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Analysis of Residual Solvents in Annatto Extracts Using a Static Headspace Gas Chromatography Method

American Journal of Analytical Chemistry 2012年第9期3卷 638-645页

作者： Yusai Ito Kyoko Ishizuki Wakana Sekiguchi Atsuko Tada Takumi Akiyama Kyoko Sato takeshi yamazaki Hiroshi Akiyama Division of Food Additives National Institute of Health Sciences: Kamiyoga Setagaya-ku Tokyo Japan

An analytical method for the quantification of residual solvents in annatto extracts, natural food colorants, was established using a static headspace gas chromatography (HSGC) coupled with a flame ionization detector (FID). As a sample diluent in a headspace sampling, dimethylformamide (DMF) was selected owing to its high capacity for dissolving both bixin-based and norbixin-based annatto extracts. The quantification of residual solvents was performed using the external standard method. The linearity of the calibration curves was assured with relative coefficients (R2) that were greater than 0.999. The recoveries of all standard solvents spiked in the annatto extracts were in the range from 95.1% to 107.1% to verify the accuracy and the relative standard deviation (RSD%) values (n = 3) were in the range from 0.57% to 3.31%. The quantification limits (QL) were sufficiently lower than the limits specified by Joint FAO/WHO Expert Committee on Food Additives (JECFA). With the established HSGC method, six residual solvents (methanol, ethanol, 2-propanol, acetone, ethyl acetate, and hexane) in 23 commercial annatto-extract products that consist of seven bixin-based and 16 norbixin-based products were quantified. The levels of residual ethyl acetate and hexane in all products were lower than the specified limits of JECFA. However, three samples of bixin-based products showed higher levels of residual 2-propanol (approximately 313.9 - 427.7 ppm) than the specified limit. Other bixin products also showed higher concentrations of residual methanol (approximately 166.6 - 394.7 ppm) and residual acetone (approximately 75.2 - 179.8 ppm) than the limits of JECFA. In the case of norbixin-based products, nine samples showed higher levels of residual acetone (approximately 42.6 - 139.5 ppm) than the limits of JECFA. This is the first survey of residual solvents in annatto extracts using the validated HSGC method.

关键词： Annatto Extracts Bixin Norbixin Headspace Gas Chromatography Residual Solvents

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Improvement of the Assay Method for Steviol Glycosides in the JECFA Specifications

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American Journal of Analytical Chemistry 2013年第4期4卷 190-196页

作者： Atsuko Tada Kyoko Ishizuki Junichi Iwamura Hirohisa Mikami Yoshiko Hirao Isao Fujita takeshi yamazaki Hiroshi Akiyama Yoko Kawamura Laboratory of Creative Science Co. Ltd. Misonocho Japan Morita Kagaku Kogyo Co. Ltd. Osaka Japan National Institute of Health Sciences Tokyo Japan Shimadzu Corporation Kyoto Japan

Steviol glycosides are natural sweetener constituents found in the leaves of Stevia rebaudiana Bertoni (Asteraceae). The specifications for steviol glycosides were established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 2008, although there was a call in the following year for the modification of this assay method to enable the determination of nine steviol glycosides rather than just seven. In response, based on a proposed method by the Japan Stevia Association, we developed an improved method by changing the HPLC conditions and including the use of an octadecylsilyl column instead of an amino-bonded column to enable the rapid and reliable determination of the nine steviol glycosides by an isocratic HPLC-UV method. With the developed method, the nine steviol glycosides can be separately determined, and identified using individual reference chemicals as standards, unlike the previous identification method, which was based on the relative retention times. In addition, the single stevioside quantification standard was replaced with both stevioside and rebaudioside A quantification standards. Importantly, the validation of the developed method was successful. The limits of quantification for the nine steviol glycosides were between 0.2% and 0.6%. The developed assay method for the nine steviol glycosides was proposed to JECFA and adopted as the revised assay method for the steviol glycosides specifications at its 73rd meeting in 2010.

