Effects In Human Skin Research Articles

Piperlongumine regulates genes involved in the skin barrier in epidermal keratinocyte HaCaT cells

ABSTRACT Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αβγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

Effects of imidazolium ionic liquids on skin barrier lipids – Perspectives for drug delivery

Ionic liquids (ILs) have great potential to facilitate transdermal and topical drug delivery. Here, we investigated the mechanism of action of amphiphilic ILs 1-methyl-3-octylimidazolium bromide (C8MIM) and 3-dodecyl-1-methylimidazolium bromide (C12MIM) in skin barrier lipid models in comparison to their complex effects in human skin. C8MIM incorporated in a skin lipid model was a better permeation enhancer than C12MIM for water and model drugs, theophylline and diclofenac. Solid state 2H NMR and X-ray diffraction indicated that both ILs prefer the cholesterol-rich regions in skin lipids without significantly perturbing their lamellar arrangement and that C8MIM induces the formation of an isotropic lipid phase to a greater extent compared to C12MIM. C12MIM applied topically to the lipid model or human skin as a pretreatment was more potent than C8MIM. When co-applied with the drugs to human skin, aqueous C12MIM was more potent than C8MIM in enhancing theophylline permeation, but neither IL affected (even decreased) diclofenac permeation. Thus, the IL’s ability to permeabilize skin lipid barrier is strongly modulated by its ability to reach the site of action and its interactions with drug and solvent. Such an interplay is far from trivial and requires detailed investigation to realize the full potential of ILs.

New developments in sunscreens.

Topical sunscreen application is one of the most important photoprotection tool to prevent sun damaging effects in human skin at the short and long term. Although its efficacy and cosmeticity have significantly improved in recent years, a better understanding of the biological and clinical effects of longer wavelength radiation, such as long ultraviolet A (UVA I) and blue light, has driven scientists and companies to search for effective and safe filters and substances to protect against these newly identified forms of radiation. New technologies have sought to imbue sunscreen with novel properties, such as the reduction of calorific radiation. Cutaneous penetration by sunscreens can also be reduced using hydrogels or nanocrystals that envelop the filters, or by binding filters to nanocarriers such as alginate microparticles, cyclodextrins, and methacrylate polymers. Finally, researchers have looked to nature as a source of healthier products, such as plant products (e.g., mycosporines, scytonemin, and various flavonoids) and even fungal and bacterial melanin, which could potentially be used as substitutes or enhancers of current filters.

1065 The topical AhR agonist tapinarof has broad in vivo immunosuppressive and immunomodulatory effects in human skin grafted mice

1065 The topical AhR agonist tapinarof has broad in vivo immunosuppressive and immunomodulatory effects in human skin grafted mice

Oral 11β-HSD1 inhibitor AZD4017 improves wound healing and skin integrity in adults with type 2 diabetes mellitus: a pilot randomized controlled trial.

BackgroundChronic wounds (e.g. diabetic foot ulcers) reduce the quality of life, yet treatments remain limited. Glucocorticoids (activated by the enzyme 11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1) impair wound healing.ObjectivesEfficacy, safety, and feasibility of 11β-HSD1 inhibition for skin function and wound healing.DesignInvestigator-initiated, double-blind, randomized, placebo-controlled, parallel-group phase 2b pilot trial.MethodsSingle-center secondary care setting. Adults with type 2 diabetes mellitus without foot ulcers were administered 400 mg oral 11β-HSD1 inhibitor AZD4017 (n = 14) or placebo (n = 14) bi-daily for 35 days. Participants underwent 3-mm full-thickness punch skin biopsies at baseline and on day 28; wound healing was monitored after 2 and 7 days. Computer-generated 1:1 randomization was pharmacy-administered. Analysis was descriptive and focused on CI estimation. Of the 36 participants screened, 28 were randomized.ResultsExploratory proof-of-concept efficacy analysis suggested AZD4017 did not inhibit 24-h ex vivoskin 11β-HSD1 activity (primary outcome; difference in percentage conversion per 24 h 1.1% (90% CI: −3.4 to 5.5) but reduced systemic 11β-HSD1 activity by 87% (69–104%). Wound diameter was 34% (7–63%) smaller with AZD4017 at day 2, and 48% (12–85%) smaller after repeat wounding at day 30. AZD4017 improved epidermal integrity but modestly impaired barrier function. Minimal adverse events were comparable to placebo. Recruitment rate, retention, and data completeness were 2.9/month, 27/28, and 95.3%, respectively.ConclusionA phase 2 trial is feasible, and preliminary proof-of-concept data suggests AZD4017 warrants further investigation in conditions of delayed healing, for example in diabetic foot ulcers.Significance statementStress hormone activation by the enzyme 11β-HSD type 1 impairs skin function (e.g. integrity) and delays wound healing in animal models of diabetes, but effects in human skin were previously unknown. Skin function was evaluated in response to treatment with a 11β-HSD type 1 inhibitor (AZD4017), or placebo, in people with type 2 diabetes. Importantly, AZD4017 was safe and well tolerated. This first-in-human randomized, controlled, clinical trial found novel evidence that 11β-HSD type 1 regulates skin function in humans, including improved wound healing, epidermal integrity, and increased water loss. Results warrant further studies in conditions of impaired wound healing, for example, diabetic foot ulcers to evaluate 11β-HSD type 1 as a novel therapeutic target forchronic wounds.

