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Involvement of the TAGE-RAGE system in non-alcoholic steatohepatitis: Novel treatment strategies

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World Journal of Hepatology 2014年第12期6卷 880-893页

作者： Masayoshi Takeuchi Jun-ichi Takino Akiko Sakasai-Sakai Takanobu Takata Tadashi Ueda Mikihiro tsutsumi Hideyuki Hyogo Sho-ichi Yamagishi Department of Advanced Medicine Medical Research Institute Kanazawa Medical University Uchinadamachi Ishikawa 920-0293 Japan Laboratory of Biochemistry Faculty of Pharmaceutical Sciences Hiroshima International University Kure Hiroshima 737-0112 Japan Department of Hepatology Kanazawa Medical University Uchinada-machi Ishikawa 920-0293 Japan Department of Gastroenterology and Metabolism Hiroshima University Hospital Hiroshima 734-8551 Japan Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications Kurume University School of Medicine Kurume Fukuoka 830-0011 Japan

Non-alcoholic fatty liver disease(NAFLD)is a major cause of liver disease around the *** includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis(NASH)and can lead to fibrosis,cirrhosis,liver failure,and/or hepatocellular *** is also associated with other medical conditions such as obesity,diabetes mellitus(DM),metabolic syn-drome,hypertension,insulin resistance,hyperlipidemia,and cardiovascular disease(CVD).In diabetes,chronic hyperglycemia contributes to the development of both macro-and microvascular conditions through a variety of metabolic ***,it can cause a variety of metabolic and hemodynamic conditions,including upregulated advanced glycation end-products(AGEs)*** our previous study,the most abundant type of toxic AGEs(TAGE);i.e.,glyceraldehyde-derived AGEs,were found to make a significant contribution to the pathogenesis of DM-induced ***,accumulating evidence suggests that the binding of TAGE with their receptor(RAGE)induces oxidative damage,promotes inflammation,and causes changes in intracellular signaling and the expression levels of certain genes in various cell populations including hepatocytes and hepatic stellate *** of these effects could facilitate the pathogenesis of hypertension,cancer,diabetic vascular complications,CVD,dementia,and ***,inhibiting TAGE synthesis,preventing TAGE from binding to RAGE,and downregulating RAGE expression and/or the expression of associated effector molecules all have potential as therapeutic strategies against ***,we examine the contributions of RAGE and TAGE to various conditions and novel treatments that target them in order to prevent the development and/or progression of NASH.

关键词： Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis Advanced glycation end-products Toxic advanced glycation end-products Receptor for advanced glycation end-products Toxic advanced glycation end-products-receptor for advanced glycation end-products system Diabetes mellitus Cardiovascular disease Dietary fructose Dietary advanced glycation end-products

Gastric linitis plastica with autoimmune pancreatitis diagnosed by an endoscopic ultrasonography-guided fine-needle biopsy: A case report

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World Journal of Clinical Cases 2022年第31期10卷 11607-11616页

作者： Ryosuke Sato Kazuyuki Matsumoto Hiromitsu Kanzaki Akihiro Matsumi Kazuya Miyamoto Kosaku Morimoto Hiroyuki Terasawa Yuki Fujii Tatsuhiro Yamazaki Daisuke Uchida Koichiro tsutsumi Shigeru Horiguchi Hironari Kato Gastroenterology and Hepatology Okayama University HospitalOkayama 700-8558Japan

BACKGROUND Gastric linitis plastica(GLP)is a subset of gastric cancer with a poor *** is difficult to obtain a definitive diagnosis by endoscopic mucosal biopsies,and the usefulness of an endoscopic ultrasonography-guided fine-needle biopsy(EUSFNB)for GLP has been recently ***,autoimmune diseases are occasionally known to coexist with malignant tumors as paraneoplastic *** herein report the usefulness of an EUS-FNB for detecting GLP and the possibility of paraneoplastic syndrome coexisting with *** SUMMARY An 81-year-old man was admitted to our hospital for a 1-mo history of epigastric pain that increased after *** laboratory data revealed high levels of serum carbohydrate antigen 19-9 and *** examinations showed giant gastric folds and reddish mucosa;however,no epithelial changes were *** gastric lumen was not distensible by air inflation,suggesting *** tomography showed the thickened gastric wall,the diffuse enlargement of the pancreas,and the peripancreatic rim,which suggested autoimmune pancreatitis(AIP)coexisting with *** the pathological findings of the endoscopic biopsy showed no malignancy,he underwent an EUSFNB and was diagnosed with *** received chemotherapy for unresectable gastric cancer due to peritoneal metastasis,after which both the gastric wall thickening and diffuse enlargement of the pancreas were *** An EUS-FNB for GLP with a negative endoscopic biopsy is useful,and AIP may develop as a paraneoplastic syndrome.

