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Neuroprotective effect of a dietary supplement against glutamate-induced excitotoxicity in retina

International Journal of Ophthalmology(English edition) 2019年第8期12卷 1231-1237页

作者： Takahiro Kurose Eriko Sugano Akihisa Sugai Raki Shiraiwa Mariyo Kato yoko Mitsuguchi Yoshihiro Takai Kitako Tabata Yoichi Honma Hiroshi Tomita Rohto Pharmaceutical Co. Ltd.6-5-4KunimidaiKizugawaKyoto619-0216Japan Laboratory of Visual Neuroscience Graduate Course inBiological SciencesIwate University Division of Science andEngineering4-3-5UedaMoriokaIwate020-8551Japan Clinical Research Innovation and Education CenterTohokuUniversity Hospital1-1SeiryoAobaSendaiMiyagi980-8574Japan

AIM: To evaluate the neuroprotective effect of a dietary supplement(ClearVision EX~?;CV) against glutamateinduced excitotoxicity in ***: We evaluated the protective effects CV on glutamate-induced cell toxicity of an immortalized mouse hippocampal cell line(HT-22) in vitro and N-methyl-Daspartate(NMDA) induced retinal injury in vivo. Once-daily oral administration of CV or vehicle(5% Arabic gum) was started the day before the NMDA injection and continued until the end of the study. Electroretinograms(ERGs) were recorded to evaluate the retinal function at 2 d after NMDA injection. Furthermore, a histological evaluation, Western blot analysis, and immunohistochemistry were performed for assessing the signal transduction pathway. RESULTS: HT-22 cell death was induced by the addition of glutamate and co-incubation with CV protected against it. Oral administration of CV inhibited the decrease in scotopic threshold response amplitudes induced by the intravitreal injection of NMDA and those of the thickness of the inner retinal layer in the histological evaluation. The increased phosphorylated levels of extracellular signalregulated kinase(ERK) but not cAMP response element binding protein(CREB) or Akt were observed 1 h after NMDA injection in both the vehicle-and CV-treated rats;however, p ERK activation was no more upregulated at 3 h after NMDA injection. pERK upregulation was observed in Müller ***: CV shows a protective effect against both glutamate-induced HT-22 cell death and NMDAinduced retinal damage. pERK upregulation in the Müller cells plays a key role in the protective effect of CV against glutamate-induced retinal toxicity.

关键词： glutamate-induced toxicity retinal ganglion cells HT-22 cells pERK

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Vascular remodeling and mobilization of bone marrow-derived cells in cuff-induced vascular injury in LDL receptor knockout mice

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Chinese Medical Journal 2008年第3期121卷 220-226页

作者： XU Yang ARAI Hidenori murayama Toshinori KITA Toru yokoDE Masayuki Institute of Medicinal Plant Development Chinese Academy ofMedical Sciences and Peking Union Medical College Beijing100094 China Department of Clinical Innovative Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Department of Geriatric Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Department of Cardiovascular Medicine Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan Translational Research Center Kyoto University Graduate School of Medicine 54 Kawahara-cho Shogoin Sakyo-ku Kyoto 606-8507 Japan

