Pitavastatin Induces Apoptosis of Cutaneous Squamous Cell Carcinoma Cells through Geranylgeranyl PyrophosphateDependent c-Jun N-Terminal Kinase Activation

Background@#Pitavastatin is a cholesterol-lowering drug and is widely used clinically. In addition to this effect, pitavastatin has shown the potential to induce apoptosis in cutaneous squamous cell carcinoma (SCC) cells. @*Objective@#The purpose of this study is to investigate the effects and possible action mechanisms of pitavastatin. @*Methods@#SCC cells (SCC12 and SCC13 cells) were treated with pitavastatin, and induction of apoptosis was confirmed by Western blot. To examine whether pitavastatin-induced apoptosis is related to a decrease in the amount of intermediate mediators in the cholesterol synthesis pathway, the changes in pitavastatin-induced apoptosis after supplementation with mevalonate, squalene, geranylgeranyl pyrophosphate (GGPP) and dolichol were investigated. @*Results@#Pitavastatin dose-dependently induced apoptosis of cutaneous SCC cells, but the viability of normal keratinocytes was not affected by pitavastatin at the same concentrations. In supplementation experiments, pitavastatin-induced apoptosis was inhibited by the addition of mevalonate or downstream metabolite GGPP. As a result of examining the effect on intracellular signaling, pitavastatin decreased Yes1 associated transcriptional regulator and Ras homolog family member A and increased Rac family small GTPase 1 and c-Jun Nterminal kinase (JNK) activity. All these effects of pitavastatin on signaling molecules were restored when supplemented with either mevalonate or GGPP. Furthermore, pitavastatininduced apoptosis of cutaneous SCC cells was inhibited by a JNK inhibitor. @*Conclusion@#These results suggest that pitavastatin induces apoptosis of cutaneous SCC cells through GGPP-dependent JNK activation.

A Case of Nodular Melanoma with a Family History of Difficult Clinical Diagnosis / 대한피부과학회지

Nodular melanoma is a malignant melanoma which presents as blackish-brown or colorless nodules. Nodular melanoma shows rapid growth compared to other melanoma subtypes, and often exhibits clinical features that do not correspond to the ABCD rules, which is key in differentiating melanoma. This makes nodular melanoma difficult to differentiate from the initially suspected melanoma. As such, diagnosis of nodular melanoma is commonly delayed, and is therefore often identified at an advanced stage. Here, we report a case of nodular melanoma in a young man with a family history of melanoma. We emphasize the importance of early diagnosis through biopsy for malignant melanoma, which is difficult to differentiate based on clinical features.

Inhibitory Effect of Mitoxantrone on Collagen Synthesis in Dermal Fibroblasts

Background@#Fibroblasts produce collagen molecules that support the structure of the skin.The decrease and hypersynthesis of collagen causes skin problems such as skin atrophy, wrinkles and scars. @*Objective@#The purpose of this study is to investigate the mechanism of mitoxantrone on collagen synthesis in fibroblasts. @*Methods@#Cultured fibroblasts were treated with mitoxantrone, and then collagen synthesis was confirmed by reverse transcription-polymerase chain reaction and Western blot. @*Results@#Mitoxantrone inhibited the expression of type I collagen in fibroblasts at both the mRNA and protein levels. In the collagen gel contraction assay, mitoxantrone significantly inhibited gel contraction compared to the control group. Mitoxantrone inhibited transforming growth factor (TGF)-β-induced phosphorylation of SMAD3. Finally, mitoxantrone inhibited the expression of LARP6, an RNA-binding protein that regulates collagen mRNA stability. @*Conclusion@#These results suggest that mitoxantrone reduces collagen synthesis by inhibiting TGF-β/SMAD signaling and LARP6 expression in fibroblasts, which can be developed as a therapeutic agent for diseases caused by collagen hypersynthesis.

