A randomized, double-blind, multi-center, placebo-controlled, Phase 2 clinical trial to evaluate the efficacy and safety of DWJ211 in the treatment of moderate to severe submental fat.

Excessive accumulation of submental fat (SMF) causes a lower face cosmetic problem. A lipolytic injectable has recently been developed as a solution. The objective of this study is to investigate the effects and safety of DWJ211 (a newly developed lipolytic injectable) in the reduction of SMF and to identify the optimum dose. In this multi-center, double-blind, placebo-controlled study, subjects with moderate to severe SMF were randomized to injections of DWJ211 0.5%, DWJ211 1%, DWJ211 2% or placebo in the submental area, every 4 weeks, up to Week 12. Efficacy was determined by improvements in physician-assisted SMF rating scales (PA-SMFRS) and subject-assisted SMF rating scales (SA-SMFRS) 4 weeks after the last treatment (Week 16). Safety was assessed by inquiries, subject diary entries of adverse events, laboratory tests, and vital sign checks. Of 140 enrolled subjects, 136 were included in the analysis. The proportions of subjects, who achieved ≥1-grade improvement on the PA-SMFRS were 41.7%, 65.7%, 84.4%, and 72.7%, and the proportions of subjects, who achieved ≥1-grade improvement on the SA-SMFRS were 50.0%, 71.4%, 93.8%, and 81.8% for the placebo, DWJ211 0.5%, DWJ211 1%, and DWJ211 2% group, respectively. Adverse drug reactions (ADRs) were more common in each of the treatment groups compared with placebo, with the most common ADR being injection site pain. No subjects experienced any serious adverse events. In conclusion, the 1% DWJ211 dose was beneficial for SMF reduction and had a tolerable safety profile. Thus, we selected 1% as the dose to be tested in a Phase 3 clinical trial.

Comparison of the effects of polynucleotide and hyaluronic acid fillers on periocular rejuvenation: a randomized, double-blind, split-face trial.

BACKGROUND: Filler injection has become an extremely popular method for facial skin rejuvenation, including the periorbital area. In the recent years, new polynucleotide (PN)-containing filler products have been used for esthetic purposes. AIM: We aimed to investigate the efficacy and safety of PN filler injection in the periorbital area. PATIENTS/METHODS: A total of 27 subjects were enrolled in this randomized, pair-matched, and active-controlled study. Each subject received filler injections thrice with two-week intervals, with a PN filler injection on one side and a non-crosslinked hyaluronic acid (HA) filler injection on the contralateral side of the periorbital area. RESULTS: Improvements in the visual analog scale and global esthetic improvement scale scores were not significantly different between the PN and HA groups. The improvement rates of skin elasticity and hydration decreased over time in both groups, with the PN group showing a higher improvement rate. The improvement rates of roughness and pore volume were higher in the PN group than in the HA group. The improvement rate of dermal density was not significantly different between the groups. No serious adverse events were reported. CONCLUSION: The PN filler injection is effective and safe for periorbital rejuvenation.

Ursodeoxycholic Acid May Inhibit Environmental Aging-Associated Hyperpigmentation.

Extrinsic aging of the skin caused by ultraviolet (UV) light or particulate matter is often manifested by hyperpigmentation due to increased melanogenesis in senescent skin. Ursodeoxycholic acid (UDCA), which has been commonly used as a health remedy for liver diseases, is known to possess antioxidant properties. This study was done to investigate whether UDCA inhibits cellular aging processes in the cells constituting human skin and it reduces melanin synthesis. ROS, intracellular signals, IL-1α, IL-8, TNF-α, cyclooxygenase (COX)-2, type I collagen, and matrix metalloproteinases (MMPs) levels were measured in human dermal fibroblasts treated with or without UDCA after UV exposure. Melanin levels and mechanistic pathways for melanogenesis were investigated. UDCA decreased ROS, senescence-associated secretory phenotype (SASP), and proinflammatory cytokines induced by UV treatment. UDCA reduced melanogenesis in normal human melanocytes cocultured with skin constituent cells. Our results suggest that UDCA could be a comprehensive agent for the treatment of environmental aging-associated hyperpigmentation disorders.

A multicenter, randomized, double-blind comparison of two hyaluronic acid fillers in mid-face volume restoration in Asians: A 2-year extension study.

