[Sun lotion and malignant malanoma].
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Biomedical subjects
Publications and source records attributed to H C Wulf.
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BACKGROUND AND OBJECTIVE: Melanin is a limiting factor for obtaining beneficial results in dermatological treatment of vascular malformations. The aim of our study was to establish a relation between pretreatment skin pigmentation and the occurrence of side effects. STUDY DESIGN/MATERIALS AND METHODS: Thirteen human volunteers selected to have a varying degree of skin pigmentation were laser-treated on the inside of the brachium with an argon laser (AL, 488 nm and 514.5 nm) and a copper vapor laser (CVL, 578 nm), both connected to a Hexascan. Total exposure areas were 1.26 cm2 and beam diameters were 1 mm. Three intensities were used, 0.7, 1.0, and 1.3 W. Pulse duration was 200 ms, resulting in fluences of 17.8, 25.5, and 33.1 J/cm2. Pretreatment skin pigmentation was objectified by skin reflectance measurements. RESULTS: At 1, 2, and 6 months after laser treatment, significant correlations were demonstrated between pretreatment skin pigmentation and laser-induced pigmentary changes and scar formation. At the 6-month assessment, the AL induced significantly higher scores of clinically evaluated scar formation as compared with the CVL (1.0 and 1.3 W/spot) and tended to induce higher clinical scores of pigmentary changes (not significant, ns). CONCLUSIONS: We recommend skin pigmentation to be taken into consideration in dermatological laser treatment of vascular malformations.
The effect of systemic treatment with the anti-inflammatory drug indomethacin on sun-induced skin carcinogenesis was examined in lightly pigmented hairless hr/hr C3H/Tif mice. Two groups of 20 mice were exposed to simulated solar ultraviolet radiation from one Phillips TL 12 and five Bellarium-S SA-1-12 tubes for 8 min/day, 4 days/week (daily dose was 12.6 kJ/m2, equivalent to 2.1 B-MED the basic minimal erythema dose). A mean dose of 1.8 mg kg-1 24 h-1 indomethacin was supplied to one of the two groups via the drinking water. The pharmacological treatment started on the first day of the trial and continued during the entire experiment. The time to first, second, and third tumour was significantly delayed in the group treated with indomethacin (P < 0.001). The mortality rate was higher in the indomethacin-treated group than in the group receiving no pharmacological treatment (P < 0.0005). Under the present conditions, our study suggests that indomethacin may be beneficial in protection against photocarcinogenesis.
Earlier studies of ultraviolet (UV) irradiated hairless mice have suggested a relation between elastosis and mast cells. To examine whether such a relation exists, we examined groups of hairless mice irradiated with equal doses of UV. The narrow UV bands had peaks at 292, 300, 307, 317 and 336 nm. The groups were irradiated 5 times per week during 1 year. It was shown that the shorter the wavelengths, the more pronounced was the degree of elastosis. Sections from dorsal skin were prepared for light microscopy and stained with orcein, making it possible to detect the elastosis at the same time as the mast cells. We used a projection microscope and a computer analyzing system connected to a video scanner for the calculations. The mast cell count was higher in the irradiated groups than in the control group. The number of mast cells was higher in the groups irradiated with the shortest wavelengths (292 and 300 nm). In groups irradiated with wavelengths shorter than 307 nm a subepidermal clearance zone containing significantly fewer mast cells than the rest of the upper dermal layer was found. We suggest that the mast cells might have a digesting function, as this layer was cleared of elastotic fibers and few mast cells were seen here.
A new in vivo method of visual scoring of pigmentation in hairless hr/hr mice with a C3H/Tif background is described. The mice were placed under a bank of 6 Philips TL08 fluorescent ultraviolet A (UVA) tubes in a dark room, and the pigmentation of the skin was compared with a Kodak Gray Scale with 20 different shades from white to black. The radiation from the tubes changed both the color of the back of the mouse and the gray scale into purple hues. The purple color of the back of each mouse could then be classified as one of 20 shades on the gray scale. An experiment was conducted exposing 3 groups of 20 mice to different doses of UV radiation from Philips TL01 tubes. One group of 20 mice was not irradiated and served as control. The pigmentation of each mouse was scored by one investigator every 2-3 weeks. After a few weeks of exposure a clear distinction between the groups was seen. To evaluate the inter- and intrapersonal variation of the method, 30 mice with various degrees of pigmentation were scored independently and blindly by two investigators. This was done twice during the study with a few days' interval. No interpersonal difference was found, but one investigator scored differently the first and second time by only 0.5 points. The described method provides a reproducible in vivo method, with very good discrimination, for estimation of pigmentation in hairless mice.