Palisaded Neutrophilic and Granulomatous Dermatitis in a Patient with Behçet’s Disease: A Case Report

Palisaded neutrophilic and granulomatous dermatitis (PNGD) is an uncommon skin eruption and characterized histopathologically by the presence of granulomatous inflammation with or without leukocytoclastic vasculitis. PNGD is known to be associated with various immune-mediated connective tissue diseases such as rheumatoid arthritis and lupus erythematosus. However, to our knowledge, a case of PNGD in a patient with Behçet’s disease is extremely rare and only one case has been reported in foreign literature to date. Herein, we report an unusual case of a 60-year-old female with Behçet’s disease who presented multiple erythematous to flesh-colored papules on the extremities, buttocks, and ear lobes and was diagnosed with PNGD. After the treatment of systemic corticosteroids, colchicine and azathioprine, the skin lesions and oral ulcers improved. The patient is under observation without recurrence of skin lesions for 6 months.

Contrast Media-induced Sweet's Syndrome / 대한피부과학회지

No abstract available.

Contrast-enhanced Magnetic Resonance Imaging of Brain Metastases at 7.0T versus 1.5T: A Preliminary Result

PURPOSE: To compare the depiction of brain metastases on contrast-enhanced images with 7.0 tesla (T) and at 1.5T MRI. MATERIALS AND METHODS: Four consecutive patients with brain metastases were scanned on 7.0T whole-body scanner and 1.5T MRI. A 3D T1-weighted gradient echo sequence (3D T1-GRE) at 1.5T (voxel size = 0.9 x 0.9 x 1.5 mm3 after double-dose, gadoterate meglumine, Gd-DOTA) was compared to a 7.0T 3D T1-GRE sequence (voxel size = 0.4 x 0.4 x 0.8 mm3, single-dose Gd-DOTA) in four patients after a 5 minute delay. The number of contrast-enhancing metastases in MPRAGE images was compared in each patient by two radiologists in consensus. We measured contrast ratio of enhancing brain metastases and white matter in 1.5T and 7.0T. RESULTS: In all four patients 7.0T 3D T1-GRE images after single-dose Gd-DOTA and 1.5T after double-dose Gd-DOTA depicted 11 brain metastases equally. In the quantitative analysis of contrast ratios of enhancing brain metastases and white matter, the 1.5T 3D T1-GRE after double-dose showed an increased contrast ratio compared to 7.0T 3D T1-GRE after single-dose (0.961 +/- 0.571 versus 0.885 +/- 0.494; n = 11 metastases). But this difference was not statistically significant (P = 0.711). CONCLUSION: Our preliminary results indicate that 7.0T single-dose Gd-enhanced images were not different to 1.5T double-dose Gd-enhanced images for the detection of brain metastases.

Measurement of Apparent Diffusion Coefficient Values from Diffusion-Weighted MRI: A Comparison of Manual and Semiautomatic Segmentation Methods

PURPOSE: To compare the interobserver and intraobserver reliability of mean apparent diffusion coefficient (ADC) values using contrast-enhanced (CE) T1 weighted image (WI) and T2WI as structural images between manual and semiautomatic segmentation methods. MATERIALS AND METHODS: Between January 2011 and May 2013, 28 patients who underwent brain MR with diffusion weighted image (DWI) and were pathologically confirmed as having glioblastoma participated in our study. The ADC values were measured twice in manual and semiautomatic segmentation methods using CE-T1WI and T2WI as structural images to obtain interobserver and intraobserver reliability. Moreover, intraobserver reliabilities of the different segmentation methods were assessed after subgrouping of the patients based on the MR findings. RESULTS: Interobserver and intraobserver reliabilities were high in both manual and semiautomatic segmentation methods on CE-T1WI-based evaluation, while interobserver reliability on T2WI-based evaluation was not high enough to be used in a clinical context. The intraobserver reliability was particularly lower with the T2WI-based semiautomatic segmentation method in the subgroups with involved lobes < or = 2, with partially demarcated tumor borders, poorly demarcated inner margins of the necrotic portion, and with perilesional edema. CONCLUSION: Both the manual and semiautomatic segmentation methods on CE-T1WI-based evaluation were clinically acceptable in the measurement of mean ADC values with high interobserver and intraobserver reliabilities.

