Histology of ex vivo skin after treatment with fractionated picosecond Nd:YAG laser in high and low-energy settings.

Background: The fractionated picosecond laser produces microscopic lesions in the epidermis and dermis, which are known as laser-induced optical breakdown (LIOB) and intra-dermal laser-induced cavitation (LIC). There have been multiple histological reports on these phenomena, although some have been challenged on the grounds of similarity to artifacts. Asian skins, with a higher melanin content, may react differently to this treatment, and present literature is also lacking in this area.Purpose: To observe and report the histological effect of different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser on Asian skin ex vivo.Methods: Six skin samples were taken from clinically normal-looking perilesional areas and treated with different energy levels and parameters of the fractional 532 nm/1064 nm picosecond laser. The specimens were then sent to the lab for H&E staining, and the slides were reviewed by a dermatopathologist.Results: Superficial, intra-epidermal LIOBs were seen in skin treating at higher laser energies; deep, intra-dermal LICs were seen in skin treated at lower energies. Lesion sizes and depths were consistent with previously reported values on Caucasian skins, and lesions were spaced in 600-µm intervals or its multiple.Conclusions: The histological findings are consistent with results from other ethnicities, and the spacing of lesions is a strong indication of their validity as LIOBs or LICs.

Effects of 308 nm excimer light treatment on the skin microbiome of atopic dermatitis patients.

BACKGROUND: The skin microbiome has been implicated in the pathophysiology of atopic dermatitis (AD). Although 308 nm excimer light treatment is an effective phototherapy for AD, its effects on the skin microbiome currently remain unclear. Therefore, we investigated the effects of the excimer light treatment on the skin bacterial and fungal microbiome of lesional skin of AD. METHODS: Swab samples were collected from 11 healthy controls, non-lesional and lesional skin of 11 AD patients. The excimer light treatment was administered to the lesional skin. The composition of the skin microbiome, the clinical score and skin barrier function of the lesional skin were examined before and after the treatment. The composition of the skin microbiome was determined by sequencing bacterial 16S and fungal internal transcribed spacer regions. RESULTS: The excimer light treatment significantly changed the composition of the bacterial microbiome in the lesional skin of AD, as well as improved the clinical score and skin barrier function. The treatment increased the relative abundance of the phylum Cyanobacteria and decreased that of the phylum Bacteroidetes in lesional skin. At the species level, the treatment significantly decreased the relative abundance of Staphylococcus aureus (S aureus) in lesional skin. There was also a significant correlation between the reduction of S aureus and improvement of the clinical outcomes. CONCLUSION: Our findings suggest that alterations of the skin microbiome with excimer light treatment, specifically the decrease in the abundance of S aureus, are partly involved in the improvement of AD lesions.

Dietary grape seed proanthocyanidins inactivate regulatory T cells by promoting NER-dependent DNA repair in dendritic cells in UVB-exposed skin.

Ultraviolet B (UVB) radiation induces regulatory T cells (Treg cells) and depletion of these Treg cells alleviates immunosuppression and inhibits photocarcinogenesis in mice. Here, we determined the effects of dietary grape seed proanthocyanidins (GSPs) on the development and activity of UVB-induced Treg cells. C3H/HeN mice fed a GSPs (0.5%, w/w)-supplemented or control diet were exposed to UVB (150 mJ/cm2) radiation, sensitized to 2,4-dinitrofluorobenzene (DNFB) and sacrificed 5 days later. FACS analysis indicated that dietary GSPs decrease the numbers of UVB-induced Treg cells. ELISA analysis of cultured sorted Treg cells indicated that secretion of immunosuppressive cytokines (interleukin-10, TGF-ß) was significantly lower in Treg cells from GSPs-fed mice. Dietary GSPs also enhanced the ability of Treg cells from wild-type mice to stimulate production of IFNγ by T cells. These effects of dietary GSPs on Treg cell function were not found in XPA-deficient mice, which are incapable of repairing UVB-induced DNA damage. Adoptive transfer experiments revealed that naïve recipients that received Treg cells from GSPs-fed UVB-irradiated wild-type donors that had been sensitized to DNFB exhibited a significantly higher contact hypersensitivity (CHS) response to DNFB than mice that received Treg cells from UVB-exposed mice fed the control diet. There was no significant difference in the CHS response between mice that received Treg cells from UVB-irradiated XPA-deficient donors fed GSPs or the control diet. Furthermore, dietary GSPs significantly inhibited UVB-induced skin tumor development in wild-type mice but not in XPA-deficient mice. These results suggest that GSPs inactivate Treg cells by promoting DNA repair in dendritic cells in UVB-exposed skin.

