of Science and Technology, 758-65 Bibi , Chitose, Hokkaido, 066-8655, Japan; 2 Meiji Seika Kaisha Limited, 760 Morooka-cho, Kohoku-ku, Yokohama, 222...Organization Name(s) and Address(es) Chitose Institute of Science and Technology, 758-65 Bibi , Chitose, Hokkaido, 066-8655, Japan Performing Organization
Shiina, Yumi; Funabashi, Nobusada; Lee, Kwangho; Murayama, Taichi; Nakamura, Koki; Wakatsuki, Yu; Daimon, Masao; Komuro, Issei
To assess the effects of the oral intake of flavonoid-rich dark chocolate on coronary circulation, we measured coronary flow velocity reserve (CFVR) by noninvasive transthoracic Doppler echocardiography (TTDE) in healthy adult subjects. The study was a randomized, single-blind design conducted for 2 weeks in 39 healthy men (mean age 29.7+/-3.9 years, range 23-40 years). Subjects were randomly assigned a daily intake of either flavonoid-rich dark chocolate (Meiji Black Chocolate 45 g, Meiji Seika kaisya Ltd, including cacao polyphenol 550 mg/day, 200 kcal) or non-flavonoid white chocolate (Meiji White Chocolate 35 g, Meiji Seika kaisya Ltd, including cacao polyphenol 0 mg/day, 140 kcal) as a control. CFVR was recorded by TTDE, and assessed before and after 2 weeks of intake. At the same time, we also assessed serum asymmetric dimethylarginine, 8-isoprostanes, and malondialdehyde-modified low-density lipoprotein (MDA-LDL) as markers of oxidative stress. Flavonoid-rich dark chocolate consumption significantly improved CFVR (3.38+/-0.49 before intake, 4.28+/-0.85 after intake; p<0.01), whereas non-flavonoid white chocolate consumption did not (3.28+/-0.49 before intake, 3.16+/-0.49 after intake; p=0.44). All predictor variables were used as dependent variables in a multiple regression model of the incremental change in CFVR after 2 weeks of chocolate intake. Intake of dark (but not white) chocolate, MDA-LDL, triglyceride (TG) and heart rate (HR) significantly influenced the change of CFVR after 2 weeks of intake (p<0.01) according to the multiple regression formula: Y=1.01X(1)-0.005X(2)-0.003X(3)-0.017X4 (Y=change in CFVR after 2 weeks of chocolate intake, X1=intake of dark (but not white) chocolate, X2=MDA-LDL, X3=TG, X4=HR). Flavonoid-rich dark chocolate intake significantly improved coronary circulation in healthy adults, independent of changes in oxidative stress parameters, blood pressure and lipid profile, whereas non-flavonoid white chocolate had no such effects.
Onozaki, Yasumichi; Horikoshi, Ryo; Ohno, Ikuya; Kitsuda, Shigeki; Durkin, Kathleen A; Suzuki, Tomonori; Asahara, Chiaki; Hiroki, Natsuko; Komabashiri, Rena; Shimizu, Rikako; Furutani, Shogo; Ihara, Makoto; Matsuda, Kazuhiko; Mitomi, Masaaki; Kagabu, Shinzo; Uomoto, Katsuhito; Tomizawa, Motohiro
A novel chemotype insecticide flupyrimin (FLP) [N-[(E)-1-(6-chloro-3-pyridinylmethyl)pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide], discovered by Meiji Seika Pharma, has unique biological properties, including outstanding potency to imidacloprid (IMI)-resistant rice pests together with superior safety toward pollinators. Intriguingly, FLP acts as a nicotinic antagonist in American cockroach neurons, and [(3)H]FLP binds to the multiple high-affinity binding components in house fly nicotinic acetylcholine (ACh) receptor (nAChR) preparation. One of the [(3)H]FLP receptors is identical to the IMI receptor, and the alternative is IMI-insensitive subtype. Furthermore, FLP is favorably safe to rats as predicted by the very low affinity to the rat α4β2 nAChR. Structure-activity relationships of FLP analogues in terms of receptor potency, featuring the pyridinylidene and trifluoroacetyl pharmacophores, were examined, thereby establishing the FLP molecular recognition at the Aplysia californica ACh-binding protein, a suitable structural surrogate of the insect nAChR. These FLP pharmacophores account for the excellent receptor affinity, accordingly revealing differences in its binding mechanism from IMI.
