Library

Notes: Background  St John's wort (SJW) is widely used as a treatment for depression. A phototoxic reaction, due to its content of hypericin, can occur in animals and in cell culture, and has been reported in humans. Hypericin displays absorption within the ultraviolet (UV) A1 spectrum and there may therefore be a potential for phototoxicity if taken during high-dose UVA1 therapy.Objectives  To assess the phototoxicity risk of SJW ingestion.Methods  Eleven adult volunteers of skin types I and II were exposed to a geometric dose series of UVA1 irradiation from a high-output source (Dermalight Ultra 1; Dr Hönle, Martinsreid, Germany; irradiance 70–77 mW cm−2) on the photoprotected lower back skin at eight 1·5-cm2 test areas. Irradiation was carried out at baseline and after 10 days of SJW extract 1020 mg (equivalent to 3000 µg of hypericin) daily. Four, 8, 24 and 48 h after each exposure, the minimal erythema dose (MED) and the presence or absence of pigmentation were recorded visually and erythema was assessed objectively with an erythema meter.Results  The median MED and D0·025, an objective measure of MED, were lower at all time-points after SJW ingestion. The visual erythemal peak (lowest median MED), which was seen at 8 h postirradiation, was lower after SJW (median 14 J cm−2, range 10–56) than at baseline (median 20 J cm−2, range 14–56) (P = 0·047). Similarly, the median D0·025 at 8 h postirradiation was lower after SJW (median 22·0 J cm−2, range 15·2–53·9) than at baseline (median 33·7 J cm−2, range 22·9–136·0) (P = 0·014). The MED and D0·025 were also significantly different at the 48-h and 4-h time-points, respectively. Significance was not reached at the 24-h time-point. Median intensity of postirradiation erythema increased at all time-points after ingestion of SJW. Despite these differences, the maximum slope of the dose–response curve was not increased after SJW ingestion.Conclusions  These data suggest that SJW extract has the potential to lower the erythemal threshold to UVA1 irradiation in a significant proportion of individuals and highlight the importance of ascertaining a full drug history, including herbal remedies, before initiating UVA1 phototherapy.

Notes: Background  Phosphorylation of the tumour suppressor p53 by the CK2/FACT pathway plays a central role in suppressing ultraviolet (UV)-induced skin cancer in animal models. Although p53 protein stabilization is induced after solar-simulated irradiation of human skin in vivo, p53 phosphorylation has not been defined.Objectives  To investigate the effects of clinically effective treatments for skin diseases including psoralen + UVA (PUVA) and photodynamic therapy (PDT) on p53 phosphorylation to determine whether the tumour-suppressing p53 kinase pathways are activated upon use of these therapies.Methods  We used antibodies to the ATM/ATR and CK2/FACT phosphorylation sites on p53.Results  We found that p53 activation was induced selectively by PUVA treatment, while 8-oxo-7,8-dihydroguanine DNA damage was induced selectively by 5-aminolaevulinic acid (ALA)-PDT treatment. Importantly, PUVA treatment resulted in p53 kinase activation, as defined by p53 modification at AT (serine-15) and CK2/FACT (serine-392) sites within the proliferative compartment.Conclusions  These data demonstrate that PUVA provokes accumulation and phosphorylation of p53 by AT and CK2/FACT within critical proliferative focal points (as determined by p63 colocalization studies) where DNA damage may lead to tumorigenesis. PDT is mechanistically distinct in that there is a lower level of induction of p53 expression with no evidence of AT- or CK2/FACT-mediated phosphorylation. This suggests that the type of DNA damage created by the reactive oxygen species generated by ALA-PDT does not induce the p53 pathway classically required for the repair of DNA photoadducts induced by UV.

Notes: Background  High-dose ultraviolet (UV) A1 therapy (doses in the order of 130 J cm−2) is effective for atopic dermatitis and scleroderma. UVA1 has been shown to induce a dose-dependent increase in p53 expression in keratinocytes.Objectives  To examine the effect of UVA1 on the activation of p53 by phosphorylation, which has not yet been studied.Methods  Five adult volunteers were exposed to dose series of UVA1 (10–100 J cm−2) and, for comparison, narrowband UVB (TL-01) (25–550 mJ cm−2) and solar-simulated radiation (SSR) (5·6–30 J cm−2) on photoprotected buttock skin and the minimal erythema dose (MED) for each was determined at 24 h. Separate sites on the buttock were subsequently irradiated with a 3-MED dose of UVA1, TL-01 and SSR. At 24 h, punch biopsies (4 mm) were taken from each irradiated site and from an adjacent unirradiated control site, and immunohistochemical staining for p53 (Do-1), activation of p53 (assessed by phosphorylation at serine 15 and serine 392) and p21 was performed. Cell staining was expressed as the mean number of cells stained per three high-power fields (HPFs) and as a percentage of 1000 cells. Sunburn cells (SBCs) were also counted per HPF.Results  UVA1 produced negligible numbers of SBCs, relatively little p53 (Do-1) staining (mean ± SD cell count per HPF 16 ± 10), no p53 activation and very little evidence of p21 expression (mean ± SD cell count per HPF 5·3 ± 7), in contrast to TL-01 (mean ± SD cell count per HPF of 11·83 ± 2·1 SBCs, 146·3 ± 38 for Do-1, 26·6 ± 15 for serine 15, 14·9 ± 12 for serine 392 and 77·9 ± 30 for p21) or SSR irradiation (mean ± SD cell count per HPF of 3·5 ± 1·2 SBCs, 147·5 ± 62 for Do-1, 54 ± 50 for serine 15, 38·9 ± 18 for serine 392 and 56·7 ± 30 for p21).Conclusions  These data indicate that there are fundamental differences in the effects of UVA1 on p53 and its activation pathways compared with TL-01 and SSR, and may in part explain the differential effects of these phototherapies.

Notes: Summary Background The subjective benefit of attendance at cosmetic clinics has not previously been reported. Objectives To assess the effect on perceived quality of life (QoL) of cosmetic camouflage advice. Methods In a three-centre study, 135 individuals were invited to complete a dermatology-specific QoL measure, the Dermatology Life Quality Index (DLQI), before and 1 month after their first visit to a cosmetic camouflage clinic. Results Eighty-two completed DLQI questionnaires were returned before the camouflage clinic appointment, and 56 corresponding questionnaires were returned 1 month after. The mean age of responders was 50 years, and the mean duration of their skin conditions was 15 years. The main conditions seen were pigmentary disorders (29%), scars (22%) and vascular disorders (13%). There was a significant difference in mean DLQI scores before and after the clinic visit (9·1 vs. 5·8, P = 0·0001). Conclusions When assessed at 1 month, attendance at a cosmetic camouflage clinic appears to improve QoL significantly.