A Theoretical Model for Wearable Thermoelectric Generators Considering the Effect of Human Skin

Wearable thermoelectric generators (w-TEGs) are attracting interest due to their ability to self-power miniaturized electronic devices by converting human body heat into electricity. However, the harvested power density utilizing w-TEGs is in the range of microwatts to milliwatts per square centimeter, which is not sufficient for powering wearable sensors and electronics. In this paper, a theoretical model for w-TEGs considering the human skin effect is developed based on one-dimensional heat transfer analysis. Human skin is geometrically modeled as a multilayer structure consisting of fat, dermis and epidermis, and metabolic heat generation and blood perfusion in skin tissues are taken into account. The influence of load resistance, skin effect, thermal contact resistance at the skin/w-TEG interface, fill factor, thermal conductivity of fill material and heat convection of the spreader on the performance of w-TEG are investigated. Numerical results show that the effect of metabolic heat generation can be negligible, but the heat transfer by blood perfusion in dermis should be considered for the power analysis of w-TEG. The simplified solutions with high accuracy which are more convenient for engineering application of w-TEGs are obtained through rigorous mathematical analysis. The closed-form optimal expressions of load resistance, fill factor and leg height corresponding to maximum power output are provided, and these results can be used to explore the design criteria of w-TEGs. The proposed model considering the effect of human skin is extremely helpful in the actual design of w-TEG devices.

Nanoliposomes codelivering bioactive peptides produce enhanced anti-aging effect in human skin

The present study aimed to develop nanoliposomes codelivering multiple bioactive peptides to achieve improved and comprehensive anti-aging effects in human skin. The nanoliposomes were simultaneously loaded with carnosine, palmitoyl tripeptide-5 and acetyl hexapeptide-3 (CPA-NLPs) for topical delivery. The CPA-NLPs were nano-scaled with narrow size distribution, and showed high encapsulation efficiency, high loading capacity and sustained release of bioactive peptides. Flow cytometry and confocal laser scanning microscopy showed that the nanoliposomes significantly enhanced the cellular uptake of the loaded cargo by human skin fibroblasts (HSF) cells. The CPA-NLPs also protected HSF cells from H2O2-induced oxidative stress damage and increased their expression levels of type Ι collagen and hyaluronic acid. In addition, treatment with CPA-NLPs inhibited catecholamine release in rat adrenal pheochromocytoma (PC12) cells. In a clinical trial, application of a lotion containing 2% CPA-NLPs in face led to a remarkable reduction of the volume, area and area ratio of wrinkles, and an improvement of skin elasticity. These results suggest that loading a combination of bioactive peptides into nanoliposomes is a promising strategy to enhance the topical delivery efficiency and the anti-aging efficacy.

Theophylline exerts complex anti-ageing and anti-cytotoxicity effects in human skin ex vivo.

