori, C. albicans, and H. vulgaris I infection contamination were studied. Using in vitro models, it was established that MGC completely depresses growth of C. albicans. MGC had an antimicrobial effect on H. pylori identical to erythromycin in all concentrations, and had a stronger action on this bacterium than other tested antibiotics. Tested MGC possesses simultaneously weak toxicity and high anti-HIV-1 activity in comparison with zidovudine (Retrovir). The obtained results show that CLUDDT therapy in Wistar rats with the application of ChGMC is, on average, 1.35-1.43 times as effective as a traditional one. Considering the absence of MGC and ChGMC toxic properties on blood cells even in very high concentrations, these complexes may be used as a source of biopolymers for the creation of essentially new agents for wide application in infectious pathology.

  20. The role of alpha-synuclein in melanin synthesis in melanoma and dopaminergic neuronal cells.

    Directory of Open Access Journals (Sweden)

    Tianhong Pan

    Full Text Available The relatively high co-occurrence of Parkinson's disease (PD and melanoma has been established by a large number of epidemiological studies. However, a clear biological explanation for this finding is still lacking. Ultra-violet radiation (UVR-induced skin melanin synthesis is a defense mechanism against UVR-induced damage relevant to the initiation of melanoma, whereas, increased neuromelanin (NM, the melanin synthesized in dopaminergic neurons, may enhance the susceptibility to oxidative stress-induced neuronal injury relevant to PD. SNCA is a PD-causing gene coding for alpha-Synuclein (α-Syn that expresses not only in brain, but also in skin as well as in tumors, such as melanoma. The findings that α-Syn can interact with tyrosinase (TYR and inhibit tyrosine hydroxylase (TH, both of which are enzymes involved in the biosynthesis of melanin and dopamine (DA, led us to propose that α-Syn may participate in the regulation of melanin synthesis. In this study, by applying ultraviolet B (UVB light, a physiologically relevant stimulus of melanogenesis, we detected melanin synthesis in A375 and SK-MEL-28 melanoma cells and in SH-SY5Y and PC12 dopaminergic neuronal cells and determined effects of α-Syn on melanin synthesis. Our results showed that UVB light exposure increased melanin synthesis in all 4 cell lines. However, we found that α-Syn expression reduced UVB light-induced increase of melanin synthesis and that melanin content was lower when melanoma cells were expressed with α-Syn, indicating that α-Syn may have inhibitory effects on melanin synthesis in melanoma cells. Different from melanoma cells, the melanin content was higher in α-Syn-over-expressed dopaminergic neuronal SH-SY5Y and PC12 cells, cellular models of PD, than that in non-α-Syn-expressed control cells. We concluded that α-Syn could be one of the points responsible for the positive association between PD and melanoma via its differential roles in melanin synthesis in

  1. An objective assessment of melanin in vitiligo skin treated with Balneo PUVA therapy.

    Science.gov (United States)

    Hegyi, V; Petrovajová, M; Novotný, M

    2014-02-01

    Visual clinical methods of skin color evaluation for diagnostic purposes are so far mostly subjective and thus inaccurate. We present a modified method of melanin amount measurement based on diffuse reflectance spectroscopy (DRS). This method is non-invasive and objective, and allows easy quantification and comparison of melanin levels. Skin pigmentation was measured by DRS method in 0-18 year old patients at the Department of Pediatric Dermatovenerology, School of Medicine Comenius University Bratislava. Patients were treated for their vitiligo by Balneo PUVA treatment twice weekly. Each patient had measured his remittance spectra from the treated vitiliginous skin before the treatment was started, after 10 irradiations of Balneo PUVA and at the end of the treatment after 25 irradiations of Balneo PUVA. In our study as a reference skin for spectroscopic assessment of melanin in vivo was used the averaged remittance spectra (measured on the inner arm) from the sample of 10 albino patients. The remittance spectra obtained from the vitiligo patients were ratioed against the newly described remittance reference albino skin. We exploited the linear behavior of the spectral curve in the 620-720 nm interval (significant for melanin absorption) and used the slope of the regression line to compute the quantification index α. By clinical examination before the Balneo PUVA therapy, after the 10th dose of Balneo PUVA therapy as well as at the end of the complete course of Balneo PUVA therapy (after 25 irradiations) we recorded a marked increase of pigmentation in all treated patients for their vitiligo. In each patient the values of melanin quantification angle α were calculated. Statistically we found a significant difference between the melanin quantification angle α in vitiliginous skin before, during the 10th dose of treatment and after the treatment. Similar significant difference was also observed between treated and non-involved skin. We could confirm a clear

  2. Screening of micro-organisms for decolorization of melanins produced by bluestain fungi.

    Science.gov (United States)

    Rättö, M; Chatani, M; Ritschkoff, A C; Viikari, L

    2001-03-01

    A total of 17 fungi and four bacteria were screened for their ability to decolorize melanin, using isolated extracellular melanin of the bluestain fungus Aureobasidium pullulans as substrate. On agar media, decolorization was observed by four fungal strains: Bjerkandera adusta VTT-D-99746, Galactomyces geotrichum VTT-D-84228, Trametes hirsuta VTT-D-95443 and Trametes versicolor VTT-D-99747. The four fungi were more efficient on nitrogen-limited medium than on complete medium. The melanin-decolorizing activity of G. geotrichum appeared to be located on the mycelium and could be liberated into the medium enzymatically.

  3. Toxic epidermal necrolysis successfully treated with etanercept.

    Science.gov (United States)

    Gubinelli, Emanuela; Canzona, Flora; Tonanzi, Tiziano; Raskovic, Desanka; Didona, Biagio

    2009-03-01

    Toxic epidermal necrolysis (TEN) is a rare and acute severe adverse reaction to drugs, characterised by massive apoptosis and widespread epidermal and mucosal detachment. Although no gold standard therapy exists, human i.v. immunoglobulins have recently been described as an effective treatment for this disease. We report a case of phenobarbital-induced TEN in a 59-year-old white woman where the epidermal detachment stopped 48 h after beginning the etanercept treatment with complete healing after 20 days. To the best of our knowledge, this is only the second reported case of TEN successfully treated with etanercept.

  4. Can a one-layer optical skin model including melanin and inhomogeneously distributed blood explain spatially resolved diffuse reflectance spectra?

    Science.gov (United States)

    Karlsson, Hanna; Pettersson, Anders; Larsson, Marcus; Strömberg, Tomas

    2011-02-01

    Model based analysis of calibrated diffuse reflectance spectroscopy can be used for determining oxygenation and concentration of skin chromophores. This study aimed at assessing the effect of including melanin in addition to hemoglobin (Hb) as chromophores and compensating for inhomogeneously distributed blood (vessel packaging), in a single-layer skin model. Spectra from four humans were collected during different provocations using a twochannel fiber optic probe with source-detector separations 0.4 and 1.2 mm. Absolute calibrated spectra using data from either a single distance or both distances were analyzed using inverse Monte Carlo for light transport and Levenberg-Marquardt for non-linear fitting. The model fitting was excellent using a single distance. However, the estimated model failed to explain spectra from the other distance. The two-distance model did not fit the data well at either distance. Model fitting was significantly improved including melanin and vessel packaging. The most prominent effect when fitting data from the larger separation compared to the smaller separation was a different light scattering decay with wavelength, while the tissue fraction of Hb and saturation were similar. For modeling spectra at both distances, we propose using either a multi-layer skin model or a more advanced model for the scattering phase function.

  5. Corticosterone mediates the condition-dependent component of melanin-based coloration

    Czech Academy of Sciences Publication Activity Database

    Roulin, A.; Almasi, B.; Rossi-Pedruzzi, A.; Ducrest, A.-L.; Wakamatsu, K.; Mikšík, Ivan; Blount, J.D.; Jenni-Eiermann, S.; Jenni, L.

    2008-01-01

    Roč. 75, č. 4 (2008), s. 1351-1358 ISSN 0003-3472 Institutional research plan: CEZ:AV0Z50110509 Keywords : coricosterone * barn owl * melanin Subject RIV: CE - Biochemistry Impact factor: 2.828, year: 2008

  6. Blood Supply--Susceptible Formation of Melanin Pigment in Hair Bulb Melanocytes of Mice

    Directory of Open Access Journals (Sweden)

    Shogo Maeda, MD

    2015-03-01

    Conclusions: Melanin pigment formation in the hair bulb melanocytes appeared to be susceptible to the blood supply, and melanocytosis was promoted in the follicles and in the epidermis of Kitl-Tg C57BL/6 mice.

  7. Minor and trace elements in melanins determined by neutron activation analysis

    International Nuclear Information System (INIS)

    Kochanska-Dziurowicz, A.A.; Wilczok, T.; Mosulishvili, L.; Kharabadze, N.

    1986-01-01

    The presence of Au, Br, Sb, Ag, Fe, Zn, Co, Cr, Ni, Hg and Sn determined by neutron activation analysis was demonstrated in melanins isolated from human dark hair, banana peels or prepared synthetically from tyrosine. (author)

  8. The role of melanin as protector against free radicals in skin and its role as free radical indicator in hair

    Science.gov (United States)

    Herrling, Thomas; Jung, Katinka; Fuchs, Jürgen

    2008-05-01

    Throughout the body, melanin is a homogenous biological polymer containing a population of intrinsic, semiquinone-like radicals. Additional extrinsic free radicals are reversibly photo-generated by UV and visible light. Melanin photochemistry, particularly the formation and decay of extrinsic radicals, has been the subject of numerous electron spin resonance (ESR) spectroscopy studies. Several melanin monomers exist, and the predominant monomer in a melanin polymer depends on its location within an organism. In skin and hair, melanin differs in content of eumelanin or pheomelanin. Its bioradical character and its susceptibility to UV irradiation makes melanin an excellent indicator for UV-related processes in both skin and hair. The existence of melanin in skin is strongly correlated with the prevention against free radicals/ROS generated by UV radiation. Especially in the skin melanin (mainly eumelanin) ensures the only natural UV protection by eliminating the generated free radicals/ROS. Melanin in hair can be used as a free radical detector for evaluating the efficacy of hair care products. The aim of this study was to investigate the suitability of melanin as protector of skin against UV generated free radicals and as free radical indicator in hair.

  9. Detection of Antibodies against Paracoccidioides brasiliensis Melanin in In Vitro and In Vivo Studies during Infection ▿

    Science.gov (United States)

    Urán, Martha E.; Nosanchuk, Joshua D.; Restrepo, Angela; Hamilton, Andrew J.; Gómez, Beatriz L.; Cano, Luz E.

    2011-01-01

    Several cell wall constituents, including melanins or melanin-like compounds, have been implicated in the pathogenesis of a wide variety of microbial diseases caused by diverse species of pathogenic bacteria, fungi, and helminthes. Among these microorganisms, the dimorphic fungal pathogen Paracoccidioides brasiliensis produces melanin in its conidial and yeast forms. In the present study, melanin particles from P. brasiliensis were injected into BALB/c mice in order to produce monoclonal antibodies (MAbs). We identified five immunoglobulin G1 (IgG1) κ-chain and four IgM melanin-binding MAbs. The five IgG1 κ-chain isotypes are the first melanin-binding IgG MAbs ever reported. The nine MAbs labeled P. brasiliensis conidia and yeast cells both in vitro and in pulmonary tissues. The MAbs cross-reacted with melanin-like purified particles from other fungi and also with commercial melanins, such as synthetic and Sepia officinalis melanin. Melanization during paracoccidioidomycosis (PCM) was also further supported by the detection of IgG antibodies reactive to melanin from P. brasiliensis conidia and yeast in sera and bronchoalveolar lavage fluids from P. brasiliensis-infected mice, as well as in sera from human patients with PCM. Serum specimens from patients with other mycoses were also tested for melanin-binding antibodies by enzyme-linked immunosorbent assay, and cross-reactivities were detected for melanin particles from different fungal sources. These results suggest that melanin from P. brasiliensis is an immunologically active fungal structure that activates a strong IgG humoral response in humans and mice. PMID:21813659

  10. Inhibitory effect of isoprenoid-substituted flavonoids isolated from Artocarpus heterophyllus on melanin biosynthesis.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2006-07-01

    Isoprenoid-substituted flavonoids were isolated from the wood of Artocarpus heterophyllus by means of activity-guided fractionation. Artocarpin (1), cudraflavone C (2), 6-prenylapigenin (3), kuwanon C (4), norartocarpin (5) and albanin A (6) inhibited melanin biosynthesis in B16 melanoma cells without inhibiting tyrosinase. A structure-activity investigation indicated that the presence of the isoprenoid-substituted moiety enhanced the inhibitory activity on melanin production in B16 melanoma cells.

  11. Screening of Auricularia auricula strains for strong production ability of melanin pigments

    OpenAIRE

    ZOU, Yu; MA, Kun

    2017-01-01

    Abstract Melanin pigments have great application value and development potential in food industry to use as nature functional food colorants. In initial study, twenty-two Auricularia auricula strains were screened for stronger production ability of melanin pigments by solid culture. Three A. auricula strains (RF201, QD2 and QD6) with higher pigment production capacity were selected for further study through submerged culture supplementing 1 g/L l-tyrosine. The maximal pigment yields of A. aur...

  12. Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

    OpenAIRE

    Park, Hwayong; Song, Kwang Hoon; Jung, Pil Mun; Kim, Ji-Eun; Ro, Hyunju; Kim, Mi Yoon; Ma, Jin Yeul

    2013-01-01

    To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plant Arctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content in ? -melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respect...

  13. An Epidermal Biosensor for Carcinoembryonic Antigen

    National Research Council Canada - National Science Library

    Schwartz, Pauline

    2001-01-01

    ...). An epidermal biosensor is a new approach for the early continuous, in vivo detection of the onset of disease by the using genetically modified skin cells to respond to molecules secreted by tumor cells...

  14. An Epidermal Biosensor for Carcinoembryonic Antigen

    National Research Council Canada - National Science Library

    Schwartz, Pauline

    2003-01-01

    ...) An epidermal biosensor was conceived as a new approach for the early continuous, in vivo detection of the onset of disease by the using genetically modified skin cells to respond to molecules secreted by tumor cells...

  15. Redox Active Transition Metal ions Make Melanin Susceptible to Chemical Degradation Induced by Organic Peroxide.

    Science.gov (United States)

    Zadlo, Andrzej; Pilat, Anna; Sarna, Michal; Pawlak, Anna; Sarna, Tadeusz

    2017-12-01

    With aging, retinal pigment epithelium melanosomes, by fusion with the age pigment lipofuscin, form complex granules called melanolipofuscin. Lipofuscin granules may contain oxidized proteins and lipid hydroperoxides, which in melanolipofuscin could chemically modify melanin polymer, while transition metal ions present in melanin can accelerate such oxidative modifications. The aim of this research was to examine the effect of selected transition metal ions on melanin susceptibility to chemical modification induced by the water-soluble tert-butyl hydroperoxide used as an oxidizing agent. Synthetic melanin obtained by DOPA autooxidation and melanosomes isolated from bovine retinal pigment epithelium were analyzed. To monitor tert-butyl hydroperoxide-induced oxidative changes of DMa and BMs, electron paramagnetic resonance spectroscopy, UV-vis absorption spectroscopy, dynamic light scattering, atomic force microscopy and electron paramagnetic resonance oximetry were employed. These measurements revealed that both copper and iron ions accelerated chemical degradation induced by tert-butyl hydroperoxide, while zinc ions had no effect. Strong prooxidant action was detected only in the case of melanosomes and melanin degraded in the presence of iron. It can be postulated that similar chemical processes, if they occur in situ in melanolipofuscin granules of the human retinal pigment epithelium, would modify antioxidant properties of melanin and its reactivity.

  16. Intraocular distribution of melanin in human, monkey, rabbit, minipig and dog eyes.

    Science.gov (United States)

    Durairaj, Chandrasekar; Chastain, James E; Kompella, Uday B

    2012-05-01

    The purpose of this study was to quantify the melanin pigment content in sclera, choroid-RPE, and retina, three tissues encountered during transscleral drug delivery to the vitreous, in human, rabbit, monkey, minipig, and dog models. Strain differences were assessed in NZW × NZR F1 and Dutch belted rabbits and Yucatan and Gottingen minipigs. The choroid-RPE and retina tissues were divided into central (posterior pole area) and peripheral (away from posterior pole) regions while the sclera was analyzed without such division. Melanin content in the tissues was analyzed using a colorimetric assay. In all species the rank order for pigment content was: choroid-RPE >retina ≥ sclera, except in humans, where scleral melanin levels were higher than retina and central choroid. The melanin content in a given tissue differed between species. Further, while the peripheral tissue pigment levels tended to be generally higher compared to the central regions, these differences were significant in human in the case of choroid-RPE and in human, monkey, and dogs in the case of retina. Strain difference was observed only in the central choroid-RPE region of rabbits (NZW × NZR F1 >Dutch Belted). Species, strain, and regional differences exist in the melanin pigment content in the tissues of the posterior segment of the eye, with Gottingen minipig being closest to humans among the animals assessed. These differences in melanin content might contribute to differences in drug binding, delivery, and toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

  17. Efektivitas kurkumin sebagai antioksidan dan inhibitor melanin pada kultur sel B16F1

    Directory of Open Access Journals (Sweden)

    Sugiharto Sugiharto

    2013-03-01

    Full Text Available Melanin inhibitors have become increasingly important ingredients in medication and cosmetics for the prevention ofhyperpigmentation. In the last few years, a huge number of natural herbal extracts have been tested as inhibitors of melanin synthesisand some of these effects are related to the antioxidant properties. The objectives of this study were to determine of curcumin propertiesas antioxidant activity and melanin inhibitors. In this study, our data indicated that antioxidant assay with DPPH showed IC50 was16,05 μg/ml. In the absence of α-MSH (α-Melanocyte Stimulating Hormone, melanin content assay in cell B16-F1 indicated thatthe highest activity of curcumin to reduce melanin content of 45,67% at 25 μg/ml. Meanwhile, in the presence of α-MSH at the sameconcentration indicated that the highest activity was 53,87%. Based on the data, curcumin has potential properties as antioxidantactivity and melanin inhibitor.

  18. Melanin from the nitrogen-fixing bacterium Azotobacter chroococcum: a spectroscopic characterization.

    Directory of Open Access Journals (Sweden)

    Aulie Banerjee

    Full Text Available Melanins, the ubiquitous hetero-polymer pigments found widely dispersed among various life forms, are usually dark brown/black in colour. Although melanins have variety of biological functions, including protection against ultraviolet radiation of sunlight and are used in medicine, cosmetics, extraction of melanin from the animal and plant kingdoms is not an easy task. Using complementary physicochemical techniques (i.e. MALDI-TOF, FTIR absorption and cross-polarization magic angle spinning solid-state (13C NMR, we report here the characterization of melanins extracted from the nitrogen-fixing non-virulent bacterium Azotobacter chroococcum, a safe viable source. Moreover, considering dihydroxyindole moiety as the main constituent, an effort is made to propose the putative molecular structure of the melanin hetero-polymer extracted from the bacterium. Characterization of the melanin obtained from Azotobacter chroococcum would provide an inspiration in extending research activities on these hetero-polymers and their use as protective agent against UV radiation.

  19. UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production

    Science.gov (United States)

    Wood, Simon R.; Berwick, Marianne; Ley, Ronald D.; Walter, Ronald B.; Setlow, Richard B.; Timmins, Graham S.

    2006-01-01

    Controversy continues both as to which wavelengths of sunlight cause melanoma and the mechanisms by which these different wavelengths act. Direct absorption of UVB by DNA is central in albino animal models, but melanin-pigmented models have shown major contributions by wavelengths longer than UVB that are thought to be mediated by photosensitized oxidant production. The only model for which the action spectrum of melanoma causation is known is a genetically melanoma-susceptible specific cross of Xiphophorus fish. We used electron paramagnetic resonance to quantitatively detect the UV induction of reactive melanin radicals in situ in the melanin-containing cells in the skin of this model and derived the action spectrum for melanin-photosensitized oxidant production (Φox). This action spectrum was identical to that for melanoma induction (Φmel). These results confirm the hypothesis that melanin-photosensitized radical production is the major causative step of melanoma in this model and demonstrate that the wavelengths and mechanisms of melanoma causation in different models are dependent on the presence of melanin. This approach should be applicable to humans, thus providing an accurate surrogate for Φmel for prevention studies. PMID:16537493

  20. Epidermal growth factor in the rat prostate

    DEFF Research Database (Denmark)

    Tørring, Niels; Jørgensen, P E; Poulsen, Steen Seier

    1998-01-01

    Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate.......Epidermal growth factor (EGF) induces proliferation in prostate epithelial and stromal cells in primary culture. This investigation was set up to characterize the time and spatial expression of EGF in the rat prostate....

  1. Foliar Epidermal Studies of Plants in Euphorbiaceae

    Directory of Open Access Journals (Sweden)

    H. A. Thakur

    2014-03-01

    Full Text Available This paper describes foliar epidermal structure in 17 species belonging to 17 genera of the family Euphoprbiaceae. Anomocytic stomata is predominant, rarely they are anisocytic, paracytic on the same foliar surface with different combinations. Leaves are hypostomatic and rarely amphistomatic. The foliar surface is smooth, rarely striated. The foliar epidermal cell walls are straight or undulate. Distribution of stomata, stomatal index, stomatal frequency, stomatal size and other cell wall contours are described in detail.

  2. Epidermal Inclusion Cysts of The Breast

    Directory of Open Access Journals (Sweden)

    Amir R. Motabar

    2009-02-01

    Full Text Available Epidermal inclusion cysts are uncommon in the breast, but the consequences can besevere when these cysts occur in the breast parenchyma. Here,we report two suchcases. The patient in case 1 was an 37-year-old woman with a 3-cm palpable mass inthe right breast. Mammography revealed a round and smoothly outlined mass, whichindicated a benign tumor, and sonography showed an irregularly shaped and heterogeneoushypoechoic mass, fibroadenoma was suspected on the basis of clinical andimage findings, but excisional biopsy revealed an epidermal inclusion cyst. The patientin case 2 was a 50-year-old woman with a 2.5-cm lesion in the left breast. Mammographyrevealed a round, dense, smoothly outlined mass, and sonography showeda well-defined, central hyperechoic mass. . Breast cancer was suspected on the basisof the sonographic findings and the age of the patient, but the resected specimen revealedan epidermal inclusion cyst. Although epidermal inclusion cysts are benign,occasionally they may play a role in the origin of squamous carcinoma of the breast. .Mammographic and sonographic features of an epidermal cyst may mimic a malignantlesion. Malignant change appears to occur more frequently in epidermal inclusioncysts in the mammary gland, compared to common epidermal inclusion cysts,and this may be associated with origination of mammary epidermal inclusion cystsfrom squamous metaplasia of the mammary duct epithelium.Epidermmoid inclusion cyst of the breast is potentially serious, although such cystsare rare, and differentiation from a malignant or benign breast tumor is required. Excisionis probably the most appropriate treatment, and can eliminate the possible riskof malignant transformation.

  3. Brief study about the distribution of recombinant human Epidermic Growth Factor (rh-EGF)

    International Nuclear Information System (INIS)

    Rodriguez Garcia, J.C.; De Dios D Espaux, R.; Bello Garciga, J.L.

    1997-01-01

    This report describes results of the study about biodistribution of I-125 recombinant human Epidermic Growth Factor (rhEGF). The radiolabelled product was administrated to Sprague Dawley rats in three different ways: intramuscular, subcutaneous and epidermic; the highest concentration of EGF in blood was found 4 hours after rhEGF administration, with a greater distribution in the plasma with regard to cellular pellet. The slowest plasma clearance corresponded to the intramuscular administration. The highest concentration of radiolabelled rhEGF was found in liver, kidney and intestine. It was found that radiolabelled EGF is excreted mainly throughout urine and faeces although other excretion pathways could exist

  4. Differences in human skin between the epidermal growth factor receptor distribution detected by EGF binding and monoclonal antibody recognition

    DEFF Research Database (Denmark)

    Green, M R; Couchman, J R

    1985-01-01

    , the eccrine sweat glands, capillary system, and the hair follicle outer root sheath, generally similar in pattern to that previously reported for full-thickness rat skin and human epidermis. The same areas also bound EGF-R1 but in addition the monoclonal antibody recognized a cone of melanin containing......Two methods have been used to examine epidermal growth factor (EGF) receptor distribution in human scalp and foreskin. The first employed [125I]EGF viable explants and autoradiography to determine the EGF binding pattern while the second used a monoclonal antibody to the human EGF receptor to map...... whether EGF-R1 could recognize molecules unrelated to the EGF receptor, the EGF binding and EGF-R1 recognition profiles were compared on cultures of SVK14 cells, a SV40 transformed human keratinocyte cell line. EGF binding and EGF-R1 monoclonal antibody distribution on these cells was found to be similar...

  5. Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

    OpenAIRE

    Negro, Juan J.; Fynlayson, Clive; Galván, Ismael

    2018-01-01

    Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures—the majority of paleo-colour studies involve melanin granules—is not without risks. In addition, ...

  6. Up-regulation of melanin synthesis by the antidepressant fluoxetine.

    Science.gov (United States)

    Liao, Sha; Shang, Jing; Tian, Xiaoli; Fan, Xueqi; Shi, Xiupu; Pei, Siran; Wang, Qian; Yu, Boyang

    2012-08-01

    Fluoxetine, a member of the class of selective serotonin reuptake inhibitors, is a potent antidepressant commonly used in clinical practice. Here, we report that fluoxetine increases cellular tyrosinase (TYR) activity, enhances the protein levels of microphthalmia-associated transcription factor (MITF), TYR and tyrosinase-related protein-1 (TRP-1) and eventually leads to a dramatic increase in melanin production in both murine B16F10 melanoma cells and normal human melanocytes (NHMCs). In well-characterized C57BL/6 mouse models, systemic application of fluoxetine increased hair pigmentation by up-regulating hair follicular MITF, TYR, TRP-1 and tyrosinase-related protein-2 (TRP-2) protein levels. Using a serotonin 1A receptor (SR1A) antagonist and RNA interference (RNAi) technique, we revealed that SR1A appears to be one of the involved pathways in the fluoxetine-induced melanogenesis in B16F10 cells. These results suggest that fluoxetine may hold a significant therapeutic potential for treating skin hypopigmentation disorders, and SR1A may serve as a novel target in modulating melanogenesis. © 2012 John Wiley & Sons A/S.

  7. New SPECT tracers: Example of tracers of proteoglycans and melanin

    International Nuclear Information System (INIS)

    Cachin, F.; Mestas, D.; Kelly, A.; Merlin, C.; Veyre, A.; Maublant, J.; Cachin, F.; Chezal, J.M.; Miot-Noirault, E.; Moins, N.; Auzeloux, P.; Vidal, A.; Bonnet-Duquennoy, M.; Boisgard, S.; D'Incan, M.; Madelmont, J.C.; Maublant, J.; Boisgard, S.; D'Incan, M.; Redini, F.; Filaire, M.

    2009-01-01

    The majority of research program on new radiopharmaceuticals turn to tracers used for positron emission tomography (PET). Only a few teams work on new non fluorine labeled tracers. However, the coming of SPECT/CT gamma cameras, the arrival of semi-conductors gamma cameras should boost the development of non-PET tracers. We exhibit in this article the experience acquired by our laboratory in the conception and design of two new non fluorine labelled compounds. The 99m Tc-N.T.P. 15-5 (N.T.P. 15-5 for N-[tri-ethyl-ammonium]-3-propyl-[15]ane-N5) which binds to proteoglycans could be used for the diagnosis and staging of osteoarthritis and chondrosarcoma. The iodo benzamides, specific to the melanin, are nowadays compared to 18 F-fluorodeoxyglucose in a phase III clinical trial for the diagnosis and detection of melanoma metastasis. Our last development focus on N-[2-(diethyl-amino)ethyl]-4 and 2-iodo benzamides respectively B.Z.A. and B.Z.A.2 hetero-aromatic analogues usable for melanoma treatment. (authors)

  8. Melanin-Like Pigment Synthesis by Soil Bacillus weihenstephanensis Isolates from Northeastern Poland.

    Directory of Open Access Journals (Sweden)

    Justyna M Drewnowska

    Full Text Available Although melanin is known for protecting living organisms from harmful physical and chemical factors, its synthesis is rarely observed among endospore-forming Bacillus cereus sensu lato. Here, for the first time, we reported that psychrotolerant Bacillus weihenstephanensis from Northeastern Poland can produce melanin-like pigment. We assessed physicochemical properties of the pigment and the mechanism of its synthesis in relation to B. weihenstephanensis genotypic and phenotypic characteristics. Electron paramagnetic resonance (EPR spectroscopy displayed a stable free radical signal of the pigment from environmental isolates which are consistent with the commercial melanin. Fourier transform infrared spectroscopy (FT-IR and physicochemical tests indicated the phenolic character of the pigment. Several biochemical tests showed that melanin-like pigment synthesis by B. weihenstephanensis was associated with laccase activity. The presence of the gene encoding laccase was confirmed by the next generation whole genome sequencing of one B. weihenstephanensis strain. Biochemical (API 20E and 50CHB tests and genetic (Multi-locus Sequence Typing, 16S rRNA sequencing, and Pulsed-Field Gel Electrophoresis characterization of the isolates revealed their close relation to the psychrotrophic B. weihenstephanensis DSMZ 11821 reference strain. The ability to synthesize melanin-like pigment by soil B. weihenstephanensis isolates and their psychrotrophic character seemed to be a local adaptation to a specific niche. Detailed genetic and biochemical analyses of melanin-positive environmental B. weihenstephanensis strains shed some light on the evolution and ecological adaptation of these bacteria. Moreover, our study raised new biotechnological possibilities for the use of water-soluble melanin-like pigment naturally produced by B. weihenstephanensis as an alternative to commercial non-soluble pigment.

  9. Melanin dependent survival of Apergillus fumigatus conidia in lung epithelial cells.

    Science.gov (United States)

    Amin, Shayista; Thywissen, Andreas; Heinekamp, Thorsten; Saluz, Hans Peter; Brakhage, Axel A

    2014-07-01

    Aspergillus fumigatus is the most important air-borne pathogenic fungus of humans. Upon inhalation of conidia, the fungus makes close contact with lung epithelial cells, which only possess low phagocytic activity. These cells are in particular interesting to address the question whether there is some form of persistence of conidia of A. fumigatus in the human host. Therefore, by also using uracil-auxotrophic mutant strains, we were able to investigate the interaction of A549 lung epithelial cells and A. fumigatus conidia in detail for long periods. Interestingly, unlike professional phagocytes, our study showed that the presence of conidial dihydroxynaphthalene (DHN) melanin enhanced the uptake of A. fumigatus conidia by epithelial cells when compared with non-pigmented pksP mutant conidia. Furthermore, conidia of A. fumigatus were able to survive within epithelial cells. This was due to the presence of DHN melanin in the cell wall of conidia, because melanised wild-type conidia showed a higher survival rate inside epithelial cells and led to inhibition of acidification of phagolysosomes. Both effects were not observed for white (non-melanised) conidia of the pksP mutant strain. Moreover, in contrast to pksP mutant conidia, melanised wild-type conidia were able to inhibit the extrinsic apoptotic pathway in A549 lung epithelial cells even for longer periods. The anti-apoptotic effect was not restricted to conidia, because both conidia-derived melanin ghosts (cell-free DHN melanin) and a different type of melanin, dihydroxyphenylalanine (DOPA) melanin, acted anti-apoptotically. Taken together, these data indicate the possibility of melanin-dependent persistence of conidia in lung epithelial cells. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. Melanin-Covered Nanoparticles for Protection of Bone Marrow During Radiation Therapy of Cancer

    International Nuclear Information System (INIS)

    Schweitzer, Andrew D.; Revskaya, Ekaterina; Chu, Peter; Pazo, Valeria; Friedman, Matthew; Nosanchuk, Joshua D.; Cahill, Sean; Frases, Susana; Casadevall, Arturo; Dadachova, Ekaterina

    2010-01-01

    Purpose: Protection of bone marrow against radiotoxicity during radioimmunotherapy and in some cases external beam radiation therapy such as hemi-body irradiation would permit administration of significantly higher doses to tumors, resulting in increased efficacy and safety of treatment. Melanin, a naturally occurring pigment, possesses radioprotective properties. We hypothesized that melanin, which is insoluble, could be delivered to the bone marrow by intravenously administrated melanin-covered nanoparticles (MNs) because of the human body's 'self-sieving' ability, protecting it against ionizing radiation. Methods and Materials: The synthesis of MNs was performed via enzymatic polymerization of 3,4-dihydroxyphenylalanine and/or 5-S-cysteinyl-3,4-dihydroxyphenylalanine on the surface of 20-nm plain silica nanoparticles. The biodistribution of radiolabeled MNs in mice was done at 3 and 24 h. Healthy CD-1 mice (Charles River Laboratories International, Inc., Wilmington, MA) or melanoma tumor-bearing nude mice were given MNs intravenously, 50 mg/kg of body weight, 3 h before either whole-body exposure to 125 cGy or treatment with 1 mCi of 188 Re-labeled 6D2 melanin-binding antibody. Results: Polymerization of melanin precursors on the surface of silica nanoparticles resulted in formation of a 15-nm-thick melanin layer as confirmed by light scattering, transmission electron microscopy, and immunofluorescence. The biodistribution after intravenous administration showed than MN uptake in bone marrow was 0.3% and 0.2% of injected dose per gram at 3 and 24 h, respectively, whereas pre-injection with pluronic acid increased the uptake to 6% and 3% of injected dose per gram, respectively. Systemic MN administration reduced hematologic toxicity in mice treated with external radiation or radioimmunotherapy, whereas no tumor protection by MNs was observed. Conclusions: MNs or similar structures provide a novel approach to protection of bone marrow from ionizing radiation based

  11. Melanocyte biology and function with reference to oral melanin hyperpigmentation in HIV-seropositive subjects.

    Science.gov (United States)

    Feller, Liviu; Chandran, Rakesh; Kramer, Beverley; Khammissa, Razia A G; Altini, Mario; Lemmer, Johan

    2014-09-01

    The color of normal skin and of oral mucosa is not determined by the number of melanocytes in the epithelium but rather by their melanogenic activity. Pigmented biopolymers or melanins are synthesized in melanosomes. Tyrosinase is the critical enzyme in the biosynthesis of both brown/black eumelanin and yellow/red pheomelanin. The number of the melanosomes within the melanocytes, the type of melanin within the melanosomes, and the efficacy of the transfer of melanosomes from the melanocytes to the neighboring keratinocytes all play an important role in tissue pigmentation. Melanin production is regulated by locally produced factors including proopiomelanocortin and its derivative peptides, particularly alpha-melanocyte-stimulating hormone (α-MSH), melanocortin 1 receptor (MC1R), adrenergic and cholinergic agents, growth factors, cytokines, and nitric oxide. Both eumelanin and pheomelanin can be produced by the same melanocytes, and the proportion of the two melanin types is influenced by the degree of functional activity of the α-MSH/MC1R intracellular pathway. The cause of HIV oral melanosis is not fully understood but may be associated with HIV-induced cytokine dysregulation, with the medications commonly prescribed to HIV-seropositive persons, and with adrenocortical dysfunction, which is not uncommon in HIV-seropositive subjects with AIDS. The purpose of this article is to discuss some aspects of melanocyte biology and HIV-associated oral melanin hyperpigmentation.

  12. Control of In Vivo Transport and Toxicity of Nanoparticles by Tea Melanin

    Directory of Open Access Journals (Sweden)

    Yu-Shiun Chen

    2012-01-01

    Full Text Available Nanoparticles are unfamiliar to researchers in toxicology. Toxicity may be generated simply due to the reduction in size. Compounds that prevent or cure toxic materials may not work on nanoparticles. Furthermore, as there are more and more applications of nanoparticles in drug delivery and in vivo imaging, controlling the transport and toxicity will be primary concerns for medical application of nanoparticles. Gold nanoparticles (GNPs if injected intraperitoneally into mice can enter hippocampus and induce cognitive impairment. GNPs caused a global imbalance of monoamine levels, specifically affecting the dopaminergic and serotonergic neurons. Pretreatment of tea melanin significantly prevented the deposition of GNPs in mouse brains, especially in the hippocampus. Pretreatment of melanin completely alleviated GNP-induced impairment of cognition. Pre-administration of melanin stably maintained monoamines at normal profiles. Melanin completely prevented the invasion of GNPs into the Cornu Ammonis region of the hippocampus shown by coherent anti-Stoke Raman scattering microscopy. Here we show that the administration of tea melanin prevented the accumulation of Au in brain, the imbalance of monoamines, and the impairment of cognition in mice. The current study provides a therapeutic approach to toxicity of nanoparticles and a novel strategy to control the transport of GNP in mouse brain.

  13. Microneedle fractional radiofrequency increases epidermal hyaluronan and reverses age-related epidermal dysfunction.

    Science.gov (United States)

    Lee, Hee Jung; Seo, Seong Rak; Yoon, Moon Soo; Song, Ji-Ye; Lee, Eun Young; Lee, Sang Eun

    2016-02-01

    Skin aging results in physiological alterations in keratinocyte activities and epidermal function, as well as dermal changes. Yet, the cellular and molecular mechanisms that cause epidermal dysfunction during skin aging are not well understood. Recently, the role of epidermal hyaluronan (HA) as an active regulator of dynamic cellular processes is getting attention and alterations in HA metabolism are thought to be important in age-related epidermal dysfunction. Microneedle fractional radiofrequency (RF) has shown effects for improving cutaneous aging. However, little is known about the effects of fractional RF on the epidermal HA and epidermal function. We investigated the effect of microneedle fractional RF on the expression of epidermal HA in young and aged mice epidermis. We performed fractional RF on the dorsal skin of 30 8-week-old (young) hairless mice and 15 47-week-old (aged) C57BL/6J mice. Skin samples were collected on day 1, 3, and 7. HA content was measured by ELISA. Gene expressions of CD 44, HABP4, and HAS3 were measured using real time RT-PCR. Immunohistochemistry for detection of HA, CD44, PCNA, and filaggrin were performed. HA content and the mRNA levels of HABP4, CD44, and HAS3 were upregulated in the epidermis of both young and aged mice after microneedle fractional RF treatment. The expression was increased from day 1 after treatment and increased expression persisted on day 7. Fractional RF treatment significantly increased PCNA and filaggrin expression only in the aged mice skin. Microneedle fractional RF increased epidermal HA and CD44 expression in both young and aged mice and reversed age-related epidermal dysfunction especially in aged mice, suggesting a new mechanism involved in the skin rejuvenation effect of microneedle fractional RF. © 2015 Wiley Periodicals, Inc.

  14. Possible role of epidermal keratinocytes in the construction of acupuncture meridians.

    Science.gov (United States)

    Denda, Mitsuhiro; Tsutsumi, Moe

    2014-04-01

    Acupuncture meridians consist of a network of acupuncture points on the skin, stimulation of which is well established to have a variety of physiological effects. We have previously demonstrated that epidermal keratinocytes contain multiple sensory systems for temperature, mechanical stimuli, electric potentials and other stimuli. These sensory systems generate changes in the calcium-ion concentration in the epidermis, so epidermal keratinocytes can generate spatially-localized electro-physiological patterns in the skin. We have previously demonstrated signaling between epidermal keratinocytes and peripheral nerve systems. Therefore, stimuli sensed by epidermal keratinocytes might be transferred to the unmyelinated nerve fibers that are known to exist in the epidermis and, thence, to the spinal cord and brain. We propose that epidermal keratinocytes form an information-gathering network in the skin and that this network plays a key role in whole-body homeostasis in response to the changing environment. We also hypothesize that this network corresponds to the acupuncture meridians. As supporting examples, we present some striking calcium propagation patterns observed in cultured human keratinocytes after adenosine-triphosphate (ATP) stimulation. These results support the ideas that keratinocytes can generate spatially-restricted signaling patterns after environmental stimulation and that the cultures might be in-vitro models of meridians as an information-gathering network in skin. Copyright © 2014. Published by Elsevier B.V.