关键词： Endoscopic ultrasound-guided fine needle aspiration Linitis plastica Autoimmune pancreatitis Paraneoplastic syndromes Case report

Inflammatory cytokines promote inducible nitric oxide synthase-mediated DNA damage in hamster gallbladder epithelial cells

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World Journal of Gastroenterology 2007年第47期13卷 6379-6384页

作者： Amane Kitasato Yoshitsugu Tajima Tamotsu Kuroki Ryuji tsutsumi Tomohiko Adachi Takehiro Mishima Takashi Kanematsu Department of Surgery Nagasaki University Graduate School of Biomedical Sciences1-7-1 SakamotoNagasaki 852-8501Japan

AIM: To investigate the link between chronic biliary inflammation and carcinogenesis using hamster gallbladder epithelial cells. METHODS: Gallbladder epithelial cells were isolated from hamsters and cultured with a mixture of inflammatory cytokines including interleukin-1β,interferon-γ,and tumor necrosis factor-α. Inducible nitric oxide synthase (iNOS) expression,nitric oxide (NO) generation,and DNA damage were evaluated. RESULTS: NO generation was increased significantly following cytokine stimulation,and suppressed by an iNOS inhibitor. iNOS mRNA expression was demonstrated in the gallbladder epithelial cells during exposure to inflammatory cytokines. Furthermore,NO-dependent DNA damage,estimated by the comet assay,was significantly increased by cytokines,and decreased to control levels by an iNOS inhibitor. CONCLUSION: Cytokine stimulation induced iNOS expression and NO generation in normal hamster gallbladder epithelial cells,which was sufficient to cause DNA damage. These results indicate that NO-mediated genotoxicity induced by inflammatory cytokines through activation of iNOS may be involved in the process of biliary carcinogenesis in response to chronic inflammation of the biliary tree.

关键词： Biliary carcinoma Inflammation Inflammatory cytokine Nitric oxide Inducible nitric oxide synthase DNA damage Gallbladder epithelial cell Hamster

ENERGETIC RADIATION INDUCED SELF-ASSEMBLY OF FULLERENE CAGES,ATOM-BRIDGED FULLERENE DIMMERS AND IN SITU SCANNING TUNNELING MICROSCOPIC STUDY

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ENERGETIC RADIATION INDUCED SELF-ASSEMBLY OF FULLERENE CAGES...

Supercritical Fluid Impregnation of Essential Bark Oil in Copolymers of L-Lactide with 7-Membered Cyclic Compounds

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作者： SOICHIRO YOSHIMOTO EISHI tsutsumi KINGO ITAYA Department of Applied Chemistry Graduate School of EngineeringTohoku UniversityAoba-yama 04Sendai 980-8579Japan Department of Applied Chemistry Graduate School of EngineeringTohoku UniversityAoba-yama 04Sendai 980-8579Japan Department of Applied Chemistry Graduate School of EngineeringTohoku UniversityAoba-yama 04Sendai 980-8579Japan

＜正＞ Following a suggestion of Osterodt and Vogtle et al, Dragoe et al. synthesized a functionalized new type of carbon nanomolecule Cm in a thermolysis reaction of C60CBr2 with C60 at a high temperature of 723 K. It is also the first and only one of the C2m-C-C2n, （m=n or m·n） type molecules that have been successfully synthesized so far. In an experiment using electronically neutral beam （neutron） to probe the uniqueness in properties of nanospaces, we found mat energetic-radiation induced self-assembly process of fullerene units was a simple and highly selective method for synthesis of C2m-X-C2n bridged molecules without formation of other byproducts. Tbe method is capable of synthesizing new C2m-X-C2n molecules by introducing X （different atoms） into the reaction system. The results revealed an intriguing new process: Energetic radiation created reactive sites for covalently-bonded bridges between fullerene molecules originally only weakly bound by van der Waals force. This observation may open a new subject and practicable approach for polymer sciences of *** the new method, C70-C-C70, C60-C-C70, C60-C-C60, and C70-O-C70 were prepared and characterized by in situ scanning tunneling microscopy. Their results together with those for direct fullerene dimers C2m=C2n （m=n or m·n）, and pristine cage unite before energetic radiation-induced self-assembly will be presented at the conference.

