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BackgroundUltraviolet (UV) irradiation induces not only local damage targeting external organs but also systemic damage targeting internal organs. Skin erythema, erosion and ulcers are representative types of local damage induced by UV irradiation (1,2). Minimum erythema dose (MED) is used as a worldwide standard biomarker for UV-mediated local damage considering individual skin characteristics (3). Immunosuppression of contact hypersensitivity (CHS) is a representative type of UV-mediated systemic damage (4).UV-mediated biological effects have been generally evaluated by UV dose (mJ/cm 2 ) calculated by multiplication of UV intensity (mW/cm 2 ) and UV exposure time (seconds). As UV dose is a worldwide standard for irradiation level in most studies in life and medical science fields, a constant UV dose is expected to present constant biological effects regardless of the intensity and exposure time. To our knowledge, however, there has been no study in which biological effects of a constant dose for single UVB irradiation with different intensities and exposure times from various angles were compared in vivo. Questions addressedThe aim of this work was to validate the biological effects of a constant dose for single UVB irradiation with different intensities and exposure times with comparison of UVB-mediated local damage and systemic damage in vivo. Experimental designHairless mice (5) were used to avoid the effect of depilation on levels of erythema, ulcer and 8-OHdG in the skin. UVB irradiation was performed according to previously reported methods (6). Results and DiscussionIn this study, mice were subjected to single ultraviolet B (UVB) irradiation with three kinds of constant dose (187.5 mJ/cm 2 ) including 0.015 mW/cm 2 9 12500 s (weak intensity and long time), 0.15 mW/cm 2 9 1250 s (intermediate intensity and intermediate time) and 1.5 mW/cm 2 9 125 s (strong intensity and short time). UVB-mediated local (erythema and ulcer) and systemic (immunosuppression) effects were compared among the groups of mice subjected to UVB irradiation at a constant dose with the different intensities and exposure times. Macroscopic appearances of dorsal skin erythema at 4 h after starting UVB irradiation were comparable among the group of mice subjected to three kinds of constant-dose UVB irradiation with different intensities and exposure times (Fig. 1a,b). Constantdose UVB irradiation resulted in comparable kinetics of skin erythema levels (a* values) objectively evaluated using a reflectance spectrophotometer despite the differences in intensity and exposure time (Fig. 1c). These results of constant skin damage (erythema) induced by a constant UV dose suggest the reason why UV dose is a global standard unit showing UV-mediated biological effects. However, the macroscopically detectable skin ulcer area at 3 days Figure 1. Level of erythema induced by constant-dose UVB with different intensities and exposed times. Three kinds of UVB irradiation at a constant dose (187.5 mJ/cm 2 ) with intensities of 0.015, 0.15 and 1.5 mW/cm...

Background: High-dose methotrexate (HD-MTX) therapy is widely implemented for leukemia, osteosarcoma, and lymphoma. Although various measures have been taken to avoid toxicity from high serum MTX concentrations, there are many cases of delayed elimination of MTX. Objective: We suspected that delayed elimination of serum MTX was caused by unknown interactions between MTX and concomitant drugs. Methods: Concerning concomitant drugs in the case of delayed elimination of MTX, we performed screening tests in 35 patients who had undergone HD-MTX therapy. We then investigated the risk factors for delayed MTX elimination in 94 patients with leukemia, lymphoma, or osteosarcoma retrospectively. Results: The percentages of concomitant use of Stronger Neo-Minophagen C (SNMC), a glycyrrhizin preparation, and vincristine were higher in the delayed group. The percentage of delayed MTX elimination in patients receiving HD-MTX therapy was 41%. Multiple logistic regression analysis revealed that the concomitant use of SNMC solely was a significant risk factor for delayed MTX (odds ratio = 12.20; 95% CI = 1.06-139.84). Conclusion and Relevance: Concomitant use of SNMC was shown to be related to delayed elimination of serum MTX, and our results suggested a previously unknown drug-drug interaction between MTX and SNMC.

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