  15. Oral melanin pigmentation in 467 Thai and Malaysian people with special emphasis on smoker's melanosis.

    Science.gov (United States)

    Hedin, C A; Axéll, T

    1991-01-01

    At the faculties of dentistry in Chiang Mai, Thailand (CM), and Kuala Lumpur, Malaysia (KL), 234 and 233 consecutive out-patients were interviewed concerning tobacco and chewing habits and examined for the presence of oral melanin pigmentation. Tobacco was regularly used by 32% and 28% of the studied populations in CM and KL. Cigarette smoking was the predominant habit, but the chewing of betel and tea leaves (miang) and the smoking of banana leaf cigars (khi yo) was also registered. The genetically acquired pigmentation dominated. Although nearly all non-tobacco users in the Malay and Indian populations had oral melanin pigmentation, it was found that tobacco smokers had significantly more oral surfaces pigmented than non-tobacco users. Among Thais, the percentage of pigmented individuals was significantly higher among tobacco smokers. It was concluded that tobacco smoking stimulates oral melanocytes to a higher melanin production also in dark-skinned ethnic groups.

  16. Melanin-targeting antibody as a potential agent for radioimmunotherapy of melanoma

    International Nuclear Information System (INIS)

    Dadachova, E.; Nosanchuk, J.D.; Shi, L.; Casadevall, A.

    2002-01-01

    Aim: Melanoma is a cancer of increasing incidence for which new methods of treatment and imaging are urgently needed. Currently there is no effective therapy for metastatic melanoma as this tumor is resistant to radiation and chemotherapy. The majority of human melanomas are pigmented with melanin. Here we investigated the possibility of using a melanin-binding antibody (mAb 6D2) which was originally developed against fungal melanin as a delivery vehicle for RIT of pigmented melanoma. Materials and Methods: MAb 6D2 (IgM type) was generated from hybridomas obtained from mice immunized with melanin isolated from Cryptococcus neoformans. The mAb was radiolabeled with 213 Bi or 111 In via bifunctional chelator CHXA'' and with 188 Re - via 'direct labeling'. The immunoreactivity of radiolabeled 6D2 mAb towards fungal melanin was tested by immunofluorescence. Cell binding of 213 Bi-6D2, 188 Re-6D2 and irrelevant IgM 12A1 was evaluated by incubating 2 μg/mL mAb with 0.23-2 x 10 6 human slightly pigmented melanoma cells SK-28-MEL (whole or lysed) which were grown with or without 110 μM L-tyrosine to promote melanin formation. In vivo binding of 111 In-6D2 was studied by scintigraphic imaging in nude mice injected IP with 2.8 x 10 6 SK-28-MEL cells 24 h before 111 In-6D2; biodistribution of 188 Re-6D2 was performed in nude mice bearing SK-28-MEL xenografted tumors. Results: The immunoreactivity of radiolabeled 6D2 mAb to melanin was demonstrated by immunofluorescence. Cell binding of 213 Bi-6D2 and 188 Re-6D2 was higher for the melanoma cells grown with 110 μM L-tyrosine suggesting melanin-specific binding. There was no significant difference (P>0.05) in binding to the whole or lysed cells which may be due to reactivity with melanin or precursors found on the cell surface. In mice injected IP with SK-28-MEL cells there was more retention of 111 In-6D2 in intraperitoneal cavity compared to irrelevant 111 In-IgM and control animals with no tumor cells. The biodistribution

  17. Transferring biomarker into molecular probe: melanin nanoparticle as a naturally active platform for multimodality imaging.

    Science.gov (United States)

    Fan, Quli; Cheng, Kai; Hu, Xiang; Ma, Xiaowei; Zhang, Ruiping; Yang, Min; Lu, Xiaomei; Xing, Lei; Huang, Wei; Gambhir, Sanjiv Sam; Cheng, Zhen

    2014-10-29

    Developing multifunctional and easily prepared nanoplatforms with integrated different modalities is highly challenging for molecular imaging. Here, we report the successful transfer of an important molecular target, melanin, into a novel multimodality imaging nanoplatform. Melanin is abundantly expressed in melanotic melanomas and thus has been actively studied as a target for melanoma imaging. In our work, the multifunctional biopolymer nanoplatform based on ultrasmall (passive nanoplatforms require complicated and time-consuming processes for prebuilding reporting moieties or chemical modifications using active groups to integrate different contrast properties into one entity. In comparison, utilizing functional biomarker melanin can greatly simplify the building process. We further conjugated αvβ3 integrins, cyclic c(RGDfC) peptide, to MNPs to allow for U87MG tumor accumulation due to its targeting property combined with the enhanced permeability and retention (EPR) effect. The multimodal properties of MNPs demonstrate the high potential of endogenous materials with multifunctions as nanoplatforms for molecular theranostics and clinical translation.

  18. Analysis of the melanin distribution in different ethnic groups by in vivo laser scanning microscopy

    International Nuclear Information System (INIS)

    Antoniou, C; Lademann, J; Richter, H; Patzelt, A; Sterry, W; Astner, S; Zastrow, L; Koch, S

    2009-01-01

    The aim of this study was to determine whether Laser scanning confocal microscopy (LSM) is able to visualize differences in melanin content and distribution in different Skin Phototypes. The investigations were carried out on six healthy volunteers with Skin Phototypes II, IV, and VI. Representative skin samples of Skin Phototypes II, V, and VI were obtained for histological analysis from remaining tissue of skin grafts and were used for LSM-pathologic correlation. LSM evaluation showed significant differences in melanin distribution in Skin Phototypes II, IV, and VI, respectively. Based on the differences in overall reflectivity and image brightness, a visual evaluation scheme showed increasing brightness of the basal and suprabasal layers with increasing Skin Phototypes. The findings correlated well with histological analysis. The results demonstrate that LSM may serve as a promising adjunctive tool for real time assessment of melanin content and distribution in human skin, with numerous clinical applications and therapeutic and preventive implications

  19. Skip areas of retained melanin: A clue to the histopathological diagnosis of idiopathic guttate hypomelanosis

    Directory of Open Access Journals (Sweden)

    Rajiv Joshi

    2014-01-01

    Full Text Available Biopsy findings in 55 cases of idiopathic guttate hypomelanosis (IGH are reported. Most cases had a flat epidermis with loss of the rete pattern and a thickened orthokeratotic basket weave stratum corneum. The epidermis had markedly decreased to absent melanin in the basal layer and reduced numbers of melanocytes at the dermoepidermal junction. One-third of patients had a sparse perivascular lymphocytic infiltrate, whereas the rest had no significant dermal inflammation. These findings are in concordance with current literature.However, small foci of retained melanin in the basal layer (skip areas alternating with larger areas of melanin loss were present in almost 80% of cases. This finding has not been reported earlier and appears to be quite specific to IGH and may be used as a clue to differentiate IGH from other similar conditions such as vitiligo and guttate morphea.

  20. Investigation of Inonotus obliquus (Pers. Pil. Extracts and Melanins after RF-plasma Treatment of Raw Material

    Directory of Open Access Journals (Sweden)

    O.Yu. Kuznetsova

    2016-03-01

    Full Text Available High-frequency capacitive discharge (RF plasma at low pressure was used as preliminary stage for the intensification of extraction from natural medicinal raw material. RF-plasma treatment was carried out in two modes differed by the nature of plasma-forming gas. Chaga (Inonotus obliquus (Pers. Pil. known as the birch mushroom was selected as a perspective source of raw material. Extraction was carried out in two ways – remaceration and maceration. The analy-sis of chaga extracts and melanins was performed using traditional techniques including determination of physical and chemical, antioxidant and spectral characteristics. The obtained extracts and melanins were compared to the control samples and literature data. RF-plasma treatment of medicinal raw material increased the yield of extractive substances, in particular of the main active component of chaga – melanin. The antioxidant activity of chaga extracts grew, while for melanins it remained at the level similar to that of control samples. The IR spectral characteristics of the studied chaga melanins are similar and agree well with the literature data. Insignificant deviations in the position and intensity of absorption strips were observed for the samples after RF treatment. IR spectra of the studied chaga melanins are similar to those for mushroom melanins, thereby confirming the similarity in their nature. RF-plasma treatment of chaga medicinal raw materials allows to modify them partially. The structural and mechanical properties of melanins modified by RF plasma remain the same.

  1. Regulation of melanin biosynthesis via the dihydroxynaphthalene pathway is dependent on sexual development in the ascomycete Sordaria macrospora.

    Science.gov (United States)

    Engh, Ines; Nowrousian, Minou; Kück, Ulrich

    2007-10-01

    The filamentous ascomycete Sordaria macrospora accumulates melanin during sexual development. The four melanin biosynthesis genes pks, teh, sdh and tih were isolated and their homology to genes involved in 1,8 dihydroxynaphthalene (DHN) melanin biosynthesis was shown. The presence of DHN melanin in S. macrospora was further confirmed by disrupting the pks gene encoding a putative polyketide synthase and by RNA interference-mediated silencing of the sdh gene encoding a putative scytalone dehydratase. Because melanin occurs in fruiting bodies that develop through several intermediate stages within 7 days of growth, a Northern analysis of a developmental time-course was conducted. These data revealed a time-dependent regulation of teh and sdh transcript levels. Comparing the transcriptional expression by real-time PCR of melanin biosynthesis genes in the wild type under conditions allowing or repressing sexual development, a significant downregulation during vegetative growth was detected. Quantitative real-time PCR and Northern blot analysis of melanin biosynthesis gene expression in different developmental mutants confirmed that melanin biosynthesis is linked to fruiting body development and is under the control of specific regulatory genes that participate in sexual differentiation.

  2. Sexual selection and the function of a melanin-based plumage ornament in polygamous penduline tits Remiz pendulinus

    NARCIS (Netherlands)

    Kingma, Sjouke A.; Szentirmai, Istvan; Szekely, Tamas; Bokony, Veronika; Bleeker, Maarten; Liker, Andras; Komdeur, Jan; McGraw, K.

    Melanin-based ornaments are often involved in signaling aggression and dominance, and their role in sexual selection is increasingly recognized. We investigated the functions of a melanin-based plumage ornament (facial 'mask') in male Eurasian penduline tits Remiz pendulinus in the contexts of

  3. Melanin deposition ruled out as cause of color changes in the red-eared sliders (Trachemys scripta elegans).

    Science.gov (United States)

    Cao, Dainan; Gong, Shiping; Yang, Jiangbo; Li, Weiye; Ge, Yan; Wei, Yufeng

    2018-03-01

    Animal coloration primarily depends on the presence of pigments and the mixing ratio of eumelanin and pheomelanin. The color of red-eared slider's carapace varies with age, from an olive green to a yellow green, and then to a yellow brown in juveniles, generally. The purpose of the present study was to investigate whether this color change is related to the difference in melanin expression. Melanin deposition levels were examined in the carapace, skin, eye and muscle of the three color-types using hematoxylin and eosin staining. Moreover, the full-length coding sequence (CDS) of red-eared slider turtle melanin biosynthesis regulatory genes TYR, TYRP1, MITF and SLC24A5 were cloned, sequenced and quantitatively analyzed. Both histological view of melanin deposition and quantitative real-time PCR test of melanin-regulated gene expressions showed that there are significant differences among different tissues of red-eared slider, but no significant difference among different color-types, indicating that melanin deposition is not associated with ontogenetic color change in the carapace of red-eared slider. This study initially explore the melanin deposition and the mRNA expression of melanin biosynthesis regulatory genes in red-eared slider, which serve as a foundation for further insight into the pigmentation patterns and the mechanism of body color change in turtles. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Melanin offers protection against induction of cyclobutane pyrimidine dimers and 6-4 photoproducts by UVB in cultured human melanocytes

    NARCIS (Netherlands)

    Smit, N.P.M.; Vink, A.A.; Kolb, R.M.; Steenwinkel, M.J.S.T.; Berg, P.T.M. van den; Nieuwpoort, F. van; Roza, L.; Pavel, S.

    2001-01-01

    The goal of this investigation was to correlate the melanin content in human pigmentary cells with the generation of UVB-induced photoproducts and to examine the relationship between the melanin content and the removal of the photoproducts. Cultured melanocytes from light-skinned individuals

  5. Condition-dependence, pleiotropy and the handicap principle of sexual selection in melanin-based colouration.

    Science.gov (United States)

    Roulin, Alexandre

    2016-05-01

    The signalling function of melanin-based colouration is debated. Sexual selection theory states that ornaments should be costly to produce, maintain, wear or display to signal quality honestly to potential mates or competitors. An increasing number of studies supports the hypothesis that the degree of melanism covaries with aspects of body condition (e.g. body mass or immunity), which has contributed to change the initial perception that melanin-based colour ornaments entail no costs. Indeed, the expression of many (but not all) melanin-based colour traits is weakly sensitive to the environment but strongly heritable suggesting that these colour traits are relatively cheap to produce and maintain, thus raising the question of how such colour traits could signal quality honestly. Here I review the production, maintenance and wearing/displaying costs that can generate a correlation between melanin-based colouration and body condition, and consider other evolutionary mechanisms that can also lead to covariation between colour and body condition. Because genes controlling melanic traits can affect numerous phenotypic traits, pleiotropy could also explain a linkage between body condition and colouration. Pleiotropy may result in differently coloured individuals signalling different aspects of quality that are maintained by frequency-dependent selection or local adaptation. Colouration may therefore not signal absolute quality to potential mates or competitors (e.g. dark males may not achieve a higher fitness than pale males); otherwise genetic variation would be rapidly depleted by directional selection. As a consequence, selection on heritable melanin-based colouration may not always be directional, but mate choice may be conditional to environmental conditions (i.e. context-dependent sexual selection). Despite the interest of evolutionary biologists in the adaptive value of melanin-based colouration, its actual role in sexual selection is still poorly understood.

  6. Structural Color Tuning: Mixing Melanin-Like Particles with Different Diameters to Create Neutral Colors.

    Science.gov (United States)

    Kawamura, Ayaka; Kohri, Michinari; Yoshioka, Shinya; Taniguchi, Tatsuo; Kishikawa, Keiki

    2017-04-18

    We present the ability to tune structural colors by mixing colloidal particles. To produce high-visibility structural colors, melanin-like core-shell particles composed of a polystyrene (PSt) core and a polydopamine (PDA) shell, were used as components. The results indicated that neutral structural colors could be successfully obtained by simply mixing two differently sized melanin-like PSt@PDA core-shell particles. In addition, the arrangements of the particles, which were important factors when forming structural colors, were investigated by mathematical processing using a 2D Fourier transform technique and Voronoi diagrams. These findings provide new insights for the development of structural color-based ink applications.

  7. Simultaneous in vivo imaging of melanin and lipofuscin in the retina with multimodal photoacoustic ophthalmoscopy

    Science.gov (United States)

    Zhang, Xiangyang; Zhang, Hao F.; Zhou, Lixiang; Jiao, Shuliang

    2012-02-01

    We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective vs. exacerbate) in the RPE in the aging process. We successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

  8. Objective evaluation of choroidal melanin contents with polarization-sensitive optical coherence tomography

    Science.gov (United States)

    Miura, Masahiro; Makita, Shuichi; Yasuno, Yoshiaki; Ikuno, Yasushi; Uematsu, Sato; Iwasaki, Takuya; Goto, Hiroshi

    2018-02-01

    We non-invasively evaluated choroidal melanin contents in human eyes with PS-OCT. We calculated the percentage area of low DOPU in the choroidal interstitial stroma for Vogt-Koyanagi- Harada disease with sunset glow fundus, without sunset glow fundus, control group and tessellated fundus with high myopia. The mean percentage area of low DOPU in the sunset group was significantly lower than the other groups. PS-OCT provides an in vivo objective evaluation of choroidal melanin loss in vivo human eyes.

  9. Prevention of melanin formation during aryl alcohol oxidase production under growth-limited conditions using an Aspergillus nidulans cell factory.

    Science.gov (United States)

    Pardo-Planas, Oscar; Prade, Rolf A; Müller, Michael; Atiyeh, Hasan K; Wilkins, Mark R

    2017-11-01

    An Aspergillus nidulans cell factory was genetically engineered to produce an aryl alcohol oxidase (AAO). The cell factory initiated production of melanin when growth-limited conditions were established using stationary plates and shaken flasks. This phenomenon was more pronounced when the strain was cultured in a trickle bed reactor (TBR). This study investigated different approaches to reduce melanin formation in fungal mycelia and liquid medium in order to increase the enzyme production yield. Removal of copper from the medium recipe reduced melanin formation in agar cultures and increased enzyme activities by 48% in agitated liquid cultures. Copper has been reported as a key element for tyrosinase, an enzyme responsible for melanin production. Ascorbic acid (0.44g/L) stopped melanin accumulation, did not affect growth parameters and resulted in AAO activity that was more than two-fold greater than a control treatment with no ascorbic acid. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. EPIDERMAL MORPHOLOGY OF WEST AFRICAN OKRA ...

    African Journals Online (AJOL)

    Administrator

    stem peels were obtained from a slight cut on the tenth internodes. Peels from fruit ... xia l su rfa ce. A b a xia l su rfa ce. Adaxial surface. Abaxial surface. L e n g th. (µ m. ) ..... Variations in epidermal cell shape of both adaxial and abaxial surfaces ...

  11. FOLIAR EPIDERMAL AND PHYTOCHEMICAL STUDIES OF THE ...

    African Journals Online (AJOL)

    Administrator

    alkaloid, saponin, inulin, cellulose, tannin and lignin; Eragrostis tremula tested negative for lignin and positive for cellulose, saponin and alkaloids while Axonopus compressus tested negative for lignin, but positive for alkaloid, saponin, inulin, cellulose and tannin respectively. Leaf epidermal studies help to determine ...

  12. Stevens Johnsons syndrom og toksisk epidermal nekrolyse

    DEFF Research Database (Denmark)

    Kaur-Knudsen, Diljit; Zachariae, Claus; Thomsen, Simon Francis

    2013-01-01

    Stevens-Johnson syndrome and toxic epidermal necrolysis are acute mucocutaneous diseases primarily due to drug intake. The diseases are characterised by the separation of epidermis from dermis which can be life-threatening. Mortality is often caused by sepsis and multiple organ failure. The most...

  13. Protection of melanized Cryptococcus neoformans from lethal dose gamma irradiation involves changes in melanin's chemical structure and paramagnetism.

    Directory of Open Access Journals (Sweden)

    Abdelahad Khajo

    Full Text Available Certain fungi thrive in highly radioactive environments including the defunct Chernobyl nuclear reactor. Cryptococcus neoformans (C. neoformans, which uses L-3,4-dihydroxyphenylalanine (L-DOPA to produce melanin, was used here to investigate how gamma radiation under aqueous aerobic conditions affects the properties of melanin, with the aim of gaining insight into its radioprotective role. Exposure of melanized fungal cell in aqueous suspensions to doses of γ-radiation capable of killing 50 to 80% of the cells did not lead to a detectable loss of melanin integrity according to EPR spectra of melanin radicals. Moreover, upon UV-visible (Xe-lamp illumination of melanized cells, the increase in radical population was unchanged after γ-irradiation. Gamma-irradiation of frozen cell suspensions and storage of samples for several days at 77 K however, produced melanin modification noted by a reduced radical population and reduced photoresponse. More direct evidence for structural modification of melanin came from the detection of soluble products with absorbance maxima near 260 nm in supernatants collected after γ-irradiation of cells and cell-free melanin. These products, which include thiobarbituric acid (TBA-reactive aldehydes, were also generated by Fenton reagent treatment of cells and cell-free melanin. In an assay of melanin integrity based on the metal (Bi(+3 binding capacity of cells, no detectable loss in binding was detected after γ-irradiation. Our results show that melanin in C. neoformans cells is susceptible to some damage by hydroxyl radical formed in lethal radioactive aqueous environments and serves a protective role in melanized fungi that involves sacrificial breakdown.

  14. 4-Acylamino-and 4-ureidobenzamides as melanin-concentrating hormone (MCH) receptor 1 antagonists

    DEFF Research Database (Denmark)

    Receveur, Jean-Marie; Bjurling, Emelie; Ulven, Trond

    2004-01-01

    Synthesis, in vitro biological evaluation and structure-activity relationships of 4-acylamino-and 4-ureidobenzamides as novel hMCH1R-antagonists are disclosed. The nature of the amine side chains could be varied considerably in contrast to the central benzamide scaffold and aromatic substituents....

  15. Menadione (Vitamin K3) decreases melanin synthesis through ERK activation in Mel-Ab cells.

    Science.gov (United States)

    Kim, Eun-Hyun; Kim, Myo-Kyoung; Yun, Hye-Young; Baek, Kwang Jin; Kwon, Nyoun Soo; Park, Kyoung-Chan; Kim, Dong-Seok

    2013-10-15

    Menadione is a synthetic vitamin K3 derivative. Here, we examined the effects of menadione on melanogenesis and its related signaling pathways. Our results showed that melanin content was significantly reduced after menadione treatment in a dose-dependent manner. However, menadione treatment did not reduce tyrosinase activity directly. Wnt signaling is known to play a major role in the control of melanin synthesis. Thus, we tested the effects of menadione treatment on GSK3β and β-catenin signaling, but found that menadione did not influence either of these signaling pathways. We also investigated changes in the phosphorylation of ERK, which is related to melanin regulation. These results indicated that menadione treatment led to the phosphorylation of ERK. Additionally, menadione treatment reduced both MITF and tyrosinase protein levels. Treatment with PD98059, a specific ERK pathway inhibitor, restored menadione-induced melanin reduction and also prevented MITF and tyrosinase downregulation by menadione. These results suggest that the hypopigmentary action of menadione is due to MITF and tyrosinase downregulation by ERK activation. © 2013 Elsevier B.V. All rights reserved.

  16. Melanin-based color of plumage: role of condition and of feathers' microstructure

    Science.gov (United States)

    D'Alba, Liliana; Van Hemert, Caroline R.; Spencer, Karen A.; Heidinger, Britt J.; Gill, Lisa; Evans, Neil P.; Monaghan, Pat; Handel, Colleen M.; Shawkey, Matthew D.

    2014-01-01

    Whether melanin-based colors honestly signal a bird's condition during the growth of feathers is controversial, and it is unclear if or how the physiological processes underlying melanogenesis or color-imparting structural feather microstructure may be adversely affected by condition. Here we report results from two experiments designed to measure the effect of condition on expression of eumelanic and pheomelanic coloration in black-capped chickadees (Poecile atricapillus) and zebra finches (Taeniopygia guttata), respectively. In chickadees, we compared feathers of birds affected and unaffected by avian keratin disorder, while in zebra finches we compared feathers of controls with feathers of those subjected to an unpredictable food supply during development. In both cases we found that control birds had brighter feathers (higher total reflectance) and more barbules, but similar densities of melanosomes. In addition, the microstructure of the feathers explained variation in color more strongly than did melanosome density. Together, these results suggest that melanin-based coloration may in part be condition-dependent, but that this may be driven by changes in keratin and feather development, rather than melanogenesis itself. Researchers should be cautious when assigning variation in melanin-based color to melanin alone and microstructure of the feather should be taken into account.

  17. Testing in mice the hypothesis that melanin is protective in malaria infections.

    Directory of Open Access Journals (Sweden)

    Michael Waisberg

    Full Text Available Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria.

  18. Technological Desition of Extraction of Melanin from the Waste of Production of Sunflower-Seed Oil

    Science.gov (United States)

    Kartushina, Yu N.; Nefedieva, E. E.; Sevriukova, G. A.; Gracheva, N. V.; Zheltobryukhov, V. F.

    2017-05-01

    The research was realized in the field of the technology for re-use of waste of sunflower-seed oil production. A technological scheme of production of melanin from sunflower husk as a waste was developed. Re-cycling will give the opportunity to reduce the amount of waste and to obtain an additional source of income.

  19. Pharmacokinetics study of Zr-89-labeled melanin nanoparticle in iron-overload mice

    International Nuclear Information System (INIS)

    Zhang, Pengjun; Yue, Yuanyuan; Pan, Donghui; Yang, Runlin; Xu, Yuping; Wang, Lizhen; Yan, Junjie; Li, Xiaotian; Yang, Min

    2016-01-01

    Melanin, a natural biological pigment present in many organisms, has been found to exhibit multiple functions. An important property of melanin is its ability to chelate metal ions strongly, which might be developed as an iron chelator for iron overload therapy. Herein, we prepared the ultrasmall water-soluble melanin nanoparticle (MP) and firstly evaluate the pharmacokinetics of MP in iron-overload mice to provide scientific basis for treating iron-overload. To study the circulation time and biodistribution, MP was labeled with 89 Zr, a long half-life (78.4 h) positron-emitting metal which is suited for the labeling of nanoparticles and large bioactive molecule. MP was chelated with 89 Zr directly at pH 5, resulting in non-decay-corrected yield of 89.6% and a radiochemical purity of more than 98%. The specific activity was at least190 MBq/μmol. The 89 Zr-MP was stable in human plasma and PBS for at least 48 h. The half-life of 89 Zr-MP was about 15.70 ± 1.74 h in iron-overload mice. Biodistribution studies and MicroPET imaging showed that 89 Zr-MP mainly accumulated in liver and spleen, which are the target organ of iron-overload. The results indicate that the melanin nanoparticle is promising for further iron overload therapy.

  20. Melanin-independent accumulation of turgor pressure in appressoria of Phakopsora pachyrhizi

    Science.gov (United States)

    In some plant pathogenic fungi, turgor pressure accumulation in appressoria produces a mechanical force enabling the direct penetration of hyphae through the plant cell epidermis. Melanin has been reported to function as an impermeable barrier to osmolytes, which allow appressoria to accumulate high...

  1. Melanins and melanogenesis: from pigment cells to human health and technological applications.

    Science.gov (United States)

    d'Ischia, Marco; Wakamatsu, Kazumasa; Cicoira, Fabio; Di Mauro, Eduardo; Garcia-Borron, Josè Carlos; Commo, Stephane; Galván, Ismael; Ghanem, Ghanem; Kenzo, Koike; Meredith, Paul; Pezzella, Alessandro; Santato, Clara; Sarna, Tadeusz; Simon, John D; Zecca, Luigi; Zucca, Fabio A; Napolitano, Alessandra; Ito, Shosuke

    2015-09-01

    During the past decade, melanins and melanogenesis have attracted growing interest for a broad range of biomedical and technological applications. The burst of polydopamine-based multifunctional coatings in materials science is just one example, and the list may be expanded to include melanin thin films for organic electronics and bioelectronics, drug delivery systems, functional nanoparticles and biointerfaces, sunscreens, environmental remediation devices. Despite considerable advances, applied research on melanins and melanogenesis is still far from being mature. A closer intersectoral interaction between research centers is essential to raise the interests and increase the awareness of the biomedical, biomaterials science and hi-tech sectors of the manifold opportunities offered by pigment cells and related metabolic pathways. Starting from a survey of biological roles and functions, the present review aims at providing an interdisciplinary perspective of melanin pigments and related pathway with a view to showing how it is possible to translate current knowledge about physical and chemical properties and control mechanisms into new bioinspired solutions for biomedical, dermocosmetic, and technological applications. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. Mechanistic insights into the bleaching of melanin by alkaline hydrogen peroxide.

    Science.gov (United States)

    Smith, R A W; Garrett, B; Naqvi, K R; Fülöp, A; Godfrey, S P; Marsh, J M; Chechik, V

    2017-07-01

    This work aims to determine the roles of reactive oxygen species HO∙ and HO 2 - in the bleaching of melanins by alkaline hydrogen peroxide. Experiments using melanosomes isolated from human hair indicated that the HO∙ radical generated in the outside solution does not contribute significantly to bleaching. However, studies using soluble Sepia melanin demonstrated that both HO 2 - and HO∙ will individually bleach melanin. Additionally, when both oxidants are present, bleaching is increased dramatically in both rate and extent. Careful experimental design enabled the separation of the roles and effects of these key reactive species, HO∙ and HO 2 - . Rationalisation of the results presented, and review of previous literature, allowed the postulation of a simplified general scheme whereby the strong oxidant HO∙ is able to pre-oxidise melanin units to o-quinones enabling more facile ring opening by the more nucleophilic HO 2 - . In this manner the efficiency of the roles of both species is maximised. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Aspergillus fumigatus melanins: Interference with the host endocytosis pathway and impact on virulence

    Directory of Open Access Journals (Sweden)

    Thorsten eHeinekamp

    2013-01-01

    Full Text Available The opportunistic human pathogenic fungus Aspergillus fumigatus produces at least two types of melanin, namely pyomelanin and dihydroxynaphthalene (DHN melanin. Pyomelanin is produced during tyrosine catabolism via accumulation of homogentisic acid. Although pyomelanin protects the fungus against reactive oxygen species and acts as a defense compound in response to cell wall stress, mutants deficient for pyomelanin biosynthesis do not differ in virulence when tested in a murine infection model for invasive pulmonary aspergillosis. DHN melanin is responsible for the characteristic grey-greenish color of A. fumigatus conidia. Mutants lacking a functional polyketide synthase PksP, the enzyme responsible for the initial step in DHN-melanin formation, i.e., the synthesis of naphthopyrone, produce white spores and are attenuated in virulence. The activity of PksP was found to be essential not only for inhibition of apoptosis of phagocytes by interfering with the host PI3K/Akt signaling cascade but also for effective inhibition of acidification of conidia-containing phagolysosomes. These features allow A. fumigatus to survive in phagocytes and thereby to escape from human immune effector cells and to become a successful pathogen.

  4. Methionine supplementation influences melanin-based plumage colouration in Eurasian kestrel, Falco tinnunculus, nestlings.

    Science.gov (United States)

    Parejo, Deseada; Silva, Nadia

    2009-11-01

    The extent to which the expression of melanin-based plumage colouration in birds is genetically or environmentally determined is controversial. Here, we performed a between-nest design supplementation with either the sulphur amino acid dl-methionine or with water to investigate the importance of the non-genetic component of melanin-based plumage colouration in the Eurasian kestrel, Falco tinnunculus. Methionine affects growth and immunity, thus we aimed to modify nestling growth and immunity before feather development. Then, we measured the effect of the experiment on colouration of two melanin-based plumage patches of nestling kestrels. We found that methionine slowed down nestling growth through treatment administration and that nestlings compensated by speeding up their growth later. We did not find any effects of methionine on nestling immunity (i.e. lymphocyte counts, natural antibody levels or complement-mediated immunity). Effects on growth seemed to be mirrored by changes in nestling colouration in the two sexes: methionine-nestlings showed less intense brown plumage on their backs compared with control nestlings. These results provide support for a non-genetic determination of a melanin-based plumage patch in the two sexes of nestling kestrels.

  5. Positive Relationship between Abdominal Coloration and Dermal Melanin Density in Phrynosomatid Lizards

    Science.gov (United States)

    Vanessa S. Quinn; Diana K. Hews

    2003-01-01

    Phrynosomatid lizards show considerable variation among species in the occurrence of a secondary sexual trait, blue abdominal coloration. The production of blue skin may be controlled by at least two cellular components, melanin in melanophores, and guanine in iridophores. To examine the hypothesis that a mechanism producing variation in abdominal coloration is...

  6. GAMMA RADIATION INTERACTS WITH MELANIN TO ALTER ITS OXIDATION-REDUCTION POTENTIAL AND RESULTS IN ELECTRIC CURRENT PRODUCTION

    Energy Technology Data Exchange (ETDEWEB)

    Turick, C.; Ekechukwu, A.; Milliken, C.

    2011-05-17

    The presence of melanin pigments in organisms is implicated in radioprotection and in some cases, enhanced growth in the presence of high levels of ionizing radiation. An understanding of this phenomenon will be useful in the design of radioprotective materials. However, the protective mechanism of microbial melanin in ionizing radiation fields has not yet been elucidated. Here we demonstrate through the electrochemical techniques of chronoamperometry, chronopotentiometry and cyclic voltammetry that microbial melanin is continuously oxidized in the presence of gamma radiation. Our findings establish that ionizing radiation interacts with melanin to alter its oxidation-reduction potential. Sustained oxidation resulted in electric current production and was most pronounced in the presence of a reductant, which extended the redox cycling capacity of melanin. This work is the first to establish that gamma radiation alters the oxidation-reduction behavior of melanin, resulting in electric current production. The significance of the work is that it provides the first step in understanding the initial interactions between melanin and ionizing radiation taking place and offers some insight for production of biomimetic radioprotective materials.

  7. Rab11b mediates melanin transfer between donor melanocytes and acceptor keratinocytes via coupled exo/endocytosis.

    Science.gov (United States)

    Tarafder, Abul K; Bolasco, Giulia; Correia, Maria S; Pereira, Francisco J C; Iannone, Lucio; Hume, Alistair N; Kirkpatrick, Niall; Picardo, Mauro; Torrisi, Maria R; Rodrigues, Inês P; Ramalho, José S; Futter, Clare E; Barral, Duarte C; Seabra, Miguel C

    2014-04-01

    The transfer of melanin from melanocytes to keratinocytes is a crucial process underlying maintenance of skin pigmentation and photoprotection against UV damage. Here, we present evidence supporting coupled exocytosis of the melanin core, or melanocore, by melanocytes and subsequent endocytosis by keratinocytes as a predominant mechanism of melanin transfer. Electron microscopy analysis of human skin samples revealed three lines of evidence supporting this: (1) the presence of melanocores in the extracellular space; (2) within keratinocytes, melanin was surrounded by a single membrane; and (3) this membrane lacked the melanosomal membrane protein tyrosinase-related protein 1 (TYRP1). Moreover, co-culture of melanocytes and keratinocytes suggests that melanin exocytosis is specifically induced by keratinocytes. Furthermore, depletion of Rab11b, but not Rab27a, caused a marked decrease in both keratinocyte-stimulated melanin exocytosis and transfer to keratinocytes. Thus, we propose that the predominant mechanism of melanin transfer is keratinocyte-induced exocytosis, mediated by Rab11b through remodeling of the melanosome membrane, followed by subsequent endocytosis by keratinocytes.

  8. Surface structure characterization of Aspergillus fumigatus conidia mutated in the melanin synthesis pathway and their human cellular immune response.

    Science.gov (United States)

    Bayry, Jagadeesh; Beaussart, Audrey; Dufrêne, Yves F; Sharma, Meenu; Bansal, Kushagra; Kniemeyer, Olaf; Aimanianda, Vishukumar; Brakhage, Axel A; Kaveri, Srini V; Kwon-Chung, Kyung J; Latgé, Jean-Paul; Beauvais, Anne

    2014-08-01

    In Aspergillus fumigatus, the conidial surface contains dihydroxynaphthalene (DHN)-melanin. Six-clustered gene products have been identified that mediate sequential catalysis of DHN-melanin biosynthesis. Melanin thus produced is known to be a virulence factor, protecting the fungus from the host defense mechanisms. In the present study, individual deletion of the genes involved in the initial three steps of melanin biosynthesis resulted in an altered conidial surface with masked surface rodlet layer, leaky cell wall allowing the deposition of proteins on the cell surface and exposing the otherwise-masked cell wall polysaccharides at the surface. Melanin as such was immunologically inert; however, deletion mutant conidia with modified surfaces could activate human dendritic cells and the subsequent cytokine production in contrast to the wild-type conidia. Cell surface defects were rectified in the conidia mutated in downstream melanin biosynthetic pathway, and maximum immune inertness was observed upon synthesis of vermelone onward. These observations suggest that although melanin as such is an immunologically inert material, it confers virulence by facilitating proper formation of the A. fumigatus conidial surface. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  9. Epidermal Growth Factor and Intestinal Barrier Function

    Directory of Open Access Journals (Sweden)

    Xiaopeng Tang

    2016-01-01

    Full Text Available Epidermal growth factor (EGF is a 53-amino acid peptide that plays an important role in regulating cell growth, survival, migration, apoptosis, proliferation, and differentiation. In addition, EGF has been established to be an effective intestinal regulator helping to protect intestinal barrier integrity, which was essential for the absorption of nutrients and health in humans and animals. Several researches have demonstrated that EGF via binding to the EGF receptor and subsequent activation of Ras/MAPK, PI3K/AKT, PLC-γ/PKC, and STATS signal pathways regulates intestinal barrier function. In this review, the relationship between epidermal growth factor and intestinal development and intestinal barrier is described, to provide a better understanding of the effects of EGF on intestine development and health.

  10. Epidermal CYP2 family cytochromes P450

    International Nuclear Information System (INIS)

    Du Liping; Hoffman, Susan M.G.; Keeney, Diane S.

    2004-01-01

    Skin is the largest and most accessible drug-metabolizing organ. In mammals, it is the competent barrier that protects against exposure to harmful stimuli in the environment and in the systemic circulation. Skin expresses many cytochromes P450 that have critical roles in exogenous and endogenous substrate metabolism. Here, we review evidence for epidermal expression of genes from the large CYP2 gene family, many of which are expressed preferentially in extrahepatic tissues or specifically in epithelia at the environmental interface. At least 13 CYP2 genes (CYP2A6, 2A7, 2B6, 2C9, 2C18, 2C19, 2D6, 2E1, 2J2, 2R1, 2S1, 2U1, and 2W1) are expressed in skin from at least some human individuals, and the majority of these genes are expressed in epidermis or cultured keratinocytes. Where epidermal expression has been localized in situ by hybridization or immunocytochemistry, CYP2 transcripts and proteins are most often expressed in differentiated keratinocytes comprising the outer (suprabasal) cell layers of the epidermis and skin appendages. The tissue-specific transcriptional regulation of CYP2 genes in the epidermis, and in other epithelia that interface with the environment, suggests important roles for at least some CYP2 gene products in the production and disposition of molecules affecting competency of the epidermal barrier

  11. A promising magnetic resonance stem cell tracer based on natural biomaterials in a biological system: manganese (II chelated to melanin nanoparticles

    Directory of Open Access Journals (Sweden)

    Liu SJ

    2018-03-01

    Full Text Available Shi-Jie Liu,1,2,* Ling-Jie Wang,1,* Ying Qiao,1 Hua Zhang,1 Li-Ping Li,1 Jing-Hua Sun,1 Sheng He,1 Wen Xu,1,2 Xi Yang,1 Wen-Wen Cai,2 Jian-Ding Li,1 Bin-Quan Wang,3 Rui-Ping Zhang2 1Medical Imaging Department, First Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China; 2Imaging Department, Affiliated Tumor Hospital of Shanxi Medical University, Taiyuan, Shanxi, China; 3Department of Otolaryngology, Head & Neck Surgery, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, China *These authors contributed equally to the paper Background: Melanin and manganese are both indispensable natural substances that play crucial roles in the human body. Melanin has been used as a multimodality imaging nanoplatform for biology science research because of its natural binding ability with metal ions (eg, 64Cu2+, Fe3+, and Gd3+. Because of its effects on T1 signal enhancement, Mn-based nanoparticles have been used in magnetic resonance (MR quantitative cell tracking in vivo. Stem cell tracking in vivo is an essential technology used to characterize engrafted stem cells, including cellular viability, biodistribution, differentiation capacity, and long-term fate.Methods: In the present study, manganese(II ions chelated to melanin nanoparticles [MNP-Mn(II] were synthesized. The characteristics, stem cell labeling efficiency, and cytotoxicity of the nanoparticles were evaluated. MR imaging of the labeled stem cells in vivo and in vitro were also further performed. In T1 relaxivity (r1, MNP-Mn(II were significantly more abundant than Omniscan. Bone marrow-derived stem cells (BMSCs can be labeled easily by coincubating with MNP-Mn(II, suggesting that MNP-Mn(II had high biocompatibility.Results: Cell Counting Kit-8 assays revealed that MNP-Mn(II had almost no cytotoxicity when used to label BMSCs, even with a very high concentration (1,600 µg/mL. BMSCs labeled with MNP-Mn(II could generate a hyperintense T1 signal both in vitro

  12. Epidermal growth factor receptor in primary human lung cancer

    International Nuclear Information System (INIS)

    Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

    1996-01-01

    Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125 I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g -1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g -1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

  13. Characterization of a polyketide synthase in Aspergillus niger whose product is a precursor for both dihydroxynaphthalene (DHN) melanin and naphtho-γ-pyrone.