关键词： Steviol Glycosides Stevioside Rebaudioside A Reversed-Phase HPLC JECFA Specifications

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夺回东京湾:16世纪外交危机前后中国对于越南海域的观点

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国家航海 2014年第3期 179-180页

作者：山崎岳

1541年,越南僭位者莫登庸(1483?~1541年)出现在明帝国的边关,表达了他对中国威权的顺服。次年,他的孙子莫福海(1541~1546年)被明王廷官方认可为合法的越南统治者。在作出该项政治决定之前,明帝国皇帝与官僚进行了长时间的辩论,即明王朝... 详细信息

1541年,越南僭位者莫登庸(1483?~1541年)出现在明帝国的边关,表达了他对中国威权的顺服。次年,他的孙子莫福海(1541~1546年)被明王廷官方认可为合法的越南统治者。在作出该项政治决定之前,明帝国皇帝与官僚进行了长时间的辩论,即明王朝是否应该对这个僭主王国给予惩罚性的攻击。

关键词：莫登庸明王朝惩罚性主王朝贡关系 Vietnam 吴朴 dispute Fujian offi

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Does a combined intervention program of repetitive transcranial magnetic stimulation and intensive occupational therapy affect cognitive function in patients with post-stroke upper limb hemiparesis?

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Neural Regeneration Research 2016年第12期11卷 1932-1939页

作者： Takatoshi Hara Masahiro Abo Kiyohito Kakita takeshi Masuda Ryunosuke yamazaki Department of Rehabilitation Medicine The Jikei University School of Medicine Department of Rehabilitation Medicine Kyoto Ohara Memorial Hospital

Low-frequency repetitive transcranial magnetic stimulation（LF-r TMS） to the contralesional hemisphere and intensive occupational therapy（i OT） have been shown to contribute to a significant improvement in upper limb hemiparesis in patients with chronic stroke. However, the effect of the combined intervention program of LF-r TMS and i OT on cognitive function is unknown. We retrospectively investigated whether the combined treatment influence patient＇s Trail-Making Test part B（TMT-B） performance, which is a group of easy and inexpensive neuropsychological tests that evaluate several cognitive functions. Twenty-five patients received 11 sessions of LF-r TMS to the contralesional hemisphere and 2 sessions of i OT per day over 15 successive days. Patients with right- and left-sided hemiparesis demonstrated significant improvements in upper limb motor function following the combined intervention program. Only patients with right-sided hemiparesis exhibited improved TMT-B performance following the combined intervention program, and there was a significant negative correlation between Fugl-Meyer Assessment scale total score change and TMT-B performance. The results indicate the possibility that LF-r TMS to the contralesional hemisphere combined with i OT improves the upper limb motor function and cognitive function of patients with right-sided hemiparesis. However, further studies are necessary to elucidate the mechanism of improved cognitive function.

关键词： nerve regeneration stroke repetitive transcranial magnetic stimulation Trail-Making Test cognitive function occupational therapy neural regeneration

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Identification of a dihydroorotate dehydrogenase inhibitor thatinhibits cancer cell growth by proteomic profiling

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肿瘤学研究(英文) 2023年第6期31卷 833-844页

作者： MAKOTO KAWATANI HARUMI AONO SAYOKO HIRANUMA takeshi SHIMIZU MAKOTO MUROI TOSHIHIKO NOGAWA TOMOKAZU OHISHI SHUN-ICHI OHBA MANABU KAWADA KANAMI yamazaki SHINGO DAN NAOSHI DOHMAE HIROYUKI OSADA Biomolecular Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Resource Development Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Chemical Biology Research Group RIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Molecular Structure Characterization Unit Technology Platform DivisionRIKEN Center for Sustainable Resource Science(CSRS)Saitama351-0198Japan Institute of Microbial Chemistry(BIKAKEN) NumazuMicrobial Chemistry Research FoundationShizuoka410-0301Japan Division of Molecular Pharmacology Cancer Chemotherapy CenterJapan Foundation for Cancer ResearchTokyo135-8550Japan Department of Pharmaceutical Sciences University of ShizuokaShizuoka422-8526Japan

