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Biomedical subjects

Robert M Sayre

Publications and source records attributed to Robert M Sayre.

13 recordsLinked to original sources

Constitutive and UV-induced metabolism of melatonin in keratinocytes and cell-free systems.

Melatonin, which can be produced in the skin, exerts a protective effect against damage induced by UV radiation (UVR). We have investigated the effect of UVB, the most damaging component of UVR, on melatonin metabolism in HaCaT keratinocytes and in a cell-free system. Four metabolites were identified by HPLC and LC-MS: 6-hydroxymelatonin, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), 2-hydroxymelatonin (the main intermediate between melatonin and AFMK), and 4-hydroxymelatonin. Concentrations of these photoproducts were directly proportional to UVR-dose and to melatonin substrate content, and their accumulation was time-dependent. The UVR-dependent increase of AFMK and 2-hydroxymelatonin was also detected in keratinocytes, where it was accompanied by simultaneous consumption of intracellular melatonin. Of note, melatonin and its two major metabolites, 2-hydroxymelatonin and AFMK, were also detected in untreated keratinocytes, neither irradiated nor preincubated with melatonin. Thus, intracellular melatonin metabolism is enhanced under exposure to UVR. The additional biological activity of these individual melatonin metabolites increases the spectrum of potential actions of the recently identified cutaneous melatoninergic system.

Anti-Bacterial Agents↗

Failure of physiologic doses of pure UVA or UVB to induce lesions in photosensitive cutaneous lupus erythematosus: implications for phototesting.

BACKGROUND: Phototesting studies in cutaneous lupus erythematosus have yielded variable results, with most trials reporting photo-induction of lesions by both UVA and UVB in substantial numbers of patients. OBJECTIVES: To determine the minimal erythema dose in patients with subacute cutaneous lupus erythematosus (SCLE) and controls. PATIENTS/METHODS: We phototested nine patients with SCLE and 14 skin type-matched controls, using repetitive dosing of UVA1 and UVB, but with filters that removed most of the shorter UVC and longer infrared and visible light. In addition, DNA was isolated from anticoagulated blood to genotype the TNF-alpha 308 region in each patient and control. RESULTS: We were unable to demonstrate a difference in minimal erythema dose (MED) between patients and controls, or any correlation of MED with either TNF genotype or systemic drug therapy for SCLE. In addition, no SCLE skin lesions were induced in the nine patients with either UVA or UVB, and one patient cleared a skin lesion after low-dose UVA1 irradiation. CONCLUSIONS: The potential role of wavelengths outside the UVA and UVB range in the photo-induction of cutaneous lupus skin lesions needs to be investigated, and there is a need to standardize phototesting equipment and procedures for patients with cutaneous lupus erythematous.

Case-Control Studies↗

Sunscreen ingredients inhibit inducible nitric oxide synthase (iNOS): a possible biochemical explanation for the sunscreen melanoma controversy.

Sunscreen products are rated upon their ability to inhibit visible redness of the skin 24 h after measured doses of ultraviolet (UV) exposure (Sun Protection Factor, SPF). Although sunscreens prevent UV-induced redness, their ability to protect against melanoma or the development of moles is less clear. UV-induced redness occurs in part by the action of nitric oxide (NO), synthesized in the skin. NO is also an important immunoregulatory molecule in the induction of the cell-mediated tumour immune response. In this study, various sunscreen ingredients were tested for their ability to inhibit the production of NO. Four of the five sunscreens tested directly inhibited the conversion of arginine to citrulline by inducible nitric oxide synthase (iNOS) in vitro. These findings suggest that sunscreens may prevent redness partly by UV absorption and partly by inhibition of the skin's inflammatory response. As such, sunscreens might promote instead of protect against melanoma.

Arginine↗

Modest in vivo exposure to solar wavelengths induces a visible absorbing chromophore in Skh-1 mouse epidermis.

BACKGROUND/PURPOSE: In the previous work, we correlated epidermal hyperplasia with increased epidermal absorption in the 250-400 nm region. During a recent review of that work, the apparent formation of a chromophore, with absorption slightly longer than 400 nm, in the epidermis of irradiated animals was noted. In this study, we have extended the transmission measurement to include the 250-800 nm region. METHODS: Age-matched Skh-1 hairless mice were separated into three groups. One group was irradiated with 6.3 J/cm(2) (0.9 minimal erythemal dose; MED) of solar simulating ultraviolet radiation (SSUVR) five times/week for 2 weeks, then increased to 1.1 MED (7.1 J/cm(2)) for two additional weeks (20-day group). A second 10-day group, added halfway through the protocol, was irradiated with 0.9 MED five times/week for 2 weeks. The control group received no UV irradiation. Routine H&E staining and epidermal absorption spectral analysis were carried out on biopsy specimens from each animal. RESULTS: This work confirms the development or enhancement of a visible chromophore with a maximum absorption at ca 412 nm. This peak appears to be radiation dose dependent. It can be discerned in both the groups, albeit more prominently in the 20-day animals. The absorption is sufficiently strong to impart a yellow to reddish appearance to skin viewed in full spectrum visible light. CONCLUSIONS: Accumulation of such a chromophore in humans may contribute to the coloration of chronically exposed skin. The absorption strength and wavelength location of the peak is strongly suggestive of a heme-like compound. We are currently conducting experiments to further characterize this chromophore.

Absorption↗

Uniformity of sunscreen product application: a problem in testing, a problem for consumers.

