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Combination of Pretreatments with Acetic Acid and Sodium Methoxide for Efficient Digoxin Preparation from Digitalis Glycosides in Digitalis lanata Leaves

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Pharmacology & Pharmacy 2016年第5期7卷 200-207页

作者： yasuhiko higashi yukari Ikeda youichi Fujii Department of Analytical Chemistry Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan

We previously developed an HPLC method for determination of lanatoside C, digoxin and α-acetyldigoxin in digitalis glycosides isolated from Digitalis lanata leaves. Here, we present an improved HPLC-UV method to determine those compounds and deslanoside. We used the improved method to examine the effects of various pretreatments on the amounts of the four compounds isolated from the leaves, with the aim of maximizing the yield of digoxin. Leaves were extracted with 50% methanol, followed by clean-up on a Sep-Pak C18 cartridge prior to HPLC analysis. The amounts of lanatoside C, digoxin and α-acetyldigoxin per 100 mg of the leaves without pretreatment were 115.6, 7.45 and 23.8 μg, respectively (deslanoside was not detected). Pretreatment with acetic acid, which activated deglucosylation mediated by digilanidase present in the leaves, increased the amounts of digoxin and α-acetyldigoxin, while lanatoside C and deslanoside were not detected. Pretreatment with sodium methoxide, which hydrolyzed lanatoside C to deslanoside, increased the yields of deslanoside and digoxin, while lanatoside C and α-acetyldigoxin were not detected. The combination of both pretreatments afforded only digoxin in a yield of 115.1 μg/100 mg leaves. Use of the combined pretreatments appears to be effective for maximizing the yield of digoxin from the leaves.

关键词： Digoxin Lanatoside C α-Acetyldigoxin Deslanoside HPLC Digitalis lanata Pretreatment

Pharmaceutical properties of insulin conjugate with glucuronylglucosyl-β-cyclodextrin

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Asian Journal of Pharmaceutical Sciences 2016年第1期11卷 120-121页

作者： Mari Sugio Tatsunori Hirotsu Taishi higashi Keiichi Motoyama Fumitoshi Hirayama Kaneto Uekama Hidetoshi Arima Graduate School of Pharmaceutical Sciences Kumamoto University5-1 Oe-honmachiChuo-kuKumamotoJapan Program for Leading Graduate Schools“HIGO(Health Life Science:Interdisciplinary and Glocal Oriented)Program ”Kumamoto University5-1 Oe-honmachiChuo-kuKumamotoJapan Faculty of Pharmaceutical Sciences Sojo University4-22-1 IkedaNishi-kuKumamotoJapan Kumamoto University KumamotoJapan

In the clinical field,insulin has been used for treatment of ***,insulin often shows low physicochemical stability,adsorption onto tubes and enzymatic degradation in injection site or ***,we demonstrated that cyclodextrins(CyDs),especially branchedβ-CyDs,improve the pharmaceutical properties of insulin through complexation with its aromatic ***,little has been reported on the insulin conjugate with branchedβ-*** the present study,to improve the pharmaceutical properties of insulin,we newly prepared 6-Ο-α-(4-Ο-α-D-glucuronyl)-D-glucosyl-β-CyD(GUG-β-CyD)conjugate with insulin,and evaluated its thermal or enzymatic stability and adsorption onto glass or polypropylene tube[1].

关键词： Glucuronylglucosyl-β-cyclodextrin Insulin Conjugate Stability Adsorption

Combined treatment of pancreatic cancer xenograft with 90y-ITGA6B4-mediated radioimmunotherapy and PI3K/m TOR inhibitor

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World Journal of Gastroenterology 2017年第42期23卷 7551-7562页

作者： Winn Aung Atsushi B Tsuji Hitomi Sudo Aya Sugyo yoshinori Ukai Katsushi Kouda yoshikazu Kurosawa Takako Furukawa Tsuneo Saga Tatsuya higashi Department of Molecular Imaging and Theranostics National Institute of Radiological SciencesNational Institutes for Quantum and Radiological Science and Technology(QST-NIRS) Perseus Proteomics Inc. Innovation Center for Advanced Medicine Fujita Health University Department of Radiological and Medical Laboratory Sciences Nagoya University Graduate School of Medicine Department of Diagnostic Radiology Kyoto University Hospital