Noninvasive red and near-infrared wavelength-induced photobiomodulation: promoting impaired cutaneous wound healing.

The innumerable intricacies associated with chronic wounds have made the development of new painless, noninvasive, biophysical therapeutic interventions as the focus of current biomedical research. Red and near-infrared light-induced photobiomodulation therapy appears to emerge as a promising drug-free approach for promoting wound healing, reduction in inflammation, pain and restoration of function owing to penetration power in conjunction with their ability to positively modulate the biochemical and molecular responses. This review will describe the physical properties of red and near-infrared light and their interaction with skin and highlight their efficacy of wound repair and regeneration. Near-infrared (800-830 nm) was found to be the most effective and widely studied wavelength range followed by red (630-680 nm) and 904 nm superpulsed light exhibiting beneficial photobiomodulatory effects on impaired dermal wound healing.

Comparison of 5-aminolevulinic acid photodynamic therapy and red light for treatment of photoaging.

OBJECTIVE: The aim of this pilot study was to compare the efficacy of ALA-PDT and red light alone in the treatment of photoaging. METHODS: A total of 14 adults with photoaging skin were recruited. ALA-PDT or red light alone was applied to the forearm extensor. Before and after treatment, the treated sites were examined by dermoscopy, the changes in straum corneum (SC) hydration, transepidermal water loss (TEWL), and the L*a*b* values were measured, and microscopic examination of collagens and elastins was performed. RESULTS: After ALA-PDT or red light illumination, the appearance of photoaging lesions improved, SC hydration increased and TEWL decreased. These changes in the ALA-PDT group were more obvious than those in the red light group. No significant change was noticed in the L*a*b* values in both groups. The signs of typical solar elastosis damage were improved in both groups. CONCLUSIONS: ALA-PDT showed better skin rejuvenation effect than red light alone.

Photoprotective effects of apple peel nanoparticles.

Plants contain enriched bioactive molecules that can protect against skin diseases. Bioactive molecules become unstable and ineffective due to unfavorable conditions. In the present study, to improve the therapeutic efficacy of phytodrugs and enhance photoprotective capability, we used poly(D,L-lactide-co-glycolide) as a carrier of apple peel ethanolic extract (APETE) on permeation-enhanced nanoparticles (nano-APETE). The in vitro toxicity of nano-APETE-treated dermal fibroblast cells were studied in a bioimpedance system, and the results coincided with the viability assay. In addition, the continuous real-time evaluations of photodamage and photoprotective effect of nano-APETE on cells were studied. Among three different preparations of nano-APETE, the lowest concentration provided small, spherical, monodispersed, uniform particles which show high encapsulation, enhanced uptake, effective scavenging, and sustained intracellular delivery. Also, the nano-APETE is more flexible, allowing it to permeate through skin lipid membrane and release the drug in a sustained manner, thus confirming its ability as a sustained transdermal delivery. In summary, 50 µM nano-APETE shows strong synergistic photoprotective effects, thus demonstrating its higher activity on target sites for the treatment of skin damage, and would be of broad interest in the field of skin therapeutics.

[Mechanisms of phototherapy]. / Wirkmechanismen der phototherapie.

