Article

Clinical and histological effects of blue light on normal skin

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Abstract

Phototherapy with visible light is gaining interest in dermatological practice. Theoretically, blue light could induce biological effects comparable to ultraviolet A (UVA) radiation. To study the effects of blue light on normal skin in terms of photodamage, skin ageing and melanogenesis. Eight healthy volunteers were included and irradiation with visible blue light was given on five consecutive days. Skin biopsies were analysed with respect to photodamage (p53, vacuolization, sunburn cells), skin ageing (elastosis, MMP-1) and melanogenesis (Melan-A). No inflammatory cells and sunburn cells were visible before or after irradiation. A significant increase in the perinuclear vacuolization of keratinocytes was demonstrated during treatment (P=0.02) with a tendency towards significance after cessation of treatment (P=0.09). No significant change in p53 expression was seen. Signs of elastosis and changes in MMP-1 expression were absent. Minimal clinical hyperpigmentation of the irradiated skin was confirmed histologically with a significant increase in Melan-A-positive cells (P=0.03). Visible blue light, as given in the present study, does not cause deoxyribonucleic acid damage or early photo-ageing. The biological effects of blue light on normal skin are transient melanogenesis and inexplicable vacuolization without resulting apoptosis. In conclusion, the (short-term) use of visible blue light in dermatological practice is safe.

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... The fact that photosensitive diseases and photosensitisation by chemical substances lower the tolerance to visible light has been well known for a century [15]. More recent studies [16][17][18][19][20] elaborate on effects of visible light on normal skin. ...
... Effects of a variety of polychromatic light sources emitting in the wavelength range 400-500 nm resulted in a "lowest observed effect level" corresponding to radiant exposures of between 5 and 200 Jcm −2 ( Table 1). Induction of observable pigmentation in human skin tissue was reported in four publications [17,[32][33][34]. This was the only endpoint consistently reported in human skin. ...
... Kleinpenning et al. [17] Human skin in vivo 400-700 (quartz-halogen lamp) Pigmentation Liebmann et al. [40] 412 ) Rascalo et al. [43] Various cell biological effects and gene expression SZA values between 35 and 90° (Online Resource 3). We consider these near constant ratios to justify the application of the proxy weighting function. ...
Article
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Advocates of skin protection against blue light express concern about exposure to indoor lighting and electronic screens as well as natural outdoor exposure. However, the nature of adverse effects in skin is unclear and the doses to induce effects are unknown. We aimed to reveal whether there is a scientific basis for promoting skin protection against violet-blue light (400-500 nm, VBL). Based on published literature, we determined the time to reach a threshold dose that induced a biological response in human skin. In the absence of an action spectrum for effects on skin, we used a hand held probe with a defined spectral response and measurements of the unweighted exposure between 400 and 500 nm to estimate the exposure by a selection of artificial light sources and solar light. For comparison, an outdoor threshold erythemally weighted UV dose was set to 1 SED (standard erythema dose). Outdoor, weighted irradiances were obtained using a radiative transfer model. Induction of pigmentation in human skin tissue was the only consistently reported endpoint after VBL exposure of about 65 Jcm-2. This threshold dose was reached in 0.5 to 20 months of exposure to indoor lighting sources. In comparison, specialised medical sources reached this dose in 0.5 min to 45 h. The time outdoors to reach 1 SED was shorter than the time to reach a VBL threshold dose throughout all seasons. Skin protection against VBL is superfluous for exposures to domestic lighting sources or screens and for solar radiation; however, it may be advantageous for patients suffering from photosensitive diseases or taking photosensitising medication.
... As an innovative non-antibiotic approach, the antimicrobial blue light (aBL) in the 400-470nm spectrum demonstrated its intrinsic antimicrobial properties resulting from the presence of photosensitive chromosomal carriers in pathogenic microbes. It is conceivable that microbes are less able to develop resistance against aBL compared to conventional antibiotics, due to the multi-target properties of aBL [23][24][25][26]. In addition, it is well accepted that aBL is less harmful to host cells than UVC irradiation [24][25][26]. ...
... It is conceivable that microbes are less able to develop resistance against aBL compared to conventional antibiotics, due to the multi-target properties of aBL [23][24][25][26]. In addition, it is well accepted that aBL is less harmful to host cells than UVC irradiation [24][25][26]. But even this method cannot replace antibiotic treatment for gum disease due to technical reasons and a limited of researches and applications for this method. ...
Article
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Abstract Background: Information on the pattern of antimicrobial susceptibility and guidelines for oral antibiotic therapy for Yemeni patients are not available for those with localized aggressive periodontitis (LAP) due to Aggregatibacter actinomycetemcomitans, a condition that often requires complementary antibiotic treatment. Aim: The primary objective of this study was to examine Aggregatibacter actinomycetemcomitans clinical isolates on a panel of antibiotics commonly used in oral / systemic therapy. Materials and Methods: The study included 30 strains of A. actinomycetemcomitans isolated from LAP patients. The subgingival plaque was plated onto Trypticase Soy Serum Bacitracin Vancomycin Agar medium and incubated for 72 h, and the suspected colonies were confirmed by phenotypic tests. Each isolate was tested against a group of 12 antibiotics using the disc diffusion method. The test was performed and interpreted according to the CLSIFDA schedule. Results: Cefotaxime, ceftriaxone and moxifloxacin showed excellent activity at 100%, 100% and 96.7% sensitivity respectively, followed by amoxiclav (90% sensitive), tetracycline (80% sensitive), cefuroxime (76.7% sensitive), cefazolin (73.3% sensitive) and azithromycin (63.3%, sensitive). The bacterial strains showed poor susceptibility to clindamycin, doxycycline, and metronidazole. All isolates were moderate or resistant to amoxicillin. Conclusion: A. actinomycetemcomitans isolates showed a high level of resistance to clindamycin, metronidazole and amoxicillin. The development of resistance to azithromycin and cefazoline also appears to be significant. Changing resistance between different members of the cephalosporin group is a factor that should be investigated further due to the lack of a sensitivity profile to this antibiotic and interpretive criterion for oral bacteria. Keywords: Aggregatibacter actinomycetemcomitans, antibiotic sensitivity, Disc diffusion method.
... As an innovative non-antibiotic approach, the antimicrobial blue light (aBL) in the 400-470nm spectrum demonstrated its intrinsic antimicrobial properties resulting from the presence of photosensitive chromosomal carriers in pathogenic microbes. It is conceivable that microbes are less able to develop resistance against aBL compared to conventional antibiotics, due to the multi-target properties of aBL [23][24][25][26]. In addition, it is well accepted that aBL is less harmful to host cells than UVC irradiation [24][25][26]. ...
... It is conceivable that microbes are less able to develop resistance against aBL compared to conventional antibiotics, due to the multi-target properties of aBL [23][24][25][26]. In addition, it is well accepted that aBL is less harmful to host cells than UVC irradiation [24][25][26]. But even this method cannot replace antibiotic treatment for gum disease due to technical reasons and a limited of researches and applications for this method. ...
Article
Full-text available
Abstract Background: Information on the pattern of antimicrobial susceptibility and guidelines for oral antibiotic therapy for Yemeni patients are not available for those with localized aggressive periodontitis (LAP) due to Aggregatibacter actinomycetemcomitans, a condition that often requires complementary antibiotic treatment. Aim: The primary objective of this study was to examine Aggregatibacter actinomycetemcomitans clinical isolates on a panel of antibiotics commonly used in oral / systemic therapy. Materials and Methods: The study included 30 strains of A. actinomycetemcomitans isolated from LAP patients. The subgingival plaque was plated onto Trypticase Soy Serum Bacitracin Vancomycin Agar medium and incubated for 72 h, and the suspected colonies were confirmed by phenotypic tests. Each isolate was tested against a group of 12 antibiotics using the disc diffusion method. The test was performed and interpreted according to the CLSIFDA schedule. Results: Cefotaxime, ceftriaxone and moxifloxacin showed excellent activity at 100%, 100% and 96.7% sensitivity respectively, followed by amoxiclav (90% sensitive), tetracycline (80% sensitive), cefuroxime (76.7% sensitive), cefazolin (73.3% sensitive) and azithromycin (63.3%, sensitive). The bacterial strains showed poor susceptibility to clindamycin, doxycycline, and metronidazole. All isolates were moderate or resistant to amoxicillin. Conclusion: A. actinomycetemcomitans isolates showed a high level of resistance to clindamycin, metronidazole and amoxicillin. The development of resistance to azithromycin and cefazoline also appears to be significant. Changing resistance between different members of the cephalosporin group is a factor that should be investigated further due to the lack of a sensitivity profile to this antibiotic and interpretive criterion for oral bacteria. Keywords: Aggregatibacter actinomycetemcomitans, antibiotic sensitivity, Disc diffusion method.
... The US Food and Drug Administration (FDA) has cleared several blue light devices for Over the Counter (OTC) use for acne and/or wrinkle treatment. Numerous studies have reported no harmful effects of blue light (405-420nm) on adult human skin (including whole body treatment at 43.7 J/cm 2 daily for 5 days, repeated 7 times) [62,63,64], reviewed in [65]. For patients undergoing whole body blue light treatment, no harmful effects on primary blood cells were observed, nor depletion of dendritic cells from the dermis, nor DNA damage or early photo-aging. ...
... For patients undergoing whole body blue light treatment, no harmful effects on primary blood cells were observed, nor depletion of dendritic cells from the dermis, nor DNA damage or early photo-aging. [62,63] On a cellular level, work with blue light at 405 nm, up to 15 J/cm 2 , indicates no harm to in vitro cultured cells [59,66], nor does it induce genotypic changes [67]. However, there are also reports that blue light (400-450nm) with fluence levels > 66 J/cm 2 may be detrimental to cultured skin cells (as determined metabolically by alamar blue reduction). ...
Preprint
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Bacterial biofilms are highly resistant to antibiotics and have been implicated in the etiology of 60-80% of chronic microbial infections. We tested a novel combination of low intensity ultrasound and blue light against biofilm and planktonic bacteria. A laboratory prototype was built which produced both energies uniformly and coincidently from a single treatment head, impinging upon a 4.45 cm^2 target. To demonstrate proof of concept, Propionibacterium acnes biofilm was cultured on Millicell hanging inserts in 6-well plates. Hanging inserts with biofilm were treated in a custom exposure chamber designed to minimize unwanted ultrasound reflections. Coincident delivery of both energies demonstrated synergy over either alone, killing both stationary planktonic and biofilm cultures of P. acnes. Biofilm killing was dose dependent on exposure time (i.e. energy delivered). P. acnes biofilms were significantly reduced by the dual energy treatment (p<0.0001), with a >1 log10 reduction after a 5 min (9 J/cm^2) and >3 log10 reduction after a 30 min (54 J/cm^2) treatment (p<0.05). Mammalian cells were found unaffected by the treatment. Both the light and the ultrasound energies are at levels previously cleared by the FDA. Therefore, this combination treatment could be used as a safe, efficacious method to treat biofilm related syndromes.
... Although UVC is an effective approach to eliminate infection, an important consideration is potential side effects on the surrounding mammalian tissue. Because UVC can be absorbed by host DNA, resulting in DNA damage (24), the application of longer wavelengths such as those within the blue light region have been shown to be considerably safer than UVC (24). ...
... Although UVC is an effective approach to eliminate infection, an important consideration is potential side effects on the surrounding mammalian tissue. Because UVC can be absorbed by host DNA, resulting in DNA damage (24), the application of longer wavelengths such as those within the blue light region have been shown to be considerably safer than UVC (24). ...
... Although UVC is an effective approach to eliminate infection, an important consideration is potential side effects on the surrounding mammalian tissue. Because UVC can be absorbed by host DNA, resulting in DNA damage (24), the application of longer wavelengths such as those within the blue light region have been shown to be considerably safer than UVC (24). ...
... Although UVC is an effective approach to eliminate infection, an important consideration is potential side effects on the surrounding mammalian tissue. Because UVC can be absorbed by host DNA, resulting in DNA damage (24), the application of longer wavelengths such as those within the blue light region have been shown to be considerably safer than UVC (24). ...
Article
With the effectiveness of antimicrobials declining as antimicrobial resistance continues to threaten public health, we must look to alternative strategies for the treatment of infections. In this study, we investigated an innovative ‘drug-free’ dual-wavelength irradiation approach that combines two wavelengths of light, 460 nm and 405 nm, against methicillin resistant Staphylococcus aureus (MRSA). MRSA was initially irradiated with 460 nm light (90-360 J/cm2) and subsequently irradiated with aliquots of 405 nm light (54-324 J/cm2). For in vivo studies, mouse skin was abraded and infected with approximately 107 CFU of MRSA and incubated for 3 hours before irradiating with 460 nm (360 J/cm2) and 405 nm (342 J/cm2). Naïve mouse skin was also irradiated to investigate apoptosis. We found that staphyloxanthin, the carotenoid pigment in MRSA cells, promoted resistance to the antimicrobial effects of 405 nm light. In addition, we found that the photolytic effect of 460 nm light on staphyloxanthin attenuated resistance of MRSA to 405 nm light killing. Irradiation of 460 nm alone did not elicit any antimicrobial effect on MRSA. In a proof-of-principle mouse skin abrasion infection model, we observed significant killing of MRSA by the dual-wavelength irradiation approach. However, when either wavelength of light was administered alone, no significant decrease in bacterial viability was observed. Moreover, exposure of the dual-wavelength irradiation to naïve mouse skin did not result in any visible apoptosis. In conclusion, dual-wavelength irradiation strategy may offer an innovative, effective and safe approach for the treatment of skin infections caused by MRSA.
