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Pathogenesis of NSAID-induced gastric damage:Importance of cyclooxygenase inhibition and gastric hypermotility

World Journal of Gastroenterology 2012年第18期18卷 2147-2160页

作者： Koji takeuchi Department of Pharmacology and Experimental Therapeutics Division of Pathological SciencesKyoto Pharmaceutical UniversityKyoto 607-8414Japan

This article reviews the pathogenic mechanism of nonsteroidal anti-inflammatory drug(NSAID)-induced gastric damage,focusing on the relation between cyclooxygenase(COX) inhibition and various functional events.NSAIDs,such as indomethacin,at a dose that inhibits prostaglandin(PG) production,enhance gastric motility,resulting in an increase in mucosal permeability,neutrophil infiltration and oxyradical production,and eventually producing gastric lesions.These lesions are prevented by pretreatment with PGE 2 and antisecretory drugs,and also via an atropine-sensitive mechanism,not related to antisecretory action.Although neither rofecoxib(a selective COX-2 inhibitor) nor SC-560(a selective COX-1 inhibitor) alone damages the stomach,the combined administration of these drugs provokes gastric lesions.SC-560,but not rofecoxib,decreases prostaglandin E 2(PGE 2) production and causes gastric hypermotility and an increase in mucosal permeability.COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib.The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility.In addition,selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions,including adrenalectomy,arthritis,and Helicobacter pylori-infection.In summary,gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage,and the response,causally related with PG deficiency due to COX-1 inhibition,occurs prior to other pathogenic events such as increased mucosal permeability;and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2,the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility,and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition.

关键词：胃粘膜损伤非甾体抗炎药发病机理 COX-2抑制剂环氧化酶 COX-1 前列腺素E 致病机制

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Understanding Interfacial Chemistry Interactions in Energy-Dense Lithium-Ion Electrodes

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Accounts of Materials Research 2023年第2期4卷 156-167页

作者： Donghee Gueon Miguel A.Gonzalez Kenneth J.takeuchi Esther S.takeuchi Amy C.Marschilok Elsa Reichmanis Department of Chemical and Bimolecular Engineering Lehigh UniversityBethlehemPennsylvania 18015United States School of Chemical and Biomolecular Engineering Georgia Institute of TechnologyAtlantaGeorgia 30332United States Interdisciplinary Science Department Brookhaven National LaboratoryUptonNew York 11973United States Institute for Energy Sustainability and Equity Stony Brook UniversityStony BrookNew York 11794United States Department of Material Science and Chemical Engineering Stony Brook UniversityStony BrookNew York 11794United States Department of Chemistry Stony Brook UniversityStony Brook 11794United States

For the past two decades,conversion and alloying-type materials have been heralded as the natural heir to commercially available graphite anodes due to their ability to deliver high gravimetric/volumetric power.Commercialization of batteries with these high-energy-density active materials could impact a variety of sectors including electric vehicles,grid storage,and consumer electronics and contribute toward an ever-increasing electrified world.However,the various failure mechanisms from inherent interfacial chemical instabilities associated with these materials make them unable to be merely substituted into currently available electrode fabrication and formulation processing techniques.As a result,realizing the high theoretical capacity and achieving commercial viability of these materials will rely on the careful manipulation of interfacial chemical interactions that dictate and control various kinetic and transport processes across multiple scales of the composite electrode.This has led to a plethora of research that has focused on systematically understanding properties of the different electrode components and designing carefully constructed electrode formulations to achieve composite electrodes with increased chemical stability,enhanced local mixed conductivities,or improved mechanical resilience.This Account relates recent progress in the understanding of synergetic opportunities for energy-dense,resilient composite anodes.By understanding the interplay between components of the composite electrode,we can construct enhanced well-integrated electrodes with performance metrics that surpass empirically derived architectures.Due to the increased complexity of high-volume-expanding electrodes,performance is more than the cumulative contributions of the individual components,and therefore energy and compatibility matching are important for robust electrochemical performance across cycling,rate capability,facile lithium-ion transport,and stability.In this Account,synergistic opportunities are framed from a chemis

关键词： composite interfacial electrode

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PPARα activator irbesartan suppresses the proliferation of endometrial carcinoma cells via SREBP1 and ARID1A

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Oncology Research 2023年第3期31卷 239-253页

