Hyperglycemia-activated 11ß-hydroxysteroid dehydrogenase type 1 increases endoplasmic reticulum stress and skin barrier dysfunction.

The diabetes mellitus (DM) skin shows skin barrier dysfunction and skin lipid abnormality, similar to conditions induced by systemic or local glucocorticoid excess and aged skin. Inactive glucocorticoid (GC) is converted into active glucocorticoid by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Hyperglycemia in DM and excessive GC are known to increase endoplasmic reticulum (ER) stress. We hypothesized that hyperglycemia affects systemic GC homeostasis and that the action of skin 11ß-HSD1 and GC contributes to increased ER stress and barrier defects in DM. We compared 11ß-HSD1, active GC, and ER stress between hyperglycemic and normoglycemic conditions in normal human keratinocytes and db/db mice. 11ß-HSD1 and cortisol increased with time in keratinocyte culture under hyperglycemic conditions. 11ß-HSD1 siRNA-transfected cells did not induce cortisol elevation in hyperglycemic condition. The production of 11ß-HSD1 and cortisol was suppressed in cell culture treated with an ER stress-inhibitor. The 14-week-old db/db mice showed higher stratum corneum (SC) corticosterone, and skin 11ß-HSD1 levels than 8-week-old db/db mice. Topical 11ß-HSD1 inhibitor application in db/db mice decreased SC corticosterone levels and improved skin barrier function. Hyperglycemia in DM may affect systemic GC homeostasis, activate skin 11ß-HSD1, and induce local GC excess, which increases ER stress and adversely affects skin barrier function.

Morphologic and molecular biologic analyses of the skin rejuvenation effect of the fractional 1064-nm picosecond laser: An animal study.

OBJECTIVES: Application of the picosecond laser in the field of dermatology has expanded from tattoo removal to skin rejuvenation on a clinical basis. Although various mechanisms of pigment removal have been elucidated, the molecular changes associated with skin rejuvenation have yet to be identified. The aim of this study was to explore the theoretical basis and to evaluate the efficacy of skin rejuvenation using a 1064-nm fractional picosecond laser in a mouse model. METHODS: We conducted an in vivo study using a fractional picosecond laser on the skin of old and young female hairless mice and performed topographical, histological, micro-, and electron microscopic assessments. RESULTS: The topography of the skin surface was enhanced and showed increased dermal thickness on histological examination. Electron microscopy revealed disarranged collagen bundles with microspaces and vascular leakage in the upper dermis. Levels of collagen synthesis markers and various inflammatory cytokines, such as procollagens, interleukin-1ß, tumor necrosis factor-α, and heat shock proteins, were elevated in the laser-treated skin. CONCLUSIONS: This study provides a possible mechanism for the skin rejuvenation effect of fractional picosecond laser that has been reported previously in clinical observations. Based on our findings, the fractional picosecond laser could be widely applied in clinical settings where dermal regeneration and promotion of skin rejuvenation is required.

Increased prevalence of transfusion-transmitted diseases among people with tattoos: A systematic review and meta-analysis.

Whether having a tattoo increases the risk of transfusion-transmitted diseases (TTDs) is controversial. Although a few studies have suggested a strong association between having tattoos and TTDs, other studies have not shown the significance of the association. In addition, previous studies mainly focused only on hepatitis C viral infections. The objective of our study was to identify the prevalence and risk of TTDs in people with tattoos as compared with the non-tattooed population. A systematic review of the studies published before January 22, 2021, was performed using the Pubmed, Embase, and Web of Science databases. Observational studies on hepatitis C virus (HCV), hepatitis B virus (HBV), human immunodeficiency virus (HIV), and syphilis infections in people with and without tattoos were included. Studies that reported disease status without serological confirmation were excluded. A total of 121 studies were quantitatively analyzed. HCV (odds ratio [OR], 2.37; 95% confidence interval [CI], 2.04-2.76), HBV (OR, 1.55; 95% CI, 1.31-1.83), and HIV infections (OR, 3.55; 95% CI, 2.34-5.39) were more prevalent in the tattooed population. In subgroup analyses, the prevalence of HCV infection was significantly elevated in the general population, hospital patient, blood donor, intravenous (IV) drug user, and prisoner groups. IV drug users and prisoners showed high prevalence rates of HBV infection. The prevalence of HIV infection was significantly increased in the general population and prisoner groups. Having a tattoo is associated with an increased prevalence of TTDs. Our approach clarifies in-depth and supports a guideline for TTD screening in the tattooed population.

