Chronological Skin Changes Through Postmastectomy Radiotherapy Based on Radiotherapy Techniques: Using Quantitative Dermatological Measurements.

BACKGROUND: There has been few research on how to measure skin status quantitatively throughout the course of radiotherapy (RT). We evaluated the changes in the skin induced by 2 different RT techniques using objective measurements in breast cancer patients. METHODS: In this prospective study, between August 2015 and March 2019, serial measurements of the dermatological factors during and after postmastectomy radiotherapy (PMRT) were made in 40 breast cancer patients. PMRT was performed using the conventional photon tangential technique (PTT) or patient-tailored bolus technique (PTB). We analyzed these measurements using a mixed effect model and compared the clinically evaluated radiation dermatitis and patient-reported outcomes (PROs). RESULTS: The trend of changes in melanin and erythema was significantly different between the PTB and PTT groups (p = 0.045 and 0.016, respectively). At the 3-month follow-up erythema intensity and melanin were higher in the PTB group than in PTT group (both p < 0.001). Eight patients (40% in the PTB group) reported grade 2 radiation dermatitis and 1 patient (5% in the PTB group) reported grade 3 radiation dermatitis. No grade 2 or higher radiation dermatitis was found in the PTT group. Ten patients (50%) in the PTB group and 3 patients (15%) in the PTT group reported severe erythema likely due to questionable clinical evaluation, but hyperpigmentation was rarely reported at the follow-up visits. CONCLUSION: The PTB group showed higher intensity of erythema at the end of RT than the PTT group and the increase in melanin lasted until the 3-month follow-up visits in the PTB group. Moreover, patients subjectively appealed more severe symptoms following PTB in PROs.

Photoreactivity of Hair Melanin from Different Skin Phototypes-Contribution of Melanin Subunits to the Pigments Photoreactive Properties.

Photoreactivity of melanin has become a major focus of research due to the postulated involvement of the pigment in UVA-induced melanoma. However, most of the hitherto studies were carried out using synthetic melanin models. Thus, photoreactivity of natural melanins is yet to be systematically analyzed. Here, we examined the photoreactive properties of natural melanins isolated from hair samples obtained from donors of different skin phototypes (I, II, III, and V). X-band and W-band electron paramagnetic resonance (EPR) spectroscopy was used to examine the paramagnetic properties of the pigments. Alkaline hydrogen peroxide degradation and hydroiodic acid hydrolysis were used to determine the chemical composition of the melanins. EPR oximetry and spin trapping were used to examine the oxygen photoconsumption and photo-induced formation of superoxide anion, and time-resolved near infrared phosphorescence was employed to determine the singlet oxygen photogeneration by the melanins. The efficiency of superoxide and singlet oxygen photogeneration was related to the chemical composition of the studied melanins. Melanins from blond and chestnut hair (phototypes II and III) exhibited highest photoreactivity of all examined pigments. Moreover, melanins of these phototypes showed highest quantum efficiency of singlet oxygen photogeneration at 332 nm and 365 nm supporting the postulate of the pigment contribution in UVA-induced melanoma.

Evaluation and visualization of facial massage effects by using ultraviolet stereo-image correlation.

BACKGROUND/PURPOSE: This study proposes a technique for visualizing the effect of facial massage using stereo-image correlation with melanin pigment. METHOD: In this method, the melanin pigment of a subject's face is made visible by using an ultraviolet light and utilized as a random pattern for stereo-image correlation. Stereo-pair images of the face with the melanin pigment before and after facial massage are recorded using a desk-sized measurement equipment. Then, the deformation of the face by the massage can be obtained based on the principle of stereovision. The effectiveness of the proposed method is demonstrated by applying it to the massage effect evaluation of eight subjects (females in their 40s). RESULTS: The results show that the massage effect can be visualized from the displacement and strain distributions across the face obtained by the proposed method. In addition, it is observed that the face is displaced significantly by the massage and individual differences between the subjects can be captured. CONCLUSION: The proposed method is effective for evaluating the effect of a facial massage when the painted pattern disappears due to the applied cream during the massage.

Iris Colour and the Risk of Developing Uveal Melanoma.

