start-ver=1.4 cd-journal=joma no-vol=13 cd-vols= no-issue=10 article-no= start-page=100463 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2020 dt-pub=202010 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Evaluation of oral immunotherapy efficacy and safety by maintenance dose dependency: A multicenter randomized study en-subtitle= kn-subtitle= en-abstract= kn-abstract=Background
Generally, oral immunotherapy (OIT) aims for daily administration. Recently, the efficacy of treatment with OIT at a low dose has been reported. However, the optimal dose and the evaluation of dose-dependent OIT outcome have not been described.
Methods
A multicenter, parallel, open-labeled, prospective, non-placebo controlled, randomized study enrolled 101 Japanese patients for treatment with OIT. We hypothesized that target dose OIT would induce short-term unresponsiveness (StU) earlier than reduced dose OIT. StU was defined as no response to 6200 mg whole egg, 3400 mg milk, and 2600 mg wheat protein, as evaluated by oral food challenge after 2-week ingestion cessation. To compare the two doses of OIT efficacy, the maximum ingestion doses during the maintenance phase of OIT were divided into 100%-dose or 25%-dose groups against their target StU dose, respectively. A total of 51 patients were assigned to the 100%-dose group [hen's egg (HE) = 26, cow's milk (CM) = 13, wheat = 12] and 50 to the 25%-dose group (HE = 25, CM = 13, wheat = 12). Primary outcome was established by comparing StU at 1 year. Secondary outcome was StU at 2 years and established by comparing allergic symptoms and immunological changes.
Results
The year 1 StU rates (%) for the 100%- and 25%-dose groups were 26.9 vs. 20.0 (HE), 7.7 vs. 15.4 (CM), and 50.0 vs. 16.7 (wheat), respectively. The year 2 StU rates were 30.8 vs. 36.0 (HE), 7.7 vs. 23.1 (CM), and 58.3 vs. 58.3 (wheat), respectively. There were no statistically significant differences in StU between years 1 and 2. The total allergic symptom rate in the 25%-dose group was lower than that in the 100%-dose group for egg, milk, and wheat. Antigen-specific IgE levels for egg-white, milk, and wheat decreased at 12 months.
Conclusions
Reduced maintenance dose of egg OIT showed similar therapeutic efficacy to the target dose. However, we were not able to clearly demonstrate the efficacy, particularly for milk and wheat. Reducing the maintenance dose for eggs, milk, and wheat may effectively lower the symptoms associated with their consumption compared to the target OIT dose. Furthermore, aggressive reduction of the maintenance dose might be important for milk and wheat, compared to the 25%-dose OIT. en-copyright= kn-copyright= en-aut-name=OguraKiyotake en-aut-sei=Ogura en-aut-mei=Kiyotake kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=YanagidaNoriyuki en-aut-sei=Yanagida en-aut-mei=Noriyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SatoSakura en-aut-sei=Sato en-aut-mei=Sakura kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=ImaiTakanori en-aut-sei=Imai en-aut-mei=Takanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=ItoKomei en-aut-sei=Ito en-aut-mei=Komei kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=KandoNaoyuki en-aut-sei=Kando en-aut-mei=Naoyuki kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=IkedaMasanori en-aut-sei=Ikeda en-aut-mei=Masanori kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=ShibataRumiko en-aut-sei=Shibata en-aut-mei=Rumiko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=MurakamiYoko en-aut-sei=Murakami en-aut-mei=Yoko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=FujisawaTakao en-aut-sei=Fujisawa en-aut-mei=Takao kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= en-aut-name=NagaoMizuho en-aut-sei=Nagao en-aut-mei=Mizuho kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=11 ORCID= en-aut-name=KawamotoNorio en-aut-sei=Kawamoto en-aut-mei=Norio kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=12 ORCID= en-aut-name=KondoNaomi en-aut-sei=Kondo en-aut-mei=Naomi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=13 ORCID= en-aut-name=UrisuAtsuo en-aut-sei=Urisu en-aut-mei=Atsuo kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=14 ORCID= en-aut-name=TsugeIkuya en-aut-sei=Tsuge en-aut-mei=Ikuya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=15 ORCID= en-aut-name=KondoYasuto en-aut-sei=Kondo en-aut-mei=Yasuto kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=16 ORCID= en-aut-name=SugaiKazuko en-aut-sei=Sugai en-aut-mei=Kazuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=17 ORCID= en-aut-name=UchidaOsamu en-aut-sei=Uchida en-aut-mei=Osamu kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=18 ORCID= en-aut-name=UrashimaMitsuyoshi en-aut-sei=Urashima en-aut-mei=Mitsuyoshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=19 ORCID= en-aut-name=TaniguchiMasami en-aut-sei=Taniguchi en-aut-mei=Masami kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=20 ORCID= en-aut-name=EbisawaMotohiro en-aut-sei=Ebisawa en-aut-mei=Motohiro kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=21 ORCID= affil-num=1 en-affil=Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital kn-affil= affil-num=2 en-affil=Department of Pediatrics, National Hospital Organization, Sagamihara National Hospital kn-affil= affil-num=3 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= affil-num=4 en-affil=Department of Pediatrics, Showa University School of Medicine kn-affil= affil-num=5 en-affil=Department of Allergy, Aichi Children's Health and Medical Center kn-affil= affil-num=6 en-affil=Department of Allergy, Aichi Children's Health and Medical