... Creators such as Philips are currently developing devices and technologies that emit a blue visible spectrum for use in the treatment of skin diseases [8][9][10]. The presence of blue light has also been reported in a number of studies that have been effective in killing bacteria associated with periodontal disease, such as Pg and Aa [11][12][13] Periodontal disease, also known as gum disease, is a group of inflammatory conditions that affect the tissues surrounding the teeth [14]. The disease start as acute tenderness of the gum tissue and untreated cases can develop to form dental pockets, and finally tooth death [14]. ...
... In addition, it is well accepted that aBL is less harmful to host cells than UVC irradiation. [12,13]. The objectives of this study were to determine the phototoxic effect of visible blue light on Pg and Aa isolates of chronic gingivitis patients, and to study their antibiotic sensitivity against selected antibiotics. ...
... Even in clear water, or other media of a high transmittance, the penetration depth of UV-C will only be in the range of 10 cm, and thus not suitable for the disinfection of deep water reservoirs. Visible light offers a much higher penetration depth in water and is relatively harmless to human tissue [8][9][10][11]. Its inactivation potency is about 1000 times weaker than that of UV-C radiation and is thus not suitable for applications with high flow rates, since the residence times are too short to reach adequate doses. ...
... An investigation of the sensitivity of legionella towards this wavelength might lead to new applications for which UV-C radiation or even violet light is still too aggressive or lacks the desired penetration depth, which is longer in the blue spectral region. This is also true for human tissue and might offer therapeutic applications because, although visible light seems to be harmful to many bacteria, human cells appear to be more resistant [8]. ...
Article
Full-text available
Despite the high number of legionella infections, there are currently no convincing preventive measures. Photoinactivation with visible light is a promising new approach and the photoinactivation sensitivity properties of planktonic Legionella rubrilucens to 450, 470, and 620 nm irradiation were thus investigated and compared to existing 405 nm inactivation data for obtaining information on responsible endogenous photosensitizers. Legionella were streaked on agar plates and irradiated with different doses by light emitting diodes (LEDs) of different visible wavelengths. When irradiating bacterial samples with blue light of 450 nm, a 5-log reduction could be achieved by applying a dose of 300 J cm−2, whereas at 470 nm, a comparable reduction required about 500 J cm−2. For red irradiation at 620 nm, no inactivation could be observed, even at 500 J cm−2. The declining photoinactivation sensitivity with an increasing wavelength is consistent with the assumption of porphyrins and flavins being among the relevant photosensitizers. These results were obtained for L. rubrilucens, but there is reason to believe that its inactivation behavior is similar to that of pathogenic legionella species. Therefore, this photoinactivation might lead to new future concepts for legionella reduction and prevention in technical applications or even on or inside the human body.
... The US Food and Drug Administration (FDA) has cleared several blue light devices for Over the Counter (OTC) use for acne and/or wrinkle treatment. Numerous studies have reported no harmful effects of blue light (405-420 nm) on adult human skin (including whole body treatment at 43.7 J/cm 2 daily for 5 days, repeated 7 times) [59][60][61][62][63][64][65][66][67], reviewed in [5]. For patients undergoing whole body blue light treatment, no harmful effects on primary blood cells were observed, nor were depletion of dendritic cells from the dermis, DNA damage, or early photo-aging [59,60]. ...
... Numerous studies have reported no harmful effects of blue light (405-420 nm) on adult human skin (including whole body treatment at 43.7 J/cm 2 daily for 5 days, repeated 7 times) [59][60][61][62][63][64][65][66][67], reviewed in [5]. For patients undergoing whole body blue light treatment, no harmful effects on primary blood cells were observed, nor were depletion of dendritic cells from the dermis, DNA damage, or early photo-aging [59,60]. On a cellular level, work with blue light at 405 nm, up to 15 J/cm 2 , indicates no harm to in vitro cultured cells [56,62], nor does it induce genotypic changes [63]. ...
Article
Full-text available
Bacterial biofilms are highly resistant to antibiotics and have been implicated in the etiology of 60%–80% of chronic microbial infections. We tested a novel combination of low intensity ultrasound and blue light against biofilm and planktonic bacteria. A laboratory prototype was built which produced both energies uniformly and coincidently from a single treatment head, impinging upon a 4.45 cm2 target. To demonstrate proof of concept, Propionibacterium acnes biofilms were cultured on Millicell hanging inserts in 6-well plates. Hanging inserts with biofilms were treated in a custom exposure chamber designed to minimize unwanted ultrasound reflections. Coincident delivery of both energies demonstrated synergy over either alone, killing both stationary planktonic and biofilm cultures of P. acnes. Reduction in biofilm bacteria was dose dependent on exposure time (i.e., energy delivered). P. acnes biofilms were significantly reduced by dual energy treatment (p < 0.0001), with a >1 log10 reduction after a 5 min (9 J/cm2) and >3 log10 reduction after a 30 min (54 J/cm2) treatment (p < 0.05). Mammalian cells were found to be unaffected by the treatment. Both the light and the ultrasound energies are at levels previously cleared by the FDA. Therefore, this combination treatment could be used as a safe, efficacious method to treat biofilm related syndromes.
... The use of blue light in milk processing industries or even in dairy farms could be extremely interesting, as it does not require special training and does not offer occupational hazards. Yet, the photoinactivation approach with visible light is more interesting than UV-C light-based inactivation for the dairy industry because UV-C presents much less penetration in light-scattering aqueous solutions, causes indiscriminate oxidation of biological material, and offers occupational risks for eyes and skin of workers (Kleinpenning et al., 2010). Using blue light is also safer and cheaper than pasteurization and UHT processing because it does not require high-power heating systems such as boilers. ...
Article
Food safety and quality management play a pivotal role in the dairy industry. Milk is a highly nutritious food that also provides an excellent medium for growth of pathogenic microorganisms. Thus, dairy industry focuses most of their processes and costs on keeping contamination levels as low as possible. Thermal processes for microbial decontamination may be effective; however, they cannot provide excellent organoleptic, nutritional, and decontamination properties simultaneously. In this scenario, microbial inactivation by exposure to blue light is a promising alternative method in the food industry due to its intrinsic antimicrobial properties free of any thermal effect. Therefore, this study aimed to determine the inactivation kinetics induced by blue light (λ = 413 nm) against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Salmonella Typhimurium, and Mycobacterium fortuitum cells suspended in whole milk or saline solution. We also performed a series of optic spectroscopies to investigate possible degradation of milk components. All species were sensitive to photoinactivation suspended either in saline solution or milk. Inactivation kinetics differs significantly depending on the suspension medium and each species is differently affected. All bacterial species tested presented more than 5 log10 of inactivation within less than 2 h of irradiation (720 J/cm2). Infrared spectroscopy did not reveal any significant alteration in any of the milk constituents (e.g., sugars, proteins, and lipids). Riboflavin (vitamin B2) was the only significantly degraded constituent found. Therefore, we conclude that microbial inactivation performed by blue light presents extraordinary potential for processes in the dairy industry.
... In addition, the effect of high irradiance on cell inhibition was better than low irradiance at the same doses (0.04, 0.07, 0.14, 0.22, 0.30, 0.37, 0.45, 0.56 or 1.12 J/cm 2 ). Kleinpenning et al. demonstrated that blue light did not cause photo-ageing or DNA damage, thus the utilization of blue light (short-term) in treating melanoma is safe [16]. Given that malignant melanoma is a very harmful cancer, it is imperative to study the light parameters of PBM aimed at providing a reference for clinical treatment. ...
Article
Melanoma is a type of aggressive cancer. Recent studies have indicated that blue light has an inhibition effect on melanoma cells, but the effect of photobiomodulation (PBM) parameters on the treatment of melanoma remains unknown. Thus, this study was aimed to investigate B16F10 melanoma cells responses to PBM with varying irradiance and doses, and further explored the molecular mechanism of PBM. Our results suggested that the responses of B16F10 melanoma cells to PBM with varying irradiance and dose were different and the inhibition of blue light on cells under high irradiance was better than low irradiance at a constant total dose (0.04, 0.07, 0.15, 0.22, 0.30, 0.37, 0.45, 0.56 or 1.12 J/cm2), presumably due to that high irradiance can produce more ROS, thus disrupting mitochondrial function.
... 6 The reduction of inflammation in laser-treated samples also confirms the safety of the approach in terms of possible photothermal damage, as proven by our experiments using a thermographic camera and in accordance with a previous study showing no burn lesions on the skin of healthy volunteers exposed to blue light. 36 Our results show for the first time that blue laser light effectively inhibits the progression of wound superinfection through the production of intracellular ROS. Additional studies will be needed to prove its potential to completely disrupt established biofilms in vivo, thus setting this approach as a powerful tool to combat P. aeruginosa epithelial infection, either alone or as an adjuvant strategy to increase the efficacy of standard antibiotic therapy. ...
Article
Full-text available
Resolution of bacterial infections is often hampered by both resistance to conventional antibiotic therapy and hiding of bacterial cells inside biofilms, warranting the development of innovative therapeutic strategies. Here, we report the efficacy of blue laser light in eradicating Pseudomonas aeruginosa cells, grown in planktonic state, agar plates and mature biofilms, both in vitro and in vivo, with minimal toxicity to mammalian cells and tissues. Results obtained using knock-out mutants point to oxidative stress as a relevant mechanism by which blue laser light exerts its anti-microbial effect. Finally, the therapeutic potential is confirmed in a mouse model of skin wound infection. Collectively, these data set blue laser phototherapy as an innovative approach to inhibit bacterial growth and biofilm formation, and thus as a realistic treatment option for superinfected wounds.
... A novel light-based antimicrobial therapy, blue light therapy, has been absorbed increasing attention because of its inherent antimicrobial effect without the involvement of exogenous photosensitizers [55,56]. In addition, it is well accepted that blue light is much less harmful than UVC irradiation to host cells [57,58]. The mechanism underlying the antimicrobial effect of blue light is yet not fully understood. ...
... Comparatively with the results from the University of Strathclyde (Glasgow, UK) considering murine fibroblasts and their viability [23], our results suggest that visible blue light (405 nm wavelength) has no noticeable effect on either alpha and beta cells, fibroblasts or isolated pancreatic islets. Furthermore, the percentage of cells with damaged DNA in all studied samples was as low as in the control group [Figs 3A, 5A, 6A, 7A], showing similarities with another study from Radboud University Nijmegen Medical Centre where they took a closer look at the effects of visible blue light on healthy human skin [24]. All these results together are in contradiction to some studies reporting that visible light (especially near-UV wavelength) may cause DNA damage [25]. ...
Article
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Introduction 3D printing is being used more extensively in modern biomedicine. One of the problems is selecting a proper crosslinking method of bioprinted material. Amongst currently used techniques we can distinguish: physical crosslinking (e.g. Ca²⁺ and Sr²⁺) and chemical crosslinking–the UV light crosslinking causing the biggest discussion. UV radiation is selectively absorbed by DNA, mainly in the UV-B region but also (to some extent) in UV-A and UV-C regions. DNA excitement results in typical photoproducts. The amount of strand breaks may vary depending on the period of exposition, it can also differ when cells undergo incubation after radiation. Aim The aim of this study was to show whether and how the time of irradiation with 405 nm and 365 nm wavelengths affect DNA damage in cell lines and micro-organs (pancreatic islets). Materials and methods The degree of DNA damage caused by different wavelengths of radiation (405 nm and 365 nm) was evaluated by a comet assay. The test was performed on fibroblasts, alpha cells, beta cells and porcine pancreatic islets after 24 hours incubation period. Samples without radiation treatment were selected as a control group. Results analysis consisted of determining the percent of cells with damaged DNA and the tail intensity evaluation. Results The degree of DNA damage in pancreatic islets after exposure to 405 nm wavelength oscillated between 2% and 6% depending on the tested time period (10 – 300 seconds). However, treating islets using 365 nm wavelength resulted in damage up to 50%. This clearly shows significantly less damage when using 405 nm wavelength. Similar results were obtained for the tested cell lines. Conclusions Crosslinking with 405 nm is better for pancreatic islets than crosslinking with 365 nm UV light.
... (2) no inflammatory cells and sunburn before and after treatment; (3) transient melanogenesis and vacuolization of keratinocytes observed, although these changes did not result in cell apoptosis [150]. Similarly, an in vitro study demonstrated that blue light (415 nm) could be used to inactivate P. aeruginosa on skin burns without inflicting any damage on the mouse skin at an effective antimicrobial dosage of 55.8 J/cm 2 [151]. ...
Article
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Blue light primarily exhibits antimicrobial activity through the activation of endogenous photosensitizers, which leads to the formation of reactive oxygen species that attack components of bacterial cells. Current data show that blue light is innocuous on the skin, but may inflict photo-damage to the eyes. Laboratory measurements indicate that antimicrobial blue light has minimal effects on the sensorial and nutritional properties of foods, although future research using human panels is required to ascertain these findings. Food properties also affect the efficacy of antimicrobial blue light, with attenuation or enhancement of the bactericidal activity observed in the presence of absorptive materials (for example, proteins on meats) or photosensitizers (for example, riboflavin in milk), respectively. Blue light can also be coupled with other treatments, such as polyphenols, essential oils and organic acids. While complete resistance to blue light has not been reported, isolated evidence suggests that bacterial tolerance to blue light may occur over time, especially through gene mutations, although at a slower rate than antibiotic resistance. Future studies can aim at characterizing the amount and type of intracellular photosensitizers across bacterial species and at assessing the oxygen-independent mechanism of blue light-for example, the inactivation of spoilage bacteria in vacuum-packed meats.