    Energy Technology Data Exchange (ETDEWEB)

    Chiang, Yi Ming; Meyer, Kristen M; Praseuth, Michael; Baker, Scott E; Bruno, Kenneth S; Wang, Clay C

    2010-12-06

    The genome sequencing of the fungus Aspergillus niger, an industrial workhorse, uncovered a large cache of genes encoding enzymes thought to be involved in the production of secondary metabolites yet to be identified. Identification and structural characterization of many of these predicted secondary metabolites are hampered by their low concentration relative to the known A. niger metabolites such as the naphtho-γ-pyrone family of polyketides. We deleted a nonreducing PKS gene in A. niger strain ATCC 11414, a daughter strain of A. niger ATCC strain 1015 whose genome was sequenced by the DOE Joint Genome Institute. This PKS encoding gene is a predicted ortholog of alb1 from Aspergillus fumigatus which is responsible for production of YWA1, a precursor of fungal DHN melanin. Our results show that the A. niger alb1 PKS is responsible for the production of the polyketide precursor for DHN melanin biosynthesis. Deletion of alb1 elimnates the production of major metabolites, naphtho-γ-pyrones. The generation of an A. niger strain devoid of naphtho-γ-pyrones will greatly facilitate the elucidation of cryptic biosynthetic pathways in this organism.

  14. Characterization of Melanin Radicals in Paraffin-embedded Malignant Melanoma and Nevus Pigmentosus Using X-band EPR and EPR Imaging.

    Science.gov (United States)

    Nakagawa, Kouichi; Minakawa, Satoko; Sawamura, Daisuke; Hara, Hideyuki

    2017-01-01

    Continuous wave electron paramagnetic resonance (CW EPR) and X-band (9 GHz) EPR imaging (EPRI) were used to nondestructively investigate the possible differentiation between malignant melanoma (MM) and nevus pigmentosus (NP) melanin radicals in paraffin-embedded specimens. The EPR spectra of both samples were analyzed using linewidth, spectral pattern, and X-band EPRI. The CW-EPR spectra of the MM showed an additional signal overlap. Eumelanin- and pheomelanin-related radicals were observed in the MM specimens. The EPR results revealed that the peak-to-peak linewidths (ΔH pp ) of paraffin-embedded MM and NP samples were 0.65 ± 0.01 and 0.69 ± 0.01 mT, respectively. The g-value was 2.005 for both samples. Moreover, the two-dimensional (2D) EPRI of the MM showed different signal intensities at the different tumor stages, unlike the NP, which displayed fewer variations in signal intensity. Thus, the present results suggest that EPR and 2D EPRI can be useful for characterization of the two melanin radicals in the MM and for determination of their size and concentration.

  15. Melanin-originated carbonaceous dots for triple negative breast cancer diagnosis by fluorescence and photoacoustic dual-mode imaging.

    Science.gov (United States)

    Xiao, Wei; Li, Yuan; Hu, Chuan; Huang, Yuan; He, Qin; Gao, Huile

    2017-07-01

    Carbonaceous dots exhibit increasing applications in diagnosis and drug delivery due to excellent photostability and biocompatibility properties. However, relative short excitation and emission of melanin carbonaceous dots (MCDs) limit the applicability in fluorescence bioimaging. Furthermore, the generally poor spatial resolution of fluorescence imaging limits potential in vivo applications. Due to a variety of beneficial properties, in this study, MCDs were prepared exhibiting great potential in fluorescence and photoacoustic dual-mode bioimaging. The MCDs exhibited a long excitation peak at 615nm and emission peak at 650nm, further highlighting the applicability in fluorescence imaging, while the absorbance peak at 633nm renders MCDs suitable for photoacoustic imaging. In vivo, the photoacoustic signal of MCDs was linearly correlated with the concentration of MCDs. Moreover, the MCDs were shown to be taken up into triple negative breast cancer cell line 4T1 in both a time- and concentration-dependent manner. In vivo fluorescence and photoacoustic imaging of subcutaneous 4T1 tumor demonstrated that MCDs could passively target triple negative breast cancer tissue by enhanced permeability and retention effects and may therefore be used for tumor dual-mode imaging. Furthermore, fluorescence distribution in tissue slices suggested that MCDs may distribute in 4T1 tumor with high efficacy. In conclusion, the MCDs studied offer potential application in fluorescence and photoacoustic dual-mode imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. N-acetylglucosamine affects Cryptococcus neoformans cell-wall composition and melanin architecture.

    Science.gov (United States)

    Camacho, Emma; Chrissian, Christine; Cordero, Radames J B; Liporagi-Lopes, Livia; Stark, Ruth E; Casadevall, Arturo

    2017-11-01

    Cryptococcus neoformans is an environmental fungus that belongs to the phylum Basidiomycetes and is a major pathogen in immunocompromised patients. The ability of C. neoformans to produce melanin pigments represents its second most important virulence factor, after the presence of a polysaccharide capsule. Both the capsule and melanin are closely associated with the fungal cell wall, a complex structure that is essential for maintaining cell morphology and viability under conditions of stress. The amino sugar N-acetylglucosamine (GlcNAc) is a key constituent of the cell-wall chitin and is used for both N-linked glycosylation and GPI anchor synthesis. Recent studies have suggested additional roles for GlcNAc as an activator and mediator of cellular signalling in fungal and plant cells. Furthermore, chitin and chitosan polysaccharides interact with melanin pigments in the cell wall and have been found to be essential for melanization. Despite the importance of melanin, its molecular structure remains unresolved; however, we previously obtained critical insights using advanced nuclear magnetic resonance (NMR) and imaging techniques. In this study, we investigated the effect of GlcNAc supplementation on cryptococcal cell-wall composition and melanization. C. neoformans was able to metabolize GlcNAc as a sole source of carbon and nitrogen, indicating a capacity to use a component of a highly abundant polymer in the biospherenutritionally. C. neoformans cells grown with GlcNAc manifested changes in the chitosan cell-wall content, cell-wall thickness and capsule size. Supplementing cultures with isotopically 15 N-labelled GlcNAc demonstrated that the exogenous monomer serves as a building block for chitin/chitosan and is incorporated into the cell wall. The altered chitin-to-chitosan ratio had no negative effects on the mother-daughter cell separation; growth with GlcNAc affected the fungal cell-wall scaffold, resulting in increased melanin deposition and assembly. In

  17. Topical microemulsion containing Punica granatum extract: its control over skin erythema and melanin in healthy Asian subjects.

    Science.gov (United States)

    Parveen, Rashida; Akhtar, Naveed; Mahmood, Tariq

    2014-12-01

    Punica granatum is apotent source of polyphenolic compounds with strong free radicals scavenging activity. The skin lightening effects of Punica granatum are assumed due to ellagic acid which acts by chelating copper at the active site of tyrosinase. To explore a topical microemulsion (O/W) of pomegranate (Punica granatum) extract for its control on skin erythema and melanin. Microemulsions were formulated using a polysorbate surfactant (Tween 80(®)) along with cosurfactant (propylene glycol) and were characterized regarding their stability. The placebo microemulsion (without extract) and the active microemulsion (containing Punica extract) were applied in a split face fashion by the volunteers (n = 11) for a period of 12 weeks. Skin erythema and melanin were measured at baseline and after every 15 days to determine any effect produced by these formulations. Active formulation showed a significant impact on skin erythema and melanin (p Punica granatum extract for conditions where elevated skin melanin and erythema have significantly prone skin physiology.

  18. Influence of chitosan and melanin-glucan complex onto gamma-exposure with low doses and acute stressful reaction

    International Nuclear Information System (INIS)

    Senyuk, O.F.; Tarasenko, P.D.; Pazukhin, Eh.M.; Gorovoj, L.F.; Varlamov, V.P.

    2004-01-01

    Possibilities of prevention and reduction of consequences of acute exposure on the background of immobilization stress with the help of chitosan preparations and of melanin - glucan complex of highest bazidiomicetes (fungi) were studied. Tested preparations were capable to protect hematological and immunological homeostasis of line BALB/c mice from stressful reaction provoked by acute exposure and two-hour immobilization. The most expressed normalizing and adapting effect had the mixture composed of chitosan and melanin-glucan complex

  19. Reptured Epidermal Inclusion Cyst in the Axilla: A Case Report

    International Nuclear Information System (INIS)

    Kim, Kyu Soon; Kim, Hak Hee; Shin, Hee Jeong; Yang, Hye Rin; Sohn, Jeong Hee; Kwon, Gui Young; Gong, Gyung Yub

    2006-01-01

    Epidermal inclusion cysts, the most common type of simple epithelial cyst, are typically well-encapsulated, subepidermal and mobile nodules. They may occur anywhere, but are mostly found on the scalp, face, neck, trunk, and back. Less than 10% of epidermal inclusion cysts occur on the extremities, and even fewer are found on the palms, soles, and breasts. If epidermal inclusion cysts rupture, foreign body reaction, granulomatous reaction or abscess formation could follow. We described here the sonographic findings of ruptured epidermal inclusion cyst of the right axilla in a 33-year-old woman who presented with a palpable axillary mass forming an inflammatory abscess

  20. Culture technique of rabbit primary epidermal keratinocytes

    Directory of Open Access Journals (Sweden)

    Marini M

    2012-10-01

    Full Text Available The epidermis is the protective covering outer layer of the mammalian skin. The epidermal cells are stratified squamous epithelia which undergo continuous differentiation of loss and replacement of cells. Ninety per cent of epidermal cells consist of keratinocytes that are found in the basal layer of the stratified epithelium called epidermis. Keratinocytes are responsible for forming tight junctions with the nerves of the skin as well as in the process of wound healing. This article highlights the method of isolation and culture of rabbit primary epidermal keratinocytes in vitro. Approximately 2cm x 2cm oval shaped line was drawn on the dorsum of the rabbit to mark the surgical area. Then, the skin was carefully excised using a surgical blade and the target skin specimens harvested from the rabbits were placed in transport medium comprising of Dulbecco’s Modified Eagle Medium (DMEM and 1% of antibiotic-antimycotic solution. The specimens were transferred into a petri dish containing 70% ethanol and washed for 5 min followed by a wash in 1 x Dulbecco’s Phosphate Buffered Saline (DBPS. Then, the skin specimens were placed in DMEM and minced into small pieces using a scalpel. The minced pieces were placed in a centrifuge tube containing 0.6% Dispase and 1% antibiotic-antimycotic solution overnight at 4°C in a horizontal orientation. The epidermis layer (whitish, semi-transparent was separated from the dermis (pink, opaque, gooey with the aid of curved forceps by fixing the dermis with one pair of forceps while detaching the epidermis with the second pair. The cells were cultured at a density of 4 x 104 cells/cm2 in culture flask at 37°C and 5% CO2. The cell morphology of the keratinocytes was analyzed using inverted microscope.

  1. Structure of melanins from the fungi Ochroconis lascauxensis and Ochroconis anomala contaminating rock art in the Lascaux Cave.

    Science.gov (United States)

    De la Rosa, José Maria; Martin-Sanchez, Pedro M; Sanchez-Cortes, Santiago; Hermosin, Bernardo; Knicker, Heike; Saiz-Jimenez, Cesareo

    2017-10-18

    Two novel species of the fungal genus Ochroconis, O. lascauxensis and O. anomala have been isolated from the walls of the Lascaux Cave, France. The interest in these fungi and their melanins lies in the formation of black stains on the walls and rock art which threatens the integrity of the paintings. Here we report solid-state cross polarization magic-angle spinning 13 C and 15 N nuclear magnetic resonance (NMR) spectroscopy and surface-enhanced Raman spectroscopy (SERS) of the melanins extracted from the mycelia of O. lascauxensis and O. anomala in order to known their chemical structure. The melanins from these two species were compared with those from other fungi. The melanins from the Ochroconis species have similar SERS and 13 C and 15 N NMR spectra. Their chemical structures as suggested by the data are not related to 3,4-dihydroxyphenylalanine, 5,6-dihydroxyindole or 1,8-dihydroxynaphthalene precursors and likely the building blocks from the melanins have to be based on other phenols that react with the N-terminal amino acid of proteins. The analytical pyrolysis of the acid hydrolysed melanin from O. lascauxensis supports this assumption.

  2. Compositional changes of human hair melanin resulting from bleach treatment investigated by nanoscale secondary ion mass spectrometry.

    Science.gov (United States)

    Kojima, Toru; Yamada, Hiromi; Isobe, Mitsuru; Yamamoto, Toshihiko; Takeuchi, Miyuki; Aoki, Dan; Matsushita, Yasuyuki; Fukushima, Kazuhiko

    2014-11-01

    It is important to understand the influence of bleach treatment on human hair because it is one of the most important chemical treatments in hair cosmetic processes. A comparison of the elemental composition of melanin between virgin hair and bleached hair would provide important information about the structural changes of melanin. To investigate the elemental composition of melanin granules in virgin black hair and bleached hair, these hair cross-sections are analyzed by using a nanoscale secondary ion mass spectrometry (NanoSIMS). The virgin black hair and bleached hair samples were embedded in resin and smooth hair cross-sections were obtained using an ultramicrotome. NanoSIMS measurements were performed using a Cs(+) primary ion beam to detect negative secondary ions. More intensive (16) O(-) ions were detected from the melanin granules of bleached hair than from those of virgin black hair in NanoSIMS (16) O(-) ion image. In addition, it was indicated that (16) O(-) ion intensity and (16) O(-) /(12) C(14) N(-) ion intensity ratio of melanin granules in bleached hair were higher than those in virgin black hair. Nanoscale secondary ion mass spectrometry analysis of the cross-sections of virgin black hair and bleached hair indicated that the oxygen content in melanin granules was increased by bleach treatment. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Antioxidative role of ocular melanin pigment in the model of lens induced uveitis.

    Science.gov (United States)

    Bilgihan, A; Bilgihan, M K; Akata, R F; Aricioğlu, A; Hasanreisoğlu, B

    1995-12-01

    Ocular melanin pigment has antioxidant effect against excess of dispersed light. To investigate whether it has a similar effect in ocular inflammations, we used albino and pigmented guinea pigs and measured retinal glutathione peroxidase activities and lipid peroxide levels (expressed as thiobarbituric acid reactive substances) in a model of lens induced uveitis. Although the increase in the levels of the retinal lipid peroxides were higher in the albino group (204%, p < 0.05), the decrease in the activities of glutathione peroxidase were higher in pigmented guinea pigs (26%, p < 0.005). The results of the study suggest that pigmentless animals are more sensitive to the ocular inflammations, and ocular melanin pigment may act as an endojen antioxidant in lens induced uveitis.

  4. Three-dimensional multispectral optoacoustic mesoscopy reveals melanin and blood oxygenation in human skin in vivo.

    Science.gov (United States)

    Schwarz, Mathias; Buehler, Andreas; Aguirre, Juan; Ntziachristos, Vasilis

    2016-01-01

    Optical imaging plays a major role in disease detection in dermatology. However, current optical methods are limited by lack of three-dimensional detection of pathophysiological parameters within skin. It was recently shown that single-wavelength optoacoustic (photoacoustic) mesoscopy resolves skin morphology, i.e. melanin and blood vessels within epidermis and dermis. In this work we employed illumination at multiple wavelengths for enabling three-dimensional multispectral optoacoustic mesoscopy (MSOM) of natural chromophores in human skin in vivo operating at 15-125 MHz. We employ a per-pulse tunable laser to inherently co-register spectral datasets, and reveal previously undisclosed insights of melanin, and blood oxygenation in human skin. We further reveal broadband absorption spectra of specific skin compartments. We discuss the potential of MSOM for label-free visualization of physiological biomarkers in skin in vivo. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. AP-1/KIF13A Blocking Peptides Impair Melanosome Maturation and Melanin Synthesis

    Directory of Open Access Journals (Sweden)

    Cécile Campagne

    2018-02-01

    Full Text Available Melanocytes are specialized cells that generate unique organelles called melanosomes in which melanin is synthesized and stored. Melanosome biogenesis and melanocyte pigmentation require the transport and delivery of melanin synthesizing enzymes, such as tyrosinase and related proteins (e.g., TYRP1, from endosomes to maturing melanosomes. Among the proteins controlling endosome-melanosome transport, AP-1 together with KIF13A coordinates the endosomal sorting and trafficking of TYRP1 to melanosomes. We identify here β1-adaptin AP-1 subunit-derived peptides of 5 amino acids that block the interaction of KIF13A with AP-1 in cells. Incubating these peptides with human MNT-1 cells or 3D-reconstructed pigmented epidermis decreases pigmentation by impacting the maturation of melanosomes in fully pigmented organelles. This study highlights that peptides targeting the intracellular trafficking of melanocytes are candidate molecules to tune pigmentation in health and disease.

  6. The Epidermal Growth Factor Receptor Is a Regulator of Epidermal Complement Component Expression and Complement Activation

    DEFF Research Database (Denmark)

    Abu-Humaidan, Anas H A; Ananthoju, Nageshwar; Mohanty, Tirthankar

    2014-01-01

    The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin...

  7. Differential effects of endoparasitism on the expression of carotenoid- and melanin-based ornamental coloration.

    OpenAIRE

    McGraw, K J; Hill, G E

    2000-01-01

    The striking diversity of sexual dimorphisms in nature begs the question: Why are there so many signal types? One possibility is that ornamental traits convey different sets of information about the quality of the sender to the receiver. The colourful, pigmented feathers of male birds seem to meet the predictions of this hypothesis. Evidence suggests that carotenoid pigmentation reflects the nutritional condition of males during moult, whereas in many instances melanin pigmentation is a relia...

  8. Melanocytes and melanin represent a first line of innate immunity against Candida albicans.

    Science.gov (United States)

    Tapia, Cecilia V; Falconer, Maryanne; Tempio, Fabián; Falcón, Felipe; López, Mercedes; Fuentes, Marisol; Alburquenque, Claudio; Amaro, José; Bucarey, Sergio A; Di Nardo, Anna

    2014-07-01

    Melanocytes are dendritic cells located in the skin and mucosae that synthesize melanin. Some infections induce hypo- or hyperpigmentation, which is associated with the activation of Toll-like receptors (TLRs), especially TLR4. Candida albicans is an opportunist pathogen that can switch between blastoconidia and hyphae forms; the latter is associated with invasion. Our objectives in this study were to ascertain whether C. albicans induces pigmentation in melanocytes and whether this process is dependent on TLR activation, as well as relating this with the antifungal activity of melanin as a first line of innate immunity against fungal infections. Normal human melanocytes were stimulated with C. albicans supernatants or with crude extracts of the blastoconidia or hyphae forms, and pigmentation and TLR2/TLR4 expression were measured. Expression of the melanosomal antigens Melan-A and gp100 was examined for any correlation with increased melanin levels or antifungal activity in melanocyte lysates. Melanosomal antigens were induced earlier than cell pigmentation, and hyphae induced stronger melanization than blastoconidia. Notably, when melanocytes were stimulated with crude extracts of C. albicans, the cell surface expression of TLR2/TLR4 began at 48 h post-stimulation and peaked at 72 h. At this time, blastoconidia induced both TLR2 and TLR4 expression, whereas hyphae only induced TLR4 expression. Taken together, these results suggest that melanocytes play a key role in innate immune responses against C. albicans infections by recognizing pathogenic forms of C. albicans via TLR4, resulting in increased melanin content and inhibition of infection. © The Author 2014. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  9. The Protective Role of Melanin Against UV Damage in Human Skin

    OpenAIRE

    Brenner, Michaela; Hearing, Vincent J.

    2008-01-01

    Human skin is repeatedly exposed to ultraviolet radiation (UVR) that influences the function and survival of many cell types and is regarded as the main causative factor in the induction of skin cancer. It has been traditionally believed that skin pigmentation is the most important photoprotective factor, since melanin, besides functioning as a broadband UV absorbent, has antioxidant and radical scavenging properties. Besides, many epidemiological studies have shown a lower incidence for skin...

  10. Genetic monitoring of experimental Drosophila populations exposed to X-radiation and treated with melanin

    International Nuclear Information System (INIS)

    Mosseh, I.B.; Savchenko, V.K.; Lyakh, I.P.

    1985-01-01

    Monitoring of laboratory populations of Drosophila over four years has demonstrated that X radiation of 0.25 C/kg, delivered during the life span of each generation, causes a decrease of 20% and 30%, on the average, in the number of individuals in 1-55 generations and 45-55 generations, respectively. The antimutagen, melanin, added to a nutrient medium has no effect on the number of individuals in populations

  11. UV causation of melanoma in Xiphophorus is dominated by melanin photosensitized oxidant production

    OpenAIRE

    Wood, Simon R.; Berwick, Marianne; Ley, Ronald D.; Walter, Ronald B.; Setlow, Richard B.; Timmins, Graham S.

    2006-01-01

    Controversy continues both as to which wavelengths of sunlight cause melanoma and the mechanisms by which these different wavelengths act. Direct absorption of UVB by DNA is central in albino animal models, but melanin-pigmented models have shown major contributions by wavelengths longer than UVB that are thought to be mediated by photosensitized oxidant production. The only model for which the action spectrum of melanoma causation is known is a genetically melanoma-susceptible specific cross...

  12. LIGHT REGULATION OF GROWTH AND MELANIN FORMATION IN Inonotus оbliquus (Pers. Pilat

    Directory of Open Access Journals (Sweden)

    N. L. Poyedinok

    2013-04-01

    Full Text Available The study aims to investigate possibilities of using different sources of low-intensity light for the regulation of mycelium growth and melanin synthesis by medicinal mushroom Inonotus obliquus (Pers. Pilat. Studies of the light’s influence on the linear growth, biomass accumulation and melanin synthesis I. obliquus were performed using experimental installations that provide both lasing (coherent light with specified parameters, as well as sources of incoherent light. It has been demonstrated that the greatest stimulating effect took place during the irradiation of mycelium with blue light. It has been found that further realization of photobiological effect is largely dependent on the method of cultivation. Irradiation with laser light within all studied wavelength ranges was more conducive to growth, biomass and melanin accumulation in the mushroom mycelium than incoherent light irradiation within the same wavelength range. Light treatment made it possible to significantly reduce the duration of fermentation. The results of studies allow considering lowintensity light in the visible part of the spectrum as a perspective growth and biosynthetic activity regulator of I. obliquus in the biotechnology of its cultivation.

  13. Substantial Effect of Melanin Influencing Factors on Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo

    Directory of Open Access Journals (Sweden)

    Touseef Amna

    2012-07-01

    Full Text Available The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH, nitric oxide (NO and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (p<0.05 the amount of total melanin in black and brindle whereas eumelanin production in brown Hanwoo muzzle melanocytes. On the contrary, L-cysteine greatly (p<0.05 depressed the eumelanin production in black color but increased in brown. Simultaneously, up regulation of Tyr by nitric oxide and α-MSH and down regulation of Tyr, Tyrp-2 and MC1R genes by L-cysteine were observed in muzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

  14. Etanercept therapy for toxic epidermal necrolysis.

    Science.gov (United States)

    Paradisi, Andrea; Abeni, Damiano; Bergamo, Fabio; Ricci, Francesco; Didona, Dario; Didona, Biagio

    2014-08-01

    Toxic epidermal necrolysis (TEN) is a severe and potentially lethal drug reaction for which no standard treatment is available. To describe a case series of patients with TEN treated with a single dose of etanercept. We observed 10 consecutive patients with TEN. For each patient, we recorded the presence of comorbidities and all the drugs recently started (ie, in the last month). In all cases, 50 mg of etanercept was administered in a single subcutaneous injection. The clinical severity of disease was computed using the SCORe of Toxic Epidermal Necrosis (SCORTEN) scale. Using the probabilities of death linked to each level of SCORTEN score, we calculated the expected probability of death in our patients. Healing was defined as complete reepithelialization, and a time to healing curve was then obtained using the Kaplan-Meier method. All patients promptly responded to treatment, reaching complete reepithelialization without complications or side effects. The median time to healing was 8.5 days. This is a small, uncontrolled case series. These preliminary results suggest the possibility that tumor necrosis factor-alfa may be an effective target for control of TEN, a dangerous skin condition for which no effective cure has yet been found. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  15. Post-female-circumcision clitoral epidermal inclusion cyst: a case ...

    African Journals Online (AJOL)

    Keywords: complication, epidermal inclusion cyst, female circumcision. Pediatric Urology Division, Department of Urology, ... transplantation of the epidermis into the subcutaneous tissue with subsequent proliferation of epidermal ... The evolution of the practice of FGM, from being performed by traditional birth attendants to.

  16. Herbal medicines that benefit epidermal permeability barrier function

    Directory of Open Access Journals (Sweden)

    Lizhi Hu

    2015-06-01

    Full Text Available Epidermal permeability barrier function plays a critical role in regulating cutaneous functions. Hence, researchers have been searching for effective and affordable regimens to enhance epidermal permeability barrier function. In addition to topical stratum corneum lipids, peroxisome proliferator-activated receptor, and liver X receptor ligands, herbal medicines have been proven to benefit epidermal permeability barrier function in both normal and diseased skin, including atopic dermatitis, glucocorticoid-induced skin damage, and UVB-damaged skin. The potential mechanisms by which herbal medicines improve the permeability barrier include stimulation of epidermal differentiation, lipid production, antimicrobial peptide expression, and antioxidation. Therefore, utilization of herbal medicines could be a valuable alternative approach to enhance epidermal permeability barrier function in order to prevent and/or treat skin disorders associated with permeability barrier abnormalities.

  17. Genetic analysis of Ras genes in epidermal development and tumorigenesis

    Science.gov (United States)

    Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

    2013-01-01

    Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

  18. Mechanical and photo-fragmentation processes for nanonization of melanin to improve its efficacy in protecting cells from reactive oxygen species stress

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yi-Cheng [Graduate Institute of Photonics and Optoelectronics, and Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan (China); Chen, Sih-Min [Graduate Institute of Biophysics, National Central University, Jhongli 32001, Taiwan (China); Liu, Jhong-Han; Hsu, Hsiang-Wei [Department of Physics, National Central University, Jhongli 32001, Taiwan (China); Lin, Hoang-Yan [Graduate Institute of Photonics and Optoelectronics, and Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Chen, Szu-yuan, E-mail: sychen@ltl.iams.sinica.edu.tw [Institute of Atomic and Molecular Sciences, Academia Sinica, Taipei 10617, Taiwan (China); Graduate Institute of Biophysics, National Central University, Jhongli 32001, Taiwan (China); Department of Physics, National Central University, Jhongli 32001, Taiwan (China)

    2015-02-14

    It has been well established ex vivo that melanin has the ability of scavenging free radicals and reactive oxygen species (ROS), besides other functions. Therefore, we propose to utilize nanonized melanin as medication against acute oxidative stress. For this purpose, we developed and characterized two techniques based on mechanical stir and photo-fragmentation using femtosecond laser pulses, respectively, for disintegration of suspended melanin powder to produce nanometer-sized and water-dispersible melanin. This resolves a major obstacle in the medical and industrial applications of melanin. The viabilities of cultured retinal pigment epithelium (RPE) cells exposed to exogenous H{sub 2}O{sub 2} stress and treated with various conditions of melanin and irradiation were compared. It was found that melanin could be nanonized very effectively with the techniques, and nanonized melanin exhibited a much stronger effect than unprocessed melanin on raising the viability of cultured RPE cells under acute ROS stress. The effect was even more prominent without simultaneous light irradiation, promising for effective in vivo application to the whole body.

  19. Mechanical and photo-fragmentation processes for nanonization of melanin to improve its efficacy in protecting cells from reactive oxygen species stress

    International Nuclear Information System (INIS)

    Liu, Yi-Cheng; Chen, Sih-Min; Liu, Jhong-Han; Hsu, Hsiang-Wei; Lin, Hoang-Yan; Chen, Szu-yuan

    2015-01-01

    It has been well established ex vivo that melanin has the ability of scavenging free radicals and reactive oxygen species (ROS), besides other functions. Therefore, we propose to utilize nanonized melanin as medication against acute oxidative stress. For this purpose, we developed and characterized two techniques based on mechanical stir and photo-fragmentation using femtosecond laser pulses, respectively, for disintegration of suspended melanin powder to produce nanometer-sized and water-dispersible melanin. This resolves a major obstacle in the medical and industrial applications of melanin. The viabilities of cultured retinal pigment epithelium (RPE) cells exposed to exogenous H 2 O 2 stress and treated with various conditions of melanin and irradiation were compared. It was found that melanin could be nanonized very effectively with the techniques, and nanonized melanin exhibited a much stronger effect than unprocessed melanin on raising the viability of cultured RPE cells under acute ROS stress. The effect was even more prominent without simultaneous light irradiation, promising for effective in vivo application to the whole body

  20. Effect of vasoactive intestinal polypeptide and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    The effect of VIP and somatostatin on secretion of epidermal growth factor and bicarbonate from Brunner's glands was investigated in the rat. Vasoactive intestinal polypeptide infused in doses of 10 and 100 ng/kg/h significantly increased epidermal growth factor and bicarbonate output......, but the concentrations did not change. Somatostatin infused at doses of 1, 10, 100 and 1000 ng/kg/h against a background of VIP 100 ng/kg/h inhibited in dose-dependent fashion the stimulated epidermal growth factor and bicarbonate outputs from rat Brunner's gland pouches. Also basal secretion was inhibited...... growth factor and bicarbonate from Brunner's glands, an effect which is inhibited by somatostatin. A possible role for somatostatin in the control of Brunner's gland secretion is suggested....

  1. Diagnostic utility of melanin production by fungi: Study on tissue sections and culture smears with Masson-Fontana stain

    Directory of Open Access Journals (Sweden)

    Challa Sundaram

    2014-01-01

    Full Text Available Background: Dematiaceous fungi appear brown in tissue section due to melanin in their cell walls. When the brown color is not seen on routine H and E and culture is not available, differentiation of dematiaceous fungi from other fungi is difficult on morphology alone. Aims and Objective: To study if melanin production by dematiaceous fungi can help differentiate them from other types of fungi. Materials and Methods: Fifty tissue sections of various fungal infections and 13 smears from cultures of different species of fungi were stained with Masson Fontana stain to assess melanin production. The tissue sections included biopsies from 26 culture-proven fungi and 24 biopsies of filamentous fungi diagnosed on morphology alone with no culture confirmation. Results: All culture-proven dematiaceous fungi and Zygomycetes showed strong positivity in sections and culture smears. Aspergillus sp showed variable positivity and intensity. Cryptococcus neoformans showed strong positivity in tissue sections and culture smears. Tissue sections of septate filamentous fungi (9/15, Zygomycetes (4/5, and fungi with both hyphal and yeast morphology (4/4 showed positivity for melanin. The septate filamentous fungi negative for melanin were from biopsy samples of fungal sinusitis including both allergic and invasive fungal sinusitis and colonizing fungal balls. Conclusion: Melanin is produced by both dematiaceous and non-dematiaceous fungi. Masson-Fontana stain cannot reliably differentiate dematiaceous fungi from other filamentous fungi like Aspergillus sp; however, absence of melanin in the hyphae may be used to rule out dematiaceous fungi from other filamentous fungi. In the differential diagnosis of yeast fungi, Cryptococcus sp can be differentiated from Candida sp by Masson-Fontana stain in tissue sections.

  2. Homologous radioimmunoassay for human epidermal growth factor (urogastrone)

    International Nuclear Information System (INIS)

    Dailey, G.E.; Kraus, J.W.; Orth, D.N.

    1978-01-01

    Epidermal growth factor (EGF), a polypeptide hormone originally discovered in the mouse submaxillary gland, stimulates growth in a variety of tissues in several species. This hormone has recently been identified in human urine. A homologous RIA for human EGF (RIA-hEGF) has been developed. In general, levels were similar to those recently reported using a heterologous RIA system. Twenty-four-hour urinary excretion of RIA-hEGF by normal adult males and females was 63.0 +- 3.0 and 52.0 +- 3.5 (mean +- SE) μg/total vol, or 29.7 +- 1.1 and 39.8 +- 1.7 μg/g creatinine, respectively. Excretion by females taking oral contraceptives was significantly greater (60.1 +- 2.7 μg/g creatinine; P 0.05). Several of those with very low values had histories of alcohol abuse. Excretion by patients with Cushing's syndrome was normal. Patients with psoriasis or recovering from major burns excreted both abnormally high and abnormally low levels of RIA-hEGF, with no obvious correlation to their clinical condition. There was no apparent diurnal or postprandial variation in urinary RIA-hEGF excretion by normal subjects. An excellent linear correlation was observed between RIA-hEGF and creatinine concentrations in each urine sample for each subject, suggesting that RIA-hEGF concentration in a random urine sample provides a valid index of 24-h RIA-hEGF excretion

  3. Human epidermal growth factor: molecular forms and application of radioimmunoassay and radioreceptor assay

    International Nuclear Information System (INIS)

    Hirata, Y.; Orth, D.N.

    1981-01-01

    Epidermal growth factor (EGF), a 53 amino acid polypeptide, was first isolated by Cohen. EGF's growth-promoting activity is not limited to epidermal cells, but is expressed on a wide variety of tissues derived from a number of different species. Human EGF (hEGF) was isolated and subsequently purified from human urine. Unexpectedly, a close structural relationship was recognized between mEGF and human β-urogastrone. The authors recently developed both an homologous hEGF radioimmunoassay (RIA) and a radioreceptor assay (RRA) using a human placental membrane fraction. Using these assays, the molecular size of hEGF in human body fluids and tissues was evaluated, and partial characterization of a high molecular weight form of hEGF isolated from human urine was carried out. The concentrations of immunoreactive hEGF were also determined in human tissues and plasma after extraction either with cationic exchange chromatography or with immunoaffinity chromatography. (Auth.)

  4. Heavy metal-induced cytotoxicity to cultured human epidermal keratinocytes and effects of antioxidants.

    Science.gov (United States)

    Kappus, H; Reinhold, C

    1994-04-01

    Human epidermal keratinocytes which have been cultured were treated with the heavy metal ions of cadmium, mercury, copper and zinc. Cytotoxicity was measured either by protein estimation or by using the neutral red assay. Antioxidants were added in order to find out whether heavy metal-induced cytotoxicity is related to oxidative stress. All metals used showed considerable cytotoxic effects within 24 h in moderate concentrations. None of the antioxidants vitamin E (alpha-tocopherol), pyrogallol, propyl gallate, BHT or ebselen showed any protective or preventive effect. This indicates that oxidative stress may not be involved in the cytotoxicity induced by heavy metals in human epidermal keratinocytes. The cells used are, however, a valuable tool to study mechanisms of cytotoxicity.

  5. Role of submandibular saliva and epidermal growth factor in gastric cytoprotection

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier

    1984-01-01

    without submandibular glands. Exogenous EGF and saliva with a high but still physiological concentration of EGF significantly reduced the median area in the stomach displaying ulcers and ulcerations, whereas saliva without EGF had no effect. Although EGF is a known inhibitor of gastric acid secretion......The role of submandibular epidermal growth factor in protection of the gastric mucosa was investigated in rats. Removal of the submandibular glands and thereby submandibular epidermal growth factor (EGF) caused rats to develop gastric lesions (ulcerations and ulcers) after administration......, the dose used in the present study had no effect on gastric acid secretion in chronic gastric fistula rats; removal of the submandibular glands also did not have any such effect. We conclude that exocrine secretion of submandibular EGF has a cytoprotective function in the stomach, an effect that may...

  6. Epidermal Growth Factor Receptor in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Oliveira-Cunha, Melissa; Newman, William G.; Siriwardena, Ajith K.

    2011-01-01

    Pancreatic cancer is the fourth leading cause of cancer related death. The difficulty in detecting pancreatic cancer at an early stage, aggressiveness and the lack of effective therapy all contribute to the high mortality. Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein, which is expressed in normal human tissues. It is a member of the tyrosine kinase family of growth factors receptors and is encoded by proto-oncogenes. Several studies have demonstrated that EGFR is over-expressed in pancreatic cancer. Over-expression correlates with more advanced disease, poor survival and the presence of metastases. Therefore, inhibition of the EGFR signaling pathway is an attractive therapeutic target. Although several combinations of EGFR inhibitors with chemotherapy demonstrate inhibition of tumor-induced angiogenesis, tumor cell apoptosis and regression in xenograft models, these benefits remain to be confirmed. Multimodality treatment incorporating EGFR-inhibition is emerging as a novel strategy in the treatment of pancreatic cancer

  7. Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

    Science.gov (United States)

    Negro, Juan J; Finlayson, Clive; Galván, Ismael

    2018-01-23

    Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures-the majority of paleo-colour studies involve melanin granules-is not without risks. In addition, animals with contrasting dorso-ventral colouration may be under different selection pressures beyond the need for camouflage, including, for instance, visual communication or ultraviolet (UV) protection. Melanin production is costly, and animals may invest less in areas of the integument where pigments are less needed. In addition, melanocytes exposed to UV radiation produce more melanin than unexposed melanocytes. Pigment economization may thus explain the colour pattern of some counter-shaded animals, including extinct species. Even in well-studied extant species, their diversity of hues and patterns is far from being understood; inferring colours and their functions in species only known from one or few specimens from the fossil record should be exerted with special prudence.

  8. Population-related genetic aspects of the low doses radiological risk and melanin influence on genetic radiosensitivity

    International Nuclear Information System (INIS)

    Mosse, I.B.; Plotnikova, S.I.; Kostrova, L.N.; Subbot, S.T.; Maksymenia, I.P.; Dubovic, B.V.

    1997-01-01

    From the genetic point of view, radiation sensitivity is a quantitative character, and the distribution of individuals in the population with different radiation sensitivities is characterized by a binomial curve. Thus rise in irradiation dose first results in a very slow increase in the number of sensitive genotypes, and then in a sharp rise. Since quantitative characters are dependent on several polymeric genes, and their manifestation is strongly affected by external conditions, radiation sensitivity of the organism depends on many hereditary and environmental factors. One of them is the presence of melanin pigment in cells. In particular, we have shown that the introduction of exogenous melanin into the organisms of mice reduces (2-4 times) the frequency of mutations, induced not only by acute, but also by chronic irradiation. It was also established, that mutational load, accumulated in drosophila populations, irradiated within 125 generations, has been decreased under melanin influence almost to the control level. Antimutagenic action of melanin is also manifested on cultured human cells. So, it was shown by the example of melanin, that it is possible to increase the radiation resistance of individuals, and in the first place of the population highly sensitive fraction. (author)

  9. Inhibitory Effects of Adlay Extract on Melanin Production and Cellular Oxygen Stress in B16F10 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Huey-Chun Huang

    2014-09-01

    Full Text Available The aim of this study was to determine the effects of adlay extract on melanin production and the antioxidant characteristics of the extract. The seeds were extracted by the supercritical fluid CO2 extraction (SFE method. The effect of adlay extract on melanin production was evaluated using mushroom tyrosinase activity assay, intracellular tyrosinase activity, antioxidant properties and melanin content. Those assays were performed spectrophotometrically. In addition, the expression of melanogenesis-related proteins was determined by western blotting. The results revealed that the adlay extract suppressed intracellular tyrosinase activity and decreased the amount of melanin in B16F10 cells. The adlay extract decreased the expression of microphthalmia-associated transcription factor (MITF, tyrosinase, tyrosinase related protein-1 (TRP-1 and tyrosinase related protein-2 (TRP-2. The extract also exhibited antioxidant characteristics such as free radical scavenging capacity and reducing power. It effectively decreased intracellular reactive oxygen species (ROS levels in B16F10 cells. We concluded that the adlay extract inhibits melanin production by down-regulation of MITF, tyrosinase, TRP-1 and TRP-2. The antioxidant properties of the extract may also contribute to the inhibition of melanogenesis. The adlay extract can therefore be applied as an inhibitor of melanogenesis and could also act as a natural antioxidant in skin care products.

