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Background@#Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. @*Objective@#To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. @*Methods@#Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. @*Results@#TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. @*Conclusion@#These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.
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Background@#Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. @*Objective@#To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. @*Methods@#Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. @*Results@#TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. @*Conclusion@#These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.
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Background@#Longitudinal melanonychia (LM) is a common clinical finding. Most cases of LM are benign, and a waitand-see approach is preferred in the management of this condition. Nevertheless, it is important for clinicians to distinguish subungual melanoma (SUM) from other benign LMs. @*Objective@#To evaluate the demographic and clinicopathologic characteristics of LM in the Korean population and to identify the predictor of SUM against other benign conditions. @*Methods@#This was a single-center retrospective cohort study including patients who underwent nail biopsy for LM from January 2000 to May 2019. To identify the predictor of SUM, receiver operating characteristic (ROC) analyses was performed. @*Results@#A total of 68 cases of biopsy-proven LM were included in the analysis. Among the 68 cases, 8 were SUM. In univariable analysis, patients diagnosed with SUM were older (p=0.035) and had a longer disease duration (p=0.004).They also showed multicolor pigmentation of LM (p=0.022),a larger width of LM (p＜0.001), and associated nail plate dystrophy (p=0.010) than patients diagnosed with benign conditions. In multivariable logistic regression, width of LM showed statistical significance (odds ratio, 1.083; 95% confidence interval, 1.018∼1.153). ROC analysis suggested that an LM width ＞28% of the whole nail was the predictor of SUM (area under the curve=0.883; p＜0.001). @*Conclusion@#SUM has distinct demographic and clinical features. The width of LM can predict SUM against other benign LMs.
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Background@#Female-pattern hair loss (FPHL) is a common hair loss disorder in women. The various treatments include topical minoxidil and 17α-estradiol, as well as oral anti-androgens. However, the clinical efficacy of 5α -reductase inhibitors remains controversial. @*Objective@#We evaluated the clinical utility of dutasteride in FPHL patients and how dutasteride promotes hair growth. @*Methods@#We evaluated hair follicle density and thickness before and after oral dutasteride treatment in 24 patients with FPHL. We measured β-catenin activity in primary cultures of human dermal papilla cells (DPCs) using the TOP Flash reporter assay and Western blotting. The expression levels of genes promoting hair growth were quantitatively assessed using quantitative polymerase chain reaction (Q-PCR). @*Results@#The mean vertex hair density increased significantly from 67±14 to 76±13/cm2 (p=0.001) and the mean occipital hair density increased from 89±11 to 94±13/cm2 (p=0.012) after dutasteride treatment. However, the mean hair thickness did not increase. When DPCs were treated with dutasteride, TOP Flash activity increased in a dose-dependent manner, and the protein level of non-phosphorylated (active) β-catenin also increased. The mRNA level of vascular endothelial growth factor increased, but the mRNA levels of the keratinocyte growth factor, insulin growth factor-1, and Noggin were not affected by dutasteride. @*Conclusion@#This study shows a novel mechanism of dutasteride in promoting hair growth and provides support for the possible clinical application of 5α-reductase inhibitors for the treatment of FPHL.
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Background@#Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed. @*Objective@#The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis. @*Methods@#We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model. @*Results@#Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis. @*Conclusion@#Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.