Increased Expression of 11ß-Hydroxysteroid Dehydrogenase Type 1 Contributes to Epidermal Permeability Barrier Dysfunction in Aged Skin.

Inactive cortisone is converted into active cortisol by 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1). Excessive levels of active glucocorticoids could deteriorate skin barrier function; barrier impairment is also observed in aged skin. In this study, we aimed to determine whether permeability barrier impairment in the aged skin could be related to increased 11ß-HSD1 expression. Aged humans (n = 10) showed increased cortisol in the stratum corneum (SC) and oral epithelium, compared to young subjects (n = 10). 11ß-HSD1 expression (as assessed via immunohistochemical staining) was higher in the aged murine skin. Aged hairless mice (56-week-old, n = 5) manifested greater transepidermal water loss, lower SC hydration, and higher levels of serum inflammatory cytokines than the young mice (8-week-old, n = 5). Aged 11ß-HSD1 knockout mice (n = 11), 11ß-HSD1 inhibitor (INHI)-treated aged wild type (WT) mice (n = 5) and young WT mice (n = 10) exhibited reduced SC corticosterone level. Corneodesmosome density was low in WT aged mice (n = 5), but high in aged 11ß-HSD1 knockout and aged INHI-treated WT mice. Aged mice exhibited lower SC lipid levels; this effect was reversed by INHI treatment. Therefore, upregulation of 11ß-HSD1 in the aged skin increases the active-glucocorticoid levels; this suppresses SC lipid biosynthesis, leading to impaired epidermal permeability barrier.

Role of 11ß-hydroxysteroid dehydrogenase type 1 in the development of atopic dermatitis.

Glucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic-pituitary-adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1), including the skin. The inactive GC cortisone is converted by 11ß-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11ß-HSD1 in inflammation is unclear. We assessed whether 11ß-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11ß-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11ß-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11ß-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11ß-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11ß-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.

All-Cause and Cause-Specific Mortality Risks Associated With Alopecia Areata: A Korean Nationwide Population-Based Study.

IMPORTANCE: Alopecia areata is associated with diverse systemic and psychiatric diseases. However, whether all-cause and cause-specific mortality in patients with alopecia areata differs from that of the general population remains unclear. OBJECTIVE: To investigate all-cause and cause-specific mortality risk in patients with alopecia areata. DESIGN, SETTING, AND PARTICIPANTS: Using the National Health Insurance Service database and National Death Registry of Korea, a retrospective cohort study of participants identified in 2006, with investigation of mortality until 2016, was carried out. Patients with alopecia areata with at least 3 documented visits to a dermatologist with an International Statistical Classification of Diseases (tenth revision) code of L63 during 2002 to 2006 were included. For comparison, 1:10 age- and sex-matched controls without documented visits with a code of L63 until 2016 were included. EXPOSURES: Patients with alopecia areata and controls without alopecia areata. MAIN OUTCOMES AND MEASURES: The study population was followed from January 1, 2007, for a period of 10 years to estimate all- and cause-specific mortality. RESULTS: The study comprised 73 107 patients with alopecia areata and 731 070 age- and sex-matched controls. Of these, 6023 were patients with alopecia totalis/universalis. No differences in all-cause mortality risk between the cohorts were found (HR, 0.97; 95% CI, 0.87-1.09). However, mortality associated with intentional self-harm/psychiatric diseases was greater in patients than in participants in the control group (HR, 1.21; 95% CI, 1.04-1.41). Adult patients aged 35 years or younger (HR, 1.68; 95% CI, 1.32-2.12) and those with alopecia totalis/universalis (HR, 1.85; 95% CI, 1.25-2.75) were particularly affected. Mortality associated with lung cancer was greater in patients with alopecia totalis/universalis (HR, 2.16; 95% CI, 1.41-3.33). However, mortality associated with diabetes mellitus was significantly lower in patients with alopecia areata (HR, 0.53; 95% CI, 0.36-0.79). CONCLUSIONS AND RELEVANCE: Patients with alopecia areata have a higher risk of mortality associated with self-harm, psychiatric diseases, and smoking-associated malignant diseases including lung cancer. For better outcomes, clinicians should appropriately treat patients to ensure emotional and psychological well-being.

