Stimulation Of Melanocytes Research Articles

Vitiligo: From Pathogenesis to Treatment.

Recent advances in vitiligo have provided promising treatment options, particularly through understanding the immune-mediated mechanisms leading to depigmentation. The inflammatory components in both vitiligo (non-segmental) and segmental vitiligo have similarities. Both are believed to result from an immune-based destruction of melanocytes by anti-melanocyte-specific cytotoxic T cells. The JAK-STAT pathway is activated with IFN-γ as the crucial cytokine and Th1-associated chemokines such as CXCL9 and CXCL10 recruit immune cells towards vitiligo skin. Nonetheless, clear differences are also present, such as the localized nature of segmental vitiligo, likely due to somatic mosaicism and increased presence of poliosis. The differing prevalence of poliosis suggests that the follicular immune privilege, which is known to involve immune checkpoints, may be more important in vitiligo (non-segmental). Immunomodulatory therapies, especially those targeting the JAK-IFNγ pathway, are currently at the forefront, offering effective inhibition of melanocyte destruction by cytotoxic T cells. Although Janus Kinase (JAK) inhibitors demonstrate high repigmentation rates, optimal results can take several months to years. The influence of environmental UV exposure on repigmentation in patients receiving immunomodulating drugs remains largely underexplored. Nonetheless, the combined effect of phototherapy with JAK inhibitors is impressive and suggests a targeted immune-based treatment may still require additional stimulation of melanocytes for repigmentation. Identifying alternative melanocyte stimulants beyond UV light remains crucial for the future management of vitiligo.

DEHP (di(2-ethylhexyl)phthalate) stimulates skin pigmentation by perturbing cytoskeletal homeostasis.

Phthalates are extensively employed plasticizers crucial for conferring flexibility and plasticity to polyvinyl chloride. Phthalates, including DEHP (di(2-ethylhexyl)phthalate), present in diverse products, have been identified in fine dust and are capable of infiltrating the body, potentially posing health hazards. Importantly, melanocytes, existing at the basal layer of the epidermis, are susceptible to toxic substances. In our study, we employed the 3D human pigmented epidermis model, MelanoDerm™, along with the B16F10 murine melanoma cell line, to examine the influence of DEHP exposure on melanocytes. The exposure to low concentrations of DEHP (~ 5μM), resulted in the extension of melanocyte dendrites, indicating the stimulation of melanocytes. Analysis of gene expression and protein profiles unveiled the up-regulation of MITF, Arpc2, and TRP1 genes subsequent to DEHP exposure, indicating alterations in cytoskeletal and melanosome-related genetic and protein components in melanocytes. Notably, increased pigmentation was observed in MelanoDerm™ following DEHP exposure. DEHP-stimulated reactive oxygen species generation appeared to be involved in these events since the antioxidant, ascorbic acid attenuated ROS generation and MITF upregulation. Collectively, our study demonstrated that DEHP exposure can induce cytoskeletal disturbance and skin pigmentation through oxidative stress.

Evaluation of the Effect of Parental Smoking on Gingival Melanin Pigmentation in Children.

The presence of melanin pigmentation of the gingiva has unfavorable effects on esthetics in children. Although there are several local and systemic factors that cause melanin pigmentation, they may also be induced by the stimulation of melanocytes by stimuli present in tobacco smoke. The aim of the study was to correlate the effect of parental smoking on the pigmentation of gingiva in children of Modinagar, Uttar Pradesh, India. The study was a cross-sectional observational study. The study sample was formed by all children between 8 and 14 years of age. Only medically compromised children were excluded from the study. The children were examined for the presence of gingival melanin pigmentation. The status was recorded as present or absent. Determination of the smoking status of family members was done by a self-formulated questionnaire. The presence of pigmentation was seen in 114 (82%) children, whereas pigmentation was absent in 26 (18%) children. Out of the total sample of 140 children, 95 had one or more family members who were smoking. The Chi-squared test performed to form an association between pigmentation and the type of tobacco used revealed high significance (p = 0.00) for the father who smokes bidi. There is a correlation between parental smoking and melanin pigmentation in the gingiva of children, and the correlation is very high when the father is a smoker, especially when he smokes bidi. Anand A, Raja T, Thakur V, et al. Evaluation of the Effect of Parental Smoking on Gingival Melanin Pigmentation in Children. Int J Clin Pediatr Dent 2024;17(2):173-175.