... Thus, blue light in the spectral range of 400-470 nm, with its closeness to the strongly antibacterially effective UV-light, but without its possibly damaging effect, has garnered great scientific interest because of its corresponding high photon energy. [26][27][28][29] There are already in vitro and in vivo successes in the fight against gram(+) as well as gram(-) pathogens, whereby various authors disagree with one another about the question which bacteria form reacts more sensitively to blue light disinfection. 26 Propionibacterium acnes, Helicobacter pylori, Pseudomonas aeruginosa and Staphylococcus aureus 13,26 have been shown to be just as photosensitive as P. intermedia and P. gingivalis, 25,30 which could be significantly reduced, depending on the power, through irradiation with blue laser light (405 nm). ...
Article
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Abstract Introduction: Cavity disinfection is necessary to prevent a progressive infection of the crown dentin and pulp. Increasing intolerance and resistance to antiseptics and antibiotics as well as the controversy over the effects of those on the dental hard tissue and composite have prompted the investigation of alternative treatment options. The objective of this pilot study is to evaluate the antibacterial potential of a diode laser with a wavelength of 445 nm in the cavity preparation using the bacterium Streptococcus salivarius associated with caries in conjunction with the characteristics and influences of dentin on light transmission. Methods: The bactericidal effect of the laser irradiation was determined in culture experiments by using caries-free human dentin samples on bacteria-inoculated agar. For this, dentin discs (horizontally cut coronal dentin) of 500 µm and 1000 µm thicknesses were produced and irradiated with the laser with irradiation parameters of 0.7-1 W in a cw-mode and exposure times of between 5-30 s. Based on the different sample thicknesses, the penetration depth effect of the irradiation was ascertained after the subsequent incubation of the bacteria-inoculated agar. Additional influential parameters on the irradiation transmission were investigated, including surface moisture, tooth color as well as the presence of a smear layer on the dentin surface. Results: The optical transmission values of the laser radiation for dentin were significantly dependent on the sample thickness (P = 0.006) as well as its moisture content (P = 0.013) and were independent of the presence of a smear layer. There was a 40% reduction in bacteria after the radiography of the 500-µm-thick dentin samples, which was shown as the lowest laser dose (443 J/cm2). Conclusion: These findings indicate that the diode laser with light emission at a wavelength of 445 nm is interesting for the supportive cavity disinfection within the scope of caries therapy and show potential for clinical applications.
... 80 More specifically, visible light absorption by DNA is weak 81 and dosages of up to 100 J/cm 2 have been shown not to alter p53 expression (cellular tumor antigen)-rendering it safe to use for short-term biomedical treatments. 82 Toxic effects can only be seen at very high irradiation dosages of 400-450 nm light emissions, 83,84 where the main biological effect is suggested to be caused by photochemical effects instead of thermal actions for dermal applications. 84,85 Yet several reports of potential thermal damage to surrounding dental-, 13,53,86-89 joint-, 90 and soft tissues 14,91 remain frequently reported and should still be considered a risk for biomedical applications as modern LED light sources are now exceeding 2000 mW/ cm 2 . ...
Article
Radical photo-cross-linking of polymers has been at the forefront in the development of biomedical applications to meet many of the biomaterial design criteria needed to address clinical and healthcare challenges, particularly in relation to regenerative and restorative medicine strategies, to treat damaged or diseased tissues and organs. Exciting new hybrid designs, elegantly expanding the range of properties and applications available to individual polymeric materials, are starting to offer detailed customization with complex and dynamic interactions similar to the events occurring within native tissue microenvironments in vivo. Yet the variety in success reported in the literature highlights the many unknown design criteria and parameters affecting functional restoration of damaged tissues and organs. The applied light curing units and radical initiating system, as well as underlying chemical reactions and resultant network structures, all require detailed consideration as means to modulate biological function while further being assessed as sources of toxicity. This is especially important when cells embedded in the polymeric material (or in surrounding tissues) are directly exposed to photo-irradiation. Ultimately, achieving successful clinical translation necessitates the chemical photo-polymerization platforms to be efficacious, safe, and customizable but also convenient for clinical use and cost-effective production. This review thus aims to summarize current and emerging toolkits to photo-polymerize biomedical polymers requiring the direct irradiation of cells and/or mammalian tissues and its associated impact on biological functionality. This specifically includes (1) in vitro photo-polymerization of cell-laden 3D-hydrogels for tissue engineering and regeneration medicine applications, (2) in vivo transdermal photo-polymerization of injectable hydrogels for cell/drug delivery, and (3) in vivo photo-polymerization of cell-free, injectable resin-based composites for load-bearing restorative surgery, all fast-growing and highly competitive fields of modern medicine. We herein summarize both design considerations and biological risk factors associated with selecting suitable light sources, photo-initiators, functional groups, chemical propagation, as well as how subsequent network properties can modulate biological function and ultimately clinical applicability. As more knowledge is continuously accumulated through materials science, matrix biology, and technology, this review provides recommendations for researchers to extend their chemical, biological, and structural characterizations to systematically enrich the paradigm of photo-polymerizable materials for biomedical applications to help ensure efficient and safe radical photo-processing.
... Whilst this study investigates the 48 antibacterial activity of a range of wavelengths between 375-450nm, and identifies a specific 49 wavelength region (~405nm) with increased antibacterial activity, decontamination was 50 dependent on bacterial species, strain, irradiation parameters and experimental conditions. wavelengths [1,2]. Notably the oxidative damage caused by UVA exposure is thought to be 68 irreparable, whereas the effects of UVC can be overcome by innate cellular DNA repair 69 mechanisms [3]. ...
Article
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Light-emitting diodes (LEDs) demonstrate therapeutic effects for a range of biomedical applications, including photodisinfection. Bands of specific wavelengths (centered at 405 nm) are reported to be the most antimicrobial; however, there remains no consensus on the most effective irradiation parameters for optimal photodisinfection. The aim of this study was to assess decontamination efficiency by direct photodisinfection of monomicrobial biofilms using a violet-blue light (VBL) single-wavelength array (SWA) and multiwavelength array (MWA). Mature biofilms of nosocomial bacteria (Acinetobacter baumannii, Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus) were grown on 96-well polypropylene PCR plates. The biofilms were then exposed to VBL for 2,700 s (SWA) and 1,170 s (MWA) to deliver 0 to 670 J/cm², and the antibacterial activity of VBL was assessed by comparing the seeding of the irradiated and the nonirradiated biofilms. Nonirradiated groups were used as controls. The VBL arrays were characterized optically (spectral irradiance and beam profile) and thermally. The SWA delivered 401-nm VBL and the MWA delivered between 379-nm and 452-nm VBL, albeit at different irradiances and with different beam profiles. In both arrays, the irradiated groups were exposed to increased temperatures compared to the nonirradiated controls. All bacterial isolates were susceptible to VBL and demonstrated reductions in the seeding of exposed biofilms compared with the nonirradiated controls. VBL at 405 nm exerted the most antimicrobial activity, exhibiting reductions in seeding of up to 94%. Decontamination efficiency is dependent on the irradiation parameters, bacterial species and strain, and experimental conditions. Controlled experiments that ameliorate the heating effects and improve the optical properties are required to optimize the dosing parameters to advance the successful clinical translation of this technology.
... It is envisioned that microbes are less able to develop resistance to aBL than to traditional antibiotics, because of the multi-target characteristics of aBL [10]. In addition, it is well accepted that aBL is much less detrimental to host cells than germicidal ultraviolet C irradiation [12,13]. However, this approach of using aBL has yet to be studied as a therapeutic for gonococcal infections, especially those caused by multidrug-resistant strains. ...
Article
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Gonorrhea is the second most prevalent sexually transmitted infection globally. Neisseria gonorrhoeae, the etiological agent of gonorrhea, is evolving into a superbug and may become untreatable due to its resistance to almost all the antibiotics available. There is a critical need for the development of alternative therapeutics. This pilot study aimed to investigate the potential of an innovative non-antibiotic approach, antimicrobial blue light (aBL), as an alternative therapeutic for gonococcal infections. We studied one ATCC strain (ATCC 700825) and one multidrug-resistant clinical strain of N. gonorrhoeae. The results demonstrated that both the strains are highly susceptible to aBL at 405nm. In planktonic suspensions, an exposure of 45 J/cm2 aBL reduced the survival fraction of colony-forming units (CFU) by 7.16-log10 for ATCC 700825 and 2.48-log10 for the clinical strain. When the aBL exposure was further increased to 54 J/cm2, a complete eradication of CFU (over 8-log10 CFU reduction) was achieved for ATCC 700825 and a reduction of 5.43-log10 CFU was obtained for the clinical strain. In addition, we observed that singlet oxygen plays a vital role in the antimicrobial effect of aBL on N. gonorrhoeae. In conclusion, the results of this pilot study suggest that aBL is a promising approach to combat gonococcal infections. Further studies are warranted in the analysis of the endogenous photosensitizers in N. gonorrhoeae cells, evaluation of the aBL efficacy against gonococcal infections in animal models, and investigation of the mechanism of action of aBL.
... Over the last decade, an innovative light-based approach, antimicrobial blue light therapy (aBL), has emerged as a potent microbicide that does not require the application of exogenous photosensitizers [19,[25][26][27][28][29][30]. Notably, aBL has been found to be far less damaging to human cells when compared to UVC [31,32]. Mechanistically, aBL excites endogenous chromophores (porphyrins and/or flavins) that are present in microbial cells, resulting in the generation of ROS, which has potent microbicidal properties [33,34]. ...
... Digital Screens' Light and Selfies noted that the complex issue of effective protection of human skin from sun exposure is a challenging issue due to unknown aspects of the interaction between visible light and human tissues [33]. As phototherapy with visible light has become popular in dermatological practice, some researchers have reported that blue light does not cause DNA damage or premature photo-aging and claimed that shortterm application of visible blue light in dermatological practice is safe [34]. Furthermore, it has been reported that exposure of human skin to moderate levels of blue light induced a significant increase in the formation of enzyme-independent cutaneous NO and NO-dependent local biological responses (increased blood flow). ...
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Since the early days of human life on the Earth, our skin has been exposed to different levels of light. Recently, due to inevitable consequences of modern life, humans are not exposed to adequate levels of natural light during the day but they are overexposed to relatively high levels of artificial light at night. Skin is a major target of oxidative stress and the link between aging and oxidative stress is well documented. Especially, extrinsic skin aging can be caused by oxidative stress. The widespread use of light emitting diodes (LEDs) and the rapidly increasing use of smartphones, tablets, laptops and desktop computers have led to a significant rise in the exposure of human eyes to short-wavelength visible light. Recent studies show that exposure of human skin cells to light emitted from electronic devices, even for exposures as short as 1 hour, may cause reactive oxygen species (ROS) generation, apoptosis, and necrosis. The biological effects of exposure to short-wavelength visible light in blue region in humans and other living organisms were among our research priorities at the Ionizing and Non-ionizing Radiation Protection Research Center (INIRPRC). Today, there is a growing concern over the safety of the light sources such as LEDs with peak emissions in the blue light range (400-490 nm). Recent studies aimed at investigating the effect of exposure to light emitted from electronic device on human skin cells, shows that even short exposures can increase the generation of reactive oxygen species. However, the biological effects of either long-term or repeated exposures are not fully known, yet. Furthermore, there are reports indicating that frequent exposure to visible light spectrum of the selfie flashes may cause skin damage and accelerated skin ageing. In this paper we have addressed the different aspects of potential effects of exposure to the light emitted from smartphones’ digital screens as well as smartphones’ photoflashes on premature aging of the human skin. Specifically, the effects of blue light on eyes and skin are discussed. Based on current knowledge, it can be suggested that changing the spectral output of LED-based smartphones’ flashes can be introduced as an effective method to reduce the adverse health effects associated with exposure to blue light.
... All of these radicals damage cell structures such as DNA, proteins or membranes [9][10][11][12][13][14][15] and can thus lead to cell death. If the irradiation dose is high enough, visible light appears to be effective against bacteria, fungi and even viruses [16][17][18] without endangering humans or human cells [19,20]. ...
Article
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The spread of infections, as in the coronavirus pandemic, leads to the desire to perform disinfection measures even in the presence of humans. UVC radiation is known for its strong antimicrobial effect, but it is also harmful to humans. Visible light, on the other hand, does not affect humans and laboratory experiments have already demonstrated that intense visible violet and blue light has a reducing effect on bacteria and viruses. This raises the question of whether the development of pathogen-reducing illumination is feasible for everyday applications. For this purpose, a lighting device with white and violet LEDs is set up to illuminate a work surface with 2,400 lux of white light and additionally with up to 2.5 mW/cm² of violet light (405 nm). Staphylococci are evenly distributed on the work surface and the decrease in staphylococci concentration is observed over a period of 46 hours. In fact, the staphylococci concentration decreases, but with the white illumination, a 90% reduction occurs only after 34 hours; with the additional violet illumination the necessary irradiation time is shortened to approx. 3.5 hours. Increasing the violet component probably increases the disinfection effect, but the color impression moves further away from white and the low disinfection durations of UVC radiation can nevertheless not be achieved, even with very high violet emissions.