Uveal melanoma (UM) is a global disease which especially occurs in elderly people. Its incidence varies widely between populations, with the highest incidence among Caucasians, and a South-to-North increase in Europe. As northern Europeans often have blond hair and light eyes, we wondered whether iris colour may be a predisposing factor for UM and if so, why. We compared the distribution of iris colour between Dutch UM patients and healthy Dutch controls, using data from the Rotterdam Study (RS), and reviewed the literature regarding iris colour. We describe molecular mechanisms that might explain the observed associations. When comparing a group of Dutch UM patients with controls, we observed that individuals from Caucasian ancestry with a green/hazel iris colour (Odds Ratio (OR) = 3.64, 95% Confidence Interval (CI) 2.57-5.14) and individuals with a blue/grey iris colour (OR = 1.38, 95% CI 1.04-1.82) had a significantly higher crude risk of UM than those with brown eyes. According to the literature, this may be due to a difference in the function of pheomelanin (associated with a light iris colour) and eumelanin (associated with a brown iris colour). The combination of light-induced stress and aging may affect pheomelanin-carrying melanocytes in a different way than eumelanin-carrying melanocytes, increasing the risk of developing a malignancy.

Anti-Melanogenic Effects of Korean Red Ginseng Oil in an Ultraviolet B-Induced Hairless Mouse Model.

A 'remedy for all' natural product widely known in the Korean Peninsula is called Panax Ginseng Meyer. Globalization represents a persistent risk to the ozone layer, leading to bountiful amounts of Ultra-Violet B beams (UVB). The variety in human skin hues is ascribed to the characteristic color called Melanin. However, Melanin overproduction due to UVB beams promotes skin staining and tumorigenesis, a process called photo aging, which damages skin quality. To assess the effects of Korean Red Ginseng Oil (KGO) on photo aging, the murine melanoma cell lines B16/F10 were used in vitro and HRM-2 hairless mice exposed to UVB were studied in vivo. Our results revealed that KGO reduced tyrosinase activity and melanin production in B16/F10 cells along with the suppression of upstream factors involved in the melanin production pathway, both transcriptionally and transitionally. In the in vivo studies, KGO suppressed the expression of Matrix Metalloproteinase (MMP) and Interleukins along with a reduction of depth in wrinkle formation and reduced collagen degradation. Moreover, the feed intake and feed efficiency ratio that decreased as a result of UVB exposure was also improved by KGO treatment. In light of our results, we conclude that KGO can have considerable benefits due to its various properties of natural skin enhancement.

The dynamics of pigment reactions of human skin to ultraviolet A radiation.

The pigment responses of human skin to broadband UVA radiation (320-400 nm) occur in three distinct phases. The first phase includes immediate pigment darkening (IPD), the pigment that appears immediately after irradiation. The second phase involves an intermediate step, termed persistent pigment darkening (PPD), which leads to the third phase of neomelanogenesis or delayed tanning (DT). Since DT results from synthesis of new melanin, it persists beyond 5-7 days. We conducted studies on human subjects to investigate the dynamic responses of the IPD and PPD reactions to broadband UVA radiation at threshold and superthreshold doses. The threshold doses for IPD, PPD, and DT were found to be approximately 1, 11, and 18 J/cm2 , respectively. The colorimetry ΔL* value corresponding to minimal clinically perceptible pigmentation was found to be 0.8 ± 0.1. IPD appeared immediately and had an associated decay constant of approximately 1.4 minutes. At doses greater than PPD threshold, IPD reaction decayed while PPD developed indicating toward IPD being used as a substrate in the formation of PPD.

Microneedle fractional radiofrequency treatment of facial photoageing as assessed in a split-face model.

