薬理と治療

Objective　The influence of fragrance components on the development of allergic rhinitis induced by toluene 2, 4-diisocyanate（TDI）were examined in F344 rats.Methods　F344 male rats（6-weeks of age）were sensitized by intranasal instillation of 10％ TDI once a day for 5 days. These rats were exposed to various concentrations of fragrance components, α-n-hexyl cinnamic aldehyde（αHCA）, 2-phenethyl ITC（2-PITC）, n-butyl ITC （nITC）, benzyl ITC（bITC）, amyl salicylate（AS）, methyl jasmonate（MJ）, citral, muscone for 4 hours/day for 5 consecutive days, which was started 10 days after final TDI instillation. Nasal symptoms, sneezes and nasal rubs for 10 minutes, induced by 10％ TDI nasal challenge were evaluated 24 hours after fragrance component exposures. To examine the influence of fragrance components on the appearance of neuropeptide, substance P（SP）, calcitonin gene-related peptide（CGRP）and nerve growth factor（NGF）in nasal mucosa, nasal lavage fluids were obtained from rats 60 min after 10％ TDI nasal challenge, and the levels of neuropeptides were examined by ELISA. Results　HCA, PITC, nITC and bITC, but not AS, MJ, citral and muscone at 0.1％ could attenuate the appearance of nasal symptoms and decreased the number of both sneezes and nasal rubs. We then examined the concentrations of neuropeptides, such as SP, CGRP, NGF in nasal lavage fluids obtained from TDI-sensitized and fragrance components-inhaled rats 60 minutes after TDI challenge. Exposure of TDI-sensitized rats to HCA, PITC, nITC and bITC could suppress the increase in SP, CGRP and NGF levels in nasal lavage fluids, which were increased by TDI challenge. On the other hand, AS, MJ, citral and muscone scarcely affected the appearance of neuropeptides in nasal lavage fluids. Conclusion　These results clearly showed that exposure to HCA, PITC, nITC and bITC, which are delivatives of cinnamic aldehyde or allyl isothiocyanate could attenuate the develop ment of allergic nasal symptoms through the suppression of neuropeptide productions in nasal walls.

Through the Pharmaceutical Intervention Record（PIR）project jointly conducted by the Gifu Pharmaceutical Association and Gifu Pharmaceutical University, we analyzed characteristics and economic effects of prescription audits initiated because of prescription inquiries about unused medicines. Before analysis, 1105 prescriptions reported in fiscal 2017 were divided into prescriptions with unused medicines（the unused group）and other prescriptions（the control group）. The amount of reduced drug cost per prescription in the unused group was 1625 yen, which was significantly larger than 906 yen in the control group. In the unused group, unused drugs were found by checking drugs bought by the patients as well as by communicating with patients and their family members, and the number of days prescribed was changed or the prescribed drug was canceled more commonly after audits. These prescription changes are likely to be the reason for the larger decrease in the drug cost in the unused group than in the control group. The classification of drugs based on efficacy that was often adjusted because of unused medicines included sedative and hypnotic agents/laxative agents, vasodilator agents, and herbal medicines.

Objectives　We aimed to determine whether the ingestion of acetic acid bacteria could reduce the symptoms of Japanese cedar-pollen allergy. Methods　We conducted a randomized double-blind placebo-controlled study. 84 Japanese males and females（mean age: 38.6±10.1 years）with allergic rhinitis triggered by Japanese cedar pollen were randomly assigned to an acetic acid bacteria group or a control group. The subjects ingested acetic acid bacteria（30 mg/day）or placebo for 8 weeks. Nasal discomfort was evaluated using the Japanese Rhinoconjunctivitis Quality of Life Questionnaire at preingestion and at 4 and 8 weeks during the ingestion period. Results　The acetic acid bacteria group had a significantly lower nasal discomfort score compared to the control group at 4 weeks after ingestion（P ＜0.05）with no adverse effects observed. Eye discomfort were not affected by acetic acid bacteria. Conclusion　Our findings suggest that the continuous ingestion z of acetic acid bacteria relieves nasal discomfort of Japanese cedar pollinosis. （JMA-IIA00432）

Objectives　We aimed to determine whether Gluconacetobacter hansenii GK-1（G. hansenii） activates immune cells via TLR4 and acts synergistically with Lactobacillus paracasei（L.paracasei）to produce antiallergic effects. Methods　We conducted three in vitro tests as follows. Test 1: For evaluation of TLR4 signal pathway, TLR4-transfected human embryonic kidney（HEK）cells were stimulated by heat-killed G. hansenii, and using L. paracasei, Bifidobacterium bifidum and Bacillus subtilis as Gram positive bacteria control. Test 2: To evaluate the synergistic macrophage activation by the combination of G. hansenii and L. paracasei, nitric oxides production was measured by stimulated RAW264.7（a mouse macrophage cell line）. Test 3: To evaluate the synergistic macrophage activation by a combination of G. hansenii and L. paracasei, the IL︱12p40 production was measured by stimulated J774.1（a mouse macrophage cell line）. Results　Test 1 showed that G. hansenii activated on TLR4 pathway and were significantly produced higher levels of IL-8 compared with the other Gram-positive bacteria（P＜0.05）. Tests 2 and 3 showed that there was a significant increase in the nitric oxide production and IL-12p40 production when G. hansenii and L. paracasei were added together to the cell culture compared with the single bacteria（P＜0.05）. Conclusion　The findings of our study show that G. hansenii specifically binds to TLR4 to cause an antiallergic effect and acts synergistically with L. paracasei.

