Biphasic increase in scratching behaviour induced by topical application of Dermatophagoides farinae extract in NC/Nga mice.

Atopic dermatitis (AD) is a chronic inflammatory skin disease accompanied by severe itching and eczematous lesion. In this study, we applied an ointment containing Dermatophagoides farinae body (Dfb) extract repeatedly on the dorsal skin of NC/Nga mice with barrier disruption to investigate the characteristics of this murine model of human AD. Following repeated topical application of Dfb ointment twice weekly for 2 weeks, the dermatitis score increased gradually, accompanied by an elevation of total immunoglobulin E level in plasma. Topical application of Dfb ointment also caused epidermal hyperplasia and accumulation of inflammatory cells in the lesional skin and increased expression of T-helper (Th) 1/Th2/Th17 cytokines in axillary lymph node cells. Furthermore, increased sprouting of intraepidermal nerve fibres was observed with an increase in the content of nerve growth factor and decrease in that of semaphorin 3A in the lesional skin. These findings suggest that the characteristics in this model were similar to those observed in patients with AD. Interestingly, it was observed for the first time that scratching behaviour increased in a biphasic fashion by topical application of Dfb ointment in addition to an increase in spontaneous scratching behaviour in this model. It is also suggested that further clarifying the underlying mechanisms of scratching behaviour in this model leads not only to elucidating the pathogenesis of AD but also to discovering novel therapeutic drugs for AD.

The simulation of long-range transport of ¹³7Cs from East Asia to Japan in 2002 and 2006.

To evaluate the quantities of ¹³7Cs from past nuclear tests being transported to and deposited in Japan by naturally-occurring phenomena, the authors developed long-range transport models for ¹³7Cs considering Asian dust. The simulation using these models backed the observed recent increase of ¹³7Cs deposition along the coast of the Sea of Japan in early spring. For the sake of public safety, it is vital to ascertain whether an increase of radioactive deposition is caused by natural phenomena or a nuclear accident. The observations in recent years have suggested that dust and soil containing ¹³7Cs is transported from the regions around Inner Mongolia to Japan by the wind. In this paper, using observation data from the early spring of 2002 and 2006, the authors have found good agreement between the simulations and the measurements. The simulations reproduced the entrainment of ¹³7Cs and subsequent transport to Japan caused by strong winds associated with low pressure areas around the Inner Mongolian grasslands. The most likely cause of high-level ¹³7Cs deposition over northern Japan during March 2002 was ¹³7Cs associated with particles transported at low-altitude (1 km) and subjected to precipitation on the 22nd to 24th.

Decrease in rat internal anal pressure with the use of a topical ointment containing a killed E. coli culture suspension.

OBJECTIVES: The present study aimed to clarify the mechanisms of a topical ointment containing an Escherichia coli culture suspension and hydrocortisone (Posterisan forte, BCS+HC) in lowering internal anal pressure in conscious rats. MATERIALS AND METHODS: Internal anal pressure was measured using a water-filled balloon system for consecutive 10-min periods. The changes in pressure were evaluated by the number of peaks above 20 mmH2O between 1 and 8 min of recording. RESULTS: Topical intra-anal application of BCS+HC ointment (160 mg/kg) significantly decreased the internal anal pressure at 3 h after the application. Thereafter, this effect reached a maximum decrease at 4 h and lasted until 6 h. BCS+HC ointment (40, 80, and 160 mg/kg) lowered the internal anal pressure at 4-5 h in a dose-dependent manner. The maximum decrease ratios of the ointment and corresponding hydrocortisone-free ointment (Posterisan, BCS) were 32.6+/-12.7 and 25.7+/-9.0%, respectively, revealing significant pressure-lowering effects compared with a placebo (P<0.05). In contrast, the same ointment containing hydrocortisone alone and other ointments containing steroids or local anesthetics had no effects. DISCUSSION: Treatment with 1 mg/kg NG-nitro-L-arginine methyl ester HCl (L-NAME), a non-selective nitric oxide synthase inhibitor, significantly suppressed the effect of BCS+HC ointment (160 mg/kg) in lowering the internal anal pressure. Furthermore, BCS+HC ointment (160 mg/kg) significantly lowered capsaicin-induced high internal anal pressure compared to a placebo. CONCLUSION: These findings suggest that BCS+HC and BCS ointments containing an E. coli culture suspension significantly lowered the internal anal pressure due to endogenous nitric oxide production in conscious rats.

Effect of heparinoid on the production of tissue inhibitor of metalloproteinases (TIMP)-3 in rheumatoid synovial fibroblasts.

Heparinoid is one of the major contents of Mobilat widely used as an antirheumatic drug. To clarify the precise mechanisms of the antirheumatic effect of heparinoid, we investigated its effects on the production of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) from rheumatoid synovial fibroblasts stimulated (or not) with interleukin-1 alpha (IL-1alpha) at 100 units mL(-1). The expression of TIMP-3 mRNA was also investigated in a similar manner. The production of both MMPs and TIMPs and the expression of TIMP-3 mRNA were investigated by western-blot analysis and northern-blot hybridization, respectively. Under the stimulation of IL-1alpha, heparinoid increased the production of TIMP-3 in a concentration-dependent manner, but not TIMP-1, TIMP-2, MMP-1 or MMP-3. Heparinoid did not affect the expression of TIMP-3 mRNA that was increased by the stimulation of IL-1alpha. These findings suggest that the anti-rheumatoid effect of heparinoid may be due to increased production of TIMP-3. This increase in TIMP-3 may help redress the imbalance between the amounts of MMPs and TIMPs as observed in the joint tissues of rheumatoid arthritis and osteoarthritis patients.