Near-infrared radiation causes sebaceous gland enlargement along with an ROS-dependent augmentation of epidermal growth factor receptor expression in hamsters.

As near-infrared radiation (NIR), which is a composition of sunlight with an 780-1400 nm wavelength, is associated with skin aging such as wrinkles and slacks, the biological actions of NIR with high dermal penetration remains unclear. In the present study, we found that NIR irradiation (40 J/cm2 ) at different levels of irradiance (95-190 mW/cm2 ) using a laboratory device with a xenon flash lamp (780-1700 nm) caused sebaceous gland enlargement concomitantly with skin thickening in the auricle skin of hamsters. The sebaceous gland enlargement resulted from the proliferation of sebocytes due to an increase in the number of proliferating cell nuclear antigen (PCNA)- and lamin B1-positive cells in vivo. In addition, NIR irradiation transcriptionally augmented the production of epidermal growth factor receptor (EGFR) accompanied with an increase in the reactive oxygen species (ROS) level in hamster sebocytes in vitro. Furthermore, the administration of hydrogen peroxide increased the level of EGFR mRNA in the sebocytes. Therefore, these results provide novel evidence that NIR irradiation causes the hyperplasia of sebaceous glands in hamsters by mechanisms in which EGFR production is transcriptionally augmented through ROS-dependent pathways in sebocytes.

Sebaceous Carcinoma Incidence and Survival Among Solid Organ Transplant Recipients in the United States, 1987-2017.

Importance: Risk of sebaceous carcinoma (SC), a rare skin cancer associated with Muir-Torre syndrome, is elevated among solid organ transplant recipients (SOTRs). However, population studies evaluating this association and assessing survival for posttransplant cases are lacking, and further understanding of SC epidemiology in this immunosuppressed population could provide etiologic and clinical insights. Objective: To assess SC incidence and patient survival after solid organ transplantation. Design, Setting, and Participants: This cohort study, conducted from January 1, 1987, to December 31, 2017, used data from the Transplant Cancer Match Study, which links transplant and cancer registry data for 17 states and 1 metropolitan area in the United States. Altogether, these registries account for approximately 46% of all US transplants. Data on demographic and transplant characteristics as well as induction and initial maintenance immunosuppressive therapies were obtained from the transplant registry. Standardized incidence ratios (SIRs) comparing SC incidence among SOTRs to the general population were calculated. Incidence rate ratios (IRRs) comparing SC risk between SOTR subgroups were calculated using multivariate Poisson regression. Cox regression was used to compare overall survival between SC cases in SOTRs and other individuals. Main Outcomes and Measures: Sebaceous carcinoma incidence and overall patient survival after transplantation compared with the general population. Results: A total of 326 282 transplant procedures were performed for 301 075 patients (No. [%] age at transplant, 126 550 [38.8%] aged 0-44 years; 82 394 [25.3%] aged 45-54 years; 82 082 [25.5%] aged 55-64 years; 35 256 [10.8%] aged ≥65 years; 201 354 male patients [61.7%]; 202 557 White patients [62.1%]). A total of 102 SCs were diagnosed in 301 075 SOTRs, corresponding to a 25-fold increased incidence (SIR, 24.8; 95% CI, 20.2-30.1). Incidence was especially elevated among lung recipients (SIR, 47.7; 95% CI, 20.6-94.0) and after a posttransplant diagnosis of cutaneous squamous cell carcinoma (SIR, 104.0; 95% CI, 62.8-163.0). Among SOTRs, factors independently associated with SC risk included male sex (IRR, 2.46; 95% CI, 1.48-4.07; P < .001), race/ethnicity (non-Hispanic Black vs non-Hispanic White, IRR, 0.28; 95% CI, 0.10-0.77; P = .01), older age (IRR, 7.85; 95% CI, 3.85-16.0; ≥65 vs 0-44 years; P < .001 for trend), use of thymoglobulin induction (IRR, 1.82; 95% CI, 1.16-2.86; P = .009), posttransplant cutaneous squamous cell carcinoma (IRR, 4.60; 95% CI, 2.67-7.94; P < .001), and longer time since transplant (IRR, 8.40; 95% CI, 3.94-17.90; ≥10 vs 0-1.9 years; P < .001 for trend). Muir-Torre syndrome-associated cancers were rare among both SOTRs and others with SC (3.3%-4.1%). Among patients with SC, prior transplantation was associated with increased overall mortality (adjusted hazard ratio, 2.09; 95% CI, 1.45-3.01), although few deaths were attributed to SC (4 of 92 SOTRs [4.3%]; 235 of 3585 non-SOTRs [6.6%]). Conclusions and Relevance: Among SOTRs, results of this large cohort study suggest that SC was associated with measures of immunosuppression, and overall survival was worse than for other patients with SC. Findings also suggest a possible role for UV radiation in carcinogenesis.