BACKGROUND: A new therapeutic device passes radiofrequency energy through microneedles to targeted tissue. Three-dimensional photography may be useful for evaluating the clinical efficacy of microneedle fractional radiofrequency (MFR) used on the appearance of rhytids and to improve facial laxity. AIM: To evaluate the efficacy and safety of MFR in the treatment of facial photoageing. METHODS: In total, participants with facial photoageing were enrolled in the study. All volunteers were randomized to receive split-face treatments with MFR 2 months apart. The participants self-evaluated at baseline, Days 1-7, and Months 1 and 3 after the final treatment. Objective evaluation was provided by a three-dimensional in vivo imaging system. In addition, skin melanin index, erythema index, immediate reactions, healing times and other adverse effects were evaluated. RESULTS: Compared with the untreated side, the treated side of most participants improved, based on clinical assessments at the 1- and 3-month follow-up visits after treatment. Both objective and participative assessments were satisfactory. The participants demonstrated a decrease of roughness parameter (Sa) value at each follow-up visit. Compared with pretreatment value, Sa decreased significantly at Months 1 and 3 on the treated side (P < 0.05). Minimal and reversible adverse effects and rapid healing were recorded. CONCLUSIONS: MFR appears to be an excellent treatment for photodamaged facial skin in Chinese patients.

Epidermal Fluence Threshold Determination by Real-Time Melanin Measurements.

BACKGROUND AND OBJECTIVE: Epidermal preservation is essential during laser treatment for vascular, hair, and benign pigment dyschromias. Epidermal tolerance is determined by epidermal melanin content, fluence, pulse width, wavelength, skin cooling, and spot size. The authors' objective was to determine the maximum epidermal tolerance for the long-pulse alexandrite 755 nm and the long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG) 1064-nm lasers for varying epidermal melanin content. MATERIALS AND METHODS: Skin melanin measurements were performed at the test sites with a melanin reader, and 0.5 to 1 second of refrigerated air precooled the skin. Then, alexandrite and Nd:YAG laser test spots of 5 to 18 mm were delivered in a series of ascending fluences using 5-, 20-, and 50-ms pulse widths. Skin response at 24 to 48 and 96 hours was scored from 0 to 15 varying from "no reaction" to "severe scabbing." RESULTS: Alexandrite laser, mean threshold fluences increased by a factor of 1.2 increasing from 5 to 20 ms, and by a factor of 1.4 increasing from 5 to 50 ms, among subjects with a melanin index (MI) from 9 to 25 (Fitzpatrick skin phototype I-III). The Nd:YAG fluence to reach epidermal tolerance was 6X the fluence with the alexandrite laser for the same MI in subjects with MI 26 to 35. CONCLUSION: Epidermal melanin measurements are quantitative and objective, therefore, improving treatment setting determination by decreasing the risk of overtreatment or undertreatment.

Infrared thermography as control of handheld IPL device for home-use.

Infrared thermography as contactless method for determining the temperature distribution on the surface is used for analyzing the impact of intense pulsed light hair removal device (IPL) on the skin. Depth of light penetration depending of wavelength is described as well as absorption curves and IPL impulse shapes. Energy balance and IPL impulse influence on the skin is analyzed. Melanin temperature rise by different fluence operation and temperature distribution in the modeled hair is used in order to determine overall skin temperature rise. Estimated energy balance provided by mathematical model has been confirmed with experimental results. Performed measurements, beside determination of the right emissivity, required the identification of most significant parameter in the process which proved to be the skin reference temperature and real temperature rise. Practical IPL application with detailed body temperature analysis is comprehensively described and thermal imaging interpretation problem and determination of the temperature rise is observed.

Mitigation of epidermal growth factor receptor inhibitor-induced side effects utilizing melanin and vascular-specific lasers: A case report series.

The advent of targeted chemotherapy has led to the emergence of new dermatologic toxicities. We sought to use lasers and light devices to treat recalcitrant cutaneous adverse effects related to cancer treatment. Three stage III or IV cancer patients with cutaneous complications due to epidermal growth factor receptor (EGFR) inhibitors were treated with melanin and vascular-specific laser and light technologies. Two patients reported reduction in papulopustular eruption following pulse dye laser (PDL) treatment. Two patients noted reduction in hair growth following intense pulsed light (IPL) and/or Alexandrite laser treatments. One patient was treated with both the PDL and IPL and reported improvement of both EGFR-induced hypertrichosis and papulopustular eruption. Laser and light devices targeting melanin and hemoglobin can be utilized to mitigate the cutaneous adverse effects associated with EGFR inhibitors in patients who have failed traditional therapies. This represents a new option for the cancer patient who is suffering from chemotherapy-induced side effects.