Dihydroorotate dehydrogenase(DHODH)is a central enzyme of the de novo pyrimidine biosynthesis pathway and is a promising drug target for the treatment of cancer and autoimmune *** study presents the identification of a potent DHODH inhibitor by proteomic ***-based screening revealed that NPD723,which is reduced to H-006 in cells,strongly induces myeloid differentiation and inhibits cell growth in HL-60 cells.H-006 also suppressed the growth of various cancer *** profiling of NPD723-treated cells in ChemProteoBase showed that NPD723 was clustered with DHODH inhibitors.H-006 potently inhibited human DHODH activity in vitro,whereas NPD723 was approximately 400 times less active than H-006.H-006-induced cell death was rescued by the addition of the DHODH product orotic ***,metabolome analysis revealed that H-006 treatment promotes marked accumulation of the DHODH substrate dihydroorotic *** results suggest that NPD723 is reduced in cells to its active metabolite H-006,which then targets DHODH and suppresses cancer cell ***,H-006-related drugs represent a potentially powerful treatment for cancer and other diseases.

关键词： Anticancer agents Differentiating agents Drug target identification

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Gallbladder Burkitt's lymphoma mimicking gallbladder cancer:A case report

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World Journal of Gastroenterology 2022年第6期28卷 675-682页

作者： Kiyotaka Hosoda Akira Shimizu Koji Kubota Tsuyoshi Notake Hikaru Hayashi Koya Yasukawa Kentaro Umemura Atsushi Kamachi Takamune Goto Hidenori Tomida Shiori yamazaki Yuri Narusawa Naoko Asano takeshi Uehara Yuji Soejima Division of Gastroenterological Hepato-Biliary-PancreaticTransplantation and Pediatric SurgeryDepartment of SurgeryShinshu University School of MedicineMatsumoto 390-8621Japan Department of Laboratory Medicine Shinshu University School of MedicineMatsumoto 390-8621Japan

BACKGROUND Malignant lymphoma is a rare form of gallbladder *** of these malignancies are diffuse large B-cell lymphomas or mucosa-associated lymphoid tissue-type lymphomas;however,Burkitt’s lymphoma of the gallbladder is extremely rare,and only two previous reports are available in the ***,we report a rare case of Burkitt’s lymphoma of the gallbladder mimicking gallbladder *** SUMMARY An 83-year-old man with no abdominal complaints was found to have a gallbladder tumor and periportal lymph node enlargement on computed tomography(CT)performed for hypertension *** laboratory data revealed slightly elevated serum levels of carcinoembryonic antigen and soluble interleukin 2 *** examinations revealed two irregular and contrastenhanced masses extending into the gallbladder lumen,but these did not infiltrate the ***,a periportal lymph node had enlarged to 30 *** on these findings,we diagnosed the patient as having gallbladder adenocarcinoma with lymph node metastasis,which was treated using bile duct resection with gallbladder bed resection and periportal lymph node ***,the patient was finally diagnosed as having Burkitt’s *** the surgical margin was pathologically negative,recurrence was noted at the hepatic radical margin and superior pancreaticoduodenal lymph nodes on positron emission tomography/CT soon after ***,he was referred to a hematologist and started receiving treatment with reduced-dose cyclophosphamide,doxorubicin,vincristine,and *** Burkitt’s lymphoma can occur in the *** can be useful in cases with findings suggestive of gallbladder malignant lymphoma.

关键词： Gallbladder Malignant lymphoma Burkitt’s lymphoma Gallbladder cancer Lymphadenopathy Case report

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Combination therapy with daclatasvir and asunaprevir for dialysis patients infected with hepatitis C virus

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World Journal of Clinical Cases 2016年第3期4卷 88-93页

作者： Ken Sato Yuichi yamazaki Tatsuya Ohyama takeshi Kobayashi Norio Horiguchi Satoru Kakizaki Motoyasu Kusano Masanobu Yamada Department of Medicine and Molecular Science Gunma University Graduate School of Medicine Department of Gastroenterology Heisei Hidaka Clinic Department of Endoscopy and Endoscopic Surgery Gunma University Hospital

The standard antiviral therapy for dialysis patients infected with hepatitis C virus(HCV) is(pegylated) interferon monotherapy, but its efficacy is insufficient. Oral direct-acting antiviral agents(DAAs) have recently been developed for chronic hepatitis C patients. However, some DAAs have contraindications for chronic renal failure(CRF). Daclatasvir and asunaprevir are metabolized largely in the liver and are not contraindicated in CRF. Combination therapy with daclatasvir and asunaprevir was used for 4 dialysis patients infected with genotype 1b HCV. One patient had viral breakthrough, and the 3 others had sustained virological response 12. One patient was admitted for heart failure and percutaneous coronary intervention due to concomitant ischemic disease. Heart failure was unlikely to be caused by the combination therapy, as it was probably due to water overload. The patient continued to receive the combination therapy after the remission of the heart failure. The combination therapy was well tolerated in the other patients.