The long-term effectiveness and safety of hyaluronic acid fillers in mid-face volume restoration in Asians remain unclear. The objective of this study was to compare the long-term effectiveness and safety of Neuramis Volume Lidocaine (SHAPE-NVL) and Juvederm Voluma with Lidocaine (VYC-20L) in mid-face volume restoration in Asians. Overall, 88 Korean subjects with moderate-to-severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received SHAPE-NVL on one side and VYC-20L on the contralateral side of the face. Of the 81 subjects who completed the 48-week primary study, 69 subjects were enrolled in an extension study lasting 104 weeks. MFVDS score and global aesthetic improvement were assessed at each visit. Response was defined as a ≥1-point reduction in MFVDS. At weeks 36 and 48, the responder rates for SHAPE-NVL were 81.93% and 80.72%, while those for VYC-20L were 85.54% and 81.92%, respectively. At the 104-week visit, the responder rates were 73.91% and 72.46% for SHAPE-NVL and VYC-20L, respectively. No subjects experienced any serious adverse events during the trial. SHAPE-NVL and VYC-20L showed comparable longevity and safety in mid-face volume restoration over 2 years in Asians. Both had durable effects for up to 2 years with minimal safety concerns.

The efficacy and safety of BM-PHA for the correction of nasolabial folds: a multicenter, randomized, double-blind, split-face clinical trial.

Background: Multiple types of fillers have been developed for soft tissue augmentation.Objective: We investigated the efficacy and safety of the novel filler BM-PHA.Methods: In this multicenter, randomized, split-face study, 91 participants received injections of BM-PHA and Restylane Perlane (PER) into the nasolabial folds. Efficacy was determined by the improvements in the Wrinkle Severity Rating Score (WSRS) and Global Esthetic Improvement Scale (GAIS), and safety by adverse events, laboratory tests, and a check of vital signs.Results: WSRS scores assessed by independent evaluators at Week 24, the primary efficacy measure, showed no significant difference between the two treatments. The treatments also showed no significant differences in WSRS scores assessed by the evaluators at Week 8 and WSRS and GAIS scores assessed by the treating investigators and participants at Weeks 8 and 24. The proportion of nasolabial folds whose WSRS scores improved by at least one grade at Week 24 was similar between the treatments. Only minor local side effects were reported without sequelae.Conclusion: BM-PHA was not inferior to PER in the treatment of moderate to severe nasolabial folds and may be an appropriate alternative product for their improvement. Further studies are needed to confirm the long-term safety of BM-PHA.

"A Multi-center, randomized, double blinded, comparative study of two hyaluronic acid fillers for temporary restoration of mid-face volume in Asians".

BACKGROUND: There have been few studies using hyaluronic acid fillers to restore mid-face volume deficit especially in Asians. AIMS: This study compared the efficacy and safety of two highly cohesive hyaluronic acid fillers, Neuramis® Volume Lidocaine and Juvederm® Voluma® with Lidocaine (VYC-20L), for temporary restoration of mid-face volume in Asians. PATIENTS/METHODS: A total of 88 subjects with moderate to severe age-related mid-face volume deficit on the Mid-Face Volume Deficit Scale (MFVDS) received Neuramis® Volume Lidocaine on one side and VYC-20L on the other side of the face. Response was defined as a ≥1 point reduction in MFVDS at 24 weeks after the injection by photographic assessment. Secondary end points included photographic and live assessments of MFVDS and its changes at week 4, 12, and 24; global aesthetic improvements, as assessed by the investigators and the subjects at each visit; and the proportion of subjects who received touch-up treatment. RESULTS: The response rates of the sides treated with Neuramis® Volume Lidocaine and VYC-20L were identical (96.39%) at week 24, demonstrating that Neuramis® Volume Lidocaine was noninferior to VYC-20L. Photographic and live assessments of MFVDS and its changes, global aesthetic improvement, and the proportion of subjects who received touch-up treatment did not differ significantly during follow-up. CONCLUSIONS: Neuramis® Volume Lidocaine was not inferior to VYC-20L in temporarily restoring mid-face volume at 24 weeks after treatment. Both of these highly cohesive hyaluronic acid fillers can be used effectively and safely for the correction of mid-face volume loss in Asians.

A case of recurrent pigmented macules in Laugier-Hunziker syndrome treated using a Q-switched Nd-YAG laser.

