Cytochrome P450 CYP1B1 interacts with 8-<i>methoxypsoralen</i> (8-MOP) and influences psoralen-Ultraviolet A (PUVA) sensitivity

Background: There are unpredictable inter-individual differences in sensitivity to psoralen-UVA (PUVA) photochemotherapy, used to treat skin diseases including psoriasis. Psoralens are metabolised by cytochrome P450 enzymes (P450), and we hypothesised that variability in cutaneous P450 expression may influence PUVA sensitivity. We previously showed that P450 CYP1B1 was abundantly expressed in human skin and regulated by PUVA, and described marked inter-individual differences in cutaneous CYP1B1 expression.Objectives: We investigated whether CYP1B1 made a significant contribution to 8-methoxypsoralen (8-MOP) metabolism, and whether individuality in CYP1B1 activity influenced PUVA sensitivity.Methods: We used E. coli membranes co-expressing various P450s and cytochrome P450 reductase (CPR) to study 8-MOP metabolism and cytotoxicity assays in CYP1B1-expressing mammalian cells to assess PUVA sensitivity.Results: We showed that P450s CYP1A1, CYP1A2, CYP1B1, CYP2A6 and CYP2E1 influence 8-MOP metabolism. As CYP1B1 is the most abundant P450 in human skin, we further demonstrated that: (i) CYP1B1 interacts with 8-MOP (ii) metabolism of the CYP1B1 substrates 7-ethoxyresorufin and 17-b-estradiol showed concentration-dependent inhibition by 8-MOP and (iii) inhibition of 7-ethoxyresorufin metabolism by 8-MOP was influenced by CYP1B1 genotype. The influence of CYP1B1 on PUVA cytotoxicity was further investigated in a Chinese hamster ovary cell line, stably expressing CYP1B1 and CPR, which was more sensitive to PUVA than control cells, suggesting that CYP1B1 metabolises 8-MOP to a more phototoxicmetabolite(s).Conclusion: Our data therefore suggest that CYP1B1 significantly contributes to cutaneous 8-MOP metabolism, and that individuality in CYP1B1 expression may influence PUVA sensitivity

Measuring daylight:a review of dosimetry in daylight photodynamic therapy

Successful daylight photodynamic therapy (DPDT) relies on the interaction of light, photosensitisers and oxygen. Therefore, the &lsquo;dose&rsquo; of light that a patient receives during treatment is a clinically relevant quantity, with a minimum dose for effective treatment recommended in the literature. However, there are many different light measurement methods used in the published literature, which may lead to confusion surrounding reliable and traceable dose measurement in DPDT, and what the most appropriate method of light measurement in DPDT might be. Furthermore, for the majority of practitioners who do not carry out any formal dosimetry and for the patients receiving DPDT, building confidence in the evidence supporting this important treatment option is of key importance. This review seeks to clarify the methodology of DPDT and discusses the literature relating to DPDT dosimetry

A review of photodiagnostic investigations over 26 years:experience of the National Scottish Photobiology Service (1989-2015)

Background The Scottish Photobiology Service is the national referral pathway for patients with cutaneous photosensitivity diseases in Scotland. We reviewed the pattern of diagnosis of photosensitivity diseases and investigations performed between 1989 and 2015. Methods and Results Data were collected from the Photodiagnostic Database, annual reports and paper records. The total number of patients assessed each year was stable over the period studied (median 242 [range 231–266]), with most being new patients (median 69 [range 62–73]%). Monochromator phototesting was the most utilised investigation, although the use of provocation testing and photopatch testing has increased. The most common diagnosis was polymorphic light eruption, and there was a trend to increasing diagnosis of photoaggravated atopic eczema. Conclusions The pattern of diagnosis of photosensitivity diseases remains fairly stable in Scotland and we wish to emphasise the importance of this Scottish specialist service for patients with photosensitivity diseases and referrers

Potential harm to the skin from unfiltered krypton-chloride “Far-UVC”lamps, even below an occupational exposure limit