Kunugi, Tomoaki; Pham, Son; Kawara, Zensaku; Yokomine, Takehiko
The annular two-phase flow on rod bundle keeps an important role in many heat exchange systems but our knowledge about it, especially the interaction between the liquid film flowing on the rods' surfaces and the spacers is very limited. This study is aimed to the investigation of how the spacer affects the disturbance waves of the flow in a 3 × 3 simulating BWR fuel rod bundle test section. Firstly, the characteristics of the disturbance waves at both upstream and downstream locations of the spacer were obtained by using reflected light arrangement with a high speed camera Phantom V7.1 (Vision Research Inc.) and a Nikon macro lens 105mm f/2.8. The data showed that the parameters such as frequency and circumferential coherence of the disturbance waves are strongly modified when they go through the spacer. Then, the observations at the locations right before and after the spacer were performed by using the back light arrangement with the same high speed camera and a Cassegrain optical system (Seika Cooperation). The obtained images at micro-scale of time and space provided the descriptions of the wavy interface behaviors right before and after the spacer as well as different droplets creation processes caused by the presence of this spacer.
Li, Liming; Aizawa, Katsuo
Photodynamic therapy (PDT) has been evolving rapidly in the recent years. A second-generation Photosensitizer mono-1-aspartyl chlorine 6 (Talaporfin / Npe6 / ME2906, Japan Meiji Seika, Ltd.) has been sanctified for the lung cancer clinical PDT by the Japan Ministry of Health, Labor and Welfare. In this paper, Talaporfin was injected to the implant cancer of a mouse a Talaporfin dose of 5mg/kg through intravenous. After 6 hours, the fluorescence images of the mouse were observed with a microscope and a 664 nm diode laser. Effects of therapy were clarified using the different irradiation energies of the laser (50, 100, 200 J/cm2). Both in plasma and in cancer, the concentrations of Talaporfin were analyzed using High Performance Liquid Chromatography (HPLC). Authors find that the higher concentrations of Talaporfin in plasma, the better PDD effect. It is experimentally verified that local microvascular embolisms in the cancer are formed for photodynamic therapy after the Talaporfin injection and the laser irradiation.
Nakae, Aya; Nakai, Kunihiro; Tanaka, Tatsuya; Hagihira, Saotoshi; Shibata, Masahiko; Ueda, Koichi; Masimo, Takashi
We examined whether infraorbital nerve injury affected the RNA editing efficiency of the serotonin (5HT) 2C receptor in the cervical spinal cord, in association with increased pain thresholds, and whether a 5HT reuptake inhibitor (fluvoxamine; Depromel, Meiji Seika, Tokyo, Japan) altered this editing. Accordingly, we injured rats with an infraorbital nerve loose ligation and examined the pain thresholds, mRNA and mRNA editing of the 5HT2C receptor. We evaluated changes in mRNA editing and 5HT2C mRNA expression using cloning along with sequence analysis and quantitative reverse transcription-polymerase chain reaction to compare samples taken at post-injury day 28 from spinal cord sites, including the trigeminal nucleus caudalis, in naive, sham and injured rats (groups of each type had also received fluvoxamine). 5HT2C receptor expression was maintained post-injury. The RNA editing efficiency was statistically significantly lower at molecular sites A and B in ipsilateral spinal cord samples from injured rats than in bilateral samples from naive and sham rats, and in contralateral samples from injured rats. After injury, the proportional presence of two receptor isoforms changed, i.e. statistically significantly less VNV and significantly more INV and ISV. The proportions reverted after fluvoxamine administration. The post-injury change might be evidence of a functional adaptation mechanism that increases the expression of 5HT2C mRNA isoforms that encode receptors that are more sensitive to 5HT. This would activate the brainstem-spinal descending 5HT systems and, in effect, suppress nociceptive signals from primary afferent neurons to the spinal trigeminal nucleus caudalis.
