Hee Joo Kim

ZnO nanoparticles induce TNF-α expression via ROS-ERK-Egr-1 pathway in human keratinocytes

BACKGROUND The area of nanotechnology continues to expand rapidly and zinc oxide (ZnO) nanoparticles (NPs) are widely being used in cosmetics and sunscreens. Although ZnO-NPs are considered materials that can potentially cause skin inflammation, the underlying mechanisms remain elusive. OBJECTIVE The aim of this study was to investigate the signaling pathways of a cutaneous inflammatory response induced by ZnO-NPs. ZnO-NPs increased the early growth response-1 (Egr-1) expression, promoter activity and its nuclear translocation in HaCaT cells. METHODS HaCaT cells and primary keratinocytes were exposed to ZnO NPs over a range of doses and time course. Protein levels and mRNA levels of Egr-1 and mitogen-activated protein kinase (MAPK) were measured by Western blot and ELISA, respectively. As an in vivo study, ZnO-NPs were applicated on mouse skin, and immunohistochemical stain with TNF-α and Egr-1 was done. RESULTS ZnO-NPs activated extracellular signal-regulated kinase (ERK) of MAPK pathways. The up-regulation of Egr-1 expression by ZnO-NPs stimulation was found to be inhibited by an ERK inhibitor, but by neither c-Jun-N-terminal kinase (JNK) nor p38 inhibitor. Antioxidative N-acetyl-cysteine (NAC) strongly inhibited the level of Egr-1 and phosphorylated ERK expression in ZnO-NPs treated cells. ZnO NPs also increased tumor necrosis factor (TNF)-α expression and secretion, which were inhibited by the blockade of Egr-1 expression. CONCLUSIONS The present study demonstrated that ZnO-NPs might induce inflammatory response via ROS-ERK-Egr-1 pathway in human keratinocytes.

Cigarette smoke‐induced early growth response‐1 regulates the expression of the cysteine‐rich 61 in human skin dermal fibroblasts

Abstract:  Tobacco smoke is known to be an element contributing to accelerate premature skin ageing. Cysteine‐rich 61 (Cyr61) is a member of the connective tissue factor CCN (Cyr61, CTGF and Nov) family, and early growth response‐1 (Egr‐1) is a generally expressed member of the zinc‐finger family of transcription factors. To investigate the regulatory potential of Egr‐1 on expression of Cyr61 by smoking, this study examined the hypothesis that cigarette smoke‐induced Egr‐1 induces expression of Cyr61 in human skin dermal fibroblasts (HSDF). HSDF were exposed to different concentrations of cigarette smoke extract (CSE) for 24 h; a cytotoxicity assay was then performed for the detection of cell proliferation. Results of Western blot and reverse transcription‐polymerase chain reaction (RT‐PCR) showed that CSE induces a transient synthesis of Egr‐1 in HSDF. Cyr61 mRNA and protein levels showed a marked increase in a time‐dependent manner after CSE exposure. Following transfection with an Egr‐1 overexpression vector, HSDF showed increased activity of the Cyr61 promoter in a dose‐dependent manner. Using Egr‐1 interfering RNA, we confirmed that CSE‐induced Cyr61 expression was dependent on Egr‐1 expression. Findings of this study indicate that Egr‐1‐dependent induction of Cyr61 may contribute to premature skin ageing by smoking.

A Prospective, Long-Term Follow-Up Study of 1,444 nm Nd:YAG Laser: A New Modality for Treating Axillary Bromhidrosis

Background Surgery for bromhidrosis has a high risk of complications such as hematoma and necrosis. New nonsurgical methods may reduce the burden on surgery and the risks for the patient. Objective This study was performed to evaluate the efficacy and side-effects of the 1,444 nm Nd:YAG interstitial laser for treating axillary bromhidrosis. Methods Eighteen bromhidrosis patients were treated with a 1,444 nm Nd:YAG laser at Korea University Ansan Hospital. The post-treatment follow-up was 6 months. After the procedure, we confirmed apocrine gland destruction through histopathological examination. At each follow-up, we measured the severity of the remaining odor, postoperative pain, degree of mobility restriction, and overall satisfaction. Results After 180 days of follow-up, malodor elimination was good in 20 axillae, fair in 12 axillae, and poor in four axillae. At the end point of the study, 14 patients were totally satisfied with the laser treatment, three patients were partially satisfied, and one patient was disatisfied. Pain and limitation of mobility were significantly reduced within 1 week post-operatively, and were almost resolved within 4 weeks post-operatively. A histopathological examination revealed decreased density and significant alterations to the apocrine glands. Conclusion Subdermal coagulation treatment with a 1,444 nm Nd:YAG interstitial laser may be a less invasive and effective therapy for axillary bromhidrosis.