The carcinogenic and melanogenic effects of a filtered metal halide source (UVASUN) that emits UV radiation in a range from 340 to 400 nm and a bank of Philips TL 09R tubes (TL 09) emitting in a range from 310 to 400 nm were studied in lightly pigmented hairless hr/hr C3H/Tif mice. Both the carcinogenic effect of the two UVA radiation sources alone and in combination with a UV source, consisting of one Philips TL 12 and five Bellarium-S SA-1-12 tubes emitting radiation somewhat similar to the UV part of the solar spectrum (SOLAR UV), were investigated. Finally, the melanogenic effect of exposure to the two UVA sources were studied. The mice were exposed to the UVA sources 30 min/day 5 days/week, in equal erythemogenic doses, calculated by using the Commission Internationale de l'Eclairage human erythema action spectrum. Equal erythemogenic doses of TL 09 and UVASUN induced the same degree of skin pigmentation, but skin tumor development was enhanced in mice exposed to TL 09 compared with UVASUN (P < 0.0005). For all but one tumor, endpoint pretreatment with TL 09 or UVASUN for 91 days did not influence tumor development during subsequent exposure to SOLAR UV radiation 10 min/day, 4 days/week. Exposure to the two UVA radiation sources after 91 days of SOLAR UV exposure significantly enhanced skin tumor development. Overall, the data on the interaction between exposure to the UVA sources and SOLAR UV indicated that the risk of SOLAR UV-induced carcinogenesis was independent of the type of prior-UVA exposure and post-UVA exposure.
Protection against the sun in Denmark is only necessary from mid April to September. The number of erythema units may reach about 16 per day in the summer sun and about 50% of the biological active radiation is found between 12 a.m. and 3 p.m. (summertime). The most biologically active wavelengths are found to be 300-325 nm and protection with sunscreens and clothes should include these wavelengths. Necessary sun protection factors for average and especially sensitive Danes were estimated. The average Dane needs a SPF of 4-8 and especially sensitive persons a SPF of 8-15 when exposed all day in summer. Most clothes meet these demands.
Thirteen human volunteers selected to have a varying degree of epidermal skin pigmentation were laser treated on the inside of the brachium in six hexagonal areas; three areas with an argon laser (AL, 488, 514.5 nm) and three corresponding areas with a copper vapour laser (CVL, 578 nm). The lasers were connected to a Hexascan device and the physical settings were identical for the two laser types, except for the wavelengths. Beam diameter was 1 mm, pulse duration 200 ms, intensities 0.7, 1.0 and 1.3 W/spot, corresponding to 14.1, 20.2 and 26.2J/cm2 per treated skin area. The skin pigmentation was objectified by skin reflectance. A correlation was demonstrated between skin pigmentation and wound healing time, maximum wound area, and the acute clinical response at days 0, 1, 4, 7, 11 and 17 after laser treatment. An increased skin pigmentation resulted in increased acute and subacute skin reactions. Comparison of the AL and the CVL demonstrated that the CVL on day 0 (0.7 and 1.0 W/spot) and on day 1 (0.7 W/spot) induced a significantly higher degree of skin reactions as compared with the AL. At 0.7 W/spot the CVL induced a significantly higher maximum wound area and a significantly prolonged wound healing time as compared with the AL. An inverse reaction existed between pigmentation and the threshold intensity required to induce wound formation.
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It is well established that in healthy humans oral intake of 5- or 8-methoxypsoralen (5- and 8-MOP) is followed by a significant increase in plasma melatonin concentrations. The effect of psoralen on rat melatonin has been studied in vitro and in vivo and a stimulation of release or secretion from the pineal gland has been suggested. In this study we examined the time-related changes in plasma concentrations of 8-MOP, melatonin and 6-sulfatoxymelatonin in 15 patients admitted for routine psoralen plus UVA therapy. On the first day of treatment blood samples were collected before, and 30, 60, 66 and 90 min after intake of 8-MOP (0.6 mg/kg). Although the rate of 8-MOP absorption varied greatly, a significant increase (P = 0.0002) in melatonin levels was found 60 min after 8-MOP intake. During UVA exposure a strongly correlated decrease in mean melatonin and mean 8-MOP concentrations was found, indicating an effect of UVA radiation, either direct or 8-MOP mediated, on circulating melatonin levels. Plasma 6-sulfatoxymelatonin concentrations decreased significantly between all time points, suggesting inhibition of melatonin metabolism.