Investigation of tryptophan to kynurenine degradation in response to interferon-γ in melanoma cell lines

Background and aimMelanoma is a fatal form of skin cancer that carries a grave prognosis if the cancer cells spread and form metastases. The Kynurenine (Kyn) pathway is activated by the enzyme indoleamine 2,3-dioxygenase 1 (IDO-1) and has been shown to have a role in tumour progression. We have previously shown that interferon-γ (IFN-γ) acts as an inducer of tryptophan (Trp) degradation to Kyn in keratinocytes of the basal layer in a 3D epidermis model. Before extending our reconstructed human epidermis model to not only contain keratinocytes but also fibroblasts and melanocytes/melanoma cells, we have in this study set out to investigate possible differences between primary adult melanocytes and six melanoma cell lines regarding the expression of the immune checkpoint inhibitors IDO-1 and programmed death ligand 1 (PD-L1) together with Kyn production. MethodsThe melanocytes and melanoma cells were stimulated with 1–20 ng/ml of IFN-γ and the levels of Trp to Kyn degradation were monitored with high-performance liquid chromatography (HPLC). To analyze the viability of the cell types after IFN-γ treatment, an MTT assay was performed. mRNA quantity of IDO-1, PD-L1 and IFN-γ receptor (IFN-GR1) was analyzed with qPCR. ResultsAfter 24 h, only the metastatic cell line WM-266-4 was affected by all concentrations of IFN-γ, whereas at 48 h, the higher IFN-γ concentrations gave a more pronounced effect on the viability in all cell types. Trp was detected at various levels in the culture medium from all cell types before and after IFN-γ treatment. The degradation to Kyn was detected in primary melanocytes, Mel Juso, and Mel Ho cell lines after 24 h of treatment and low levels of IFN-γ. However, the higher concentration of IFN-γ, 20 ng/ml, induced Kyn to various degrees in all cell types after 24 h. The change in mRNA quantity of IDO-1 and PD-L1 was similar in all cell types. ConclusionTo conclude, no significant difference in upregulation of the immune checkpoint inhibitors PD-L1 and IDO-1 was seen between primary tumour and metastatic melanoma. IFN-γ stimulation of melanocytes and different stages of melanoma cell lines resulted in an increased Kyn/Trp ratio in the more aggressive melanoma cells when a high concentration was used (20 ng/ml) but when a lower concentration of IFN-γ (5 ng/ml) was used an increased Kyn/Trp ratio were detected in media from primary melanocytes and early-stage melanoma.

Naturally-Occurring Tyrosinase Inhibitors Classified by Enzyme Kinetics and Copper Chelation.

Currently, there are three major assaying methods used to validate in vitro whitening activity from natural products: methods using mushroom tyrosinase, human tyrosinase, and dopachrome tautomerase (or tyrosinase-related protein-2, TRP-2). Whitening agent development consists of two ways, melanin synthesis inhibition in melanocytes and downregulation of melanocyte stimulation. For melanin levels, the melanocyte cell line has been used to examine melanin synthesis with the expression levels of TRP-1 and TRP-2. The proliferation of epidermal surfaced cells and melanocytes is stimulated by cellular signaling receptors, factors, or mediators including endothelin-1, α-melanocyte-stimulating hormone, nitric oxide, histamine, paired box 3, microphthalmia-associated transcription factor, pyrimidine dimer, ceramide, stem cell factors, melanocortin-1 receptor, and cAMP. In addition, the promoter region of melanin synthetic genes including tyrosinase is upregulated by melanocyte-specific transcription factors. Thus, the inhibition of growth and melanin synthesis in gene expression levels represents a whitening research method that serves as an alternative to tyrosinase inhibition. Many researchers have recently presented the bioactivity-guided fractionation, discovery, purification, and identification of whitening agents. Melanogenesis inhibition can be obtained using three different methods: tyrosinase inhibition, copper chelation, and melanin-related protein downregulation. There are currently four different types of inhibitors characterized based on their enzyme inhibition mechanisms: competitive, uncompetitive, competitive/uncompetitive mixed-type, and noncompetitive inhibitors. Reversible inhibitor types act as suicide substrates, where traditional inhibitors are classified as inactivators and reversible inhibitors based on the molecule-recognizing properties of the enzyme. In a minor role, transcription factors can also be downregulated by inhibitors. Currently, the active site copper iron-binding inhibitors such as kojic acid and chalcone exhibit tyrosinase inhibitory activity. Because the tyrosinase catalysis site structure is important for the mechanism determination of tyrosinase inhibitors, understanding the enzyme recognition and inhibitory mechanism of inhibitors is essential for the new development of tyrosinase inhibitors. The present review intends to classify current natural products identified by means of enzyme kinetics and copper chelation to exhibit tyrosinase enzyme inhibition.