Objective　This study aimed to investigate the effects of a test food on healthy Japanese subjects with knee joint discomfort. Methods　A total of 66 healthy, disease-free Japanese subjects experiencing discomfort in the knee joint participated in a randomized, double-blinded, placebo-controlled study from July2018-April 2019. All subjects were randomly allocated into the intervention or the placebo group（n＝33 in each group）using a computerized random-number generator. Each group was administered with six tablets［active（containing test food）or placebo］daily for 12 weeks. The total score of Japanese Knee Osteoarthritis Measure（JKOM; primary outcome）, other parameters of JKOM, the Japanese Orthopaedic Association score for osteoarthritic knees, and subjective symptoms related to knee pain were assessed, and 30-second chair stand test, 10-meter walking test, blood test, and safety assessments were performed. Results　At 12 weeks after ingestion of tablets, the total score of JKOM for the intervention group exhibited a significant decrease compared with the placebo group（P＝0.006）. In addition, consumption of the test food significantly reduced the subjective symptoms of discomfort in the knee joint associated with standing and sitting, ascending and descending the stairs, and changing clothes（P＜0.050）. No safety concerns were noted. Conclusions　The consumption of test food containing glucosamine hydrochloride, methylsulfonylmethane, boswellia serrata extract, and olive extract for 12 weeks resulted in the relief from the discomfort in the knee joint in healthy Japanese subjects. Trial Registration　UMIN-CTR: UMIN000033446Funding　DHC Corporation

Objective　The aim of this study was to investigate the effect of a dietary supplement containing porcine skin collagen peptides on hair on healthy subjects. Moreover, to discuss the mechanism on these effects, we evaluated the effects of treatment with collagen peptides in human follicle dermal papilla cells. Methods 　①A randomized, double-blind, placebo-controlled parallel-group, comparison study was conducted in 65 healthy subjects（20︱69 years old）. The subjects were randomized into two groups and given either the test product（125 mL drink containing 10 g collagen peptides derived from porcine skin）per day or the control product（placebo drink）for 8 weeks. Visual analogue scale（VAS）for hair and two dimension mood scale（TDMS-ST）were evaluated. ②We also evaluated whether hydroxyproline（Hyp）, prolyl-hydroxyproline（Pro-Hyp）, and glycyl-prolyl-hydroxyproline（Gly-Pro-Hyp）promote the proliferation of dermal papilla cells and induce the mRNA expression level of vascular endothelial growth factor （VEGF）and fibroblast growth factor-7（FGF-7）in human follicle dermal papilla cells. Results　①The VAS score onʻless hair lossʼandʻstrong hairʼ, and the TDMS-ST score on ʻlivelyʼandʻvitalityʼwere significantly improved at 8 weeks in the test product group who took collagen peptides compared to the placebo group. ②Hyp and Pro-Hyp enhanced cell proliferation, and Pro-Hyp and Gly-Pro-Hyp upregulated the mRNA expression of VEGF in human follicle dermal papilla cells. Conclusions　The results suggested that daily supplementation of collagen peptides derived from porcine skin may be effective for hair by stimulating cell proliferation and the upregulation of VEGF expression（. UMIN-CTR000036892）

Objective　Chondroitin sulfate is a type of mucopolysaccharide that combines with core proteins to form proteoglycan in animal cartilage. Proteoglycan has good water retention and high viscosity properties, and, thus, contributes to cushioning the knee joints. The present study investigated the effects of pig-derived chondroitin sulfate on the attenuation of knee joint pain in healthy middle and old aged people in a randomized, double-blind, placebo-controlled trial. Methods　Forty-eight subjects were randomly assigned to the test food（350 mg of pig-derived chondroitin sulfate） and placebo groups. Test food or placebo was administrated to each group for 12 weeks. A visual analogue scale（VAS）of pain, stiffness, and discomfort in both knees as well as the Japanese Knee Osteoarthritis Measure（JKOM）were the primary outcomes. Results　Among subjects with a VAS score of pain in both knees of less than 30（mild pain）, the VAS score of pain was significantly lower in the test food group than in the placebo group. No significant differences were observed in JKOM between the two groups. Conclusion　Pig-derived chondroitin sulfate attenuated mild knee joint pain; therefore, its administration has potential as a more appropriate treatment than anti-inflammatory analgesics for healthy middle and old aged people（. UMIN ID: UMIN000025992）