Phototherapy represents one of the essential options in the treatment of skin diseases by dermatologists. The beginnings of phototherapy were based on empirical observations and only later the underlying molecular and cellular mechanisms of the different modalities of phototherapy were unravelled by scientific research. Due to these findings, some phototherapeutic indications were subsequently altered. In this article, the known photobiological effects of ultraviolet radiation will be discussed and put in relation to the different forms of phototherapy as they are applied in the daily practice by dermatologists.

The sun--our friend or foe?

INTRODUCTION AND OBJECTIVE: Sunlight is the major source of the energy on Earth. Visible light, ultraviolet and infrared radiation are necessary to sustain life on our planet. However, besides the range of positive effects, such as photosynthesis in plants, warmth, vision, and synthesis of vitamin D, sunlight may also be responsible for negative biologic effects - sunburn, induction of photodermatoses or carcinogenesis. Ultraviolet is regarded as the major environmental, physical hazard to the human skin. ABBREVIATED DESCRIPTION OF THE STATE OF KNOWLEDGE: The acute clinical effect of ultraviolet involves melanogenesis, i.e. tanning, which protects from sunburn if exposure is overdosed. A single exposure, as well as acute suberythemal irradiation, suppresses sensitization of the contact hypersensitivity. The chronic biological effects are photoageing and skin cancer, especially squamous cell carcinoma (SCC). Vitamin D synthesis is regarded as a benefit of natural acute and chronic exposure to ultraviolet. Ultraviolet also plays an important role in aetiology of the group of disorders characterized by photosensitivity. On the other hand ultraviolet is a known inducer of immunosuppression in the skin; therefore, phototherapy is a therapeutic option for patients with activation of dermal immunity. SUMMARY: Without sunlight, the existence of life on Earth is not possible. On the other hand, UVR radiation is regarded as representing one of the most important environmental hazards for human skin. For a better understanding of the mechanisms related to the influence of UVR on human skin, and the most dangerous chronic effects of carcinogenesis, it is necessary to undertake some protective activities. Moreover, UVR may become our ally in the treatment of selected skin disorders.

Reflection modeling in ultraviolet phototherapy.

PURPOSE: Ultraviolet phototherapy is a widely used treatment which has exceptional success with a variety of skin conditions. Over-exposure to ultraviolet radiation (UVR) can however be detrimental and cause side effects such as erythema, photokeratisis, and even skin cancer. Quantifying patient dose is therefore imperative to ensure biologically effective treatment while minimizing negative repercussions. A dose model for treatment would be valuable in achieving these ends. METHODS: Prior work by the authors concentrated on modeling the output of the lamps used in treatment and it was found a line source model described the output from the sources to a high degree. In practice, these lamps are surrounded by reflective anodized aluminum in patient treatment cabins and this work extends the model to quantify specular reflections from these planes on patient dose. RESULTS: The extension of the model to allow for reflected images in addition to tube output shows a remarkably good fit to the actual data measured. CONCLUSIONS: The reflection model yields impressive accuracy and is a good basis for full UVR cabin modeling.

Cutaneous sensory nerves: mediators of phototherapeutic effects?

Exposures to ultraviolet radiation (UVR) during accidental or voluntary sun exposure or treatment with phototherapy or photochemotherapy have a significant impact on the skin. Many skin diseases such as psoriasis, atopic dermatitis, or cutaneous T-cell lymphoma significantly improve by photo(chemo)therapy, though the mechanisms behind the therapeutic effects of photo(chemo)therapy are still far from understood. Various pathways and means through which the energy of UVR from natural or artificial sources is ultimately transformed into biologic effects within the skin have been suggested and cutaneous sensory nerves, neuropeptides, neurotrophins, and certain nerve-related receptors have been among them. In fact a three-dimensional network of sensory nerve fibers derived from dorsal root ganglia intersperses all layers of the skin including the epidermis. In this forefront of defense against environmental impacts (including UVR) on the skin, sensory nerve fibers become targets by itself and closely contact resident and infiltrating cutaneous cells. Thus, terminals of cutaneous sensory nerve fibers, and neuropeptides within these fibers, are in a central position to participate in mediating therapeutic effects of photo(chemo)therapy.