  10. Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

    Science.gov (United States)

    Negro, Juan J.; Finlayson, Clive; Galván, Ismael

    2018-01-01

    Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures—the majority of paleo-colour studies involve melanin granules—is not without risks. In addition, animals with contrasting dorso-ventral colouration may be under different selection pressures beyond the need for camouflage, including, for instance, visual communication or ultraviolet (UV) protection. Melanin production is costly, and animals may invest less in areas of the integument where pigments are less needed. In addition, melanocytes exposed to UV radiation produce more melanin than unexposed melanocytes. Pigment economization may thus explain the colour pattern of some counter-shaded animals, including extinct species. Even in well-studied extant species, their diversity of hues and patterns is far from being understood; inferring colours and their functions in species only known from one or few specimens from the fossil record should be exerted with special prudence. PMID:29360744

  11. The pbrB gene encodes a laccase required for DHN-melanin synthesis in conidia of Talaromyces (Penicillium) marneffei.

    Science.gov (United States)

    Sapmak, Ariya; Boyce, Kylie J; Andrianopoulos, Alex; Vanittanakom, Nongnuch

    2015-01-01

    Talaromyces marneffei (Basionym: Penicillium marneffei) is a significant opportunistic fungal pathogen in patients infected with human immunodeficiency virus in Southeast Asia. T. marneffei cells have been shown to become melanized in vivo. Melanins are pigment biopolymers which act as a non-specific protectant against various stressors and which play an important role during virulence in fungi. The synthesis of the two most commonly found melanins in fungi, the eumelanin DOPA-melanin and the allomelanin DHN-melanin, requires the action of laccase enzymes. The T. marneffei genome encodes a number of laccases and this study describes the characterization of one of these, pbrB, during growth and development. A strain carrying a PbrB-GFP fusion shows that pbrB is expressed at high levels during asexual development (conidiation) but not in cells growing vegetatively. The pbrB gene is required for the synthesis of DHN-melanin in conidia and when deleted results in brown pigmented conidia, in contrast to the green conidia of the wild type.

  12. Melanins in Fossil Animals: Is It Possible to Infer Life History Traits from the Coloration of Extinct Species?

    Directory of Open Access Journals (Sweden)

    Juan J. Negro

    2018-01-01

    Full Text Available Paleo-colour scientists have recently made the transition from describing melanin-based colouration in fossil specimens to inferring life-history traits of the species involved. Two such cases correspond to counter-shaded dinosaurs: dark-coloured due to melanins dorsally, and light-coloured ventrally. We believe that colour reconstruction of fossils based on the shape of preserved microstructures—the majority of paleo-colour studies involve melanin granules—is not without risks. In addition, animals with contrasting dorso-ventral colouration may be under different selection pressures beyond the need for camouflage, including, for instance, visual communication or ultraviolet (UV protection. Melanin production is costly, and animals may invest less in areas of the integument where pigments are less needed. In addition, melanocytes exposed to UV radiation produce more melanin than unexposed melanocytes. Pigment economization may thus explain the colour pattern of some counter-shaded animals, including extinct species. Even in well-studied extant species, their diversity of hues and patterns is far from being understood; inferring colours and their functions in species only known from one or few specimens from the fossil record should be exerted with special prudence.

  13. Ultrastructural changes produced in Ehrlich ascites carcinoma cells by ultraviolet-visible radiation in the presence of melanins

    Energy Technology Data Exchange (ETDEWEB)

    Lea, P.J.; Pawlowski, A.; Persad, S.D.; Menon, I.A.; Haberman, H.F.

    1988-01-01

    Irradiation of Ehrlich ascites carcinoma (EAC) cells in the presence of pheomelanin, i.e., red hair melanin (RHM), has been reported to produce extensive cell lysis. Irradiation in the presence of eumelanin, i.e., black hair melanin (BHM), or irradiation in the absence of either type of melanin did not produce this effect. We observed that RHM particles penetrated the cell membrane without apparent structural damage to the cell or the cell membrane. Irradiation of the cells in the absence of melanin did not produce any changes in the ultrastructure of the cells. Incubation of the cells in the dark in the presence of RHM produced only minor structural, mainly cytoplasmic changes. Irradiation of the cells in the presence of RHM produced extensive ultrastructural changes prior to complete cell lysis; these changes were more severe than the effects of incubation of the cells in the dark in the presence of RHM. When the cells incubated in the dark or irradiated in the presence of latex particles or either one of the eumelanins particles, viz. BHM or synthetic dopa melanin, these particles did not penetrate into the cells or produce any ultrastructural changes. These particles were in fact not even ingested by the cells.

  14. Spatiotemporal Expression of p63 in Mouse Epidermal Commitment

    Directory of Open Access Journals (Sweden)

    Qian Zhao

    2015-12-01

    Full Text Available The embryonic surface ectoderm is a simple flat epithelium consisting of cells that express the cytokeratins K8/K18. Before stratification, K5/K14 expression substitutes K8/K18 expression, marking the event called epidermal commitment. Previous studies show that the transcription factor p63 plays an essential role in epidermal commitment. However, detailed expression information of p63 during early epidermal development in mice is still unclear. We systematically studied the expression pattern of p63 in mouse epidermal commitment, together with K8 and K5. We show that p63 expression could be detected as early as E8.5 in mouse embryos preceding epidermal commitment. p63 expression first appears near the newly formed somites and the posterior part of the embryo, further expanding to the whole embryonic surface with particular enrichment in the first branchial arches and the limb buds. ΔNp63 is the major class of isoforms expressed in this period. Relative expression intensity of p63 depends on the embryonic position. In summary, there is a sequential and regular expression pattern of K8, p63 and K5 in mouse epidermal commitment. Our study not only contributes to understanding the early events during epidermal development but also provides a basal tool to study the function of p63 in mammals.

  15. Polymeric membranes modulate human keratinocyte differentiation in specific epidermal layers.

    Science.gov (United States)

    Salerno, Simona; Morelli, Sabrina; Giordano, Francesca; Gordano, Amalia; Bartolo, Loredana De

    2016-10-01

    In vitro models of human bioengineered skin substitutes are an alternative to animal experimentation for testing the effects and toxicity of drugs, cosmetics and pollutants. For the first time specific and distinct human epidermal strata were engineered by using membranes and keratinocytes. To this purpose, biodegradable membranes of chitosan (CHT), polycaprolactone (PCL) and a polymeric blend of CHT-PCL were prepared by phase-inversion technique and characterized in order to evaluate their morphological, physico-chemical and mechanical properties. The capability of membranes to modulate keratinocyte differentiation inducing specific interactions in epidermal membrane systems was investigated. The overall results demonstrated that the membrane properties strongly influence the cell morpho-functional behaviour of human keratinocytes, modulating their terminal differentiation, with the creation of specific epidermal strata or a fully proliferative epidermal multilayer system. In particular, human keratinocytes adhered on CHT and CHT-PCL membranes, forming the structure of the epidermal top layers, such as the corneum and granulosum strata, characterized by withdrawal or reduction from the cell cycle and cell proliferation. On the PCL membrane, keratinocytes developed an epidermal basal lamina, with high proliferating cells that stratified and migrated over time to form a complete differentiating epidermal multilayer system. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Epidermal stem cells: location, potential and contribution to cancer.

    Science.gov (United States)

    Ambler, C A; Määttä, A

    2009-01-01

    Epidermal stem cells have been classically characterized as slow-cycling, long-lived cells that reside in discrete niches in the skin. Gene expression studies of niche-resident cells have revealed a number of stem cell markers and regulators, including the Wnt/beta-catenin, Notch, p63, c-Myc and Hedgehog pathways. A new study challenges the traditional developmental paradigm of slow-cycling stem cells and rapid-cycling transit amplifying cells in some epidermal regions, and there is mounting evidence to suggest that multi-lineage epidermal progenitors can be isolated from highly proliferative, non-niche regions. Whether there is a unique microenvironment surrounding these progenitors remains to be determined. Interestingly, cancer stem cells derived from epidermal tumours exist independent of the classic skin stem cell niche, yet also have stem cell properties, including multi-lineage differentiation. This review summarizes recent studies identifying the location and regulators of mouse and human epidermal stem cells and highlights the strategies used to identify cancer stem cells, including expression of normal epidermal stem cell markers, expression of cancer stem cell markers identified in other epidermal tumours and characterization of side-population tumour cells.

  17. Transcription factor Amr1 induces melanin biosynthesis and suppresses virulence in Alternaria brassicicola.

    Directory of Open Access Journals (Sweden)

    Yangrae Cho

    Full Text Available Alternaria brassicicola is a successful saprophyte and necrotrophic plant pathogen. Several A. brassicicola genes have been characterized as affecting pathogenesis of Brassica species. To study regulatory mechanisms of pathogenesis, we mined 421 genes in silico encoding putative transcription factors in a machine-annotated, draft genome sequence of A. brassicicola. In this study, targeted gene disruption mutants for 117 of the transcription factor genes were produced and screened. Three of these genes were associated with pathogenesis. Disruption mutants of one gene (AbPacC were nonpathogenic and another gene (AbVf8 caused lesions less than half the diameter of wild-type lesions. Unexpectedly, mutants of the third gene, Amr1, caused lesions with a two-fold larger diameter than the wild type and complementation mutants. Amr1 is a homolog of Cmr1, a transcription factor that regulates melanin biosynthesis in several fungi. We created gene deletion mutants of Δamr1 and characterized their phenotypes. The Δamr1 mutants used pectin as a carbon source more efficiently than the wild type, were melanin-deficient, and more sensitive to UV light and glucanase digestion. The AMR1 protein was localized in the nuclei of hyphae and in highly melanized conidia during the late stage of plant pathogenesis. RNA-seq analysis revealed that three genes in the melanin biosynthesis pathway, along with the deleted Amr1 gene, were expressed at low levels in the mutants. In contrast, many hydrolytic enzyme-coding genes were expressed at higher levels in the mutants than in the wild type during pathogenesis. The results of this study suggested that a gene important for survival in nature negatively affected virulence, probably by a less efficient use of plant cell-wall materials. We speculate that the functions of the Amr1 gene are important to the success of A. brassicicola as a competitive saprophyte and plant parasite.

  18. Duration of reappearance of gingival melanin pigmentation after surgical removal - A clinical study

    Directory of Open Access Journals (Sweden)

    Kaur Harjit

    2010-01-01

    Full Text Available Background: In dentistry, esthetics has a special place. Although gingival melanin pigmentation does not present a medical problem, clinicians are often faced with a challenge of achieving gingival esthetics. Materials and Methods: A method of de-epithelialization of the pigmented gingiva using Kirkland′s gingivectomy knife is described. Twenty patients who were conscious about their gingival melanin pigmentation were selected. The gingiva of the whole of the arch was abraded until the entire visible pigmentation was removed. Clinical observations for intensity of pigmentation were recorded at baseline and then after surgery at monthly intervals over a period of 9 months according to Dummett-Gupta Oral Pigmentation Index scoring criteria proposed by Dummett C. O. in 1964. Results: The mean gingival melanin pigmentation score came down to 0.407 after 9 months as compared to preoperative score, which was 2.24. No repigmentation occurred in fair-complexioned persons. In persons with wheatish complexion, repigmentation was seen in 85.71% of the cases, but scores came down to 0.38 postoperatively as compared to 2.27 preoperatively. In dark complexioned persons, repigmentation occurred in all cases, but the mean scores were 0.93 as compared to 2.40 preoperatively. The difference between preoperative and postoperative mean scores for each segment was put to statistical analysis by applying paired t test and was found to be significant. Conclusion: As this method has shown statistically significant results, it can be used in patients who are conscious of pigmented gingiva and want an esthetically satisfactory color.

  19. Transcription Factor Amr1 Induces Melanin Biosynthesis and Suppresses Virulence in Alternaria brassicicola

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Yangrae; Srivastava, Akhil; Ohm, Robin A.; Lawrence, Christopher B.; Wang, Koon-Hui; Grigoriev, Igor V.; Marahatta, Sharadchandra P.

    2012-05-01

    Alternaria brassicicola is a successful saprophyte and necrotrophic plant pathogen. Several A. brassicicola genes have been characterized as affecting pathogenesis of Brassica species. To study regulatory mechanisms of pathogenesis, we mined 421 genes in silico encoding putative transcription factors in a machine-annotated, draft genome sequence of A. brassicicola. In this study, targeted gene disruption mutants for 117 of the transcription factor genes were produced and screened. Three of these genes were associated with pathogenesis. Disruption mutants of one gene (AbPacC) were nonpathogenic and another gene (AbVf8) caused lesions less than half the diameter of wild-type lesions. Unexpectedly, mutants of the third gene, Amr1, caused lesions with a two-fold larger diameter than the wild type and complementation mutants. Amr1 is a homolog of Cmr1, a transcription factor that regulates melanin biosynthesis in several fungi. We created gene deletion mutants of ?amr1 and characterized their phenotypes. The ?amr1 mutants used pectin as a carbon source more efficiently than the wild type, were melanin-deficient, and more sensitive to UV light and glucanase digestion. The AMR1 protein was localized in the nuclei of hyphae and in highly melanized conidia during the late stage of plant pathogenesis. RNA-seq analysis revealed that three genes in the melanin biosynthesis pathway, along with the deleted Amr1 gene, were expressed at low levels in the mutants. In contrast, many hydrolytic enzyme-coding genes were expressed at higher levels in the mutants than in the wild type during pathogenesis. The results of this study suggested that a gene important for survival in nature negatively affected virulence, probably by a less efficient use of plant cell-wall materials. We speculate that the functions of the Amr1 gene are important to the success of A. brassicicola as a competitive saprophyte and plant parasite.

  20. Monitoring the metabolic state of fungal hyphae and the presence of melanin by nonlinear spectral imaging.

    Science.gov (United States)

    Knaus, Helene; Blab, Gerhard A; Agronskaia, Alexandra V; van den Heuvel, Dave J; Gerritsen, Hans C; Wösten, Han A B

    2013-10-01

    Label-free nonlinear spectral imaging microscopy (NLSM) records two-photon-excited fluorescence emission spectra of endogenous fluorophores within the specimen. Here, NLSM is introduced as a novel, minimally invasive method to analyze the metabolic state of fungal hyphae by monitoring the autofluorescence of NAD(P)H and flavin adenine dinucleotide (FAD). Moreover, the presence of melanin was analyzed by NLSM. NAD(P)H, FAD, and melanin were used as biomarkers for freshness of mushrooms of Agaricus bisporus (white button mushroom) that had been stored at 4°C for 0 to 17 days. During this period, the mushrooms did not show changes in morphology or color detectable by eye. In contrast, FAD/NAD(P)H and melanin/NAD(P)H ratios increased over time. For instance, these ratios increased from 0.92 to 2.02 and from 0.76 to 1.53, respectively, at the surface of mushroom caps that had been harvested by cutting the stem. These ratios were lower under the skin than at the surface of fresh mushrooms (0.78 versus 0.92 and 0.41 versus 0.76, respectively), indicative of higher metabolism and lower pigment formation within the fruiting body. Signals were different not only between tissues of the mushroom but also between neighboring hyphae. These data show that NLSM can be used to determine the freshness of mushrooms and to monitor the postharvest browning process at an early stage. Moreover, these data demonstrate the potential of NLSM to address a broad range of fundamental and applied microbiological processes.

  1. A regulator of ubiquitin-proteasome activity, 2-hexyldecanol, suppresses melanin synthesis and the appearance of facial hyperpigmented spots.

    Science.gov (United States)

    Hakozaki, T; Laughlin, T; Zhao, S; Wang, J; Deng, D; Jewell-Motz, E; Elstun, L

    2013-07-01

    2-Hexyldecanol has long been used in skin-care products, but has not previously been reported as an active ingredient for skin benefits. To evaluate 2-hexyldecanol in in vitro and ex vivo systems and, if found to be active, progress it to topical clinical testing to determine effects on pigmentation in skin. 2-Hexyldecanol was tested in melanocyte cell culture systems (B16 mouse melanoma cells and normal human melanocytes) for its effect on proteolytic activity and melanin production, in the absence and presence of the proteasome-specific inhibitor, MG132. It was further tested in a human skin explant model for its effect on melanin production. Lastly, topically applied 2-hexyldecanol was evaluated for its effect on the appearance of facial pigmentation in an 8-week, randomized, double-blind, vehicle-controlled, split-face incomplete block design study in Chinese women. In submerged cell culture, 2-hexyldecanol upregulated proteolytic activity and decreased melanin synthesis. These effects were antagonized by the proteasome-specific inhibitor MG132. MG132, tested in the absence of 2-hexyldecanol, increased melanin production. In a human skin explant model, topical 2-hexyldecanol suppressed the production of melanin vs. a vehicle control. In a human clinical study in Chinese women (n = 110 observations per test material), a 2-hexyldecanol-containing formulation significantly reduced the appearance of facial hyperpigmented spots vs. its control. These data indicate that regulation of proteasome activity is a viable target for control of melanin production, that 2-hexyldecanol upregulates proteasomal activity in melanocytes, and that topical 2-hexyldecanol reduces the appearance of hyperpigmentation. © 2013 The Authors BJD © 2013 British Association of Dermatologists.

  2. Retinoic acid modulation of ultraviolet light-induced epidermal ornithine decarboxylase activity

    International Nuclear Information System (INIS)

    Lowe, N.J.; Breeding, J.

    1982-01-01

    Irradiation of skin with ultraviolet light of sunburn range (UVB) leads to a large and rapid induction of the polyamine biosynthetic enzyme ornithine decarboxylase in the epidermis. Induction of epidermal ornithine decarboxylase also occurs following application of the tumor promoting agent 12-0-tetradecanoylphorbol-13 acetate and topical retinoic acid is able to block both this ornithine decarboxylase induction and skin tumor promotion. In the studies described below, topical application of retinoic acid to hairless mouse skin leads to a significant inhibition of UVB-induced epidermal ornithine decarboxylase activity. The degree of this inhibition was dependent on the dose, timing, and frequency of the application of retinoic acid. To show significant inhibition of UVB-induced ornithine decarboxylase the retinoic acid had to be applied within 5 hr of UVB irradiation. If retinoic acid treatment was delayed beyond 7 hr following UVB, then no inhibition of UVB-induced ornithine decarboxylase was observed. The quantities of retinoic acid used (1.7 nmol and 3.4 nmol) have been shown effective at inhibiting 12-0-tetradecanoyl phorbol-13 acetate induced ornithine decarboxylase. The results show that these concentrations of topical retinoic acid applied either before or immediately following UVB irradiation reduces the UVB induction of epidermal ornithine decarboxylase. The effect of retinoic acid in these regimens on UVB-induced skin carcinogenesis is currently under study

  3. Fatal toxic epidermal necrolysis associated with minoxidil.

    Science.gov (United States)

    Karaoui, Lamis R; Chahine-Chakhtoura, Corinne

    2009-04-01

    Minoxidil is a direct-acting peripheral vasodilator for the treatment of symptomatic hypertension, or refractory hypertension associated with target organ damage, that is not manageable with a diuretic and two other antihypertensive drugs. The most frequent adverse events associated with minoxidil include hypertrichosis and cardiovascular events related to its powerful antihypertensive effect, and less frequently, rashes, bullous eruptions, and Stevens-Johnson syndrome (SJS). Evidence suggests that SJS and toxic epidermal necrolysis (TEN) are variants of a single disease with common causes and mechanisms, but differing severities. Epidermal detachment is mild in SJS, moderate in overlap SJS-TEN, and severe (> 30% of body surface area) in TEN. We describe a case of minoxidil-associated SJS that evolved into fatal TEN. A 69-year-old African-American woman with a history of chronic kidney disease was admitted to the hospital for a cerebrovascular accident and uncontrolled hypertension. On hospital day 12, oral minoxidil was added to her drug regimen. On day 23, she developed a maculopapular rash on her face that gradually diffused to her chest and back. Vesicles and papular lesions extended to her extremities and mucosal membranes; results of a skin biopsy revealed SJS. A positive Nikolsky's sign (blisters spread on application of pressure) was detected. On days 27-31, diffuse bullae developed with rash exacerbation. Skin detachment exceeded 30% and was consistent with TEN. The patient died on day 39. An evaluation of the causality and time course suggested that minoxidil was the most likely culpable drug, with a Naranjo adverse drug reaction probability scale score indicating that the likelihood of the association was possible (score of 3). The mechanism of this reaction has not been well elucidated. It may be related to an impaired clearance of the minoxidil metabolite, or an immune stimulation resulting in apoptosis and epidermis destruction. To our knowledge, this

  4. Simultaneous in vivo imaging of melanin and lipofuscin in the retina with photoacoustic ophthalmoscopy and autofluorescence imaging

    Science.gov (United States)

    Zhang, Xiangyang; Zhang, Hao F.; Puliafito, Carmen A.; Jiao, Shuliang

    2011-08-01

    We combined photoacoustic ophthalmoscopy (PAOM) with autofluorescence imaging for simultaneous in vivo imaging of dual molecular contrasts in the retina using a single light source. The dual molecular contrasts come from melanin and lipofuscin in the retinal pigment epithelium (RPE). Melanin and lipofuscin are two types of pigments and are believed to play opposite roles (protective versus exacerbate) in the RPE in the aging process. We have successfully imaged the retina of pigmented and albino rats at different ages. The experimental results showed that multimodal PAOM system can be a potentially powerful tool in the study of age-related degenerative retinal diseases.

  5. Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis ...

    African Journals Online (AJOL)

    REVIEW. Introduction. Stevens-Johnson syndrome (SJS) and toxic epidermal ... that affect the skin and mucous membranes. ... Open Access article distributed under the terms of the .... pathogenic components are removed from plasma. The.

  6. Epidermal and dermal integumentary structures of ankylosaurian dinosaurs.

    Science.gov (United States)

    Arbour, Victoria M; Burns, Michael E; Bell, Phil R; Currie, Philip J

    2014-01-01

    Ankylosaurian dinosaurs are most notable for their abundant and morphologically diverse osteoderms, which would have given them a spiky appearance in life. Isolated osteoderms are relatively common and provide important information about the structure of the ankylosaur dermis, but fossilized impressions of the soft-tissue epidermis of ankylosaurs are rare. Nevertheless, well-preserved integument exists on several ankylosaur fossils that shows osteoderms were covered by a single epidermal scale, but one or many millimeter-sized ossicles may be present under polygonal, basement epidermal scales. Evidence for the taxonomic utility of ankylosaurid epidermal scale architecture is presented for the first time. This study builds on previous osteological work that argues for a greater diversity of ankylosaurids in the Dinosaur Park Formation of Alberta than has been traditionally recognized and adds to the hypothesis that epidermal skin impressions are taxonomically relevant across diverse dinosaur clades. Copyright © 2013 Wiley Periodicals, Inc.

  7. "Cut-and-paste" manufacture of multiparametric epidermal electronic systems

    Science.gov (United States)

    Lu, Nanshu; Yang, Shixuan; Wang, Pulin

    2016-05-01

    Epidermal electronics is a class of noninvasive and unobstructive skin-mounted, tattoo-like sensors and electronics capable of vital sign monitoring and establishing human-machine interface. The high cost of manpower, materials, vacuum equipment, and photolithographic facilities associated with its manufacture greatly hinders the widespread use of disposable epidermal electronics. Here we report a cost and time effective, completely dry, benchtop "cut-and-paste" method for the freeform and portable manufacture of multiparametric epidermal sensor systems (ESS) within minutes. This versatile method works for all types of thin metal and polymeric sheets and is compatible with any tattoo adhesives or medical tapes. The resulting ESS are multimaterial and multifunctional and have been demonstrated to noninvasively but accurately measure electrophysiological signals, skin temperature, skin hydration, as well as respiratory rate. In addition, planar stretchable coils exploiting double-stranded serpentine design have been successfully applied as wireless, passive epidermal strain sensors.

  8. Epidermal Nevus Syndrome Associated with Brain Malformations and Medulloblastoma

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-01-01

    Full Text Available Researchers at Juntendo University and Tokyo Women’s Medical University, Japan; and University of California, San Francisco, Ca, report a male infant with epidermal nevus syndrome associated with brainstem and cerebellar malformations and neonatal medulloblastoma.

  9. Optimal allocation of leaf epidermal area for gas exchange

    OpenAIRE

    de Boer, Hugo J.; Price, Charles A.; Wagner-Cremer, Friederike; Dekker, Stefan C.; Franks, Peter J.; Veneklaas, Erik J.

    2016-01-01

    Summary A long?standing research focus in phytology has been to understand how plants allocate leaf epidermal space to stomata in order to achieve an economic balance between the plant's carbon needs and water use. Here, we present a quantitative theoretical framework to predict allometric relationships between morphological stomatal traits in relation to leaf gas exchange and the required allocation of epidermal area to stomata. Our theoretical framework was derived from first principles of ...

  10. [Quantity research on epidermal growth factor in saliva and epidermal growth factor receptor in biopsy samples of recurrent aphthous ulcer patients].

    Science.gov (United States)

    Gu, Yang; Zhang, Gang; Lin, Mei

    2008-02-01

    To examine the change of epidermal growth factor (EGF) concentration in saliva of recurrent aphthous ulcer (RAU) patients during the ulcerous and interval period and epidermal growth factor receptor (EGFR) in ulcer biopsy samples. ECF data of the samples, which were 27 saliva samples from RAU gained not only in the ulcerous period but also in interval period and 33 ones from normal persons, were acquired through enzyme linked immunosorhent assay (ELISA) and EGF standard curve. ECFR-RNA date of RAU biopsies, which were 31 biopsy samples from RAU got during the ulcerous period and 35 ones from normal persons, were surveyed by QF-RT-PCR. All RAU samples were obtained under the same level, which were the whole patients were minor aphthous ulcers and their ulcers occurred not over the first four days. All patients and normal persons were selected seriously under the rule of physical situations without any other diseases and histories of using medicines. The EGF concentration of saliva in RAU group at ulcer occurrence was higher than that in the interval period and the normal control with a significant test (F = 3.24, P ulcer occurrence was higher than the normal control with a significant test (t = 3.15, P ulcer occasion of RAU patients could be related with the decreasing of EGF in saliva during interval period, and that the ulcer sell-cure of RAU patients would be contributed to

  11. 4-(Phenylsulfanylbutan-2-One Suppresses Melanin Synthesis and Melanosome Maturation In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Shing-Yi Sean Wu

    2015-08-01

    Full Text Available In this study, we screened compounds with skin whitening properties and favorable safety profiles from a series of marine related natural products, which were isolated from Formosan soft coral Cladiella australis. Our results indicated that 4-(phenylsulfanylbutan-2-one could successfully inhibit pigment generation processes in mushroom tyrosinase platform assay, probably through the suppression of tyrosinase activity to be a non-competitive inhibitor of tyrosinase. In cell-based viability examinations, it demonstrated low cytotoxicity on melanoma cells and other normal human cells. It exhibited stronger inhibitions of melanin production and tyrosinase activity than arbutin or 1-phenyl-2-thiourea (PTU. Also, we discovered that 4-(phenylsulfanylbutan-2-one reduces the protein expressions of melanin synthesis-related proteins, including the microphthalmia-associated transcription factor (MITF, tyrosinase-related protein-1 (Trp-1, dopachrome tautomerase (DCT, Trp-2, and glycoprotein 100 (GP100. In an in vivo zebrafish model, it presented a remarkable suppression in melanogenesis after 48 h. In summary, our in vitro and in vivo biological assays showed that 4-(phenylsulfanylbutan-2-one possesses anti-melanogenic properties that are significant in medical cosmetology.

  12. Melanin photosensitization and the effect of visible light on epithelial cells.

    Directory of Open Access Journals (Sweden)

    Orlando Chiarelli-Neto

    Full Text Available Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2 generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm and visible (532 nm light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications; these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.

  13. Singlet molecular oxygen generation by light-activated DHN-melanin of the fungal pathogen Mycosphaerella fijiensis in black Sigatoka disease of bananas.

    Directory of Open Access Journals (Sweden)

    Miguel J Beltrán-García

    Full Text Available In pathogenic fungi, melanin contributes to virulence, allowing tissue invasion and inactivation of the plant defence system, but has never been implicated as a factor for host cell death, or as a light-activated phytotoxin. Our research shows that melanin synthesized by the fungal banana pathogen Mycosphaerella fijiensis acts as a virulence factor through the photogeneration of singlet molecular oxygen O2 (1Δg. Using analytical tools, including elemental analysis, ultraviolet/infrared absorption spectrophometry and MALDI-TOF mass spectrometry analysis, we characterized both pigment content in mycelia and secreted to the culture media as 1,8-dihydroxynaphthalene (DHN-melanin type compound. This is sole melanin-type in M. fijiensis. Isolated melanins irradiated with a Nd:YAG laser at 532 nm produced monomol light emission at 1270 nm, confirming generation of O2 (1Δg, a highly reactive oxygen specie (ROS that causes cellular death by reacting with all cellular macromolecules. Intermediary polyketides accumulated in culture media by using tricyclazole and pyroquilon (two inhibitors of DHN-melanin synthesis were identified by ESI-HPLC-MS/MS. Additionally, irradiation at 532 nm of that mixture of compounds and whole melanized mycelium also generated O2 (1Δg. A pigmented-strain generated more O2 (1Δg than a strain with low melanin content. Banana leaves of cultivar Cavendish, naturally infected with different stages of black Sigatoka disease, were collected from field. Direct staining of the naturally infected leaf tissues showed the presence of melanin that was positively correlated to the disease stage. We also found hydrogen peroxide (H2O2 but we cannot distinguish the source. Our results suggest that O2 (1Δg photogenerated by DHN-melanin may be involved in the destructive effects of Mycosphaerella fijiensis on banana leaf tissues. Further studies are needed to fully evaluate contributions of melanin-mediated ROS to microbial pathogenesis.

  14. Singlet molecular oxygen generation by light-activated DHN-melanin of the fungal pathogen Mycosphaerella fijiensis in black Sigatoka disease of bananas.

    Science.gov (United States)

    Beltrán-García, Miguel J; Prado, Fernanda M; Oliveira, Marilene S; Ortiz-Mendoza, David; Scalfo, Alexsandra C; Pessoa, Adalberto; Medeiros, Marisa H G; White, James F; Di Mascio, Paolo

    2014-01-01

    In pathogenic fungi, melanin contributes to virulence, allowing tissue invasion and inactivation of the plant defence system, but has never been implicated as a factor for host cell death, or as a light-activated phytotoxin. Our research shows that melanin synthesized by the fungal banana pathogen Mycosphaerella fijiensis acts as a virulence factor through the photogeneration of singlet molecular oxygen O2 (1Δg). Using analytical tools, including elemental analysis, ultraviolet/infrared absorption spectrophometry and MALDI-TOF mass spectrometry analysis, we characterized both pigment content in mycelia and secreted to the culture media as 1,8-dihydroxynaphthalene (DHN)-melanin type compound. This is sole melanin-type in M. fijiensis. Isolated melanins irradiated with a Nd:YAG laser at 532 nm produced monomol light emission at 1270 nm, confirming generation of O2 (1Δg), a highly reactive oxygen specie (ROS) that causes cellular death by reacting with all cellular macromolecules. Intermediary polyketides accumulated in culture media by using tricyclazole and pyroquilon (two inhibitors of DHN-melanin synthesis) were identified by ESI-HPLC-MS/MS. Additionally, irradiation at 532 nm of that mixture of compounds and whole melanized mycelium also generated O2 (1Δg). A pigmented-strain generated more O2 (1Δg) than a strain with low melanin content. Banana leaves of cultivar Cavendish, naturally infected with different stages of black Sigatoka disease, were collected from field. Direct staining of the naturally infected leaf tissues showed the presence of melanin that was positively correlated to the disease stage. We also found hydrogen peroxide (H2O2) but we cannot distinguish the source. Our results suggest that O2 (1Δg) photogenerated by DHN-melanin may be involved in the destructive effects of Mycosphaerella fijiensis on banana leaf tissues. Further studies are needed to fully evaluate contributions of melanin-mediated ROS to microbial pathogenesis.

  15. Tight junction regulates epidermal calcium ion gradient and differentiation

    International Nuclear Information System (INIS)

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-01-01

    Research highlights: → We disrupted epidermal tight junction barrier in reconstructed epidermis. → It altered Ca 2+ distribution and consequentially differentiation state as well. → Tight junction should affect epidermal homeostasis by maintaining Ca 2+ gradient. -- Abstract: It is well known that calcium ions (Ca 2+ ) induce keratinocyte differentiation. Ca 2+ distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca 2+ gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca 2+ gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca 2+ flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca 2+ gradient.

  16. Extracellular Matrix as a Regulator of Epidermal Stem Cell Fate.

    Science.gov (United States)

    Chermnykh, Elina; Kalabusheva, Ekaterina; Vorotelyak, Ekaterina

    2018-03-27

    Epidermal stem cells reside within the specific anatomic location, called niche, which is a microenvironment that interacts with stem cells to regulate their fate. Regulation of many important processes, including maintenance of stem cell quiescence, self-renewal, and homeostasis, as well as the regulation of division and differentiation, are common functions of the stem cell niche. As it was shown in multiple studies, extracellular matrix (ECM) contributes a lot to stem cell niches in various tissues, including that of skin. In epidermis, ECM is represented, primarily, by a highly specialized ECM structure, basement membrane (BM), which separates the epidermal and dermal compartments. Epidermal stem cells contact with BM, but when they lose the contact and migrate to the overlying layers, they undergo terminal differentiation. When considering all of these factors, ECM is of fundamental importance in regulating epidermal stem cells maintenance, proper mobilization, and differentiation. Here, we summarize the remarkable progress that has recently been made in the research of ECM role in regulating epidermal stem cell fate, paying special attention to the hair follicle stem cell niche. We show that the destruction of ECM components impairs epidermal stem cell morphogenesis and homeostasis. A deep understanding of ECM molecular structure as well as the development of in vitro system for stem cell maintaining by ECM proteins may bring us to developing new approaches for regenerative medicine.

  17. Pathophysiology and prevention of photoaging : the role of melanin, reactive oxygen species and infiltrating neutrophils

    NARCIS (Netherlands)

    Rijken, F.

    2011-01-01

    Photoaging of human skin involves epidermal and dermal changes. The hallmark of photoaged skin is an accumulation of elastotic material in the mid and upper dermis, so-called solar elastosis. This elastotic material is mostly derived from degraded elastic fibers and consists mainly of insoluble

  18. Epidermal growth factor and insulin-like growth factor I upregulate the expression of the epidermal growth factor system in rat liver

    DEFF Research Database (Denmark)

    Bor, M V; Sørensen, B S; Vinter-Jensen, L

    2000-01-01

    BACKGROUND/AIM: Both epidermal growth factor and insulin-like growth factor I play a role in connection with the liver. In the present study, the possible interaction of these two growth factor systems was studied by investigating the effect of epidermal growth factor or insulin-like growth factor...... I treatment on the expression of the epidermal growth factor receptor, and its activating ligands, transforming growth factor-alpha and epidermal growth factor. METHODS: Fifty-five male rats received no treatment, human recombinant epidermal growth factor or human recombinant insulin-like growth.......8+/-1.6 fmol/mg protein epidermal growth factor and 144+/-22 fmol/mg protein transforming growth factor-alpha. Both epidermal growth factor and insulin-like growth factor I treatment increased the expression of mRNA for transforming growth factor-alpha and epidermal growth factor receptor, as well...

  19. Epidermal Overexpression of Xenobiotic Receptor PXR Impairs the Epidermal Barrier and Triggers Th2 Immune Response.

    Science.gov (United States)

    Elentner, Andreas; Schmuth, Matthias; Yannoutsos, Nikolaos; Eichmann, Thomas O; Gruber, Robert; Radner, Franz P W; Hermann, Martin; Del Frari, Barbara; Dubrac, Sandrine

    2018-01-01

    The skin is in daily contact with environmental pollutants, but the long-term effects of such exposure remain underinvestigated. Many of these toxins bind and activate the pregnane X receptor (PXR), a ligand-activated transcription factor that regulates genes central to xenobiotic metabolism. The objective of this work was to investigate the effect of constitutive activation of PXR in the basal layer of the skin to mimic repeated skin exposure to noxious molecules. We designed a transgenic mouse model that overexpresses the human PXR gene linked to the herpes simplex VP16 domain under the control of the keratin 14 promoter. We show that transgenic mice display increased transepidermal water loss and elevated skin pH, abnormal stratum corneum lipids, focal epidermal hyperplasia, activated keratinocytes expressing more thymic stromal lymphopoietin, a T helper type 2/T helper type 17 skin immune response, and increased serum IgE. Furthermore, the cutaneous barrier dysfunction precedes development of the T helper type 2/T helper type 17 inflammation in transgenic mice, thereby mirroring the time course of atopic dermatitis development in humans. Moreover, further experiments suggest increased PXR signaling in the skin of patients with atopic dermatitis when compared with healthy skin. Thus, PXR activation by environmental pollutants may compromise epidermal barrier function and favor an immune response resembling atopic dermatitis. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Epidermal growth factor and growth in vivo

    International Nuclear Information System (INIS)

    Rhodes, J.A.

    1986-01-01

    Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of 3 H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of 3 H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated

  1. New SPECT tracers: Example of tracers of proteoglycans and melanin; Nouveaux traceurs TEMP: exemple des traceurs des proteoglycanes et de la melanine

    Energy Technology Data Exchange (ETDEWEB)

    Cachin, F.; Mestas, D.; Kelly, A.; Merlin, C.; Veyre, A.; Maublant, J. [CRLCC Jean-Perrin, Service de Medecine Nucleaire, 63 - Clermont-Ferrand (France); Cachin, F.; Chezal, J.M.; Miot-Noirault, E.; Moins, N.; Auzeloux, P.; Vidal, A.; Bonnet-Duquennoy, M.; Boisgard, S.; D' Incan, M.; Madelmont, J.C.; Maublant, J. [Universite d' Auvergne, EA 4231, 63 - Clermont-Ferrand (France); Boisgard, S. [CHRU Gabriel-Montpied, Service d' Orthopedie, 63 - Clermont-Ferrand (France); D' Incan, M. [CHRU Gabriel-Montpied, Service de Dermatologie, 63 - Clermont-Ferrand (France); Redini, F. [Inserm, U957-EA3822, Faculte de Medecine, 44 - Nantes (France); Filaire, M. [Universite d' Auvergne, Lab. d' Anatomie, 63 - Clermont-Ferrand (France)

    2009-02-15

    The majority of research program on new radiopharmaceuticals turn to tracers used for positron emission tomography (PET). Only a few teams work on new non fluorine labeled tracers. However, the coming of SPECT/CT gamma cameras, the arrival of semi-conductors gamma cameras should boost the development of non-PET tracers. We exhibit in this article the experience acquired by our laboratory in the conception and design of two new non fluorine labelled compounds. The {sup 99m}Tc-N.T.P. 15-5 (N.T.P. 15-5 for N-[tri-ethyl-ammonium]-3-propyl-[15]ane-N5) which binds to proteoglycans could be used for the diagnosis and staging of osteoarthritis and chondrosarcoma. The iodo benzamides, specific to the melanin, are nowadays compared to {sup 18}F-fluorodeoxyglucose in a phase III clinical trial for the diagnosis and detection of melanoma metastasis. Our last development focus on N-[2-(diethyl-amino)ethyl]-4 and 2-iodo benzamides respectively B.Z.A. and B.Z.A.2 hetero-aromatic analogues usable for melanoma treatment. (authors)

  2. Bioproduction and characterization of extracellular melanin-like pigment from industrially polluted metagenomic library equipped Escherichia coli.

