The effect of synthetic acetylhexapeptide-8 (AH8) on sebaceous function.

OBJECTIVE: This study aims to evaluate the in vitro and clinical effects of topical acetylhexapeptide-8 (AH8) on the appearance of oily skin. METHOD: In vitro SEB-1 human sebocyte cell lines were exposed to different concentrations of AH8, then the lipid content of the sebocytes was measured. For the randomized, controlled, split-face clinical study, participants received AH8 10% lotion formulated in Cetaphil Moisturizing Facial Lotion on one side of their face and the control vehicle lotion on the other side of their face. Facial oiliness was assessed by a trained physician using a three-point grading system, high-resolution digital photographs, and a sebumeter (SM815). Participants also filled out self-assessments of their skin oiliness. RESULTS: The in vitro experiments showed that sebocyte lipid content significantly decreased after AH8 treatment (p < 0.05 at 0.00005% AH8, p = 0.09 at 0.0005% AH8, p < 0.05 at 0.005% AH8, and p < 0.001 at 0.025% AH8). In the clinical study, participants trended towards a 10% reduction (p = 0.16) in sebum production after AH8 treatment in comparison to the vehicle treatment. CONCLUSION: AH8 inhibits the accumulation of lipids in sebocytes in vitro without altering cell proliferation or SREBP-1 expression. Topical AH8 trended towards decreased sebum production in human participants. The use of AH8 may serve as a promising agent to reduce sebocyte lipid production and the appearance of oily skin. RÉSUMÉ: Objectif Cette étude vise à évaluer les effets in vitro et cliniques de l'acétylhexapeptide-8 (AH8) topique sur l'aspect de la peau grasse. Méthode Des lignées cellulaires de sébocytes humains SEB-1 in vitro ont été exposées à différentes concentrations d'AH8, à la suite de quoi la teneur en lipides des sébocytes a été mesurée. Pour l'étude clinique randomisée, contrôlée, en hémi-visage, les participants ont reçu une lotion AH8 10 % formulée dans la lotion hydratante pour le visage Cetaphil d'un côté de leur visage et la lotion témoin de l'autre côté de leur visage. Le sébum du visage a été évalué par un médecin formé à l'aide d'un système de classification à trois points, de photographies numériques à haute résolution et d'un sébumètre (SM815). Les participants ont également rempli des auto-évaluations du sébum de leur peau. Résultats Les expériences in vitro ont montré que la teneur en lipides des sébocytes diminuait significativement après le traitement par AH8 (p < 0.05 à 0.00005 % AH8, p = 0.09 à 0.0005 % AH8, p < 0.001 à 0.025 % AH8). Dans l'étude clinique, les participants avaient tendance à voir leur production de sébum diminuer de 10 % (p = 0.16) après le traitement par AH8, par rapport au traitement par excipient. Conclusion L'AH8 inhibe l'accumulation de lipides dans les sébocytes in vitro sans altérer la prolifération cellulaire ou l'expression de SREBP-1. L'AH8 topique tendait à diminuer la production de sébum chez les participants humains. L'utilisation d'AH8 peut servir d'agent prometteur pour réduire la production de lipides sébocytaires et l'apparence de peau grasse.

Human sebum requires de novo lipogenesis, which is increased in acne vulgaris and suppressed by acetyl-CoA carboxylase inhibition.

Sebum plays important physiological roles in human skin. Excess sebum production contributes to the pathogenesis of acne vulgaris, and suppression of sebum production reduces acne incidence and severity. We demonstrate that sebum production in humans depends on local flux through the de novo lipogenesis (DNL) pathway within the sebocyte. About 80 to 85% of sebum palmitate (16:0) and sapienate (16:1n10) were derived from DNL, based on stable isotope labeling, much higher than the contribution of DNL to triglyceride palmitate in circulation (~20%), indicating a minor contribution by nonskin sources to sebum lipids. This dependence on local sebocyte DNL was not recapitulated in two widely used animal models of sebum production, Syrian hamsters and Göttingen minipigs. Confirming the importance of DNL for human sebum production, an acetyl-CoA carboxylase inhibitor, ACCi-1, dose-dependently suppressed DNL and blocked synthesis of fatty acids, triglycerides, and wax esters but not free sterols in human sebocytes in vitro. ACCi-1 dose-dependently suppressed facial sebum excretion by ~50% (placebo adjusted) in human individuals dosed orally for 2 weeks. Sebum triglycerides, wax esters, and free fatty acids were suppressed by ~66%, whereas non-DNL-dependent lipid species, cholesterol, and squalene were not reduced, confirming selective modulation of DNL-dependent lipids. Last, individuals with acne vulgaris exhibited increased sebum production rates relative to individuals with normal skin, with >80% of palmitate and sapienate derived from DNL. These findings highlight the importance of local sebocyte DNL for human skin sebaceous gland biology and illuminate a potentially exploitable therapeutic target for the treatment of acne vulgaris.