Differentiation of True Recurrence from Delayed Radiation Therapy-related Changes in Primary Brain Tumors Using Diffusion-weighted Imaging, Dynamic Susceptibility Contrast Perfusion Imaging, and Susceptibility-weighted Imaging

PURPOSE: To compare dynamic susceptibility contrast imaging, diffusion-weighted imaging, and susceptibility-weighted imaging (SWI) for the differentiation of tumor recurrence and delayed radiation therapy (RT)-related changes in patients treated with RT for primary brain tumors. MATERIALS AND METHODS: We enrolled 24 patients treated with RT for various primary brain tumors, who showed newly appearing enhancing lesions more than one year after completion of RT on follow-up MRI. The enhancing-lesions were confirmed as recurrences (n=14) or RT-changes (n=10). We calculated the mean values of normalized cerebral blood volume (nCBV), apparent diffusion coefficient (ADC), and proportion of dark signal intensity on SWI (proSWI) for the enhancing-lesions. All the values between the two groups were compared using t-test. A multivariable logistic regression model was used to determine the best predictor of differential diagnosis. The cutoff value of the best predictor obtained from receiver-operating characteristic curve analysis was applied to calculate the sensitivity, specificity, and accuracy for the diagnosis. RESULTS: The mean nCBV value was significantly higher in the recurrence group than in the RT-change group (P=.004), and the mean proSWI was significantly lower in the recurrence group (P<.001). However, no significant difference was observed in the mean ADC values between the two groups. A multivariable logistic regression analysis showed that proSWI was the only independent variable for the differentiation; the sensitivity, specificity, and accuracy were 78.6% (11 of 14), 100% (10 of 10), and 87.5% (21 of 24), respectively. CONCLUSION: The proSWI was the most promising parameter for the differentiation of newly developed enhancing-lesions more than one year after RT completion in brain tumor patients.

A Clinical and Epidemiological Study of Scabies in Korea: A Multicenter Prospective Study / 대한피부과학회지

BACKGROUND: Scabies is an old and common contagious skin disease. The incidence of scabies has decreased through the economic growth of Korea. However, recent outbreaks in medical facilities have created a suspicion that the infection of scabies is an emerging public health problem. OBJECTIVE: We evaluated the epidemiological and clinical aspects of patients diagnosed with scabies in Korea. This prospective study follows the retrospective study already performed by the same authors in 2011. METHODS: A multicenter, prospective study of scabies was performed at 25 hospitals in Korea. We included 914 patients who were diagnosed with scabies. Microscopic examination revealed scabies mites or eggs, or clinical improvement after treatment. Patients were asked to provide information on scabies, especially regarding the contact source, and the physicians examined them. RESULTS: Of the participants, 432 patients were men and 482 were women. Patients aged younger than 10 years and 60~69 years were the most common groups. Scabies more commonly affected patients during the fall and winter. Of the patients, 68.0% were thought to be infected at their homes, followed by nursing homes or hospitals (25.7%), and 31.6% through contact with other patients or, occasionally, staff members, including caregivers. CONCLUSION: We confirmed that scabies is an emerging threat in institutions, especially medical facilities. In addition, we suggest that public and in-hospital education is essential to minimize the problems associated with scabies.

Epidemiological and Clinical Study of Scabies in Korea: Multicenter Retrospective Study / 대한피부과학회지

BACKGROUND: Scabies is one of the common skin diseases observed in developing countries. The incidence of scabies has decreased dramatically since the late 1980s in Korea. However, recent outbreaks in nursing homes or hospitals have been raising public health concerns. OBJECTIVE: We intended to evaluate the epidemiological and clinical aspects of patients diagnosed with scabies in Korea. In particular, we tried to investigate the changing trend of contact sources in our society. METHODS: A multi-center cross sectional study was performed at 25 hospitals in Korea. We included 1,539 patients who were diagnosed with scabies. These patients showed scabies mites or eggs under microscopic examination, or clinical improvement after treatment. Their medical records with information of contact sources were reviewed. RESULTS: Six hundred and ninety-three patients were males and 826 were females. Patients' age from 70 to 79 was the most common followed by patients below 10 years of age. More patients were found in the fall and winter months. 66.7% of patients were thought to be infected at their homes which were situated next to nursing homes or hospitals (23.1%). Place of infection could not be verified in 39.3% of patients. 25.8% of patients were suggested to be infected through contact with medical staff or patients from hospitals or nursing homes. CONCLUSION: We confirmed that the contact sources of scabies are changing in our society; nursing homes and hospitals are emerging sources of infection. The majority of patients are old or very young who are vulnerable to many diseases. Therefore, dermatologists should pay attention to new contact sources and appropriate care of patients.