    Science.gov (United States)

    Amin, Shivani; Rastogi, Rajesh P; Sonani, Ravi R; Ray, Arabinda; Sharma, Rakesh; Madamwar, Datta

    2018-04-15

    To explore the potential genes from the industrially polluted Amlakhadi canal, located in Ankleshwar, Gujarat, India, its community genome was extracted and cloned into E. coli EPI300™-T1 R using a fosmid vector (pCC2 FOS™) generating a library of 3,92,000 clones with average size of 40kb of DNA-insert. From this library, the clone DM1 producing brown colored melanin-like pigment was isolated and characterized. For over expression of the pigment, further sub-cloning of the clone DM1 was done. Sub-clone containing 10kb of the insert was sequenced for gene identification. The amino acids sequence of a protein 4-Hydroxyphenylpyruvate dioxygenase (HPPD), which is know to be involved in melanin biosynthesis was obtained from the gene sequence. The sequence-homology based 3D structure model of HPPD was constructed and analyzed. The physico-chemical nature of pigment was further analysed using 1 H and 13 C NMR, LC-MS, FTIR and UV-visible spectroscopy. The pigment was readily soluble in DMSO with an absorption maximum around 290nm. Based on the genetic and chemical characterization, the compound was confirmed as melanin-like pigment. The present results indicate that the metagenomic library from industrially polluted environment generated a microbial tool for the production of melanin-like pigment. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Clinical study on the removal of gingival melanin pigmentation: comparison between Nd:YAG laser ablation and mechanical abrasion

    International Nuclear Information System (INIS)

    Lopes, Luis Mario de Melo

    2002-01-01

    Melanin pigmentation occurs as a result of excessive deposition of melanin, produced by the melanocytes present in the basal layer of the epithelium. This study compares clinical parameters such as inflammation and/or hemorrhage, healing process and re-pigmentation, caused by the Nd:YAG laser ablation and the mechanical abrasion of the melanin, by means of photographic images, taken during the first 30 days after the treatment. The patients comfort was monitored during the first ten days after the treatment using the method of the Visual Analog Scale to measure the pain. Six patients with gingival melanin pigmentation were selected. The left upper gingival quadrant was treated with the Nd:YAG laser using 125 mJ per pulse and 20 Hz, the right upper gingival quadrant received mechanical abrasion and the lower quadrants served for control. Both techniques did not result in inflammation and/or hemorrhage. The healing process was slower with the laser. Using mechanical abrasion, ali patients showed remaining pigmentation or re-pigmentation of varying intensity after a period of 30 days. With the laser 50 % of the patients did not show any re-pigmentation after this period. The pain analysis showed that the pain sensed 24 hours after the treatment with the laser is higher than using mechanical abrasion. (author)

  4. Preparation of a Sepia Melanin and Poly(ethylene-alt-maleic Anhydride Hybrid Material as an Adsorbent for Water Purification

    Directory of Open Access Journals (Sweden)

    Guido Panzarasa

    2018-01-01

    Full Text Available Meeting the increasing demand of clean water requires the development of novel efficient adsorbent materials for the removal of organic pollutants. In this context the use of natural, renewable sources is of special relevance and sepia melanin, thanks to its ability to bind a variety of organic and inorganic species, has already attracted interest for water purification. Here we describe the synthesis of a material obtained by the combination of sepia melanin and poly(ethylene-alt-maleic anhydride (P(E-alt-MA. Compared to sepia melanin, the resulting hybrid displays a high and fast adsorption efficiency towards methylene blue (a common industrial dye for a wide pH range (from pH 2 to 12 and under high ionic strength conditions. It is easily recovered after use and can be reused up to three times. Given the wide availability of sepia melanin and P(E-alt-MA, the synthesis of our hybrid is simple and affordable, making it suitable for industrial water purification purposes.

  5. A Comparative Study of Melanin Content and Skin Morphology for Three Commonly Used Laboratory Swine (Sus scrofa domestica)

    Science.gov (United States)

    2012-09-01

    Air Force Research Laboratory 711th Human Performance Wing Human Effectiveness Directorate Bioeffects Division Optical Radiation Bioeffects...Branch AFRL-RH-FS-TR-2013-0004 A Comparative Study of Melanin Content and Skin Morphology for Three Commonly Used Laboratory Swine (Sus scrofa...Jindra Human Effectiveness Directorate Directed Energy Bioeffects Division Optical Radiation Branch Robert W. Kornegay Rick Figueroa Human

  6. Evaluation of Melanogenesis in A-375 Cells in the Presence of DMSO and Analysis of Pyrolytic Profile of Isolated Melanin

    Science.gov (United States)

    Chodurek, Ewa; Orchel, Arkadiusz; Orchel, Joanna; Kurkiewicz, Sławomir; Gawlik, Natalia; Dzierżewicz, Zofia; Stępień, Krystyna

    2012-01-01

    The increase of a skin malignant melanoma (melanoma malignum) incidence in the world has been observed in recent years. The tumour, especially in advanced stadium with metastases, is highly resistant to conventional treatment. One of the strategies is to modulate melanogenesis using chemical compounds. In this study, the processes of differentiation and melanogenesis induced by dimethylsulfoxide (DMSO) in human melanoma cells (A-375) were investigated. Natural melanin isolated from A-375 melanoma cell line treated with 0.3% DMSO was analyzed by pyrolysis-gas chromatography-mass spectrometry (Py-GC/MS) method. The products derived from pheomelanin have not been stated in the pyrolytic profile of analyzed melanin. Within all products derived from eumelanins, 1,2-benzenediol has been predominated. It has been shown that in the melanoma cells stimulated with 0.3% and 1% DMSO, the increase of transcriptional activity of the tyrosinase gene took place. It was accompanied by the rise of tyrosinase activity and an accumulation of melanin in the cells. The better knowledge about the structure of melanins can contribute to establish the uniform criteria of malignant melanoma morbidity risk. PMID:22654640

  7. Melanin and carotenoid ornaments are related to the individual condition in free-living grey partridges (Perdix perdix)

    Czech Academy of Sciences Publication Activity Database

    Svobodová, J.; Gabrielová, B.; Hyršl, P.; Albrecht, Tomáš; Vinkler, M.

    2016-01-01

    Roč. 157, č. 4 (2016), s. 1007-1015 ISSN 0021-8375 Institutional support: RVO:68081766 Keywords : complement * Condition-dependent sexual signalling * Carotenoid and melanin colouration * Game bird * Haematology * Phytohaemagglutinin Subject RIV: EG - Zoology Impact factor: 1.468, year: 2016

  8. Interpretation of Ocular Melanin Drug Binding Assays. Alternatives to the Model of Multiple Classes of Independent Sites.

    Science.gov (United States)

    Manzanares, José A; Rimpelä, Anna-Kaisa; Urtti, Arto

    2016-04-04

    Melanin has a high binding affinity for a wide range of drugs. The determination of the melanin binding capacity and its binding affinity are important, e.g., in the determination of the ocular drug distribution, the prediction of drug effects in the eye, and the trans-scleral drug delivery. The binding parameters estimated from a given data set vary significantly when using different isotherms or different nonlinear fitting methods. In this work, the commonly used bi-Langmuir isotherm, which assumes two classes of independent sites, is confronted with the Sips isotherm. Direct, log-log, and Scatchard plots are used, and the interpretation of the binding curves in the latter is critically analyzed. In addition to the goodness of fit, the emphasis is placed on the physical meaning of the binding parameters. The bi-Langmuir model imposes a bimodal distribution of binding energies for the sites on the melanin granules, but the actual distribution is most likely continuous and unimodal, as assumed by the Sips isotherm. Hence, the latter describes more accurately the distribution of binding energies and also the experimental results of melanin binding to drugs and metal ions. Simulations are used to show that the existence of two classes of sites cannot be confirmed on the sole basis of the shape of the binding curve in the Scatchard plot, and that serious doubts may appear on the meaning of the binding parameters of the bi-Langmuir model. Experimental results of melanin binding to chloroquine and metoprolol are used to illustrate the importance of the choice of the binding isotherm and of the method used to evaluate the binding parameters.

  9. Bioinspired Multifunctional Melanin-Based Nanoliposome for Photoacoustic/Magnetic Resonance Imaging-Guided Efficient Photothermal Ablation of Cancer

    Science.gov (United States)

    Zhang, Liang; Sheng, Danli; Wang, Dong; Yao, Yuanzhi; Yang, Ke; Wang, Zhigang; Deng, Liming; Chen, Yu

    2018-01-01

    Background: The construction of theranostic nanosystems with concurrently high biosafety and therapeutic performance is a challenge but has great significance for the clinical translation of nanomedicine for combating cancer. Methods: Bio-inspired melanin-based nanoliposomes (Lip-Mel) as theranostic agents were constructed for simultaneous photoacoustic (PA) imaging- and T1-weighted magnetic resonance (MR) imaging-guided photothermal ablation of tumors, which was demonstrated both in vitro and in vivo. The high biosafety of Lip-Mel was also systematically evaluated. Results: The achieved Lip-Mel nanoliposomes demonstrated their imaging capability for both PA and T1-weighted MR imaging (r1 = 0.25 mM-1·s-1) both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Importantly, the desirable photothermal-conversion efficiency of the as-prepared Lip-Mel achieved complete eradication of tumors in breast cancer-bearing mice, exhibiting remarkable photothermal-based therapeutic performance. In particular, the efficient encapsulation of melanin into the PEGylated liposome mitigated the potential toxicity of melanin and improved the photothermal performance of the loaded melanin. Systematic in vivo biosafety evaluations demonstrated the high biocompatibility of Lip-Mel at a high dose of 100 mg/kg. Conclusion: In this work, we reported a bioinspired strategy where melanin, a natural product in the human body, is encapsulated into PEGylated nanoliposomes for efficient theranostics with high biocompatibility. This work provides a new strategy for creating desirable theranostic agents with concurrent high biocompatibility and satisfactory theranostic performance through the use of materials that totally originate from biosystems. PMID:29556343

  10. Oral mucosa: an alternative epidermic cell source to develop autologous dermal-epidermal substitutes from diabetic subjects

    Directory of Open Access Journals (Sweden)

    Daniela GUZMÁN-URIBE

    Full Text Available Abstract Oral mucosa has been highlighted as a suitable source of epidermal cells due to its intrinsic characteristics such as its higher proliferation rate and its obtainability. Diabetic ulcers have a worldwide prevalence that is variable (1%-11%, meanwhile treatment of this has been proven ineffective. Tissue-engineered skin plays an important role in wound care focusing on strategies such autologous dermal-epidermal substitutes. Objective The aim of this study was to obtain autologous dermal-epidermal skin substitutes from oral mucosa from diabetic subjects as a first step towards a possible clinical application for cases of diabetic foot. Material and Methods Oral mucosa was obtained from diabetic and healthy subjects (n=20 per group. Epidermal cells were isolated and cultured using autologous fibrin to develop dermal-epidermal in vitro substitutes by the air-liquid technique with autologous human serum as a supplement media. Substitutes were immunocharacterized with collagen IV and cytokeratin 5-14 as specific markers. A Student´s t- test was performed to assess the differences between both groups. Results It was possible to isolate epidermal cells from the oral mucosa of diabetic and healthy subjects and develop autologous dermal-epidermal skin substitutes using autologous serum as a supplement. Differences in the expression of specific markers were observed and the cytokeratin 5-14 expression was lower in the diabetic substitutes, and the collagen IV expression was higher in the diabetic substitutes when compared with the healthy group, showing a significant difference. Conclusion Cells from oral mucosa could be an alternative and less invasive source for skin substitutes and wound healing. A difference in collagen production of diabetic cells suggests diabetic substitutes could improve diabetic wound healing. More research is needed to determine the crosstalk between components of these skin substitutes and damaged tissues.

  11. Immune sensitization against epidermal antigens in polymorphous light eruption

    International Nuclear Information System (INIS)

    Gonzalez-Amaro, R.; Baranda, L.; Salazar-Gonzalez, J.F.; Abud-Mendoza, C.; Moncada, B.

    1991-01-01

    To get further insight into the pathogenesis of polymorphous light eruption, we studied nine patients with polymorphous light eruption and six healthy persons. Two skin biopsy specimens were obtained from each person, one from previously ultraviolet light-irradiated skin and another one from unirradiated skin. An epidermal cell suspension, skin homogenate, or both were prepared from each specimen. Autologous cultures were made with peripheral blood mononuclear cells combined with irradiated or unirradiated skin homogenate and peripheral blood mononuclear cells combined with irradiated or unirradiated epidermal cell suspension. Cell proliferation was assessed by 3H-thymidine incorporation assay. The response of peripheral blood mononuclear cells to unirradiated epidermal cells or unirradiated skin homogenate was similar in both patients and controls. However, peripheral blood mononuclear cells from patients with polymorphous light eruption showed a significantly increased proliferative response to both irradiated epidermal cells and irradiated skin homogenate. Our results indicate that ultraviolet light increases the stimulatory capability of polymorphous light eruption epidermal cells in a unidirectional mixed culture with autologous peripheral blood mononuclear cells. This suggests that an immune sensitization against autologous ultraviolet light-modified skin antigens occurs in polymorphous light eruption

  12. Adhesive coatings based on melanin-like nanoparticles for surgical membranes.

    Science.gov (United States)

    Scognamiglio, Francesca; Travan, Andrea; Turco, Gianluca; Borgogna, Massimiliano; Marsich, Eleonora; Pasqua, Mattia; Paoletti, Sergio; Donati, Ivan

    2017-07-01

    Adhesive coatings for implantable biomaterials can be designed to prevent material displacement from the site of implant. In this paper, a strategy based on the use of melanin-like nanoparticles (MNPs) for the development of adhesive coatings for polysaccharidic membranes was devised. MNPs were synthesized in vitro and characterized in terms of dimensions and surface potential, as a function of pH and ionic strength. The in vitro biocompatibility of MNPs was investigated on fibroblast cells, while the antimicrobial properties of MNPs in suspension were evaluated on E. coli and S. aureus cultures. The manufacturing of the adhesive coatings was carried out by spreading MNPs over the surface of polysaccharidic membranes; the adhesive properties of the nano-engineered coating to the target tissue (intestinal serosa) were studied in simulated physiological conditions. Overall, this study opens for novel approaches in the design of naturally inspired nanostructured adhesive systems. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Genomic regions associated with the sex-linked inhibitor of dermal melanin in Silkie chicken

    Directory of Open Access Journals (Sweden)

    Ming TIAN,Rui HAO,Suyun FANG,Yanqiang WANG,Xiaorong GU,Chungang FENG,Xiaoxiang HU,Ning LI

    2014-09-01

    Full Text Available A unique characteristic of the Silkie chicken is its fibromelanosis phenotype. The dermal layer of its skin, its connective tissue and shank dermis are hyperpigmented. This dermal hyperpigmentation phenotype is controlled by the sex-linked inhibitor of dermal melanin gene (ID and the dominant fibromelanosis allele. This study attempted to confirm the genomic region associated with ID. By genotyping, ID was found to be closely linked to the region between GGA_rs16127903 and GGA_rs14685542 (8406919 bp on chromosome Z, which contains ten functional genes. The expression of these genes was characterized in the embryo and 4 days after hatching and it was concluded that MTAP, encoding methylthioadenosinephosphorylase, would be the most likely candidate gene. Finally, target DNA capture and sequence analysis was performed, but no specific SNP(s was found in the targeted region of the Silkie genome. Further work is necessary to identify the causal ID mutation located on chromosome Z.

  14. Novel Inhibitory Effect of N-(2-Hydroxycyclohexylvaliolamine on Melanin Production in a Human Skin Model

    Directory of Open Access Journals (Sweden)

    Bum-Ho Bin

    2014-07-01

    Full Text Available Hyper-pigmentation causes skin darkness and medical disorders, such as post-inflammatory melanoderma and melasma. Therefore, the development of anti-melanogenic agents is important for treating these conditions and for cosmetic production. In our previous paper, we demonstrated that the anti-diabetic drug voglibose, a valiolamine derivative, is a potent anti-melanogenic agent. In addition, we proposed an alternative screening strategy to identify valiolamine derivatives with high skin permeability that act as anti-melanogenic agents when applied topically. In this study, we synthesized several valiolamine derivatives with enhanced lipophilicity and examined their inhibitory effects in a human skin model. N-(2-hydroxycyclohexylvaliolamine (HV possesses a stronger inhibitory effect on melanin production than voglibose in a human skin model, suggesting that HV is a more potent anti-melanogenic agent for the skin.

  15. Organelle-specific injury to melanin-containing cells in human skin by pulsed laser irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, G.F.; Shepard, R.S.; Paul, B.S.; Menkes, A.; Anderson, R.R.; Parrish, J.A.

    1983-12-01

    Physical models predict that ultraviolet laser radiation of appropriately brief pulses can selectively alter melanin-containing cellular targets in human skin. Skin of normal human volunteers was exposed to brief (20 nanosecond) 351-nm wave length pulses from a XeF excimer laser, predicting that those cells containing the greatest quantities of melanized melanosomes (lower half of the epidermis) would be selectively damaged. Transmission electron microscopy revealed the earliest cellular alteration to be immediate disruption of melanosomes, both within melanocytes and basal keratinocytes. This disruption was dose dependent and culminated in striking degenerative changes in these cells. Superficial keratinocytes and Langerhans cells were not affected. It was concluded that the XeF excimer laser is capable of organelle-specific injury to melanosomes. These findings may have important clinical implications in the treatment of both benign and malignant pigmented lesions by laser radiations of defined wave lengths and pulse durations.

  16. Radiotherapy and receptor of epidermal growth factor

    International Nuclear Information System (INIS)

    Deberne, M.

    2009-01-01

    The expression level of the receptor of the epidermal growth factor is in correlation with the tumor cells radiosensitivity. An overexpression of the E.G.F.R. is often present in the bronchi cancer, epidermoid carcinomas of the O.R.L. sphere, esophagus, uterine cervix, and anal duct but also in the rectum cancers and glioblastomas. At the clinical level, the E.G.F.R. expression is in correlation with an unfavourable prognosis after radiotherapy in numerous tumoral localizations. In the rectum cancers it is an independent prognosis factor found in multifactorial analysis: increase of the rate of nodes and local recurrence when the E.G.F.R. is over expressed. In the uterine cervix cancers, the survival is is negatively affected in multifactorial analysis by the E.G.F.R. membranes expression level. At the therapy level, the development of anti E.G.F.R. targeted therapies (tyrosine kinase inhibitors and monoclonal antibodies) opens a new therapy field at radio-sensitivity potentiality. The irradiation makes an activation of the E.G.F.R. way that would be partially responsible of the post irradiation tumoral repopulation. This activation leads the phosphorylation of the PI3 kinase ways and M.A.P. kinase ones, then the Akt protein one that acts an apoptotic modulator part. It has been shown that blocking the E.G.F.R. way acts on three levels: accumulation of ells in phase G1, reduction of the cell repair and increasing of apoptosis. he inhibition of post irradiation action of the E.G.F.R. signal way is a factor explaining the ionizing radiation - anti E.G.F.R. synergy. The preclinical data suggest that the E.G.F.R. blocking by the monoclonal antibodies is more important than the use of tyrosine kinase inhibitors. A first positive randomized study with the cetuximab, published in 2006 in the epidermoid carcinomas of the O.R.L. sphere lead to its authorization on the market with the radiotherapy for this localization. The use of cetuximab in other indication with or in

  17. Digital dermoscopy to determine skin melanin index as an objective indicator of skin pigmentation

    Directory of Open Access Journals (Sweden)

    Sara Majewski

    2016-04-01

    Full Text Available Clinical assessment of skin photosensitivity is subjectively determined by erythema and tanning responses to sunlight recalled by the subject, alternatively known as Fitzpatrick Skin Phototype (SPT. Responses may be unreliable due to recall bias, subjective bias by clinicians and subjects, and lack of cultural sensitivity of the questions. Analysis of red-green-blue (RGB color spacing of digital images may provide an objective determination of SPT. This paper presents the studies to assess the melanin index (MI, as determined by RGB images obtained by both standard digital camera as well as by videodermoscope, and to correlate the MI with SPT based upon subjects’ verbal responses to standardized questions administered by a dermatologist.A sample of subjects representing all SPTs I–VI was selected. Both the digital camera and videodermoscope were calibrated at standard illumination, light source and white balance. Images of constitutive skin of the upper ventral arm were taken of each subject using both instruments.The studies showed that 58 subjects (20 M, 38 F were enrolled in the study (mean age: 47 years; range: 20–89, stratified to skin phototype I–VI. MI obtained by using both digital camera and videodermoscope increased significantly as the SPT increased p = 0.004 and p < 0.0001, respectively and positively correlated with dermatologist-assessed SPT (Spearman correlation, r = 0.48 and r = 0.84, respectively.Digital imaging can quantify melanin content in order to quantitatively approximate skin pigmentation in all skin phototypes including Type VI skin. This methodology holds promise as a simple, non-invasive, rapid and objective approach to reliably determine skin phototype and, with further investigation, may prove to be both practical and useful in the prediction of skin cancer risk.

  18. Coloration principles of nymphaline butterflies - thin films, melanin, ommochromes and wing scale stacking.

    Science.gov (United States)

    Stavenga, Doekele G; Leertouwer, Hein L; Wilts, Bodo D

    2014-06-15

    The coloration of the common butterflies Aglais urticae (small tortoiseshell), Aglais io (peacock) and Vanessa atalanta (red admiral), belonging to the butterfly subfamily Nymphalinae, is due to the species-specific patterning of differently coloured scales on their wings. We investigated the scales' structural and pigmentary properties by applying scanning electron microscopy, (micro)spectrophotometry and imaging scatterometry. The anatomy of the wing scales appears to be basically identical, with an approximately flat lower lamina connected by trabeculae to a highly structured upper lamina, which consists of an array of longitudinal, parallel ridges and transversal crossribs. Isolated scales observed at the abwing (upper) side are blue, yellow, orange, red, brown or black, depending on their pigmentation. The yellow, orange and red scales contain various amounts of 3-OH-kynurenine and ommochrome pigment, black scales contain a high density of melanin, and blue scales have a minor amount of melanin pigment. Observing the scales from their adwing (lower) side always revealed a structural colour, which is blue in the case of blue, red and black scales, but orange for orange scales. The structural colours are created by the lower lamina, which acts as an optical thin film. Its reflectance spectrum, crucially determined by the lamina thickness, appears to be well tuned to the scales' pigmentary spectrum. The colours observed locally on the wing are also due to the degree of scale stacking. Thin films, tuned pigments and combinations of stacked scales together determine the wing coloration of nymphaline butterflies. © 2014. Published by The Company of Biologists Ltd.

  19. Inhibition of epidermal cell proliferation by borderline rays

    Energy Technology Data Exchange (ETDEWEB)

    Born, W [Freiburg Univ.; Daikeler, G

    1976-08-01

    Treatment of guinea pig flanks with very soft x-rays (borderline rays) directly caused a partial block of epidermal DNA synthesis which had been determined by measuring the /sup 3/H-Tdr incorporation. Higher doses and repeated applications would undoubtedly cause lasting damage to the tissue. The enhanced epidermal DNA synthesis which is sometimes observed should not be misinterpreted as a sign of a directly biopositive utilisation of the quantum energy supplied. Rather, it is a secondary repair process following initial phases of depression. A reparative increase in DNA synthesis may also occur as a primary process if the radiation is almost completely absorbed above the germinative layer.

  20. Epidermal growth factor in mammary glands and milk from rats

    DEFF Research Database (Denmark)

    Thulesen, J; Raaberg, Lasse; Nexø, Ebba

    1993-01-01

    Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF-immunoreact......Epidermal growth factor (EGF) is one of the major growth-promoting agents in milk. Using immunohistochemistry we localized EGF in the mammary glands of lactating rats to the luminal border of the secretory cells. Following proteolytic pretreatment of the histological sections, the EGF...

  1. Low calcium culture condition induces mesenchymal cell-like phenotype in normal human epidermal keratinocytes

    International Nuclear Information System (INIS)

    Takagi, Ryo; Yamato, Masayuki; Murakami, Daisuke; Sugiyama, Hiroaki; Okano, Teruo

    2011-01-01

    Highlights: → Normal human epidermal keratinocytes serially cultured under low calcium concentration were cytokeratin and vimentin double positive cells. → The human keratinocytes expressed some epithelial stem/progenitor cell makers, mesenchymal cell markers, and markers of epithelial-mesenchymal transition. → Mesenchymal cell-like phenotype in the keratinocytes was suppressed under high-calcium condition. -- Abstract: Epithelial-mesenchymal transition (EMT) is an important cellular phenomenon in organ developments, cancer invasions, and wound healing, and many types of transformed cell lines are used for investigating for molecular mechanisms of EMT. However, there are few reports for EMT in normal human epithelial cells, which are non-transformed or non-immortalized cells, in vitro. Therefore, normal human epidermal keratinocytes (NHEK) serially cultured in low-calcium concentration medium (LCM) were used for investigating relations between differentiation and proliferation and mesenchymal-like phenotype in the present study, since long-term cultivation of NHEK is achieved in LCM. Interestingly, NHEK serially cultured in LCM consisted essentially of cytokeratin-vimentin double positive cells (98%), although the NHEK exhibited differentiation under high-calcium culture condition with 3T3 feeder layer. The vimentin expression was suppressed under high-calcium condition. These results may indicate the importance of mesenchymal-like phenotype for serially cultivation of NHEK in vitro.

  2. Epidermal hydrogen peroxide is not increased in lesional and non-lesional skin of vitiligo.

    Science.gov (United States)

    Zailaie, Mohammad Z

    2017-01-01

    It is widely believed that the loss of the epidermal melanocytes in vitiligo is basically due to excessive oxidative stress. Previous research work described abnormal elevation of the absolute concentration of the epidermal hydrogen peroxide (H 2 O 2 ) in lesional and non-lesional skin of vitiligo. Based on this finding, our primary research objective was to use this feature as a screening marker in individuals at a great risk of developing vitiligo. Ninety-six patients of non-segmental vitiligo (NSV) of varying durations, skin phototypes, and treatment modalities (psoralen UVA-, narrow band UVB-treated) were recruited for this study. Raman spectroscopic measurements, using an external probehead, of the lesional and non-lesional skin were obtained, and the resulting spectra were analyzed using the Opus software package of the MultiRam spectrometer and the intensity of the peak at 875 cm -1 that represents the absolute concentration of H 2 O 2 was calculated. Contrary to previous reports, in patients of skin phototype IV, the absolute concentrations of H 2 O 2 in non-lesional and lesional NSV of all groups were non-significantly decreased compared to normal control. In patients of NSV of skin phototype V, the decrease in the absolute concentrations of H 2 O 2 was not significant in the untreated group, and a slight non-significant increase in the NBUVB-treated group was noted. However, in the PUVA-treated group, the non-lesional skin demonstrated significant increase in the absolute concentration of H 2 O 2 , whereas the lesional skin showed only a slight non-significant increase compared to normal control. In NSV patients of skin phototype VI who were previously treated with PUVA, the non-lesional skin showed a slight non-significant increase in the absolute concentration of H 2 O 2 ; however, the lesional skin showed a marked significant decrease compared to normal control and the non-lesional skin. Thereof, one can conclude that the epidermal H 2 O 2 is not

  3. Constitutive melanin density is associated with higher 25-hydroxyvitamin D and potentially total body BMD in older Caucasian adults via increased sun tolerance and exposure.

    Science.gov (United States)

    Thompson, M J W; Jones, G; Aitken, D A

    2018-06-01

    Greater skin pigmentation reduces dose equivalent cutaneous vitamin D3 production, potentially impacting lifetime vitamin D status and fracture risk. We show that melanin density was positively associated with 25-hydroxyvitamin D and total body bone mineral density. These relationships were partially explained by greater sun exposure due to more permissive skin phenotype. Higher cutaneous melanin reduces vitamin D3 production. This may impact lifetime vitamin D status and increase fracture risk. This study aimed to describe the relationship between spectrophotometrically determined constitutive melanin density, osteoporotic risk factors and potential intermediaries in a cohort of exclusively older Caucasian adults. One thousand seventy-two community-dwelling adults aged 50-80 years had constitutive melanin density quantified using spectrophotometry. Sun exposure, skin phenotype, non-melanoma skin cancer (NMSC) prevalence and smoking status were assessed by questionnaire. Bone mineral density (BMD), falls risk, physical activity and 25-hydroxyvitamin D were measured using DXA, the short form Physiological Profile Assessment, pedometer and radioimmunoassay, respectively. Higher melanin density was independently associated with greater ability to tan (RR = 1.27, p density and sun exposure (RR = 1.05-1.11, p density (β = 1.71-2.05, p = 0.001). The association between melanin density and total body BMD (β = 0.007, p = 0.04) became non-significant after adjustment for 25-hydroxyvitamin D. There was no association between melanin density and physical activity, falls risk or BMD at other sites. Our data support a model of higher constitutive melanin density underpinning a less photosensitive skin phenotype, permitting greater sun exposure with fewer sequelae and yielding higher 25-hydroxyvitamin D and, potentially, total body BMD.

  4. Micromorphology and development of the epicuticular structure on the epidermal cell of ginseng leaves

    Directory of Open Access Journals (Sweden)

    Kyounghwan Lee

    2015-04-01

    Conclusion: The outwardly projected cuticle and epidermal cell wall (i.e., an epicuticular wrinkle acts as a major barrier to block out sunlight in ginseng leaves. The small vesicles in the peripheral region of epidermal cells may suppress the cuticle and parts of epidermal wall, push it upward, and consequently contribute to the formation of the epicuticular structure.

  5. Retrospective Study of Epidermal Parasitic Skin Diseases amongst ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: A ten year retrospective study (1997-2006) was undertaken to determine the prevalence of. Epidermal Parasitic Skin Diseases (EPSD) among out-patients from the skin diseases hospital in Maiduguri, Borno state. Out of 10,000 out-patients examined during the study period, 3527(35.27%) where infected with ...

  6. An immunologic approach to induction of epidermal growth factor deficiency

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier

    1995-01-01

    Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency....

  7. Clinical Studies on conformal radiotherapy combined with epidermal ...

    African Journals Online (AJOL)

    Purpose: To study the effect of conformal radiotherapy combined with epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in the second-line treatment of non-small cell lung cancer (NSCLC). Methods: A total of 316 patients attending Shanghai Pulmonary Hospital affiliated to Tongji University, were divided ...

  8. Assessment of the Developmental Toxicity of Epidermal Growth ...

    African Journals Online (AJOL)

    Purpose: To determine whether epidermal growth factor (EGF) is involved in reproductive developmental toxicity, using the embryonic stem cell test (EST), as well as ascertain how EGF influences embryonic development. Methods: To predict developmental toxicity on the basis of reducing cell viability and inhibition of ...

  9. Pattern of hormone receptors and human epidermal growth factor ...

    African Journals Online (AJOL)

    Introduction: Breast cancer is the most common cancer among women globally. With immunohistochemistry (IHC), breast cancer is classified into four groups based on IHC profile of estrogen receptor (ER)/progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2/neu) expression, positive (+) and/or ...

  10. Adding a Piece to the Leaf Epidermal Cell Shape Puzzle.

    Science.gov (United States)

    von Wangenheim, Daniel; Wells, Darren M; Bennett, Malcolm J

    2017-11-06

    The jigsaw puzzle-shaped pavement cells in the leaf epidermis collectively function as a load-bearing tissue that controls organ growth. In this issue of Developmental Cell, Majda et al. (2017) shed light on how the jigsaw shape can arise from localized variations in wall stiffness between adjacent epidermal cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Gastric luminal epidermal growth factor is affected by diet | Iputo ...

    African Journals Online (AJOL)

    Objective. Diet is an area of major interest to those investigating the causes of cancer of the oesophagus in the Transkei. This study looked at the associations between intragastric epidermal growth factor level, diet and intragastric pH. Setting and subjects. A dietary survey was co-ordinated with studies of gastric luminal ...

  12. Epidermal hydration levels in rosacea patients improve after minocycline therapy.

    LENUS (Irish Health Repository)

    Ní Raghallaigh, S

    2013-12-06

    Patients with rosacea frequently report increased skin sensitivity, with features suggestive of an abnormal stratum corneum (SC) permeability barrier. Sebum, pH and hydration levels influence epidermal homeostasis. The correlation of the change in these parameters with clinically effective treatment has not been previously analysed.

  13. Inflammatory linear verrucous epidermal naevus: Report of three ...

    African Journals Online (AJOL)

    Background: Epidermal naevi are congenital harmatomas that arise from embryonal ectodermal cells. The inflammatory linear verrucous variant is rare and presents with disturbing symptoms. In blacks the classical erythema is not common but pruritus and discharge are the commonest features. Methods and results: We ...

  14. Identification of grazed grasses using epidermal characters | R ...

    African Journals Online (AJOL)

    The use of anatomical features of the abaxial epidermis of grasses is discussed for the identification of fragments of epidermis present in samples of rumen. The reliability of this technique, and the variation of the epidermal characters in two widely distributed species of grass, is given. A "Key" to identity certain genera of ...

  15. Improvement of arbutin trans-epidermal delivery using ...

    African Journals Online (AJOL)

    Purpose: To assess the ability of radiofrequency (RF) microporation to promote trans-epidermal delivery of arbutin. Methods: To investigate the enhancing effect of RF microchannels on skin permeation of arbutin, in vitro skin permeability studies were performed with RF microporation-treated Hartley albino guinea pig skin ...

  16. Dynamic changes in nicotinamide pyridine dinucleotide content in normal human epidermal keratinocytes and their effect on retinoic acid biosynthesis

    International Nuclear Information System (INIS)

    Pinkas-Sarafova, Adriana; Markova, N.G.; Simon, M.

    2005-01-01

    The function of many enzymes that regulate metabolism and transcription depends critically on the nicotinamide pyridine dinucleotides. To understand the role of NAD(P)(H) in physiology and pathophysiology, it is imperative to estimate both their amount and ratios in a given cell type. In human epidermis and in cultured epidermal keratinocytes, we found that the total dinucleotide content is in the low millimolar range. The dinucleotide pattern changes during proliferation and maturation of keratinocytes in culture. Differences in the concentrations of NAD(P)(H) of 1.5- to 12-fold were observed. This resulted in alteration of the NAD(P)H/NAD(P) ratio, which could impact the differential regulation of both transcriptional and metabolic processes. In support of this notion, we provide evidence that the two-step oxidation of retinol to retinoic acid, a nuclear hormone critical for epidermal homeostasis, can be regulated by the relative physiological amounts of the pyridine dinucleotides

  17. Photobiological implications of melanin photoprotection after UVB-induced tanning of human skin but not UVA-induced tanning.

    Science.gov (United States)

    Coelho, Sergio G; Yin, Lanlan; Smuda, Christoph; Mahns, Andre; Kolbe, Ludger; Hearing, Vincent J

    2015-03-01

    Repetitive suberythemal UVA and/or UVB exposures were used to generate comparable UV-induced tans in human skin over the course of 2 weeks. To evaluate the potential photoprotective values of those UVA- and/or UVB- induced tans and to avoid the confounding issue of residual UV-induced DNA damage, we waited 1 week before challenging those areas with a 1.5 MED of UVA+UVB after which we measure DNA damage. The results show that the type of UV used to induce skin pigmentation affects the redistribution of melanin in the skin and/or de novo melanin synthesis. The UVA-induced tans failed to even provide a minimal SPF of 1.5, which suggests that producing a tan with UVA-rich sunlamps prior to a holiday or vacation is completely counterproductive. Published 2014. This article is a US Government work and is in the public domain in the USA.

  18. Tomographic reconstruction of melanin structures of optical coherence tomography via the finite-difference time-domain simulation

    Science.gov (United States)

    Huang, Shi-Hao; Wang, Shiang-Jiu; Tseng, Snow H.

    2015-03-01

    Optical coherence tomography (OCT) provides high resolution, cross-sectional image of internal microstructure of biological tissue. We use the Finite-Difference Time-Domain method (FDTD) to analyze the data acquired by OCT, which can help us reconstruct the refractive index of the biological tissue. We calculate the refractive index tomography and try to match the simulation with the data acquired by OCT. Specifically, we try to reconstruct the structure of melanin, which has complex refractive indices and is the key component of human pigment system. The results indicate that better reconstruction can be achieved for homogenous sample, whereas the reconstruction is degraded for samples with fine structure or with complex interface. Simulation reconstruction shows structures of the Melanin that may be useful for biomedical optics applications.

  19. Poly(ethylene oxide) layers grafted to dopamine-melanin anchoring layer: stability and resistance to protein adsorption

    Czech Academy of Sciences Publication Activity Database

    Pop-Georgievski, Ognen; Popelka, Štěpán; Houska, Milan; Chvostová, Dagmar; Proks, Vladimír; Rypáček, František

    2011-01-01

    Roč. 12, č. 9 (2011), s. 3232-3242 ISSN 1525-7797 R&D Projects: GA AV ČR KJB400500904; GA ČR GAP108/11/1857; GA ČR GPP207/10/P569 Institutional research plan: CEZ:AV0Z40500505; CEZ:AV0Z10100522 Keywords : dopamine -melanin * polydopamine * poly(ethylene oxide) Subject RIV: CD - Macromolecular Chemistry Impact factor: 5.479, year: 2011

  20. Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1984-01-01

    The present study was undertaken to investigate the effect of alpha- and beta-adrenergic agonists on secretion of epidermal growth factor (EGF) from the rat submandibular glands and to test the possibility of intestinal absorption of EGF. Alpha-adrenergic agonists increased the concentration...... of salivary EGF by approximately a hundred times, while the serum concentration of EGF was unchanged. The contents of EGF in the submandibular glands decreased upon administration of the alpha-adrenergic agonist noradrenaline, and this was confirmed on immunohistochemical investigation of the glands. Beta-adrenergic....... This study shows that alpha-adrenergic agonists stimulate exocrine secretion of submandibular EGF and that EGF in physiological amounts are not absorbed in the gastrointestinal tract....

  1. Diversion of the melanin synthetic pathway by dopamine product scavengers: A quantum chemical modeling of the reaction mechanisms

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    T. B. Demissie

    2017-01-01

    Full Text Available We report the stability and reactivity of the oxidation products as well as L-cysteine and N-acetylcysteine adducts of dopamine studied using quantum chemical calculations. The overall reactions studied were subdivided into four reaction channels. The first reaction channel is the oxidation of dopamine to form dopaminoquinone. The second reaction channel leads to melanin formation through subsequent reactions. The third and fourth reaction channels are reactions leading to the formation of dopaminoquinone adducts which are aimed to divert the synthesis of melanin. The results indicate that L-cysteine and N-acetylcysteine undergo chemical reactions mainly at C5 position of dopaminoquinone. The analyses of the thermodynamic energies indicate that L-cysteine and N-acetylcysteine covalently bind to dopaminoquinone by competing with the internal cyclization reaction of dopaminoquinone which leads to the synthesis of melanin. The analysis of the results, based on the reaction free energies, is also supported by the investigation of the natural bond orbitals of the reactants and products.

  2. Determination of the optical properties of melanin-pigmented human skin equivalents using terahertz time-domain spectroscopy

    Science.gov (United States)

    Lipscomb, Dawn; Echchgadda, Ibtissam; Peralta, Xomalin G.; Wilmink, Gerald J.

    2013-02-01

    Terahertz time-domain spectroscopy (THz-TDS) methods have been utilized in previous studies in order to characterize the optical properties of skin and its primary constituents (i.e., water, collagen, and keratin). However, similar experiments have not yet been performed to investigate whether melanocytes and the melanin pigment that they synthesize contribute to skin's optical properties. In this study, we used THz-TDS methods operating in transmission geometry to measure the optical properties of in vitro human skin equivalents with or without normal human melanocytes. Skin equivalents were cultured for three weeks to promote gradual melanogenesis, and THz time domain data were collected at various time intervals. Frequency-domain analysis techniques were performed to determine the index of refraction (n) and absorption coefficient (μa) for each skin sample over the frequency range of 0.1-2.0 THz. We found that for all samples as frequency increased, n decreased exponentially and the μa increased linearly. Additionally, we observed that skin samples with higher levels of melanin exhibited greater n and μa values than the non-pigmented samples. Our results indicate that melanocytes and the degree of melanin pigmentation contribute in an appreciable manner to the skin's optical properties. Future studies will be performed to examine whether these contributions are observed in human skin in vivo.

