Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.

BACKGROUND: Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). METHODS: The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. KEY RESULTS: Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. CONCLUSIONS & INFERENCES: Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.

Isolation of lactic acid bacteria from kuruma shrimp (Marsupenaeus japonicus) intestine and assessment of immunomodulatory role of a selected strain as probiotic.

Fifty-one lactic acid bacteria (LAB) strains were isolated and identified based on 16S ribosomal DNA sequence from the intestinal tracts of 142 kuruma shrimps (Marsupenaeus japonicus) collected from Kanmon Strait, Fukuoka and Tachibana Bay, Nagasaki, Japan. Cellular immunomodulatory function of 51 isolated LAB strains was assessed by measuring the level of interferon (IFN)-γ induction in mouse spleen cell culture. The strain Lactococcus lactis D1813 exhibited the highest amount of IFN-γ production and also bactericidal activity and was selected for testing its immunomodulatory role as a probiotic in kuruma shrimp. We also assessed the effect of dietary incorporation of this probiotic on resistance to Vibrio penaeicida infection in the kuruma shrimp. Our results demonstrate that probiotic L. lactis D1813-containing diet-fed (105 cfu g⁻¹) shrimps displayed a significant up-regulation of lysozyme gene expressions in the intestine and hepatopancreas. However, insignificantly higher expression of anti-lipopolysaccharide factor, super oxide dismutase, prophenoloxidase, and toll-like receptor 1 was recorded in the intestine of shrimps fed the probiotic diet. Moreover, significantly increased (P < 0.01) resistance to the bacterial pathogen in term of better post-infection survival (61.7 %) was observed in the shrimps fed with the probiotic-incorporated diet compared with the control diet-fed group (28.3 %). The present study indicates the immunomodulatory role of the LAB L. lactis D1813 on the kuruma shrimp immune system and supports its potential use as an effective probiotic in shrimp aquaculture.

Positional relationship between recurrent intracerebral hemorrhage/lacunar infarction and previously detected microbleeds.

BACKGROUND AND PURPOSE: Although MBs, ICH, and LI are secondary to cerebral microangiopathy, it remains unclear whether the location of subsequent ICH/LI corresponds to the previous location of MBs. We performed this study to clarify the positional relationship between recurrent ICH/LI and previously detected MBs. MATERIALS AND METHODS: We evaluated patients with recurrent ICH/LI who had MBs, as shown on prior T2*-weighted MR imaging. We assessed retrospectively whether the location of recurrent ICH/LI corresponded to that of the prior MB. Patients with ICH were divided into the deep ICH group and the lobar ICH group, and the positional relationship between hematoma and previously detected MBs was evaluated. RESULTS: A total of 55 patients, including 34 with recurrent ICH and 21 with recurrent LI were evaluated. Although the location of the LI corresponded to prior MBs in only 1 patient (4.8%), the location of ICH corresponded to prior locations of MBs in 21 patients (61.8%) (OR, 32.3; 95% CI, 3.86-270.3; P < .001). Among the patients with ICH, the correspondence ratio was higher in the deep ICH group (19 of 24 patients, 79.2%) than in the lobar ICH group (2 of 10 patients, 20%) (OR, 15.2; 95% CI, 2.42-95.3; P < .002). CONCLUSIONS: The close positional association between recurrent ICH and prior MBs suggests that MBs represent hemorrhage-prone microangiopathy. In addition, different correspondence ratios between the deep ICH group and the lobar ICH group may be attributable to their different pathogenesis.

The prevalence and risk factors of post-inflammatory hyperpigmentation after fractional resurfacing in Asians.