Ultraviolet-C (UVC) radiation can effectively inactivate pathogens on surfaces and in the air. Due to the potential for harm to skin and eyes, human exposure to UVC should be limited within the guideline exposure limits produced by the International Commission on Non-Ionising Radiation Protection (ICNIRP) or the American Conference of Governmental Industrial Hygienists (ACGIHs). Both organisations state an effective spectrally weighted limit of 3 mJ cm−2, although the spectral weighting factors of the two organisations diverged following a revision of the ACGIH guidelines in 2022. Using existing published human exposure data, the effective spectrally weighted radiant exposure was calculated for both unfiltered and filtered (to reduce UV emissions above 230 nm) krypton chloride (KrCl*) excimer lamps. The effective radiant exposure of the filtered KrCl* lamp was greater than 3 mJ cm−2 when applying ICNIRP or either of the revised ACGIH spectral weightings. This indicates that both guidelines are appropriately conservative for this specific lamp. However, the effective radiant exposure of the unfiltered KrCl* lamp was as low as 1 mJ cm−2 with the revised ACGIH weighting function that can be applied to the skin if the eyes are protected. Erythema has therefore been directly observed in a clinical study at an exposure within the revised ACGIH guideline limits. Extrapolating this information means that a mild sunburn could be induced in Fitzpatrick skin types I and II if that particular ACGIH weighting function were applied and an individual received an effective exposure of 3 mJ cm−2. Whilst it is improbable that such an effect would be seen in current deployment of KrCl* lamp technology, it does highlight the need for further research into skin sensitivity and irradiance–time reciprocity for UVC wavelengths.Publisher PDFPeer reviewe

Who attends out-of-hours general practice appointments? Analysis of a patient cohort accessing new out-of-hours units

Objectives This report describes the patients who used additional out-of-hours (OOH) appointments offered through a UK scheme intended to increase patient access to primary care by extending OOH provision. Design Cohort study and survey data. Setting OOH appointments offered in four units in one region in England (October 2015 to November 2016). Methods Unidentifiable data on all patients were abstracted from a bespoke appointment system and the responses to a patient opinion questionnaire about this service. Descriptive analysis of the appointment data was conducted. Multivariate analysis of the opinion survey data examined the characteristics of the patients who would have gone to the emergency department (ED) had the OOH appointments not been available. Results There were 24 448 appointments for 19 701 different patients resulting in 29 629 service outcomes. Women dominated the uptake and patients from the poorest fifth of the population used nearly 40% of appointments. The patient survey found OOH appointments were extremely popular—93% selecting ‘extremely likely’ or ‘likely’ to recommend the service. Multivariate analysis of patient opinion survey data on whether ED would have been an alternative to the OOH service found that men, young children, people of Asian heritage and the most deprived were more likely to have gone to ED without this service. Conclusions The users of the OOH service were substantially different from in-hours service users with a large proportion of children under age 5, and the poor, which support the idea that there may be unmet need as the poor have the least flexible working conditions. These results demonstrate the need for equality impact assessment in planning service improvements associated with policy implementation. It suggests that OOH need to take account of patients expectations about convenience of appointments and how patients use services for urgent care needs

Extreme Exposure to Filtered Far-UVC:A Case Study^†

Far-UVC devices are being commercially sold as "safe for humans" for the inactivation of SARS-CoV-2, without supporting human safety data. We felt there was a need for rapid proof-of-concept human self-exposure, to inform future controlled research and promote informed discussion. A Fitzpatrick Skin Type II individual exposed their inner forearms to large radiant exposures from a filtered Krypton-Chloride (KrCl) far-UVC system (SafeZoneUVC, Ushio Inc., Tokyo, Japan) with peak emission at 222 nm. No visible skin changes were observed at 1,500 mJcm-2, whereas skin yellowing that appeared immediately and resolved within 24 hours occurred with a 6,000 mJcm-2 exposure. No erythema was observed at any time point with exposures up to 18,000 mJcm-2. These results combined with Monte Carlo Radiative Transfer computer modelling suggest that filtering longer ultraviolet wavelengths is critical for the human skin safety of far-UVC devices. This work also contributes to growing arguments for the exploration of exposure limit expansion, which would subsequently enable faster inactivation of viruses.Publisher PDFPeer reviewe