BACKGROUND/AIMS: Testing of sunscreen products requires application of uniform films of product of defined thickness to test volunteers. In spite of the seeming importance of product application to defining sunscreen efficacy, there have been few studies determining how well uniformity is achieved. The purpose of this work was to evaluate the uniformity of sunscreen products of different sun protection factors (SPFs) and vehicles on a variety of substrates by in vitro testing techniques. The results of a variety of testing strategies are reported. METHODS: Five commercial sunscreen products of labelled SPF 4-50 were tested using a variety of substrates: Transpore Tape, Vitro-Skin trade mark, and lambskin condom. Two experienced sunscreen testers applied the products. In vitro SPFs were determined using an Optometric 290 analyser or an Optronic Laboratories OL754 spectroradiometer configured for this application. RESULTS: SPFs for several locations on each film applied to a substrate were determined and the mean SPF and RSD percentage of the mean calculated. For all substrates and testing techniques the average RSD percentage was 18.6, with a range of 10-40%. CONCLUSION: The expected uncertainty of SPF due to product application non-uniformity is 20% when applied under optimal test conditions. Clearly SPF tests reported by different laboratories must exhibit significant variability, because of product application non-uniformity.

Administration, Cutaneous↗

Simplified method to substantiate SPF labeling for sunscreen products.

BACKGROUND/PURPOSE: Worldwide, sunscreen sun protection factor (SPF) testing is based on 30-year-old technology. At the time the SPF test came into being, the highest SPFs available were in the 6-8 range. The SPF test is reasonably accurate for SPFs up to 15, but is much less reliable for measuring SPFs of 30 and higher. The method we propose addresses two primary reasons for this unreliability: 1) difficulties in applying products uniformly and 2) the subjectivity and variability of perception in evaluating and grading responses to UV doses. METHODS: Our proposed SPF substantiation method differs from the current SPF test in that sunscreen-protected test sites receive the same UV dose in four uniformly spaced sub-sites, which are graded as passing if no response is seen or failing if any response is seen. The response may be tanning, erythema, or a combination of both. To demonstrate the method, two commercial products with labeled SPFs of 30 and 45 and the P2 sunscreen standard were tested at two different laboratories. RESULTS: The SPF 30 product and SPF 15 standard were shown to be correctly labeled. However, it is questionable as to whether the SPF 45 product provides protection against 45 minimal erythema doses. CONCLUSIONS: Our proposed SPF substantiation method is not dependent on subjective evaluation of responses, accounts for non-uniform product application, and provides a conservative estimate of sunscreen protection. The method consists of a systematic repetition of identical tests that are considerably more rigorous than the current methods that are based on single data points per test subject. While the current SPF test remains necessary and valuable as a dose ranging tool, we propose that this SPF substantiation method supersede the old method for final SPF label determination.

Administration, Cutaneous↗

Dermatological risk of indoor ultraviolet exposure from contemporary lighting sources.

Discussions of risks and implications of cutaneous exposure to indoor lighting, including hypothetical contribution to causality of melanoma, have mainly concentrated on ultraviolet (UV) A and B (UVA, UVB) spectral emissions from fluorescent bulbs. Only studies of quartz halogen lamps have suggested that users might sustain UVC-induced injury. Examination of light sources in the home and school of a child with xeroderma pigmentosum revealed that several different types emitted surprising levels of UV. Our purpose was to assess the extent of UV emissions from a variety of commonly used light sources to identify potential dermatological risks. UV and visible spectral emissions of commercially obtained lamps of several types were measured using a calibrated spectral radiometer traceable to the National Institute of Standards and Technology. Indoor light sources including fluorescent, quartz halogen and even tungsten filament incandescent lamps provided UVA, UVB and sometimes UVC emissions. Intensities of some emissions were of similar magnitude to those in sunlight. Chronic exposure to indoor lighting may deliver unexpected cumulative UV exposure to the skin and eyes. Patients with UV-exacerbated dermatoses should be cautioned about potential adverse reactions from indoor lighting.

Air Pollution, Indoor↗

Unexpected photolysis of the sunscreen octinoxate in the presence of the sunscreen avobenzone.

A major concern raised about photostability studies of sunscreen products is that the photodegradation of sunscreens does not readily translate into changes in product performance. This study examines the correlation between photochemical degradation of sunscreen agents and changes in protection provided by sunscreen films. Films of a commercial sunscreen product containing avobenzone, oxybenzone and octinoxate were irradiated using a fluorescent UV-A phototherapy lamp with additional UV-B blocking filter. Periodically, during irradiation the transmittances of the films were measured and samples collected for chemical analysis of the sunscreen agents using high-performance liquid chromatography techniques. The results show that UV-induced changes in UV transmittance of sunscreen films correlate with changes in concentration of sunscreen agents. In a parallel experiment, we also irradiated a thin film of the same product in the cavity of an electron spin resonance (ESR) spectrometer. We report the concomitant photolysis of avobenzone and octinoxate that predominates over expected E/Z photoisomerization and that irradiation of a film of this product produced free radicals detected by ESR spectroscopy that persisted even after exposure had ended.

Chalcones↗

Darkness at noon: sunscreens and vitamin D3.

We are assured by responsible scientific and governmental organizations that sunscreens should be routinely worn to reduce skin cancer risk. We are also advised that wearing sunscreens will not hinder our ability to produce sufficient previtamin D3 (preD3) from casual sunlight exposure. We report the examination of a series of 166 solar spectra, obtained on different days throughout a year, evaluated for erythemic and preD3 effectiveness and the relative effects of recommended Sun protection factor (SPF) 15 sunscreen. The results show that the sunscreen is much more effective in blocking the formation of preD3, than its labeled SPF for preventing sunburn. In fact with sunscreen applied only miniscule amounts of preD3 are predicted to be made outdoors even with extensive exposure. This raises important questions regarding the safest way to use sunlight exposure to promote healthy vitamin D3 levels and suggests the need to modify the public safety "Safe Sun" messages.

Cholecalciferol↗