BACKGROUND: Ablative laser resurfacing is considered to be the main therapeutic option for the treatment of wrinkles and acne scarring. However, in Asians, post-inflammatory hyperpigmentation (PIH) is a common adverse effect of laser resurfacing. Fractional resurfacing is a new concept of skin rejuvenation whereby zones of micro thermal injury are generated in the skin with the use of a 1,540-nm laser. The risk and prevalence of hyperpigmentation in dark-skinned patients using this approach have not been studied. OBJECTIVE: To assess the prevalence and risk factors of PIH that is associated with the use of fractional resurfacing in Asians. METHOD: A retrospective study of 37 Chinese patients who were treated with fractional resurfacing for acne scarring, skin rejuvenation, and pigmentation was carried out. In all of the cases, pre- and post-treatment clinical photographs (from standardized and cross-polarized views) were taken using the Canfield CR system. Two independent observers assessed the photographs. A prospective study of treatments of nine different density and energy levels that were applied to the forearms of 18 volunteers was also performed. Clinical photographs were assessed pre- and post-treatment for evidence of PIH. RESULT: In the retrospective study, 119 treatment sessions were performed. Sixty-eight treatment sessions were high energy, low density; 51 sessions were low energy, high density. Patients who underwent a high energy but low-density treatment (range of energy 7-20 mJ; average energy 16.3 mJ, 1,000 MTZ) were associated with a lower prevalence of generalized PIH (7.1% vs. 12.4%) than those who underwent a low energy but high-density (range of energy 6-12 mJ; average energy 8.2 mJ, 2,000 MTZ) treatment. However, the difference was not statistically significant. Localized PIH occurred in the peri-oral area among patients who did not receive air cooling as an adjunctive therapy. CONCLUSION: Both the density and energy of the treatment determines the risk of PIH in dark-skinned patients. Density may be of more important but further studies are necessary to determine this. Cooling to prevent bulk tissue heating is also important, especially in small anatomical areas. By using adequate parameters, the risk of PIH in dark-skinned patients can be significantly reduced.

Effect of ecabet sodium enema on mildly to moderately active ulcerative proctosigmoiditis: an open-label study.

OBJECTIVES: Ecabet sodium (ES), a nonabsorbable antigastric ulcer agent, has been shown to adhere to the region of an ulcer. It topically enhances gastric mucosal defensive factors such as the endogenous prostaglandins, capsaicin-sensitive sensory nerves, nitric oxide, and mucin. All of these mucosal defensive factors play an important role in maintaining the mucosal integrity of the colon and rectum. Therefore, we investigated the effect of ES in patients with mildly to moderately active ulcerative proctosigmoiditis. METHODS: In an open-label study, seven patients with mildly to moderately active ulcerative colitis (UC) who had an inflamed mucosa in the rectum and/or sigmoid and were resistant to 4-wk topical and systemic standard treatment were treated with an ES enema b.i.d. for 14 days. The enema consisted of ES (1 g) and tepid water (20 or 50 ml). These patients were assessed by the Clinical Activity Index, colonoscopically, and histologically before and after the ES therapy. The ES therapy was started after obtaining informed consent from the patients. RESULTS: Six of the seven patients responded to therapy and achieved clinical, endoscopic, and histological remissions. One patient was withdrawn because of increased stool frequency. All six patients who completed the study showed a significant change in the mean Clinical Activity Index score from 5.3+/-1.4 (mean +/- SD) to 0.5+/-0.8 (p < 0.05), in the colonoscopic score from 3.0+/-0.9 to 0.8+/-0.4 (p < 0.05), and in the histological score from 2.7+/-0.5 to 0.5+/-0.6 (p < 0.05), and achieved remission at the end of the study. There were no side effects attributable to the ES therapy. Five of the six patients are still in clinical remission after a median follow-up period of 5 months. CONCLUSIONS: The ES enemas proved to be a safe and potentially useful adjuvant therapy currently available for treating patients with mildly to moderately active ulcerative proctosigmoiditis. A controlled study is necessary to confirm our results.

Purification and cloning of pierisin-2, an apoptosis-inducing protein from the cabbage butterfly, Pieris brassicae.