Treatment of Sebaceous Hyperplasia by Laser Modalities: A Review of the Literature and Presentation of Our Experience With Erbium-doped Yttrium Aluminium Garnet (Er:YAG).

INTRODUCTION: Sebaceous hyperplasia (SH) is a common skin presentation in adults. Due to their unwanted yellow papular appearance, patients may desire their removal. Although several treatment modalities have been reported, the full range and efficacy of options are unclear. OBJECTIVE: To determine the efficacy of laser modalities in the treatment of SH. The authors will also specifically assess the efficacy, recurrence rate and side effect profile of SH treatment with Er:YAG wavelength using a variable long pulsed (VLP) Er:YAG laser (SP Dynamis Fotona laser, Ljubljana, Slovenia) Methods & Materials: A comprehensive literature search was performed through PubMed, EMBASE, and Web of Science, using the search terms [(sebaceous hyperplasia)] and [(laser[s], Er:Yag, Er:Glass, Fraxel, CO2, PDL, Pulse dye laser, Diode, Xe-Cl, Excimer, Argon, KTP, Ruby, Alexandrite or Nd:YAG)]. The search yielded a total of 119 results and 8 were identified as relevant to this reviewResults: Pulse dye laser (PDL) provides a wide range of treatment results from complete reduction to flattening of the SH without significant adverse events; recurrence rates were unreported. Short PDL showed faster treatment response than long PDL. CO2 laser can produce considerable positive cosmetic outcomes with marked clinical improvement without any recurrence, but significant adverse effects have been reported. The 1450-nm diode laser has been described to produce good (75%) clinical improvement and lesion shrinkage ranging from 50% to greater than 75% without lasting adverse effects. In our clinic, Er:YAG has provided very significant cosmetic outcomes with a low recurrence rate and minimal adverse effects. CONCLUSIONS: Laser modalities can provide satisfactory results for removing SH. It is crucial that the laser is being used by an expert who is familiar with the device as well as understand the laser tissue interaction to minimize patient adverse effects while providing the best cosmetic outcome. In our experience, Er:YAG laser can provide a safe and highly effective solution for SH.

Damage to sebaceous gland and the efficacy of moisturizer after whole breast radiotherapy: a randomized controlled trial.

BACKGROUND: We conducted a randomized trial to evaluate the efficacy of heparinoid moisturization for radiation dermatitis. We report the time-course of sebum content after whole breast radiotherapy (WBRT) and the efficacy of heparinoid moisturizer. METHODS: Patients receiving adjuvant breast RT were randomly assigned into three groups; prophylaxis, post-WBRT and control groups. Patients used moisturizer on the irradiated breast from the beginning of RT in the prophylaxis group, 2 weeks post-RT in the post-WBRT group, and no moisturizer in the control group. Sebum content of the irradiated and non-irradiated breast was measured to assess sebaceous gland damage. Sebum composition was also analyzed. RESULTS: A total of 76 patients were analyzed; 30 in the post-WBRT group, 32 in the control group, 14 in the prophylaxis group. The sebum content in the irradiated breast significantly decreased after WBRT in the post-WBRT and control groups. The decrease was sustained in the control group. In the non-irradiated breast, sebum content also decreased after WBRT in the post-WBRT and control groups. After moisturizer application, sebum content by sebumeter returned to pre-RT level in the post-WBRT group, while the decrease was sustained in the control group. Sebum content measured by evaporative light scattering detector and sebumeter was similar in the control group, but the dissociation was observed after moisturizer application in the post-WBRT group. The proportion of wax esters decreased in the irradiated breast after WBRT. CONCLUSIONS: Radiotherapy significantly reduced sebum content in both irradiated and non-irradiated breast, indicating that RT caused quantifiably persistent sebaceous gland damage in irradiated sites and the surrounding tissue. Combined with the results from our previous study, heparinoid moisturizer treatment effectively prevents water loss by retaining oil contents on the skin surface. TRIAL REGISTRATION: UMIN, UMIN000005532 . Registered 1 April 2011.