... It is envisioned that microbes are less able to develop resistance to aBL than to traditional antibiotics because of the multi-target characteristics of aBL [8]. In addition, it is well accepted that aBL is much less detrimental to host cells than germicidal ultraviolet C irradiation [16,17]. The present study aimed to investigate the efficacy, safety, and mechanism of action of aBL for the inactivation of N. gonorrhoeae. ...
Article
Background and Objectives The aim of this study was to investigate the efficacy, safety, and mechanism of action of antimicrobial blue light (aBL) for the inactivation of Neisseria gonorrhoeae, the etiological agent of gonorrhea. Study Design/Materials and Methods The susceptibilities of N. gonorrhoeae (ATCC 700825) in planktonic suspensions to aBL at 405‐ and 470‐nm wavelengths were compared. The roles of oxygen in the anti‐gonococcal activity of aBL were studied by examining the effects of hypoxic condition (blowing N2) on the anti‐gonococcal efficiency of 405‐nm aBL. The presence, identification, and quantification of endogenous photosensitizers in N. gonorrhoeae cells and human vaginal epithelial cells (VK2/E6E7 cells) were determined using fluorescence spectroscopy and ultra‐performance liquid chromatography (UPLC). Finally, the selectivity of aBL inactivation of N. gonorrhoeae over the host cells were investigated by irradiating the co‐cultures of N. gonorrhoeae and human vaginal epithelial cells using 405‐nm aBL. Results About 3.12‐log10 reduction of bacterial colony forming units (CFU) was achieved by 27 J/cm ² exposure at 405 nm, while about 3.70‐log10 reduction of bacterial CFU was achieved by 234 J/cm² exposure at 470 nm. The anti‐gonococcal efficacy of 405‐nm aBL was significantly suppressed under hypoxic condition. Spectroscopic and UPLC analyses revealed the presence of endogenous porphyrins and flavins in N. gonorrhoeae. The concentrations of endogenous photosensitizers in N. gonorrhoeae (ATCC 700825) cells were more than 10 times higher than those in the VK2/E6E7 cells. In the co‐cultures of N. gonorrhoeae and VK2/E6E7 cells, 405‐nm aBL at 108 J/cm² preferentially inactivated N. gonorrhoeae cells while sparing the vaginal epithelial cells. Conclusions aBL at 405‐nm wavelength is more effective than 470‐nm wavelength in inactivating N. gonorrhoeae while sparing the vaginal epithelial cells. Reactive oxygen species generated from the photochemical reactions between aBL and endogenous photosensitizers play a vital role in the anti‐gonococcal activity of 405‐nm aBL. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
... Over the last decade, an innovative light-based approach, antimicrobial blue light therapy (aBL), has emerged as a potent microbicide that does not require the application of exogenous photosensitizers [19,[25][26][27][28][29][30]. Notably, aBL has been found to be far less damaging to human cells when compared to UVC [31,32]. Mechanistically, aBL excites endogenous chromophores (porphyrins and/or flavins) that are present in microbial cells, resulting in the generation of ROS, which has potent microbicidal properties [33,34]. ...
... In consequence, blue light could reduce wound infections and probably contribute to a better wound healing in these difficult wounds. All these findings suggest that irradiation with blue light might serve as a promising alternative wound healing therapy, especially for wound infections (and burn wound infections) and chronic inflammatory skin diseases with only minor side effects, since short-term irradiation with visible blue light in dermatological practice is regarded to be safe [23]. ...
Article
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Phototherapy is gaining more attention in the treatment of various diseases. Especially, blue light seems to be a promising approach for wound healing promotion due to its antimicrobial and immune-modulating properties. Despite this, there is only little research focusing on the immune-modulating properties of blue light and its possible effects on wound healing. Therefore, we investigated the effects of blue light irradiation on peripheral blood mononuclear cells (PBMC) and the influence on reepithelization in vitro. PBMCs were irradiated with DermoDyne® (DermoDyne HealthCare, Berlin, Germany) and effects on cell viability, cytokine expression, and scratch wound closure were evaluated afterwards. Irradiated cells showed a higher Interleukin-γ concentration while irradiation reduced resazurin concentration in a time-dependent manner. No differences in reepithelization were detectable when keratinocytes were treated with the supernatant of these blue light irradiated PBMCs. Blue light–mediated ex vivo stimulation of PBMCs does not cause faster reepithelization in an in vitro setting. Further research is needed to investigate the wound healing effects of phototherapy with blue light.
... It is commonly accepted that b-LED is much less harmful to host cells than UV irradiation [28]. The DNA damage caused by UV results in (i) misincorporation of bases during replication process, (ii) hydrolytic damage, which results in deamination of bases, depurination, and depyrimidination, and (iii) oxidative damage through ROS induction [29]. ...
Article
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While blue LED (b-LED) light is increasingly being studied for its cytotoxic activity towards bacteria in therapy of skin-related infections, its effects on eukaryotic cells plasticity are less well characterized. Moreover, since different protocols are often used, comparing the effect of b-LED towards both microorganisms and epithelial surfaces may be difficult. The aim of this study was to analyze, in the same experimental setting, both the bactericidal activity and the effects on human keratinocytes. Exposure to b-LED induced an intense cytocidal activity against Gram-positive (i.e, Staphylococcus aureus) and Gram-negative (i.e., Pseudomonas aeruginosa) bacteria associated with catheter-related infections. Treatment with b-LED of a human keratinocyte cell line induced a transient cell cycle arrest. At the molecular level, exposure to b-LED induced a transient downregulation of Cyclin D1 and an upregulation of p21, but not signs of apoptosis. Interestingly, a transient induction of phosphor-histone γ-H2Ax, which is associated with genotoxic damages, was observed. At the same time, keratinocytes underwent a transient epithelial to mesenchymal transition (EMT)-like phenotype, characterized by E-cadherin downregulation and SNAIL/SLUG induction. As a functional readout of EMT induction, a scratch assay was performed. Surprisingly, b-LED treatment provoked a delay in the scratch closure. In conclusion, we demonstrated that b-LED microbicidal activity is associated with complex responses in keratinocytes that certainly deserve further analysis.
... More recently, it has been demonstrated that repeated VL exposure increases pigmentation more significantly than single exposures, with increased tyrosinase activity signifying a response comparable to that of UVR-induced DT [19]. Pigmentation induced by longwave UVR/blue light (λ Max = 420 nm) has also been demonstrated histologically through a substantial increase in melan-A positive cells (a melanocyte differentiation antigen) after 5 days of irradiation with a cumulative dose of 100 J/cm 2 [20]. Differences in pigmentation response between UVR (λ max = 311 nm), blue (λ max = 450 nm) and green (λ max = 530 nm) light have also been assessed in FST I-III ex vivo skin cultures. ...
Article
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Skin pigmentation by solar ultraviolet radiation (UVR; ~295–400 nm) is well established. More recently, visible light (VL; 400–740 nm) has been shown to induce rapid pigmentation. Such pigmentation is thought to be caused by oxidative stress, which has associations with skin cancer and photoageing. However, the UVR-VL boundary region has been less well studied. The lower back of healthy Fitzpatrick skin type II-IV individuals was irradiated with increasing doses of narrow-band 385 nm and 405 nm radiation. Pigmentation change was measured immediately, 6 h and 24 h post-irradiation using two reflectance spectroscopy devices and visual grading. Pigmentation was dose-dependently increased in all skin types and time points for both spectra. Two sunscreens, both labelled SPF 15 and UVA protective in the EU and USA (but with different Boots star rating in the UK, 2* vs 5*) were compared. Their formulations were the same apart from the addition of a new organic filter bis-(diethylaminohydroxybenzoyl benzoyl) piperazine (BDBP) that absorbs between 385 and 405 nm. The product that lacked BDBP provided minimal protection against pigmentation, but its addition provided almost complete protection. This demonstrates the needs to improve photoprotection at the UVR-visible border and for sunscreens to act as neutral density filters.
... These intracellular reactive oxygen species attack DNA, proteins or membranes and, if the produced damage becomes too great, the cell dies. Human cells also contain such photosensitizers, but they have nevertheless proven to be very resistant to visible light [16][17][18][19][20][21][22][23][24]. ...
Article
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The COVID-19 pandemic is driving the search for new antiviral techniques. Bacteria and fungi are known to be inactivated not only by ultraviolet radiation but also by visible light. Several studies have recently appeared on this subject, in which viruses were mainly irradiated in media. However, it is an open question to what extent the applied media, and especially their riboflavin concentration, can influence the results. A literature search identified appropriate virus photoinactivation publications and, where possible, viral light susceptibility was quantitatively determined in terms of average log-reduction doses. Sensitivities of enveloped viruses were plotted against assumed riboflavin concentrations. Viruses appear to be sensitive to visible (violet/blue) light. The median log-reduction doses of all virus experiments performed in liquids is 58 J/cm2. For the non-enveloped, enveloped and coronaviruses only, they were 222, 29 and 19 J/cm2, respectively. Data are scarce, but it appears that (among other things) the riboflavin concentration in the medium has an influence on the log-reduction doses. Experiments with DMEM, with its 0.4 mg/L riboflavin, have so far produced results with the greatest viral susceptibilities. It should be critically evaluated whether the currently published virus sensitivities are really only intrinsic properties of the virus, or whether the medium played a significant role. In future experiments, irradiation should be carried out in solutions with the lowest possible riboflavin concentration.
... These were either found within the epidermal layer (hyperkeratosis and/or parakeratosis, mild to severe hyperplasia, stratification disorders, squamatization of epidermal basal cells, atypia or apoptosis of keratinocytes) and in the dermis (fibrosis and elastosis). Similar histological features are described in the photodamaged skin of humans and are related to the type and amount of UV radiation [5,11,30]. Interestingly, solar-induced lesions observed in the skin adjacent to the epithelioid melanoma were limited to the dermis (solar dermatosis) without the typical epidermal involvement seen for actinic keratosis [9]. This could be linked to the total amount of UV radiation that reaches the skin, which is directly influenced by the quantity of hair, amount of cutaneous pigment, and duration of exposure [9]. ...
Article
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The photoinduced etiopathology of actinic keratosis and squamous cell carcinoma in feline species is well known. This etiology has also been reported for non-epithelial cutaneous tumors in other species. To date, no cases of auricular non-epithelial cutaneous neoplasms erased in a contest of actinic keratosis in cats have been reported. The aim of this study was to describe feline auricular non-epithelial cutaneous neoplasms associated with typical UV-induced cutaneous lesions and solar elastosis. The study was conducted on five feline cases diagnosed with auricular non-epithelial cutaneous tumors (two fibrosarcomas, one mixosarcoma, one epithelioid melanoma and one hemangiosarcoma), selected from the Tumor Registry of the Department of Veterinary Sciences of the University of Pisa (1998-2018). Ten and six feline auricular biopsies of normal skin and skin with actinic keratosis, respectively, were used as controls. Orcein stain was used to investigate solar elastosis. Histological changes related to chronic solar irradiation were documented in the skin adjacent to the neoplastic lesions in the five cats. Considering the anatomical localization and the results of histopathology, this study suggests that non-epithelial cutaneous neoplasms may have a UV-induced etiopathogenesis in the feline species.
... In line with PTN penetration, massive tumour necrosis up to a depth of 4 mm was observed in PTN-PDT treated tumours. Although blue light penetration into normal skin has been reported to be around 1 mm 41 , it had been used successfully in the treatment of skin cancers such as human basal cell carcinomas 42 and melanoma mice lesions of 100-120 mm 343 . In addition, a bystander effect that may propagate the cellular death triggered by the initial photoreaction may be also occurring 44 . ...
Article
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Abstract Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p
... HEV light and UVA induce photo-oxidation of melanogenic precursors leading to immediate pigment darkening (IPD) and persistent pigment darkening (PPD). IPD is characterized by a greyish darkening observed immediately after irradiation and fading shortly afterward, whereas a brownish-black pigmentation can develop over several weeks in PPD without the involvement of melanogenesis processes (99). Staying indoors gives a false sense of security against harmful ultraviolet radiation, so less care is taken in closed environments, such as the use of photoprotective substances. ...
Article
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A new coronavirus emerged in 2019 in Wuhan, China named Severe Acute Respiratory Syndrome type 2 coronavirus (SARS-CoV-2). Later, this virus spread worldwide, causing a disease called coronavirus disease (COVID-19). To control the outbreak, many countries announced mandatory quarantine; thus, people changed their lifestyles and started engaging in most activities from home. This review explains how some dermatological pathologies may be precipitated by prolonged stays at home, considering that quarantine was a widely used public health measure during 2020. Most of these dermatoses had to be seen, diagnosed, and treated through tele-dermatology, a remote health care system that took force during the COVID-19 pandemic because of its ease and efficiency in connecting health care professionals and their patients; therefore, reducing the risk of contagion and costs associated to medical care. This review of the principal dermatologic conditions during confinement could allow for a better preparation of health professionals.
... It has potential antibacterial or bactericidal ability without photosensitizers. Also, Blu-ray is less harmful to mammalian cells (Kleinpenning et al., 2010). The mechanism of Blu-ray sterilization is cell death induced by oxidative stress caused by reactive oxygen species (ROS) generated by the endogenous photosensitizers of bacteria after absorbing Blu-ray (Dietel et al., 2007, Lukšiene, 2005. ...