The αMSH-Dependent PI3K Pathway Supports Energy Metabolism, via Glucose Uptake, in Melanoma Cells.

Stimulation of melanocytes and murine melanoma cells with αMSH plus the PI3K inhibitor LY294002 resulted in ROS increase, oxidative DNA damage, and pigment retention. We performed cellular and molecular biology assays (Western blot, FACS, immunofluorescence analysis, scratch assay) on murine and human melanoma cells. Treatment with αMSH plus LY294002 altered cortical actin architecture. Given that cytoskeleton integrity requires energy, we next evaluated ATP levels and we observed a drop in ATP after exposure to αMSH plus LY294002. To evaluate if the αMSH-activated PI3K pathway could modulate energy metabolism, we focused on glucose uptake by analyzing the expression of the Glut-1 glucose translocator. Compared with cells treated with αMSH alone, those exposed to combined treatment showed a reduction of Glut-1 on the plasma membrane. This metabolic alteration was associated with changes in mitochondrial mass. A significant decrease of the cell migratory potential was also observed. We demonstrated that the αMSH-dependent PI3K pathway acts as a regulator of energy metabolism via glucose uptake, influencing the actin cytoskeleton, which is involved in melanosome release and cell motility. Hence, these results could constitute the basis for innovative therapeutical strategies.

Preferential stimulation of melanocytes by M2 macrophages to produce melanin through vascular endothelial growth factor

Post-inflammatory hyperpigmentation is a skin discoloration process that occurs following an inflammatory response or wound. As the skin begins to heal, macrophages first exhibit a proinflammatory phenotype (M1) during the early stages of tissue repair and then transition to a pro-healing, anti-inflammatory phenotype (M2) in later stages. During this process, M1 macrophages remove invading bacteria and M2 macrophages remodel surrounding tissue; however, the relationship between macrophages and pigmentation is unclear. In this study, we examined the effect of macrophages on melanin pigmentation using human induced pluripotent stem cells. Functional melanocytes were differentiated from human induced pluripotent stem cells and named as hiMels. The generated hiMels were then individually cocultured with M1 and M2 macrophages. Melanin synthesis decreased in hiMels cocultured with M1 macrophages but significantly increased in hiMels cocultured with M2 macrophages. Moreover, the expression of vascular endothelial growth factor was increased in M2 cocultured media. Our findings suggest that M2 macrophages, and not M1 macrophages, induce hyperpigmentation in scarred areas of the skin during tissue repair.

What Is the Most Important and Impactful Paper Related to Movement Disorder Therapy Published in the 20th Century?

What Is the Most Important and Impactful Paper Related to Movement Disorder Therapy Published in the 20th Century?

Blue Lunula Due to a Combination Chemotherapy Not Reported Before.

