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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  Dead Sea (DS) salt solution soaks are used in combination with narrowband ultraviolet B (NB-UVB) to treat psoriasis in many centres, particularly in continental Europe. No previously published controlled study has assessed DS salt + NB-UVB balneophototherapy.Objectives  To compare DS salt balneophototherapy with NB-UVB monotherapy for chronic plaque psoriasis.Methods  Sixty patients with chronic plaque psoriasis participated in this paired, controlled study, with pretreatment DS salt soaks randomly allocated to each participant's right or left study limb. Psoriasis severity was assessed with a Scaling, Erythema and Induration score by a blinded observer. Assessments were weekly during the therapy course, and thereafter 8-weekly until relapse or for up to 1 year after clearance.Results  The mean area under the psoriasis severity–time curves during treatment was not detectably lower with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0·099). The psoriasis severity score fell slightly more from beginning to end of courses with DS salt balneophototherapy than with NB-UVB monotherapy (P = 0·019). There was no detectable difference in times to relapse.Conclusions  In this population the addition of pretreatment DS salt soaks to NB-UVB did not result in a clinically important improvement in clearance of psoriasis.

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: Background  Limited information is available on the carcinogenic risk associated with narrowband TL-01 UVB phototherapy in humans.Objectives  To determine the skin cancer incidence in a population treated with TL-01 phototherapy.Patients and methods  All TL-01-treated patients were identified from the departmental computerized database. Patients with malignant melanoma (MM), squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were identified by record linkage with the Scottish Cancer Registry. The incidence of each was compared with the normal Scottish population matched for age and sex.Results  Data were obtained from 1908 patients. The median follow-up duration was 4 years (range 0·04–13). The median cumulative number of TL-01 treatments and dose were 23 (1–199) and 13 337 (30–284 415) mJ cm−2, respectively. No increased incidence of SCC or MM was observed. Ten patients developed BCC compared with an expected 4·7 in the Scottish population [standardized rate ratio 213 (95% confidence interval 102–391); P 〈 0·05].Conclusions  A small but significant increase of BCC was detected in the TL-01 group. This could be explained by a number of factors, including ascertainment bias. To determine the true carcinogenic risk of TL-01 phototherapy, longer follow-up is essential.