Baumann Skin Type in the Korean Male Population.

BACKGROUND: Research into the Baumann skin type (BST) has recently expanded, with growing interest in the development of an efficient and effective skin type classification system for better understanding of this skin condition. OBJECTIVE: We aimed to identify male-specific skin type characteristics with investigation into the distribution of BST by age and region in the Korean male population and to determine the intrinsic and extrinsic factors related to skin type. METHODS: A questionnaire was administered to collect information about age, region, working behavior, drinking behavior, smoking behavior, usual habit of sun protection, medical history, and the BST which consisted of four parameters; oily (O) or dry (D), sensitive (S) or resistant (R), pigmented (P) or non-pigmented (N), and wrinkled (W) or tight (T). RESULTS: We surveyed 1,000 Korean males aged between 20 and 60 years who were divided equally by age and region. Of the total respondents, OSNW type accounted for the largest percentage and ORPW type the lowest. In terms of Baumann parameters, O type was 53.5%, S type was 56.1%, N type was 84.4% and W type was 57.5%. Several behavioral factors were found to have various relationships with the skin type. CONCLUSION: The predominant skin type in the Korean male respondents was OSNW type, and the distribution of skin types with regards to age and region was reported to be distinct. Therefore, skin care should be customized based on detailed skin types considering the various environmental factors.

Adverse Sexual Effects of Treatment with Finasteride or Dutasteride for Male Androgenetic Alopecia: A Systematic Review and Meta-analysis.

Treatment of male androgenetic alopecia with 5α-reductase inhibitors is efficacious. However, the risk of adverse sexual effects remains controversial. This systematic review and meta-analysis investigated the risk of adverse sexual effects due to treatment of androgenetic alopecia in male patients with finasteride, 1 mg/day, or dutasteride, 0.5 mg/day. Fifteen randomized double-blinded placebo-controlled trials (4,495 subjects) were meta-analysed. Use of 5α-reductase inhibitors carried a 1.57-fold risk of sexual dysfunction (95% confidence interval (95% CI) 1.19-2.08). The relative risk was 1.66 (95% CI 1.20-2.30) for finasteride and 1.37 (95% CI 0.81-2.32) for dutasteride. Both drugs were associated with an increased risk, although the increase was not statistically significant for dutasteride. As studies into dutasteride were limited, further trials are required. It is important that physicians are aware of, and assess, the possibility of sexual dysfunction in patients treated with 5α-reductase inhibitors.

Screening of thyroid function and autoantibodies in patients with alopecia areata: A systematic review and meta-analysis.

BACKGROUND: Several studies have reported associations between alopecia areata and diverse thyroid diseases. OBJECTIVE: To investigate the odds ratio and prevalence rate of thyroid dysfunction and autoimmune thyroid diseases in patients with alopecia areata. METHODS: A systematic review of the studies published before March 20, 2018, was performed by using the MEDLINE, Embase, Web of Science, and Cochrane Library databases. The clinical and laboratory findings associated with thyroid dysfunction and autoimmunity were extracted for quantitative analysis. RESULTS: A total of 50 studies were analyzed. Patients with alopecia areata had higher odds of abnormal findings on thyroid function tests, thyroid dysfunction, positive thyroid autoantibodies, and autoimmune thyroid diseases. Moreover, their prevalence rate was much higher than that in the general population. LIMITATIONS: The heterogeneity in baseline characteristics and outcome reporting across the studies. CONCLUSION: Current evidence suggests that thyroid dysfunction and autoimmune thyroid diseases are more prevalent in patients with alopecia areata. Clinicians may be encouraged to screen for the associated signs and symptoms to achieve better outcomes.