Egr-1 is a key regulator of IL-17A-induced psoriasin upregulation in psoriasis

The early growth response (Egr)‐1 is a transcriptional factor which plays an important role in the regulation of cell growth, differentiation, cell survival and immune responses. Emerging evidences including our data demonstrate that the Egr‐1 expression is up‐regulated in the psoriatic skin lesions. The purpose of this study was to investigate the significance and regulatory mechanism of Egr‐1 in the pathogenesis of psoriasis. Through microarray analysis, we found out that psoriasin (S100A7) expression was increased in the Egr‐1 overexpressed cells. Our results showed that IL‐17A increased Egr‐1 expression in the skin of psoriatic patients and cultured human keratinocytes. We then investigated activation of mitogen‐activated protein kinase as an upstream signal regulator of Egr‐1 expression. IL‐17A‐induced Egr‐1 expression was suppressed by ERK inhibitor. In addition, IL‐17A induced psoriasin expression in cultured keratinocytes and the skin of IL‐17A intradermally injected mouse. IL‐17A‐mediated psoriasin upregulation was reduced after treatment of small interfering RNAs against Egr‐1. Furthermore, the results of chromatin immunoprecipitation assays demonstrated that Egr‐1 directly binds the psoriasin promoter. Our findings present a novel signalling mechanism by which IL‐17A can induce the Egr‐1‐dependent psoriasin expression via the ERK pathway in human keratinocytes. This study suggests that Egr‐1 may be a novel and important modulator in IL‐17A‐mediated immune response in psoriasis.

Successful Treatment of Multiple Cutaneous Neurofibromas Using a Combination of Shave Excision and Laser Photothermocoagulation with a 1,444-nm Neodymium-Doped Yttrium Aluminum Garnet Laser

Neurofibromatosis type 1 (NF-1) is an autosomal-dominant disorder of chromosome 17q11.2. Multiple cutaneous neurofibromas, one of the most characteristic clinical features, are mainly a cosmetic problem. Because of their sheer number and visibility, cutaneous neurofibromas are a major source of morbidity and psychological concern in NF-1, and most patients are willing to undergo removal of as many neurofibromas as possible. Although excision could completely remove the neurofibroma, it is time consuming and painful, and treatment of dozens of lesions at the same time is difficult.

A firm, bluish, hemorrhagic nodule on the left heel

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A case of squamous cell carcinoma and arsenic keratoses in a patient with vitiligo taking Chinese arsenic medicine

Chronic arsenic intoxication can still be found in environmental and industrial settings. The trivalent inorganic form of arsenic is known to be carcinogenic. Drinking water contaminated with inorganic arsenic is the primary route of exposure, and diet or medication is another major source of arsenic. We herein report a case of squamous cell carcinoma (SCC) from arsenic keratosis due to chronic ingestion of arsenical herbal medicine for vitiligo.