Article
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This article reviews the research progress of non-thermal disinfection technologies in food and introduces the principles of non-thermal disinfection technologies such as ultra-high pressure, ozone, acid electrolyzed water, irradiation, magnetic sterilization, high-pressure carbon dioxide, and natural antibacterial. We discuss the characteristics and application progress of non-thermal disinfection technologies in food processing and analyze their development trend based on their application and promotion in food processing and storage.
... In contrast, visible light is less harmful than UV [7]. Within the visible spectrum, blue light at the wavelength range of 400-450 nm has the highest bactericidal property associated with its absorbance by endogenous porphyrins, leading to cell death [2,8]. ...
Article
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Antimicrobial resistance is a global, mounting and dynamic issue that poses an immediate threat to human, animal, and environmental health. Among the alternative antimicrobial treatments proposed to reduce the external use of antibiotics is electromagnetic radiation, such as blue light. The prevailing mechanistic model is that blue light can be absorbed by endogenous porphyrins within the bacterial cell, inducing the production of reactive oxygen species, which subsequently inflict oxidative damages upon different cellular components. Nevertheless, it is unclear whether other mechanisms are involved, particularly those that can affect the efficacy of antimicrobial blue light treatments. In this review, we summarize evidence of inherent factors that may confer protection to a selected group of bacteria against blue light-induced oxidative damages or modulate the physiological characteristics of the treated bacteria, such as virulence and motility. These include descriptions of three major photoreceptors in bacteria, chemoreceptors, SOS-dependent DNA repair and non-SOS protective mechanisms. Future directions are also provided to assist with research efforts to increase the efficacy of antimicrobial blue light and to minimize the development of blue light-tolerant phenotypes.
... Mavi ışıkla yapılan bir çalışmada 450 nm dalga boyunda kısa süre tedavi amaçlı kullanıldığında DNA hasarının olmadığı ve erken yaşlanmaya yol açmadığı gösterilmiştir. 53 İn vitro hücre kültürü çalışmalarında 450 nm dalga boyunda kullanılan mavi ışığın T-hücreleri üzerinde proapoptik etkisi olduğu ve keratinosit üzerinde de apoptoz olmaksızın antiproliferatif etkisi olduğu görülmüştür. 54 Bu sonuç psöriyazis vulgaris belirtilerini tedavi amaçlı kullanımın yolunu açmaktadır. ...
... Mavi ışıkla yapılan bir çalışmada 450 nm dalga boyunda kısa süre tedavi amaçlı kullanıldığında DNA hasarının olmadığı ve erken yaşlanmaya yol açmadığı gösterilmiştir. 53 İn vitro hücre kültürü çalışmalarında 450 nm dalga boyunda kullanılan mavi ışığın T-hücreleri üzerinde proapoptik etkisi olduğu ve keratinosit üzerinde de apoptoz olmaksızın antiproliferatif etkisi olduğu görülmüştür. 54 Bu sonuç psöriyazis vulgaris belirtilerini tedavi amaçlı kullanımın yolunu açmaktadır. ...
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azın plaja giden mutlu tatilcilerin çoğu çantalarına krem, losyon/süt veya sprey şeklinde yapısı olan ve güneşin zararlı etkilerine karşı koruyan ürün-lerden (güneş ürünü) birkaçını koyar. Güneş ürünü kullanım oranı ve tü-ketici alışkanlıkları konusunda ülkemizde yapılmış güvenilir bir istatistik çalışma yoktur, ancak yaş ve cinsiyetin ürün kullanımı ile yakından ilgili olduğu tahmin Güneşin Cilde Etkisi ve Güneşten Koruyucu Ürünler ÖZET Güneşe etrafımızı görmemizi sağladığı, bizi ısıttığı, yiyeceklerimizin çoğunun üretimini sağladığı ve dünyamıza hayat verdiği için her gün minnettar olmamıza karşın, son yıllarda sağlıkla ilgili mesajlar dünya yüzeyine ulaşan güneş ışınlarının tehlike ve zararları üzerine yo-ğunlaşmıştır. Pek çok bilim adamı ultraviyole (UV), görünür ışığın bazı dalga boyları ve kızıl-ötesi (IR) ışınlarının zararlı etkilerini tartışmaktadır. Bu tartışma ışınların bazı dermatolojik tedavi işlemleri için yararlı etkileri akılda tutuluyorsa da, güneş ışınlarına fazla maruz kalın-masının zararları konusundadır. Güneş ışınları derinin katmanlarına geçerek DNA'ya zarar ve-recek moleküller oluşturur veya DNA ile doğrudan etkileşerek, kanser veya erken hücre ölümüyle sonuçlanan hücre mutasyonlarına yol açar. 1920'lerden bu yana kanser olgularının artması erken yaşlanma belirtilerinden güneş ışınları sorumlu tutulduğu için zararlı güneş ışınlarından korunma öne çıkan konu haline gelmiştir. Bu makale güneş ışınlarının zararlı et-kilerini var olan bilgilere dayanarak özetlemeyi ve deriyi bu etkilerden koruma stratejilerini gözden geçirmeyi hedeflemektedir. Anahtar Kelimeler: : Güneş ışını; deri kanseri; fotoyaşlanma; güneşten koruma ABSTRACT Although we are everyday grateful to sun for enabling us to see objects around us, keeping us warm, letting plants to produce most of our food and bringing life to our planet, recent public health messages have concentrated on the dangers and hazards of sun rays that reach the earth surface. Very many scientists are discussing the damaging effects of ultraviolet (UV), some wavelengths of visible and infra-red (IR) rays. This discussion is about the hazards of extreme sun exposure keeping beneficial effects of sun in some dermatological treatment procedures in mind. Sun rays can penetrate into deep skin layers and generate some DNA damaging molecules or interact directly with DNA and cause mutations leading to cancer or early death of cells. Since sun rays are held responsible for increasing number of cancer cases since 1920s for premature ageing, protection against sun rays became a prominent issue. This paper aims to review the available information to summarize the damaging effects of sun rays and strategies for skin protection. Keywords: : Sun rays; skin cancers; foto aging; sun protection Yasemin YAĞAN UZUNER Farmasötik Teknoloji AD, Acıbadem Üniversitesi Eczacılık Fakültesi, İstanbul Geliş Tarihi/Re ceived: 23.02.2017 Kabul Tarihi/Accepted: 02.03.2017
... Kleinpenning et al. analyzed skin biopsies of patients with no skin lesions after 5 days of blue light irradiations (Waldmann 450L photodynamic therapy lamp, 20 J/cm 2 two times a day) and a mild hyperpigmentation was noted, confirmed by Melan-A-positive cells found in the skin exposed to blue light. However, no impact on DNA damage of skin cells, early photoaging, and inflammatory cell infiltration was seen [41]. ...
Article
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Phototherapy is an important method of dermatological treatments. Ultraviolet (280–400 nm) therapy is of great importance; however, there are concerns of its long-term use, as it can lead to skin aging and carcinogenesis. This review aims to evaluate the role and the mechanism of action of blue light (400–500 nm), a UV-free method. The main mediators of cellular responses to blue light are nitric oxide (NO) and reactive oxygen species (ROS). However, the detailed mechanism is still not fully understood. It was demonstrated that blue light induces an anti-inflammatory and antiproliferative effect; thus, it may be beneficial for hyperproliferative and chronic inflammatory skin diseases such as atopic dermatitis, eczema, and psoriasis. It was also found that blue light might cause the reduction of itching. It may be beneficial on hair growth and may be used in the treatment of acne vulgaris by reducing follicular colonization of Propionibacterium acnes. Further studies are needed to develop accurate protocols, as the clinical effects depend on the light parameters as well as the treatment length. There are no major adverse effects observed yet, but long-term safety should be monitored as there are no studies considering the long-term effects of blue light on the skin.
... Stimulation of immune system and promotion of wound healing are some of the UV-light's effects [10]. Conversely, blue light is less harmful than the UV radiation and induces lower levels of photodegradation than UV light [14]. LED blue (470 nm) light treats superficial conditions due to its smaller penetration ability -1mm the most [3]. ...
Article
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Due to their effects, similar to low-intensity therapy light sources such as light-emitting diodes (LED) and broadband spectrum lamps have recently become commonly used in the diagnosis and treatment of neurodegenerative pathologies, cancer, as well as ageing. Despite the proven positive effects of such therapies, deeper understanding of the light therapies’ biological effects remains unclear. Even more, the molecular mechanisms through which different neurotransmitters, namely serotonin (5-hydroxytryptamine, 5-HT), mediate the organism’s response to radiation are yet indistinct. In this paper, we present the design and development of a specialized system for irradiation of biological objects, which is composed of LED 365 nm and LED 470 nm and a broadband lamp source of UVA/B (350 nm) with intensity, power density and direction, which can be optimized experimentally. The system, named a “water organ bath (wob)”, is used in the current work to irradiate smooth muscle stomach strips of rats. The obtained results prove that the modulation of the spontaneous contractile smooth muscle activity and the potentiation of the effects of major neurotransmitters are executed by the emitted light. The probable explanation for the neurotransmitters photoactivation is that it is the resultant effect of electromagnetic radiation on intracellular enzymes signaling systems.
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Platelet (PLT) storage is currently limited to 5 days in clinics in the United States, in part, due to an increasing risk for microbial contamination over time. In light of well‐documented antimicrobial activity of blue light (405‐470 nm), we investigated potentials to decontaminate microbes during PLT storage by antimicrobial blue light (aBL). We found that PLTs produced no detectable levels of porphyrins or their derivatives, the chromophores that specifically absorb blue light, in marked contrast to microbes that generated porphyrins abundantly. The difference formed a basis with which aBL selectively inactivated contaminated microbes prior to and during the storage, without incurring any harm to PLTs. In accordance with this, when contamination with representative microbes was simulated in PLT concentrates supplemented with 65% of PLT additive solution (PAS) in a standard storage bag, all “contaminated” microbes tested were completely inactivated after exposure of the bag to 405 nm aBL at 75 J/cm2 only once. While killing microbes efficiently, this dose of aBL irradiation exerted no adverse effects on the viability, activation or aggregation of PLTs ex vivo and could be used repeatedly during PLT storage. PLT survival in vivo was also unaltered by aBL irradiation after infusion of aBL‐irradiated mouse PLTs into mice. The study provides proof‐of‐concept evidence for a potential of aBL to decontaminate PLTs during storage. This article is protected by copyright. All rights reserved.
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Sunscreen formulations have been developed to provide an artificial protective barrier against the deleterious effects of overexposure to ultraviolet (UV) radiation in humans. Ultrafast pump-probe spectroscopy techniques have been an invaluable tool in recent years for determining the photochemistry of active ingredients in sunscreen formulations, predominantly UV filters, in both the gas- and solution-phases. These measurements have enabled the elucidation of molecular relaxation pathways and photoprotection mechanisms, which are in turn insightful for assessing a filter's photostability and suitability for sunscreen use. In this review, we discuss the benefits of a bottom-up approach: the progression from the study of UV filters for sunscreens in vacuum, away from the influences of any solvent; in solution, to investigate the relaxation pathways of potential sunscreen filters in closer to real-life conditions, whilst exploring the merits of selective functionalisation to improve their characteristics; and beyond, to current advances that are mimicking the application of sunscreen formulations to the surface of the skin.
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In the last few years, the focus of phototherapy has shifted towards the visible (400‐700 nm) part of the electromagnetic spectrum of light. Lately, it has been demonstrated that visible light (VL) can have both beneficial and detrimental effects, especially on the skin. Previously and until now, the most harmful effects on the skin are associated with Ultraviolet radiation (UVR). After exposure to natural light, the most evident and immediate change is observed on skin pigmentation. Various wavelengths within the visible spectrum have been reported to alter skin pigmentation. However, the underlying mechanisms are incompletely understood so far. The article aims to shed light on the progress made in the photobiology field (photobiomodulation PBM) to study the role of visible light on skin melanocytes.
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Background Red and blue light therapies are safe and effective treatments for mild to moderate acne vulgaris. However, very few previous studies have directly compared the characteristics of these two methods. Objective To compare the efficacy and side effects of red light (RL) and blue light (BL) for acne vulgaris and to assess these two therapies in different types of lesions. Materials and Methods A total of 28 subjects with mild to moderate acne vulgaris were randomized into the RL group or the BL group. Subjects in each group received different light treatments, and they were followed up regularly until 2 weeks after the last treatment. The improvement rates of different types of acne lesions were compared between the 2 groups, as well as the incidence of adverse reactions. Results At the 2-week follow-up, the average improvement rate of total acne lesions was 36.2% in the RL group and 30.7% in the BL group (P>0.05). The average improvement rate of inflammatory and non-inflammatory lesions was 51.5% and 17.3% in the RL group, compared with 26.4% and 10.0% in the BL group (all P>0.05). Treatment-related adverse reactions were observed distinctly in the BL group. Conclusions RL and BL therapies have similar efficacy in mild to moderate acne vulgaris, especially for inflammatory lesions. RL had advantages with fewer adverse reactions compared with BL.