Laugier-hunziker syndrome (LHS) is a sporadic and acquired melanotic pigmentation of lips and oral mucosa which is not associated with gastrointestinal hamartomas in contrast to Peutz-Jeghers syndrome. Treatment using Q-switched neodymium: yttrium-aluminum-garnet (QS-ND:YAG) laser, Q-switched alexandrite laser and, cryotherapy have been reported. However, to the best of our knowledge, there is no report regarding long-term follow-up for recurrence. Herein we report the clinical features and the treatment of recurrent pigmented lesions in LHS patients. A patient diagnosed with LHS seven years ago presented with recurrent labial macules. She had undergone QS-ND:YAG laser 7 years ago and the labial macules have been gone several years. A physical examination revealed the macules were mainly on new locations and the spots on the site where the laser was previously done rarely recur. The untreated pigmented macules on gum were maintained in the same shape for seven years. Recurrent lesions of the lips and previously untreated macules on the gums were successfully treated again with the QS-ND:YAG laser as done in 7 years ago. Our case shows a long-term clinical course of laser-treated labial macules in LHS and treatment response of recurred lesions.

Skin equivalent assay: An optimized method for testing for hair growth reconstitution capacity of epidermal and dermal cells.

Hair follicle reconstitution requires highly organized epithelial-mesenchymal interactions. Skin equivalents containing the epidermal and dermal cells with hair reconstitution capacity can reproduce these processes, but have not been established. This study was conducted to develop a hair follicle-producing three-dimensional (3D) skin equivalent assay using neonate mouse epidermal and dermal cells. A skin equivalent comprised of mouse dermal cells (MDCs) embedded in type I collagen and overlaid with mouse epidermal cells (MECs) was used. MDCs were mixed with type I collagen and cultured for 7 days. One day after adding MECs on top, the composites were grafted onto nude mice. MDCs cultured on a two-dimensional (2D) plate for 7 days and mixed with MECs as a negative control, and freshly isolated MDCs and MECs mixture (chamber assay) as a positive control were also grafted. Six weeks after grafting, regenerated hair follicles were analysed. Our 3D skin equivalent culture assay reproducibly regenerated hair follicles, while MDCs precultured in the 2D model with MECs did not. Compared to the chamber assay, which produced randomly oriented hair follicles, nearly all regenerated hair follicles in our assay extruded through the skin and numerous regenerated hair follicles were higher than those in the chamber assay. Several representative genes associated with hair induction showed higher expression in our assay than in the 2D model. When Wnt3a was added, the number of regenerated hairs increased. Organized hair follicle regeneration was accomplished using our assay. This approach can be applied to assess a test agent with hair growth-promoting effects.

Association Between Premature Hair Greying and Metabolic Risk Factors: A Cross-sectional Study.

The association of hair greying with metabolic syndrome is not well known, while association with obesity and coronary artery disease has been suggested. A cross-sectional study was conducted to identify an association between premature hair greying and metabolic risk factors. Of the 1,929 young healthy subjects (1,067 men and 862 women), 704 (36.4%) were categorized in the premature hair greying group. Waist circumference (means of non-premature hair greying vs. premature hair greying, 74.3 vs. 76.3 cm; p < 0.001), systolic (109.2 vs. 111.7 mmHg; p<0.001) and diastolic (65.0 vs. 66.2 mmHg; p = 0.003) blood pressures, and fasting blood sugar (90.8 vs. 91.6 mg/dl; p = 0.013) were higher and serum high-density lipoprotein cholesterol (68.1 vs 65.4 mg/dl; p < 0.001) was lower in premature hair greying group. Multivariate logistic regression analysis showed that metabolic risk factors ≥ 2 was independently associated with premature hair greying after controlling for confounding factors (odds ratio 1.725; p = 0.036). The present study revealed an association between premature hair greying and metabolic risk factors.

Allergen Sensitization Pattern by Sex: A Cluster Analysis in Korea.