Background Vascular remodeling is an important pathologic process in vascular injury for various vascular disorders such as atherosclerosis, postangioplasty restenosis and transplant arteriopathy. Recently, pathologic change and the role of bone marrow derived cells were wildly studied in atherosclerosis and restenosis. But the manner of lesion formation in neointima and cell recruitment in vascular remodeling lesion in the present of hypercholesterolemia is not yet fully understood. Methods Double-transgenic mice knockout of LDL receptor gene （LDL-/-） and expressing ubiquitously green fluorescent protein （GFP） were obtained by cross-breeding LDL -/- mice with the GFP-expressing transgenic mice. LDL-/- mice （22-24 weeks of age） fed high fat diet containing 1.25% （w/w） cholesterol were subjected to 9Gy irradiation and received bone marrow （BM） cells from the double-transgenic mice. Four weeks later, a nonconstrictive cuff was placed around the right femoral artery. After another 2 weeks, both right and left femoral arteries were harvested and subjected to histochemical analysis. Apoptosis was analyzed in situ using TUNEL assay. Results Two weeks after cuff placement, atherosclerotic lesions developed in the intima consisting of a massive accumulation of foam cells. The tissue stained with anti-α smooth muscle actin （SMA） antibody, showed a number of SMA-positive cells in the intimal lesion area. They were also positive for GFP, indicating that BM-derived cells can differentiate to SMCs in the intima in cuff-induced vascular remodeling lesions. Numerous small vessels in the adventitia as well as the endothelial lining of the intima were positive both for CD31 and GFP. The intima and media showed a large number of TUNEL-positive signals after 2 weeks cuff injury, indicating the presence of apoptosis in vascular remodeling. Conclusions Atherosclerotic lesions in mice can be developed in the intima after 2 weeks of cuff-induced vascular injury under the hypercholes

关键词： vascular remodeling macrophage smooth muscle cell endothelial cell bone marrow

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Structure and Oscillation of Underexpanded Jet

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Open Journal of Fluid Dynamics 2013年第2期3卷 85-91页

作者： Hiromasa Suzuki Masaki Endo yoko Sakakibara Division of Electronic and Mechanical Engineering Tokyo Denki University Saitama Japan Graduate School of Advanced Science and Technology Tokyo Denki University Saitama Japan

In this study, flow characteristics are experimentally and numerically discussed, especially concerning shock-cell structure and oscillatory phenomena of supersonic jet. The jet becomes underexpanded when the nozzle pressure ratio of convergent nozzle exceeds the critical value. The underexpanded jet is not uniform because of the presence of the expansion wave, the compression wave and the shock wave formed in it. Many vortices are induced in jet boundary region by shearing stress generated between supersonic jet flow and atmospheric air. They interact with shock waves composing cell node of jet, which is closely related to a noise radiating from the jet. In experiment, flow field is visualized and the shape of cell structure is examined. Furthermore, frequency of vortex generation is measured. The jet is simulated using TVD scheme and the results are compared with the experimental ones. Distortion of cell structure caused by three dimensional oscillation of jet and behavior of vortices are discussed.

关键词： Underexpanded Jet Plate Shock Incident Shock Visualization TVD Scheme

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Recent advances in endoscopic ultrasonography-guided biliary interventions

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World Journal of Gastroenterology 2015年第32期21卷 9494-9502页

作者： Kazumichi Kawakubo Hiroshi Kawakami Masaki Kuwatani Shin Haba Shuhei Kawahata yoko Abe Yoshimasa Kubota Kimitoshi Kubo Hiroyuki Isayama Naoya Sakamoto Department of Gastroenterology and Hepatology Hokkaido University Graduate School of Medicine Department of Gastroenterology Graduate School of Medicine The University of Tokyo

Interventional endoscopic ultrasonography(EUS) based on EUS-guided fine-needle aspiration has rapidly spread as a minimally invasive procedure. Especially in patients with failed endoscopic retrograde cholangiopancreatography, EUS-guided biliary intervention is reported to be useful as salvage therapy. EUS-guided biliary interventions are carried out using three techniques: EUS-guided bilioenteric anastomosis, EUS-guided rendezvous procedure, and EUS-guided antegrade treatment. Although interventional EUS is not yet a standardized procedure, there have been recent advances in this field that address various biliary diseases. Here, we summarize the indications, techniques, clinical results of previous studies, and future perspectives.

