While oxytocinase is known to exist in pregnancy serum and placenta, the present study describes the expression of the mRNA for this enzyme in a wide variety of other human tissues. Northern blot analysis was used to detect the mRNA, with a probe derived from a cDNA for oxytocinase/placental leucine aminopeptidase (P-LAP). Both the distribution and localization of immunoreactive oxytocinase/P-LAP protein have been determined immunohistochemically by use of an anti-P-LAP antibody in normal placental, fetal and adult tissues. In placental tissues, only syncytiotrophoblasts were stained positively. In both fetal and adult tissues, positive staining was obtained in vascular endothelial cells, gastrointestinal mucosal cells, epithelial cells of hepato-biliary, pancreato-biliary, bronchial-alveolar and renal tubular systems as well as islet cells of pancreas and neurons in the central nervous systems. Sweat-gland cells, seminal vesicles and prostate gland in the adult, as well as adipocytes and skeletal muscle cells in the fetus were also stained. The widespread distribution of P-LAP suggests its involvement in a variety of physiological events not restricted to the regulation of the amounts of bioactive peptides such as arginine vasopressin (AVP) and oxytocin (OT) in pregnancy. The presence of P-LAP in syncytiotrophoblasts supports the idea that P-LAP in pregnancy serum is derived from the placenta.

Xeroderma pigmentosum (XP) is a rare autosomal recessive hereditary disease caused by deficiency in repair of DNA lesions generated by ultraviolet radiation and other compounds. Patients with XP display pigmentary change and numerous skin cancers in sun‐exposed sites, and some patients show exaggerated severe sunburns even upon minimum sun exposure as well as neurological symptoms. We conducted a nationwide survey for XP since 1980. In Japan, the frequency of the XP complementation group A is the highest, followed by the variant type; while in the Western countries, those of groups C or D are the highest. Regarding skin cancers in XP, basal cell carcinoma was the most frequent cancer that afflicted patients with XP, followed by squamous cell carcinoma, and malignant melanoma. The frequency of these skin cancers in patients with XP has decreased in these 20 years, and the age of onset of developing skin cancers is higher than those previously observed, owing to early diagnosis and education to patients and care takers on strict prevention from sunlight for patients with XP. On the other hand, the effective therapy for neurological XP has not been established yet, and this needs to be done urgently.

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4-(4-Hydroxyphenyl)-2-butanol (rhododendrol, RD), a skin-whitening agent, was reported to cause skin depigmentation in some users, which is attributed to its cytotoxicity to melanocyte. It was reported that cytotoxicity to melanocyte is possibly mediated by oxidative stress in a tyrosinase activity-dependent manner. We examined the effect of UV radiation (UVR) on RD-induced melanocyte cytotoxicity as an additional aggravating factor. UVR enhanced RD-induced cytotoxicity in normal human epidermal melanocytes (NHEMs) via the induction of endoplasmic reticulum (ER) stress. Increased generation of intracellular reactive oxygen species (ROS) was detected. Pretreatment with N-acetyl cysteine (NAC), antioxidant and precursor of glutathione significantly attenuated ER stress-induced cytotoxicity in NHEMs treated with RD and UVR. Increase in cysteinyl-RD-catechol and RD-pheomelanin in NHEMs treated with RD and UVR suggested that, after UVR excitation, RD or RD metabolites are potent ROS-generating substances and that the tendency to produce RD-pheomelanin during melanogenesis amplifies ROS generation in melanocytes. Our results help to elucidate the development mechanisms of RD-induced leukoderma and provide information for innovation of safe skin-whitening compounds.