[Different faces of phenoloxidase in animals]. / Rózne oblicza oksydazy fenolowej u zwierzat.

Phenoloxidases are oxidoreducting enzymes whose main function is the oxidation of phenols. The term phenoloxidase is often used interchangeably to describe three different enzymes: tyrosinase (EC 1.14.18.1), catechol oxidase, and laccase. Of these, only tyrosinase has two activities: (1) oxygenase activity to hydroxylate monophenols to ortho-diphenols and (2) oxidase activity responsible for further oxidation of ortho-diphenols to ortho-quinones. Tyrosinase is a key enzyme involved in the melanogenesis process, resulting in the formation of black-brown eumelanin and yellow-red feomelanin. In addition to the pigmentary role, human melanin protects against harmful ultraviolet radiation, while in invertebrate animals melanin is involved in the process of cuticle hardening, wound healing, clot formation, maintenance of intestinal homeostasis and defense reactions. In invertebrates, the tyrosinase is synthesized as a proenzyme that is activated by a serine proteases' cascade known as the phenoloxidase system. This system is considered as one of the innate immunity mechanisms.

Clue to Understanding the Janus Behavior of Eumelanin: Investigating the Relationship between Hierarchical Assembly Structure of Eumelanin and Its Photophysical Properties.

The contradictory biological function of eumelanin (photoprotection vs photosensitization) has long been a topic of debate in a wide range of disciplines such as chemistry, physics and biology. For understanding full spectrum of eumelanin's photobiological aspect, revealing how eumelanin's complex structural organization dictates its photophysical properties is critical step. Here, we report a practical approach to controlling the hierarchically assembled structure of natural eumelanin, which leads to disassembly of its structure into subunits and oxidized subunits, respectively. Based on the well-characterized model system, it was possible to systematically determine how the photophysical properties of eumelanin are ruled by its hierarchical assembly organization. Particularly, our experiments reveal that the chemical oxidation of eumelanin's subunits, which leads to delamination of their stacked layer structure, is critical to significantly increase their photochemical reactivity to generate ROS under UV irradiation. This result provides clear experimental evidence that oxidative degradation of eumelanin, which might be induced by phagosomal enzymatic activity in the process of melanomagenesis, is responsible for triggering the negative photobiological role of eumelanin such as ROS source needed for development of malignant melanoma.

UV-induced Melanin Chemiexcitation: A New Mode of Melanoma Pathogenesis.

Mutations in sunlight-induced melanoma arise from cyclobutane pyrimidine dimers (CPDs), DNA photoproducts usually created picoseconds after an ultraviolet (UV) photon is absorbed at thymine or cytosine. Surprisingly, we found that, in melanocytes, CPDs were generated for hours after UVA or UVB exposure. These "dark CPDs" constituted the majority of CPDs in cultured human and murine melanocytes and in mouse skin, and they were most prominent in skin containing pheomelanin, the melanin responsible for blonde and red hair. The mechanism was also a surprise. Dark cyclobutane pyrimidine dimers (CPDs) arise when ultraviolet (UV)-induced superoxide and nitric oxide combine to form peroxynitrite, one of the few biological molecules capable of exciting an electron. This process, termed "chemiexcitation," is the source of bioluminescence in lower organisms. Excitation occurred in fragments of melanin, creating a quantum triplet state that had the energy of a UV photon but which induced CPDs by radiationless energy transfer to DNA. UVA and peroxynitrite also solubilized melanin and permeabilized the nuclear membrane, allowing melanin to enter. Melanin is evidently carcinogenic as well as protective. Chemiexcitation may also trigger pathogenesis in internal tissues because the same chemistry should arise wherever superoxide and nitric oxide arise near cells that contain melanin.

Theoretical insights into the photo-protective mechanisms of natural biological sunscreens: building blocks of eumelanin and pheomelanin.