Laser-Assisted Photodynamic Therapy: Two Novel Protocols for Enhanced Treatment Results.

Photodynamic therapy (PDT) uses a topical photosensitizing agent which is activated by a light source to cause destruction of specific cells. Commonly used for the treatment of actinic keratoses and photodamage, PDT can also be used for other conditions including acne and sebaceous hyperplasia. Here we report our experience with two treatment protocols. The first protocol utilizes laser assisted delivery of topical 5-aminolevulinic acid for enhanced efficacy of blue light photodynamic therapy in the treatment of actinic keratoses and photodamage. The second protocol utilizes red light photodynamic therapy followed by pulsed dye laser to effectively target sebaceous glands in patients with extensive sebaceous hyperplasia.

J Drugs Dermatol. 2017;16(4):329-331.

ALA-PDT suppressing the cell growth and reducing the lipogenesis in human SZ95 sebocytes by mTOR signaling pathway in vitro.

BACKGROUND: 5-Aminolevulinic acid mediated -photodynamic therapy (ALA-PDT) is known to be effective in treating acne vulgaris and other sebaceous gland-related diseases. However, the therapeutic mechanisms of ALA-PDT still remain undetermined. In this study, we aimed to investigate the effects and mechanisms of ALA-PDT on the cell growth and lipogenesis of human SZ95 sebocytes. MATERIAL AND METHODS: Human SZ95 sebocytes were treated with different concentration of ALA-PDT.CCK-8 assay was used to detect cell proliferation activity. Fluorescence microscope and flow cytometry were used to observe the secretion of lipids in SZ95 cells after Nile red staining. Western blotting was used to detect and analyze the protein expression level of P-p70 S6K/p70 S6K, P-4E-BP1/4E-BP1, SREBP-1, PPARγ, P-mTOR/mTOR, and P-Raptor/Raptor. Mean while, mTOR pathway activator IGF-1 and mTORC1 inhibitor rapamycin were added to observe the interferences on the ALA-PDT treatment of SZ95 cells. RESULTS: ALA-PDT suppressed the cell growth and reduced the secretion of lipids in a dose-dependent manner in SZ95 cells. ALA-PDT reduced the protein levels of P-p70 S6K (T389), SREBP-1, PPARγ, P-mTOR and P-Raptor. IGF-1 had counter effects on ALA-PDT, and rapamycin enhanced the effects of ALA-PDT in SZ95 cells in suppressing the cell growth and reducing the secretion of lipids. CONCLUSION: ALA-PDT suppressed the cell growth in SZ95 cells by mTOR-p70 S6K(T389) signaling and reduced the lipogenesis in SZ95 cells by mTOR-SREBP-1/PPARγ signaling. Sebaceous glands atrophy and reduction of sebum secretion after ALA-PDT may be caused by the suppression of lipogenesis and cell growth in sebocytes.

Targeting of sebaceous glands to treat acne by micro-insulated needles with radio frequency in a rabbit ear model.