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Background@#The clinical features of inflammatory papulardermatoses of the face are very similar. Their clinical manifestationshave been described on the basis of a small numberof case reports and are not specific. @*Objective@#This studyaimed to use computer-aided image analysis (CAIA) to comparethe clinical features and parameters of inflammatorypapular dermatoses of the face and to develop a formalizeddiagnostic algorithm based on the significant findings. @*Methods@#The study included clinicopathologically confirmedinflammatory papular dermatoses of the face: 8 casesof eosinophilic pustular folliculitis (EPF), 13 of granulomatousperiorificial dermatitis-lupus miliaris disseminatusfaciei (GPD-LMDF) complex, 41 of granulomatous rosacea-papulopustular rosacea complex (GR-PPR) complex,and 4 of folliculitis. Clinical features were evaluated, andarea density of papular lesions was quantitatively measuredwith CAIA. Based on these variables, we developed a predictivemodel for differential diagnosis using classificationand regression tree analysis. @*Results@#The EPF group showedlesion asymmetry and annular clusters of papules in all cases.The GPD-LMDF complex group had significantly higher perioculardensity. The GR-PPR complex group showed a higherarea density of unilateral cheek papules and the highest total area density. According to the predictive model, 3 variableswere used for differential diagnosis of the 4 diseasegroups, and each group was diagnosed with a predictedprobability of 67%∼100%. @*Conclusion@#We statisticallyconfirmed the distinct clinical features of inflammatory papulardermatoses of the face and proposed a diagnostic algorithmfor clinical diagnosis.
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Vitiligo is an acquired depigmenting skin disorder that affects 0.5% to 2% of the population. Skin lesions from vitiligo, white macules and patches on the skin, can pose a substantial psychological burdencan, causing a significant decrease in one’s quality of life. Recent basic and clinical studies have found that vitiligo is an autoimmune disorder, mediated by CD8+ T-cell and interferon-γ-mediated cytokine/chemokines. Although no treatment modality presents a complete cure for vitiligo, current treatment modalities have a modest effect on vitiligo by reversing the disease’s progression, inducing its stabilization, and promoting melanocyte regeneration. Current non-surgical treatment modalities include topical corticosteroids, topical calcineurin inhibitors, systemic corticosteroids, and phototherapy such as narrowband ultraviolet B phototherapy and excimer laser. In addition, clinicians have used and combined non-surgical treatment modalities based on the activity and extent of vitiligo. Moreover, considering the high risk of vitiligo relapse, maintenance therapy for re-pigmented lesions has also been introduced. Lastly, based on the results of recent translational research, new and emerging treatment modalities have been introduced, such as Janus kinase inhibitors. This review presents an overview of the current non-surgical treatment modalities for vitiligo and discusses emerging treatments.
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Vitiligo is an acquired depigmenting skin disorder that affects 0.5% to 2% of the population. Skin lesions from vitiligo, white macules and patches on the skin, can pose a substantial psychological burdencan, causing a significant decrease in one’s quality of life. Recent basic and clinical studies have found that vitiligo is an autoimmune disorder, mediated by CD8+ T-cell and interferon-γ-mediated cytokine/chemokines. Although no treatment modality presents a complete cure for vitiligo, current treatment modalities have a modest effect on vitiligo by reversing the disease’s progression, inducing its stabilization, and promoting melanocyte regeneration. Current non-surgical treatment modalities include topical corticosteroids, topical calcineurin inhibitors, systemic corticosteroids, and phototherapy such as narrowband ultraviolet B phototherapy and excimer laser. In addition, clinicians have used and combined non-surgical treatment modalities based on the activity and extent of vitiligo. Moreover, considering the high risk of vitiligo relapse, maintenance therapy for re-pigmented lesions has also been introduced. Lastly, based on the results of recent translational research, new and emerging treatment modalities have been introduced, such as Janus kinase inhibitors. This review presents an overview of the current non-surgical treatment modalities for vitiligo and discusses emerging treatments.
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BACKGROUND: Accurate assessment of the severity of psoriasis is important in daily practice and clinical studies. However, the assessment of psoriasis area and severity index (PASI) reflects the physician's experience, and thus evaluations by physicians are inherently subjective, with intra-rater and inter-rater variability. OBJECTIVE: To elucidate the effectiveness of PASI educational lectures and the use of reference photographs on the improvement of accuracy and reliability in PASI assessments and to develop effective educational programs for PASI assessments. METHODS: We performed a before-and-after comparison study during nation-wide PASI educational workshops. The participants were asked to assess the severity components of PASI (erythema, thickness, scale, and affected area) three times: in the test administered before an educational lecture, the test immediately after the lecture, and lastly the test with the use of reference photographs. The improvement of accuracy and reliability was analyzed by comparing the results of three tests. RESULTS: Ninety-six board-certified dermatologists and residents participated and 72 participants completed all three tests. The accuracy and reliability of the assessment of severity components of PASI increased significantly after the educational lecture and the use of reference photographs. Use of reference photographs resulted in limited improvements when the recognition of three-dimensional structures was required, such as in the assessment of thickness or scale. CONCLUSION: Our study confirmed that the combination of standardized educational training and reference photographs can improve the accuracy and reliability of PASI assessments. Understanding how to evaluate three-dimensional psoriatic lesions can help with proper assessment of the severity of psoriasis.