Induction of Melanogenesis by Rapamycin in Human MNT-1 Melanoma Cells

BACKGROUND: Melanogenesis is one of the characteristic parameters of differentiation in melanocytes and melanoma cells. Specific inhibitors of phosphatidylinositol 3-kinase (PI3K), such as wortmannin and LY294002, stimulate melanin production in mouse and in human melanoma cells, suggesting that PI3K and mammalian target of rapamycin (mTOR) might be involved in the regulation of melanogenesis. OBJECTIVE: The involvement of the mTOR pathway in regulating melanogenesis was examined using human MNT-1 melanoma cells, and the effects of the potent inhibitor of mTOR, rapamycin, in the presence or absence of alpha-melanocyte-stimulating hormone (alpha-MSH) were evaluated. METHODS: In cells treated with rapamycin, cell viability, melanin content, and tyrosinase (TYR) activity were measured and compared with untreated controls. Protein levels of TYR, tyrosinase-related protein (TYRP)-1, TYRP-2, and microphthalmia-associated transcription factor (MITF) were also analyzed by Western blot. RESULTS: In rapamycin-treated cells, the melanin content increased concomitantly with an elevation in TYR activity, which plays a major role in melanogenesis. There was also an up-regulation of TYR, TYRP-1, and MITF proteins. Combined treatment with rapamycin or wortmannin and alpha-MSH increased melanogenesis more strongly than alpha-MSH alone. CONCLUSION: Rapamycin-induced melanin formation may be mediated through the up-regulation of TYR protein and activity. Furthermore, rapamycin and wortmannin, inhibitors of mTOR and PI3K, respectively, have co-stimulatory effects with alpha-MSH in enhancing melanogenesis in melanocyte cells.

Pseudo Continuous Arterial Spin Labeling MR Imaging of Status Epilepticus

PURPOSE: The purpose of this study was to describe arterial spin labeling MR image findings of status epilepticus. MATERIALS AND METHODS: A retrospective chart review within our institute revealed six patients who had been clinically diagnosed as status epilepticus and had also undergone MR imaging that included ASL in addition to routine sequences. RESULTS: Six patients with status epilepticus were studied by conventional MR and arterial spin labeling imaging. All patients showed increased regional CBF correlating with EEG pathology. Notably, in two patients, conventional MRI and DWI showed no abnormal findings whereas pCASL demonstrated regional increased CBF in both patients. CONCLUSION: Arterial spin labeling might offer additional diagnostic capabilities in the evaluation of patients with status epilepticus.

Long Term Results of Right Ventricular Outflow Tract Reconstruction with Homografts

BACKGROUND: Homograft cardiac valves and valved-conduits have been available in our institute since 1992. We sought to determine the long-term outcome after right ventricular outflow tract (RVOT) reconstruction using homografts, and risk factors for reoperation were analyzed. MATERIALS AND METHODS: We retrospectively reviewed 112 patients who had undergone repair using 116 homografts between 1992 and 2008. Median age and body weight at operation were 31.2 months and 12.2 kg, respectively. The diagnoses were pulmonary atresia or stenosis with ventricular septal defect (n=93), congenital aortic valve diseases (n=15), and truncus arteriosus (N=8). Mean follow-up duration was 79.2+/-14.8 months. RESULTS: There were 10 early and 4 late deaths. Overall survival rate was 89.6%, 88.7%, 86.1% at postoperative 1 year, 5 years and 10 years, respectively. Body weight at operation, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were identified as risk factors for death. Forty-three reoperations were performed in thirty-nine patients. Freedom from reoperation was 97.0%, 77.8%, 35.0% at postoperative 1 year, 5 years and 10 years respectively. Small-sized graft was identified as a risk factor for reoperation. CONCLUSION: Although long-term survival after RVOT reconstruction with homografts was excellent, freedom from reoperation was unsatisfactory, especially in patients who had small grafts upon initial repair. Thus, alternative surgical strategies not using small grafts may need to be considered in this subset.