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Bacteria belonging to the group of ESKAPE pathogens are responsible for the majority of nosocomial infections. Due to the increase of antibiotic resistance, alternative treatment strategies are of high clinical relevance. In this context visible light as disinfection technique represents an interesting option as microbial pathogens can be inactivated without adjuvants. However cytotoxic effects of visible light on host cells have also been reported. We compared the cytotoxicity of violet and blue light irradiation on monocytic THP-1 and alveolar epithelium A549 cells with the inactivation effect on ESKAPE pathogens. THP-1 cells displayed a higher susceptibility to irradiation than A549 cells with first cytotoxic effects occurring at 300 J cm ⁻² (405 nm) and 400 J cm ⁻² (450 nm) in comparison to 300 J cm ⁻² and 1000 J cm ⁻² , respectively. We could define conditions in which a significant reduction of colony forming units for all ESKAPE pathogens, except Enterococcus faecium , was achieved at 405 nm while avoiding cytotoxicity. Irradiation at 450 nm demonstrated a more variable effect which was species and medium dependent. In summary a significant reduction of viable bacteria could be achieved at subtoxic irradiation doses, supporting a potential use of visible light as an antimicrobial agent in clinical settings.
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Objective: To determine effective treatment strategies against bacterial infections of chronic wounds, we tested different blue light (BL)-emitting light-emitting diode arrays (420, 455, and 480 nm) against wound pathogens and investigated in parallel BL-induced toxic effects on human dermal fibroblasts. Background: Wound infection is a major factor for delayed healing. Infections with Pseudomonas aeruginosa and Staphylococcus aureus are clinically relevant caused by their ability of biofilm formation and their quickly growing antibiotics resistance. BL has demonstrated antimicrobial properties against various microbes. Methods: Determination of antibacterial and cell toxic effects by colony-forming units (CFUs)/biofilm/cell viability assays, and live cell imaging. Results: A single BL irradiation (180 J/cm2), of P. aeruginosa at both 420 and 455 nm resulted in a bacterial reduction (>5 log10 CFU), whereas 480 nm revealed subantimicrobial effects (2 log10). All tested wavelengths of BL also revealed bacteria reducing effects on Staphylococcus epidermidis and Escherichia coli (maximum 1-2 log10 CFU) but not on S. aureus. Dealing with biofilms, all wavelengths using 180 J/cm2 were able to reduce significantly the number of P. aeruginosa, E. coli, and S. epidermidis. Here, BL420nm achieved reductions up to 99%, whereas BL455nm and BL480nm were less effective (60-83%). Biofilm-growing S. aureus was more BL sensitive than in the planktonic phase showing a reduction by 63-75%. A significant number of cell toxic events (>40%) could be found after applying doses (>30 J/cm2) of BL420nm. BL455nm showed only slight cell toxicity (180 J/cm2), whereas BL480nm was nontoxic at any dose. Conclusions: BL treatment can be effective against bacterial infections of chronic wounds. Nevertheless, using longer wavelengths >455 nm should be preferred to avoid possible toxic effects on skin and skin cells. To establish BL therapy for infected chronic wounds, further studies concerning biofilm formation and tissue compatibility are necessary.
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Photodynamic therapy (PDT) is a treatment for superficial tumours involving the administration of a photosensitiser followed by irradiation. The potential of the natural anthraquinone parietin (PTN) in PDT is still relatively unexploited. In the present work, PTN isolated from the lichen Teoloschistes nodulifer (Nyl.) Hillman (Telochistaceae) was evaluated as a potential photosensitiser on tumour cells employing UVA-Vis and blue light. Blue light of 2 J/cm² induced 50% death of K562 leukaemic cells treated 1 h with 30 μM PTN (Protocol a). Higher light doses (8 J/cm²) were needed to achieve the same percentage of cell death employing lower PTN concentrations (3 μM) and higher exposure times (24 h) (Protocol b). Cell cycle analysis after both protocols of PTN-PDT revealed a high percentage of sub-G1 cells. PTN was found to be taken up by K562 cells mainly by passive diffusion. Other tumour cells such as ovary cancer IGROV-1 and LM2 mammary carcinoma, as well as the normal keratinocytes HaCaT, were also photosensitised with PTN-PDT. We conclude that PTN is a promising photosensitiser for PDT of superficial malignancies and purging of leukaemic cells, when illuminated with blue light. Thus, this light wavelength is proposed to replace the Vis-UVA lamps generally employed for the photosensitisation of anthraquinones.
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Background: Blue light is emitted visible light between the wavelengths of 400 to 500 nm. The main source of blue light is sunlight, but digital screens, light-emitting diodes (LEDs), and fluorescent lighting serve as additional sources. Concerns about the negative effects of blue light on the skin have rapidly increased over the past 15 years, and consequently, the urge to learn more about this topic is increasing as well. Aims: Part I of this article provides up-to-date information on the definition of blue light and the negative and positive effects of blue light on the skin. Methods: An Internet search was completed using the Google scholar database for relevant literature. Results: Blue light can be both harmful and beneficial to the skin, depending on intensity and wavelength. Short-term safety information is more readily available from clinical studies; however, the biological effects of repeated and/or longer-term exposure are not fully understood yet. Conclusions: Low-energy and low exposure times to high-energy blue light can help prevent skin diseases, while studies have revealed that longer exposure to high-energy blue light can increase the amount of DNA damage, cell and tissue death, and injury, eye damage, skin barrier damage, and photoaging.
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Background The purpose of this study is to compare the efficacy of blue light therapy (BLT) and 5% topical benzoyl peroxide (BPO) gel in combination with standard chlorhexidine (CHX) prep in eradicating Cutibacterium acnes (C. acnes) at the deltopectoral interval (DPI) measured by positive, quantitative cultures. Methods Adult male volunteers were randomized to one of three treatment groups: BPO, BLT, and BPO followed by BLT. Contralateral shoulders served as matched controls. Volunteers randomized to BPO applied the gel for a total of 5 treatments. For BLT group, a single 23-minute treatment was administered at an estimated irradiance of 40 mW/cm² (radiant exposure 55.2 J/cm²). For BPO+BLT group, volunteers received both treatments as described above. After treatment with either BPO, BLT, or both, a single swab culture was taken from the treatment shoulder. Next, control and treatment shoulders were prepped with CHX, and cultures were taken from each shoulder. Cultures were sent for anaerobic quantitative growth with both polymerase chain reaction and Sanger sequencing confirmation of presumptive C. acnes colonies. Results Sixty male volunteers, 20 per group, were enrolled, with no loss to follow-up. All culture samples for the BPO group and BLT group following treatment, but prior to CHX administration grew C. acnes. Sixteen (80%) samples in the BPO+BLT grew C. acnes prior to CHX. On quantitative analysis, the BPO group and BPO+BLT group had significantly less growth of C. acnes compared to the BLT group after treatment but prior to CHX (p<0.05 each, respectively). Following CHX administration, BPO and BPO+BLT groups had significantly fewer positive cultures (Odds Ratio 0.03 and 0.29, respectively) and less quantity of growth compared to their control arms (p<0.05). This was not seen in BLT group. For quantitative between group analysis, no significant synergistic effects were seen in the BPO+BLT group compared to BPO only (p=0.688). There was no difference in side effects between groups. Conclusion Combination topical BPO and CHX is effective at eliminating C. acnes in most cases. Blue light therapy alone did not demonstrate effective antimicrobial properties against C. acnes, at the radiant exposure administered in this study. Combining BPO and BLT did not lead to significant synergistic antimicrobial effects. Both BPO and BLT are safe with few, transient side effects reported. More work is needed to determine if BLT at higher radiant exposures or serial treatments results in bactericidal effects against C. acnes in vivo.
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The LED blue light (BL) phototherapy, using photo-converter chromophores, provides long-term efficacy and safety in the treatment of acne vulgaris. Treatment with BL turns out to be safe and effective as well as pleasant. The results seem to be long lasting with negligible or completely absent downtime. The only side effects appear to be a fleeting erythema and a bronze effect that, in some cases, could also be aesthetically pleasing.
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New developments in the field of the commonly used photodiagnostic and phototherapeutic methods help to continuously improve the results in the daily practise. Edited by internationally renowned experts, the new edition offers up-to-date, comprehensive and clinically relevant information on every aspect of photodiagnostic and phototherapy. The book is structured in following parts:Photochemotherapy in daily practice, special phototherapeutic modalities and photoprotection in daily practice. Due to the detailed structure this new edition is even more reader-friendly and has a strong focus on clinical aspects. It includes: Guidelines for the treatment selections of specific diseases, practical guidelines for phototherapy with information about basic principles of photobiology, standardized test protocols for photodermatoses and diagnosis for skin tumors.
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Sunlight influences the physiology of the human skin in beneficial as well as harmful ways, as has been shown for UV light. However, little is known about the effects of other wavelengths of solar irradiation. In this study we irradiated human keratinocytes and skin-derived endothelial cells with light-emitting-diode devices of distinct wavelengths to study the effects on cell physiology. We found that light at wavelengths of 632-940 nm has no effect, but irradiation with blue light at 412-426 nm exerts toxic effects at high fluences. Light at 453 nm is nontoxic up to a fluence of 500 J/cm(2). At nontoxic fluences, blue light reduces proliferation dose dependently by up to 50%, which is attributable to differentiation induction as shown by an increase of differentiation markers. Experiments with BSA demonstrate that blue-light irradiation up to 453 nm photolytically generates nitric oxide (NO) from nitrosated proteins, which is known to initiate differentiation in skin cells. Our data provide evidence for a molecular mechanism by which blue light may be effective in treating hyperproliferative skin conditions by reducing proliferation due to the induction of differentiation. We observed a photolytic release of NO from nitrosated proteins, indicating that they are light acceptors and signal transducers up to a wavelength of 453 nm.
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Photodynamic therapy (PDT) consists of the combination of photosensitizers absorbing light mainly in the red spectral region and irradiation with light of corresponding wavelengths. We analysed its effects on the cytokine secretion (IL-1 beta, TNF alpha, IL-6) of freshly isolated peripheral mononuclear cells from six patients with chronic plaque-stage psoriasis in comparison with PUVA. PUVA treatment resulted in a decreased production of all three cytokines, but most pronounced in the case of IL-6. PDT caused a similar change in the cytokine pattern, but its effectiveness was lower. In vivo fluorescence recordings were performed on psoriatic plaque lesions after topical application of the photosensitizer Photosan-3. Under irradiation, progressive photobleaching was noted with increasing radiation dosage. This is the first reported study of photochemical reactions using on-line fluorescence recordings during PDT of psoriatic lesions in vivo. Our results demonstrate the capacity of PDT to cause immunomodulatory effects similar to PUVA, thus indicating its potential application to the treatment of this common disease.
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The temporo-spatial expression of fibrillin and elastin in skin regenerating from autologous keratinocyte grafts was studied in three burned children. Skin biopsies taken between 5 days and 17 months after grafting were investigated by conventional immunofluorescence, confocal laser scanning, and electron microscopy. Fibrillin, the major component of 10-12nm microfibrils, appeared 5 days after grafting in a band-like fashion similar to collagen VII at the prospective basement membrane, and the formed the characteristic microfibrillar candelabra at the dermo-epidermal junction by fusion of several fine microfibrils to communicating microfibrils projecting downward into the reticular layer of the neodermis. Four to five months after grafting, several communicating microfibrils were connected to a web of horizontally undulating microfibrils of the neodermis which had developed independently. Elastin was first identified in the deeper neodermis 1 month after grafting as granular aggregates and 4 months after grafting on fibrillar structures and surrounding capillaries of the upper neodermis. Association of elastin with microfibrils in the papillary dermis was not detectable before month 17. Our findings suggest that the cutaneous microfibrillar apparatus develops simultaneously at both the dermo-epidermal junction and the reticular dermis and is a prerequisite for elastic fiber formation. In addition, it might be a driving force for the formation of the papilla-rete ridge pattern.
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The tumor suppressor protein, p53, is part of the cell's emergency team that is called upon following cellular insult. How do cells sense DNA damage and other cellular stresses and what signal transduction pathways are used to alert p53? How is the resulting nuclear accumulation of p53 accomplished and what determines the outcome of p53 induction? Many posttranslational modifications of p53, such as phosphorylation, dephosphorylation, acetylation and ribosylation, have been shown to occur following cellular stress. Some of these modifications may activate the p53 protein, interfere with MDM2 binding and/or dictate cellular localization of p53. This review will focus on recent findings about how the p53 response may be activated following cellular stress.
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New developments in the field of the commonly used photodiagnostic and phototherapeutic methods help to continuously improve the results in the daily practice. Edited by internationally renowned experts, the new edition offers again up-to-date, comprehensive and clinically relevant information on every aspect of photodiagnostics and phototherapy. This eagerly awaited 2nd edition will become the bible of this field. It is structured in following parts: Photochemotherapy in daily practice, special phototherapeutic modalities and photoprotection. Due to the detailed structure the book is more reader-friendly and has a strong focus on clinical aspects. It includes: Guidelines for the treatment selections of specific diseases, practical guidelines for phototherapy with information about basic principles of photobiology, standardized test protocols for photodermatoses and diagnosis for skin tumors. The book is an invaluable resource for dermatologists, oncologists and all other physicians treating dermatological patients.