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Educação , Aula , Psoríase , Índice de Gravidade de DoençaRESUMO
BACKGROUND: No study to date has focused on the changes in laboratory test results and related risk factors in patients with psoriasis treated with prolonged Cyclosporine A (CsA) therapy. OBJECTIVE: The objective of this study was to investigate the changes of laboratory values and related risk factors in patients with psoriasis treated with CsA in a real-world setting. METHODS: Records of patients with psoriasis treated with CsA at an outpatient clinic were collected, and a Cox proportional hazards regression model was used. RESULTS: Of the 128 patients included in this study, 28 patients (21.9%) showed laboratory test abnormalities over a mean medication period of 11.6 months. Older age (hazard ratio [HR], 1.174; 95% confidence interval [CI], 1.068~1.370; p=0.007) and pre-existing kidney disease (HR, 0.008; 95% CI, 0~0.205; p=0.001) significantly increased the risk of renal dysfunction. Male sex was the only significant risk factor for liver enzyme elevation (HR, 0.284; 95% CI, 0.081~0.784; p=0.026) and uric acid abnormality (HR, 0.048; 95% CI, 0~0.372; p=0.046). CONCLUSION: This is an in-depth analysis of laboratory changes and related risk factors in patients with psoriasis treated with CsA. Liver is the most commonly affected organ of CsA toxicity. Older age, male sex, and presence of kidney disease were risk factors associated with laboratory abnormality during CsA treatment.
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Humanos , Masculino , Instituições de Assistência Ambulatorial , Técnicas de Laboratório Clínico , Ciclosporina , Nefropatias , Fígado , Psoríase , Fatores de Risco , Ácido ÚricoRESUMO
BACKGROUND: The continuous use of biologic agents in the treatment of psoriasis has been reported to result in successful and sustained therapeutic effects and safety. However, some patients choose intermittent and repetitive treatment. OBJECTIVE: To determine the factors for selecting intermittent and repetitive ustekinumab treatment for the management of psoriasis. METHODS: From January 2011 to October 2016, we enrolled 30 psoriasis patients who discontinued ustekinumab treatment and were followed up for psoriasis treatment. We reviewed data regarding patients' clinical characteristics and the treatment they received, and investigated the factors for selecting intermittent treatment. RESULTS: A total of 52 ustekinumab treatment periods were administered to the 30 patients. Of the 52 treatment periods, 34.6% were covered by insurance and 82.4% were discontinued after sufficient improvement had been made or at the patient's request. Further analysis comparing the first and second ustekinumab treatments revealed that the patients who used ustekinumab in second treatment were more likely to be insured. In addition, the rate of patients reaching psoriasis area and severity index (PASI)75 and PASI90 was similar between the first and subsequent ustekinumab treatments. CONCLUSION: We found that the patients who used ustekinumab intermittently were those who were satisfied with the outcome of ustekinumab treatment but could not afford the treatment. These results suggested that economic burden can be a factor for the patients' choice of short-term intermittent treatment. The expansion of insurance coverage can increase the effectiveness of, and patients' satisfaction with, the management of psoriasis.