AIM To investigate the therapeutic effect of combined integrin α6β4-targeted radioimmunotherapy(RIT) and PI3 K/m TOR inhibitor BEZ235 in a pancreatic cancer *** Phosphorylation of Akt, m TOR, the downstream effectors eukaryotic initiation factor 4 E binding protein 1(4 EBP1) and S6 ribosomal protein(S6) were evaluated in Bx PC-3 human pancreatic cancer cells treated with yttrium-^(90)(^(90) y) labeled anti-integrin α6β4 antibody(ITGA6 B4) and BEZ235 by western blotting. The cytotoxic effect of BEZ235 was investigated using a colony formation assay. Therapeutic efficacy enhancement by oral BEZ235 administration was assessed using mice bearing Bx PC-3 xenograft tumors. Tumor volume measurements and immunohistochemical analyses(cell proliferation marker Ki-67, DNA damage marker p-H2 AX and p-4 EBP1 staining) of tumors were performed for evaluation of combined treatment with ^(90) y-ITGA6 B4 plus BEZ235, or each arm *** We found that phosphorylation of Akt(p-Akt), 4 EBP1(p-4 EBP1) and S6(p-S6) was inhibited by BEZ235. Colony formation in Bx PC-3 cells was additively suppressed by the combination of ^(90) y-ITGA6 B4 and BEZ235. Pretreatment with BEZ235 before ^(90) y-ITGA6 B4 exposure resulted in significant reduction of cells plating efficiency(PE)(0.54 ± 0.11 vs 2.81 ± 0.14 with 185 k Bq/m L ^(90) y-ITGA6 B4 exposure, P y-ITGA6 B4 exposure, P y-ITGA6 B4 plus BEZ235 enhanced the inhibition of tumor growth and statistically significant differences of relative tumor volume were observed for 27 d after the treatment start date when compared with the ^(90) y-ITGA6 B4 single injection treatment(1.03 ± 0.38 vs 1.5 ± 0.15 at Day 27, P y 41, P < 0.05). Tumors from treatment groups showed reduction in volumes, dec

关键词： Radioimmunotherapy Pancreatic cancer Anti-integrin α6β4 antibody yttrium-90 NVP-BEZ235

Development of X-band accelerating structures for high gradients

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Chinese Physics C 2012年第7期36卷 639-647页

作者： S. Bini V. Chimenti A. Marcelli L. Palumbo B. Spataro V. A. Dolgashev S. Tantawi A. D. yeremian y. higashi M. G. Grimaldi L. Romano F. Ruffino R. Parodi INFN-LNF Via E. Fermi 40 00044 Frascati (RM) Italy University of Rome Sapienza Dipartimento di EnergeticaVia A. Scarpa 14 00185 Rome Italy SLAC National Accelerator Laboratory 2575 Sand Hill Road Menlo Park CA 94025 USA KEK 1-1 Oho Tsukuba Ibaraki 305 Japan University of Catania Dipartimento di Fisica e Astronomia & MATIS-IMM-CNRVia S. Sofia 64 95123 Catania Italy INFN-Genova Via Dodecaneso 33 16146 Genova Italy

Short copper standing wave （SW） structures operating at an X-band frequency have been recently designed and manufactured at the Laboratori Nazionali di Frascati of the Istituto Nazionale di Fisica Nucleare （INFN） using the vacuum brazing technique. High power tests of the structures have been performed at the SLAC National Accelerator Laboratory. In this manuscript we report the results of these tests and the activity in progress to enhance the high gradient performance of the next generation of structures, particularly the technological characterization of high performance coatings obtained via molybdenum sputtering.

关键词： high-gradients soft X-ray FEL RF cavities for particle accelerators RF sputtering

细胞内可视化技术在解析天然药物作用机理上的应用

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细胞内可视化技术在解析天然药物作用机理上的应用

Development of Highly Specific Enzyme Immunoassay for Monitoring Serum Digitoxin Level in Patients

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作者：陈乃宏谭茹 higashi H 山西中医学院三菱化学生命科学研究所国立琦玉大学

＜正＞随着科技水平的提高,对急性病、传染病等的治疗手段有了较大进展。但对一些慢性疾患,仍无大的进步,甚至随着人均寿命的延长,其发病率有逐渐增多的趋势。在经济发达国家,老年痴呆是常见的难治疾患,现已居疾病死亡原因的第4位。在...