A dermatology consultation was sought for a 32-year-old lady admitted to the medical oncology ward. She was a known case of acute myeloid leukemia (AML) on chemotherapy. The cutaneous examination revealed blue pigmentation of the lunulae of all her fingernails, bilateral great toenails, and two adjacent toenails [Figures 1 and 2]. The oral cavity and other mucosae were within normal limits. The present nail changes occurred around 20 days ago, 10 days after she underwent bone marrow transplantation. These nail changes had been appearing 10 to 15 days after each chemotherapy cycle and would resolve partially until the next chemotherapy cycle [Figure 3a and 3b]. She had received five such cycles, comprising fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin (FLAG IDA) regimen) and azacytidine plus sorafenib.Figure 1: Blue pigmentation of the lunula of all fingernailsFigure 2: Blue pigmentation of the lunula of bilateral great toenails and two adjacent toenailsFigure 3: After 6 weeks, (a) near-complete resolution of the blue pigmentation of fingernails. (b) partial resolution of the pigmentation of toenailsBlue lunula can be caused by multiple chemotherapeutic drugs including hydroxyurea,[12] docetaxel, and combination chemotherapy (cyclophosphamide, vincristine, doxorubicin; 5-fluorouracil, doxorubicin, cyclophosphamide; vinblastine, dactinomycin, bleomycin).[3] The drugs implicated in our case have not been reported before. It is, however, difficult to ascribe it to a particular drug(s) in our patient. The mechanism by which this pigmentation occurs is not very clear; it is, however, postulated to be due to the toxic effect on the distal nail matrix basal cells or the pigment deposition in the nail matrix, or due to focal stimulation of melanocytes to produce melanin.[24] Apart from chemotherapeutic drugs, blue lunula can also be caused by zidovudine, phenolphthalein, and silver. It can also occur in Wilson’s disease, and as a normal finding in black races.[13] This case adds another chemotherapy combination as a cause of blue lunula. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

A Simple Drug Delivery System for Platelet-Derived Bioactive Molecules, to Improve Melanocyte Stimulation in Vitiligo Treatment.

Vitiligo is the most common depigmentation disorder of the skin. Currently, its therapy focuses on the halting of the immune response and stimulation of the regenerative processes, leading to the restoration of normal melanocyte function. Platelet-rich plasma (PRP) represents a safe and cheap regenerative therapy option, as it delivers a wide spectrum of native growth factors, cytokines and other bioactive molecules. The aim of this study was to develop a simple delivery system to prolong the effects of the bioactive molecules released from platelets. The surface of electrospun and centrifugally spun poly-ε-caprolactone (PCL) fibrous scaffolds was functionalized with various concentrations of platelets; the influence of the morphology of the scaffolds and the concentration of the released platelet-derived bioactive molecules on melanocytes, was then assessed. An almost two-fold increase in the amount of the released bioactive molecules was detected on the centrifugally spun vs. electrospun scaffolds, and a sustained 14-day release of the bioactive molecules was demonstrated. A strong concentration-dependent response of melanocyte to the bioactive molecules was observed; higher concentrations of bioactive molecules resulted in improved metabolic activity and proliferation of melanocytes. This simple system improves melanocyte viability, offers on-site preparation and is suitable for prolonged topical PRP administration.

Evaluation of chitosan gel on burn wound healing and keratinocytes function

Skin burns are common skin injuries that can result from exposure to various sources of heat by which, depending on the cause, different degrees of burns are generated. In restoration of superficial burns by re-epithelialization, the skin is rebuilt, but the skin color is different than the healthy tissue. Keratinocytes represent the major cells of the epidermis. These cells are sourced from ectoderm and are continuously being formed from the basal level. The main task of these cells is to make the protein keratin. During differentiation, keratinocytes move toward the superficial layers of the epidermis and generate more keratin. These cells are colorless, but by manipulating melanocytes (the melanocyte cells produce pigment in the skin), one can control the darkness degree of the skin. Keratinocytes, in particular, produce chemical signals which, in turn, are responsible for regulating the distribution and amount of melanin pigment in melanocytes. In this study, using an aluminum stamp weighing 85 grams, at a temperature of 80 ◦C, superficial burns, of 2nd degree, were generated on six rabbits. The rabbits were divided into two groups; a control group and the second one in which a chitosan (CHI) gel was used as a dressing. After treatment, histopathology tests and the TEM results confirmed that, in the CHI treatment group, the restoration led to acceptable results. It was shown that if the repair was performed with a CHI based gel, the keratinocyte appeared with their original structure after restoration, but if the treatment was done without the CHI dressing, the number of these cells increased, more stimulation of melanocytes occurred and, ultimately, it led to an unwanted color change of the burnt area.