作者： YU LU TSUTOMU MIYAMOTO HODAKA takeuchi FUMI TSUNODA NAOKI TANAKA TANRI SHIOZAWA Department of Obstetrics and Gynecology School of MedicineShinshu UniversityMatsumoto390-8621Japan Department of Global Medical Research Promotion School of MedicineShinshu University GraduateMatsumotoNagano390-8621Japan International Relations Office School of MedicineShinshu UniversityMatsumotoNagano390-8621Japan Research Center for Social Systems Shinshu UniversityMatsumotoNagano390-8621Japan

Endometrial carcinoma(EMC)is associated with obesity;however,the underlying mechanisms have not yet been elucidated.Peroxisome proliferator-activated receptor alpha(PPARα)is a nuclear receptor that is involved in lipid,glucose,and energy metabolism.PPARαreportedly functions as a tumor suppressor through its effects on lipid metabolism;however,the involvement of PPARαin the development of EMC remains unclear.The present study demonstrated that the immunohistochemical expression of nuclear PPARαwas lower in EMC than in normal endometrial tissues,suggesting the tumor suppressive nature of PPARα.A treatment with the PPARαactivator,irbesartan,inhibited the EMC cell lines,Ishikawa and HEC1A,by down-regulating sterol regulatory element-binding protein 1(SREBP1)and fatty acid synthase(FAS)and up-regulating the tumor suppressor genes p21 and p27,antioxidant enzymes,and AT-rich interaction domain 1A(ARID1A).These results indicate the potential of the activation of PPARαas a novel therapeutic approach against EMC.

关键词： Peroxisome proliferator-activated receptor alpha Sterol regulatory element-binding protein 1 Antioxidant Migration

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Reproducible reformation of a bilayer lipid membrane using microair bubbles

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液滴(英文) 2023年第3期2卷 90-98页

作者： Izumi Hashimoto Toshihisa Osaki Hirotaka Sugiura Hisatoshi Mimura Sho Takamori Norihisa Miki Shoji takeuchi Artificial Cell Membrane Systems Group Kanagawa Institute of Industrial Science and TechnologyKanagawaJapan Department of Mechanical Engineering Keio UniversityKanagawaJapan Institute of Industrial Science The University of TokyoTokyoJapan Graduate School of Information Science and Technology The University of TokyoTokyoJapan

Planar bilayer lipid membranes(BLMs)are widely used as models for cell membranes in various applications,including drug discovery and biosensors.However,the nanometer-thick bilayer structure,assembled through hydrophobic interactions of amphiphilic lipid molecules,makes such BLM systems mechanically and electrically unstable.In this study,we developed a device to reform BLMs using a microair bubble.The device consists of a double well divided by a separator with a microaperture,where a BLM was formed by infusing a lipiddispersed solvent and an aqueous droplet into each well in series.When the BLM ruptured,a microair bubble was injected from the bottom of the well to split the merged aqueous droplet at the microaperture,which resulted in the reformation of two lipid monolayers on the split droplets.By bringing the two droplets into contact,a new BLM was formed.An angled step design was introduced in the BLM device to guide the bubble and ensure the splitting of the merged droplet.We also elucidated the optimal bubble inflow rate for the reproducible BLM reformation.Using a 4-channel parallel device,we demonstrated the individual and repeatable reformation of BLMs.Our approach will aid the development of automated and arrayed BLM systems.

关键词： bubble bringing unstable

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Preparation and incubation conditions affect the DNA integrity of ejaculated human spermatozoa

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Asian Journal of Andrology 2010年第5期12卷 753-759页

作者： Rieko Matsuura Takumi takeuchi Atsumi Yoshida The Reproduction Center Kiba Park Clinic Tokyo 135-0042 Japan

Appropriate semen processing and assessment are critical for successful infertility treatment. We investigated whether laboratory procedures including semen preparation and incubation affect sperm DNA integrity. A total of 153 infertile men were involved. Conventional semen parameters and sperm chromatin structure assay （SCSA） parameters, that is, DNA fragmentation index （%DFI） and high DNA stainability （%HDS）, were assessed on the flesh ejaculated semen samples, which were treated and incubated under different conditions. Negative correlations were identified between the %DFI and sperm concentration, motility, progressive motility and morphology. A lower percentage of DFI was detected in spermatozoa when density gradient centrifugation （DGC） was followed by swimup treatment in comparison with DGC alone （P 〈 0.01）. Although the %DFI increased in a time-dependent manner with incubation both at room temperature （RT） and at 37℃ in air, the %DFI after 24 h at RT was significantly lower than that at 37℃ （P 〈 0.05）. Incubation with 5% CO2 was effective in maintaining sperm motility （P 〈 0.01）; however, it induced further elevation of %DFI （P 〈 0.001）. Thus, sperm DNA damage was associated with longer incubation periods. Interestingly, common culture conditions, such as maintaining pH and temperature, compromised the sperm DNA integrity.