＜正＞随着科技水平的提高,对急性病、传染病等的治疗手段有了较大进展。但对一些慢性疾患,仍无大的进步,甚至随着人均寿命的延长,其发病率有逐渐增多的趋势。在经济发达国家,老年痴呆是常见的难治疾患,现已居疾病死亡原因的第4位。在日本痴呆是常见的难治疾病,现已居疾病死亡原因的第4位。仅

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Journal of Analytical Sciences, Methods and Instrumentation 2016年第2期6卷 15-22页

作者： yasuhiko higashi yukari Ikeda Mayumi Douno youichi Fujii Department of Analytical Chemistry Faculty of Pharmaceutical Sciences Hokuriku University Kanazawa Japan

We previously developed radioimmunoassays (RIAs) for digitoxin and digoxin using antisera raised against digitoxin 3’-hemisuccinate-bovine serum albumin and digoxin 3’-hemisuccinate-bovine serum albumin conjugates, respectively. Very recently, we converted the RIA for digoxin to an enzyme immunoassay (EIA) system. Here, we aimed to convert the RIA for digitoxin to an EIA suitable for measuring serum digitoxin level in patients, using digitoxin 3’-hemisuccinate-β-D-galactosidase as an enzyme-labeled antigen. The developed EIA showed a quantification range of 1 to 70 ng/mL and exhibited high specificity for digitoxin, with low cross-reactivity to digitoxin metabolites. Compared with a commercial anti-digitoxin antiserum clinically used to monitor serum digitoxin level in patients, our antiserum showed much higher specificity for intact digitoxin. Intra- and inter-assay variations were less than 10.0% and 8.5%, respectively. Recovery was within the range of 93.7% - 107.5%. Mean digitoxin concentrations measured in serum samples (n = 26) from digitoxin-treated patients by EIA using our new antiserum and the commercial anti-digitoxin antiserum were 11.0 and 13.8 ng/mL, respectively. The present EIA, which is superior to RIA in terms of convenience and disposal of waste materials, is expected to be practically useful for clinical monitoring of intact digitoxin in serum.

关键词： Digitoxin Digitoxin 3’-Hemisuccinate-β-D-Galactosidase Digitoxin 3’-Hemisuccinate-Bovine Serum Albumin Antiserum Enzyme Immunoassay Cross-Reactivity

Ectopic hepatocellular carcinoma mimicking a retroperitoneal tumor:A case report

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World Journal of Gastroenterology 2020年第18期26卷 2268-2275页

作者： yuki Adachi Hiromitsu Hayashi Toshihiko yusa Toru Takematsu Kazuki Matsumura Takaaki higashi Kensuke yamamura Takanobu yamao Katsunori Imai yo-ichi yamashita Hideo Baba Department of Gastroenterological Surgery Graduate School of Life SciencesKumamoto UniversityKumamoto 8608556Japan

BACKGROUND An ectopic hepatocellular carcinoma(EHCC)arises from the ectopic liver which is defined as a hepatic organ or tissue not connected to surrounding *** is a rare disease and it is difficult to diagnose ***,the clinical features are not fully *** SUMMARy A retroperitoneal tumor(6 cm)was located at the dorsal side of the pancreas head on abdominal ultrasonography in an 81-year old woman positive for hepatitis C virus *** enhanced-computed tomography and gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging showed viable HCC patterns with early enhancement and delayed *** tumor markers-serum alphafetoprotein and alpha-fetoprotein-L3%-were increased to 30.1 ng/m L and83.1%,*** induced by vitamin K absence or antagonist-Ⅱwas within normal levels(17 m AU/m L).Positron emission tomography-computed tomography showed strong accumulation into the tumor(Standardized Uptake Value max:13.8),and the tumor cytology following endoscopic ultrasoundguided fine needle aspiration showed poorly differentiated *** extirpation was performed,and operative findings showed that the retroperitoneal tumor was disconnected from the pancreas and the *** lymph nodes near the tumor were histologically *** histological examination,the tumor was finally diagnosed as EHCC with Arginase-1 positive *** We report our experience of a rare EHCC which was difficult to diagnose,and we present a review of the literature.

