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Identification of some benproperine metabolites in humans and investigation of their antitussive effect

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Acta Pharmacologica sinica 2005年第12期26卷 1519-1526页

作者： Isamu MAEBA Faculty of Pharmacy Meijo university Japan nagoya 460-8503

Aim:To identify 4 unknown metabolites of benproperine(BPP,1)in human urineafter a po dose,and to investigate the antitussive effect of ***:The putative metabolite references were prepared usingchemical *** structures were identified using ~1H and13C nuclearmagnetic resonance,and mass *** metabolites in human urinewere separated and assayed using liquid chromatography-ion trap mass spec-trometry(LC/Ms/Ms),and further confirmed by comparison of their mass spectraand chromatographic retention times with those of synthesized *** antitussive effects of metabolites were evaluated on coughsinduced by 7.5% citric acid in conscious guinea ***:1-[1-Methyl-2-[2-(phenylmethyl)phenoxy]-ethyl]-4-piperidinol(2),1-[1-methyl-2-[2-(phenylmethyl)phenoxy]ethyl]-3-piperidinol(3)and their glucuronides 4 and 5 were obtainedfrom chemical *** urinary metabolites in human urine showed peakswith the same chromatographic retention times and mass spectra in LC/Ms/Ms assynthetic substances 2,3,4 and *** of compounds 2 and 3 prolongedthe latency of cough and reduced the number of coughs during the 3 rain testusing citric acid,but did not reduce the number of coughs during the 5 min imme-diately after the test in conscious guinea ***:Compounds 2,3,4,and 5 were identified as the metabolites of BPP in human *** them,compounds 2 and 3 are inactive in the antitussive effect.

关键词： benproperine metabolism antitussive agents hydroxylation glucuronide high performance liquid chromatography mass spectrometry

Chemotherapy as a component of multimodal therapy for gastric carcinoma

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World Journal of Gastroenterology 2006年第13期12卷 2000-2005页

作者： Yasuhiro Kodera Michitaka Fujiwara Masahiko Koike Akimasa Nakao Department of surgery Ⅱ nagoya university Graduate school of Medicine 65Tsurumai-choShowa-kuNagoyaAichi 466-8550Japan

Prognosis of locally advanced gastric cancer remains poor, and several multimodality strategies involving surgery, chemotherapy, and radiation have been tested in clinical trials. Phase Ⅲ trial testing the benefit of postoperative adjuvant chemotherapy over treatment with surgery alone have revealed little impact on survival, with the exception of some small trials in Western nations. A large trial from the United states exploring postoperative chemoradiation was the first major success in this category. Results from Japanese trials suggest that moderate chemotherapy with oral fluoropyrimidines may be effective against less-advanced （T2-stage） cancer, although another confirmative trial is needed to prove this point. Investigators have recently turned to neoadjuvant chemotherapy, and some promising results have been reported from phase Ⅱ trials using active drug combinations. In 2005, a large phase Ⅲ trial testing preand postoperative chemotherapy has proven its survival benefit for resectable gastric cancer. since the rate of pathologic complete response is considered to affect treatment results of this strategy, neoadjuvant chemoradiation that further increases the incidence of pathologic complete response could be a breakthrough, and phase Ⅲ studies testing this strategy may be warranted in the near future.

关键词： surgery Radiation Anticancer drug Adjuvant chemotherapy Neoadjuvant chemotherapy

VIsUALIZATION OF TURBULENT REACTIVE JET BY UsING DIRECT NUMERICAL sIMULATION

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International Journal of Modeling, simulation, and scientific Computing 2013年第S1期4卷 70-85页

作者： TOMOAKI WATANABE YAsUHIKO sAKAI KOUJI NAGATA OsAMU TERAsHIMA HIROKI sUZUKI TOsHIYUKI HAYAsE YAsUMAsA ITO Department of Mechanical science and Engineering nagoya university Nagoya Aichi464-8603Japan Department of Engineering Physics nagoya Institute of Technology nagoya Aichi466-8555Japan Institute of Fluid science Tohoku University SendaiMiyagi980-8577Japan