Eumelanin (EM) and pheomelanin (PM) are ubiquitous in mammalian skin and hair--protecting against harmful radiation from the sun. Their primary roles are to absorb solar radiation and efficiently dissipate the excess excited state energy in the form of heat without detriment to the polymeric structure. EU and PM exist as polymeric chains consisting of exotic arrangements of functionalised heteroaromatic molecules. Here we have used state-of-the-art electronic structure calculations and on-the-fly surface hopping molecular dynamics simulations to study the intrinsic deactivation paths of various building blocks of EU and PM. Ultrafast excited state decay, via electron-driven proton transfer (in EU and PM) and proton-transfer coupled ring-opening (in PM) reactions, have been identified to proceed along hitherto unknown charge-separated states in EU and PM oligomers. These results shed light on the possible relaxation pathways that dominate the photochemistry of natural skin melanins. Extrapolation of such findings could provide a gateway into engineering more effective molecular constituents in commercial sunscreens--with reduced phototoxicity.

Treatment of infraorbital dark circles using 694-nm fractional Q-switched ruby laser.

The objective of this study was to evaluate the efficacy and safety of using a 694-nm fractional Q-switched ruby laser to treat infraorbital dark circles. Thirty women with infraorbital dark circles (predominant color: dark/brown) participated in this open-labeled study. The participants received eight sessions of 694-nm fractional Q-switched ruby laser treatment using a fluence of 3.0-3.5 J/cm2, at an interval of 7 days. The melanin deposition in the lesional skin was observed in vivo using reflectance confocal microscopy (RCM). The morphological changes were evaluated using a global evaluation, an overall self-assessment, and a Mexameter. Twenty-eight of the 30 patients showed global improvements that they rated as excellent or good. Twenty-six patients rated their overall satisfaction as excellent or good. The melanin index indicated a substantial decrease from 240.44 (baseline) to 194.56 (P < 0.05). The RCM results showed a dramatic decrease in melanin deposition in the upper dermis. The adverse effects were minimal. The characteristic finding of dark/brown infraorbital dark circles is caused by increased melanin deposition in the upper dermis. The treatment of these infraorbital dark circles using a 694-nm fractional QSR laser is safe and effective.

2-Mercaptonicotinoyl glycine prevents UV-induced skin darkening and delayed tanning in healthy subjects: A randomized controlled clinical study.

BACKGROUND: Chronic nonextreme sun exposure induces two mechanisms of skin pigmentation, causing immediate darkening and delayed tanning. A new molecule, 2-mercaptonicotinoyl glycine (2-MNG), has been shown in vitro to inhibit both immediate darkening and new melanin synthesis via covalent conjugation of the thiol group of 2-MNG to melanin precursors. OBJECTIVE: To evaluate 2-MNG in preventing both mechanisms in vivo. METHODS: In a randomized, intra-individual and controlled study, 33 subjects with melanin-rich skin were exposed to UV daylight on designated areas on the back and treated with a cosmetic formula containing 0.5% or 1% 2-MNG alone or 0.5% 2-MNG in association with lipohydroxy acid (LHA, 0.3%) plus Mexoryl-SX (MSX, 1.5%). The respective vehicles were used as controls and 4-n-butyl-resorcinol (4-n-BR, 2.5%) as a positive reference. RESULTS: 2-MNG alone significantly reduced immediate darkening and inhibited new melanin production when compared with vehicle, with higher performance at 1% than at 0.5%. 2-MNG at 0.5% in association with LHA and MSX showed significantly higher performance than 2-MNG 0.5% alone. 2-MNG at 0.5% and 1% showed significantly better performance than 4-n-BR. CONCLUSIONS: 2-MNG inhibited both UV-induced skin pigmentation mechanisms in vivo. The association of 2-MNG with LHA plus MSX showed the highest efficacy on melanin-rich skin with pigmentation induced by UV exposure.

Lasers.