关键词： Bridged fullerene dimer In situ scanning tunneling microscopy.

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Journal of Biomaterials and Nanobiotechnology 2014年第3期5卷 159-172页

作者： Chikara tsutsumi Teruyuki Hara Yuka Ueno Yuushou Nakayama Takeshi Shiono Department of Applied Chemistry and Biotechnology Niihama National College of Technology NiihamaJapan Department of Applied Chemistry Graduate School of Engineering Hiroshima University Higashi-Hiroshima Japan

In order to develop a novel controlled-release material, we previously attempted to impregnate poly(L-lactide) (poly(L-LA)), poly(L-LA-ran-CL) (CL: ε-caprolactone) or poly(L-LA-ran-TEMC) (TEMC: tetramethylene carbonate) with low boiling point, organic useful compounds using supercritical carbon dioxide (scCO2) as the solvent. In this work, the factors influencing impregnation of poly (L-LA) random copolymers with useful compounds were investigated under scCO2 using the copolymers previously used. The influence of temperature, pressure, and time on the impregnation contents of the useful compounds on the copolymers was evaluated. The polymer used, which is a base of this material, was poly(L-LA-ran-CL), poly(L-LA-ran-TEMC), or poly(L-LA-ran-DXO) (DXO: 1,5-dioxepan-2-one). Statistical random copolymers of L-LA with CL, TEMC, or DXO were synthesized using Sn(oct)2 as a catalyst at 150°C for 24 h without solvent. Preparation of the controlled-release materials was carried out using essential bark oil from Thujopsis dolabrata var. hondae and synthetic L-LA random copolymers as a base material under scCO2. The impregnation experiment, which investigated the influence of pressure, was conducted in the range of 10 to 20 MPa. The influence of temperature on impregnation was carried out at 40°C to 100°C. Impregnation time was varied from 1 to 5 h. The pressure of essential oil impregnated into poly(L-LA) random copolymers was the highest at 14 MPa. In the influence of temperature on impregnation, the amount of essential oil increased with increasing temperature.

关键词： Biodegradable Polyester L-Lactide Copolymer Supercritical Carbon Dioxide Impregnation

Hepatitis B virus reactivation with rituximab-containing regimen

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World Journal of Hepatology 2013年第11期5卷 612-620页

作者： Yutaka tsutsumi Yoshiya Yamamoto Joji Shimono Hiroyuki Ohhigashi Takanori Teshima Department of Hematology Hakodate Municipal Hospital Department of Gastroenterology Ha-kodate Municipal Hospital Takanori Teshima Department of Hematology Hokkaido University Graduate School of Medicine

Rituximab is recognized as a useful drug for the treatment of B-cell non-Hodgkin’s lymphoma and its use has been extended to such diseases as idiopathic thrombocytopenic purpura,thrombotic thrombocytopenic purpura,chronic rheumatoid arthritis and ANCA-associated *** serious complication associated with its use is the reactivation of hepatitis B virus and the search for methods to prevent this occurrence has resulted in the rapid accumulation of *** this review,we discuss case analyses from our department and other groups and outline the current knowledge on the topic and the remaining issues.

关键词： Rituximab Hepatitis B virus Reactivation Chemotherapy Lamivudine Non-Hodgkin’s lymphoma

Numerical Investigation for the Effect of Unsaturated Aliphatic Hydrocarbons Addition on Precursors on Carbon Black

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Journal of Chemistry and Chemical Engineering 2012年第10期6卷 936-941页

作者： Kiminori Ono Shunsuke takeya Yasuhiro Saito Hideyuki Aoki Okiteru Fukuda Takayuki Aoki TogoYamaguchi Department of Chemical Engineering Graduate School of Engineering Tohoku University Miyagi 980-8579 Japan ASAHI CARBON CO. LTD. Niigata 950-0883 Japan