Theophylline is a phosphodiesterase inhibitor that is being used clinically for asthma therapy. In addition, it is recognized as a cosmetic agent with possible anti-ageing and anti-oxidative properties. Nevertheless, how it affects human skin is still poorly examined. Theophylline (10 or 100µM) was administered to the culture medium of full-thickness human skin ex vivo for 24 or 72h. Theophylline stimulated protein expression of the anti-oxidant metallothionein-1 and mRNA levels of collagen I and III. Assessment of fibrillin-1 immunohistology revealed enhanced structural stability of dermal microfibrils. Theophylline also exerted extracellular matrix-protective effects by decreasing MMP-2 and MMP-9 mRNA levels, partially antagonizing the effects of menadione, the potent, toxic ROS donor. In addition, it decreased menadione-stimulated epidermal keratinocytes apoptosis. Interestingly, theophylline also increased the level of intracutaneously produced melatonin, that is the most potent ROS-protective and DNA damage repair neuromediator, and tendentially increased protein expression of MT1, the melatonin receptor. Theophylline also increased the expression of keratin 15, the stem cell marker, in the epidermal basal layer but did not change mitochondrial activity or epidermal pigmentation. This ex vivo pilot study in human skin shows that theophylline possesses several interesting complex skin-protective properties. It encourages further examination of theophylline as a topical candidate for anti-ageing treatment.

911 Theophylline exerts complex anti-aging and anti-cytotoxicity effects in human skin ex vivo

911 Theophylline exerts complex anti-aging and anti-cytotoxicity effects in human skin ex vivo

Mechanisms of and variables affecting UVR photoadaptation in human skin.

Humans have been exposed to solar UV radiation since their appearance on Earth and evolution has enabled most individuals to adapt to this exposure, to some degree. UV radiation produces several deleterious effects in human skin and light-skinned individuals are at greatest risk for both acute and long-term negative effects such as DNA damage, sunburn, immune suppression and skin cancer. The benefits of photoadaptation, which leads to a decreased response after acclimatization, are that humans who have skin that is capable of photoadaptation can work and play in the sun with reduced fear of painful sunburn. However, the effects of photoadaptation on DNA damage and development of skin cancer are quite complex and less well-understood. In this article, we have reviewed the current state of knowledge of UVR photoadaptation in human skin. However, more studies are needed to explore the use of UVR photoadaptation to protect against critical endpoints, such as skin cancer.

BMAL1 and CLOCK proteins in regulating UVB-induced apoptosis and DNA damage responses in human keratinocytes.

A diverse array of biological processes are under circadian controls. In mouse skin, ultraviolet ray (UVR)-induced apoptosis and DNA damage responses are time-of-day dependent, which are controlled by core clock proteins. This study investigates the roles of clock proteins in regulating UVB responses in human keratinocytes (HKCs). We found that the messenger RNA expression of brain and muscle ARNT-like 1 (BMAL1) and circadian locomotor output cycles kaput (CLOCK) genes is altered by low doses (5 mJ/cm2 ) of UVB in the immortalized HaCat HKCs cell line. Although depletion of BMAL1 or CLOCK has no effect on the activation of Rad3-related protein kinases-checkpoint kinase 1-p53 mediated DNA damage checkpoints, it leads to suppression of UVB-stimulated apoptotic responses, and downregulation of UVB-elevated expression of DNA damage marker γ-H2AX and cell cycle inhibitor p21. Diminished apoptotic responses are also observed in primary HKCs depleted of BMAL1 or CLOCK after UVB irradiation. While CLOCK depletion shows a suppressive effect on UVB-induced p53 protein accumulation, depletion of either clock gene triggers early keratinocyte differentiation of HKCs at their steady state. These results suggest that UVB-induced apoptosis and DNA damage responses are controlled by clock proteins,but via different mechanisms in the immortalized human adult low calcium temperature and primary HKCs. Given the implication of UVB in photoaging and photocarcinogenesis, mechanistic elucidation of circadian controls on UVB effects in human skin will be critical and beneficial for prevention and treatment of skin cancers and other skin-related diseases.