Resveratrol as a Multifunctional Topical Hypopigmenting Agent.

Melanin is produced in melanocytes and stored in melanosomes, after which it is transferred to keratinocytes and, thus, determines skin color. Despite its beneficial sun-protective effects, abnormal accumulation of melanin results in esthetic problems. A range of topical hypopigmenting agents have been evaluated for their use in the treatment of pigmentary disorders with varying degrees of success. Hydroquinone (HQ), which competes with tyrosine, is the main ingredient in topical pharmacological agents. However, frequent occurrence of adverse reactions is an important factor that limits its use. Thus, efforts to discover effective topical hypopigmenting agents with less adverse effects continue. Here, we describe the potential of resveratrol to function as an effective hypopigmenting agent based on its mechanism of action. Resveratrol is not only a direct tyrosinase inhibitor but an indirect inhibitor as well. Additionally, it can affect keratinocytes, which regulate the function of melanocytes. Resveratrol regulates the inflammatory process of keratinocytes and protects them from oxidative damage. In this way, it prevents keratinocyte-induced melanocyte stimulation. Furthermore, it has a rescuing effect on the stemness of interfollicular epidermal cells that can repair signs of photoaging in the melasma, a typical pigmentary skin disorder. Overall, resveratrol is a promising potent hypopigmenting agent.

Functional characterization of the extranasal OR2A4/7 expressed in human melanocytes.

Olfactory receptors (ORs) were first described as specialized chemoreceptors in the nasal epithelium. In the last two decades, ORs have also been detected to be functionally expressed and active in different nonolfactory tissues of the human body, because they used to react to specific odour stimuli. In this study, we conducted a characterization of the extranasal OR2A4/7 expressed in primary human melanocytes and sections of the human skin. OR2A4/7 expression could be demonstrated at the transcript and protein level. We uncovered elevated intracellular cAMP and Ca2+ levels accompanied by elevated p38 and reduced p42/44 MAPK phosphorylation following odourant (cyclohexyl salicylate; CHS) stimulation of melanocytes. These results were associated with enhanced melanin biosynthesis in conjunction with the growth inhibition and differentiation of melanocytes. Our findings highlight the participation of OR2A4/7 in human primary melanocyte physiology and suggest an alternate mechanism that regulates melanogenesis.

Functional Characterization of the Odorant Receptor 51E2 in Human Melanocytes

Olfactory receptors, which belong to the family of G-protein-coupled receptors, are found to be ectopically expressed in non-sensory tissues mediating a variety of cellular functions. In this study we detected the olfactory receptor OR51E2 at the transcript and the protein level in human epidermal melanocytes. Stimulation of primary melanocytes with the OR51E2 ligand β-ionone significantly inhibited melanocyte proliferation. Our results further showed that β-ionone stimulates melanogenesis and dendritogenesis. Using RNA silencing and receptor antagonists, we demonstrated that OR51E2 activation elevated cytosolic Ca(2+) and cAMP, which could mediate the observed increase in melanin synthesis. Co-immunocytochemical stainings using a specific OR51E2 antibody revealed subcellular localization of the receptor in early endosomes associated with EEA-1 (early endosome antigen 1). Plasma membrane preparations showed that OR51E2 protein is present at the melanocyte cell surface. Our findings thus suggest that activation of olfactory receptor signaling by external compounds can influence melanocyte homeostasis.

Aesthetic Depigmentation of Gingival Smoker's Melanosis Using Carbon Dioxide Lasers.

Melanic pigmentation results from melanin produced by the melanocytes present in the basal layer of the oral epithelium. One of the most common causes of oral pigmentation is smoker melanosis, a condition associated with the melanocyte stimulation caused by cigarette smoke. This paper aims to illustrate the use of a carbon dioxide laser in the removal of the gingival melanic pigmentation for aesthetic reasons in a 27-year-old female patient with history of a smoking habit. The carbon dioxide laser vaporisation was performed on the gingival mucosa with effective and quick results and without any complications or significant symptoms after the treatment. We conclude that a carbon dioxide laser could be a useful, effective, and safe instrument to treat the aesthetic complications caused by oral smoker melanosis.