Lasers are a very effective approach for treating many hyperpigmented lesions. They are the gold standard treatment for actinic lentigos and dermal hypermelanocytosis, such as Ota nevus. Becker nevus, hyperpigmented mosaicisms, and lentigines can also be successfully treated with lasers, but they could be less effective and relapses can be observed. However, lasers cannot be proposed for all types of hyperpigmentation. Thus, freckles and café-au-lait macules should not be treated as the relapses are nearly constant. Due to its complex pathophysiology, melasma has a special place in hyperpigmented dermatoses. Q-switched lasers (using standard parameters or low fluency) should not be used because of consistent relapses and the high risk of post-inflammatory hyperpigmentation. Paradoxically, targeting the vascular component of the melasma lesion with lasers could have a beneficial effect. However, these results have yet to be confirmed. In all cases, a precise diagnosis of the type of hyperpigmentation is mandatory before any laser treatment, and the limits and the potential side effects of the treatment must be clearly explained to patients.

Epidermal photoprotection: comparative study of narrowband ultraviolet B minimal erythema doses with and without stratum corneum stripping in normal and vitiligo skin.

BACKGROUND: Recent accumulating data in the literature have indicated a complex photoprotective role of the epidermis, and the role of melanin as the major epidermal photoprotective mechanism has become debatable. AIM: Comparative assessment of the photoprotective roles played by different epidermal structures and compounds. METHODS: In total, 64 participants, comprising patients with vitiligo (n = 32) and healthy volunteers (n = 32), with skin phototypes (SPTs) II to V, were enrolled in the study. Areas of skin were delineated; for both lesional and nonlesional skin, the stratum corneum (the SC) was stripped, followed 24 h later by exposure to narrowband ultraviolet B (NB-UVB) irradiation, to measure the minimal erythema dose (MED) in normal, stripped normal, vitiliginous and stripped vitiliginous skin models. These MED values were used to assess the photoprotective role of epidermal structures: melanin, viable epidermis (VE) and the SC. RESULTS: In the vitiligo group, the MED values were significantly (P < 0.05) different between the skin models, being highest in normal skin, followed by stripped normal, vitiliginous and stripped vitiliginous skin. A similar significance level was found within each SPT for almost all comparisons. There was also a significant (P < 0.001) positive correlation between MED and SPTs. There were also significant (P < 0.05) differences in MED values calculated for epidermal structures, being highest for VE, followed by melanin and then the SC, and there was a significant (P < 0.05) positive correlation between MED and SPTs. CONCLUSION: Epidermal photoprotection may extend beyond melanin production, involving several factors such as epidermal layer thickness, optical properties and chromophores. Such a role was perceived to be reactive to UV irradiation, and more efficient in those with higher SPTs.

A triple-stimulus responsive melanin-based nanoplatform with an aggregation-induced emission-active photosensitiser for imaging-guided targeted synergistic phototherapy/hypoxia-activated chemotherapy.

Multimodal synergistic therapy has gained increasing attention in cancer treatment to overcome the limitations of monotherapy and achieve high anticancer efficacy. In this study, a synergistic phototherapy and hypoxia-activated chemotherapy nanoplatform based on natural melanin nanoparticles (MPs) loaded with the bioreduction prodrug tirapazamine (TPZ) and decorated with hyaluronic acid (HA) was developed. A self-reporting aggregation-induced emission (AIE)-active photosensitizer (PS) (BATTMN) was linked to the prepared nanoparticles by boronate ester bonds. The MPs and BATTMN-HA played roles as quenchers for PS and cancer targeting/photodynamic moieties, respectively. As a pH sensitive bond, the borate ester bonds between HA and BATTMN are hydrolysed in the acidic cancer environment, thereby separating BATTMN from the nanoparticles and leading to the induction of fluorescence for imaging-guided synergistic phototherapy/hypoxia-activated chemotherapy under dual irradiation. TPZ can be released upon activation by pH, near-infrared (NIR) and hyaluronidase (Hyal). Particularly, the hypoxia-dependent cytotoxicity of TPZ was amplified by oxygen consumption in the tumor intracellular environment induced by the AIE-active PS in photodynamic therapy (PDT). The nanoparticles developed in our research showed favorable photothermal conversion efficiency (η = 37%), desired cytocompatibility, and excellent synergistic therapeutic efficacy. The proposed nanoplatform not only extends the application scope of melanin materials with AIE-active PSs, but also offers useful insights into developing multistimulus as well as multimodal synergistic tumor treatment.