Observation of coiled blood plexus in rat skin with diffusive light illumination.

Blood plexuses are characteristic anatomical features of acupuncture points (APs). We developed an optical technique using diffusive light illumination to increase the brightened area of skin for observation of the blood plexuses in skin. We found that the blood plexuses were coiled blood vessels which came out of the perforations in the fascia of muscle. The coiled vessels could be straightened by stretching the skin. We observed a series of blood plexuses at the putative APs along the left and right kidney meridian lines in the abdominal skin of rats. In addition, the locations of the plexuses on the muscle fascia were just above the putative acupuncture muscle channels along the kidney meridians. Furthermore, immunohistochemical analysis of the skin specimens of the plexuses revealed its neurovascular bundle nature as expected from known anatomical features of the APs.

Laser light influences cellular viability and proliferation in diabetic-wounded fibroblast cells in a dose- and wavelength-dependent manner.

Phototherapy stimulates metabolic processes in healing wounds. Despite worldwide interest, phototherapy is not firmly established or practiced in South Africa. This study aimed to determine which dose and wavelength would better induce healing in vitro. Diabetic-induced wounded fibroblasts were irradiated with 5 or 16 J/cm(2) at 632.8, 830, or 1,064 nm. Cellular morphology, viability (Trypan blue and apoptosis), and proliferation (basic fibroblast growth factor) were then determined. Cells irradiated with 5 J/cm(2) at 632.8 nm showed complete wound closure and an increase in viability and basic fibroblast growth factor (bFGF) expression. Cells irradiated at 830 nm showed incomplete wound closure and an increase in bFGF expression. Cells irradiated at 1,064 nm showed incomplete closure and increased apoptosis. All cells irradiated with 16 J/cm(2) at all three wavelengths showed incomplete wound closure, increased apoptosis, and decreased bFGF expression. This study showed that diabetic-wounded cells respond in a dose- and a wavelength-dependent manner to laser light. Cells responded the best when irradiated with a fluence of 5 J/cm(2) at a wavelength of 632.8 nm.

Irradiation with a 632.8 nm helium-neon laser with 5 J/cm2 stimulates proliferation and expression of interleukin-6 in diabetic wounded fibroblast cells.

BACKGROUND: The use of lasers has been shown to stimulate wound healing in vivo and in vitro. There is an increase in wound closure, cell viability, proliferation, and cytokine expression. If laser parameters can be optimized and standardized, and the underlying mechanisms better understood, this phototherapy can become an alternative safe treatment to slow-to-heal wounds, such as in patients with diabetes. This study aimed to determine the effect on cellular proliferation, migration, and cytokine [interleukin-6 (IL-6)] expression in diabetic and diabetic wounded fibroblast cells (WS1) post-laser irradiation. METHODS: Diabetic and diabetic wounded WS1 cells were irradiated at 632.8 nm (23 mW) with 5 J/cm(2) or 16 J/cm(2). IL-6 level, cellular proliferation (neutral red assay), and morphology were then determined. RESULTS: Diabetic cells irradiated with 5 J/cm(2) showed no significant change, while diabetic wounded cells showed an increase in IL-6 level, proliferation, and migration. On the other hand, diabetic and diabetic wounded cells irradiated with 16 J/cm(2) showed a significant decrease in proliferation and evidence of cellular damage, and wounded cells showed no migration. CONCLUSION: This study showed that phototherapy at the correct fluence stimulates IL-6 expression, proliferation, and cellular migration in diabetic wounded cells. A fluence of 5 J/cm(2) stimulates diabetic wound healing in vitro, while 16 J/cm(2) is inhibitive.