1162 BMAL1 and CLOCK proteins in regulating the sensitivity of human keratinocytes to UVB-induced apoptosis

A diverse array of biological processes is under circadian controls. It has been reported that UV-induced apoptosis and DNA damage responses in mouse skin are time-of-day dependent and regulated by core clock proteins, including BMAL1, CLOCK, PERs, and CRYs. The aim of this study is to investigate the circadian controls of UV responses in human keratinocytes, using the siRNA-mediated loss-of-function approach. We found that low-dose (5 mJ/cm2) of UVB triggered an oscillation of BMAL1 and CLOCK mRNA expression in the immortal HaCat human keratinocyte cell line, as well as primary human keratinocytes. In HaCat cells, depletion of BMAL1 or CLOCK reduced the percentage of UVB-induced apoptotic cells from 43% (in controls) to 29% (p < 0.001) and 31% (P < 0.05), respectively. Moreover, knockdown of either clock gene strongly blocked UVB-induced expression of tumor necrosis factor α (TNFα) and phosphorylation of NF-κB. These results suggest that BMAL1-CLOCK proteins may promote cell death by regulating the TNFα-NF-κB mediated extrinsic apoptotic pathway in UVB-irradiated HaCat keratinocytes. Given the critical impact of UVB on photo-aging and photo-carcinogenesis, mechanistic elucidation and understanding of circadian controls on UVB effects in human skin will be beneficial for prevention and treatment of skin-related diseases including cancers.

Intrinsic Photosensitivity Enhances Motility of T Lymphocytes.

Sunlight has important biological effects in human skin. Ultraviolet (UV) light striking the epidermis catalyzes the synthesis of Vitamin D and triggers melanin production. Although a causative element in skin cancers, sunlight is also associated with positive health outcomes including reduced incidences of autoimmune diseases and cancers. The mechanisms, however, by which light affects immune function remain unclear. Here we describe direct photon sensing in human and mouse T lymphocytes, a cell-type highly abundant in skin. Blue light irradiation at low doses (<300 mJ cm−2) triggers synthesis of hydrogen peroxide (H2O2) in T cells revealed by the genetically encoded reporter HyPerRed. In turn, H2O2 activates a Src kinase/phospholipase C-γ1 (PLC-γ1) signaling pathway and Ca2+ mobilization. Pharmacologic inhibition or genetic disruption of Lck kinase, PLC-γ1 or the T cell receptor complex inhibits light-evoked Ca2+ transients. Notably, both light and H2O2 enhance T-cell motility in a Lck-dependent manner. Thus, T lymphocytes possess intrinsic photosensitivity and this property may enhance their motility in skin.

Resveratrol‐Enriched Rice Protects Human Skin against UVB‐Induced Photoaging

Ultraviolent radiation can cause skin photoaging, skin wrinkle and pigmentations. Synthetic cosmaceuticals as well as medicines have number of side effects as well as drawbacks so natural therapies are the best way of protecting human skin and looking young and smart. Genetically engineered Resveratrol‐enriched rice (RR) has been reported to have excellent anti‐obesity and depigmenting effects in human skin however its effect in UVB induced skin aging was not studied yet. In this study, we evaluated the effects of normal rice (NR), resveratrol‐enriched rice (RR), and resveratrol (R) on ultraviolet B (UVB)‐irradiated human dermal fibroblasts (HDFs) and reconstructed skin tissue to determine the therapeutic potential of these agents in skin wrinkling and skin photoaging. We measured the cellular levels of procollagen type I (PIP‐1) and matrix metalloproteinase (MMP)‐1 using ELISA in NHDF cells after UVB irradiation. UVB‐irradiated NHDF cells that were treated with NR, RR, and R exhibited higher PIP‐1 levels and lower MMP‐1 levels than untreated cells. Among the treatments, RR was found to have the maximum potential to prevent skin damage in both, for MMP‐1 inhibition as well as PIP induction. Taken together, our findings demonstrated that the anti‐wrinkle properties of RR might be superior to those of R or NR alone. Additionally, RR possesses anti‐skin photoaging effects, via downregulating the MMP‐1 levels and upregulating the pro‐collagen production in UVB‐irradiated reconstructed skin as well. In conclusion, RR may provide a non‐toxic and convenient means of preventing UVB‐induced skin wrinkles and related diseases.Support or Funding InformationThis work was supported by a grant from the Next‐Generation BioGreen 21 Program (No. PJ01118803), Rural Development Administration, Republic of Korea