To investigate the effect of unsaturated aliphatic hydrocarbons on PAHs （polycyclic aromatic hydrocarbons） formation, numerical analysis using detailed reaction mechanism is performed. For the carbon black produced by benzene feedstock, three kinds of unsaturated aliphatic hydrocarbons （acetylene, diacetylene, and vinylacetylene） are added. The detailed reaction mechanism which is proposed by Wang and Frenklach is consisted by 527 reactions and 99 chemical species. The formations of PAHs and nuclei are promoted by unsaturated aliphatic hydrocarbons addition. There exits optimal benzene/acetylene ratio （XA/XB = 0.50）, benzene/diacetylene mixture ratio （XD/XB = 0.60）, benzene/vinyl-acetylene mixture ratio （XV/XB = 0.25）. The formation of nuclei is most promoted by acetylene addition, and the benzene/acetylene mixture ratio is 0.50.

关键词： Carbon black soot unsaturated hydrocarbon.

Urban-Design Process with Snow and Wind Simulations： A Study on the Kitami City Hall

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Journal of Civil Engineering and Architecture 2017年第2期11卷 107-120页

作者： Norihiro Watanabe Tsuyoshi Setoguchi Shota Yokoyama Zhiming Guo Takuya tsutsumi Graduate School of Engineering Hokkaido University Sapporo 060-8628 Japan Northern Regional Building Research Institute Hokkaido Research Organization Asahikawa 078-8801 Japan

Regional climatic conditions should be considered while designing urban development plans, with special attention to the impact of snowfall on public spaces in cities with harsh winters. The Kitami-city-hall-renewal project in Hokkaido, Japan was studied as an environmental assessment of snow drifting. Assessments of the two site plans proposed during the architectural planning process （A-type and B-type） were conducted in terms of the following three items：（1） The two site plans indicate snow-drifting problems around the main entrance; （2） More number of local snowdrifts on the main-street sidewalks were suggested in the B-type design; （3） Less number of snowdrifts in the parking area beside the railroad were indicated in the A-type design. These results were reflected in the architectural planning process. On the basis of this study, a desirable design process incorporating environmental assessments has been identified for cities with harsh winters.

关键词： Winter cities snow simulations wind tunnel urban design environmental assessments.

Effects of 5-HT2B, 5-HT3 and 5-HT4 receptor antagonists on gastrointestinal motor activity in dogs

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World Journal of Gastroenterology 2013年第39期19卷 6604-6612页

作者： Hiroki Morita Erito Mochiki Nobuyuki Takahashi Kiyoshi Kawamura Akira Watanabe Toshinaga Sutou Atsushi Ogawa Mitsuhiro Yanai Kyoichi Ogata Takaaki Fujii Tetsuro Ohno Souichi tsutsumi Takayuki Asao Hiroyuki Kuwano Department of General Surgical Science (Surgery 1) Gunma UniversityGraduate School of MedicineGunma 371-8511Japan RaQualia Pharma Inc. Research and Development5-2 TaketoyoAichi 470-2341Japan

AIM:To study the effects of 5-hydroxytryptamine(5-HT)receptor antagonists on normal colonic motor activity in conscious ***:Colonic motor activity was recorded using a strain gauge force transducer in 5 dogs before and after 5-HT2B,5-HT3 and 5-HT4 receptor antagonist *** force transducers were implanted on the serosal surfaces of the gastric antrum,terminal ileum,ileocecal sphincter and *** materials or vehicle alone was administered as an intravenous bolus injection during a quiescent period of the whole colon in the interdigestive *** effects of these receptor antagonists on normal gastrointestinal motor activity were ***:5-HT2B,5-HT3 and 5-HT4 receptor antagonists had no contractile effect on the fasting canine terminal *** 5-HT3 and 5-HT4 receptor antagonists inhibited phaseⅢof the interdigestive motor complex of the antrum and significantly inhibited colonic motor *** the proximal colon,the inhibitory effect was dose *** dependency,however,was not observed in the distal *** 5-HT2B receptor antagonist had no contractile effect on normal colonic motor ***:The 5-HT3 and 5-HT4 receptor antagonists inhibited normal colonic motor ***5-HT2B receptor antagonist had no contractile effect on normal colonic motor activity.

关键词： 5-hydroxytryptamine receptor antagonist Colonic motility Irritable bowel syndrome