A multimodal assessment of melanin and melanocyte activity in abnormally pigmented hypertrophic scar.

Using a validated swine model of human scar formation, hyperpigmented and hypopigmented scar samples were examined for their histological and optical properties to help elucidate the mechanisms and characteristics of dyspigmentation. Full-thickness wounds were created on the flanks of red Duroc pigs and allowed to heal. Biopsies from areas of hyperpigmentation, hypopigmentation, and uninjured tissue were fixed and embedded for histological examination using Azure B and primary antibodies to S100B, HMB45, and α-melanocyte-stimulating hormone (α-MSH). Spatial frequency domain imaging (SFDI) was then used to examine the optical properties of scars. Hyperpigmentation was first noticeable in healing wounds around weeks 2 to 3, gradually becoming darker. There was no significant difference in S100B staining for the presence of melanocytes between hyperpigmented and hypopigmented scar samples. Azure B staining of melanin was significantly greater in histological sections from hyperpigmented areas than in sections from both uninjured skin and hypopigmented scar (P < .0001). There was significantly greater staining for α-MSH in hyperpigmented samples compared with hypopigmented samples (P = .0121), and HMB45 staining was positive for melanocytes in hyperpigmented scar. SFDI at a wavelength of 632 nm resulted in an absorption coefficient map correlating with visibly hyperpigmented areas of scars. In a red Duroc model of hypertrophic scar formation, melanocyte number is similar in hyperpigmented and hypopigmented tissues. Hyperpigmented tissues, however, show a greater amount of melanin and α-MSH, along with immunohistochemical evidence of stimulated melanocytes. These observations encourage further investigation of melanocyte stimulation and the inflammatory environment within a wound that may influence melanocyte activity. Additionally, SFDI can be used to identify areas of melanin content in mature, pigmented scars, which may lead to its usefulness in wounds at earlier time points before markedly apparent pigmentation abnormalities.

Akt and PI3K-dependent but CREB-independent upregulation of MCAM by endothelin-3 in human melanocytes.

Melanoma cell adhesion molecule (MCAM) is upregulated during melanoma progression, and associated with invasion and metastasis. Little is known about the factors that regulate MCAM expression in vivo. Mutations that upregulate MCAM have not been found, and AKT activating mutations are rare in melanomas. This suggests that an epigenetic factor may be responsible for upregulating MCAM and activating AKT in vivo. Although endothelin-1 and endothelin-3 (ET-1, ET-3) are physiologically relevant factors capable of upregulating MCAM in melanocytic cells, a mechanism of action has never been established. Here we show that pharmacologic inhibition of map kinase kinase (MEK) or phosphoinositol 3 kinase (PI3K) blocks MCAM upregulation by ET-3, implicating MEK and PI3K/Akt kinases in ET-3 regulation of MCAM. Despite the fact that there are cAMP response element binding protein (CREB) sites in the MCAM promoter, suppression of CREB expression by siRNA silencing does not block ET-3 mediated upregulation of MCAM. Rather, ET-3 stimulation of melanocytes promotes Akt phosphorylation at Ser 473, which is suppressed by PI3K inhibition or silencing of Akt, in turn blocking ET-3 upregulation of MCAM. We conclude therefore that ETs upregulate MCAM in an Akt and ERK/MEK-dependent, but CREB-independent manner, providing an understanding for possible pharmacologic intervention in progressing melanoma.

Class III β-tubulin, a novel biomarker in the human melanocyte lineage

It is generally thought that class III β-tubulin expression is limited to cells of the neural lineage and is therefore often used to identify neurons amongst other cell types, both in vivo and in vitro. Melanocytes are derived from the neural crest and share both morphological features and functional characteristics with peripheral neurons. Here, we show that these similarities extend to class III β-tubulin (TUBB3) expression, and that human melanocytes express this protein both in vivo and in vitro. In addition, we studied the expression of class III β-tubulin in two murine melanogenic cell lines and show that expression of this protein starts as melanoblasts mature into melanocytes. Melanin bleaching experiments revealed close proximity between melanin and TUBB3 proteins. In vitro stimulation of primary human melanocytes by α-MSH indicated separate regulatory mechanisms for melanogenesis and to TUBB3 expression. Together, these observations imply that human melanocytes express TUBB3 and that this protein should be recognized as a wider marker for multiple neural crest-derived cells.