关键词： Endosonography-guided biliary intervention Choledo

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中国知识产权执法机制研究

中国知识产权执法机制研究

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作者： yoko Ouchi 华东政法大学

学位级别：硕士

知识产权保护是一项系统的工程。在立法保护方面，中国用短短20年的时间，走完了西方发达国家上百年的历程。但是知识产权的执法状况令人堪忧，全社会知识产权意识较为淡薄，侵权现象大量存在、屡禁不止，而执法体制以及执法队伍也存在... 详细信息

知识产权保护是一项系统的工程。在立法保护方面，中国用短短20年的时间，走完了西方发达国家上百年的历程。但是知识产权的执法状况令人堪忧，全社会知识产权意识较为淡薄，侵权现象大量存在、屡禁不止，而执法体制以及执法队伍也存在着诸多问题和矛盾。在知识产权理论研究方面尚不成熟，缺乏纵深、透彻、全面和具有中国特有的研究，还不能圆满及时地回答和解决立法、司法实践中提出的急迫的重要问题，不能起到指导立法、执法的作用。本文对当前中国知识产权执法机制作了全面的研究和分析，对中国目前的双轨制(Duo System)之行政保护作了详细论述，并对执法当中存在的问题作了初步的分析，并提出建议。本文的导论部分对知识产权执法机制进行了简要的介绍，分析了TRIPS协议对各成员的执法要求，并概括了中国为落实TRIPS协议而在知识产权法执法机制方面所作出的完善。文章的第二部分对中国知识产权的司法保护进行了详细介绍，分别从民事司法保护、行政司法保护、刑事司法保护和司法保护临时措施几个方面勾勒出中国知识产权司法保护的现状及具体的法律规则。文章的第三部分对中国知识产权的行政保护进行了详细介绍，从行政保护的执法机构、行政保护的法律依据、具体规则及执行情况等方面进行了论述，并特别介绍了知识产权的海关保护。文章的最后一部分对中国知识产权执法的双轨制(Duo System)进行了分析。从执法的重点、执法的地区差异、刑事打击力度、行政执法专项活动等方面概括了中国知识产权执法所面临的情况。然后对知识产权的司法保护和行政保护之间的关系进行了整理，并从文化的角度、公众的知识产权保护意识角度、法院的公信力角度、行政执法在形式和效果角度详细论证了，在中国的知识产权保护体系中，行政保护是最具效率、最具中国特有的保护机制，它正在、并将在一个很长的时间里在中国的知识产权保护工作中发挥重要作用。在此基础上，文章最后提出，应从完善司法、行政的衔接、加强司法、行政部门之间的沟通、加强地区间的协调配合、充分利用司法解释的作用、提高执法队伍素质、积极参与保护知识产权国际交流等六个方面完善中国的知识产权执法机制。

关键词：执法机制知识产权司法保护双轨制

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Analysis of <i>N</i>-Nitrosamine Migration from Rubber Teats and Soothers

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American Journal of Analytical Chemistry 2013年第6期4卷 277-285页

作者： Motoh Mutsuga Miku Yamaguchi yoko Kawamura Division of Food Additives National Institute of Health Sciences Tokyo Japan

A testing method for N-nitrosamines and N-nitrosatable substances in rubber teats and soothers was modified. N-Nitrosamines are generally analyzed using either a nitrogen chemiluminescence detector (NCD) or a thermal energy analyzer (TEA). However, because few testing laboratories are equipped with these devices, it is difficult to conduct these tests. Therefore, an analysis method for N-nitrosamines using the more widespread gas chromatography-mass spectrometry (GC-MS) method was improved. In addition, EN 12868 was used to prepare the test solutions because of its worldwide use and compliance with EU regulations. Using GC-MS, EN 12868 method targeting ten kinds of N-nitrosamines was modified. The determination limits of the method were 1.0 -1.5 μg/kg for N-nitrosamines and 4 -6 μg/kg for N-nitrosatable substances. Quantification was possible at 1/5 or less and 1/15 or less, respectively, of the regulation values listed in EU Directive 93/11/EEC. In terms of application, there were no problems with the selectivity of the detector. The recoveries were 58% -109% for N-nitrosamines and 59% -102% for N-nitrosatable substances. Screening and verification were possible by measuring the amount of secondary amines in the boiled solution and migration solution.