The cabbage butterfly Pieris rapae contains a strong apoptosis-inducing substance, pierisin, against human cancer cell lines, which is thought to act via ADP-ribosylation. Here we report the purification and cloning of an apoptosis-inducing substance, designated as pierisin-2, from another cabbage butterfly, Pieris brassicae. Pierisin-2 was purified from pupae by sequential chromatography and its cytotoxic and apoptosis-inducing activities to various cancer cells were similar to those of pierisin, designated as pierisin-1, from P. rapae. cDNA cloning of pierisin-2 was performed on the basis of the partial amino-acid sequence. The nucleotide sequence indicated that the cDNA encodes an 850-amino-acid protein with a calculated molecular mass of 97 986. The deduced amino-acid sequence of pierisin-2 was 91% identical with that of pierisin-1. In vitro expressed protein in the reticulocyte lysate exhibited apoptosis-inducing activities against human gastric carcinoma TMK-1 and cervical carcinoma HeLa cells, similar to the purified native pierisin-2 from the pupae. Pierisin-2 shows regional sequence similarities with certain ADP-ribosylating toxins such as the A-subunit of cholera toxin. The results from site-directed mutagenesis at Glu165, a conserved residue among ADP-ribosylating enzymes necessary for NAD binding, and from experiments with ADP-ribosylating enzyme inhibitors suggested that pierisin-2 could be considered as an ADP-ribosylating toxin like pierisin-1.

The cytoprotective role of lipopolysaccharide-induced nitric oxide against liver damage during early phase of endotoxemia in rats.

Lipopolysaccharide (LPS)-induced endotoxemia produces nitric oxide (NO); however, the role of the NO during endotoxemia is still controversial. The aim of this study was to investigate a role of LPS-induced NO during the early phase of endotoxemia. Wistar rats were intraperitoneally injected with saline or LPS at various doses (0.001, 0.01, or 5 mg/kg), and intra-abdominal NO concentration was determined by chemiluminescence before and after LPS administration at indicated times (1, 2, 6, 10, and 18 h). Serum aspartate aminotransferase and alanine aminotransferase levels were determined and histological examination was performed 10 h after LPS administration to assess liver damage. N(G)-nitro-L-arginine-methyl ester (L-NAME), a nonselective inhibitor of NO synthase, was used to investigate the possible roles of NO during LPS-induced endotoxemia. The intra-abdominal NO concentration was elevated within 2 h and reached a maximal level at 10 h after low doses of LPS injection (0.001 and 0.01 mg/kg) while liver damage was not observed. After high-dose LPS (5 mg/kg) administration, liver damage was observed and intra-abdominal NO was elevated continuously until 18 h. A time course study revealed very similar patterns of intra-abdominal NO increase after the three different dose of LPS at each times points during the first 10 h. Pretreatment of L-NAME inhibited the intra-abdominal NO release and aggravated the liver damage caused by low doses (0.001 and 0.01 mg/kg) of LPS as well as high dose (5 mg/kg) of LPS. Therefore, NO, released during the first 10 h after LPS injection, may play a cytoprotective role in the liver.

Effects of arctiin on PhIP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MeIQx-induced hepatocarcinogenesis in male F344 rats.

Chemopreventive effects of arctiin, a lignan isolated from Arctium lappa (burdock) seeds, on the initiation or post initiation period of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induced mammary carcinogenesis in female rats and on 2-amino-3, 8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-associated hepatocarcinogenesis in male rats were examined. In experiment 1, female Sprague-Dawley (SD) rats were given intragastric doses of 100 mg/kg body wt of PhIP once a week for 8 weeks as initiation. Groups of 20 rats each were treated with 0.2 or 0.02% arctiin during or after PhIP initiation. Control rats were fed 0.2 or 0.02% arctiin, or basal diet alone during the experimental period. Animals were killed at the end of week 48. Although the incidence of mammary carcinomas did not significantly differ among the PhIP-treated groups, multiplicity was significantly decreased in rats given 0.2 (0.7+/-0.7, P<0.05) or 0.02% (1.0+/-1.1, P<0.05) arctiin after PhIP initiation as compared with the PhIP alone controls (2.1+/-2.5). The average number of colon aberrant crypt foci was also significantly decreased in these two groups. Pancreas acidophilic foci were induced in PhIP treated animals with slight decrease in the multiplicity with arctiin during the initiation phase. For liver carcinogenesis, groups of 15 male F344 rats were given a single intraperitoneal injection of diethylnitrosamine (DEN) and starting 2 weeks later, they were administered 0.03% MeIQx in the diet, MeIQx together with 0.5% arctiin, 0.1% arctiin or basal diet for 6 weeks. They were subjected to two-third partial hepatectomy 3 weeks after DEN initiation and killed at the end of week 8 for glutathione S-transferase placental form (GST-P) immunohistochemistry. The numbers and areas of preneoplastic GST-P positive foci were elevated by the treatment with MeIQx, and further increased by the simultaneous treatment with arctiin. These results indicate that arctiin has a protective effect on PhIP-induced carcinogenesis particularly in the mammary gland in the promotion period. On the other hand, it may have a weak co-carcinogenic influence on MeIQx-induced hepatocarcinogenesis. In addition, the results suggested that PhIP is a weak pancreatic carcinogen in female SD rats, targeting acinar cells.