关键词： Ectopic hepatocellular carcinoma Differential diagnosis Retroperitoneal tumor Case report

Impact of Smoking on Lifestyle and Vitality in College Students

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Open Journal of Preventive Medicine 2021年第5期11卷 199-210页

作者： Fumihiro Omasu Azusa Komori Kaeko higashi Haruka yoshimura Department of Health and Nutrition Faculty of Health and Nutrition Yamagata Prefectural Yonezawa University of Nutrition Sciences Yamagata Japan Department of School Health Faculty of Education Kumamoto University Kumamoto Japan

There is a long history of studies on the bad influence of smoking on our bodies, with many study results accumulated to date indicating a decline in the smoking rate. However, the smoking rate in Japan is still higher than that in other countries. In order to reveal the various influences due to smoking, we examined the changes in lifestyle and vitality prior to and the following smoking, targeting college students who are at the early age of starting to smoke. The subjects were 213 college students (83 men and 130 women). Smoking frequency as well as sleeping, eating habits, exercise, and vitality as a lifestyle were surveyed through a questionnaire survey. As a result of comparing smoking and lifestyle between the smoking group and non-smoking group, in terms of sleep, the bedtime and wake-up time tended to be late in the smoking group. Regarding eating habits, there was a tendency for the smoking group to have a high rate of skipping breakfast and a high intake rate of midnight snacks. Regarding exercise, the number of people exercising on a daily basis was small in both the smoking group and the non-smoking group, with no significant difference observed. Therefore, this study revealed that smoking has a negative influence on some aspects of lifestyle. There was no significant relationship in terms of the effects of smoking on vitality. Going forward, it will be necessary to clarify the negative effects of smoking on mental health.

关键词： Smoking Lifestyle Vitality College Students

Human papillomavirus in upper digestive tract tumors from three countries

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World Journal of Gastroenterology 2011年第48期17卷 5295-5304页

作者： Andres Castillo Chihaya Koriyama Michiyo higashi Muhammad Anwar Mulazim Hussain Bukhari Edwin Carrascal Lida Mancilla Hiroshi Okumura Masataka Matsumoto Kazumasa Sugihara Shoji Natsugoe yoshito Eizuru Suminori Akiba Department of Epidemiology and Preventive Medicine Kagoshima University Graduate School of Medicaland Dental Sciences Department of Human Pathology Kagoshima University Graduate School of Medical and Dental Sciences King Edward Medical University Department of Pathology Universidad del Valle Universidad Santiago de Cali Department of Surgical Oncology and Digestive Surgery Ka-goshima University Graduate School of Medical and Dental Sci-ences Department of Maxillofacial Diagnostic and Surgical Science Kagoshima University Graduate School of Medical and Dental Sciences Department of Surgical Oncology and Digestive Surgery Ka-goshima University Graduate School of Medical and Dental Sciences Division of Oncogenic and Persistent Viruses Kagoshima University Graduate School of Medical and Dental Sciences

AIM: To clarify human papillomavirus (HPV) involvement in carcinogenesis of the upper digestive tract of virological and pathological analyses. METHODS: The present study examined the presence of HPV in squamous cell carcinomas of the oral cavity (n = 71), and esophagus (n = 166) collected from Japan, Pakistan and Colombia, with different HPV exposure risk and genetic backgrounds. The viral load and physical status of HPV16 and HPV16-E6 variants were examined. Comparison of p53 and p16INK4a expression in HPV-positive and HPV-negative cases was also made. RESULTS: HPV16 was found in 39 (55%) oral carcinomas (OCs) and 24 (14%) esophageal carcinomas (ECs). This site-specific difference in HPV detection between OCs and ECs was statistically significant (P ypes were found in 13 ECs, but multiple infections were not found in OCs. This difference was statistically significant (P = 0.001). The geometric means (95% confidence interval) of HPV16 viral load in OCs and ECs were 0.06 (0.02-0.18) and 0.12 (0.05-0.27) copies per cell, respectively. The expression of p16INK4a proteins was increased by the presence of HPV in ECs (53% and 33% in HPV-positive and-negative ECs, respectively; P = 0.036), and the high-risk type of the HPV genome was not detected in surrounding normal esophageal mucosa of HPV-positive ECs. CONCLUSION: Based on our results, we cannot deny the possibility of HPV16 involvement in the carcinogenesis of the esophagus.

关键词：人的乳头状瘤病毒病毒的负担物理地位 E6 p53 p16INK4a