BACKGROUND AND OBJECTIVES: Many studies have investigated the application of micro-insulated needles with radio frequency (RF) to treat acne in humans; however, the use of a micro-insulated needle RF applicator has not yet been studied in an animal model. The purpose of this study was to evaluate the effectiveness of a micro-insulated needle RF applicator in a rabbit ear acne (REA) model. STUDY DESIGN/MATERIALS AND METHODS: In this study, we investigated the effect of selectively destroying the sebaceous glands using a micro-insulated needle RF applicator on the formation of comedones induced by application of 50% oleic acid and intradermal injection of P. acnes in the orifices of the external auditory canals of rabbits. The effects of the micro-insulated needle RF applicator treatment were evaluated using regular digital photography in addition to 3D Primos imaging evaluation, Skin Visio Meter microscopic photography, and histologic analyses. RESULTS: Use of the micro-insulated needle RF applicator resulted in successful selective destruction of the sebaceous glands and attenuated TNF-alpha release in an REA model. The mechanisms by which micro-insulated needles with RF using 1 MHz exerts its effects may involve inhibition of comedone formation, triggering of the wound healing process, and destruction of the sebaceous glands and papules. CONCLUSION: The use of micro-insulated needles with RF applicators provides a safe and effective method for improving the appearance of symptoms in an REA model. The current in vivo study confirms that the micro-insulated needle RF applicator is selectively destroying the sebaceous glands. Lasers Surg. Med. 49:395-401, 2017. © 2016 Wiley Periodicals, Inc.

In vivo characterization of early-stage radiation skin injury in a mouse model by two-photon microscopy.

Ionizing radiation (IR) injury is tissue damage caused by high energy electromagnetic waves such as X-ray and gamma ray. Diagnosis and treatment of IR injury are difficult due to its characteristics of clinically latent post-irradiation periods and the following successive and unpredictable inflammatory bursts. Skin is one of the many sensitive organs to IR and bears local injury upon exposure. Early-stage diagnosis of IR skin injury is essential in order to maximize treatment efficiency and to prevent the aggravation of IR injury. In this study, early-stage changes of the IR injured skin at the cellular level were characterized in an in vivo mouse model by two-photon microscopy (TPM). Various IR doses were applied to the mouse hind limbs and the injured skin regions were imaged daily for 6 days after IR irradiation. Changes in the morphology and distribution of the epidermal cells and damage of the sebaceous glands were observed before clinical symptoms. These results showed that TPM is sensitive to early-stage changes of IR skin injury and may be useful for its diagnosis.

Randomized split-face controlled study to evaluate 1550-nm fractionated erbium glass laser for treatment of acne vulgaris--an image analysis evaluation.

BACKGROUND: Novel and promising results in acne treatment with infrared lasers have been reported. The 1,550-nm erbium glass laser is one of the infrared lasers that may be useful in the treatment of acne. OBJECTIVE: The aim of this study was to evaluate the efficacy of an erbium glass laser in treatment of active acne and to study the effect of this type of laser on sebaceous glands. PATIENTS AND METHODS: Twenty-four patients with active acne lesions were treated using 1,550-nm (30-40 mJ) fractional erbium glass laser. Every patient received 4 sessions with a 2-week interval. Follow-up was done every 3 months for 1 year. The image analyzer computer system was used to measure the sebaceous gland size. RESULTS: A significant reduction (p < .0001) in the mean count of lesions was observed after treatment and in the follow-up period. A significant reduction in the size of sebaceous glands was also evident after laser treatment. CONCLUSION: Treatment of active acne with the 1,550-nm erbium glass laser is effective. Papules, pustules, and nodules all respond well to therapy. The sebaceous gland size decreased significantly, which accounts for the long remission period.

Ultraviolet B irradiation increases the expression of inflammatory cytokines in cultured sebocytes.

Sebaceous gland hyperplasia and increased sebum secretion after irradiation of ultraviolet (UV)-B has been widely accepted. This study was performed to clarify expression of inflammatory cytokines after irradiating UV-B in cultured sebocytes. Reverse transcription polymerase chain reaction was performed to measure gene expression of inflammatory cytokines, including interleukin (IL)-1ß, IL-6, IL-8 and tumor necrosis factor-α, in cultured sebocytes after exposure to 40 and 70 mJ/cm(2) UV-B. Protein expression of inflammatory cytokines and lipid production in cultured sebocytes after exposure to UV-B were measured using enzyme-linked immunoassay and lipid analysis kit. The expression of inflammatory cytokines, especially IL-1ß and IL-8, was significantly increased in cultured sebocytes after treatment with UV-B. Many more studies on the effect of UV-B on sebaceous glands should be performed to reveal the pathogenic mechanism of acne.