Molecular cloning of an apoptosis-inducing protein, pierisin, from cabbage butterfly: possible involvement of ADP-ribosylation in its activity.

We have previously reported that the cabbage butterfly, Pieris rapae, contains a 98-kDa protein, named pierisin, that induces apoptosis in a variety of human cancer cell lines. In the present study, sequencing and cloning of a cDNA encoding pierisin was accomplished. PCR-direct sequencing showed that the gene encodes an 850-amino acid protein with a calculated molecular weight of 98,081. An intact clone at the amino acid level encompassing the entire coding region was obtained by recombination of two independent clones, and the molecular mass of its in vitro expressed protein was about 100 kDa on SDS/PAGE, the same as that of purified native pierisin. The expressed protein induced apoptosis in human gastric carcinoma TMK-1 and cervical carcinoma HeLa cells, like the native protein, indicating functional activity. The deduced amino acid sequence of pierisin showed 32% homology with a 100-kDa mosquitocidal toxin from Bacillus sphaericus SSII-1. In addition, pierisin showed regional sequence similarities with ADP-ribosylating toxins, such as the A subunit of cholera toxin. A glutamic acid residue at the putative NAD-binding site, conserved in all ADP-ribosylating toxins, was also found in pierisin. Substitution of another amino acid for glutamic acid 165 resulted in a great decrease in cytotoxicity and induction of apoptosis. Moreover, inhibitors of ADP-ribosylating enzymes reduced pierisin-induced apoptosis. These results suggest that the apoptosis-inducing protein pierisin might possess ADP-ribosylation activity that leads to apoptosis of the cells.

Adenosquamous carcinoma of the rectum showing endocrine-cell differentiation: report of a case.

PURPOSE: Previous records of adenosquamous carcinomas with endocrinologic features rarely have been reported. Although the disease behaves in an extremely aggressive manner, chemotherapy after surgery has never been proposed. We used regional chemotherapy for treatment of unresectable liver metastases. METHODS: Hartmann colostomy was performed and 5-fluorouracil was infused into the hepatic artery for 15 weeks after the operation. RESULTS: Multiple liver metastases were present at the initial operation. Three months after the start of the chemotherapy, computed tomography showed that metastatic tumors in the liver had disappeared. The patient survived 18 months after the initial operation. CONCLUSION: This case report describes the first successful treatment with adjuvant regional chemotherapy of a patient who had an adenosquamous carcinoma with endocrine-cell differentiation in the rectum and liver metastases.

[Peripheral 5-FU blood concentration after high-dose injection into the hepatic artery: potential preventive effect on extrahepatic metastatic foci].

To clarify the effect of high-dose 5-FU injection into the hepatic artery (1,000 mg/m2 weekly) on liver metastases of colorectal cancer, the peripheral venous 5-FU concentration was measured in two groups of patients, one which had undergone hepatectomy and the other which had not. The area under the concentration-time curve (AUC) was calculated and the preventive effect of 5-FU on extrahepatic lesions was examined. The peripheral venous 5-FU concentration and AUC were higher in patients who received the drug via the hepatic artery after hepatectomy, and 5-FU was effective for the prevention of extrahepatic lesions as well as against recurrence in the residual liver.

Effect of magnetite on the hematocrit value in exsanguinated rats.