关键词： Hepatitis C Oral drug Daclatasvir Asunaprevir Dialysis

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gastrointestinal symptom prevalence depends on disease duration and gastrointestinal region in type 2 diabetes mellitus

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World Journal of Gastroenterology 2017年第36期23卷 6694-6704页

作者： Midori Fujishiro Akifumi Kushiyama Hiroki yamazaki Sunao Kaneko Yuko Koketsu takeshi Yamamotoya Takako Kikuchi Hideyuki Sakoda Ryo Suzuki Takashi Kadowaki Department of Diabetes and Metabolic Diseases Graduate School of Medicine the University of Tokyo Division of Diabetes and Metabolism Institute for Adult Diseases Asahi Life Foundation Department of Diabetes and Metabolic Diseases Shinko Hospital Department of Medical Science Graduate School of Medicine University of Hiroshima Division of Neurology Respirology Endo-crinology and Metabolism Department of Internal Medicine Faculty of Medicine University of Miyazaki

AIM To unravel relationships between gastrointestinal(GI)symptoms impairing quality of life(QOL)and clinical profiles of diabetes mellitus(DM)patients. METHODS We enrolled 134 outpatients with type 2 *** age was 64.7 years,mean body mass index was 24.7 RESULTS Lower abdominal symptoms were found to be more frequent than those affecting the upper *** duration and medications showed associations with GI *** identified differences in peak prevalences of the five ***(P=0.02vs 10-14 years)and total GI symptoms(P=0.01 and P=0.02 vs 5-9 years and 10-14 years,respectively)peaked at a diabetes duration of 15-19 ***(P=0.004)and postprandial fullness(P=0.03)tended to increase with disease *** and diarrhea showed bimodal peaks,with the first early and the second late(e.g.,P=0.03 at 15-19 years vs 10-14years for diarrhea)in the disease ***,GI symptoms showed clustering that reflected the region of the GI tract affected,i.e.,constipation and diarrhea had similar frequencies(P<0.0001). CONCLUSION Our study highlights the importance of questioning patients about QOL impairment due to abdominal symptoms,especially in the early and the late periods of diabetes.

关键词： Gastrointestinal symptoms Questionnaire survey Disease duration Type 2 diabetes Quality of life Gastrointestinal tract regions

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Sofosbuvir/Ribavirin therapy for patients experiencing failure of ombitasvir/paritaprevir/ritonavir + ribavirin therapy: Two cases report and review of literature

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World Journal of Clinical Cases 2019年第9期7卷 1043-1052页

作者： Ken Sato Yuichi yamazaki takeshi Kobayashi Satoshi Takakusagi Norio Horiguchi Satoru Kakizaki Masayasu Andou Yoshihiro Matsuda Toshio Uraoka Hiroshi Ohnishi Hiroaki Okamoto Department of Gastroenterology and Hepatology Gunma University Graduate School of Medicine Department of Nephrology and Rheumatology Gunma University Graduate School of Medicine Department of Diagnostic Radiology and Nuclear Medicine Gunma University Graduate School of Medicine Division of Virology Department of Infection and Immunity Jichi Medical University School of Medicine