关键词： density gradient centrifugation DNA damage male infertility sperm chromatin structure assay spermatozoa

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Glycer-AGEs-RAGE signaling enhances the angiogenic potential of hepatocellular carcinoma by upregulating VEGF expression

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World Journal of Gastroenterology 2012年第15期18卷 1781-1788页

作者： Junichi Takino Shoichi Yamagishi Masayoshi takeuchi Department of Biochemistry Faculty of Pharmaceutical SciencesHiroshima International UniversityHiroshima 737-0112Japan Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications Kurume University School of MedicineKurume 830-0011Japan Department of Advanced Medicine Medical Research InstituteKanazawa Medical UniversityIshikawa 920-0293Japan

AIM:To investigate the effect of glyceraldehyde-derived advanced glycation end-products(Glycer-AGEs) on hepatocellular carcinoma(HCC)cells.METHODS:Two HCC cell lines(Hep3B and HepG2 cells)and human umbilical vein endothelial cells(HUVEC)were used.Cell viability was determined using the WST-8 assay.Western blotting,enzyme linked immunosorbent assay,and real-time reverse transcriptionpolymerase chain reactions were used to detect protein and mRNA.Angiogenesis was evaluated by assessing the proliferation,migration,and tube formation of HUVEC.RESULTS:The receptor for AGEs(RAGE)protein was detected in Hep3B and HepG2 cells.HepG2 cells werenot affected by the addition of Glycer-AGEs.GlycerAGEs markedly increased vascular endothelial growth factor(VEGF)mRNA and protein expression,which is one of the most potent angiogenic factors.Compared with the control unglycated bovine serum albumin(BSA) treatment,VEGF mRNA expression levels induced by the Glycer-AGEs treatment were 1.00±0.10 vs 1.92 ±0.09(P<0.01).Similarly,protein expression levels induced by the Glycer-AGEs treatment were 1.63±0.04 ng/mL vs 2.28±0.17 ng/mL for the 24 h treatment and 3.36±0.10 ng/mL vs 4.79±0.31 ng/mL for the 48 h treatment,respectively(P<0.01).Furthermore,compared with the effect of the control unglycated BSA-treated conditioned medium,the Glycer-AGEstreated conditioned medium significantly increased the proliferation,migration,and tube formation of HUVEC,with values of 122.4%±9.0%vs 144.5%±11.3%for cell viability,4.29±1.53 vs 6.78±1.84 for migration indices,and 71.0±7.5 vs 112.4±8.0 for the number of branching points,respectively(P<0.01).CONCLUSION:These results suggest that Glycer-AGEs-RAGE signaling enhances the angiogenic potential of HCC cells by upregulating VEGF expression.

关键词：血管生成因子 VEGF RAGE 肝癌细胞信号增强 mRNA表达水平血管内皮生长因子 HepG2细胞

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Gastrointestinal stromal tumor of the stomach with axillary lymph node metastasis: A case report

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World Journal of Gastroenterology 2017年第9期23卷 1720-1724页

作者： Naoki Kubo Nobumichi takeuchi Department of Surgery Ina central HospitalInashiNagano 396-8555Japan

Gastrointestinal stromal tumors (GISTs) are the most common type of gastrointestinal mesenchymal tumors, although metastasis to the perigastric lymph nodes is relatively rare, compared with liver or peritoneal metastasis. In this report, we describe a case of stomach GIST with a solitary simultaneous metastasis in the left axillary lymph node. A 68-year-old man was diagnosed with a large upper-stomach GIST, and computed tomography and positron emission tomography revealed masses in the left axilla and right mediastinum. We did not detect evidence of metastases to the liver, or other sites including the perigastric lymph nodes, although findings from the surgically resected axillary lymph nodes were compatible with GIST metastasis. Treatment using imatinib markedly reduced the gastric and mediastinal lesions, and this response persisted for 3 years. The patient subsequently experienced rapid growth of the gastric lesion without mediastinal or axilla recurrence, which required palliative surgery. Despite continuing medical treatment(sunitinib and regorafenib), the patient died of liver metastases 23 mo after the surgery. Based on our findings, it appears that the axillary lymph nodes can be a potential metastatic site for GIST metastasis.