Magnetite prepared by an enzyme-dependent reaction gradually released iron ion into the acidic-to-neutral buffer solution. A preparatory experiment was performed to examine the efficiency of magnetite as an iron supplement. Feeding exsanguinated rats with being magnetite resulted in the hematocrit value being recovered without any serious adverse effect on the digestive organs.

Functional characterization and localization of a cardiac-type inwardly rectifying K+ channel.

We cloned inwardly rectifying K+ channel cDNAs from porcine, rat and human, which were structurally almost identical with recently reported CIR(cKATP-1). The expression of CIR alone was low and unstable in Xenopus oocytes. The CIR/GIRK1 co-expression showed an increased current amplitude. Both the CIR and CIR/GIRK1 currents increased by coexpressing G beta gamma. The CIR and CIR/GIRK1 currents displayed two qualitative differences. (1) The conductance of the CIR channel did not saturate, but that of the CIR/GIRK1 channel showed saturation at hyperpolarized potential. (2) The CIR current showed instantaneous activation upon hyperpolarization, whereas the CIR/GIRK1 current exhibited slow activation, which was fitted by the sum of two exponentials. The CIR/GIRK1 current was also different from the GIRK1 current. The activation of the CIR/GIRK1 current was approximately ten times faster than that of the GIRK1 current. The increase in current amplitude and the qualitative differences imply the formation of functional heteromultimer. The CIR/GIRK1 channel showed differences from the native muscarinic K+ channel in that the basal level before m2 receptor activation is significantly large, and that the activation kinetics are much faster. Using anti-CIR antiserum, the CIR was detected in myocardial cells of the atrium and the ventricular subendocardial layer, and in the cardiac ganglion.

Effects of ultraviolet-B and PUVA on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity in mouse skin.

Ultraviolet-B and PUVA share several biological events with phorbol ester tumor promoters. The effects of ultraviolet-B irradiation and topical PUVA treatment on ornithine decarboxylase activity, DNA synthesis, and protein kinase C activity, which are known to be induced or activated by phorbol ester tumor promoter, were investigated in hairless mouse skin. Ornithine decarboxylase activity was remarkably enhanced by ultraviolet-B and PUVA. Although PUVA did not affect DNA synthesis significantly, ultraviolet-B stimulated epidermal DNA synthesis approximately 5-fold over control values at 48 h. However, unexpectedly, neither cytosolic nor membrane-bound protein kinase C activity showed any change during the 2 h after either treatment. These results suggest that the protein kinase C system is not involved in the initial signal transduction system of ultraviolet-B or PUVA, unlike the case with phorbol ester tumor promoter.

[Effects of Gomishi and Shosaiko-to on lipid peroxidation of rat brain].

Gomishi and Shosaiko-to were administered to the rats at a dose of 10-100 mg/kg daily for 2 weeks, and their effects on lipid peroxidation of rat brain were compared with that of alpha-tocopherol. Administration of Gomishi and Shosaiko-to showed almost the same suppressive action on the lipid peroxidation. Gomishi and Shosaiko-to exhibited a radical-trapping action on a stable free radical, 1, 1-diphenyl-2-picrylhydrazyl (DPPH), which was estimated photometrically. The effects of Gomishi or Shosaiko-to at concentrations of 10(-3) to 10(-5)g/ml on lipid peroxidation of rat brain homogenates were investigated. The lipid peroxidation was inhibited by the addition of these drugs, and the suppressive effect was also dependent on the concentration. These suppressive effects with Shosaiko-to were stronger than those of Gomishi. These results suggest that the radical trapping action of Gomishi or Shosaiko-to is the likely mechanism suppressing brain lipid peroxidation; Particularly, the suppressive effect on the brain's lipid peroxidation by Shosaiko-to is at least in part due to its radical trapping action and inhibition of O2-. production.

Effects of butylated hydroxyanisole on ornithine decarboxylase activity induced by ultraviolet-B and PUVA in mouse skin.