BACKGROUND: Allergens tend to sensitize simultaneously. Etiology of this phenomenon has been suggested to be allergen cross-reactivity or concurrent exposure. However, little is known about specific allergen sensitization patterns. OBJECTIVE: To investigate the allergen sensitization characteristics according to gender. METHODS: Multiple allergen simultaneous test (MAST) is widely used as a screening tool for detecting allergen sensitization in dermatologic clinics. We retrospectively reviewed the medical records of patients with MAST results between 2008 and 2014 in our Department of Dermatology. A cluster analysis was performed to elucidate the allergen-specific immunoglobulin (Ig)E cluster pattern. RESULTS: The results of MAST (39 allergen-specific IgEs) from 4,360 cases were analyzed. By cluster analysis, 39items were grouped into 8 clusters. Each cluster had characteristic features. When compared with female, the male group tended to be sensitized more frequently to all tested allergens, except for fungus allergens cluster. CONCLUSION: The cluster and comparative analysis results demonstrate that the allergen sensitization is clustered, manifesting allergen similarity or co-exposure. Only the fungus cluster allergens tend to sensitize female group more frequently than male group.

Development of a Model for Chemotherapy-Induced Alopecia: Profiling of Histological Changes in Human Hair Follicles after Chemotherapy.

Optimized research models are required to further understand the pathogenesis and prophylaxis of chemotherapy-induced alopecia. Our aim was to develop a mouse model for chemotherapy-induced alopecia by follicular unit transplantation of human hair follicles onto immunodeficient mice. Twenty-two weeks after transplantation, a single dose of cyclophosphamide (Cph) was administered to mice in the Cph100 (100 mg/kg) and Cph150 (150 mg/kg) groups. On day 6, hair follicles showed dystrophic changes, with swollen dermal papilla and ectopic melanin clumping in the hair bulb. In addition, upregulated expression of apoptotic regulators [P53, Fas/Fas-ligand, tumor necrosis factor-related apoptosis-inducing ligand/tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAIL/TRAIL receptor), and Bax], increased apoptotic matrix keratinocytes, downregulated Ki67 expression, and decreased melanogenic protein in the hair bulb were noted in both groups. After 12 treatment days, hair follicles in Cph100 mice appeared to diminish dystrophic changes. In contrast, hair follicles of Cph150 mice prematurely entered a dystrophic catagen phase after 9 treatment days, and immunofluorescence staining for Ki67 and melanogenic protein expressions was barely visible. Two hair follicle damage response pathways were observed in this model, namely dystrophic anagen (Cph100) and catagen (Cph150) pathways. Our model might be useful for further understanding the impact of chemotherapy on human hair follicles.

Long-term utility and durability of the therapeutic effects of bimatoprost 0.03% for eyelash augmentation in healthy Asian subjects.

BACKGROUND: Eyelashes of Asians differ from those of Caucasians in morphology and growth characteristics. Ethnic differences also exist for the tolerability profile of prostaglandin analogues. OBJECTIVE: To evaluate the long-term utility and durability of bimatoprost 0.03% in eyelash augmentation in Asian females. METHODS: One cohort received bimatoprost 0.03% for 36 weeks and another for 20 weeks, with the latter cohort followed for 16 weeks after treatment cessation. The primary endpoint was the percent change in eyelash length at week 20. Secondary measures included percent change in eyelash thickness and darkness, physician's Global Eyelash Assessment and patient satisfaction. RESULTS: At week 20, eyelash length was enhanced in a time-dependent manner, with maximum improvement achieved (19.3%; p < 0.0001). Significant improvements in thickness and darkness were also achieved (22.9%, 6.0%; p < 0.0001). 77.8% of subjects improved by ≥1 grade on Global Eyelash Assessment, with 83.1% satisfied/very satisfied. Improvements were maintained with ongoing treatment to 36 weeks, while these effects were progressively lost with discontinuation. CONCLUSION: Bimatoprost 0.03% safely enhanced eyelashes in Asian females, maintained with ongoing treatment. Cessation of treatment was associated with progressive loss of effects.

Topical valproic acid increases the hair count in male patients with androgenetic alopecia: a randomized, comparative, clinical feasibility study using phototrichogram analysis.

Valproic acid (VPA), a widely used anticonvulsant, inhibits glycogen synthase kinase 3ß and activates the Wnt/ß-catenin pathway, which is associated with hair growth cycle and anagen induction. To assess the efficacy of topical VPA for treating androgenetic alopecia (AGA), we performed a randomized, double-blind, placebo-controlled clinical trial. Male patients with moderate AGA underwent treatment with either VPA (sodium valproate, 8.3%) or placebo spray for 24 weeks. The primary end-point for efficacy was the change in hair count during treatment, which was assessed by phototrichogram analysis. Of the 40 patients enrolled in the study, 27 (n = 15, VPA group; n = 12, placebo group) completed the entire protocol with good compliance. No statistical differences in age, hair loss duration and total hair count at baseline were found between the groups. The mean change in total hair count was significantly higher in the VPA group than in the placebo group (P = 0.047). Both groups experienced mostly mild and self-limited adverse events, but their differences in prevalence rates were similar between the two groups (P = 0.72). A subject treated with topical VPA developed ventricular tachycardia, but it did not seem to be related to the VPA spray. Topical VPA increased the total hair counts of our patients; therefore, it is a potential treatment option for AGA.