Acne vulgarism treatment using ultra-short laser pulse generated by micro- and nano-ring resonator system.

Acne vulgaris is adebilitating dermatologic disease, and is conventionally treated by laser therapy using a microring resonator system. An evolving understanding of laser-tissue interactions involving Propioni bacterium acneproducing porphyrins, and the development of lasers to target the sebaceous glands, has led to the development of an escalating number of laser light for acne treatment. The results show that the full width at half maximum of the proposed laser pulse of 0.15 nm can be generated using a microring resonator system. The power of the laser is 200 W and the wavelength laser is 1,032 nm, which is proposed as a treatment of acne vulgaris diseases.

Selective photothermolysis to target sebaceous glands: theoretical estimation of parameters and preliminary results using a free electron laser.

BACKGROUND AND OBJECTIVES: The success of permanent laser hair removal suggests that selective photothermolysis (SP) of sebaceous glands, another part of hair follicles, may also have merit. About 30% of sebum consists of fats with copious CH(2) bond content. SP was studied in vitro, using free electron laser (FEL) pulses at an infrared CH(2) vibrational absorption wavelength band. METHODS: Absorption spectra of natural and artificially prepared sebum were measured from 200 to 3,000 nm, to determine wavelengths potentially able to target sebaceous glands. The Jefferson National Accelerator superconducting FEL was used to measure photothermal excitation of aqueous gels, artificial sebum, pig skin, human scalp, and forehead skin (sebaceous sites). In vitro skin samples were exposed to FEL pulses from 1,620 to 1,720 nm, spot diameter 7-9.5 mm with exposure through a cold 4°C sapphire window in contact with the skin. Exposed and control tissue samples were stained using H&E, and nitroblue tetrazolium chloride staining (NBTC) was used to detect thermal denaturation. RESULTS: Natural and artificial sebum both had absorption peaks near 1,210, 1,728, 1,760, 2,306 and 2,346 nm. Laser-induced heating of artificial sebum was approximately twice that of water at 1,710 and 1,720 nm, and about 1.5× higher in human sebaceous glands than in water. Thermal camera imaging showed transient focal heating near sebaceous hair follicles. Histologically, skin samples exposed to ~1,700 nm, ~100-125 milliseconds pulses showed evidence of selective thermal damage to sebaceous glands. Sebaceous glands were positive for NBTC staining, without evidence of selective loss in samples exposed to the laser. Epidermis was undamaged in all samples. CONCLUSIONS: SP of sebaceous glands appears to be feasible. Potentially, optical pulses at ~1,720 or ~1,210 nm delivered with large beam diameter and appropriate skin cooling in approximately 0.1 seconds may provide an alternative treatment for acne.

Photothermolysis of sebaceous glands in human skin ex vivo with a 1,708 nm Raman fiber laser and contact cooling.

BACKGROUND AND OBJECTIVES: Wavelengths near ∼1,720 nm are of interest for targeting fat/lipid-rich tissues due to the high absorption coefficient of human fat and low water scattering and absorption. In this study, a 1,708 nm laser was built and shown to selectively target fat/lipid adjacent to porcine heart and dermis and then used to damage dermal sebaceous glands in human skin. STUDY DESIGN AND MATERIALS: An all-fiber 1,708 nm laser with ∼4 W maximum power was designed and built. Selectivity for targeting fat/lipid was studied by exposing porcine heart and skin tissue cross-sections to the 1,708 nm laser. Human skin treatments to damage sebaceous glands were performed both with and without cold window cooling. Histochemical evaluation on the frozen sections was performed using methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. RESULTS: Histochemical analysis of porcine tissue cross-sections showed that 1,708 nm laser can selectively damage pericardial fat(heart) and subcutaneous fat(skin) with little to no damage to the myocardium and the dermis, respectively. In human skin, histochemical evaluation without contact cooling showed damage to both epidermis and dermis. With cooling, epidermis was spared and damage was observed in dermis extending ∼0.4-1.65 mm from the skin surface at an average laser fluence of ∼80 J/cm(2). Selective damage of sebaceous glands was suggested but not definitively demonstrated. CONCLUSIONS: We have developed an all-fiber 1,708 nm laser capable of damaging majority of the sebaceous glands in the dermis and thus may have potential applications in the treatment of conditions such as acne vulgaris whose pathophysiology involves disorders of sebaceous glands.