Fujii, Tatsuya; Fang, Xu; Inoue, Hiroyuki; Murakami, Katsuji; Sawayama, Shigeki
Bioethanol isolated from lignocellulosic biomass represents one of the most promising renewable and carbon neutral alternative liquid fuel sources. Enzymatic saccharification using cellulase has proven to be a useful method in the production of bioethanol. The filamentous fungi Acremonium cellulolyticus and Trichoderma reesei are known to be potential cellulase producers. In this study, we aimed to reveal the advantages and disadvantages of the cellulase enzymes derived from these fungi. We compared A. cellulolyticus and T. reesei cellulase activity against the three lignocellulosic materials: eucalyptus, Douglas fir and rice straw. Saccharification analysis using the supernatant from each culture demonstrated that the enzyme mixture derived from A. cellulolyticus exhibited 2-fold and 16-fold increases in Filter Paper enzyme and beta-glucosidase specific activities, respectively, compared with that derived from T. reesei. In addition, culture supernatant from A. cellulolyticus produced glucose more rapidly from the lignocellulosic materials. Meanwhile, culture supernatant derived from T. reesei exhibited a 2-fold higher xylan-hydrolyzing activity and produced more xylose from eucalyptus (72% yield) and rice straw (43% yield). Although the commercial enzymes Acremonium cellulase (derived from A. cellulolyticus, Meiji Seika Co.) demonstrated a slightly lower cellulase specific activity than Accellerase 1000 (derived from T. reesei, Genencor), the glucose yield (over 65%) from lignocellulosic materials by Acremonium cellulase was higher than that of Accellerase 1000 (less than 60%). In addition, the mannan-hydrolyzing activity of Acremonium cellulase was 16-fold higher than that of Accellerase 1000, and the conversion of mannan to mannobiose and mannose by Acremonium cellulase was more efficient. We investigated the hydrolysis of lignocellulosic materials by cellulase derived from two types of filamentous fungi. We found that glucan-hydrolyzing activity of the culture
Furukawa, Kinya; Katsumi, Tohichiro; Shibuya, Hiroshi; Okunaka, Tetsuya; Kuroiwa, Yukari; Yoshiteru, II; Kaneda, Akira; Saito, Kouichi; Konaka, Chimori; Aizawa, Katsuo; Kato, Harubumi
The authors developed a new high-power red laser diode system (Matsushita Industrial Equipment Co., Ltd., Osaka) for photodynamic therapy (PDT) with mono-L-aspartyl chlorin e6 (NPe6, Meiji Seika Kaisha LTD.). The laser wavelength was adjusted to 664 nm and the power output could be varied in the range of 50-500 mW at the fiber tip in a continuous wave (cw) mode. The delivered energy could be adjusted from 50 - 1000 J. The system has a size of 49 by 20 by 40 cm, weighs 20 kg, and is readily portable. It runs on 100 V current. The laser power is easily controlled and the wavelength is stable (less than plus or minus 0.2 nm). The output beam is delivered via a quartz fiber. Furthermore, the full width at half-maximum power is less than 2 nm, which enables uniform, high-density photoirradiation. The power density distribution of the laser, analyzed by a CCD camera, was uniform throughout the photoirradiated field. In an animal study, tumor-bearing Balb/c mice were treated with the diode laser 5 hours after intravenous administration of NPe6 at a dose of 1.25 to 12.5 mg/kg i.v.. Total photoirradiation ranged from 3.13 to 250 J/cm2 which the energy density was adjusted to 100 mW/cm2. Percentages of cures were determined histopathologically from numbers of mice apparently disease-free 1 week after treatment. The results show that a laser energy of more than 12.5 J/cm2 was necessary to obtain 90% tumor cure rate at a maximum dose of NPe6 (12.5 mg/kg) and NPe6 dose of more than 2.5 mg/kg was necessary to obtain 90% cure rate at high laser energy of 200 J/cm2.