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‐ ) and a Fenton reaction — could be involved. endonuclease V (i.e. cyclobutane pyrimidine dimers) was Yet another possibility is a release of Ca 21 from intracellular constant (~1:200), indicating that the direct excitation of stores which could activate cellular nucleases and thus induce DNA is responsible for both types of damage in this range DNA damage (18,19). of the spectrum. While the yield of pyrimidine dimers per The ratio of pyrimidine dimers and oxidative DNA modiunit dose continued to decrease exponentially beyond 315 fications at various wavelengths depends on the relative connm, the yield of Fpg-sensitive modifications increased to a tribution of direct and indirect mechanisms and is of major second maximum between 400 and 450 nm. The damage interest for the estimation of the mutagenic risk associated spectrum in this wavelength range consisted of only a with solar irradiation and the impact of spectral changes caused few other modifications (strand breaks, abasic sites and by ozone layer depletion. Here, we report a quantification of pyrimidine modifications sensitive to endonuclease III) cyclobutane pyrimidine dimers and various types of oxidative and is attributed to endogenous photosensitizers that give modifications induced in cultured cells by wavelengths between rise to oxidative DNA damage via singlet oxygen and/or 290 and 500 nm. The lesions were quantified by means of type I reactions. The generation of Fpg-sensitive modifica- several repair endonucleases (Table I) and an alkaline elution tions by visible light was not linear with dose but followed technique (28). a saturation curve. It is calculated that the exposure of the The results indicate that the generation of oxidative DNA cells to low doses of solar radiation results in the formation base modifications by solar radiation has a second maximum of cyclobutane pyrimidine dimers and Fpg-sensitive modi- between 400 and 450 nm due to the excitation of (unidentified) fications in a ratio of 10:1. endogenous photosensitizers and that in cells exposed to sunlight these indirectly induced base modifications account for ~10% of the total endonuclease-sensitive base damage.
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The stratum corneum and DNA repair do not completely protect keratinocytes from ultraviolet B. A third defense prevents cells with DNA photoproducts from becoming precancerous mutant cells: apoptosis of ultraviolet-damaged keratinocytes ("sunburn cells"). As signals for ultraviolet-induced apoptosis, some studies implicate DNA photoproducts in actively transcribed genes; other studies implicate non-nuclear signals. We traced and quantitated the in vivo DNA signal through several steps in the apoptosis-signaling pathway in haired mice. Homozygous inactivation of Xpa, Csb, or Xpc nucleotide excision repair genes directed the accumulation of DNA photoproducts to specific genome regions. Repair-defective Xpa–/– mice were 7–10-fold more sensitive to sunburn cell induction than wild-type mice, indicating that 86–90% of the ultraviolet B signal for keratinocyte apoptosis involved repairable photoproducts in DNA; the remainder involves unrepaired DNA lesions or nongenomic targets. Csb–/– mice, defective only in excising photoproducts from actively transcribed genes, were as sensitive as Xpa–/–, indicating that virtually all of the DNA signal originates from photoproducts in active genes. Conversely, Xpc–/– mice, defective in repairing the untranscribed majority of the genome, were as resistant to apoptosis as wild type. Sunburn cell formation requires the Trp53 tumor suppressor protein; 90–96% of the signal for its induction in vivo involved transcribed genes. Mdm2, which regulates the stability of Trp53 through degradation, was induced in vivo by low ultraviolet B doses but was suppressed at erythemal doses. DNA photoproducts in actively transcribed genes were involved in 89% of the Mdm2 response.Keywords: apoptosis, Cockayne syndrome, mdm2 protein, MeSH, protein p53, ultraviolet rays, xeroderma pigmentosum
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DNA damage by UV radiation plays an essential role in skin cancer induction. We report that even sub-erythemal doses of solar simulating radiation, are capable of inducing substantial nuclear damage, namely pyrimidine dimers and p53 induction in human skin in situ. The quantity and distribution of p53 induced in human skin by UV radiation depended highly on the waveband and dose of UV used. Solar simulating radiation induced very high levels of p53 throughout all layers in epidermal keratinocytes 24 hr following an erythemal dose (230+/-15.9/1000 cells), and the induction followed a dose response. Following UVA I + II and UVA I radiations, p53 expression was approximately half of that seen with equivalent biological doses of solar simulating radiation (63.5+/-28.5 and 103+/-15.9, respectively). Expression of p53 was seen in basal cell keratinocytes at lower doses of UVA, but all layers of the epidermis were affected at higher doses. Pyrimidine dimer induction, however, was seen to be the same for equivalent biological doses of UVA I, UVA I + II and solar simulating radiations, which coincides with previous findings that pyrimidine dimers initiate the erythemal response and are implicated in skin carcinogenesis. When equivalent biological doses of pure UVA are used with no UVB contamination, significant nuclear alterations occur in human skin in situ, which can approach those seen with UVB radiation. Our results suggest that DNA damage assessed in vivo by immunohistochemistry could provide a very sensitive endpoint for determining the efficacy of protective measures, such as sunscreens or protective clothing, against both UVB- and UVA-induced damage in human skin.
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Photodynamic therapy (PDT) using 5-aminolevulinic acid (5-ALA) or its methyl ester (MAL) is a very effective method to treat actinic keratosis (AK). New developments will contribute to optimization of this treatment modality. This will partly be based on a better understanding of the nature of AKs. Since pain during treatment is a frequent side effect of PDT, new methods of alleviating pain are of high interest, especially when large areas are treated. A better understanding of the underlying mechanism of specific protoporphyrin IX (PPIX) accumulation can lead to further increase the response rates. New formulations might contribute to a wider acceptance of the treatment, for example a self-adhesive patch containing 5-ALA, promises easy handling, while maintaining high efficacy. New concepts in illumination, such as ambulatory PDT or daylight illumination might contribute to the further acceptance of this method.
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Acne is common and can lead to scarring of the skin, as well as to psychological distress and reduced self-esteem. Most topical or oral treatments for acne are inconvenient and have side-effects. Laser and other light therapies have been reported to be convenient, safe and effective in treating acne. To carry out a systematic review of randomized controlled trials of light and laser therapies for acne vulgaris. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycInfo, LILACS, ISI Science Citation Index and Dissertation Abstracts International for relevant published trials. We identified 25 trials (694 patients), 13 of light therapy and 12 of light therapy plus light-activated topical cream (photodynamic therapy, PDT). Overall, the results from trials of light alone were disappointing, but the trials of blue light, blue-red light and infrared radiation were more successful, particularly those using multiple treatments. Red-blue light was more effective than topical 5% benzoyl peroxide cream in the short term. Most trials of PDT showed some benefit, which was greater with multiple treatments, and better for noninflammatory acne lesions. However, the improvements in inflammatory acne lesions were not better than with topical 1% adapalene gel, and the side-effects of therapy were unacceptable to many participants. Some forms of light therapy were of short-term benefit. Patients may find it easier to comply with these treatments, despite the initial discomfort, because of their short duration. However, very few trials compared light therapy with conventional acne treatments, were conducted in patients with severe acne or examined long-term benefits of treatment.
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Chronic wounds resistant to conventional therapy have been treated successfully with low energy lasers and light emitting diodes (LEDs) in the visible and near IR region. It has been proposed that production of low level reactive oxygen species (ROS) following illumination is the first step of photobiomodulation. It was also shown that white light (400-800 nm) has similar stimulatory effects as lasers and LEDs. ROS at higher levels are toxic to cells and bacteria. In the present study, we examined the phototoxicity of broadband (400-800 nm, 120 J/cm(2)) visible light on the survival of several pathogenic bacteria: Staphylococcus aureus 195, Pseudomonas aeruginosa 1316, Escherichia coli 1313, and Serratia marcescens. These bacteria were chosen due to their high prevalence in infected wounds. The survival of bacterial cells following illumination was monitored by counting the number of colony forming units before and after exposure to light. Illumination with white light, 120 J/cm(2), caused a reduction of 62%, 83%, and 56% in the colony count of E. coli 1313, S. aureus 195 and S. marcescens, respectively, though no reduction in the viability of P. aeruginosa 1316 was demonstrated. The phototoxic effect was found to involve induction of ROS production by the bacteria. It was also found that illumination of S. aureus 195 and E. coli 1313 in the presence of pyocyanin, known to be secreted by P. aeruginosa, had a stronger bactericidal effect compared to illumination alone. Visible light at high intensity can kill bacteria in infected wounds. Thus, illumination of infected wounds with intense visible light, prior to low intensity illumination for stimulating wound closure, may reduce infection and promote healing.
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Emollients, moisturizers, and keratolytic agents are essential in the topical treatment of psoriasis. They are adjuvants for classic treatments and help to reduce the scale load of individual patients. The major role for emollients and moisturizers is the supportive role in normalizing hyperproliferation, differentiation, and apoptosis; furthermore, they exert anti-inflammatory effects, for example, through physiologic lipids. Subsequently, an improved barrier function and stratum corneum hydration makes the epidermis more resistant to external stressors and reduces the induction of Koebner phenomena. Most of the emollients are lipid-rich (sometimes oily). The keratolytic agents, especially salicylic acid, and higher concentration of urea should be used in the initial keratolytic phase, whereas moisturizing products and emollients are especially suitable in the intermediate phase and the chronic/remission phase of psoriasis. They should be combined with bath oils.
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Exposure of normal skin to visible light (400-700 nm) resulted in the induction of immediate pigment darkening (IPD), immediate erythema and a persistent (delayed) tanning reaction. The intensity of pigmentation and time course of the reaction were monitored by measuring chromaticity coordinates. Both IPD and immediate erythema faded over a 24-h period but, unlike erythema, the pigmentation did not totally disappear and the residual tanning response remained unchanged for the rest of the 10-day observation period. The threshold dose for IPD with visible light was between 40 and 80 J/cm2, while the threshold dose for "persistent" pigmentation was greater than or equal to 80 J/cm2.
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We find a dramatic difference in the efficiency of removal of UV-induced pyrimidine dimers from the transcribed and nontranscribed strands of the dihydrofolate reductase (DHFR) gene in cultured hamster and human cells. In hamster cells, 80% of the dimers are removed from the transcribed strand in 4 hr, but little repair occurs in the nontranscribed strand even after 24 hr. In human cells, repair is significantly faster in the transcribed strand than in the other strand. Furthermore, in the 5' flanking region of the human DHFR gene, selective rapid repair occurs in the opposite DNA strand relative to the transcribed strand of the DHFR gene. This strand is thought to serve as a template for transcription of a divergent transcript. These results have important implications for excision repair pathways and mutagenesis in mammalian cells.
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—Propionibacterium acnes (P. acnes), grown on Eagles medium with different pH. were irradiated with monochromatic light in the range 320 to 440 nm. Different pH leads to different porphyrin concentrations in the cells. The light sensitivity of the bacteria was estimated from the reduction in their ability to form colonies after radiation. The sensitivity was highest for the lowest wavelength (320 nm). and decreased continuously with increasing wavelength up to 380 nm. In the region between 380 and 440 nm there was a second maximum (at 415 nm) which corresponds to the maximum absorption ol the fluorescing porphyrins in P. acnes. The sensitivity to 415 nm light was found to be dependent on the endogenous porphyrin concentration in the cells. while the sensitivity to 320 nm radiation was independent of the amount of porphyrin present. These results indicate that porphyrins produced by the bacteria are important for the light sensitivity of these bacteria.
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An integrated review of the transfer of optical radiation into human skin is presented, aimed at developing useful models for photomedicine. The component chromophores of epidermis and stratum corneum in general determine the attenuation of radiation in these layers, moreso than does optical scattering. Epidermal thickness and melanization are important factors for UV wavelengths less than 300 nm, whereas the attenuation of UVA (320-400 nm) and visible radiation is primarily via melanin. The selective penetration of all optical wavelengths into psoriatic skin can be maximized by application of clear lipophilic liquids, which decrease regular reflectance by a refractive-index matching mechanism. Sensitivity to wavelengths less than 320 nm can be enhanced by prolonged aqueous bathing, which extracts urocanic acid and other diffusible epidermal chromophores. Optical properties of the dermis are modelled using the Kubelka-Munk approach, and calculations of scattering and absorption coefficients are presented. This simple approach allows estimates of the penetration of radiation in vivo using noninvasive measurements of cutaneous spectral remittance (diffuse reflectance). Although the blood chromophores Hb, HbO2, and bilirubin determine dermal absorption of wavelengths longer than 320 nm, scattering by collagen fibers largely determines the depths to which these wavelengths penetrate the dermis, and profoundly modifies skin colors. An optical "window" exists between 600 and 1300 nm, which offers the possibility of treating large tissue volumes with certain long-wavelength photosensitizers. Moreover, whenever photosensitized action spectra extend across the near UV and/or visible spectrum, judicious choice of wavelengths allows some selection of the tissue layers directly affected.
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Squamous cell carcinoma of the skin (SCC) can progress by stages: sun-damaged epidermis, with individual disordered keratinocytes; actinic keratosis (AK), spontaneously regressing keratinized patches having aberrant cell differentiation and proliferation; carcinoma in situ; SCC and metastasis. To understand how sunlight acts as a carcinogen, we determined the stage at which sunlight mutates the p53 tumour-suppressor gene and identified a function for p53 in skin. The p53 mutations induced by ultraviolet radiation and found in > 90% of human SCCs were present in AKs. Inactivating p53 in mouse skin reduced the appearance of sunburn cells, apoptotic keratinocytes generated by overexposure to ultraviolet. Skin thus appears to possess a p53-dependent 'guardian-of-the-tissue' response to DNA damage which aborts precancerous cells. If this response is reduced in a single cell by a prior p53 mutation, sunburn can select for clonal expansion of the p53-mutated cell into the AK. Sunlight can act twice: as tumour initiator and tumour promoter.