  3. Bleaching of melanin in the epidermis of South American fur seal and its application on enzyme immunohistochemistry

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    A.P. Silva

    2011-03-01

    Full Text Available The South American fur seal (Arctocephalus australis is an amphibious marine mammal distributed along the Atlantic and Pacific coasts of South America. The species is well adjusted to different habitats due to the morphology of its fin-like members and due to some adaptations in their integumentary system. Immunohistochemical studies are very important to evaluate the mechanisms of skin adaptation due the differential expression of the antigens present in the tissue depending of the region of the body surface. However, its strongly pigmented (melanin epidermis prevents the visualization of the immuno-histochemical chromogens markers. In this study a melanin bleaching method was developed aimed to allow the visualization of the chromogens without interfering in the antigen-antibody affinity for immunohistochemistry. The analysis of PCNA (proliferating cell nuclear antigen index in the epidermis of A. australis by immunohistochemistry with diaminobenzidine (DAB as chromogen was used to test the method. The bleaching of the melanin allowed to obtain the cell proliferation index in epidermis and to avoid false positive results without affecting the immunohistochemical results.

  4. Epicutaneous aeroallergen sensitization in atopic dermatitis infants - determining the role of epidermal barrier impairment.

    Science.gov (United States)

    Boralevi, F; Hubiche, T; Léauté-Labrèze, C; Saubusse, E; Fayon, M; Roul, S; Maurice-Tison, S; Taïeb, A

    2008-02-01

    Sensitization to atopens is an early phenomenon that overlaps with the onset of atopic dermatitis (AD) in infancy. Early epidermal barrier impairment may facilitate the epicutaneous penetration of atopens. To correlate transepidermal water loss (TEWL) and aeroallergen sensitization in infants with AD. In this cross-sectional study we enrolled 59 AD children and 30 controls aged 3-12 months. Transepidermal water loss in uninvolved skin, specific immunoglobulin E, atopy patch test (APT) and skin prick tests were performed with respect to seven aeroallergens, i.e., Dermatophagoides pteronyssinus, D. farinae, cat, dog, birch pollen, ambrosia, and cockroach. Environmental conditions were assessed by a questionnaire, and the house dust mite (HDM) concentration was determined in dust samples. Eighty-nine percent of AD infants had a positive APT vs one out of eleven controls. AD infants had a significantly higher mean TEWL than controls (27.4 vs 11.1 g/m(2)/h, P cats, and dogs at home. This study confirms the high prevalence of delayed sensitization to indoor and outdoor aeroallergens in AD infants, and shows that the higher the TEWL, the higher the prevalence of sensitization to aeroallergens. These data are in favor of a major role of a constitutive epidermal barrier impairment in determining early atopen sensitization in infants with AD.

  5. Long-term organ culture of rabbit skin: Effect of EGF on epidermal structure in vitro

    International Nuclear Information System (INIS)

    Kondo, S.; Hozumi, Y.; Aso, K.

    1990-01-01

    A method is described for maintaining the epidermal structure of normal rabbit ear skin explants in organ culture for up to 12 weeks. Split-thickness skin specimens were put in diffusion chambers made of either millipore filters or bovine collagen membranes, and then submitted to a roller tube culture at 15 rpm and 36 degrees C. The culture medium was Dulbecco's modified Eagle's medium (DMEM) supplemented with 20% fetal calf serum (FCS) + 0.4 micrograms/ml hydrocortisone. The gas used in the culture tube was air + 5% CO2. Autoradiography revealed the incorporation of [3H]-glycine into the 68-kD keratin band of explants for up to 12 weeks, indicating that normal keratinization was maintained throughout the entire culture period. The turnover time of the epidermis from basal layer to granular layer was around 7 d in both the early and late stages of culture. The addition of epidermal growth factor (EGF) to the culture caused the epidermis to become acanthotic with orthokeratosis, but with high concentrations of EGF (greater than or equal to 10 ng/ml) parakeratosis and increased proliferation of the epidermis occurred. Dexamethasone (DMS) strongly inhibited the EGF effect

  6. Identification of a phenoloxidase- and melanin-dependent defence mechanism in Achatina fulica infected with Angiostrongylus vasorum.

    Science.gov (United States)

    Coaglio, Aytube Lucas; Ferreira, Mônica Alves Neves Diniz; Dos Santos Lima, Walter; de Jesus Pereira, Cíntia Aparecida

    2018-02-27

    Angiostrongylus vasorum has different freshwater aquatic and terrestrial gastropod molluscs as an intermediate host, e.g. Arion spp. The mollusc Achatina fulica is a danger to public health, given the large diversity of nematodes utilizing it as an intermediate host, such as the parasites of the genus Angiostrongylus, of importance in human and veterinary medicine. Achatina fulica has been shown to have an excellent capacity for maintaining outbreaks and natural infections with A. cantonensis in Asia. Within the mollusc, the nematode parasites activate haemocytes and/or haemolymph factors and in some invertebrates, phenoloxidase (PO), that induces the release of toxic elements and eliminates the parasites. Despite the importance of A. fulica in the life-cycle of nematodes, little is known regarding the defence mechanisms involving PO in molluscs infected with nematodes. Here, the presence of PO and nitric oxide (NO) in the haemolymph and haemocytes of A. fulica infected with first-stage (L1) larvae of Angiostrongylus vasorum was evaluated, together with the presence of melanin in the cephalopod mollusc tissue. An increase in PO at one day post infection (dpi), in comparison with the control using the substrates L-tyrosine (F (4,90)  = 6.73, P = 0.00006), L-DOPA (F (4,90)  = 22.67, P = 0.02) and p-phenylenediamine (PPD) (F (4,90)  = 27.58, P = 0.0019), was observed. PO increase coincided with the presence of melanin in the cephalopodal tissue. At 8 dpi, PO activity, compared to L-DOPA (F (4,90)  = 22.67, P = 0.00002) and PPD (F (4,90)  = 27.58, P = 0.079) decreased, while melanin increased. At 13 dpi, PO decreased with PPD (F (4,90)  = 27.58, P = 0.000015) and also the amount of melanin observed in histology. At 30 dpi, PO increased along with the substrates L-DOPA and PPD, while melanin decreased. NO levels increased until 8 dpi, and decreased after 13 dpi. To our knowledge, this is the first study that

  7. Targeted Disruption of Melanin Biosynthesis Genes in the Human Pathogenic Fungus Lomentospora prolificans and Its Consequences for Pathogen Survival

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    Ayat Al-Laaeiby

    2016-03-01

    Full Text Available The dematiaceous (melanised fungus Lomentospora (Scedosporium prolificans is a life-threatening opportunistic pathogen of immunocompromised humans, resistant to anti-fungal drugs. Melanin has been shown to protect human pathogenic fungi against antifungal drugs, oxidative killing and environmental stresses. To determine the protective role of melanin in L. prolificans to oxidative killing (H2O2, UV radiation and the polyene anti-fungal drug amphotericin B, targeted gene disruption was used to generate mutants of the pathogen lacking the dihydroxynaphthalene (DHN-melanin biosynthetic enzymes polyketide synthase (PKS1, tetrahydroxynapthalene reductase (4HNR and scytalone dehydratase (SCD1. Infectious propagules (spores of the wild-type strain 3.1 were black/brown, whereas spores of the PKS-deficient mutant ΔLppks1::hph were white. Complementation of the albino mutant ΔLppks1::hph restored the black-brown spore pigmentation, while the 4HNR-deficient mutant ΔLp4hnr::hph and SCD-deficient mutant ΔLpscd1::hph both produced orange-yellow spores. The mutants ΔLppks1::hph and ΔLp4hnr::hph showed significant reductions in spore survival following H2O2 treatment, while spores of ΔLpscd1::hph and the ΔLppks1::hph complemented strain ΔLppks1::hph:PKS showed spore survivals similar to strain 3.1. Spores of the mutants ΔLp4hnr::hph and ΔLpscd1::hph and complemented strain ΔLppks1::hph:PKS showed spore survivals similar to 3.1 following exposure to UV radiation, but survival of ΔLppks1::hph spores was significantly reduced compared to the wild-type strain. Strain 3.1 and mutants ΔLp4hnr::hph and ΔLppks1::hph:PKS were resistant to amphotericin B while, paradoxically, the PKS1- and SCD1-deficient mutants showed significant increases in growth in the presence of the antifungal drug. Taken together, these results show that while melanin plays a protective role in the survival of the pathogen to oxidative killing and UV radiation, melanin does not

  8. Targeted Disruption of Melanin Biosynthesis Genes in the Human Pathogenic Fungus Lomentospora prolificans and Its Consequences for Pathogen Survival.

    Science.gov (United States)

    Al-Laaeiby, Ayat; Kershaw, Michael J; Penn, Tina J; Thornton, Christopher R

    2016-03-24

    The dematiaceous (melanised) fungus Lomentospora (Scedosporium) prolificans is a life-threatening opportunistic pathogen of immunocompromised humans, resistant to anti-fungal drugs. Melanin has been shown to protect human pathogenic fungi against antifungal drugs, oxidative killing and environmental stresses. To determine the protective role of melanin in L. prolificans to oxidative killing (H₂O₂), UV radiation and the polyene anti-fungal drug amphotericin B, targeted gene disruption was used to generate mutants of the pathogen lacking the dihydroxynaphthalene (DHN)-melanin biosynthetic enzymes polyketide synthase (PKS1), tetrahydroxynapthalene reductase (4HNR) and scytalone dehydratase (SCD1). Infectious propagules (spores) of the wild-type strain 3.1 were black/brown, whereas spores of the PKS-deficient mutant ΔLppks1::hph were white. Complementation of the albino mutant ΔLppks1::hph restored the black-brown spore pigmentation, while the 4HNR-deficient mutant ΔLp4hnr::hph and SCD-deficient mutant ΔLpscd1::hph both produced orange-yellow spores. The mutants ΔLppks1::hph and ΔLp4hnr::hph showed significant reductions in spore survival following H₂O₂ treatment, while spores of ΔLpscd1::hph and the ΔLppks1::hph complemented strain ΔLppks1::hph:PKS showed spore survivals similar to strain 3.1. Spores of the mutants ΔLp4hnr::hph and ΔLpscd1::hph and complemented strain ΔLppks1::hph:PKS showed spore survivals similar to 3.1 following exposure to UV radiation, but survival of ΔLppks1::hph spores was significantly reduced compared to the wild-type strain. Strain 3.1 and mutants ΔLp4hnr::hph and ΔLppks1::hph:PKS were resistant to amphotericin B while, paradoxically, the PKS1- and SCD1-deficient mutants showed significant increases in growth in the presence of the antifungal drug. Taken together, these results show that while melanin plays a protective role in the survival of the pathogen to oxidative killing and UV radiation, melanin does not

  9. To compare the gingival melanin repigmentation after diode laser application and surgical removal

    Directory of Open Access Journals (Sweden)

    Gaurav Mahajan

    2017-01-01

    Full Text Available Aim: The aim of the present study is to compare the gingival melanin repigmentation after diode laser application and surgical removal done by scraping with Kirkland knife. Materials and Methods: This study was a randomized split-mouth study where 10 patients presenting with unattractive, diffuse, dark brown to black gingival discoloration on the facial aspect of the maxillary gingiva were treated by diode laser application and surgical removal and followed up for 3-, 6-, and 9-month intervals. Results: The results showed a statistically significant difference in repigmentation between the groups at the interval of 3 months (P = 0.040, but the difference was statistically not significant at 6 months (P = 0.118 and 9 months (P = 0.146. On surgically treated sites, all cases showed repigmentation of the gingiva, but in laser treated, there were two individuals which did not show repigmentation of the gingiva even at the end of 9-month observation time. Conclusion: The incidence of repigmentation was slightly less in laser-treated sites as compared to surgical depigmentation although the difference was statistically significant only up to 3 months.

  10. To compare the gingival melanin repigmentation after diode laser application and surgical removal.

    Science.gov (United States)

    Mahajan, Gaurav; Kaur, Harjit; Jain, Sanjeev; Kaur, Navnit; Sehgal, Navneet Kaur; Gautam, Aditi

    2017-01-01

    The aim of the present study is to compare the gingival melanin repigmentation after diode laser application and surgical removal done by scraping with Kirkland knife. This study was a randomized split-mouth study where 10 patients presenting with unattractive, diffuse, dark brown to black gingival discoloration on the facial aspect of the maxillary gingiva were treated by diode laser application and surgical removal and followed up for 3-, 6-, and 9-month intervals. The results showed a statistically significant difference in repigmentation between the groups at the interval of 3 months ( P = 0.040), but the difference was statistically not significant at 6 months ( P = 0.118) and 9 months ( P = 0.146). On surgically treated sites, all cases showed repigmentation of the gingiva, but in laser treated, there were two individuals which did not show repigmentation of the gingiva even at the end of 9-month observation time. The incidence of repigmentation was slightly less in laser-treated sites as compared to surgical depigmentation although the difference was statistically significant only up to 3 months.

  11. Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma

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    M. Klein

    2013-01-01

    Full Text Available There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

  12. Mechanisms relevant to the enhanced virulence of a dihydroxynaphthalene-melanin metabolically engineered entomopathogen.

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    Min-Nan Tseng

    Full Text Available The entomopathogenic fungus Metarhizium anisopliae MA05-169 is a transformant strain that has been metabolically engineered to express dihydroxynaphthalene-melanin biosynthesis genes. In contrast to the wild type strain, the transformant displays a greater resistance to environmental stress and a higher virulence toward target insect host. However, the underlying mechanisms for these characteristics remain unclear; hence experiments were initiated to explore the possible mechanism(s through physiological and molecular approaches. Although both transformant and wild type strains could infect and share the same insect host range, the former germinated faster and produced more appressoria than the latter, both in vivo and in vitro. The transformant showed a significantly shorter median lethal time (LT50 when infecting the diamondback moth (Plutella xylostella and the striped flea beetle (Phyllotreta striolata, than the wild type. Additionally, the transformant was more tolerant to reactive oxygen species (ROS, produced 40-fold more orthosporin and notably overexpressed the transcripts of the pathogenicity-relevant hydrolytic enzymes (chitinase, protease, and phospholipase genes in vivo. In contrast, appressorium turgor pressure and destruxin A content were slightly decreased compared to the wild type. The transformant's high anti-stress tolerance, its high virulence against five important insect pests (cowpea aphid Aphis craccivora, diamondback moth Pl. xylostella, striped flea beetle Ph. striolata, and silverleaf whitefly Bemisia argentifolii and its capacity to colonize the root system are key properties for its potential bio-control field application.

  13. Methylquercetins stimulate melanin biosynthesis in a three-dimensional skin model.

    Science.gov (United States)

    Yamauchi, Kosei; Mitsunaga, Tohru

    2018-03-01

    In a previous study, we found that both synthetic 3-O-methylquercetin (3MQ) and 3,4',7-O-trimethylquercetin (34'7TMQ) increased extracellular melanin content. 34'7TMQ increased the activity of melanogenic enzymes by stimulating the p38 pathway and the expression of microphthalmia-associated transcription factor (MITF). In contrast, 3MQ increased the activity of melanogenic enzymes without the involvement of MITF, which suggests that 3MQ inhibits the degradation of melanogenic enzymes. In the present study, we investigated the effects of 3MQ and 34'7TMQ on melanogenesis in normal human melanocytes and using a commercial three-dimensional (3D) skin model system. Both 3MQ and 34'7TMQ elongated the dendrites of normal human melanocytes from a Caucasian donor, but did not stimulate melanogenesis in the melanocytes. In the 3D skin model, which included melanocytes from an Asian donor, 3MQ and 34'7TMQ increased and elongated the melanocytes and showed a tendency to stimulate melanogenesis. These results suggest that 3MQ and 34'7TMQ could be put to practical use in skin care products and agents aimed at preventing hair graying.

  14. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin

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    Nisma Mujahid

    2017-06-01

    Full Text Available The presence of dark melanin (eumelanin within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in “redhaired” Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk.

  15. A UV-Independent Topical Small-Molecule Approach for Melanin Production in Human Skin.

    Science.gov (United States)

    Mujahid, Nisma; Liang, Yanke; Murakami, Ryo; Choi, Hwan Geun; Dobry, Allison S; Wang, Jinhua; Suita, Yusuke; Weng, Qing Yu; Allouche, Jennifer; Kemeny, Lajos V; Hermann, Andrea L; Roider, Elisabeth M; Gray, Nathanael S; Fisher, David E

    2017-06-13

    The presence of dark melanin (eumelanin) within human epidermis represents one of the strongest predictors of low skin cancer risk. Topical rescue of eumelanin synthesis, previously achieved in "redhaired" Mc1r-deficient mice, demonstrated significant protection against UV damage. However, application of a topical strategy for human skin pigmentation has not been achieved, largely due to the greater barrier function of human epidermis. Salt-inducible kinase (SIK) has been demonstrated to regulate MITF, the master regulator of pigment gene expression, through its effects on CRTC and CREB activity. Here, we describe the development of small-molecule SIK inhibitors that were optimized for human skin penetration, resulting in MITF upregulation and induction of melanogenesis. When topically applied, pigment production was induced in Mc1r-deficient mice and normal human skin. These findings demonstrate a realistic pathway toward UV-independent topical modulation of human skin pigmentation, potentially impacting UV protection and skin cancer risk. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  16. G2 accumulation and melanin overproduction in malignant melanocytes treated with a new nitrosourea.

    Science.gov (United States)

    Buchdahl, C; Papon, J; Communal, Y; Bourges, M; Madelmont, J C

    1998-12-01

    Cystemustine (N'-(2-chloroethyl)-N-(2-(methylsulphonyl)ethyl)-N'-nitrosourea), a new anticancer chloroethylnitrosourea (CENU) is being tested in a phase II clinical trial of disseminated melanoma. The antitumour effect of this drug is mainly due to DNA damage in malignant melanocytes. Recently, we have shown that this damage can induce apoptosis in some melanoma cell lines. In others, apoptosis is not clearly observed, although there is a strong cytostatic effect. In this paper, we have characterized the cytological effect of cystemustine on murine malignant melanocytes (B16 cell line) which are resistant to apoptosis induced by this CENU. The results show that 3 days after cystemustine treatment, these melanocytes had accumulated in phase G2 of the cell cycle. There was then a strong morphological modification during a long cytostatic phase up to 30 days after treatment. During this cytostatic phase, there was uncontrolled DNA synthesis and marked swelling. Also, tyrosinase activity, melanin content and the number of mature melanosomes were greatly increased. These results suggest that when malignant melanocytes are not able to undergo apoptosis after treatment with CENU, they accumulate in G2 and this is followed by enhancement of melanogenesis.

  17. Internal dosimetry through GATE simulations of preclinical radiotherapy using a melanin-targeting ligand

    International Nuclear Information System (INIS)

    Perrot, Y; Donnarieix, D; Maigne, L; Degoul, F; Auzeloux, P; Bonnet, M; Cachin, F; Chezal, J M; Labarre, P; Moins, N; Papon, J; Rbah-Vidal, L; Vidal, A; Miot-Noirault, E

    2014-01-01

    The GATE Monte Carlo simulation platform based on the Geant4 toolkit is under constant improvement for dosimetric calculations. In this study, we explore its use for the dosimetry of the preclinical targeted radiotherapy of melanoma using a new specific melanin-targeting radiotracer labeled with iodine 131. Calculated absorbed fractions and S values for spheres and murine models (digital and CT-scan-based mouse phantoms) are compared between GATE and EGSnrc Monte Carlo codes considering monoenergetic electrons and the detailed energy spectrum of iodine 131. The behavior of Geant4 standard and low energy models is also tested. Following the different authors’ guidelines concerning the parameterization of electron physics models, this study demonstrates an agreement of 1.2% and 1.5% with EGSnrc, respectively, for the calculation of S values for small spheres and mouse phantoms. S values calculated with GATE are then used to compute the dose distribution in organs of interest using the activity distribution in mouse phantoms. This study gives the dosimetric data required for the translation of the new treatment to the clinic. (paper)

  18. Utility of sun-reactive skin typing and melanin index for discerning vitamin D deficiency.

    Science.gov (United States)

    Khalid, Arshad T; Moore, Charity G; Hall, Christopher; Olabopo, Flora; Rozario, Nigel L; Holick, Michael F; Greenspan, Susan L; Rajakumar, Kumaravel

    2017-09-01

    BackgroundSkin color, a vitamin D status determinant, can be assessed subjectively by Fitzpatrick sun-reactive skin typing (FST) and objectively by melanin index (MI). FST was validated against MI for discerning vitamin D deficiency (serum 25-hydroxyvitamin D (25(OH)D) serum 25(OH)D in healthy, 8- to 18-year-old children from one of two vitamin D trials. MI from forehead, hand, and upper arm split at the median of the more racially balanced study cohort and FST (I-III vs. IV-V) were used for discriminating vitamin D deficiency.ResultsA total of 296 participants (mean age, 12.3±2.3 years; black, 208; FST IV-V, 209; 25(OH)D Serum 25(OH)D was negatively associated with MI and FST. Sensitivity, specificity, and predictive values were similar for discriminating vitamin D deficiency between higher vs. lower MI and between FST I-III vs. IV-V. ROC area under the curves for FST (0.59) and MI (forehead (0.63); hand (0.62); and arm (0.64)) were similar.ConclusionsFST is comparable to MI for discerning vitamin D deficiency and can be deemed as an inexpensive, useful surrogate measure of skin color in the context of vitamin D research.

  19. Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN): could retinoids play a causative role?

    Science.gov (United States)

    Mawson, Anthony R; Eriator, Ike; Karre, Sridhar

    2015-01-12

    Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are overlapping manifestations on a spectrum of acute drug-induced conditions associated with severe blistering, skin peeling, and multi-organ damage. TEN is an eruption resembling severe scalding, with ≥30% skin detachment. SJS is a mild form of TEN, characterized histologically by epidermal keratinocyte apoptosis with dermo-epidermal separation and extensive small blisters with <10% body surface skin detachment. The syndrome can be induced by numerous medications and typically occurs 1-4 weeks after the initiation of therapy. Granulysin is found in the lesions of patients with SJS/TEN and plays a significant pathogenic role in the condition, but the overall mechanisms linking medications, granulysin, and disease manifestations remain obscure. This paper reviews evidence suggesting that the different medications implicated in SJS/TEN have the common property of interacting and synergizing with endogenous retinoids (vitamin A and its congeners), in many instances causing the latter to accumulate in and damage the liver, the main storage organ for vitamin A. It is hypothesized that liver damage leads to the spillage of toxic retinoid compounds into the circulation, resulting in an endogenous form of hypervitaminosis A and cytotoxicity with widespread apoptosis, mediated by granulysin and recognized as SJS/TEN. Subject to testing, the model suggests that symptom worsening could be arrested at onset by lowering the concentration of circulating retinoids and/or granulysin via phlebotomy or plasmapheresis or by pharmacological measures to limit their expression.

  20. [4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03) inhibits SCF/c-kit signaling in 501mel human melanoma cells and abolishes melanin production in mice and brownish guinea pigs.

    Science.gov (United States)

    Na, Yong Joo; Baek, Heung Su; Ahn, Soo Mi; Shin, Hyun Jung; Chang, Ih-Seop; Hwang, Jae Sung

    2007-09-01

    It is well known that c-kit is related to pigmentation as well as to the oncology target protein. The objective of this study was to discover a skin-whitening agent that regulates c-kit activity. We have developed a high-throughput screening system using recombinant human c-kit protein. Approximately 10,000 synthetic compounds were screened for their effect on c-kit activity. Phenyl-imidazole sulfonamide derivatives showed inhibitory activity on c-kit phosphorylation in vitro. The effects of one derivative, [4-t-butylphenyl]-N-(4-imidazol-1-yl phenyl)sulfonamide (ISCK03), on stem-cell factor (SCF)/c-kit cellular signaling in 501mel human melanoma cells were examined further. Pretreatment of 501mel cells with ISCK03 inhibited SCF-induced c-kit phosphorylation dose dependently. ISCK03 also inhibited p44/42 ERK mitogen-activated protein kinase (MAPK) phosphorylation, which is known to be involved in SCF/c-kit downstream signaling. However ISCK03 did not inhibit hepatocyte growth factor (HGF)-induced phosphorylation of p44/42 ERK proteins. To determine the in vivo potency of ISCK03, it was orally administered to depilated C57BL/6 mice. Interestingly, oral administration of ISCK03 induced the dose-dependent depigmentation of newly regrown hair, and this was reversed with cessation of ISCK03 treatment. Finally, to investigate whether the inhibitory effect of ISCK03 on SCF/c-kit signaling abolished UV-induced pigmentation, ISCK03 was applied to UV-induced pigmented spots on brownish guinea pig skin. The topical application of ISCK03 promoted the depigmentation of UV-induced hyperpigmented spots. Fontana-Masson staining analysis showed epidermal melanin was diminished in spots treated with ISCK03. These results indicate that phenyl-imidazole sulfonamide derivatives are potent c-kit inhibitors and might be used as skin-whitening agents.

  1. The epidermal biosynthesis of cholecalciferol (vitamin D3)

    International Nuclear Information System (INIS)

    Beadle, P.C.

    1977-01-01

    An attempt has been made to calculate the rate of ultraviolet absorption by 7-dehydrocholesterol, provitamin D 3 , in the epidermis as a function of latitude, season and skin type, in the hope that it will provide an upper-limit estimate of the epidermal vitamin production. The results indicate that a significant fraction of the total epidermal production may occur in the stratum corneum with figures of 15 and 31% being found for non-pigmented and pigmented epidermises, respectively. Total production in negroid epidermis is predicted to be about 40% of that in the caucasian one and the latitudinal variation is greater than the seasonal variation, in agreement with the behaviour of the available solar ultraviolet. Overall production rates were sufficiently high for it to be unnecessary to invoke an enhanced absorption mechanism for the provitamin, although the results do indicate that there may be a risk of deficient production above about 40 0 N. (author)

  2. Steroid hormone and epidermal growth factor receptors in meningiomas.

    Science.gov (United States)

    Horsfall, D J; Goldsmith, K G; Ricciardelli, C; Skinner, J M; Tilley, W D; Marshall, V R

    1989-11-01

    A prospective study of steroid hormone and epidermal growth factor receptor expression in 57 meningiomas is presented. Scatchard analysis of radioligand binding identified 20% of meningiomas as expressing classical oestrogen receptors (ER) at levels below that normally accepted for positivity, the remainder being negative. ER could not be visualized in any meningioma using immunocytochemistry. Alternatively, 74% of meningiomas demonstrated the presence of progesterone receptors (PR) by Scatchard analysis, the specificity of which could not be attributed to glucocorticoid or androgen receptors. Confirmation of classical PR presence was determined by immunocytochemical staining. The presence of epidermal growth factor receptor (EGFR) was demonstrated in 100% of meningiomas using immunocytochemical staining. These data are reviewed in the context of previously reported results and are discussed in relation to the potential for medical therapy as an adjunct to surgery.

  3. Immunohistochemical localization of epidermal growth factor in rat and man

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1986-01-01

    Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands is...... antisera against human urinary EGF worked in rat as well as man. EGF was found only in cells with an exocrine function.......Epidermal growth factor (EGF) is a peptide which stimulates cell mitotic activity and differentiation, has a cytoprotective effect on the gastroduodenal mucosa, and inhibits gastric acid secretion. The immunohistochemical localization of EGF in the Brunner's glands and the submandibular glands...... is well documented. The localization of EGF in other tissues is still unclarified. In the present study, the immunohistochemical localization of EGF in tissues from rat, man and a 20 week human fetus were investigated. In man and rat, immunoreaction was found in the submandibular glands, the serous glands...

  4. Rapid and dynamic subcellular reorganization following mechanical stimulation of Arabidopsis epidermal cells mimics responses to fungal and oomycete attack

    Directory of Open Access Journals (Sweden)

    Takemoto Daigo

    2008-06-01

    Full Text Available Abstract Background Plant cells respond to the presence of potential fungal or oomycete pathogens by mounting a basal defence response that involves aggregation of cytoplasm, reorganization of cytoskeletal, endomembrane and other cell components and development of cell wall appositions beneath the infection site. This response is induced by non-adapted, avirulent and virulent pathogens alike, and in the majority of cases achieves penetration resistance against the microorganism on the plant surface. To explore the nature of signals that trigger this subcellular response and to determine the timing of its induction, we have monitored the reorganization of GFP-tagged actin, microtubules, endoplasmic reticulum (ER and peroxisomes in Arabidopsis plants – after touching the epidermal surface with a microneedle. Results Within 3 to 5 minutes of touching the surface of Arabidopsis cotyledon epidermal cells with fine glass or tungsten needles, actin microfilaments, ER and peroxisomes began to accumulate beneath the point of contact with the needle. Formation of a dense patch of actin was followed by focusing of actin cables on the site of contact. Touching the cell surface induced localized depolymerization of microtubules to form a microtubule-depleted zone surrounding a dense patch of GFP-tubulin beneath the needle tip. The concentration of actin, GFP-tubulin, ER and peroxisomes remained focused on the contact site as the needle moved across the cell surface and quickly dispersed when the needle was removed. Conclusion Our results show that plant cells can detect the gentle pressure of a microneedle on the epidermal cell surface and respond by reorganizing subcellular components in a manner similar to that induced during attack by potential fungal or oomycete pathogens. The results of our study indicate that during plant-pathogen interactions, the basal defence response may be induced by the plant's perception of the physical force exerted by the

  5. Grafting of human epidermal cells, presence and perspectives

    Czech Academy of Sciences Publication Activity Database

    Smetana, Karel; Dvořánková, B.; Labský, Jiří; Vacík, Jiří; Holíková, Z.

    2001-01-01

    Roč. 102, č. 1 (2001), s. 1-6 ISSN 0036-5327 R&D Projects: GA ČR GA203/00/1310; GA AV ČR IBS4050005; GA MZd ND6340; GA MŠk LN00A065; GA AV ČR KSK4055109 Institutional research plan: CEZ:AV0Z4050913 Keywords : cell therapy-keratinocyte-epidermal stem cell * skin defect Subject RIV: CD - Macromolecular Chemistry

  6. Epidermal electronics with advanced capabilities in near-field communication.

    Science.gov (United States)

    Kim, Jeonghyun; Banks, Anthony; Cheng, Huanyu; Xie, Zhaoqian; Xu, Sheng; Jang, Kyung-In; Lee, Jung Woo; Liu, Zhuangjian; Gutruf, Philipp; Huang, Xian; Wei, Pinghung; Liu, Fei; Li, Kan; Dalal, Mitul; Ghaffari, Roozbeh; Feng, Xue; Huang, Yonggang; Gupta, Sanjay; Paik, Ungyu; Rogers, John A

    2015-02-25

    Epidermal electronics with advanced capabilities in near field communications (NFC) are presented. The systems include stretchable coils and thinned NFC chips on thin, low modulus stretchable adhesives, to allow seamless, conformal contact with the skin and simultaneous capabilities for wireless interfaces to any standard, NFC-enabled smartphone, even under extreme deformation and after/during normal daily activities. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Expression and analysis of exogenous proteins in epidermal cells.

    Science.gov (United States)

    Dagnino, Lina; Ho, Ernest; Chang, Wing Y

    2010-01-01

    In this chapter we review protocols for transient transfection of primary keratinocytes. The ability to transfect primary epidermal cells regardless of their differentiation status allows the biochemical and molecular characterization of multiple proteins. We review methods to analyze exogenous protein abundance in transfected keratinocytes by immunoblot and immunoprecipitation. We also present protocols to determine the subcellular distribution of these proteins by indirect immunofluorescence microscopy approaches.

  8. A review of toxic epidermal necrolysis management in Japan

    Directory of Open Access Journals (Sweden)

    Yuri Kinoshita

    2017-01-01

    Full Text Available Toxic epidermal necrolysis (TEN is a severe adverse drug reaction characterized by necrosis of the epidermis. Its incidence is approximately 1 per million a year and average mortality rate is high at 25–50%. TEN has a flu-like prodrome, followed by atypical, targetoid erythematous or purpuric macules on the skin. These macules coalesce to form flaccid blisters that slough off as areas of epidermal necrosis. Drugs such as allopurinol, sulfonamides, and carbamazepine are the most common causes. The human leukocyte antigen (HLA-B*15:02 in Asians being administered carbamazepine and the HLA-B*58:01 antigen in patients of all ethnicities being administered allopurinol are known to be high-risk factors. Rapid diagnosis, discontinuation of the causative drug, and supportive treatment are essential for better prognosis and improvement of sequelae. Till now, systemic corticosteroids and intravenous immunoglobulins have been used as the most common active interventions; however, no gold standard has been established. In Japan, physicians follow a unique diagnostic criteria and treatment guideline to improve the diagnosis rate and streamline treatments. This may be a contributing factor for the lower mortality rate (14.3%. The efficacy of systemic corticosteroids, immunoglobulins, and plasmapheresis may have been beneficial as well. In Japan, TEN is defined as an epidermal detachment of over 10% of the body surface area (BSA, while the globally accepted definition established by Bastuji-Garin describes it as an epidermal detachment of over 30% of the BSA. In Japanese individuals, HLA-A*02:06, HLA-A*02:07, HLA-A*31:01 and HLA-B*51:01 may be linked to higher risks of TEN.

  9. "Cut-and-Paste" Manufacture of Multiparametric Epidermal Sensor Systems.

    Science.gov (United States)

    Yang, Shixuan; Chen, Ying-Chen; Nicolini, Luke; Pasupathy, Praveenkumar; Sacks, Jacob; Su, Becky; Yang, Russell; Sanchez, Daniel; Chang, Yao-Feng; Wang, Pulin; Schnyer, David; Neikirk, Dean; Lu, Nanshu

    2015-11-04

    Multifunctional epidermal sensor systems (ESS) are manufactured with a highly cost and time effective, benchtop, and large-area "cut-and-paste" method. The ESS made out of thin and stretchable metal and conductive polymer ribbons can be noninvasively laminated onto the skin surface to sense electrophysiological signals, skin temperature, skin hydration, and respiratory rate. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Epidermal growth in the bottlenose dolphin, Tursiops truncatus

    International Nuclear Information System (INIS)

    Hicks, B.D.; St Aubin, D.J.; Geraci, J.R.; Brown, W.R.

    1985-01-01

    Epidermal growth in two mature female bottlenose dolphins, Tursiops truncatus, was investigated by following the movement of a cohort of tritiated thymidine-labeled epidermal cells for 59 days. The majority of the cells migrated in a cluster which was estimated to reach the skin surface in 73 days. The authors calculate that the outermost cell layer is sloughed 12 times per day. Turnover time and sloughing rate are estimated to be 1.7 times longer and 8.5 times faster than the respective values for epidermal cell kinetics in humans. This apparent inconsistency of slow transit time and rapid sloughing rate is reconciled by the convoluted structure of the stratum germinativum in the dolphin which results in a ratio of germinatival to superficial cells of 876:1. The stratum germinativum of dolphin epidermis appears to lack morphologically distinct, spatially segregated subpopulations of anchoring and stem cells. Dolphin epidermis has a large capacity for cell population, relatively long turnover time, and rapid sloughing rate. The adaptive advantages of these characteristics are discussed

  11. Epidermal growth factor receptor expression in urinary bladder cancer

    Directory of Open Access Journals (Sweden)

    Dayalu S.L. Naik

    2011-01-01

    Full Text Available Objective : To evaluate the expression pattern of epidermal growth factor receptor (EGFR in urinary bladder cancer and its association with human epidermal growth factor receptor 2 (HER2, epidermal growth factor (EGF, interleukin-6 (IL-6, and high risk human papilloma virus (HPV types 16 and 18. Materials and Methods : Thirty cases of urothelial carcinoma were analyzed. EGFR, HER2, EGF, and IL-6 expressions in the tissue were evaluated by immunohistochemical staining. For HPV, DNA from tissue samples was extracted and detection of HPV was done by PCR technique. Furthermore, evaluation of different intracellular molecules associated with EGFR signaling pathways was performed by the western blot method using lysates from various cells and tissues. Results : In this study, the frequencies of immunopositivity for EGFR, HER2, EGF, and IL-6 were 23%, 60%, 47%, and 80%, respectively. No cases were positive for HPV-18, whereas HPV-16 was detected in 10% cases. Overall, expression of EGFR did not show any statistically significant association with the studied parameters. However, among male patients, a significant association was found only between EGFR and HER2. Conclusions : Overexpression of EGFR and/or HER2, two important members of the same family of growth factor receptors, was observed in a considerable proportion of cases. Precise knowledge in this subject would be helpful to formulate a rational treatment strategy in patients with urinary bladder cancer.

  12. Fatty acids are required for epidermal permeability barrier function.

    Science.gov (United States)

    Mao-Qiang, M; Elias, P M; Feingold, K R

    1993-08-01

    The permeability barrier is mediated by a mixture of ceramides, sterols, and free fatty acids arranged as extracellular lamellar bilayers in the stratum corneum. Whereas prior studies have shown that cholesterol and ceramides are required for normal barrier function, definitive evidence for the importance of nonessential fatty acids is not available. To determine whether epidermal fatty acid synthesis also is required for barrier homeostasis, we applied 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA), an inhibitor of acetyl CoA carboxylase, after disruption of the barrier by acetone or tape stripping. TOFA inhibits epidermal fatty acid by approximately 50% and significantly delays barrier recovery. Moreover, coadministration of palmitate with TOFA normalizes barrier recovery, indicating that the delay is due to a deficiency in bulk fatty acids. Furthermore, TOFA treatment also delays the return of lipids to the stratum corneum and results in abnormalities in the structure of lamellar bodies, the organelle which delivers lipid to the stratum corneum. In addition, the organization of secreted lamellar body material into lamellar bilayers within the stratum corneum interstices is disrupted by TOFA treatment. Finally, these abnormalities in lamellar body and stratum corneum membrane structure are corrected by coapplication of palmitate with TOFA. These results demonstrate a requirement for bulk fatty acids in barrier homeostasis. Thus, inhibiting the epidermal synthesis of any of the three key lipids that form the extracellular, lipid-enriched membranes of the stratum corneum results in an impairment in barrier homeostasis.

  13. Epidermal growth in the bottlenose dolphin, Tursiops truncatus

    Energy Technology Data Exchange (ETDEWEB)

    Hicks, B.D.; St. Aubin, D.J.; Geraci, J.R.; Brown, W.R.

    1985-07-01

    Epidermal growth in two mature female bottlenose dolphins, Tursiops truncatus, was investigated by following the movement of a cohort of tritiated thymidine-labeled epidermal cells for 59 days. The majority of the cells migrated in a cluster which was estimated to reach the skin surface in 73 days. The authors calculate that the outermost cell layer is sloughed 12 times per day. Turnover time and sloughing rate are estimated to be 1.7 times longer and 8.5 times faster than the respective values for epidermal cell kinetics in humans. This apparent inconsistency of slow transit time and rapid sloughing rate is reconciled by the convoluted structure of the stratum germinativum in the dolphin which results in a ratio of germinatival to superficial cells of 876:1. The stratum germinativum of dolphin epidermis appears to lack morphologically distinct, spatially segregated subpopulations of anchoring and stem cells. Dolphin epidermis has a large capacity for cell population, relatively long turnover time, and rapid sloughing rate. The adaptive advantages of these characteristics are discussed.

  14. Optimal allocation of leaf epidermal area for gas exchange.

    Science.gov (United States)

    de Boer, Hugo J; Price, Charles A; Wagner-Cremer, Friederike; Dekker, Stefan C; Franks, Peter J; Veneklaas, Erik J

    2016-06-01

    A long-standing research focus in phytology has been to understand how plants allocate leaf epidermal space to stomata in order to achieve an economic balance between the plant's carbon needs and water use. Here, we present a quantitative theoretical framework to predict allometric relationships between morphological stomatal traits in relation to leaf gas exchange and the required allocation of epidermal area to stomata. Our theoretical framework was derived from first principles of diffusion and geometry based on the hypothesis that selection for higher anatomical maximum stomatal conductance (gsmax ) involves a trade-off to minimize the fraction of the epidermis that is allocated to stomata. Predicted allometric relationships between stomatal traits were tested with a comprehensive compilation of published and unpublished data on 1057 species from all major clades. In support of our theoretical framework, stomatal traits of this phylogenetically diverse sample reflect spatially optimal allometry that minimizes investment in the allocation of epidermal area when plants evolve towards higher gsmax . Our results specifically highlight that the stomatal morphology of angiosperms evolved along spatially optimal allometric relationships. We propose that the resulting wide range of viable stomatal trait combinations equips angiosperms with developmental and evolutionary flexibility in leaf gas exchange unrivalled by gymnosperms and pteridophytes. © 2016 The Authors New Phytologist © 2016 New Phytologist Trust.