Khota, Waroon; Pholsen, Suradej; Higgs, David; Cai, Yimin
Natural lactic acid bacteria (LAB) populations in tropical grasses and their fermentation characteristics on silage prepared with cellulase enzyme and LAB inoculants were studied. A commercial inoculant Lactobacillus plantarum Chikuso 1 (CH), a local selected strain Lactobacillus casei TH14 (TH14), and 2 cellulases, Acremonium cellulase (AC) and Maicelase (MC; Meiji Seika Pharma Co. Ltd., Tokyo, Japan), were used as additives to silage preparation with fresh and wilted (6 h) Guinea grass and Napier grass. Silage was prepared using a laboratory-scale fermentation system. Treatments were CH, TH14, AC at 0.01% fresh matter, AC 0.1%, MC 0.01%, MC 0.1%, CH+AC 0.01%, CH+AC 0.1%, CH+MC 0.01%, CH+MC 0.1%, TH14+AC 0.1%, TH14+AC 0.01%, TH14+MC 0.1%, and TH14+MC 0.01%. Microorganism counts of Guinea grass and Napier grass before ensiling were 10(2) LAB and 10(6) aerobic bacteria; these increased during wilting. Based on morphological and biochemical characteristics, and 16S rRNA gene sequence analysis, natural strains from both grasses were identified as L. plantarum, L. casei, Lactobacillus acidipiscis, Leuconostoc pseudomesenteroides, Leuconostoc garlicum, Weissella confusa, and Lactococcus lactis. Lactobacillus plantarum and L. casei are the dominant species and could grow at lower pH and produce more lactic acid than the other isolates. Crude protein and neutral detergent fiber were 5.8 and 83.7% of dry matter (DM) for Guinea grass, and 7.5 and 77.1% of DM for Napier grass. Guinea grass had a low level of water-soluble carbohydrates (0.39% of DM). Guinea grass silage treated with cellulase had a lower pH and higher lactic acid content than control and LAB treatments. The 0.1% AC and MC treatments had the best result for fermentation quality. All high water-soluble carbohydrate (2.38% DM) Napier grass silages showed good fermentation quality. Compared with control and LAB-inoculated silage, the cellulase-treated silages had significantly higher crude protein content and
Kondo, Shinsuke; Kumakura, Yousuke; Kanehara, Akiko; Nagato, Daisuke; Ueda, Taro; Matsuoka, Tsuneo; Tao, Yukiko; Kasai, Kiyoto
Premature death in individuals with severe mental illness (SMI) in countries without nationally collected data, including Japan, is structurally underreported. To elucidate excess mortality among individuals with SMI in Japan. We retrospectively investigated all deaths among users of a non-clinical community-based mental health service provider in suburban Tokyo from 1992 to 2015. During the study period, 45 individuals died among 254 qualified registrants. Deaths were by natural causes in 33 cases (73.3%). The mean years of life lost was 22.2 years and the overall standard mortality ratio (SMR) was 3.28 (95% CI 2.40-4.39). The cause-specific SMR was 5.09 (95% CI 2.33-9.66) for cardiovascular disease and 7.38 (95% CI 2.40-17.22) for suicide. Although Japan leads the world in longevity, individuals with SMI suffer premature death and excess mortality due to physical conditions as well as suicide. Revealing this underreported disparity of life is the first step to improving physical care for individuals with SMI. S.K. received personal fees from Pfizer and Dainippon-Sumitomo, outside the submitted work, and was a medical adviser to Sudachi-kai. Y.K. received grants from Japan Foundation for Neuroscience and Mental Health (JFNMH), during the conduct of the study, and personal fees from Dainippon-Sumitomo, outside the submitted work. K.K. received grants from Japan Society for the Promotion of Science (JSPS) and Japan Agency for Medical Research and Development (AMED), during the conduct of the study; personal fees from Daiichi-Sankyo, Otsuka, Meiji-Seika Pharma, Yoshitomi, Mochida and Fuji-Film RI Pharma; grants and personal fees from MSD, Astellas, Dainippon-Sumitomo and Eisai; and grants from Lily, Takeda and Tanabe-Mitsubishi, outside the submitted work. © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.
Frequently used in a pejorative sense, "disease mongering" connotes a widening of the diagnostic boundaries of illness. Pharmaceutical companies conduct disease awareness campaigns on the pretext of educating the public about the prevention of illness or the promotion of health. Encouraged by disease awareness advertisements, people gradually become filled with concern that they are ill and need medical treatment. As a result, pharmacotherapy is increasingly being applied to ever-milder conditions, leading to potentially unnecessary medication, wasted resources, and even adverse side effects. Among all fields of clinical medicine, psychiatry is undoubtedly the most vulnerable to the danger of disease mongering. In Japan, depression provides the most drastic example of the impact of disease awareness campaigns on the number of patients seeking treatment. Until the late 1990s, Japanese psychiatrists focused almost exclusively on psychosis and endogenous depression, the latter being severe enough to require conventional forms of antidepressants, known as tricyclic antidepressants, and even hospitalization. At this time, people's attitude toward depression was generally unfavorable. Indeed, the Japanese word for clinical depression, utubyo, has a negative connotation, implying severe mental illness. This situation, however, changed immediately after fluvoxiamine (Luvox-Fujisawa, Depromel-Meiji Seika), the first selective serotonin re-uptake inhibitor (SSRI) to receive approval in Japan, was introduced in 1999. In order to aid the drug's acceptance by the Japanese public, pharmaceutical companies began using the catchphrase kokoro no kaze, which literally means "a cold of the soul". Thus armed with this phrase, the pharmaceutical industry embarked on a campaign to lessen the stigma surrounding depression. According to national data from the Ministry of Health and Welfare, the number of patients with a diagnosis of mood disorder increased from 327,000 in 1999 to 591