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Humanos , Fatores Biológicos , Efeitos Psicossociais da Doença , Esquema de Medicação , Seguro , Cobertura do Seguro , Psoríase , Usos Terapêuticos , UstekinumabRESUMO
BACKGROUND: Drug survival, defined as the time until discontinuation, is a parameter reflecting real-world therapeutic effectiveness. Few studies have examined the influence of economic factors on the drug survival of biologic agents for psoriasis, particularly in Asian countries. OBJECTIVE: To determine the drug survival for ustekinumab in real-life settings and investigate the factors affecting drug survival for psoriasis patients in Korea. METHODS: We evaluated 98 psoriasis patients who were treated with ustekinumab at a single center. We analyzed the efficacy and drug survival of ustekinumab. Cox proportional hazard analysis and competing risk regression analysis were performed to reveal the factors affecting the drug survival of ustekinumab. RESULTS: The overall mean drug survival was 1,596 days (95% confidence interval [CI], 904~2,288). Among the 39 cessations of ustekinumab treatment, 9 (23.1%) patients discontinued treatment after experiencing satisfactory results. Multivariate Cox proportional hazard analysis revealed that paying on patients' own expense was the major predictor for the discontinuation of ustekinumab (hazard ratio [HR], 9.696; 95% CI, 4.088~22.998). Competing risk regression analysis modeling of discontinuation because of factors other than satisfaction of an event also revealed that ustekinumab treatment at the patient's expense (HR, 4.138; 95% CI, 1.684~10.168) was a predictor of discontinuation rather than satisfaction. CONCLUSION: The results of our study revealed that the cost of biologics treatment affects the drug survival of ustekinumab and suggested that economic factors affect the drug survival of ustekinumab treatment in Korea.
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Humanos , Povo Asiático , Fatores Biológicos , Produtos Biológicos , Custos e Análise de Custo , Coreia (Geográfico) , Psoríase , UstekinumabRESUMO
BACKGROUND: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. OBJECTIVE: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). METHODS: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. RESULTS: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. CONCLUSION: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.
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Animais , Camundongos , Expressão Gênica , Estudo de Associação Genômica Ampla , Imuno-Histoquímica , Incidência , Interleucinas , Queratinócitos , Psoríase , Pele , DermatopatiasRESUMO
BACKGROUND: Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. OBJECTIVE: To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. METHODS: From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. RESULTS: A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were 497.81±512.06 days and 115.68±184.34 g in cyclosporine and 264.19±264.71 days and 448.71±448.63 mg in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. CONCLUSION: We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis.
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Humanos , Ácido Aspártico , Testes de Química Clínica , Terapia Combinada , Ciclosporina , Seguimentos , Hipertensão , Metotrexato , Psoríase , Ácido ÚricoRESUMO
BACKGROUND: Psoriasis is a chronic inflammatory disease. In the treatment of psoriasis, cyclosporine is commonly prescribed systemic agents. However, long-term use of cyclosporine is not recommended because of side effects such as nephrotoxicity or hypertension. OBJECTIVE: To ascertain the improved safety of rotational therapy using cyclosporine and methotrexate, we investigated the frequency of abnormal results in laboratory test after long term rotational therapy using cyclosporine and methotrexate. METHODS: From January 2009 to June 2014, patients who were treated with cyclosporine or methotrexate were enrolled. The clinical data and usage of medications were reviewed. Laboratory tests were conducted before starting the treatment and regularly follow-up. The occurrences of any laboratory abnormalities during the treatments were investigated. RESULTS: A total of 21 psoriatic patients were enrolled. The mean of medication period and cumulative dose of cyclosporine and methotrexate were 497.81±512.06 days and 115.68±184.34 g in cyclosporine and 264.19±264.71 days and 448.71±448.63 mg in methotrexate. Laboratory abnormalities were found in total two patients after rotational therapy: two patients (9.5%) in aspartate aminotransferase/alanine aminotransferase and one patient (4.8%) in uric acid. No laboratory abnormalities were found in renal function test. CONCLUSION: We found that the rotational approaches using cyclosporine and methotrexate reduced the possibility of the development of nephrotoxicity. In addition to other advantage such as quick switching from one agent to another, the rotational therapy using cyclosporine and methotrexate can minimize the adverse events during the systemic treatment of chronic plaque psoriasis.