The pattern of hair dyeing in koreans with gray hair.

BACKGROUND: Hair graying is considered as a part of normal ageing process. Nonetheless, this process raises a significant cosmetic concern, especially among ethnic Korean elderly whose baseline hair color is black. For this reason, Korean elderly dye their hair with frequency despite the risk of dermatologic problems such as allergic contact dermatitis. OBJECTIVE: In this study, the authors investigate the prevalence and pattern of hair dyeing and its relation with scalp diseases in Korea. METHODS: Six hundred twenty subjects (330 men and 290 women) with graying hair were given a questionnaire survery and underwent a physical examination. RESULTS: Of the 620 total, 272 subjects (43.9%) dyed their hair. Hair dyeing was significantly more frequent among women than among men (p<0.001). Subjects from 50 to 69 years of age showed higher prevalence of hair dyeing when compared to either younger or older groups. Subjective self-assessment of the extent of hair graying was associated with increased prevalence of hair dyeing, that is, individuals who feel graying has advanced by more than 20% of the overall hair were much more likely to dye their hair (p<0.001). Hair dyeing did not correlate with either alopecia or scalp disease. CONCLUSION: Our survey has found that the prevalence of hair dyeing is higher among Korean women than men. People in their fifties and sixties and people with more than 20% extent of grayness were more likely to dye their hair than otherwise. Hair dyeing was not associated with any increase in the prevalence of scalp diseases.

Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapy-induced alopecia.

Epidermal growth factor (EGF) is not only a cell growth stimulant but also has a catagen-inducing effect. Because chemotherapeutic agents primarily damage anagen hair follicles, it would be important to investigate whether catagen inducers have beneficial effects in chemotherapy-induced alopecia (CIA). We pretreated hair follicles with topical EGF-liposomal solution in the C57BL/6 mouse model of cyclophosphamide-induced alopecia and observed the catagen-inducing property and damage response pathway after CIA. We confirmed that topical EGF application induced a catagen-like stage and found that these catagen-like hairs were protected from chemotherapy-mediated damage. Moreover, our results showed that EGF treatment favoured primary hair recovery via the dystrophic anagen pathway after CIA. Given that hair follicles subjected to less severe chemotherapeutic insult enter the dystrophic anagen pathway followed by primary recovery, the results of this study suggest that catagen inducers could be useful as a new alopecia-protection strategy, especially in the context of CIA.

Efficacy and Safety of Pueraria lobata Extract in Gray Hair Prevention: A Randomized, Double-Blind, Placebo-Controlled Study.

BACKGROUND: Graying of hair-a sign of aging-raises cosmetic concerns. Individuals with gray hair often look older than others their age; therefore, some dye their hair for aesthetic purposes. However, hair colorants can induce many problems including skin irritation, allergic reaction and hair-breakage. OBJECTIVE: This randomized, double-blind clinical trial was performed in order to examine the effects of APHG-1001, a compound including an extract from Pueraria lobata, on graying hair. METHODS: A total of 44 female subjects were randomly treated with either APHG-1001 or placebo twice daily for 24 weeks. Using the phototrichogram analysis, a count of newly developed gray hair was estimated. Investigator assessment and subject self-assessment were also performed in order to evaluate the efficacy of the compound. RESULTS: The mean number of newly developed gray hair at 24 weeks was 6.3/cm(2) in the APHG-1001 group and 11.4/cm(2) in the placebo group; the difference was statistically significant (p<0.05). However, the investigator assessment and subject self-assessment did not show any significant change in the gross appearance of hair grayness by the end of the study. No severe adverse events in either group were observed. Moreover, the incidence of adverse events did not differ between the groups. CONCLUSION: This clinical trial revealed that APHG-1001, which contains an extract of P. lobata, could prevent the development of new gray hair without any remarkable adverse effects. Thus, it can be considered as a viable treatment option for the prevention of gray hair.