Whitening Effects of Marine Pseudomonas Extract

BACKGROUND: Bacteria associated with marine invertebrates are a rich source of bioactive metabolites. OBJECTIVE: The effects of marine bacteria extracts on pigmentation were investigated to find novel whitening agents. METHODS: The marine bacteria collected near Gangwha Island in Korea were isolated and extracted using organic solvent. The organic extracts were screened and selected using the cell free tyrosinase activity. The whitening effects of the selected extract were further investigated using cultured melanocytes, cultured skin and in vivo zebrafish. The whitening mechanism of the marine extract was also investigated. RESULTS: The marine bacterial methylene chloride extract reduced the pigmentation of Melan-a cells, human melanocytes, cultured skin and in vivo zebrafish. The decrease in pigmentation was due to the inhibition of tyrosinase activity and the expression of tyrosinase and microphthalmia-associated transcription factor protein. These bacteria were identified as a novel Pseudomonas species. CONCLUSION: The methylene chloride extract of marine pseudomonas species possesses a whitening effect. Further chemical isolation and characterization of the active compounds from this marine bacterial extract are needed.

Stimulation of the Extracellular Matrix Production in Dermal Fibroblasts by Velvet Antler Extract

BACKGROUND: Fibroblasts produce many components of the extracellular matrix (ECM) and so they contribute to the maintenance of connective tissue integrity. OBJECTIVE: The aim of this study is to evaluate the effect of velvet antler extract (VAE) on the ECM production of dermal fibroblasts cultured in vitro. METHODS: Primary cultured human dermal fibroblasts were treated with VAE, and then the ECM production was determined by RT-PCR, ELISA and Western blot analysis. Furthermore, the change of gene expression according to VAE treatment was evaluated by cDNA microarray. RESULTS: VAE accelerated the growth of fibroblasts in a dose-dependent manner. VAE increased the production of several ECM components, including type 1 collagen, fibronectin and elastin. In line with these results, the phosphorylations of p42/44 ERK and p38 mitogen-activated protein kinase were markedly increased by VAE, suggesting that the enhancement of ECM production may be linked to the activation of intracellular signaling cascades. VAE also significantly increased cell migration on an in vitro scratch wound test. In cDNA microarray, many genes related with connective tissue integrity were identified to be up-regulated by VAE. CONCLUSION: These results suggest that VAE has a potential to stimulate ECM production, and VAE may be applicable for maintaining the skin's texture.

Angiolymphoid Hyperplasia with Eosinophilia on the Palm

Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon dermal angioproliferating tumor, characterized by red to brown papules or nodules on the head and neck, though also occurring in the mouth, trunk, extremities and inguinal area. The palm is a very unusual site for ALHE, and there have been very few cases reported globally thus far. ALHE can be pruritic and painful and histopathologic findings show vascular proliferation with infiltration of eosinophils and lymphocytes in the dermis. Plump endothelial cells protrude into the lumen. We report a case of ALHE occurring at an unusual site, the right palm, in a 62-year-old man, who had suffered from a solitary pinkish-colored, central depressed round hyperkeratotic plaque on his palm for 4 years. On the basis of clinical and histopathologic data, a diagnosis of ALHE was made. To our knowledge, this is the first report of ALHE on the palm in Korean dermatologic literature.

A Case of Diffuse Subcutaneous Sarcoidosis Presenting as Thickened Extremities / 대한류마티스학회지

Sarcoidosis is multi-systemic disorder of an unknown etiology, and this is histologically characterized by noncaseating granulomatous inflammation. Sarcoidosis may affect the lung, skin, lymph nodes and eyes, but it rarely affects the subcutaneous tissue. There has been no report of diffuse subcutaneous sarcoidosis in Korea. We experienced a 57-year-old female with diffuse subcutaneous sarcoidosis that presented as thickened extremities. The patient complained of edema and skin thickening on both upper extremities. Magnetic resonance imaging revealed the reticular form of sarcoidosis on the forearm and the biopsy showed noncaseating granuloma. She was finally diagnosed as diffuse subcutaneous sarcoidosis and she improved after treatment with corticosteroid. We report here on this unusual case along with a review of the relevant literature.