  15. Histamine and epidermal growth factor in women with fibrocystic changes of the breast.

    Science.gov (United States)

    Sieja, K; Stanosz, S; Glowińska, N

    2003-04-01

    In this study, the blood serum concentrations of histamine (HA) and epidermal growth factor (EGF) of women with fibrocystic changes (FCCs) of the breast were estimated. The control group comprised 32 women (mean age 44.9+/-4.4 years) without any pathologic changes in their breasts. The study group was made up of 81 women (mean age 44.5+/-3.5 years) with FCCs. The changes were divided into three subtypes: fibrous, cystic, and fibrocystic. In women with FCCs the concentrations of HA (Pbreasts (control group). The concentration of EGF in blood serum was significantly higher in women with the fibrocystic subtype of FCC (P<0.001) than in healthy women. No correlations between the blood serum concentrations of HA and of EGF were found in either the control group or the study group. The significantly higher blood serum concentrations of HA and EGF women with FCCs than in healthy women suggest that HA and EGF have a role in the development of this disease.

  16. Aqueous fraction from Cuscuta japonica seed suppresses melanin synthesis through inhibition of the p38 mitogen-activated protein kinase signaling pathway in B16F10 cells.

    Science.gov (United States)

    Jang, Ji Yeon; Kim, Ha Neui; Kim, Yu Ri; Choi, Yung Hyun; Kim, Byung Woo; Shin, Hwa Kyoung; Choi, Byung Tae

    2012-05-07

    Semen cuscutae has been used traditionally to treat pimples and alleviate freckles and melasma in Korea. The present study aimed to investigate the inhibitory effect of Cuscuta japonica Choisy seeds on alpha-melanocyte-stimulating hormone (α-MSH)-induced melanogenesis. The aqueous fraction from Semen cuscutae (AFSC) was used to determine anti-melanogenic effects by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay and Western blot analysis for melanin synthesis-related signaling proteins in B16F10 mouse melanoma cells. AFSC markedly inhibited α-MSH-induced melanin synthesis and tyrosinase activity, and also decreased α-MSH-induced expression of microphthalmia-associated transcription factor (MITF) and tyrosinase-related proteins (TRPs). Moreover, AFSC significantly decreased the level of phosphorylated p38 mitogen-activated protein kinase (MAPK) signaling through the down-regulation of α-MSH-induced cAMP. Furthermore, we confirmed that the specific inhibitor of p38 MAPK (SB203580)-mediated suppressed melanin synthesis and tyrosinase activity was further attenuated by AFSC. AFSC also further decreased SB203580-mediated suppression of MITF and TRP expression. These results indicate that AFSC inhibits p38 MAPK phosphorylation with suppressed cAMP levels and subsequently down-regulate MITF and TRP expression, which results in a marked reduction of melanin synthesis and tyrosinase activity in α-MSH-stimulated B16F10 cells. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Autoradiography of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): Uptake in the monoaminergic pathways and in melanin containing tissues

    Energy Technology Data Exchange (ETDEWEB)

    Lyden, A; Lindquist, N G; Bondesson, U; Larsson, B S; Olsson, L -I

    1985-01-01

    A recently discovered neurotoxic compound, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, has been found to cause a parkinsonian-like syndrome in man and monkey, but not in laboratory animals such as rat, mouse and guinea pig. MPTP seems to selectively destroy the melanin containing dopaminergic cells in pars compacta of substantia nigra. Lower mammalian species do not have melanin in these cells, which indicates that the presence of neuromelanin may be of importance for the development of MPTP-induced lesions. By means of whole-body autoradiography of TH-MPTP in mice, accumulation and retention was observed in the dopaminergic pathways, in locus ceruleus and in structures in the medulla oblongata and spinal cord. A high uptake was also seen in melanin-containing tissues such as in the eyes of pigmented mice. MPTP has earlier been found to have high affinity in vitro for dopamine melanin, which is similar to the pigment in substantia nigra. The typical features of the MPTP-induced neurotoxicity with destruction of pigmented nerve cells and development of parkinsonism may be due to accumulation adn retention of MPTP and its metabolites in these cells. In species with pigmented nerve cells, such as man and monkey, the accumulation may be much more pronounced because of the melanin affinity of MPTP and its metabolites. (author).

  18. Adrenergic effects on renal secretion of epidermal growth factor in the rat

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1985-01-01

    Urinary epidermal growth factor (EGF) has been demonstrated recently to originate from the kidneys. The present study was undertaken to investigate the adrenergic and cholinergic influence on secretion of renal EGF. beta-Adrenergic agonists increased the level of urinary EGF, while propranolol......, a beta-adrenergic blocking agent, decreased basal and beta-adrenergic stimulated total output of urinary EGF. Acetylcholine and the anticholinergic agent atropine had no effect on the output of EGF in urine. Also chemical sympathectomy induced by 6-hydroxydopamine reduced the urinary output of EGF. None...... of the experimental groups had a median serum concentration above the detection limit of the assay. The present study shows that secretion of renal EGF is under the influence of the sympathetic nervous system and release of EGF is stimulated by activation of beta-adrenergic receptors in the kidneys....

  19. Epidermal growth factor-mediated effects on equine vascular smooth muscle cells

    International Nuclear Information System (INIS)

    Grosenbaugh, D.A.; Amoss, M.S.; Hood, D.M.; Morgan, S.J.; Williams, J.D.

    1988-01-01

    Epidermal growth factor (EGF) receptor binding kinetics and EGF-mediated stimulation of DNA synthesis and cellular proliferation were studied in cultured vascular smooth muscle cells (VSMC) from the equine thoracic aorta. Binding studies, using murine 125 I-labeled EGF, indicate the presence of a single class of high-affinity binding sites, with an estimated maximal binding capacity of 5,800 sites/cells. EGF stimulated [ 3 H]thymidine uptake in confluent quiescent monolayers in a dose-dependent fashion, half-maximal stimulation occurring at 7.5 x 10 -11 M. Likewise, EGF-mediated cellular proliferation was dose dependent under reduced serum concentrations. Equine VSMC contain specific receptors for EGF, and EGF can stimulate DNA synthesis and proliferation in these cultured cells, which suggests that EGF may participate in the proliferative changes observed in equine distal digital peripheral vascular disease

  20. Stimulation of allogeneic lymphocytes by skin epidermal cells in the rat

    International Nuclear Information System (INIS)

    Tanaka, S.; Sakai, A.

    1979-01-01

    The ability of skin epidermal cells to induce allogeneic lymphocytes into proliferation was examined in mixed skin cell-lymphocyte culture reaction (MSLR). The stimulatng capacity of skin cells was reduced significantly by trypsin digestion, although the damage was repaired by incubation at 37 C for 3 hr. The optimal concentration of mitomycin C for treatment of stimulating cells in the MSLR differed from that in mixed lymphocyte culture reaction (MLR). Irradiation rendered them three to four times more stimulatory than did mitomycin C. Removal of adherent cells from responding cells by passage through a nylon-wool column gave a substantial elevation of the MSLR. The lymphocytes cocultured with skin cells in the primary MSLR incorporated 3 H-thymidine, with the peak at the 6th day of culture. If the lymphocytes primed in the MSLR were restimulated with skin cells from the same stimulating strain, the primed lymphocytes responded promptly and in great magnitude

  1. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    Energy Technology Data Exchange (ETDEWEB)

    Gibbs, Susan, E-mail: S.Gibbs@VUMC.nl [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Corsini, Emanuela [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Spiekstra, Sander W. [Department of Dermatology, VU University Medical Centre, Dept of Oral Cell Biology, ACTA, Amsterdam (Netherlands); Galbiati, Valentina [Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano (Italy); Fuchs, Horst W. [CellSystems GmbH, Troisdorf (Germany); DeGeorge, George; Troese, Matthew [MB Research Labs, Spinnerstown, PA (United States); Hayden, Patrick; Deng, Wei [MatTek Corporation, Ashland, MA (United States); Roggen, Erwin [3Rs Management and Consultancy (Denmark)

    2013-10-15

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC{sub 50}) with human and animal data showed a superior correlation with human DSA{sub 05} (μg/cm{sup 2}) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA{sub 05} = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA{sub 05} data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency

  2. An epidermal equivalent assay for identification and ranking potency of contact sensitizers

    International Nuclear Information System (INIS)

    Gibbs, Susan; Corsini, Emanuela; Spiekstra, Sander W.; Galbiati, Valentina; Fuchs, Horst W.; DeGeorge, George; Troese, Matthew; Hayden, Patrick; Deng, Wei; Roggen, Erwin

    2013-01-01

    The purpose of this study was to explore the possibility of combining the epidermal equivalent (EE) potency assay with the assay which assesses release of interleukin-18 (IL-18) to provide a single test for identification and classification of skin sensitizing chemicals, including chemicals of low water solubility or stability. A protocol was developed using different 3D-epidermal models including in house VUMC model, epiCS® (previously EST1000™), MatTek EpiDerm™ and SkinEthic™ RHE and also the impact of different vehicles (acetone:olive oil 4:1, 1% DMSO, ethanol, water) was investigated. Following topical exposure for 24 h to 17 contact allergens and 13 non-sensitizers a robust increase in IL-18 release was observed only after exposure to contact allergens. A putative prediction model is proposed from data obtained from two laboratories yielding 95% accuracy. Correlating the in vitro EE sensitizer potency data, which assesses the chemical concentration which results in 50% cytotoxicity (EE-EC 50 ) with human and animal data showed a superior correlation with human DSA 05 (μg/cm 2 ) data (Spearman r = 0.8500; P value (two-tailed) = 0.0061) compared to LLNA data (Spearman r = 0.5968; P value (two-tailed) = 0.0542). DSA 05 = induction dose per skin area that produces a positive response in 5% of the tested population Also a good correlation was observed for release of IL-18 (SI-2) into culture supernatants with human DSA 05 data (Spearman r = 0.8333; P value (two-tailed) = 0.0154). This easily transferable human in vitro assay appears to be very promising, but additional testing of a larger chemical set with the different EE models is required to fully evaluate the utility of this assay and to establish a definitive prediction model. - Highlights: • A potential epidermal equivalent assay to label and classify sensitizers • Il-18 release distinguishes sensitizers from non sensitizers • IL-18 release can rank sensitizer potency • EC50 (chemical

  3. Black perithecial pigmentation in Fusarium species is due to the accumulation of 5-deoxybostrycoidin-based melanin

    DEFF Research Database (Denmark)

    Frandsen, Rasmus John Normand; Rasmussen, Silas Anselm; Knudsen, Peter Boldsen

    2016-01-01

    Biosynthesis of the black perithecial pigment in the filamentous fungus Fusarium graminearum is dependent on the polyketide synthase PGL1 (oPKS3). A seven-membered PGL1 gene cluster was identified by over-expression of the cluster specific transcription factor pglR. Targeted gene replacement showed...... anthrone (4) and purpurfusarin (5). The novel dimeric bostrycoidin purpurfusarin (5) was found to inhibit the growth of Candida albicans with an IC50 of 8.0 +/-1.9 mu M. The results show that Fusarium species with black perithecia have a previously undescribed form of 5-deoxybostrycoidin based melanin...

  4. Human corpus luteum: presence of epidermal growth factor receptors and binding characteristics

    International Nuclear Information System (INIS)

    Ayyagari, R.R.; Khan-Dawood, F.S.

    1987-01-01

    Epidermal growth factor receptors are present in many reproductive tissues but have not been demonstrated in the human corpus luteum. To determine the presence of epidermal growth factor receptors and its binding characteristics, we carried out studies on the plasma cell membrane fraction of seven human corpora lutea (days 16 to 25) of the menstrual cycle. Specific epidermal growth factor receptors were present in human corpus luteum. Insulin, nerve growth factor, and human chorionic gonadotropin did not competitively displace epidermal growth factor binding. The optimal conditions for corpus luteum-epidermal growth factor receptor binding were found to be incubation for 2 hours at 4 degrees C with 500 micrograms plasma membrane protein and 140 femtomol 125 I-epidermal growth factor per incubate. The number (mean +/- SEM) of epidermal growth factor binding sites was 12.34 +/- 2.99 X 10(-19) mol/micrograms protein; the dissociation constant was 2.26 +/- 0.56 X 10(-9) mol/L; the association constant was 0.59 +/- 0.12 X 10(9) L/mol. In two regressing corpora lutea obtained on days 2 and 3 of the menstrual cycle, there was no detectable specific epidermal growth factor receptor binding activity. Similarly no epidermal growth factor receptor binding activity could be detected in ovarian stromal tissue. Our findings demonstrate that specific receptors for epidermal growth factor are present in the human corpus luteum. The physiologic significance of epidermal growth factor receptors in human corpus luteum is unknown, but epidermal growth factor may be involved in intragonadal regulation of luteal function

  5. Arctigenin induced gallbladder cancer senescence through modulating epidermal growth factor receptor pathway.

    Science.gov (United States)

    Zhang, Mingdi; Cai, Shizhong; Zuo, Bin; Gong, Wei; Tang, Zhaohui; Zhou, Di; Weng, Mingzhe; Qin, Yiyu; Wang, Shouhua; Liu, Jun; Ma, Fei; Quan, Zhiwei

    2017-05-01

    Gallbladder cancer has poor prognosis and limited therapeutic options. Arctigenin, a representative dibenzylbutyrolactone lignan, occurs in a variety of plants. However, the molecular mechanisms involved in the antitumor effect of arctigenin on gallbladder cancer have not been fully elucidated. The expression levels of epidermal growth factor receptor were examined in 100 matched pairs of gallbladder cancer tissues. A positive correlation between high epidermal growth factor receptor expression levels and poor prognosis was observed in gallbladder cancer tissues. Pharmacological inhibition or inhibition via RNA interference of epidermal growth factor receptor induced cellular senescence in gallbladder cancer cells. The antitumor effect of arctigenin on gallbladder cancer cells was primarily achieved by inducing cellular senescence. In gallbladder cancer cells treated with arctigenin, the expression level of epidermal growth factor receptor significantly decreased. The analysis of the activity of the kinases downstream of epidermal growth factor receptor revealed that the RAF-MEK-ERK signaling pathway was significantly inhibited. Furthermore, the cellular senescence induced by arctigenin could be reverted by pcDNA-epidermal growth factor receptor. Arctigenin also potently inhibited the growth of tumor xenografts, which was accompanied by the downregulation of epidermal growth factor receptor and induction of senescence. This study demonstrates arctigenin could induce cellular senescence in gallbladder cancer through the modulation of epidermal growth factor receptor pathway. These data identify epidermal growth factor receptor as a key regulator in arctigenin-induced gallbladder cancer senescence.

  6. Structure-activity relationship of prenyl-substituted polyphenols from Artocarpus heterophyllus as inhibitors of melanin biosynthesis in cultured melanoma cells.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Kondo, Ryuichiro

    2007-09-01

    A series of prenylated, flavone-based polyphenols, compounds 1-8, were isolated from the wood of Artocarpus heterophyllus. These compounds, which have previously been shown not to inhibit tyrosinase activity, were found to be active inhibitors of the in vivo melanin biosynthesis in B16 melanoma cells, with little or no cytotoxicity. To clarify the structural requirement for inhibition, some structure-activity relationships were studied, in comparison with related compounds lacking prenyl side chains. Our experiments indicate that both prenyl and OH groups, as well as the type of substitution pattern, are crucial for the inhibition of melanin production in B16 melanoma cells.

  7. Estimate of the melanin content in human hairs by the inverse Monte-Carlo method using a system for digital image analysis

    International Nuclear Information System (INIS)

    Bashkatov, A N; Genina, Elina A; Kochubei, V I; Tuchin, Valerii V

    2006-01-01

    Based on the digital image analysis and inverse Monte-Carlo method, the proximate analysis method is deve-loped and the optical properties of hairs of different types are estimated in three spectral ranges corresponding to three colour components. The scattering and absorption properties of hairs are separated for the first time by using the inverse Monte-Carlo method. The content of different types of melanin in hairs is estimated from the absorption coefficient. It is shown that the dominating type of melanin in dark hairs is eumelanin, whereas in light hairs pheomelanin dominates. (special issue devoted to multiple radiation scattering in random media)

  8. Radiologic Findings of Epidermal Cysts in the Trunk

    International Nuclear Information System (INIS)

    Kim, Myung Hyun; Chung, Jae Joon; Park, Kyoung Seuk; Park, Su Mi

    2005-01-01

    To evaluate the ultrasonographic (US) or computer tomography (CT) findings of surgically proven epidermal cysts in the trunk, and to compare the echogenicity of cysts with internal contents. Forty-five patients were retrospectively evaluated. US and CT findings of epidermal cysts were assessed in regard to location, size, shape, number, echogenicity, posterior sound enhancement, internal density, septa, mural nodule and calcification, perilesional infiltration, contrast enhancement, and internal contents. All 45 patients (M:F=29:16; US in 26, CT in 19) had only one cyst, and they were located in the buttocks (n=19), back (n=13), inguinal (n=4), posterior neck (n=3), perineum (n=2), abdominal wall (n=2), presternal (n=1), and axilla (n=1). Of 26 patients who underwent US, there were 8 cases of homogeneously hypoechoic mass (30.8%), 8 of inhomogeneously hypoechoic mass (30.8%), 7 of homogeneously hypoechoic mass with internal hypoechoic lines and echogenic spots (26.9%) and 3 of homogeneously hypoechoic mass with internal echogenic spots (11.5%). Posterior sound enhancement was noted in 21 patients (80.8%). Of 19 patients who underwent CT, there were 14 cases of simple cyst (73.7%) and 5 of abscess-like lesion (26.3%). Overlying skin thickening (n=13), contrast enhancement of cystic wall (n=11), perilesional infiltration (n=7), and internal septa (n=6) were demonstrated. The internal contents of the cysts were keratinous (n=27, 60.0%) or greasy (n=15, 33.3%) material. There was no statistical significance between the echogenicity of the cysts and the internal contents (p > 0.2). Epidermal cysts showed homogeneous or inhomogeneous hypoechoic mass with posterior sound enhancement on US. There was no relationship between the echogenicity of the cysts and the internal contents. In the case of ruptured cyst, an abscess-like lesion with wall enhancement and perilesional infiltration was noted on CT scan

  9. Exudative epidermitis in pigs caused by toxigenic Staphylococcus chromogenes.

    Science.gov (United States)

    Andresen, Lars Ole; Ahrens, Peter; Daugaard, Lise; Bille-Hansen, Vivi

    2005-02-25

    Staphylococcus chromogenes is closely related to Staphylococcus hyicus, which is recognised as the causative agent of exudative epidermitis (EE) in pigs. S. chromogenes is part of the normal skin flora of pigs, cattle and poultry and has so far been considered non-pathogenic to pigs. A strain of S. chromogenes producing exfoliative toxin type B, ExhB, was identified by the use of a multiplex PCR specific for the exfoliative toxins from S. hyicus. The exfoliative toxin from S. chromogenes reacted in immunoblot analysis with polyclonal and monoclonal antibodies specific to ExhB from S. hyicus and had an apparent molecular weight of 30 kDa. Sequencing the gene encoding the exfoliative toxin from S. chromogenes revealed that the molecular weight of the toxin with the signal peptide and the mature toxin was 30,553 and 26,694 Da, respectively. Comparison of the exhB genes from S. chromogenes strain VA654 and S. hyicus strain 1289D-88 showed differences in seven base pairs of the DNA sequences and in two amino acid residues in the deduced amino acid sequences. Pigs were experimentally inoculated with S. chromogenes strain VA654. By clinical observations and histopathological evaluation of the skin alterations, all pigs revealed development of generalized exudative epidermitis. No toxin producing S. hyicus was isolated from the pigs and all ExhB-positive bacterial isolates were identified as S. chromogenes. This confirmed that the disease-causing agent was the inoculated S. chromogenes strain VA654. The results of this study show that S. chromogenes may cause exudative epidermitis in pigs.

  10. Toxic epidermal necrolysis and Stevens-Johnson syndrome

    Directory of Open Access Journals (Sweden)

    French Lars E

    2010-12-01

    Full Text Available Abstract Toxic epidermal necrolysis (TEN and Stevens Johnson Syndrome (SJS are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. Both are rare, with TEN and SJS affecting approximately 1or 2/1,000,000 annually, and are considered medical emergencies as they are potentially fatal. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Currently, TEN and SJS are considered to be two ends of a spectrum of severe epidermolytic adverse cutaneous drug reactions, differing only by their extent of skin detachment. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the aetiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Genetic susceptibility to SJS and TEN is likely as exemplified by the strong association observed in Han Chinese between a genetic marker, the human leukocyte antigen HLA-B*1502, and SJS induced by carbamazepine. Diagnosis relies mainly on clinical signs together with the histological analysis of a skin biopsy showing typical full-thickness epidermal necrolysis due to extensive keratinocyte apoptosis. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP, disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS. Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, evaluation of the prognosis

  11. Isolation and In Vitro Characterization of Epidermal Stem Cells

    DEFF Research Database (Denmark)

    Moestrup, Kasper S; Andersen, Marianne Stemann; Jensen, Kim Bak

    2017-01-01

    flow cytometry. Using markers that define the spatial origin of epidermal cells, it is possible to interrogate the specific characteristics of subpopulations of cells based on their in vivo credentials. Here, we describe how to isolate, culture, and characterize keratinocytes from murine back and tail......Colony-forming assays represent prospective methods, where cells isolated from enzymatically dissociated tissues or from tissue cultures are assessed for their proliferative capacity in vitro. Complex tissues such as the epithelial component of the skin (the epidermis) are characterized...

  12. Expression of epidermal growth factor receptors in human endometrial carcinoma

    DEFF Research Database (Denmark)

    Nyholm, H C; Nielsen, Anette Lynge; Ottesen, B

    1993-01-01

    Little data exist on the expression of epidermal growth factor receptors (EGF-Rs) in human endometrial cancer. EGF-R status was studied in 65 patients with endometrial carcinomas and in 26 women with nonmalignant postmenopausal endometria, either inactive/atrophic endometrium or adenomatous...... hyperplasia. EGF-R was identified on frozen tissue sections by means of an indirect immunoperoxidase technique with a monoclonal antibody against the external domain of the EGF-R. Seventy-one percent of the carcinomas expressed positive EGF-R immunoreactivity. In general, staining was most prominent...

  13. Acyl-CoA binding protein and epidermal barrier function

    DEFF Research Database (Denmark)

    Bloksgaard, Maria; Neess, Ditte; Færgeman, Nils J

    2014-01-01

    The acyl-CoA binding protein (ACBP) is a 10kDa intracellular protein expressed in all eukaryotic species and mammalian tissues investigated. It binds acyl-CoA esters with high specificity and affinity and is thought to act as an intracellular transporter of acyl-CoA esters between different...... includes tousled and greasy fur, development of alopecia and scaling of the skin with age. Furthermore, epidermal barrier function is compromised causing a ~50% increase in transepidermal water loss relative to that of wild type mice. Lipidomic analyses indicate that this is due to significantly reduced...

  14. Radiosensitivity of normal human epidermal cells in culture

    International Nuclear Information System (INIS)

    Dover, R.; Potten, C.S.

    1983-01-01

    Using an in vitro culture system the authors have derived #betta#-radiation survival curves over a dose range 0-8 Gy for the clonogenic cells of normal human epidermis. The culture system used allows the epidermal cells to stratify and form a multi-layered sheet of keratinizing cells. The cultures appear to be a very good model for epidermis in vivo. The survival curves show a population which is apparently more sensitive than murine epidermis in vivo. It remains unclear whether this is an intrinsic difference between the species or is a consequence of the in vitro cultivation of the human cells. (author)

  15. Inhibitory and Acceleratory Effects of Inonotus obliquus on Tyrosinase Activity and Melanin Formation in B16 Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Zheng-Fei Yan

    2014-01-01

    Full Text Available The aim of the present study is to preliminarily investigate the antimelanogenesis effect of Inonotus obliquus extracts by cell-free mushroom tyrosinase assay. It was found that petroleum ether and n-butanol extracts might contain unknown potential tyrosinase inhibitors, while its ethyl acetate extract might contain some unknown accelerators. Six compounds were isolated and their structures were identified by interpretation of NMR data and nicotinic acid was first discovered in Inonotus obliquus. In cells testing, betulin and trametenolic acid decreased tyrosinase activity and melanin content, while inotodiol and lanosterol significantly increased tyrosinase activity and melanin content, showing an AC⁡50 of 9.74 and 8.43 μM, respectively. Nicotinie acid, 3β,22,25-trihydroxy-lanosta-8-ene, had a little or no effect on tyrosinase. Betulin exhibited a mode of noncompetitive inhibition with a KI=KIS of 0.4 μM on tyrosinase activity showing an IC50 of 5.13 μM and being more effective than kojic acid (6.43 μM, and trametenolic acid exhibited a mode of mixed inhibition with a KI of 0.9 μM, KIS of 0.5 μM, and an IC50 of 7.25 μM. We proposed betulin and trametenolic acid as a new candidate of potent tyrosinase inhibitors and inotodiol and lanosterol as accelerators that could be used as therapeutic agent.

  16. Substantial Effect of Melanin Influencing Factors on In vitro Melanogenesis in Muzzle Melanocytes of Differently Colored Hanwoo.

    Science.gov (United States)

    Amna, Touseef; Park, Kyoung Mi; Cho, In-Kyung; Choi, Tae Jeong; Lee, Seung Soo; Seo, Kang-Seok; Hwang, Inho

    2012-07-01

    The present study was designed to investigate the effect of α-melanocyte-stimulating hormone (α-MSH), nitric oxide (NO) and L-cysteine on melanin production and expression of related genes MC1R, Tyr, Tyrp-1 and Tyrp-2 in muzzle melanocytes of differently colored three native Hanwoo cattle. Muzzle samples were taken from black, brindle and brown Hanwoo and purified melanocytes were cultured with α-MSH, nitric oxide and L-cysteine at 100 nM, 50 µM and 0.07 mg/ml of media respectively. The amounts of total melanin, eumelanin and mRNA expression at Tyr, Tyrp-1, Tyrp-2 and MC1R levels were quantified. α-MSH and nitric oxide significantly increased (pmuzzle melanocytes. On the contrary, L-cysteine greatly (pmuzzle melanocytes of all three phenotypes. The results of this study revealed nitric oxide and α-MSH contribute hyper-pigmentation by enhancing eumelanogenesis whereas L-cysteine contributes to pheomelanin production in different colored Hanwoo muzzle melanocytes.

  17. Haste makes waste: accelerated molt adversely affects the expression of melanin-based and depigmented plumage ornaments in house sparrows.

    Directory of Open Access Journals (Sweden)

    Csongor I Vágási

    2010-12-01

    Full Text Available Many animals display colorful signals in their integument which convey information about the quality of their bearer. Theoretically, these ornaments incur differential production and/or maintenance costs that enforce their honesty. However, the proximate mechanisms of production costs are poorly understood and contentious in cases of non-carotenoid-based plumage ornaments like the melanin-based badge and depigmented white wing-bar in house sparrows Passer domesticus. Costly life-history events are adaptively separated in time, thus, when reproduction is extended, the time available for molt is curtailed and, in turn, molt rate is accelerated.We experimentally accelerated the molt rate by shortening the photoperiod in order to test whether this environmental constraint is mirrored in the expression of plumage ornaments. Sparrows which had undergone an accelerated molt developed smaller badges and less bright wing-bars compared to conspecifics that molted at a natural rate being held at natural-like photoperiod. There was no difference in the brightness of the badge or the size of the wing-bar.These results indicate that the time available for molt and thus the rate at which molt occurs may constrain the expression of melanin-based and depigmented plumage advertisements. This mechanism may lead to the evolution of honest signaling if the onset of molt is condition-dependent through the timing of and/or trade-off between breeding and molt.

  18. Acetazolamide Inhibits the Level of Tyrosinase and Melanin: An Enzyme Kinetic, In Vitro, In Vivo, and In Silico Studies.

    Science.gov (United States)

    Abbas, Qamar; Raza, Hussain; Hassan, Mubashir; Phull, Abdul Rehman; Kim, Song Ja; Seo, Sung-Yum

    2017-09-01

    Melanin is the major factor that determines skin color and protects from ultraviolet radiation. In present study we evaluated the anti-melanogenesis effect of acetazolamide (ACZ) using four different approaches: enzyme kinetic, in vitro, in vivo and in silico. ACZ demonstrated significant inhibitory activity (IC 50 7.895 ± 0.24 μm) against tyrosinase as compared to the standard drug kojic acid (IC 50 16.84 ± 0.64 μm) and kinetic analyses showed that ACZ is a non-competitive inhibitor without cytotoxic effect. In in vitro experiments, A375 human melanoma cells were treated with 20 or 40 μm of ACZ with or without 50 μm of l-DOPA. Western blot results showed that ACZ significantly (P melanin and it could be used as a lead for developing the drugs for hyperpigmentary disorders and skin whitening. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

  19. Parental investment and its sensitivity to corticosterone is linked to melanin-based coloration in barn owls.

    Science.gov (United States)

    Almasi, Bettina; Roulin, Alexandre; Jenni-Eiermann, Susanne; Jenni, Lukas

    2008-06-01

    Behavioral and physiological responses to unpredictable changes in environmental conditions are, in part, mediated by glucocorticoids (corticosterone in birds). In polymorphic species, individuals of the same sex and age display different heritable melanin-based color morphs, associated with physiological and reproductive parameters and possibly alternative strategies to cope with variation in environmental conditions. We examined whether the role of corticosterone in resolving the trade-off between self-maintenance and reproductive activities covaries with the size of melanin-based spots displayed on the ventral body side of male barn owls. Administration of corticosterone to simulate physiological stress in males revealed pronounced changes in their food-provisioning rates to nestlings compared to control males. Corticosterone-treated males with small eumelanic spots reduced nestling provisioning rates as compared to controls, and also to a greater degree than did corticosterone-treated males with large spots. Large-spotted males generally exhibited lower parental provisioning and appear insensitive to exogenous corticosterone suggesting that the size of the black spots on the breast feathers predicts the ability to cope with stressful situations. The reduced provisioning rate of corticosterone-treated males caused a temporary reduction in nestling growth rates but, did not affect fledgling success. This suggests that moderately elevated corticosterone levels are not inhibitory to current reproduction but rather trigger behavioral responses to maximize lifetime reproductive success.

  20. A sensitive electrochemiluminescence cytosensor for quantitative evaluation of epidermal growth factor receptor expressed on cell surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Tang, Yanjuan; Zhang, Shaolian; Wen, Qingqing; Huang, Hongxing; Yang, Peihui, E-mail: typh@jnu.edu.cn

    2015-06-30

    Highlights: • EGF-cytosensor was used for evaluating EGFR expression level on cell surfaces. • CdSQDs and EGF were coated on magnetic beads (MBs) for ECL-probe. • Good sensitivity was achieved due to the signal amplification of ECL-probe. - Abstract: A sensitive electrochemiluminescence (ECL) strategy for evaluating the epidermal growth factor receptor (EGFR) expression level on cell surfaces was designed by integrating the specific recognition of EGFR expressed on MCF-7 cell surfaces with an epidermal growth factor (EGF)-funtionalized CdS quantum dots (CdSQDs)-capped magnetic bead (MB) probe. The high sensitivity of ECL probe of EGF-funtionalized CdSQD-capped-MB was used for competitive recognition with EGFR expressed on cell surfaces with recombinant EGFR protein. The changes of ECL intensity depended on both the cell number and the expression level of EGFR receptor on cell surfaces. A wide linear response to cells ranging from 80 to 4 × 10{sup 6} cells mL{sup −1} with a detection limit of 40 cells mL{sup −1} was obtained. The EGF-cytosensor was used to evaluate EGFR expression levels on MCF-7 cells, and the average number of EGFR receptor on single MCF-7 cells was 1.35 × 10{sup 5} with the relative standard deviation of 4.3%. This strategy was further used for in-situ and real-time evaluating EGFR receptor expressed on cell surfaces in response to drugs stimulation at different concentration and incubation time. The proposed method provided potential applications in the detection of receptors on cancer cells and anticancer drugs screening.

  1. Niclosamide inhibits epithelial-mesenchymal transition and tumor growth in lapatinib-resistant human epidermal growth factor receptor 2-positive breast cancer.

    Science.gov (United States)

    Liu, Junjun; Chen, Xiaosong; Ward, Toby; Mao, Yan; Bockhorn, Jessica; Liu, Xiaofei; Wang, Gen; Pegram, Mark; Shen, Kunwei

    2016-02-01

    Acquired resistance to lapatinib, a human epidermal growth factor receptor 2 kinase inhibitor, remains a clinical problem for women with human epidermal growth factor receptor 2-positive advanced breast cancer, as metastasis is commonly observed in these patients. Niclosamide, an anti-helminthic agent, has recently been shown to exhibit cytotoxicity to tumor cells with stem-like characteristics. This study was designed to identify the mechanisms underlying lapatinib resistance and to determine whether niclosamide inhibits lapatinib resistance by reversing epithelial-mesenchymal transition. Here, two human epidermal growth factor receptor 2-positive breast cancer cell lines, SKBR3 and BT474, were exposed to increasing concentrations of lapatinib to establish lapatinib-resistant cultures. Lapatinib-resistant SKBR3 and BT474 cells exhibited up-regulation of the phenotypic epithelial-mesenchymal transition markers Snail, vimentin and α-smooth muscle actin, accompanied by activation of nuclear factor-кB and Src and a concomitant increase in stem cell marker expression (CD44(high)/CD24(low)), compared to naive lapatinib-sensitive SKBR3 and BT474 cells, respectively. Interestingly, niclosamide reversed epithelial-mesenchymal transition, induced apoptosis and inhibited cell growth by perturbing aberrant signaling pathway activation in lapatinib-resistant human epidermal growth factor receptor 2-positive cells. The ability of niclosamide to alleviate stem-like phenotype development and invasion was confirmed. Collectively, our results demonstrate that lapatinib resistance correlates with epithelial-mesenchymal transition and that niclosamide inhibits lapatinib-resistant cell viability and epithelial-mesenchymal transition. These findings suggest a role of niclosamide or derivatives optimized for more favorable bioavailability not only in reversing lapatinib resistance but also in reducing metastatic potential during the treatment of human epidermal growth factor receptor

  2. Oxygen dependency of epidermal growth factor receptor binding and DNA synthesis of rat hepatocytes

    International Nuclear Information System (INIS)

    Hirose, Tetsuro; Terajima, Hiroaki; Yamauchi, Akira

    1997-01-01

    Background/Aims: Changes in oxygen availability modulate replicative responses in several cell types, but the effects on hepatocyte replication remain unclear. We have studied the effects of transient nonlethal hypoxia on epidermal growth factor receptor binding and epidermal growth factor-induced DNA synthesis of rat hepatocytes. Methods: Lactate dehydrogenase activity in culture supernatant, intracellular adenosine triphosphate content, 125 I-epidermal growth factor specific binding, epidermal growth factor receptor protein expression, and 3 H-thymidine incorporation were compared between hepatocytes cultured in hypoxia and normoxia. Results: Hypoxia up to 3 h caused no significant increase in lactate dehydrogenase activity in the culture supernatant, while intracellular adenosine triphosphate content decreased time-dependently and was restored to normoxic levels by reoxygenation (nonlethal hypoxia). Concomitantly, 125 I-epidermal growth factor specific binding to hepatocytes decreased time-dependently (to 54.1% of normoxia) and was restored to control levels by reoxygenation, although 125 I-insulin specific binding was not affected. The decrease in 125 I-epidermal growth factor specific binding was explained by the decrease in the number or available epidermal growth factor receptors (21.37±3.08 to 12.16±1.42 fmol/10 5 cells), while the dissociation constant of the receptor was not affected. The change in the number of available receptors was not considered to be due to receptor degradation-resynthesis, since immuno-detection of the epidermal growth factor receptor revealed that the receptor protein expression did not change during hypoxia and reoxygenation, and since neither actinomycin D nor cycloheximide affected the recovery of 125 I-epidermal growth factor binding by reoxygenation. Inhibition of epidermal growth factor-induced DNA synthesis after hypoxia (to 75.4% of normoxia by 3 h hypoxia) paralleled the decrease in 125 I-epidermal growth factor binding

  3. Carbon-concentrating mechanisms in seagrasses.

    Science.gov (United States)

    Larkum, Anthony William D; Davey, Peter A; Kuo, John; Ralph, Peter J; Raven, John A

    2017-06-01

    Seagrasses are unique angiosperms that carry out growth and reproduction submerged in seawater. They occur in at least three families of the Alismatales. All have chloroplasts mainly in the cells of the epidermis. Living in seawater, the supply of inorganic carbon (Ci) to the chloroplasts is diffusion limited, especially under unstirred conditions. Therefore, the supply of CO2 and bicarbonate across the diffusive boundary layer on the outer side of the epidermis is often a limiting factor. Here we discuss the evidence for mechanisms that enhance the uptake of Ci into the epidermal cells. Since bicarbonate is plentiful in seawater, a bicarbonate pump might be expected; however, the evidence for such a pump is not strongly supported. There is evidence for a carbonic anhydrase outside the outer plasmalemma. This, together with evidence for an outward proton pump, suggests the possibility that local acidification leads to enhanced concentrations of CO2 adjacent to the outer tangential epidermal walls, which enhances the uptake of CO2, and this could be followed by a carbon-concentrating mechanism (CCM) in the cytoplasm and/or chloroplasts. The lines of evidence for such an epidermal CCM are discussed, including evidence for special 'transfer cells' in some but not all seagrass leaves in the tangential inner walls of the epidermal cells. It is concluded that seagrasses have a CCM but that the case for concentration of CO2 at the site of Rubisco carboxylation is not proven. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. Epidermolytic hyperkeratosis in inflammatory linear verrucous epidermal nevus

    Directory of Open Access Journals (Sweden)

    Naser Tayyebi Meibodi

    2011-01-01

    Full Text Available Epidermolytic hyperkeratosis presents with perinuclear vacuolization of the keratinocytes in spinous and granular layers, keratinocytes with ill-defined limits, which leads to a reticulate appearance of the epidermis, an increased number of variously shaped and sized basophilic keratohyalin granules and the same sized eosinophilic trichohyalin granules, at any level of epidermis, mainly in the stratum granulosum, and compact hyperkeratosis. This minor reactive pathologic reaction pattern of skin is found in large variety of diseases. This paper is the first case report of such pattern in inflammatory linear verrucous epidermal nevus. Our case is of a 23-year-old man with pruritic verrucous lesions of trunk and extremities initiated since 13 years ago. Physical examination revealed white linear hyperkeratotic lesions, some of them on erythematous background and also classic epidermal nevus. No skeletal, ophthalmic, and nervous system involvement was detected. Microscopic study of pruritic verrucous lesions showed psoriasiform acanthosis, mild papillomatous, hyperkeratosis, and epidermolytic hyperkeratotic changes in hair follicles and acrosyrinx accompanied with moderate perivascular inflammation.