BACKGROUND The effectiveness of sofosbuvir/ribavirin(SOF/RBV) combination therapy,which is one of the 1 st-choice therapeutic options for patients with hepatitis C virus(HCV) genotype 2(HCV-G2) in Japan according to the most recent version of the Japan Society of Hepatology guideline, for patients who experienced failure of the ombitasvir/paritaprevir/ritonavir plus ribavirin(OBV/PTV/r+RBV) combination therapy, which was another option for patients with HCV-G2, is *** SUMMARY We evaluated the effects of SOF/RBV combination therapy in two patients with genotype 2 a who could not achieve a sustained virological response(SVR) by OBV/PTV/r+RBV combination therapy. One patient was complicated with VogtKoyanagi-Harada(VKH) disease. Resistance-associated variations before SOF/RBV combination therapy were not detected in two patients. Both patients had an SVR at 12 wk after the treatment(SVR12). Regarding adverse events(AEs), itching, chill, a dull feeling in the throat and cough as well as increase of alanine transaminase level were shown in one patient, while a headache and deterioration of light aversion probably due to the recurrence of VKH disease were shown in the other patients. In addition, the latter patient developed arthralgia and morning stiffness approximately 7 wk after the therapy and turned out to be diagnosed with rheumatoid *** SOF/RBV therapy might be effective for patients experiencing failure of OBV/PTV/r+RBV therapy, but caution should be taken regarding the AEs.

关键词： Direct-acting antiviral agent failure Hepatitis C Genotype 2 Ribavirin Sofosbuvir Case report

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Ipragliflozin-induced improvement of liver steatosis in obese mice may involve sirtuin signaling

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World Journal of Hepatology 2020年第7期12卷 350-362页

作者： Takayoshi Suga Ken Sato Tatsuya Ohyama Sho Matsui takeshi Kobayashi Hiroki Tojima Norio Horiguchi Yuichi yamazaki Satoru Kakizaki Ayaka Nishikido Takashi Okamura Masanobu Yamada TadahiroKitamura Toshio Uraoka Department of Gastroenterology and Hepatology Gunma University Graduate School of MedicineMaebashi 371-8511GunmaJapan Metabolic Signal Research Center Institute for Molecular and Cellular RegulationGunma UniversityMaebashi 371-8512GunmaJapan Department of Medicine and Molecular Science Gunma Graduate School of MedicineMaebashi 371-8511GunmaJapan

BACKGROUND Sodium glucose cotransporter 2(SGLT2)inhibitors are newly developed oral antidiabetic ***2 is primarily expressed in the kidneys and reabsorbs approximately 90%of the glucose filtered by the renal ***2 inhibitors lower glucose levels independently of insulin action by facilitating urinary glucose *** SGLT2 inhibitor ipragliflozin has reportedly improved liver steatosis in animal models and clinical ***,the mechanisms by which SGLT2 inhibitors improve liver steatosis are not fully *** To investigate the ameliorative effects of ipragliflozin on liver steatosis and the mechanisms of these effects in obese *** We analyzed 8-wk-old male obese(ob/ob)mice that were randomly divided into a group receiving a normal chow diet and a group receiving a normal chow diet supplemented with ipragliflozin(3 mg/kg or 10 mg/kg)for 4 *** also analyzed their lean sex-matched littermates receiving a normal chow diet as another control group. Body weight and liver weight were evaluated, and liverhistology, immunoblotting, and reverse transcription-polymerase chain reactionanalyses were *** lipid accumulation was significantly ameliorated in ob/ob mice treatedwith 10 mg/kg ipragliflozin compared to untreated ob/ob mice irrespective ofbody weight changes. Ipragliflozin had no appreciable effects on hepatic oxidativestress-related gene expression levels or macrophage infiltration, but significantlyreduced hepatic interleukin-1β (IL-1β) mRNA expression levels. Ipragliflozinincreased both the mRNA and protein expression levels of sirtuin 1 (SIRT1) in theliver. The hepatic mRNA levels of peroxisome proliferator-activated receptor γcoactivator 1α (PGC-1α), peroxisome proliferator-activated receptor α (PPARα),and fibroblast growth factor-21 (FGF21) were also significantly higher inipragliflozin-treated ob/ob mice than in untreated ob/ob *** study suggests that the liver steatosis-ameliorati

关键词： Selective sodium glucose cotransporter 2 Nonalcoholic fatty liver disease Sirtuin 1 Peroxisome proliferator-activated receptorγcoactivator 1α Peroxisome proliferator-activated receptorα Fibroblast growth factor-21

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