Direct numerical simulation(DNs)of turbulent planar jet with a second-order chemical reaction(A+B→R)is performed to investigate the processes of mixing and chemical reactions in spatially developing turbulent free shear *** A is premixed into the jet flow,and reactant B is premixed into the ambient *** is performed at three different Damk¨ohler numbers(Da=0.1,1,and 10).Damk¨ohler number is a ratio of a time scale of a flow to that of chemical reactions,and in this study,the large Da means a fast chemical reaction,and the small Da means a slow chemical *** visualization of velocity field shows that the jet flow is developed by entraining the ambient *** visualization of concentration of reactant A shows that concentration of reactant A for Da=1 and 10 becomes very small in the downstream region because the chemical reaction consumes the reactants and reactant A is diffused with the jet *** comparison of the profiles of chemical reaction rate and concentration of product R,it is found that product R for Da=10 is produced by the chemical reaction at the interface between the jet and the ambient fluids and is diffused into the jet flow,whereas product R for Da=0.1 is produced in the jet flow after reactants A and B are well mixed.

关键词： Turbulent flow direct numerical simulation jet.

Role of microRNAs in gastric cancer

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World Journal of Gastroenterology 2014年第19期20卷 5694-5699页

作者： Hideyuki Ishiguro Masahiro Kimura Hiromitsu Takeyama Department of Gastroenterological surgery Nagoya City University Graduate School of Medical SciencesNagoya 467-8601Japan

Although gastric cancer(GC)is one of the leading causes of cancer-related death,major therapeutic advances have not been made,and patients with GC still face poor *** prognosis of GC also remains poor because the molecular mechanisms of GC progression are incompletely ***(miRNAs)are noncoding RNAs that are associated with gastric *** investigating the regulation of gene expression by miRNAs have made considerable progress in recent years,and abnormalities in miRNA expression have been shown to be associated with the occurrence and progression of *** contribute to gastric carcinogenesis by altering the expression of oncogenes and tumor suppressors,affecting cell proliferation,apoptosis,motility,and ***,a number of miRNAs have been shown to be associated with tumor type,tumor stage,and patient survival and therefore may be developed as novel diagnostic or prognostic *** this review,we discuss the involvement of miRNAs in GC and the mechanisms through which they regulate gene expression and biological ***,we review recent research on the involvement of miRNAs in GC prognosis,their potential use in chemotherapy,and their effects on Helicobacter pylori infections in GC.A greater understanding of the roles of miRNAs in gastric carcinogenesis could provide insights into the mechanisms of tumor development and could help to identify novel therapeutic targets.

关键词： MicroRNA Gastric cancer Reverse transcription-polymerase chain reaction Chemosensitivity Helicobacter pylori Circulating MicroRNA

Micronization of curcumin with biodegradable polymer by supercritical anti-solvent using micro swirl mixer

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Frontiers of Chemical science and Engineering 2018年第1期12卷 184-193页

作者： Kimthet Chhouk Wahyudiono Hideki Kanda shin-Ichro Kawasaki Motonobu Goto Department of Chemical Engineering Nagoya University Nagoya 464-8603 Japan Department of Chemical Engineering and Food Technology Institute of Technology of Cambodia Phnom Penh Cambodia Department of Materials Process Engineering Nagoya University Nagoya 464-8603 Japan Research Institute for Chemical Engineering Process Technology National Institute of Advanced Industrial Science and Technology Sendai 983-8551 Japan