  5. A novel role of RASSF9 in maintaining epidermal homeostasis.

    Directory of Open Access Journals (Sweden)

    Chiou-Mei Lee

    Full Text Available The physiological role of RASSF9, a member of the Ras-association domain family (RASSF, is currently unclear. Here, we report a mouse line in which an Epstein-Barr virus Latent Membrane Protein 1 (LMP1 transgene insertion has created a 7.2-kb chromosomal deletion, which abolished RASSF9 gene expression. The RASSF9-null mice exhibited interesting phenotypes that resembled human ageing, including growth retardation, short lifespan, less subcutaneous adipose layer and alopecia. In the wild-type mice, RASSF9 is predominantly expressed in the epidermal keratinocytes of skin, as determined by quantitative reverse-transcription PCR, immunofluorescence and in situ hybridization. In contrast, RASSF9-/- mice presented a dramatic change in epithelial organization of skin with increased proliferation and aberrant differentiation as detected by bromodeoxyuridine incorporation assays and immunofluorescence analyses. Furthermore, characteristic functions of RASSF9-/- versus wild type (WT mouse primary keratinocytes showed significant proliferation linked to a reduction of p21Cip1 expression under growth or early differentiation conditions. Additionally, in RASSF9-/- keratinocytes there was a drastic down-modulation of terminal differentiation markers, which could be rescued by infection with a recombinant adenovirus, Adv/HA-RASSF9. Our results indicate a novel and significant role of RASSF9 in epidermal homeostasis.

  6. Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

    Science.gov (United States)

    Tamayol, Ali; Akbari, Mohsen; Zilberman, Yael; Comotto, Mattia; Lesha, Emal; Serex, Ludovic; Bagherifard, Sara; Chen, Yu; Fu, Guoqing; Ameri, Shideh Kabiri; Ruan, Weitong; Miller, Eric L; Dokmeci, Mehmet R; Sonkusale, Sameer; Khademhosseini, Ali

    2016-03-01

    Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Extraordinarily Stretchable All-Carbon Collaborative Nanoarchitectures for Epidermal Sensors

    KAUST Repository

    Cai, Yichen

    2017-06-16

    Multifunctional microelectronic components featuring large stretchability, high sensitivity, high signal-to-noise ratio (SNR), and broad sensing range have attracted a huge surge of interest with the fast developing epidermal electronic systems. Here, the epidermal sensors based on all-carbon collaborative percolation network are demonstrated, which consist 3D graphene foam and carbon nanotubes (CNTs) obtained by two-step chemical vapor deposition processes. The nanoscaled CNT networks largely enhance the stretchability and SNR of the 3D microarchitectural graphene foams, endowing the strain sensor with a gauge factor as high as 35, a wide reliable sensing range up to 85%, and excellent cyclic stability (>5000 cycles). The flexible and reversible strain sensor can be easily mounted on human skin as a wearable electronic device for real-time and high accuracy detecting of electrophysiological stimuli and even for acoustic vibration recognition. The rationally designed all-carbon nanoarchitectures are scalable, low cost, and promising in practical applications requiring extraordinary stretchability and ultrahigh SNRs.

  8. Steven johnsons syndrome and toxic epidermal necrolysis: A review

    Directory of Open Access Journals (Sweden)

    Sri ram Anne

    2014-12-01

    Full Text Available Toxic epidermal necrolysis (TEN and Stevens Johnson Syndrome (SJS are severe adverse cutaneous drug reactions that predominantly involve the skin and mucous membranes. They are characterized by mucocutaneous tenderness and typically hemorrhagic erosions, erythema and more or less severe epidermal detachment presenting as blisters and areas of denuded skin. Drugs are assumed or identified as the main cause of SJS/TEN in most cases, but Mycoplasma pneumoniae and Herpes simplex virus infections are well documented causes alongside rare cases in which the etiology remains unknown. Several drugs are at "high" risk of inducing TEN/SJS including: Allopurinol, Trimethoprim-sulfamethoxazole and other sulfonamide-antibiotics, aminopenicillins, cephalosporins, quinolones, carbamazepine, phenytoin, phenobarbital and NSAID's of the oxicam-type. Differential diagnosis includes linear IgA dermatosis and paraneoplastic pemphigus, pemphigus vulgaris and bullous pemphigoid, acute generalized exanthematous pustulosis (AGEP, disseminated fixed bullous drug eruption and staphyloccocal scalded skin syndrome (SSSS. Due to the high risk of mortality, management of patients with SJS/TEN requires rapid diagnosis, identification and interruption of the culprit drug, specialized supportive care ideally in an intensive care unit, and consideration of immunomodulating agents such as high-dose intravenous immunoglobulin therapy.

  9. Hybrid Enhanced Epidermal SpaceSuit Design Approaches

    Science.gov (United States)

    Jessup, Joseph M.

    A Space suit that does not rely on gas pressurization is a multi-faceted problem that requires major stability controls to be incorporated during design and construction. The concept of Hybrid Epidermal Enhancement space suit integrates evolved human anthropomorphic and physiological adaptations into its functionality, using commercially available bio-medical technologies to address shortcomings of conventional gas pressure suits, and the impracticalities of MCP suits. The prototype HEE Space Suit explored integumentary homeostasis, thermal control and mobility using advanced bio-medical materials technology and construction concepts. The goal was a space suit that functions as an enhanced, multi-functional bio-mimic of the human epidermal layer that works in attunement with the wearer rather than as a separate system. In addressing human physiological requirements for design and construction of the HEE suit, testing regimes were devised and integrated into the prototype which was then subject to a series of detailed tests using both anatomical reproduction methods and human subject.

  10. Extraordinarily Stretchable All-Carbon Collaborative Nanoarchitectures for Epidermal Sensors

    KAUST Repository

    Cai, Yichen; Shen, Jie; Dai, Ziyang; Zang, Xiaoxian; Dong, Qiuchun; Guan, Guofeng; Li, Lain-Jong; Huang, Wei; Dong, Xiaochen

    2017-01-01

    Multifunctional microelectronic components featuring large stretchability, high sensitivity, high signal-to-noise ratio (SNR), and broad sensing range have attracted a huge surge of interest with the fast developing epidermal electronic systems. Here, the epidermal sensors based on all-carbon collaborative percolation network are demonstrated, which consist 3D graphene foam and carbon nanotubes (CNTs) obtained by two-step chemical vapor deposition processes. The nanoscaled CNT networks largely enhance the stretchability and SNR of the 3D microarchitectural graphene foams, endowing the strain sensor with a gauge factor as high as 35, a wide reliable sensing range up to 85%, and excellent cyclic stability (>5000 cycles). The flexible and reversible strain sensor can be easily mounted on human skin as a wearable electronic device for real-time and high accuracy detecting of electrophysiological stimuli and even for acoustic vibration recognition. The rationally designed all-carbon nanoarchitectures are scalable, low cost, and promising in practical applications requiring extraordinary stretchability and ultrahigh SNRs.

  11. Growth of melanocytes in human epidermal cell cultures

    International Nuclear Information System (INIS)

    Staiano-Coico, L.; Hefton, J.M.; Amadeo, C.; Pagan-Charry, I.; Madden, M.R.; Cardon-Cardo, C.

    1990-01-01

    Epidermal cell cultures were grown in keratinocyte-conditioned medium for use as burn wound grafts; the melanocyte composition of the grafts was studied under a variety of conditions. Melanocytes were identified by immunohistochemistry based on a monoclonal antibody (MEL-5) that has previously been shown to react specifically with melanocytes. During the first 7 days of growth in primary culture, the total number of melanocytes in the epidermal cultures decreased to 10% of the number present in normal skin. Beginning on day 2 of culture, bipolar melanocytes were present at a mean cell density of 116 +/- 2/mm2; the keratinocyte to melanocyte ratio was preserved during further primary culture and through three subpassages. Moreover, exposure of cultures to mild UVB irradiation stimulated the melanocytes to proliferate, suggesting that the melanocytes growing in culture maintained their responsiveness to external stimuli. When the sheets of cultured cells were enzymatically detached from the plastic culture flasks before grafting, melanocytes remained in the basal layer of cells as part of the graft applied to the patient

  12. Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo-epidermal separation of 4 mm human skin biopsies

    DEFF Research Database (Denmark)

    Clemmensen, Anders; Thomassen, Mads; Clemmensen, Ole

    2009-01-01

    To obtain a separation of the epidermal and dermal compartments to examine compartment specific biological mechanisms in the skin, we incubated 4 mm human skin punch biopsies in ammonium thiocyanate. We wanted to test (i) the histological quality of the dermo-epidermal separation obtained...... by different incubation times; (ii) the amount and quality of extractable epidermal RNA and (iii) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30-min incubation, the split between dermis and epidermis...... and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove...

  13. Identification of SLURP-1 as an epidermal neuromodulator explains the clinical phenotype of Mal de Meleda

    DEFF Research Database (Denmark)

    Chimienti, Fabrice; Hogg, Ronald C; Plantard, Laure

    2003-01-01

    alpha 7 nicotinic acetylcholine receptors that are present in keratinocytes. These results identify SLURP-1 as a secreted epidermal neuromodulator which is likely to be essential for both epidermal homeostasis and inhibition of TNF-alpha release by macrophages during wound healing. This explains both...

  14. Periostin contributes to epidermal hyperplasia in psoriasis common to atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Kazuhiko Arima

    2015-01-01

    Conclusions: Periostin plays an important role during epidermal hyperplasia in IMQ-induced skin inflammation, independently of the IL-23–IL-17/IL-22 axis. Periostin appears to be a mediator for epidermal hyperplasia that is common to AD and psoriasis.

  15. Enrichment of unlabeled human Langerhans cells from epidermal cell suspensions by discontinuous density gradient centrifugation

    NARCIS (Netherlands)

    Teunissen, M. B.; Wormmeester, J.; Kapsenberg, M. L.; Bos, J. D.

    1988-01-01

    In this report we introduce an alternative procedure for enrichment of human epidermal Langerhans cells (LC) from epidermal cell suspensions of normal skin. By means of discontinuous Ficoll-Metrizoate density gradient centrifugation, a fraction containing high numbers of viable, more than 80% pure

  16. Determination of catechol O-methyltransferase activity in relation to melanin metabolism using high-performance liquid chromatography with fluorimetric detection

    NARCIS (Netherlands)

    Smit, N. P.; Pavel, S.; Kammeyer, A.; Westerhof, W.

    1990-01-01

    A new sensitive method for the determination of catechol O-methyltransferase activity has been developed. The method is based on the O-methylation of the indolic intermediates of melanin metabolism. The substrate, 5,6-dihydroxyindole-2-carboxylic acid, is converted by the enzyme to two O-methylated

  17. Investigating the role of melanin in UVA/UVB- and hydrogen peroxide-induced cellular and mitochondrial ROS production and mitochondrial DNA damage in human melanoma cells.

    Science.gov (United States)

    Swalwell, Helen; Latimer, Jennifer; Haywood, Rachel M; Birch-Machin, Mark A

    2012-02-01

    Skin cancer incidence is dramatically increasing worldwide, with exposure to ultraviolet radiation (UVR) a predominant factor. The UVA component initiates oxidative stress in human skin, although its exact role in the initiation of skin cancer, particularly malignant melanoma, remains unclear and is controversial because there is evidence for a melanin-dependent mechanism in UVA-linked melanoma studies. Nonpigmented (CHL-1, A375), moderately pigmented (FM55, SKmel23), and highly pigmented (FM94, hyperpigmented FM55) human melanoma cell lines have been used to investigate UVA-induced production of reactive oxygen species using FACS analysis, at both the cellular (dihydrorhodamine-123) and the mitochondrial (MitoSOX) level, where most cellular stress is generated. For the first time, downstream mtDNA damage (utilizing a quantitative long-PCR assay) has been investigated. Using UVA, UVB, and H(2)O(2) as cellular stressors, we have explored the dual roles of melanin as a photoprotector and photosensitizer. The presence of melanin has no influence over cellular oxidative stress generation, whereas, in contrast, melanin protects against mitochondrial superoxide generation and mtDNA damage (one-way ANOVA with post hoc Tukey's analysis, Pmelanin binds directly to DNA, it acts as a direct photosensitizer of mtDNA damage during UVA irradiation (Pmelanin. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Discovering the role of the apolipoprotein gene and the genes in the putative pullulan biosynthesis pathway on the synthesis of pullulan, heavy oil and melanin in Aureobasidium pullulans.

    Science.gov (United States)

    Guo, Jian; Huang, Siyao; Chen, Yefu; Guo, Xuewu; Xiao, Dongguang

    2017-12-18

    Pullulan produced by Aureobasidium pullulans presents various applications in food manufacturing and pharmaceutical industry. However, the pullulan biosynthesis mechanism remains unclear. This work proposed a pathway suggesting that heavy oil and melanin may correlate with pullulan production. The effects of overexpression or deletion of genes encoding apolipoprotein, UDPG-pyrophosphorylase, glucosyltransferase, and α-phosphoglucose mutase on the production of pullulan, heavy oil, and melanin were examined. Pullulan production increased by 16.93 and 8.52% with the overexpression of UDPG-pyrophosphorylase and apolipoprotein genes, respectively. Nevertheless, the overexpression or deletion of other genes exerted little effect on pullulan biosynthesis. Heavy oil production increased by 146.30, 64.81, and 33.33% with the overexpression of UDPG-pyrophosphorylase, α-phosphoglucose mutase, and apolipoprotein genes, respectively. Furthermore, the syntheses of pullulan, heavy oil, and melanin can compete with one another. This work may provide new guidance to improve the production of pullulan, heavy oil, and melanin through genetic approach.

  19. Excision of pyrimidine dimers from epidermal DNA and nonsemiconservative epidermal DNA synthesis following ultraviolet irradiation of mouse skin

    International Nuclear Information System (INIS)

    Bowden, G.T.; Trosko, J.E.; Shapas, B.G.; Boutwell, R.K.

    1975-01-01

    Pyrimidine dimer production and excision in epidermal DNA were studied at five different dose levels of ultraviolet light in the skin of intact mice. Dimer production increased with dose up to 50,400 ergs/sq mm. Approximately 30 percent of the thymine-containing dimers were excised by 24 hr after irradiation at three lower dose levels of ultraviolet light. Nonsemiconservative DNA replication in ultraviolet-irradiated mouse skin was shown to continue for at least 18 hr. The rate of nonsemiconservative replication decreased with time, but did so slowly. The initial rates of nonsemiconservative replication increased with ultraviolet light dose levels up to about 4200 ergs/sq mm, after which the initial rates were decreased. Semiconservative epidermal DNA synthesis was shown to be inhibited by hydroxyurea, but hydroxyurea had no effect on ultraviolet light-induced nonsemiconservative DNA replication. The observed pyrimidine dimer excision and nonsemiconservative DNA replication suggest that in the intact mouse the cells of the epidermis are capable of DNA excision repair after ultraviolet irradiation of mouse skin

  20. Epidermal growth factor in alkali-burned corneal epithelial wound healing.

    Science.gov (United States)

    Singh, G; Foster, C S

    1987-06-15

    We conducted a double-masked study to evaluate the effect of epidermal growth factor on epithelial wound healing and recurrent erosions in alkali-burned rabbit corneas. Epithelial wounds 10 mm in diameter healed completely under the influence of topical epidermal growth factor, whereas the control corneas did not resurface in the center. On reversal of treatment, the previously nonhealing epithelial defects healed when treated with topical epidermal growth factor eyedrops. Conversely, the epidermal growth factor-treated and resurfaced corneas developed epithelial defects when treatment was discontinued. Histopathologic examination disclosed hyperplastic epithelium growing over the damaged stroma laden with polymorphonuclear leukocytes when treated with epidermal growth factor eyedrops, but it did not adhere to the underlying tissue. Hydropic changes were seen intracellularly as well as between the epithelial cells and the stroma.

  1. Effects of Wnt3a on proliferation and differentiation of human epidermal stem cells

    International Nuclear Information System (INIS)

    Jia Liwei; Zhou Jiaxi; Peng Sha; Li Juxue; Cao Yujing; Duan Enkui

    2008-01-01

    Epidermal stem cells maintain development and homeostasis of mammalian epidermis throughout life. However, the molecular mechanisms involved in the proliferation and differentiation of epidermal stem cells are far from clear. In this study, we investigated the effects of Wnt3a and Wnt/β-catenin signaling on proliferation and differentiation of human fetal epidermal stem cells. We found both Wnt3a and active β-catenin, two key members of the Wnt/β-catenin signaling, were expressed in human fetal epidermis and epidermal stem cells. In addition, Wnt3a protein can promote proliferation and inhibit differentiation of epidermal stem cells in vitro culture. Our results suggest that Wnt/β-catenin signaling plays important roles in human fetal skin development and homeostasis, which also provide new insights on the molecular mechanisms of oncogenesis in human epidermis

  2. Penile epidermal inclusion cyst: a late complication of penile girth enhancement surgery.

    Science.gov (United States)

    Park, Hyun Jun; Park, Nam Cheol; Park, Sung Woo; Jern, Tae Kyung; Choi, Kyung-Un

    2008-09-01

    Epidermal inclusion cysts are benign lesions that can develop in any part of the body. However, the finding of an epidermal inclusion cyst in the penis is rare. The aim of this article was to present the management of a case of a penile epidermal inclusion cyst that occurred because of late complications of a penile girth enhancement surgery. A 52-year-old man presented with a painless, slowly growing mass in the penis, which was first noted after a penile girth enhancement surgery 20 years ago. A cystic mobile mass about 2 cm in depth was found surrounding the coronal sulcus. Excision of the mass was performed for diagnosis and treatment. There was no communication with the urethra. The pathological diagnosis was an epidermal inclusion cyst of the penis. A penile epidermal inclusion cyst in adult men is rare. It can develop after an inadequate procedure for penile girth enhancement, and should be treated by complete resection.

  3. Epidermal stem cells response to radiative genotoxic stress

    International Nuclear Information System (INIS)

    Marie, Melanie

    2013-01-01

    Human skin is the first organ exposed to various environmental stresses, which requires the development by skin stem cells of specific mechanisms to protect themselves and to ensure tissue homeostasis. As stem cells are responsible for the maintenance of epidermis during individual lifetime, the preservation of genomic integrity in these cells is essential. My PhD aimed at exploring the mechanisms set up by epidermal stem cells in order to protect themselves from two genotoxic stresses, ionizing radiation (Gamma Rays) and ultraviolet radiation (UVB). To begin my PhD, I have taken part of the demonstration of protective mechanisms used by keratinocyte stem cells after ionizing radiation. It has been shown that these cells are able to rapidly repair most types of radiation-induced DNA damage. Furthermore, we demonstrated that this repair is activated by the fibroblast growth factor 2 (FGF2). In order to know if this protective mechanism is also operating in cutaneous carcinoma stem cells, we investigated the response to gamma Rays of carcinoma stem cells isolated from a human carcinoma cell line. As in normal keratinocyte stem cells, we demonstrated that cancer stem cells could rapidly repair radio-induced DNA damage. Furthermore, fibroblast growth factor 2 also mediates this repair, notably thanks to its nuclear isoforms. The second project of my PhD was to study human epidermal stem cells and progenitors responses to UVB radiation. Once cytometry and irradiation conditions were set up, the toxicity of UVB radiation has been evaluate in the primary cell model. We then characterized UVB photons effects on cell viability, proliferation and repair of DNA damage. This study allowed us to bring out that responses of stem cells and their progeny to UVB are different, notably at the level of part of their repair activity of DNA damage. Moreover, progenitors and stem cells transcriptomic responses after UVB irradiation have been study in order to analyze the global

  4. Transcription factor VdCmr1 is required for pigment production, protection from UV irradiation, and regulates expression of melanin biosynthetic genes in Verticillium dahliae.

    Science.gov (United States)

    Wang, Yonglin; Hu, Xiaoping; Fang, Yulin; Anchieta, Amy; Goldman, Polly H; Hernandez, Gustavo; Klosterman, Steven J

    2018-04-01

    Verticillium dahliae is a soilborne fungus that causes vascular wilt diseases on numerous plant species worldwide. The production of darkly melanized microsclerotia is crucial in the disease cycle of V. dahliae, as these structures allow for long-term survival in soil. Previously, transcriptomic and genomic analysis identified a cluster of genes in V. dahliae that encodes some dihydroxynaphthalene (DHN) melanin biosynthetic pathway homologues found in related fungi. In this study, we explored the roles of cluster-specific transcription factor VdCmr1, as well as two other genes within the cluster encoding a polyketide synthase (VdPKS1) and a laccase (VdLac1), enzymes at initial and endpoint steps in DHN melanin production. The results revealed that VdCmr1 and VdPKS1 are required for melanin production, but neither is required for microsclerotia production. None of the three genes were required for pathogenesis on tobacco and lettuce. Exposure of ΔVdCmr1 and wild-type strains to UV irradiation, or to high temperature (40 °C), revealed an approx. 50 % reduction of survival in the ΔVdCmr1 strain, relative to the wild-type strain, in response to either condition. Expression profiles revealed that expression of some melanin biosynthetic genes are in part dependent on VdCmr1. Combined data indicate VdCmr1 is a key regulator of melanin biosynthesis, and that via regulation of melanogenesis, VdCmr1 affects survival of V. dahliae in response to abiotic threats. We conclude with a model showing regulation of VdCmr1 by a high osmolarity glycerol response (Hog)-type MAP kinase pathway.

  5. Towards the development of a novel bioinspired functional material: synthesis and characterization of hybrid TiO2/DHICA-melanin nanoparticles.

    Science.gov (United States)

    Pezzella, Alessandro; Capelli, Luigia; Costantini, Aniello; Luciani, Giuseppina; Tescione, Fabiana; Silvestri, Brigida; Vitiello, Giuseppe; Branda, Francesco

    2013-01-01

    A large number of recent literature data focus on modification/modulation of surface chemistry of inorganic materials in order to improve their functional properties. Melanins, a wide class of natural pigments, are recently emerging as a powerful organic component for developing bioinspired active material for a large number of applications from organoelectronics to bioactive compounds. Here we report the use of the approach referred as "chimie douce", involving in situ formation of the hybrids through reactions of precursors under mild conditions, to prepare novel hybrid functional architectures based on eumelanin like 5,6 dihydroxyindole-2-carboxylic acid (DHICA) polymer and TiO2. Two synthesis procedures were carried out to get DHICA-melanin coated TiO2 nanoparticles as well as mixed DHICA/TiO2 hybrid nanostructures. Such systems were characterized through EPR, FT-IR and fluorescence spectroscopy, thermogravimetric analysis (TGA), X-ray diffraction (XRD), and TEM microscopy in order to assess the effect of synthesis path as well as of DHICA content on structural, morphological and optical properties of TiO2 nanostructures. In particular, EPR, FT-IR spectra and TGA analysis confirmed the presence of DHICA-melanin in these samples. TEM measurements indicated the formation of the nanoparticles having relatively narrow size distribution with average particle size of about 10nm. DHICA-melanin does act as a morphological agent affecting morphology of hybrid nanostructures. XRD analysis proved that TiO2 hybrid nanoparticles kept anatase structures for DHICA-melanin contents within the range of investigated compositions, i.e. up to 50% wt/wt. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. Tissue remodeling induced by hypersecreted epidermal growth factor and amphiregulin in the airway after an acute asthma attack.

    Science.gov (United States)

    Enomoto, Yukinori; Orihara, Kanami; Takamasu, Tetsuya; Matsuda, Akio; Gon, Yasuhiro; Saito, Hirohisa; Ra, Chisei; Okayama, Yoshimichi

    2009-11-01

    Epidermal growth factor receptor ligands, such as epidermal growth factor (EGF) and amphiregulin, may play key roles in tissue remodeling in asthma. However, the kinetics of EGF and amphiregulin secretion in the airway after an acute asthma attack and the effect of prolonged airway exposure to these ligands on airway remodeling are unknown. To measure the EGF and amphiregulin concentrations in sputa obtained from patients with asthma under various conditions, and to examine the effects of EGF and amphiregulin on the proliferation or differentiation of airway structural cells. Epidermal growth factor and amphiregulin levels were measured by ELISA in sputum specimens collected from 14 hospitalized children with asthma during an acute asthma attack, 13 stable outpatients with asthma, 8 healthy control children, and 7 children with respiratory tract infections. The effects of EGF and amphiregulin on the proliferation and/or differentiation of normal human bronchial epithelial cells (NHBE), bronchial smooth muscle cells (BSMC), and normal human lung fibroblasts (NHLF) were examined. The sputum levels of EGF were significantly higher for about a week after an acute asthma attack compared with the levels in stable subjects with asthma and control subjects. In contrast, upregulation of amphiregulin in the sputa of patients with asthma was observed only during the acute attack. EGF caused proliferation of NHBE, BSMC, and NHLF, whereas amphiregulin induced proliferation of only NHBE. Prolonged exposure of NHBE to EGF and amphiregulin induced mucous cell metaplasia in an IL-13-independent manner. Acute asthma attacks are associated with hypersecretion of EGF and amphiregulin in the airway. Recurrent acute attacks may aggravate airway remodeling.

  7. Effects of disrupting the polyketide synthase gene WdPKS1 in Wangiella [Exophiala] dermatitidis on melanin production and resistance to killing by antifungal compounds, enzymatic degradation, and extremes in temperature

    Directory of Open Access Journals (Sweden)

    Mandal Piyali

    2006-06-01

    Full Text Available Abstract Background Wangiella dermatitidis is a human pathogenic fungus that is an etiologic agent of phaeohyphomycosis. W. dermatitidis produces a black pigment that has been identified as a dihydroxynaphthalene melanin and the production of this pigment is associated with its virulence. Cell wall pigmentation in W. dermatitidis depends on the WdPKS1 gene, which encodes a polyketide synthase required for generating the key precursor for dihydroxynaphthalene melanin biosynthesis. Results We analyzed the effects of disrupting WdPKS1 on dihydroxynaphthalene melanin production and resistance to antifungal compounds. Transmission electron microscopy revealed that wdpks1Δ-1 yeast had thinner cell walls that lacked an electron-opaque layer compared to wild-type cells. However, digestion of the wdpks1Δ-1 yeast revealed small black particles that were consistent with a melanin-like compound, because they were acid-resistant, reacted with melanin-binding antibody, and demonstrated a free radical signature by electron spin resonance analysis. Despite lacking the WdPKS1 gene, the mutant yeast were capable of catalyzing the formation of melanin from L-3,4-dihyroxyphenylalanine. The wdpks1Δ-1 cells were significantly more susceptible to killing by voriconazole, amphotericin B, NP-1 [a microbicidal peptide], heat and cold, and lysing enzymes than the heavily melanized parental or complemented strains. Conclusion In summary, W. dermatitidis makes WdPKS-dependent and -independent melanins, and the WdPKS1-dependent deposition of melanin in the cell wall confers protection against antifungal agents and environmental stresses. The biological role of the WdPKS-independent melanin remains unclear.

  8. Accumulation of dietary and aqueous cadmium into the epidermal mucus of the discus fish Symphysodon sp

    International Nuclear Information System (INIS)

    Maunder, Richard J.; Buckley, Jonathan; Val, Adalberto L.; Sloman, Katherine A.

    2011-01-01

    The discus fish Symphysodon sp. is an Amazonian cichlid with a unusual form of parental care where fry obligately feed from parental mucus for the first few weeks of life. Here, we investigated the possible impact of environmental cadmium on this species, particularly with respect to mucus contamination. We exposed groups of fish to cadmium either through their food (400 mg kg -1 ) or through the water (3 μg l -1 ) for 4 weeks, and measured tissue concentrations and ATPase activities at weekly intervals. Cadmium significantly accumulated in all tissues (except for muscle) after 7 days, and tissue concentrations increased until the end of the experiment. Significant alterations in ATPase activities of intestine and kidney were observed at day 7 and 14, but no alterations in gill ATPase activities occurred. The epidermal mucus showed a high accumulation of cadmium from both exposures, but particularly from the diet, indicating that dietary cadmium can be transferred from gut to mucus. Combining this data with approximations of fry bite volumes and bite frequencies, we constructed daily estimates of the cadmium that could potentially be consumed by newly hatched fry feeding on this mucus. These calculations suggest that feeding fry might consume up to 11 μg g -1 day -1 , and hence indicate that this species' dependency on parental mucus feeding of fry could make them particularly susceptible to cadmium contamination of their native habitat.

  9. Possible physiological role of milk epidermal growth factor in neonatal eyelid opening

    International Nuclear Information System (INIS)

    Tsutsumi, O.; Tsutsumi, A.; Oka, T.

    1987-01-01

    The eyelid opening of newborn mice occurs normally on day 13.9 +/- 1.8 after birth. When newborn mice were injected with anti-epidermal growth factor (EGF) antibody every other day starting on day 1 after birth, the eyelid opening was delayed by ∼ 3 days. The effect of anti-EGF became less prominent as the treatment was started at later times: when it was give from day 7, no delay in eyelid opening was observed. On the other hand, eyelid opening was enhanced by ∼ 3 days by EGF injection given on day 3 for every other day. This effect of EGF was antagonized by simultaneous administration of anti-EGF antibody. EGF was present at a concentration of 6.6 ng/ml in the plasma of 1-wk-old pups nursed by their mother, but it was not detectable in the plasma of 3-wk-old weaned pups. EGF concentration in the submandibular glands, however, was 17 times greater in 3- than in 1-wk-old pups. EGF was measured by radioimmunoassay. These results suggest that milk EGF may play a physiological role in eyelid opening during the neonatal period

  10. Accumulation of dietary and aqueous cadmium into the epidermal mucus of the discus fish Symphysodon sp

    Energy Technology Data Exchange (ETDEWEB)

    Maunder, Richard J., E-mail: richard.maunder@astrazeneca.com [School of Marine Science and Engineering, University of Plymouth, Drake Circus, Plymouth, PL4 8AA (United Kingdom); Buckley, Jonathan, E-mail: jonathan.buckley@plymouth.ac.uk [School of Marine Science and Engineering, University of Plymouth, Drake Circus, Plymouth, PL4 8AA (United Kingdom); Val, Adalberto L., E-mail: dalval@inpa.gov.br [Department of Ecology, Laboratory of Ecophysiology and Molecular Evolution, INPA, Manaus (Brazil); Sloman, Katherine A., E-mail: katherine.sloman@uws.ac.uk [School of Science, University of the West of Scotland, Paisley, PA1 2BE, Scotland (United Kingdom)

    2011-06-15

    The discus fish Symphysodon sp. is an Amazonian cichlid with a unusual form of parental care where fry obligately feed from parental mucus for the first few weeks of life. Here, we investigated the possible impact of environmental cadmium on this species, particularly with respect to mucus contamination. We exposed groups of fish to cadmium either through their food (400 mg kg{sup -1}) or through the water (3 {mu}g l{sup -1}) for 4 weeks, and measured tissue concentrations and ATPase activities at weekly intervals. Cadmium significantly accumulated in all tissues (except for muscle) after 7 days, and tissue concentrations increased until the end of the experiment. Significant alterations in ATPase activities of intestine and kidney were observed at day 7 and 14, but no alterations in gill ATPase activities occurred. The epidermal mucus showed a high accumulation of cadmium from both exposures, but particularly from the diet, indicating that dietary cadmium can be transferred from gut to mucus. Combining this data with approximations of fry bite volumes and bite frequencies, we constructed daily estimates of the cadmium that could potentially be consumed by newly hatched fry feeding on this mucus. These calculations suggest that feeding fry might consume up to 11 {mu}g g{sup -1} day{sup -1}, and hence indicate that this species' dependency on parental mucus feeding of fry could make them particularly susceptible to cadmium contamination of their native habitat.

  11. 3-Prenyl luteolin, a new prenylated flavone with melanin biosynthesis inhibitory activity from wood of Artocarpus heterophyllus.

    Science.gov (United States)

    Arung, Enos Tangke; Shimizu, Kuniyoshi; Tanaka, Hiroyuki; Kondo, Ryuichiro

    2010-09-01

    In our efforts to find new whitening agent from natural resources, we focused on wood of Artocarpus heterophyllus which shows anti-melanogenesis activity. By activity-guided fractionation of A. heterophyllus wood extract, a new prenylated flavonoid, 3-prenyl luteolin (1) was isolated. The IC(50) of mushroom tyrosinase inhibitory activity of 1 was 76.3 microM. The results of the comparison with that of luteolin showed the prenyl substituent at C-3 position of 1 play an important role for revealing tyrosinase inhibition. In melanin formation inhibition on B16 melanoma cells, IC(50) of 1 was 56.7 microM with less cytotoxicity. Copyright (c) 2010 Elsevier B.V. All rights reserved.

  12. Perforated Sigmoid Diverticulitis in the Presence of Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    P. Heye

    2014-02-01

    Full Text Available Even though the incidence of toxic epidermal necrolysis (TEN is low, it is also associated with a high mortality rate. The condition predominantly affects the skin, but may also affect the gastrointestinal tract, dramatically increasing mortality. We present a case of perforated sigmoid diverticulitis in the presence of TEN. The patient was taking medication, known to be a risk factor, and presented an affected total body surface area and temporal development similar to previously reported cases of TEN. Characteristic abdominal symptoms, however, were missing. Gastrointestinal involvement in TEN appears to be a poor prognostic factor; medical staff must therefore be alert to patients with TEN who complain of abdominal discomfort. The exact pathogenesis, however, remains unclear.

  13. Epidermal Growth Factor Receptor (EGFR) Crosstalks in Liver Cancer

    International Nuclear Information System (INIS)

    Berasain, Carmen; Latasa, María Ujue; Urtasun, Raquel; Goñi, Saioa; Elizalde, María; Garcia-Irigoyen, Oihane; Azcona, María; Prieto, Jesús; Ávila, Matías A.

    2011-01-01

    Hepatocarcinogenesis is a complex multistep process in which many different molecular pathways have been implicated. Hepatocellular carcinoma (HCC) is refractory to conventional chemotherapeutic agents, and the new targeted therapies are meeting with limited success. Interreceptor crosstalk and the positive feedback between different signaling systems are emerging as mechanisms of targeted therapy resistance. The identification of such interactions is therefore of particular relevance to improve therapeutic efficacy. Among the different signaling pathways activated in hepatocarcinogenesis the epidermal growth factor receptor (EGFR) system plays a prominent role, being recognized as a “signaling hub” where different extracellular growth and survival signals converge. EGFR can be transactivated in response to multiple heterologous ligands through the physical interaction with multiple receptors, the activity of intracellular kinases or the shedding of EGFR-ligands. In this article we review the crosstalk between the EGFR and other signaling pathways that could be relevant to liver cancer development and treatment

  14. Epidermal segmentation in high-definition optical coherence tomography.

    Science.gov (United States)

    Li, Annan; Cheng, Jun; Yow, Ai Ping; Wall, Carolin; Wong, Damon Wing Kee; Tey, Hong Liang; Liu, Jiang

    2015-01-01

    Epidermis segmentation is a crucial step in many dermatological applications. Recently, high-definition optical coherence tomography (HD-OCT) has been developed and applied to imaging subsurface skin tissues. In this paper, a novel epidermis segmentation method using HD-OCT is proposed in which the epidermis is segmented by 3 steps: the weighted least square-based pre-processing, the graph-based skin surface detection and the local integral projection-based dermal-epidermal junction detection respectively. Using a dataset of five 3D volumes, we found that this method correlates well with the conventional method of manually marking out the epidermis. This method can therefore serve to effectively and rapidly delineate the epidermis for study and clinical management of skin diseases.

  15. Exudative epidermitis in pigs caused by toxigenic Staphylococcus chromogenes

    DEFF Research Database (Denmark)

    Andresen, Lars Ole; Ahrens, Peter; Daugaard, Lise

    2005-01-01

    Staphylococcus chromogenes is closely related to Staphylococcus hyicus, which is recognised as the causative agent of exudative epidermitis (EE) in pigs. S. chromogenes is part of the normal skin flora of pigs, cattle and poultry and has so far been considered non-pathogenic to pigs. A strain of S....... chromogenes producing exfoliative toxin type B, ExhB, was identified by the use of a multiplex PCR specific for the exfoliative toxins from S. hyicus. The exfoliative toxin from S. chromogenes reacted in immunoblot analysis with polyclonal and monoclonal antibodies specific to ExhB from S. hyicus and had...... an apparent molecular weight of 30 kDa. Sequencing the gene encoding the exfoliative toxin from S. chromogenes revealed that the molecular weight of the toxin with the signal peptide and the mature toxin was 30,553 and 26,694 Da, respectively. Comparison of the exhB genes from S. chromogenes strain VA654...

  16. EPIDERMAL CHARACTERS OF BACCHARIS (ASTERACEAE SPECIES USED IN TRADITIONAL MEDICINE

    Directory of Open Access Journals (Sweden)

    FREIRE SUSANA E.

    2007-06-01

    Full Text Available A morphological study of 38 species of Baccharis used in traditional medicinewas carried out to provide some epidermal characters that will contribute to theknowledge of the genus. The present study revealed: 1 seven different types oftrichomes: conical, aseptate fl agellate, fi liform fl agellate, 1-armed, 2-4-armed,bulbiferous fl agellate, and glandular biseriate; 2 that 28 of the total of 38 specieshave trichomes in tufts; 3 six different types of stomata: anomocytic, anisocytic,cyclocytic, actinocytic, tetracytic, and staurocytic; 4 that some trichome types,such as 2-4-armed (B. dracunculifolia and aseptate fl agellate branched (B. trinervis,show a high diagnostic value; 5 that the stomata types can be used to differentiatespecies with similar trichomes type (e.g. B. trimera and B. articulata.Illustrations of the studied characters are provided.

  17. Epidermal growth factor pathway substrate 15, Eps15

    DEFF Research Database (Denmark)

    Salcini, A E; Chen, H; Iannolo, G

    1999-01-01

    Eps15 was originally identified as a substrate for the kinase activity of the epidermal growth factor receptor (EGFR). Eps15 has a tripartite structure comprising a NH2-terminal portion, which contains three EH domains, a central putative coiled-coil region, and a COOH-terminal domain containing...... multiple copies of the amino acid triplet Aspartate-Proline-Phenylalanine. A pool of Eps15 is localized at clathrin coated pits where it interacts with the clathrin assembly complex AP-2 and a novel AP-2 binding protein, Epsin. Perturbation of Eps15 and Epsin function inhibits receptor-mediated endocytosis...... of EGF and transferrin, demonstrating that both proteins are components of the endocytic machinery. Since the family of EH-containing proteins is implicated in various aspects of intracellular sorting, biomolecular strategies aimed at interfering with these processes can now be envisioned...

  18. Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells

    International Nuclear Information System (INIS)

    Belsito, D.V.; Baer, R.L.; Thorbecke, G.J.; Gigli, I.

    1984-01-01

    The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics

  19. Analysis of E2F factors during epidermal differentiation.

    Science.gov (United States)

    Chang, Wing Y; Dagnino, Lina

    2005-01-01

    The multigene E2F family of transcription factors is central in the control of cell cycle progression. The expression and activity of E2F proteins is tightly regulated transcriptionally and posttranslationally as a function of the proliferation and differentiation status of the cell. In this chapter, we review protocols designed to determine E2F mRNA abundance in tissues by in situ hybridization techniques. The ability to culture primary epidermal keratinocytes and maintain them as either undifferentiated or terminally differentiated cells allows the biochemical and molecular characterization of changes in E2F expression and activity. Thus, we also discuss in detail methods to analyze E2F protein abundance by immunoblot and their ability to bind DNA in cultured cells using electrophoretic mobility shift assays.

  20. Collagen sheet dressings for cutaneous lesions of toxic epidermal necrolysis

    Directory of Open Access Journals (Sweden)

    S Bhattacharya

    2011-01-01

    Full Text Available Toxic epidermal necrolysis (TEN is associated with a significant mortality of 30-50% and long-term sequelae. Treatment includes early admission to a burn unit, where management with precise fluid, electrolyte, protein, and energy supplementation, moderate mechanical ventilation, and expert wound care can be provided. Specific treatment with immunosuppressive drugs or immunoglobulins did not show an improved outcome in most studies and remains controversial. We have treated the cutaneous lesions of seven patients of TEN with collagen sheet dressings and have found a significant reduction in morbidity. The sheets are a one-time dressing, easy to apply and they reduce fluid loss, prevent infection, reduce pain, avoid repeated dressings and gradually peal off as the underlying lesions heal.