Hair Regrowth Outcomes of Contact Immunotherapy for Patients With Alopecia Areata: A Systematic Review and Meta-analysis.

Importance: Contact immunotherapy with diphenylcyclopropenone or squaric acid dibutyl ester is a preferred treatment for severe alopecia areata; however, the defined criteria for therapeutic hair regrowth and regrowth rate have been highly heterogeneous across studies. Objective: To summarize the clinical outcomes of contact immunotherapy for alopecia areata according to standardized criteria for therapeutic hair regrowth and several prognostic factors. Data Source: A database search of MEDLINE, Embase, and Cochrane Library was performed for articles published before November 20, 2017, using the search terms areata, totalis, universalis, sensitizer, sensitization, immunotherapy, DPCP, diphenylcyclopropenone, diphencyprone, SADBE, and squaric. Study Selection: Clinical trials or observational studies that investigated contact immunotherapy for alopecia areata and subgrouped the disease into patchy alopecia or alopecia totalis/universalis and reported their hair regrowth rates were included, whereas studies that investigated combination therapy or nonconventional protocol and case series or reviews were excluded. Data Extraction and Synthesis: The following data were extracted from each of the studies included in this meta-analysis: study year and setting, sensitizer type, study population, study population composition by disease subtype, defined criteria for therapeutic hair regrowth, and regrowth rate of contact immunotherapy. The incidence of adverse effects and recurrence rate were also recorded. A random effects model was used for data synthesis because of the expected high heterogeneity of the included studies. Main Outcomes and Measures: The main outcome was therapeutic hair regrowth rate according to the 4-grade criteria for therapeutic regrowth. Secondary outcomes included incidence of treatment-related adverse effects and recurrence rate. Results: Forty-five studies comprising 2227 patients were analyzed. The overall rate of any hair regrowth was 65.5% among patients with alopecia areata (74.6% in the patchy alopecia and 54.5% in the alopecia totalis/universalis subgroups). However, the complete regrowth rate was 32.3% (24.9% in the patchy alopecia and 32.3% in the alopecia totalis/universalis subgroups). Disease extent of 50% or greater (odds ratio [OR], 3.05; 95% CI, 2.26-4.12), atopic history (OR, 1.61; 95% CI, 1.03-2.50), and nail involvement (OR, 2.06; 95% CI. 1.26-3.36) were associated with poorer therapeutic outcome. Recurrence rates were 38.3% among patients receiving maintenance treatment and 49.0% among those not receiving maintenance treatment. Conclusions and Relevance: Various factors were associated with the clinical outcomes of contact immunotherapy for alopecia areata, with significant differences in hair regrowth rates according to the level of expected therapeutic regrowth. Quantitative summarization may improve patient education and lead to better therapeutic adherence and outcomes.

Implantable batteryless device for on-demand and pulsatile insulin administration.

Many implantable systems have been designed for long-term, pulsatile delivery of insulin, but the lifetime of these devices is limited by the need for battery replacement and consequent replacement surgery. Here we propose a batteryless, fully implantable insulin pump that can be actuated by a magnetic field. The pump is prepared by simple-assembly of magnets and constituent units and comprises a drug reservoir and actuator equipped with a plunger and barrel, each assembled with a magnet. The plunger moves to noninvasively infuse insulin only when a magnetic field is applied on the exterior surface of the body. Here we show that the dose is easily controlled by varying the number of magnet applications. Also, pump implantation in diabetic rats results in profiles of insulin concentration and decreased blood glucose levels similar to those observed in rats treated with conventional subcutaneous insulin injections.