The production and composition of rat sebum is unaffected by 3 Gy gamma radiation.

PURPOSE: The aim of this work was to use metabolomics to evaluate sebum as a source of biomarkers for gamma-radiation exposure in the rat, and potentially in man. Proof of concept of radiation metabolomics was previously demonstrated in both mouse and rat urine, from the radiation dose- and time-dependent excretion of a set of urinary biomarkers. MATERIALS AND METHODS: Rats were gamma-irradiated (3 Gy) or sham irradiated and groups of rats were euthanised at 1 h or 24 h post-irradiation. Sebum was collected by multiple washings of the carcasses with acetone. Nonpolar lipids were extracted, methylated, separated and quantitated using gas chromatography-mass spectrometry (GCMS). Metabolomic analysis of the GCMS data was performed using both orthogonal projection to latent structures-discriminant analysis and random forests machine learning algorithm. RESULTS: Irradiation did not alter sebum production. A total of 35 lipids were identified in rat sebum, 29 fatty acids, five fatty aldehydes, and cholesterol. Metabolomics showed that three fatty acids, palmitic, 2-hydroxypalmitic, and stearic acids were potential biomarkers. Sebaceous palmitic acid was marginally statistically significantly elevated (7.5-8.4%) at 24 h post-irradiation. CONCLUSIONS: Rat sebaceous gland appears refractory to 3 Gy gamma-irradiation. Unfortunately, collection of sebum shortly after gamma-irradiation is unlikely to form the basis of high-throughput non-invasive radiation biodosimetry in man.

Clinical applicability of a 1 450 nm diode laser as adjunctive treatment for refractory acne.

Acne is a multifactorial disease of the pilosebaceous units of the face and trunk, most commonly affecting young adolescents. Acne still represents the most common concern in dermatologic consultations and despite aggressive multi-treatment regimens, many patients demonstrate a poor response. A number of recent studies have evaluated the role of laser and light therapy in the treatment of acne vulgaris, with variable clinical outcomes. Among them, a 1450 nm diode laser has been shown to improve refractory acne in a clinical setting. The content of this manuscript draws upon current literature and will critically review the role of mid-infrared lasers as adjunctive therapy for acne.

Photoperiodic and hormonal influences on fur density and regrowth in two hamster species.

Temperate and boreal mammals undergo seasonal changes in pelage that facilitate thermoregulation in winter and summer. We investigated photoperiodic influences on pelage characteristics of male Siberian and Syrian hamsters. Fur density (mg fur/cm2 skin) was measured by weighing the shavings of fur patches removed from the dorsal and ventral surfaces of hamsters maintained in long days (LDs) or transferred to short days (SDs). Patches were reshaved 3 wk later to assess fur regrowth (mg regrown fur/cm2 skin). Fur density was greater in SD than in LD Siberian hamsters after 11 wk of differential phototreatment. The onset of increased fur density in SDs was accompanied by a transient increase in fur regrowth (11-14 wk on the dorsal surface and 7-10 and 11-14 wk on the ventral surface), suggestive of a seasonal molting process. Fur density, body mass, and pelage color of Siberian hamsters returned to values characteristic of LD males after a similar duration of prolonged (>27 wk) SD treatment and appear to be regulated by a similar or common interval-timing mechanism. In Syrian hamsters, dorsal fur density, fur regrowth, and hair lengths were greater in SD than in LD males. Castration increased and testosterone (T) treatment decreased dorsal and ventral fur regrowth in LD and SD hamsters, but the effects of T manipulations on fur density were limited to a decrease in dorsal fur density after T treatment. Decreased circulating T in SDs likely contributes to the seasonal molt of male hamsters by increasing the rate of fur growth during the transition to the winter pelage.