The carcinogenic effect of 4 ultraviolet (UV) sources was studied in lightly pigmented hairless mice. Two narrow-band UV sources, Philips TL01 and Philips TL12 with a Tempax filter, and two broad-spectrum UV sources, Philips TL12 and Bellarium S, were used. Exposure doses were calculated from the CIE erythema action spectrum. Four groups of mice (n = 20) were exposed to a nonerythemogenic dose (low dose), and 4 groups were exposed to an erythemogenic dose (high dose) of each of the 4 UV sources. One group (control) was not irradiated. The mice in the 4 low-dose groups were all exposed to 0.6 basic minimal erythema doses (B-MED) 5 days/week, and all the mice in the high-dose groups to 1.2 B-MED 5 days/week. After 16 weeks of acclimatization, the doses were doubled. Bellarium S and Philips TL12 were equally carcinogenic in the low-dose regimen and the high-dose regimen. Mice exposed to Philips TL12 with a Tempax filter developed tumors significantly earlier compared with Bellarium and Philips TL12. Philips TL01 was more carcinogenic than any of the other UV sources. Equally erythemogenic doses calculated from the CIE erythema action spectrum seem to be more carcinogenic when derived from narrow-band UVB sources than from broad-band UV sources.
The melanogenic potential of multiple suberythemogenic doses of 6 different ultraviolet (UV) sources was investigated. The UV sources emitted different amounts of UVA and UVB. The backs of 12 volunteers were exposed to the 6 UV sources 10 times during 4 weeks. Every volunteer was exposed to the same suberythemogenic dose (0.75 basic minimal erythema dose) of each of the UV sources. The changes in pigmentation and minimal erythema dose of the UV exposed test sites were registered during the 10 sessions. Three UVA sources with a low emission in the UVB area (0.2-3.1%) had a high melanogenic potential. Two UVB sources (UVB emission 74.3% and 94.5%) were unable to induce a significant increase in skin pigmentation. The 3 UVA sources with a low UVB output increased skin pigmentation significantly better than a UVA source with a UVB output of 6.9%. All 6 lamps were able to increase photoprotection significantly. The increase in photoprotection was not significantly different between any of the 6 UV sources. This study shows that, if humans are exposed to equally suberythemogenic doses of different types of UV radiation, then radiation obtained from UVA sources greatly enhances melanogenesis, whereas UVB radiation sources are unable to induce pigmentation.
BACKGROUND AND DESIGN: Twenty-eight subjects were phototested to determine their erythemal responses to oral methoxsalen with UV-A and UV-B irradiation. Skin pigmentation was measured by skin reflectance at 550 and 660 nm before irradiation. The smallest UV radiation dose to produce erythema (minimal phototoxic dose and minimal erythema dose, respectively) was determined. The serum concentration of methoxsalen was measured at the time of UV-A irradiation. RESULTS: There was a positive correlation between skin pigmentation and both 72-hour minimal phototoxic dose and 24-hour minimal erythema dose. No correlation was demonstrated between methoxsalen serum concentration and minimal phototoxic dose. The combination of skin pigmentation and methoxsalen level did not give a better prediction of minimal phototoxic dose than skin pigmentation alone. CONCLUSIONS: Skin pigmentation measurements can be used to predict the minimal phototoxic and erythema doses. Skin pigmentation measurements are easy to perform and should be included in both phototherapy and photochemotherapy to improve the efficiency and reliability of the treatment.
In legislation the CIE human erythema action spectrum is used to assess the risk of UV radiation appliances for household use. The most popular type of UV radiation source for private use is the low pressure 'UVA' radiation source, which mainly emits in the UVA area, but also has some emission in the UVB area. Recently reports have raised doubt whether the CIE erythema action spectrum is a good approximation for the carcinogenic risk. Therefore, it was investigated whether the carcinogenic potential of differing UV tanning sources, which mainly emit in the UVA area, could be assessed by using the CIE erythema spectrum. Two groups of lightly pigmented C3H/Tif mice were initially exposed to broad spectrum UV radiation with a high output of UVB (UVB emission 16.7%) during 84 days, in a daily dose of 4.67 Basic minimal erythema doses (Basic-MED). Subsequently, one group was exposed to Bellarium-S SA-1-12 (UVB emission 6.9%), the other to Philips TL 09R (UVB emission 2.2%), in a daily dose of 1 Basic-MED. The time to occurrence of seven tumour end-points was almost identical in the two groups, p > 0.4. To obtain further information on the relationship between the daily dose of common UV tanning sources measured in Basic-MED and tumour development, we combined the result of this experiment with the results of two others. There existed a negative correlation between the daily exposure dose measured in Basic-MED and the tumour induction time, p < or = 0.05. This inverse relationship was observed both when the UV tanning sources were administered with or without a prior exposure to broad spectrum UV irradiation. Our results indicate that the carcinogenic risk of UV tanning sources in the hairless C3H/Tif mouse can be estimated by the CIE erythema action spectrum.