An Effective Modality for Argyria Treatment: Q-Switched 1,064-nm Nd:YAG Laser

Dear Editor: Argyria is a rare condition caused by improper exposure to products containing silver. Argyria will display as a blue-to-slate-gray color change in the field when exposed to sunlight1, and this may play an important role in the pigmentation. With respect to the pathologic findings, argyria is distinguished by the deposition of fine, brown-black granules mostly surrounding the basement membrane of the eccrine sweat glands and connective tissues in the dermis2. Unfortunately, an effective treatment is yet to be found. We experienced a example of argyria that showed noteworthy change after a Q-switched 1,064-nm Nd:YAG laser was used. A 36-year-old woman was referred to the dermatologic department of Samsung Medical Center with a blue-gray color change of the face (Fig. 1A). According to her history, she had been ingesting colloidal silver for two years as a folk remedy. A dermatologic check up showed widespread blue-gray color change of the face. Histopathological examination results from her forehead skin showed spherical small brown-black granules deposited in the basement membrane around the eccrine glands, and scattered in the dermis (Fig. 2). The laboratory tests were unremarkable. The skin color change was dealt with using a Q-switched 1,064 nm Nd:YAG laser (Medlite IV; Continuum, Santa Clara, CA, USA). The laser was used at a fluence of 8 J/cm2 and pulse duration of 6 nanoseconds with a 4-mm spot size. There was no on-the-spot complications or any sequelae. Afterwards, we dealt with the patient's other part of the face after an interval of two to three months. Thereafter, with three lots of treatment, the treated area showed significant improvement (Fig. 1B). Agree on the use of patient photos obtained. Fig. 1 (A) Blue-gray pigmentation of the face. (B) Significant improvement after three sessions of laser treatment. Black dotted rectangle displays the untreated area. Fig. 2 Round, tiny brown-black granules deposited in the area surrounding the eccrine glands (arrows). The pathophysiology of silver deposition in the development of argyria is not completely known. Like photography, sunlight reduces elemental silver to silver sul?de and selenide in the skin. This mechanism, combined with melanocyte stimulation, provokes cutaneous color changes3. Treatment of argyria is very difficult. The underlying mechanisms of argyria treatment by Q-switched lasers may be analogous to tattoo removal4. The 1,064-nm wave-length laser is weakly absorbed by melanin or water, which can penetrate into the deep dermis where eccrine sweat glands and silver granules exist. The present case showed significant improvement after four sessions of Q-switched Nd:YAG laser. The patient was highly satisfied with the result, and is continuously receiving the treatment to date. In conclusion, Q-switched 1,064-nm Nd:YAG laser is a useful modality for the treatment of argyria, even though more research is necessary to confirm whether the beneficial effect is coherent.

A case of early-onset obesity, hypocortisolism, and skin pigmentation problem due to a novel homozygous mutation in the proopiomelanocortin (POMC) gene in an Indian boy

Proopiomelanocortin (POMC) is the polypeptide precursor of several biologically active melanocortin peptides that have important roles in the regulation of food intake and energy homeostasis, adrenal steroidogenesis, melanocyte stimulation, and immune modulation. Mutation of the POMC gene has been associated with adrenal insufficiency, early-onset obesity, and red hair pigmentation. We describe an Indian boy with secondary hypocortisolism, hyperphagia, early-onset obesity, and skin pigmentation problem. Genetics analysis revealed a novel homozygous mutation in the POMC gene (p.Arg86Term). The boy also had central hypothyroidism in addition to the secondary hypocortisolism. Genetics analysis for the POMC gene should be considered in patients with secondary hypocortisolism, early-onset obesity, and pigmentary problems.