Effects of atopic dermatitis and gender on sebum lipid mediator and fatty acid profiles.

Skin disease alters cutaneous lipid mediator metabolism, and if skin secretions contain evidence of these changes, they may constitute useful clinical matrices with low associated subject burden. The influences of skin diseases on sebum lipid mediators are understudied. Here, sebum oxylipins, endocannabinoids, sphingolipids, and fatty acids were quantified from the non-lesional bilateral cheeks of subjects with and without quiescent atopic dermatitis (AD) using LC-MS/MS and GC-MS. AD decreased C36 [NS] and [NdS] ceramide concentrations. Compared to males, females demonstrated increased concentrations of oxylipin alcohols and ketones, and saturated and monounsaturated non-esterified fatty acids, as well as decreased concentrations of C42 [NS] and [NdS] ceramides. Additionally, contemporaneously collected sweat lipid mediator profiles were distinct, with sebum showing higher concentrations of most targets, but fewer highly polar lipids. Therefore, AD and gender appear to alter sebum lipid metabolism even in non-lesional skin of quiescent subjects.

Effect of Expedited Microneedle-Assisted Photodynamic Therapy for Field Treatment of Actinic Keratoses: A Randomized Clinical Trial.

Importance: Photodynamic therapy (PDT) is an effective and cosmetically favorable treatment modality for actinic keratoses (AKs). However, prolonged incubation times and pain associated with treatment are burdensome to the patient and a hindrance to widespread use of PDT as standard field therapy for AK. Objective: To evaluate efficacy and pain associated with microneedle expedited PDT. Design, Setting, and Participants: The Microneedle Photodynamic Therapy II (MNPDT-II) study was a randomized, single-blinded, split-face controlled, 2-arm clinical trial. Thirty-three participants with AK on the face were recruited in a university dermatology outpatient clinic from 2015 to 2016, and 32 participants completed the study. Interventions: Participants were randomized into 2 incubations arms, either 10-minute or 20-minute aminolevulinic acid (ALA) incubation times, after pretreatment with a microneedle roller (200 um) vs a sham roller. They were blinded to the laterality of microneedle and sham roller assignments. After incubation, they were exposed to blue light (Blu-U, Dusa Pharmaceuticals) for 1000 seconds for a total fluence of 10 J/cm2. Main Outcomes and Measures: The primary outcome was to quantitatively measure AK resolution, and the secondary outcome was to assess pain associated with microneedle pretreatment. Results: Thirty-three individuals were recruited and randomized to either the 20-minute or the 10-minute incubation arm. Thirty-two participants completed the study with a mean follow-up time of 34.5 days in the 20-minute group, and 30.2 days in the 10-minute group. For the 20-minute incubation arm, average AK clearance was 76% vs 58% on the sham side (P < .01), including 3 patients with complete clearance, although not statistically significant (P = .25). Pain assessment on the visual analog scale (VAS) during blue light illumination was not significantly different between the microneedle and sham sides (0.7 and 0.4; P = .28), respectively. For the 10-minute incubation arm AK clearance for the microneedle pretreated side was 43% compared with 38% on the sham side (P = .66). Pain during the blue light exposure was not significantly different between the microneedle and sham sides, 4.5 mm and 3.4 mm (P = .21), respectively. Conclusions and Relevance: Photodynamic therapy with microneedle pretreatment at a 20-minute ALA incubation time significantly improved AK clearance with efficacy similar to that of a conventional 1-hour ALA incubation time. The additional advantage to expedited treatment was that the procedure was virtually painless. However, expedited exposure of a 10-minute ALA incubation time did not reach significantly different AK clearance from the sham control. Trial Registration: clinicaltrials.gov Identifier: NCT02594644.