Comparison of adverse events of laser and light-assisted hair removal systems in skin types IV-VI.

Photoepilation, utilizing lasers and noncoherent light sources, is designed to irradiate as much of the follicular unit as possible, with melanin as the target chromophore. Wavelength absorption should generate energy sufficient to heat and destroy the hair follicle, while preserving the surrounding tissue. When performing photoepilation on African-American skin (Fitzpatrick skin types IV-VI) a greater risk of potential epidermal adverse events, such as dyspigmentation, blistering, crusting, edema, and subsequent scarring, is possible. To reduce epidermal melanin absorption of energy longer wavelengths are considered safer for use on Fitzpatrick skin types IV to VI. This article reviews and compares the reported incidences of adverse events in African-American skin, utilizing lasers and noncoherent light sources for assisted hair removal.

Comparison of biophysical properties of skin measured by using non-invasive techniques in the KM mice following 595 nm pulsed dye, 1064 nm Q-Switched Nd:YAG and 1320 nm Nd:YAG laser non-ablative rejuvenation.

BACKGROUNDS/AIMS: The aim of the study was to compare the changes of the biophysical properties and to objectify the effects of 595 nm pulsed dye, 1064 nm Q-switched Nd:YAG and 1320 nm Nd:YAG lasers non-ablative rejuvenation by non-invasive techniques. METHODS: KM mice were used for the study. The 595 nm pulsed dye, 1064 nm Q-switched Nd:YAG and 1320 nm Nd:YAG laser treatments were evaluated with biophysical parameter measurements including skin elasticity, skin color, skin trans-epidermal water loss (TEWL) and skin hydration. RESULTS: All three lasers improved the biophysical properties in the skin of KM mice. In skin elasticity measurements, the 1064 nm laser treatment showed the lowest ratio (0.61+/-0.09) while the 1320 nm laser showed the highest one (0.76+/-0.07) on day 60. For erythema values, a significant increase was observed immediately after the 1064 nm laser treatment (196.67+/-19.17), but the lowest values occurred with the 1320 nm laser treatment (189.83+/-16.54). None of the three lasers resulted in obvious changes of skin melanin. TEWL increased immediately after laser irradiation, then began to recover and decreased 60 days after the 595 and 1064 nm laser treatments. With the 1320 nm laser treatment the TEWL began to decrease from day 7 and obtained the lowest mean values (5.23+/-1.13). The water-holding capacity increased initially for the 595 and 1320 nm laser irradiation, while decreased for the 1064 nm laser. At day 60 of the experiment, skin hydration values in all animals were superior to those of the controls. The 1320 nm laser treatment caused the highest ratio (1.29+/-0.26). Both the values of TEWL and skin hydration for the 1320 nm laser treated areas differed significantly from the other two lasers. CONCLUSIONS: Our data showed the 1064 nm Q-switched Nd:YAG laser treatment was most effective in improving the skins' mechanical properties, while the 1320 nm Nd:YAG laser can enhance greatly the skin barrier function and the water-holding capacity. Moreover, we demonstrated the biophysical properties differed considerably between different areas.

Three-dimensional model on thermal response of skin subject to laser heating.

A three-dimensional (3D) multilayer model based on the skin physical structure is developed to investigate the transient thermal response of human skin subject to laser heating. The temperature distribution of the skin is modeled by the bioheat transfer equation, and the influence of laser heating is expressed as a source term where the strength of the source is a product of a Gaussian shaped incident irradiance, an exponentially shaped axial attenuation, and a time function. The water evaporation and diffusion is included in the model by adding two terms regarding the heat loss due to the evaporation and diffusion, where the rate of water evaporation is determined based on the theory of laminar boundary layer. Cryogen spray cooling (CSC) in laser therapy is studied, as well as its effect on the skin thermal response. The time-dependent equation is discretized using the finite difference method with the Crank-Nicholson scheme and the stability of the numerical method is analyzed. The large sparse linear system resulted from discretizing the governing partial differential equation is solved by a GMRES solver and the expected simulation results are obtained.