关键词： N-Nitrosamine N-Nitrosatable Substances Secondary Amine Rubber Teat and Soother GC-MS

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Effects of Nonpharmacological Therapies for Diseases of the Elderly

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Psychology Research 2014年第5期4卷 389-396页

作者： Yoshihisa Koike yoko Yamanishi Yoshio Kano Prefectural University of Hiroshima Mihara Japan Kibi International University Takahashi Japan

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A Parallel Algorithm for the Spanning Forest Problem on Proper Circle Graphs

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Journal of Computer and Communications 2017年第14期5卷 48-55页

作者： Hirotoshi Honma yoko Nakajima Atsushi Sasaki National Institute of Technology Kushiro College Kushiro Japan

Given a simple graph G with n vertices, m edges and k connected components. The spanning forest problem is to find a spanning tree for each connected component of G. This problem has applications to the electrical power demand problem, computer network design, circuit analysis, etc. In this paper, we present an?time parallel algorithm with processors for constructing a spanning forest on proper circle graph G on EREW PRAM.

关键词： Design and Analysis of Parallel Algorithms Proper Circle Graphs Spanning Forest

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The effects of 90-day feeding of D-psicose syrup in male wistar rats

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Open Journal of Preventive Medicine 2011年第2期1卷 66-71页

作者： Tatsuhiro Matsuo Reika Ishii yoko Shirai Faculty of Agriculture Kagawa University Ikenobe Miki-cho Kita-gun Kagawa 761-0795 Japan

D-Psicose is a rare sugar present in small quantities in natural products. In a previous study, we showed that D-psicose suppresses increase in plasma glucose and reduces body fat accumulation in rats. Based on acute and chronic toxicity testing in rats, D-psicose is classified as an ordinary and safe substance. Recently, we developed a high D-psicose syrup (PS) made from high fructose corn syrup (HFCS) by the alkaline isomerization method. However, the safety of PS as a food additive has not been demonstrated. In this study, we investigated the effects of 90-day feeding of PS in male Wistar rats. The rats were fed diets containing 3% D-psicose (control) or 4.3% PS for 90 days. The body weight gain and intra-abdominal adipose tissue weight did not differ between the control and PS group. The weights of the tissues did not differ between the two dietary groups. In clinical chemistry and hematological analyses, no differences were found between the control and PS groups. No gross pathological findings were evident at dietary doses of 4.3% PS. Therefore, the present study found no adverse effects of PS in rats fed a diet containing 4.3% PS for 90 days.

关键词： D-Psicose D-Psicose Syrup 90-Day Feeding Pathological Tests Rat

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Quantifying the Effect of Metformin 1000 mg/day in Japanese Patients with Type 2 Diabetes

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International Journal of Clinical Medicine 2014年第15期5卷 894-901页

作者： Katsunori Suzuki Taishi Yoshioka yoko Wakui Division of Endocrinology and Metabolism Saiseikai Niigata Daini Hospital Niigata Japan

Objective: To examine the effect of high-dose metformin on glucose metabolism in Japanese patients with type 2 diabetes. Method: A total of 144 patients with type 2 diabetes who could be followed up for 6 months after their dose of metformin was increased to 1000 mg/day (from 750 mg/day or less) were examined. The dose of metformin was increased from 750 mg/day in 70 subjects (250-mg dose increase) and from 500 mg/day in 74 subjects (500-mg dose increase). Results: After the dose increased to 1000 mg/day, HbA1c was significantly decreased by 0.65% ± 0.7%, 0.42% ± 0.5%, and 0.87% ± 0.7% in all subjects, the 250-mg dose increase group, and the 500-mg dose increase group, respectively. No significant change was observed in weight. Analysis by BMI (2 and ≥25 kg/m2) revealed a comparable significant decrease in HbA1c in all subjects, the 250-mg dose increase group, and the 500-mg dose increase group. Analysis by duration of diabetes showed a significant decrease in HbA1c regardless of the duration. Conclusion: Increasing the metformin dose to 1000 mg/day showed a significant antihyperglycemic effect over 6 months in Japanese patients with type 2 diabetes. Blood glucose improved regardless of the duration of diabetes or the presence or absence of obesity. Overall tolerability was favorable.

关键词： High-Dose Metformin Type 2 Diabetes HbA1c

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