Curcumin is a hydrophobic polyphenol compound exhibiting a wide range of biological activities such as anti-inflammatory, anti-bacterial, anti-fungal, anti-carcinogenic, anti-human immunodeficiency virus, and antimicrobial activity. In this employed to produce the work, a swirl mixer was micronized curcumin with polyvinylpyrrolidone （PVP） by the supercritical antisolvent process to improve the bioavailability of curcumin. The effects of operating parameters such as curcumin/PVP ratio, feed concentration, temperature, pressure, and CO2 flow rate were investigated. The characterization and solubility of particles were determined by using scanning electron microscopy, Fourier Transform Infrared spectroscopy, and ultra-violet-visible spectroscopy. The result shows that the optimal condition for the production of curcumin/PVP particles is at curcumin/PVP ratio of 1：30, feed concentration of 5 mg·mL^-1, temperature of 40 ℃, pressure of 15 MPa, and CO2 flow rate of 15 mL·min^-1. Moreover, the dissolution of curcumin/PVP particles is faster than that of raw curcumin.

关键词： micronization curcumin polyvinylpyrrolidone supercritical anti-solvent swirl mixer

A comparative study of automotive trip characteristics between older drivers and others among densely inhabited district and other areas

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Journal of Modern Transportation 2016年第3期24卷 177-186页

作者： Yanning Zhao Toshiyuki Yamamoto Takayuki Morikawa Department of Civil Engineering Nagoya University Institute of Materials and systems for sustainability Nagoya University Institute of Innovation for Future society Nagoya University

This paper examines older driver＇s automotive trip （abbreviation： trip） characteristics which include trip frequency, trip length, destination distribution, and non- home-based （NHB） trips. A two-month experiment of 108 participants was carried out to collect GPs tracking data in Aichi Prefecture, Japan. To identify the effect of living area, a comparative analysis between older drivers and others is conducted in densely inhabited district （DID, i.e., urban） and other areas （non-DID, i.e., suburban, rural, etc）, separately. The present study found that there was no sig- nificant difference between the trip characteristics of older drivers and others who were living in DID. Thus, we suggest that the education of safety driving and the rec- ommendation of public transportation should be given to DID-living older drivers. However, the results of non-DID reflected that older drivers＇ trip frequency, trip length, destination, and NHB trips rate were shorter and lower than others＇. This implies that electric vehicles may be suit- able for promotion among older drivers in suburban and rural area. Furthermore, the regression analysis confirmed that ＂older driver＂ was a significant independent variable on trip frequency, trip length, and NHB trips, and there were interaction effects between ＂older driver＂ and ＂living areas＂ on all trip characteristics.

关键词： Older driver Travel behavior Living areaTrip frequency - Trip length Destination distribution Non-home-based (NHB) trips

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Advances in refractory ulcerative colitis treatment: A new therapeutic target, Annexin A2

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World Journal of Gastroenterology 2015年第29期21卷 8776-8786页

作者： satoshi Tanida Tsutomu Mizoshita Keiji Ozeki Takahito Katano Hiromi Kataoka Takeshi Kamiya Takashi Joh Department of Gastroenterology and Metabolism Nagoya City University Graduate School of Medical Sciences Nagoya city Aichi prefecture

Medical treatment has progressed significantly over the past decade towards achieving and maintaining clinical remission in patients with refractory ulcerative colitis(UC). Proposed mediators of inflammation in UC include pro-inflammatory cytokines such as tumor necrosis factor-α(TNF-α) and interleukin-2, and the cellsurface adhesive molecule integrin α4β7. Conventional therapeutics for active UC include 5-aminosalicylic acid, corticosteroids and purine analogues(azathioprine and 6-mercaptopurine). Patients who fail to respond to conventional therapy are treated with agents such as the calicineurin inhibitors cyclosporine and tacrolimus, the TNF-α inhibitors infliximab or adalimumab, or a neutralizing antibody(vedolizumab) directed against integrin α4β7. These therapeutic agents are of benefit for patients with refractory UC, but are not universally effective. Our recent research on TNF-α shedding demonstrated that inhibition of annexin(ANX) A2 may be a new therapeutic strategy for the prevention of TNF-α shedding during inflammatory bowel disease(IBD) inflammation. In this review, we provide an overview of therapeutic treatments that are effective and currently available for UC patients, as well as some that are likely to be available in the near future. We also propose the potential of ANX A2 as a new molecular target for IBD treatment.