Comparison of diffusion approximation and Monte Carlo based finite element models for simulating thermal responses to laser irradiation in discrete vessels.

Both diffusion approximation (DA) and Monte Carlo (MC) models have been used to simulate light distribution in multilayered human skin with or without discrete blood vessels. However, no detailed comparison of the light distribution, heat generation and induced thermal damage between these two models has been done for discrete vessels. Three models were constructed: (1) MC-based finite element method (FEM) model, referred to as MC-FEM; (2) DA-based FEM with simple scaling factors according to chromophore concentrations (SFCC) in the epidermis and vessels, referred to as DA-FEM-SFCC; and (3) DA-FEM with improved scaling factors (ISF) obtained by equalizing the total light energy depositions that are solved from the DA and MC models in the epidermis and vessels, respectively, referred to as DA-FEM-ISF. The results show that DA-FEM-SFCC underestimates the light energy deposition in the epidermis and vessels when compared to MC-FEM. The difference is nonlinearly dependent on wavelength, dermal blood volume fraction, vessel size and depth, etc. Thus, the temperature and damage profiles are also dramatically different. DA-FEM-ISF achieves much better results in calculating heat generation and induced thermal damage when compared to MC-FEM, and has the advantages of both calculation speed and accuracy. The disadvantage is that a multidimensional ISF table is needed for DA-FEM-ISF to be a practical modelling tool.

Changes in skin physiology during bath PUVA therapy.

BACKGROUND: Frequent bathing leads to a skin barrier damage with various changes in physiological skin parameters. Conversely, ultraviolet (UV) irradiation may improve the impaired skin barrier by reducing inflammatory reactions. OBJECTIVES: The aim of this study was to investigate the changes of physiological skin parameters during a therapy with 8-methoxypsoralen (8-MOP) bathing and subsequent UVA irradiation. METHODS: Thirty patients with a skin disease without barrier disruption were treated with daily bathing in a 8-MOP solution (0.0005%) and subsequent UVA irradiation. Multiple physiological skin parameters (transepidermal water loss, skin blood flow, skin colour, sebum content, skin hydration) were measured repeatedly on clinically non-affected skin on the back, forearm and forehead. In addition, patch testing with sodium lauryl sulphate (SLS) (0.5%) was performed on the forearm and on the back. RESULTS: We found a moderate but significant disturbance of skin barrier and hydration on the forearm and the back (bathing + irradiation) after increasing dosages of therapy. In addition, SLS testing leads to stronger reactions. CONCLUSIONS: We conclude that on clinically healthy skin the impairment of skin barrier by frequent bathing cannot be completely compensated by subsequent UVA irradiation. When conducting a treatment with 8-MOP bathing and UVA irradiation a concomitant therapy supporting the recovery of skin barrier, e.g. with moisturizer, should be performed.

Skin temperature measurements during intense pulsed light emission.

BACKGROUND: Although lasers and intense pulsed light sources have improved the capability of injuring veins without affecting the overlying skin, work is needed to improve the procedure. OBJECTIVE: To create a method for predicting skin reaction to pulsed light. METHODS: Twenty patients were divided into four groups according to skin type (I-IV). An industrial thermometer equipped with a laser-aiming system was adapted to the intense pulsed light source handpiece. Patients received shots of increasing intensity while the skin temperature was measured. RESULTS: Fluence and temperature data were analyzed by logistic regression to evaluate possible injury. The stepwise method selected skin type and temperature variation as predictors of skin injury. Logistic curves indicated the maximum temperature variation tolerable for each skin type. More pigmented skin types tolerated less temperature increase. CONCLUSION: Skin type can predict cutaneous reaction to intense pulsed light through measurements of temperature variation. This method may help achieve successful selective photothermolysis.