The effects of butylated hydroxyanisole (BHA), a representative phenolic antioxidant, on the activity of ornithine decarboxylase (ODC, an indicator of tumor promotion and epidermal hyperproliferation) induced by ultraviolet-B (UVB) or PUVA in mouse skin were investigated. By topical application of BHA (55 mumol), PUVA-induced ODC activity was suppressed by about 60% at both 12 h and 24 h after treatment. In contrast, BHA failed to suppress UVB-induced ODC activity in mouse skin. These results suggest that the induction of ODC activity by UVB or PUVA is mediated by different pathways.

[Effects of kamikihi-to, a Chinese traditional medicine, on various cholinergic biochemical markers in the brains of aged rats].

The effects of kamikihi-to (EK-49) on various cholinergic biochemical markers, muscarinic receptors, acetylcholinesterase (AChE), choline acetyltransferase (CAT) and choline uptake, in aged rat brains were examined. Administration of kamikihi-to in daily doses of 200 mg/kg, p.o. for 4 weeks to aged rats (24-months-old) significantly increased the density of muscarinic receptors (Bmax) for 3H-QNB (quinuclidinyl benzilate), but did not affect the apparent dissociation constant (Kd). After repeated administration of kamikihi-to to aged rats, AChE activity and choline uptake were not significantly different in the kamikihi-to treated aged rats as compared with the control aged rats. However, administration of kamikihi-to for 4 weeks resulted in a significant increase in Vmax values of CAT in kamikihi-to treated aged rats as compared with those of the control rats. These results indicate that long-term treatment with kamikihi-to enhances both the Bmax and Vmax for QNB binding and CAT activity in aged rats, respectively.

Differential effects of cyclosporine A on ornithine decarboxylase activity induced by ultraviolet-B and PUVA in mouse skin.

The inhibitory effect of cyclosporine A (CsA) on the activity of ornithine decarboxylase (ODC) induced by phorbol ester tumor promoter has been reported. In the present study, the effects of CsA on ODC activity induced by ultraviolet-B (UV-B) and PUVA in the skin of the SKH/hr 1 hairless mouse were investigated. Topical application of CsA (1.7 mumol) to the dorsal skin irradiated with 50 mJ/cm2 UV-B did not remarkably change ODC activity. On the other hand, if CsA was applied simultaneously with 3 J/cm2 UV-A 1 h after treatment with 0.3% 8-methoxypsoralen, PUVA-induced ODC activity was suppressed by about 60% at 12 and 24 h after UV-A irradiation. In the dot blotting analysis of ODC-specific mRNA level, a significant but slight decrease in ODC mRNA level (about 20% inhibition) was observed in the PUVA-treated group compared with the control group (vehicle and UV-A). The inhibition of PUVA-induced ODC activity by CsA may have been caused in part by the decrease in ODC mRNA level and in part by a post-transcriptional regulation mechanism.

A case of prurigo pigmentosa considered to be contact allergy to chromium in an acupuncture needle.

A 53-year-old male developed prurigo pigmentosa on his back, after undergoing acupuncture for 3 years. The eruptions were ceased on discontinuing the therapy but recurred with its resumption. The acupuncture needle contained 18.12% chromium. Erythema was induced by patch testing with potassium dichromate, and a flare-up was observed in the area of the patch test on resumption of acupuncture. We consider that the eruptions were induced by contact allergy to the chromium component of the acupuncture needles.

Effect of PUVA radiation on anaphylactic histamine release from rat dermal tissues.

We have devised a new in vitro model of type I cutaneous anaphylaxis. Male albino rats were sensitized with DNP-Ascaris. Abdominal skin was shaved, and thin, split-thickness slices of skin were cut with a dermatome. The dermis was excised and cut into 100 mg pieces. The dermal tissue was incubated with antigen in Tyrode's solution for 30 min at 37 degrees C. Antigen-induced histamine release from dermal tissue was measured fluorimetrically. Using this system, we measured histamine release from PUVA-irradiated and non-irradiated dermal tissues. A single PUVA irradiation inhibited type I cutaneous anaphylaxis, but did not affect spontaneous histamine release or total dermal histamine. Our model is considered to be useful for investigation of the mechanism of suppression of type I cutaneous anaphylaxis by PUVA.