Combined cholinergic urticaria and cold-induced cholinergic urticaria with acquired idiopathic generalized anhidrosis Dear EditorCholinergic urticaria (CU) was first described in 1924 by Duke. 1 It is characterized by pinpoint-sized, highly pruritic wheals with surrounding erythema that occur after sweating. In cold urticaria, patients experience pruritus and wheals within a few minutes after exposure to the cold. Idiopathic cold contact urticaria is the most common, whereas other types are rare. Cold-induced CU is an unusual disorder characterized by small punctate urticarial lesions induced by systemic cold challenge rather than the local cold challenge. 2 Some rare cases of combined CU and cold-induced CU have been reported. 3,4 Acquired idiopathic generalized anhidrosis (AIGA) is a rare disorder with widespread loss of sweating caused by isolated failure of sympathetic sudomotor activity in the absence of other detectable abnormalities. AIGA is sometimes accompanied by CU. Here, we report the first case of combined CU and cold-induced CU accompanied with AIGA.A 19-year-old female had a three-year history of the development of punctate wheals during physical exercise, bathing, emotional stress, and chilling of the body upon systemic exposure to the cold. She presented with eyelid oedema, lip oedema and dyspnea during sweating. In a previous medical facility, her symptoms were resistant to H 1 antagonists, H 2 antagonists and oral corticosteroids.Laboratory tests demonstrated normal complete blood cell counts except for slight elevation of circulating eosinophils (7.6%) and normal biochemical findings except for total IgE levels (594.3 mg/dl). Normal levels of complement excluded hereditary angioedema. The patient also suffered discomfort, heat stroke and hypohidrosis in hot environments. She had to move house to avoid heat in the extremely hot and humid Japanese summer. CU was confirmed by the development of numerous small wheals and angioedema 15 min after an exercise test on a treadmill ( Fig. 1A and B). Simultaneously, we tried to collect sweat from her forearm after exercise but no sweat was collected, suggesting that she had exhibited hypohidrosis. Her clinical history showed systemic exposure to cold induced punctate wheals similar to those seen in CU. Hence, a systemic cold challenge test (sitting in a room at 4 C for 7 min) was undertaken. 2 Small punctate urticarial lesions with haloes were seen on areas covered by clothing, as well as under clothing uncovered after the test (Fig. 1C). Other accompanied symptoms such as fever and arthralgia were not observed, suggesting that familial cold autoinflammatory syndorome (cryopyrinassociated periodic syndrome) was excluded. Thus, she was diagnosed as having combined CU and cold-induced CU.

Food-dependent exercise-induced anaphylaxis (FDEIA) is a severe systemic syndrome induced by physical exercise after ingesting causative food. Aspirin is a well-known trigger for anaphylaxis in patients with FDEIA. Possible mechanisms by which symptoms are aggravated by aspirin include enhanced antigen absorption and mast cell activation. The aim of this study was to determine whether aspirin intake has an influence on mast cell/basophil activation in patients with FDEIA. Provocation tests revealed that adding aspirin to the causative food challenge in 7 of 9 (77.8%) patients with FDEIA provoked symptoms. In most cases, pretreatment with aspirin did not enhance skin tests (71.4%) or histamine release tests (88.9%) with food allergen challenges. The study confirms that histamine release and skin prick tests can be adjunctive tools for diagnosing FDEIA. In addition, our results suggest that exacerbation of FDEIA symptoms by aspirin is not mediated by direct effects of aspirin on mast cell/basophil activation.

Dakup P, Gaddameedhi S. Impact of the circadian clock on UV-Induced DNA damage response and photocarcinogenesis. Photochem Photobiol 2017;93:296e303. Decraene D, Agostinis P, Pupe A, de Haes P, Garmyn M. Acute response of human skin to solar radiation: regulation and function of the p53 protein. J Photochem Photobiol B 2001;63: 78e83. Diffey BL, Oliver RJ, Farr PM. A portable instrument for quantifying erythema induced by ultraviolet radiation. Br J Dermatol 1984;111: 663e72. Fitzpatrick TB. The validity and practicality of sunreactive skin types I through VI. Arch Dermatol 1988;124:869e71.

Ultraviolet (UV) radiation induces a variety of biological effects, including DNA damage response and cell signaling pathways. We performed transcriptome analysis using microarray in human primary cultured fibroblasts irradiated with UV-C (0.5 or 5 J/m2) and harvested at 4 or 12 h following UV exposure. All transcript data were analyzed by comparison with the corresponding results in non-irradiated (control) cells. The number of genes with significantly altered expression (≥2-fold difference relative to the control) is higher in the sample irradiated with high dose of UV, suggesting that gene expression was UV dose-dependent. Pathway analysis on the upregulated genes at 12 h indicates that the expression of some cell cycle-related genes was predominantly induced irrespective of UV-dose. Interestingly, almost all the genes with significant altered expression were cell cycle-related genes designated as ‘Mitotic Genes’, which function in the spindle assembly checkpoint. Therefore, even a low dose of UV could affect the transcriptional profile.