Comparison of the Efficacy of Topical Antihistamine/Mast Cell Stabilizers in vitro

PURPOSE: To investigate the biologic effects of topical anti-allergic agents with H1-receptor antagonism and inhibition of histamine release from mast cells in the cultured conjunctival cells of patients with vernal keratoconjunctivitis in vitro. METHODS: Conjunctival cells of vernal keratoconjunctivitis were exposed to the anti-allergic agents SCD-P101 (Fexofenadine, Samchundang, Korea), Patanol(R) (Alcon, USA), Zaditen(R) (Novartis, USA), and Azelan(R) (Taejoon, Korea). Efficacy of the topical antihistamine/mast cell stabilizers was evaluated using the MTT assay, measuring the concentration of procollagen and inflammatory cytokines. Cell damage was determined using the lactate dehydrogenase (LDH) assay with dilution rates of 10, 20, and 30% and compared with the balanced salt solution-treated group. Cellular morphologic results were examined by inverted light microscopy and transmission electromicroscopy. RESULTS: Metabolic activity of conjunctival cells decreased at higher concentrations and longer exposure durations, except for the SCD-P101 agent. The procollagen, laminin, IL-6 and IL-8 titers tended to be lower than that of the control in the eyes exposed to all the anti-allergic drugs tested in this study, but the concentration of TNF-beta was similar to that of the control group. Zaditen(R) and Azelan(R) tended to show a greater LDH titer and edema, as well as cytoplasmic and nuclear degeneration of the conjunctival cells than did SCD-P101 or Patanol(R). CONCLUSIONS: Cellular metabolic activity was the highest in the new anti-allergic agent SCD-P101. SCD-P101 and Patanol(R) caused marginally less damage to cultured conjunctival cells than did Zaditen(R) and Azelan(R).

Enhancement of Keratinocyte Differentiation by Rose Absolute Oil

BACKGROUND: Through differentiation processes, keratinocytes provide a physical barrier to our bodies and control skin features such as moisturization, wrinkles and pigmentation. Keratinocyte differentiation is disturbed in several skin diseases such as psoriasis and atopic dermatitis. OBJECTIVE: The aim of this study is to evaluate the keratinocyte differentiation-enhancing effect of rose absolute oil (RAO). METHODS: Primary cultured human normal keratinocytes were treated with RAO, and differentiation then checked by the expression of marker genes. RESULTS: RAO did not induce cytotoxicity on cultured keratinocytes at a dose of 10microM. The level of involucrin, an early marker for keratinocyte differentiation, was significantly increased by RAO. Concomitantly, RAO increased involucrin promoter activity, indicating that RAO increased involucrin gene expression at the mRNA level. Furthermore, RAO increased the level of filaggrin in cultured keratinocytes, and in the granular layer of mouse skin. In line with these results, RAO decreased the proliferation of keratinocytes cultured in vitro. When RAO was applied topically on the tape-stripped mouse skins, it accelerated the recovery of disturbed barrier function. CONCLUSION: These results suggest that RAO may be applicable for the control of skin texture and keratinocyte differentiation-related skin diseases.

A Case of Atypical Granuloma Annulare Involving Both Ears

We report a rare case of granuloma annulare (GA), affecting both ear antihelixes, in a 28-year old male patient that presented with a 1-year history of non-tender, firm, skin-colored, 1~5 mm papules on both ear antihelixes. There was no history of trauma. An excisional biopsy specimen taken from one of the lesions of the right ear revealed infiltration of histiocytes and lymphocytes around a zone of collagen alteration in the dermis. Based on the clinical and pathological findings, the patient was diagnosed with a rare case of bilateral GA of both antihelixes; this is the first report in the Korean dermatology literature.