Center kn-affil= affil-num=7 en-affil=Department of Pediatric Acute Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences kn-affil= affil-num=8 en-affil=Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital kn-affil= affil-num=9 en-affil=Department of Pediatrics, National Hospital Organization, Fukuoka National Hospital kn-affil= affil-num=10 en-affil=Institute for Clinical Research, National Hospital Organization, Mie National Hospital kn-affil= affil-num=11 en-affil=Institute for Clinical Research, National Hospital Organization, Mie National Hospital kn-affil= affil-num=12 en-affil=Department of Pediatrics, Graduate School of Medicine, Gifu University kn-affil= affil-num=13 en-affil=Department of Pediatrics, Graduate School of Medicine, Gifu University kn-affil= affil-num=14 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=15 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=16 en-affil=Department of Pediatrics, Fujita Health University, The Second Teaching Hospital kn-affil= affil-num=17 en-affil=Department of Pediatrics, National Hospital Organization, Yokohama Medical Center kn-affil= affil-num=18 en-affil=Department of Pediatrics, National Hospital Organization, Yokohama Medical Center kn-affil= affil-num=19 en-affil=Division of Molecular Epidemiology, The Jikei University School of Medicine kn-affil= affil-num=20 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= affil-num=21 en-affil=Course of Allergy and Clinical Immunology, Juntendo University Graduate School of Medicine kn-affil= en-keyword=Food hypersensitivity kn-keyword=Food hypersensitivity en-keyword=Immunotherapy kn-keyword=Immunotherapy en-keyword=Dose-response relationship kn-keyword=Dose-response relationship en-keyword=Desensitization kn-keyword=Desensitization END start-ver=1.4 cd-journal=joma no-vol=5 cd-vols= no-issue=6 article-no= start-page=e01945 end-page= dt-received= dt-revised= dt-accepted= dt-pub-year=2019 dt-pub=201906 dt-online= en-article= kn-article= en-subject= kn-subject= en-title= kn-title=Anti-stress effects of the hydroalcoholic extract of Rosa gallica officinalis in mice en-subtitle= kn-subtitle= en-abstract= kn-abstract=Rosa gallica, a plant of the Rosa genus, has been used widely since the 13th century and is cultivated in many areas as a medicinal plant for the preparation of herbal medicines. However, details of the neuropsychological effects of R. gallica remain unclear; therefore we aimed to investigate the neuropsychological effects of a water-soluble extract of R. gallica in male C57BL/6N mice under normal conditions and under chronic stress. We administered a water-soluble extract of R. gallica to mice and performed a series of behavioral experiments to compare the treated animals with the untreated controls. No significant differences in activity level, anxiety-like behavior, depression-like behavior, body weight, and body temperature were observed between R. gallica-treated mice and control mice. However, in mice subjected to chronic stress, the observed decrease in activity was smaller in the R. gallica-treated mice than in the control mice. The oral administration of R. gallica did not affect the normal behavior of mice. However, when the mice were subjected to stress, R. gallica exerted an anti-stress effect. Therefore, R. gallica has potential as a medicinal plant for the purpose of stress prevention. en-copyright= kn-copyright= en-aut-name=UenoHiroshi en-aut-sei=Ueno en-aut-mei=Hiroshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=1 ORCID= en-aut-name=ShimadaAtsumi en-aut-sei=Shimada en-aut-mei=Atsumi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=2 ORCID= en-aut-name=SuemitsuShunsuke en-aut-sei=Suemitsu en-aut-mei=Shunsuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=3 ORCID= en-aut-name=MurakamiShinji en-aut-sei=Murakami en-aut-mei=Shinji kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=4 ORCID= en-aut-name=KitamuraNaoya en-aut-sei=Kitamura en-aut-mei=Naoya kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=5 ORCID= en-aut-name=WaniKenta en-aut-sei=Wani en-aut-mei=Kenta kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=6 ORCID= en-aut-name=MatsumotoYosuke en-aut-sei=Matsumoto en-aut-mei=Yosuke kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=7 ORCID= en-aut-name=OkamotoMotoi en-aut-sei=Okamoto en-aut-mei=Motoi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=8 ORCID= en-aut-name=FujiwaraYuko en-aut-sei=Fujiwara en-aut-mei=Yuko kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=9 ORCID= en-aut-name=IshiharaTakeshi en-aut-sei=Ishihara en-aut-mei=Takeshi kn-aut-name= kn-aut-sei= kn-aut-mei= aut-affil-num=10 ORCID= affil-num=1 en-affil=Department of Medical Technology, Kawasaki University of Medical Welfare kn-affil= affil-num=2 en-affil=Division of Food and Nutrition, Nakamura Gakuen University Junior College kn-affil= affil-num=3 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=4 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=5 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=6 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= affil-num=7 en-affil=Department of Neuropsychiatry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University kn-affil= affil-num=8 en-affil=Department of Medical Technology, Graduate School of Health Sciences, Okayama University kn-affil= affil-num=9 en-affil=Department of Health and Sports Science, Kawasaki University of Medical Welfare kn-affil= affil-num=10 en-affil=Department of Psychiatry, Kawasaki Medical School kn-affil= en-keyword=Neuroscience kn-keyword=Neuroscience en-keyword=Physiology kn-keyword=Physiology END