Molecular Characterization of Human Skin Response to Diphencyprone at Peak and Resolution Phases: Therapeutic Insights

Diphencyprone (DPCP) is a hapten that induces delayed-type hypersensitivity (DTH) reactions. It is used as an immune modulating therapeutic, but its molecular effects in human skin are largely unknown. We studied cellular and molecular characteristics of a recall response to 0.04% DPCP at 3 day (peak) and 14 day (resolution) timepoints using immune markers, RT-PCR and gene array approaches. A peak response showed modulation of ~7,500 mRNA transcripts, with high expression of cytokines that define all major effector T-cell subsets. Concomitant increases in T-cell and CD11c+ dendritic cell (DC) infiltrates were measured. The resolution reaction was characterized by unexpectedly high levels of T-cells and mature (DC-LAMP+) DCs, but with marked decreases in expression of IL-2, IFNγ, and other T-cell derived cytokines. However, negative immune regulators such as IDO1 that were high in peak reactions, continued to have high expression in resolution reactions. In the resolution reaction, ~1,500 mRNA transcripts were significantly different from placebo-treated skin. These data suggest the response to DPCP evolves from an inflammatory/effector peak at day 3 to a more regulated immune response after 14 days. This model system could be useful for further dissection of mechanisms of immune activation or negative immune regulation in human skin.

Penetration and biological effects of topically applied cyclosporin A nanoparticles in a human skin organ culture inflammatory model

Systemic antipsoriatic therapies have potentially life-threatening, long-term side effects. The efficacy of topical drugs is poor, but may be improved by the use of delivery systems based on drug nanoparticles. To produce nanoparticles (NP) composed of cyclosporin A, a classical antipsoriatic drug, and to investigate their penetration and biological effects in human skin affected by psoriatic symptoms, poly-ε-caprolactone (PCL) and cyclosporin A (CsA) NP were prepared by the solvent evaporation method. Skin penetration was followed using fluorescently labeled NP in human skin organ cultures (hSOC). Psoriatic symptoms were mimicked in hSOC by the treatment with epidermal growth factor (EGF) and bacterial lipopolysaccharide (LPS). Cell viability in hSOC was evaluated by the resazurin test, and cytokine secretion into the growth medium was measured by immunodetection. We showed that topically applied NP diffused throughout the epidermis within two hours and through the dermis within the following day. They significantly reduced the secretion of inflammatory cytokines IL-1β, IL-6, IL-8, IL-20 and IL-23. At active doses, no cytotoxicity was detected. This type of NP display relevant properties for the use as topical anti-inflammatory agents and may help to resorb psoriatic lesions.

Dynamic changes in cellular infiltrates with repeated cutaneous vaccination: a histologic and immunophenotypic analysis

BackgroundMelanoma vaccines have not been optimized. Adjuvants are added to activate dendritic cells (DCs) and to induce a favourable immunologic milieu, however, little is known about their cellular and molecular effects in human skin. We hypothesized that a vaccine in incomplete Freund's adjuvant (IFA) would increase dermal Th1 and Tc1-lymphocytes and mature DCs, but that repeated vaccination may increase regulatory cells.MethodsDuring and after 6 weekly immunizations with a multipeptide vaccine, immunization sites were biopsied at weeks 0, 1, 3, 7, or 12. In 36 participants, we enumerated DCs and lymphocyte subsets by immunohistochemistry and characterized their location within skin compartments.ResultsMature DCs aggregated with lymphocytes around superficial vessels, however, immature DCs were randomly distributed. Over time, there was no change in mature DCs. Increases in T and B-cells were noted. Th2 cells outnumbered Th1 lymphocytes after 1 vaccine 6.6:1. Eosinophils and FoxP3+ cells accumulated, especially after 3 vaccinations, the former cell population most abundantly in deeper layers.ConclusionsA multipeptide/IFA vaccine may induce a Th2-dominant microenvironment, which is reversed with repeat vaccination. However, repeat vaccination may increase FoxP3+T-cells and eosinophils. These data suggest multiple opportunities to optimize vaccine regimens and potential endpoints for monitoring the effects of new adjuvants.Trail RegistrationClinicalTrials.gov Identifier: NCT00705640