A systematic review of lactoferrin use in dermatology.

Lactoferrin is a glycoprotein widely present in mammalian secretions and possesses documented protective effects, including antimicrobial and anti-inflammatory properties. While its therapeutic use is being investigated for a myriad of diseases, there is increasing interest in its application for skin disease. Our objective was to systematically review the clinical evidence for the use and efficacy of lactoferrin for the treatment of dermatological conditions. Pubmed and Embase databases were searched for clinical studies evaluating lactoferrin for dermatological conditions. A total of six studies were reviewed. Of the current clinical trials, there is encouraging evidence to suggest that lactoferrin may be beneficial in acne, psoriasis, and diabetic ulcerations. Although the current evidence is promising, further research is necessary to establish lactoferrin as complementary therapy in the clinical setting.

Sweat lipid mediator profiling: a noninvasive approach for cutaneous research.

Recent advances in analytical and sweat collection techniques provide new opportunities to identify noninvasive biomarkers for the study of skin inflammation and repair. This study aims to characterize the lipid mediator profile including oxygenated lipids, endocannabinoids, and ceramides/sphingoid bases in sweat and identify differences in these profiles between sweat collected from nonlesional sites on the unflared volar forearm of subjects with and without atopic dermatitis (AD). Adapting routine procedures developed for plasma analysis, over 100 lipid mediators were profiled using LC-MS/MS and 58 lipid mediators were detected in sweat. Lipid mediator concentrations were not affected by sampling or storage conditions. Increases in concentrations of C30-C40 [NS] and [NdS] ceramides, and C18:1 sphingosine, were observed in the sweat of study participants with AD despite no differences being observed in transepidermal water loss between study groups, and this effect was strongest in men (P < 0.05, one-way ANOVA with Tukey's post hoc HSD). No differences in oxylipins and endocannabinoids were observed between study groups. Sweat mediator profiling may therefore provide a noninvasive diagnostic for AD prior to the presentation of clinical signs.

Ustekinumab to target granulomatous dermatitis in recalcitrant ulcerative necrobiosis lipoidica: case report and proposed mechanism.

We present a 42-year-old woman with no history of diabetes or glucose intolerance who had a 5-year history of ulcerative necrobiosis lipoidica (NL). Despite failure of multiple medications, she experienced clearing of her ulcers after her treatment was changed to ustekinumab. We discuss our patient's disease course and elaborate upon mechanistic reasons for her improvement related to ustekinumab therapy.

The use of hormonal agents in the treatment of acne.

Hormones and androgens play an important role in the pathogenesis of acne. Multiple hormonal modulators are now available for the treatment of acne. The efficacies and side effects of currently available hormonal agents are reviewed here including the use of oral contraceptives, spironolactone, flutamide, cyproterone acetate, finasteride, and cortexolone 17α-propionate. Hormonal therapies are an efficacious treatment option for acne among females. With the growing need to reduce antibiotic exposures, hormonal therapies should be more widely studied and incorporated into acne treatment strategies.

Cedarwood Oil as Complementary Treatment in Refractory Acne.

Acne vulgaris is a widely prevalent chronic skin disease. Although multiple treatments are available, acne can sometimes be refractory to these treatments. The use of alternative medical therapies has increased within dermatology and for acne. This case report describes a patient in whom the addition of cedarwood oil was helpful in controlling acne.

Role of sebaceous glands in inflammatory dermatoses.

Skin is an important interface between the host and its environment. Inflammatory dermatoses often have disrupted skin barrier function, rendering patients more susceptible to allergenic triggers leading to an exaggerated immune response. The skin surface lipid film, an important component of the skin barrier, comprises a mixture of keratinocyte and sebaceous gland-derived lipids. Recent evidence demonstrated that defective keratinocyte lipid synthesis predisposes for the development of atopic dermatitis. However, the important role of sebaceous gland-derived lipids in skin inflammatory diseases may be underrecognized. This overview focuses on the importance of the contribution of sebaceous glands to barrier function. Sebaceous gland alteration may play a role in the pathogenesis of common skin diseases including acne vulgaris, atopic dermatitis, psoriasis, rosacea, and seborrheic dermatitis.