Acute Vesico-Bullous Eruption from Methotrexate Overdose in a Psoriasis Patient

Dear Editor: Methotrexate (MTX) is a folic acid analog that potently blocks folate-dependent enzymes integral to DNA synthesis1. It is one of the most common systemic immunosuppressive agents used by dermatologists, particularly in the control of psoriasis. Fatal complications are rare in a dermatological low dose regimen. We herein report a case of acute cutaneous toxicity of MTX representing bullous eruption after a weekly dose of MTX was taken daily for a short period. A 73-year-old male had been treated for psoriasis since 2008 with narrow band ultraviolet B phototherapy. His psoriatic arthritis had been well controlled with etanercept subcutaneous injection for 1 year and he had stopped etanercept for 1 year. MTX was considered after the psoriatic arthritis worsened, and a rheumatologist prescribed 10 mg/week MTX for 5 days. He accidentally misunderstood the prescription and took 10 mg/day MTX for a period of 5 days. After 1 week, he presented with erythematous vesicobullae and erosions on the arms and face and ulcers in mucosal areas, including the lips (Fig. 1). There was no other skin disease history except psoriasis. Laboratory studies revealed thrombocytopenia (110,000/mm3) and alanine aminotransferase (ALT) was elevated to 99I U/L, whereas all laboratory data prior to MTX therapy, including complete blood count, liver function test, had been within normal limits. Other laboratory results including levels of albumin, blood urea nitrogen, and creatinine were within normal limits. With discontinuation of MTX and methylprednisolone 24 mg/day taken for a week, the skin bullous eruption and labial ulceration rapidly resolved without sequelae (Fig. 2), and the platelet count and ALT value returned to normal. Unfortunately, the patient refused pathologic evaluation. Clinical history, however, indicated MTX overdose-associated bullous eruption; the onset of the eruption was 5 days after initiation of MTX ingestion, and the eruption began to resolve immediately after discontinuation of MTX. After 2 weeks, MTX was restarted at a dose of 10 mg/week and he is taking MTX without misunderstanding or adverse events. Fig. 1 Acute vesicobullous eruption after administration of methotrexate for 5 consecutive days (A) on oral mucosa (B) on the left arm. Fig. 2 Ruptured bullous eruption healing with re-epithelization on the left arm. Although MTXs precise mechanism of action in cutaneous autoimmune disease remains unclear, the effects are believed to include inhibition of cell division of tumoral, hematopoietic, and other rapidly proliferating cells1. MTX has been associated with a number of mucocutaneous side effects, such as photosensitivity, erosions, necrolysis, and diffuse noninflammatory alopecia1. More rarely, cutaneous ulceration within diseased skin has been reported2,3. In this case, the latest psoriatic lesions of the patient were mainly on his arms, and the MTX cutaneous toxicity occurred on the diseased skin. Lawrence and Dahl3 reported that histologic evaluation of the ulcer edge showed swollen epidermal cells with vacuolated or dyskeratotic cells, indicating incipient epidermal necrolysis. Although rare, severe side effects, such as bone marrow suppression, liver failure, and pulmonary fibrosis can occur even in low-dose therapy4. As was the case in this instance, drugs available in once-weekly formulations require extra vigilance5. One of the once-weekly dosing drugs, MTX, can be life-threatening when the drug is administered daily as a result of physician, pharmacy, or patient error. Pre-MTX counseling needs to focus on ensuring that patients clearly understand this dosing schedule1. In order to avoid a significant risk, patients should be given written, personalized information about the use of a once-weekly drug, and preparation of a time table can help the patient to establish a routine for taking doses as prescribed5.

The duration of hyaluronidase and optimal timing of hyaluronic acid (HA) filler reinjection after hyaluronidase injection

ABSTRACT Background: Hyaluronidase injection is a commonly performed treatment for overcorrection or misplacement of hyaluronic acid (HA) filler. Many patients often wants the HA filler reinjection after the use of hyaluronidase, though the optimal timing of reinjection of HA filler still remains unknown. Objectives: To provide the optimal time interval between hyaluronidase injections and HA filler reinjections. Methods: 6 Sprague–Dawley rats were injected with single monophasic HA filler. 1 week after injection, the injected sites were treated with hyaluronidase. Then, HA fillers were reinjected sequentially with differing time intervals from 30 minutes to 14 days. 1 hour after the reinjection of the last HA filler, all injection sites were excised for histologic evaluation. Results: 3 hours after reinjection of HA filler, the appearance of filler material became evident again, retaining its shape and volume. 6 hours after reinjection, the filler materials restored almost its original volume and there were no significant differences from the positive control. Conclusions: Our data suggest that the hyaluronidase loses its effect in dermis and subcutaneous tissue within 3–6 hours after the injection and successful engraftment of reinjected HA filler can be accomplished 6 hours after the injection.

Dystrophic calcifications after autologous fat injection on face.

Abstract Autologous fat injection is widely used procedure for various functional and aesthetic purposes. However, it could result in many immediate or delayed complications including dystrophic calcifications. Almost all of the case reports about dystrophic calcification after autologous fat injection were result from the iatrogenic tissue trauma of breast augmentation. This is a report of a 30-year-old patient who developed pathologically proven multiple dystrophic calcifications on the face after autologous fat injection.