Pharmacokinetics of amitriptyline in rabbit skin and plasma following iontophoretic administrations

Background: Amitriptyline (AMT) is a tricyclic antidepressant with demonstrated local analgesic effects in human skin. Aim: We investigated the feasibility and mechanisms of iontophoretic delivery of AMT to rabbit dermis and plasma. Method: Two microdialysis probes were inserted into the upper dorsal shaved skin of tranquilized rabbits. After 1 hour, an iontophoresis cartridge was placed on top of one probe. The cartridge consisted of a stainless steel electrode covered with a pad that was filled with a 4.3 % AMT glycerin/water (50:50). Iontophoresis was performed at 100, 200, or 300 μA/cm2 constant-current density for 60 minutes. Dialysate samples were collected every 8 minutes for 3 hours and analyzed for AMT via a validated high-performance liquid chromatographic assay. Retrodialysis was performed at the other site. Blood samples were collected serially for 4 hours. Results: In vivo retrodialysis recovery was 89 ± 2%. AMT skin exposure increased non-proportionally with current density: AUCs were 19 ± 7, 119 ± 56, and 615 ± 302 mg/L/min for the 100, 200, and 300 μA/cm2, respectively, and Cmax were 107 ± 15, 1070 ± 537, and 5870 ± 1289 μg/L. In vivo plasma concentrations were always below LLOQ (0.1 μg/mL). Conclusion: AMT can be administered by iontophoresis and produces significant skin concentrations and negligible plasma levels.

Grape seed proanthocyanidines and skin cancer prevention: Inhibition of oxidative stress and protection of immune system

Overexposure of the skin to UV radiation has a variety of adverse effects on human health, including the development of skin cancers. There is a need to develop nutrition-based efficient chemopreventive strategies. The proanthocyanidins present in grape seeds (Vitis vinifera) have been shown to have some biological effects, including prevention of photocarcinogenesis. The present communication discusses the in vitro and in vivo studies of the possible protective effect of grape seed proanthocyanidins (GSPs) and the molecular mechanism for these effects. In SKH-1 hairless mice, dietary supplementation with GSPs is associated with a decrease of UVB-induced skin tumor development in terms of tumor incidence, tumor multiplicity, and a decrease in the malignant transformation of papillomas to carcinomas. It is suggested that the chemopreventive effects of dietary GSPs are mediated through the attenuation of UV-induced: (i) oxidative stress; (ii) activation of mitogen-activated protein kinases and nuclear factor-kappa B (NF-kappaB) signaling pathways; and (iii) immunosuppression through alterations in immunoregulatory cytokines. Collectively, these studies indicate protective potential of GSPs against experimental photocarcinogenesis in SKH-1 hairless mice, and the possible mechanisms of action of GSPs, and suggest that dietary GSPs could be useful in the attenuation of the adverse UV-induced health effects in human skin.

Die Infrarot-Erytheme

Infrared (IR) radiation can cause some effects in human skin as well as intensify or diminish effects which are caused by ultraviolet (UV), visible light or other physical or chemical means. Compared to UV, our knowledge of IR effects on human beings is rather low. Following intensive irradiation with wIRA (water-filtered IR, 3000 W/m 2 ; 1440 kJ/m 2 ) skin surface temperature rose up to 45.3 °C within six minutes. Intensive reddening appeared which just a little bit spread over the non-exposed skin and disappeared within some 120 minutes. IRC (long-wave IR, 500 - 1000 W/m 2 ; 900 - 1800 kJ/m 2 ) quickly provoked a predominately homogenous erythema, which soon spread out of the border of exposed skin, and, contrary to moderate IRA fluences, soon transformed itself reticular or dendritic, and was still clearly recognisable after some hours. There were distinctive differences between morphology and time course of erythemas provoked by UV, IRA or IRC. Due to some conspicuous similarities between IRC erythemas and ERYTHEMA AB IGNE, it is speculated that experimental IR erythemas could give hints for fluence, irradiance, frequency and doses which are critical of premature skin aging or cancer development.