关键词： Tumor necrosis factor-α shedding Integrin α4β7 Epidermal growth factors

Nicotiana benthamiana XYLEM CYsTEINE PROTEAsE genes facilitate tracheary element formation in interfamily grafting

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Horticulture Research 2023年第6期10卷 70-81页

作者： Chaokun Huang Ken-ichi Kurotani Ryo Tabata Nobutaka Mitsuda Ryohei sugita Keitaro Tanoi Michitaka Notaguchi Graduate school of Bioagricultural sciences Nagoya UniversityFuro-choChikusa-kuNagoya 464-8601Japan Bioscience and Biotechnology Center Nagoya UniversityFuro-choChikusa-kuNagoya 464-8601Japan Bioproduction Research Institute National Institute of Advanced Industrial Science and Technology(AIST)TsukubaIbaraki 305-8566Japan Isotope Facility for Agricultural Education and Research Graduate School of Agricultural and Life SciencesThe University of TokyoYayoiBunkyo-kuTokyo 113-8657Japan Radioisotope Research Center Nagoya UniversityFuro-choChikusa-kuNagoya 464-8602Japan Institute of Transformative Bio-Molecules Nagoya UniversityFuro-choChikusa-kuNagoya 464-8601Japan

Grafting is a plant propagation technique widely used in agriculture.A recent discovery of the capability of interfamily grafting in Nicotiana has expanded the potential combinations of *** this study,we showed that xylem connection is essential for the achievement of interfamily grafting and investigated the molecular basis of xylem formation at the graft *** and gene network analyses revealed gene modules for tracheary element(TE)formation during grafting that include genes associated with xylem cell differentiation and immune *** reliability of the drawn network was validated by examining the role of the Nicotiana benthamiana XYLEM CYsTEINE PROTEAsE(NbXCP)genes in TE formation during interfamily *** activities of NbXCP1 and NbXCP2 genes were found in differentiating TE cells in the stem and callus tissues at the graft *** of a Nbxcp1;Nbxcp2 loss-of-function mutant indicated that NbXCPs control the timing of de novo TE formation at the graft ***,grafts of the NbXCP1 overexpressor increased the scion growth rate as well as the fruit ***,we identified gene modules for TE formation at the graft boundary and demonstrated potential ways to enhance Nicotiana interfamily grafting.

关键词： grafting element graft

Finite element polycrystal model simulation of cold rolling textures in deformation processed two-phase Nb/Al metal-metal composites

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中国有色金属学会会刊：英文版 2005年第1期15卷 64-71页

作者：陈礼清 KANETAKE Naoyuki Institute of Metal Research Chinese Academy of SciencesShenyang 110016China school of Engineering Nagoya UniversityFuro-choChikusa-kuNagoya 464-8603Japan

The finite element polycrystal model (FEPM) was extended and applied to simulate the development of the cold rolling textures of matrix aluminum in deformation processed two-phase 10% and 20%Nb/Al(in volume fraction) metal-metal composites on the basis of slip deformation of individual grains. This simulation method can assure the continuity of stress and displacement at the boundary during heterogeneous deformation and take arbitrary boundary conditions into consideration. The starting hot-extruded textures, as initial input condition, were taken into account in the FEPM simulation. The simulation results show that the main texture components and their evolution after various cold rolling reductions in 10% and 20%Nb/Al metal-metal composites are well qualitatively in agreement with the experimental ones. The initially extruded textures are rather weak, so they have no much influence on the simulated final cold rolling textures of the matrix aluminum for Nb/Al composites.

关键词： metal-matrix composites FEPM Nb/Al composite texture rolling

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