Article
DNA damage induced by UV radiation and visible light (290-500 nm) in AS52 Chinese hamster cells was analysed by an alkaline elution assay with specific repair endonucleases. Cells were exposed to extensively filtered monochrome or broad-band radiation. Between 290 and 315 nm, the ratio of base modifications sensitive to Fpg protein (i.e. 8-hydroxyguanine and formamidopyrimidines) and T4 endonuclease V (i.e. cyclobutane pyrimidine dimers) was constant (approximately 1:200), indicating that the direct excitation of DNA is responsible for both types of damage in this range of the spectrum. While the yield of pyrimidine dimers per unit dose continued to decrease exponentially beyond 315 nm, the yield of Fpg-sensitive modifications increased to a second maximum between 400 and 450 nm. The damage spectrum in this wavelength range consisted of only a few other modifications (strand breaks, abasic sites and pyrimidine modifications sensitive to endonuclease III) and is attributed to endogenous photosensitizers that give rise to oxidative DNA damage via singlet oxygen and/or type I reactions. The generation of Fpg-sensitive modifications by visible light was not linear with dose but followed a saturation curve. It is calculated that the exposure of the cells to low doses of solar radiation results in the formation of cyclobutane pyrimidine dimers and Fpg-sensitive modifications in a ratio of 10:1.
Article
The narrow-band UVB (TL01) lamp (311 nm emission) was developed for use in phototherapy, as an alternative to a broad-band UVB source and to photochemotherapy, both of which have significant side effects and carry a risk of carcinogenesis. This new lamp has proved to be particularly effective at clearing psoriasis. It is now acknowledged that the TL01 lamp is probably 2-3 times more carcinogenic per minimum erythema dose than broad-band UVB, but the cumulative dose required in therapy is considerably less than when using broad-band UVB sources. In terms of irradiation dose, the TL01 lamp is about 5-10-fold less potent than broad-band UVB for erythema induction, hyperplasia, oedema, sunburn cell formation and Langerhans cell depletion from skin. However, the broad-band UVB to TL01 potency ratio for cis-urocanic acid formation in the skin is approximately unity. In addition, the TL01 lamp, as used in phototherapy, has relatively more suppressive effects than broad-band UVB on systemic immune responses as judged by natural killer cell activity, lymphoproliferation and cytokine responses. However, the TL01 lamp is less effective at reducing epidermal antigen presentation, inducing dendritic cell migration to lymph nodes draining irradiated sites and suppressing contact hypersensitivity at the doses tested. Therefore the use of the TL01 lamp in phototherapy should be considered carefully after weighing up its diverse effects on the skin and immune system.
Article
Long-term exposure to ultraviolet irradiation from sunlight causes premature skin aging (photoaging), characterized in part by wrinkles, altered pigmentation, and loss of skin tone. Photoaged skin displays prominent alterations in the collagenous extracellular matrix of connective tissue. We investigated the role of matrix-degrading metalloproteinases, a family of proteolytic enzymes, as mediators of collagen damage in photoaging. We studied 59 whites (33 men and 26 women, ranging in age from 21 to 58 years) with light-to-moderate skin pigmentation, none of whom had current or prior skin disease. Only some of the participants were included in each of the studies. We irradiated their buttock skin with fluorescent ultraviolet lights under standard conditions and obtained skin samples from irradiated and nonirradiated areas by keratome or punch biopsy. In some studies, tretinoin and its vehicle were applied to skin under occlusion 48 hours before ultraviolet irradiation. The expression of matrix metalloproteinases was determined by in situ hybridization, immunohistology, and in situ zymography. Irradiation-induced degradation of skin collagen was measured by radioimmunoassay of soluble cross-linked telopeptides. The protein level of tissue inhibitor of matrix metalloproteinases type 1 was determined by Western blot analysis. A single exposure to ultraviolet irradiation increased the expression of three matrix metalloproteinases -- collagenase, a 92-kd gelatinase, and stromelysin -- in skin connective tissue and outer skin layers, as compared with nonirradiated skin. The degradation of endogenous type I collagen fibrils was increased by 58 percent in irradiated skin, as compared with nonirradiated skin. Collagenase and gelatinase activity remained maximally elevated (4.4 and 2.3 times, respectively) for seven days with four exposures to ultraviolet irradiation, delivered at two-day intervals, as compared with base-line levels. Pretreatment of skin with tretinoin (all-trans-retinoic acid) inhibited the induction of matrix metalloproteinase proteins and activity (by 70 to 80 percent) in both connective tissue and outer layers of irradiated skin. Ultraviolet irradiation also induced tissue inhibitor of matrix metalloproteinases-1, which regulates the enzyme. Induction of the inhibitor was not affected by tretinoin. Multiple exposures to ultraviolet irradiation lead to sustained elevations of matrix metalloproteinases that degrade skin collagen and may contribute to photoaging. Treatment with topical tretinoin inhibits irradiation-induced matrix metalloproteinases but not their endogenous inhibitor.
Article
We have investigated the clinical response of 22 patients with plaque psoriasis to photodynamic therapy using topical application of 5-aminolaevulinic acid followed by a single exposure to broad-band visible radiation. Light doses in the range 2-16 J/cm2 delivered at dose of 10-40 mW/ cm2 resulted in a variable clinical response. Seven (35%) patients showed clearing of psoriasis at some treated sites. The intensity of protoporphyrin IX fluorescence was recorded before, during and after treatment. Pre-illumination fluorescence intensity varied considerably between sites on the same patient and between patients. Protoporphyrin IX fluorescence recovered and persisted after treatment for up to 14 days and became higher than preillumination levels at 25% of sites. The rate of protoporphyrin IX photo-oxidation during treatment was proportional to both initial fluorescence intensity and incident light dose rate and was almost complete after 16 J/cm2. We have defined the photodynamic dose as the product of time-dependent protoporphyrin IX concentration and light dose and demonstrated that only in those patients who showed clearance of psoriasis was there a relationship between photodynamic dose and clinical response. Discomfort ranged from stinging through to burning, was significant in some patients and tended to be more severe with increasing photodynamic dose but was not predictable. Efficacy may improve by achieving consistent protoporphyrin IX levels or by using multiple treatments.
Article
Several mechanisms are likely to be involved in the solar radiation-mediated modifications of cellular DNA. Direct excitation of DNA bases by the UVB component (290-320 nm) of solar light gives rise, mostly through oxygen independent reactions, to the formation of dimeric pyrimidine lesions including cyclobutadipyrimidines, pyrimidine (6-4) pyrimidone photoproducts and related valence Dewar isomers. In addition, photoexcitation of cytosine and guanine may lead to the formation in relatively minor yields of 6-hydroxy-5,6-dihydrocytosine and 8-oxo-7,8-dihydroguanine, respectively. A second mechanism that requires the participation of endogenous photosensitizers together with oxygen is at the origin of most of the DNA damage generated by the UVA (320-400 nm) and visible light. Singlet oxygen, which arises from a type II mechanism, is likely to be mostly involved in the formation of 8-oxo-7,8-dihydroguanine that was observed within both isolated and cellular DNA. However, it may be expected that the latter oxidized purine lesion together with DNA strand breaks and pyrimidine base oxidation products are also generated with a lower efficiency through Fenton type reactions. A more definitive assessment of these mechanisms would require further studies aimed at the identification and quantification of the different DNA photolesions including both dimeric pyrimidine photoproducts and photooxidized lesions.
Article
Understanding the mechanisms responsible for photodamage to the skin is most important for dermatology. 3-D cultures have been used as tools to mimic the in vivo situation for several years. We irradiated such a system containing human dermal fibroblasts cultured in collagen gels, a well-known model considered to be a dermal equivalent, which reproduces the interaction between cells and the surrounding extracellular matrix. The effects of solar irradiation (315-800 nm) on the steady-state levels of the mRNAs of extracellular matrix components (type I and III collagens) and their degrading enzymes (interstitial collagenase, MMP-1 and stromelysin 1, MMP-3) were measured. Exposure to low levels of solar radiation (0-10 J cm-2 in the UVA, i.e. suberythemal UVA doses) caused a transient decrease in type I procollagen mRNA, an increase in MMP-mRNA, and no change in type III procollagen mRNA steady-state levels. These results describe the early changes in the connective tissue of the skin following exposure to low-level solar stimulation, and may help explain the long-term changes in photodamaged skin.
Article
In evaluating the autofluorescence properties of normal and diseased skin we discovered that psoriatic plaques can emit a distinct red fluorescence when illuminated with UVA or blue light. Using a macrospectrofluorometer equipped with a 442 nm excitation laser, a sharp in vivo fluorescence emission peak around 635 nm could be demonstrated within the plaques of 34 of 75 (45%) patients with psoriasis. This peak was absent from normal appearing skin of psoriatic patients and also from the skin of 66 patients with other dermatologic diseases. A microspectrofluorometer coupled with the same excitation laser was used to obtain emission spectra of separated epidermal sheets and dermis from plaques demonstrating macroscopic red autofluorescence. An emission peak around 635 nm was observed in all three patients thus studied, but only on spectra obtained from the epidermis. Additional spectra of vertical microscopic sections of intact psoriatic skin from five other patients revealed that the peak originated from the stratum corneum. Emission spectra from other microlocations including the mid-epidermis and dermis of psoriatic and normal skin, as well as the stratum corneum of normal skin, failed to demonstrate a 635 nm peak. The excitation and emission fluorescence spectra of acid extracts of psoriatic scale from five patients were all similar to those of protoporphyrin IX in acid solution. High performance liquid chromatography identified the presence of protoporphyrin IX in the acid extracts from psoriatic scale of the same patients. We conclude that native psoriatic plaques can exhibit red autofluorescence that is due to elevated levels of protoporphyrin IX within scales.
Article
In 1998 it is appropriate to commemorate the 50th anniversary of el Mofty's use of purified 8-methoxypsoralen (8-MOP) in the treatment of vitiligo (el Mofty AM. A preliminary clinical report on the treatment of leukoderma with Ammi majus linn. J R Egypt Med Assn 1948,31:651 65. el Mofty AM, el Sawalhy H, el Mofty M. Clinical study of a new preparation of 8-methoxypsoralen in photochemotherapy. Int J Dermatol 1994;8:588 92). Two young American dermatologists (Aaron Lerner and Thomas Fitzpatrick) were intrigued by the potency of this material. After Lerner determined that artificial long wavelength ultraviolet (320-400 nm, UVA) radiation was the most efficient for activating 8-MOP. the development of artificial sources enabled the efficient delivery of these photons to skin containing 8-MOP. Their initial studies for vitiligo led to further development of this therapy for the treatment of psoriasis (Parrish JA, Fitzpatrick TB, Tannenbaum L, et al. Photochemotherapy of psoriasis with oral methoxsalen and long-wave ultraviolet light. New Engl J Med 1974;291:1207-11. Honigsmann H, Fitzpatrick TB, Pathak MA, et al. Oral photochemotherapy with psoralen and UVA (PUVA): principles and practice. In: Fitzpatrick TB, Eisen AZ, Wolf K, editors. Dermatology in General Medicine. New York: McGraw-Hill, 1987:1728-54). This photochemotherapy came to be called 'PUVA' (psoralen + UVA). The position PUVA holds today as one of the most common procedures performed in dermatology can be traced to their initial curiosity and their subsequent ingenuity. Further developments in more recent years capitalized on their seminal work. The therapy met with unprecedented success from the outset, leaving little perceived need to understand underlying science. However, in recent years there has been a new found interest in the basic aspects of psoralen photobiology and molecular mechanistic events contributing to therapeutic responses as well as to the development of skin cancers in PUVA patients. These will be surveyed in this review commemorating the 50 years of modern psoralen photobiology and photomedicine.
Article
The adverse outcome of increased ultraviolet (UV) irradiation on human health is currently of concern. While many experiments have been carried out in rodent models, fewer have been designed to test the effects of UV exposure in human subjects. This review concentrates on the modulations induced in the human immune system by UV, and outlines changes in antigen presentation by Langerhans cells and macrophages, in the activities of natural killer cells and T cells, and in cytokine regulation. Precautionary measures which might be taken to help protect people against the immunosuppressive action of UV irradiation are considered.
Article
Cytochrome c oxidase is discussed as a possible photoacceptor when cells are irradiated with monochromatic red to near-IR radiation. Four primary action mechanisms are reviewed: changes in the redox properties of the respiratory chain components following photoexcitation of their electronic states, generation of singlet oxygen, localized transient heating of absorbing chromophores, and increased superoxide anion production with subsequent increase in concentration of the product of its dismutation, H2O2. A cascade of reactions connected with alteration in cellular homeostasis parameters (pHi, [Cai], cAMP, Eh, [ATP] and some others) is considered as a photosignal transduction and amplification chain in a cell (secondary mechanisms).
Article
We investigated the clinical response of 10 patients with plaque psoriasis to multiple treatments with photodynamic therapy, using topical application of 5-aminolaevulinic acid followed by exposure to broad-band visible radiation. Treatment was performed up to 3 times per week, with a maximum of 12 treatments, using a light dose of 8 Jcm(-2) delivered at a dose-rate of 15 mW cm(-2). Eight patients showed a clinical response. Out of 19 treated sites, 4