关键词：胃肠的 stromal 肿瘤腋淋巴节点转移 Imatinib

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Appropriate Heart Rate in a Patient with Repaired Tetralogy of Fallot

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Congenital Heart Disease 2022年第6期17卷 647-652页

作者： Aya Miyazaki Hideki Uemura Yasuyo takeuchi Junya Tomida Yasuo Ono Yoshifumi Fujimoto Norie Mitsushita Akio Ikai Department of Transitional Medicine Division of Congenital Heart DiseaseShizuoka General HospitalShizuokaJapan Congenital Heart Disease Center Nara Medical UniversityKashiharaJapan Department of Cardiology Shizuoka General HospitalShizuokaJapan Department of Clinical Engineering Shizuoka General HospitalShizuokaJapan

Appropriate heart rate in a failing pulmonary ventricle remains unknown, particularly in congenital heart diseasewith unique hemodynamics. A 71-year-old male with repaired tetralogy of Fallot and a pacemaker for a sinusnode dysfunction suffered from heart failure symptoms with preserved left ventricular function. Simply changingthe pacemaker’s lower rate from 60 to 75 bpm, New York Heart Association classification improved from III to II,and hemodynamic parameters drastically improved. We regarded this case as informative. Appropriate heart ratecould be higher in congenital patients with failing right and non-failing left ventricles than in adults with malfunctioningLV.

关键词： Heart rate repaired tetralogy of Fallot failing right ventricle pacemaker lower rate the right-left ventricular interaction

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Thermal stability and mechanical properties of Gd-Co-Al bulk glass alloys

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中国有色金属学会会刊：英文版 2007年第6期17卷 1220-1224页

作者：陈鼎 A. takeuchi A. Inoue Institute for Metal Research Hunan University Institute for Materials Research Toho ku University Sendai 980-8577 Japan

The glass forming ability of Gd-Co-Al ternary alloy systems with a composition ranging from 50% to 70% (molar fraction) for Gd and from 5% to 40% (molar fraction) for Al were investigated by copper mold casting and Gd60Co25Al15 bulk glass alloy cylinders with the maximum diameter of 5 mm were obtained. The reduced glass transformation temperature (Tg/Tm) and the distance of supercooling region △Tx are 0.616 and 45 K, respectively for this Gd-Co-Al alloy. The compressive fracture strength (σf) and elastic modulus (E) of Gd-Co-Al glassy alloys are 1 170-1 380 MPa and 59-70 GPa, respectively. The Gd-Al-Co bulk glassy alloys with high glass forming ability and good mechanical properties are promising for the future development as a new type function materials.

关键词： Gd-Co-A1合金热稳定性机械性质玻璃合金

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Formulation design of granules prepared by wet granulation method using a multi-functional single-punch tablet press to avoid tableting failures

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Asian Journal of Pharmaceutical Sciences 2018年第2期13卷 113-119页

作者： Takashi Osamura Yoshiko takeuchi Risako Onodera Masahiro Kitamura Yoshiteru Takahashi Kohei Tahara Hirofumi takeuchi Laboratory of Pharmaceutical Engineering Gifu Pharmaceutical University Pharmaceutical Technology Department Sawai Pharmaceutical Co.Ltd

We previously determined "Tableting properties" by using a multi-functional single-punch tablet press(GTP-1). We plotted "Compactability" on the x-axis against "Manufacturability"on the y-axis to allow visual evaluation of "Tableting properties". Here, we examined whether this evaluation method can be used in the formulation design of tablets prepared by wet granulation. We used the GTP-1 to measure "Tableting properties" with different amounts of binder, disintegrant, and lubricant, and compared the results with those of tableting on a commercial rotary tableting machine. Tableting failures(capping and binding in particular) occurred when samples that had been evaluated as having poor "Compactability" or"Manufacturability" on the GTP-1 were compressed on the rotary tableting machine. Thus,our evaluation method predicted tableting failure at the commercial scale. The method will prove useful for scaling up production.

关键词： tableting formulation design wet granulation capping binding single-punch tablet press

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