Vitronectin is a multifunctional glycoprotein known to be associated with the dermal elastic fiber network in human adults, with various types of human amyloid and with apoptotic keratin bodies in human skin. It has also been shown to bind to human keratin intermediate filaments and to intranuclear material in vitro. To learn more of its function and mode of tissue deposition, vitronectin in mouse skin was studied. Vitronectin was purified from mouse plasma and a polyclonal anti-vitronectin antiserum was produced. This was used in an avidin-biotin-peroxidase complex technique and in an immunofluorescence technique on biopsy sections of dorsal skin from mice. Hairless lightly pigmented mice, known to develop dermal amyloid deposits at advanced ages, were used, making it possible to study vitronectin's association not only with elastic fibers but also with amyloid. Association of vitronectin with elastotic material was investigated in mice exposed to ultraviolet radiation. No vitronectin immunoreactivity could be demonstrated in association with elastin-stained material in skin specimens from any of the mice, whether exposed to ultraviolet radiation or not. In contrast, vitronectin was constantly found to be associated with dermal amyloid deposits. Moreover, mouse vitronectin was found to bind to mouse keratinocytes when studied by immunofluorescence staining of skin sections that had been pre-incubated with mouse plasma as sources of vitronectin. The results indicate that vitronectin is associated with amyloid and can bind to intracellular structures in epidermal keratinocytes in mice as in humans, and that mouse tissue may be used for the study of vitronectin's interactions with amyloid and with intracellular structures.
The effect of solar exposure during a one-week sunbathing vacation in May at 29 degrees N latitude was investigated in 22 volunteers. The following end-points were measured before and after the holiday: skin reflectance at 507 nm, transmission of radiation from 289 nm to 448 nm through the epidermis, epidermal thickness, minimal erythema dose (MED), total white cell, neutrophil, lymphocyte, and lymphocyte subpopulation counts in blood, spontaneous DNA synthesis, DNA strand breaks and sister-chromatid exchange in lymphocytes, and the UVC tolerance of lymphocytes. There was a statistically significant decrease in skin reflectance (p < 0.001) and epidermal transmission (p < 0.01) after the holiday, reflecting increased pigmentation and epidermal thickening. There was a statistically significant increase in epidermal thickness (p < 0.001), MED (p < 0.05), spontaneous DNA synthesis (p < 0.01) and DNA strand breaks in lymphocytes (p < 0.02) after the holiday. The other end-points were not significantly changed. We report that changes in skin pigmentation and epidermal thickness occur after one week of UV exposure. It was also observed that a one-week UV exposure increased both spontaneous DNA repair and the amount of DNA strand breaks in the lymphocytes of the volunteers, while no changes in T-cell subsets were detected.
The carcinogenic effect of three UVA tanning sources was studied in lightly pigmented hairless mice. The three tanning sources (Bellarium-S SA-1-12, Philips TL 09R and Philips TL 10R) have different emission spectra, and emit different amounts of UVB. Radiation from the tanning sources was administered for 20 min/day, 5 day/week in daily doses equivalent to those used in suntan salons. The radiation was given alone or after 12 weeks of exposure to solar-simulated UV radiation (SOLAR UV) (10 min/day, 4 day/week; daily dose, 19.5 kJ/m2 UVA and 3.9 kJ/m2 UVB). Irradiation with Bellarium-S SA-1-12 for 47 weeks and Philips TL 09R for 74 weeks induced skin tumours in 20/20 and 13/20 of the animals, respectively. When irradiation with Bellarium-S SA-1-12 and PHilips TL 09R was administered after 12 weeks of SOLAR-UV exposure, a strong enhancement of SOLAR-UV-induced photocarcinogenesis was observed (p < 0.001). Irradiation with Philips TL 10R was only slightly carcinogenic, and during 85 weeks of irradiation only one skin tumor appeared in a group of 20 mice. However, when irradiation with Philips TL 10R was administered after 12 weeks of exposure to SOLAR UV, an enhancement of SOLAR-UV-induced carcinogenesis was observed (p < 0.001). Our results suggest that the hazards of exposure to commercial tanning devices are increased when they are used after a period of natural sun exposure. Even tanning sources with a low carcinogenic potential are able to increase SOLAR-UV-induced carcinogenesis significantly.