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World Journal of Gastroenterology 2013年第32期19卷 5393-5394页

作者： Masahide Hamaguchi Takao kojima Department of Experimental Immunology World Premier International Immunology Frontier Research CenterOsaka University Department of Gastroenterology Murakami Memorial HospitalAsahi University

We previously reported that modest alcohol consumption was significantly inversely associated with fatty liver *** et al pointed out a discrepancy of statistical significance between our current larger scale cohort and a previous ***,the prevalence of non-alcoholic fatty liver disease was higher in non or minimal drinkers than those in light drinkers in both *** also argue that some potential co-factors such as soft drink consumption and genetic variations should be discussed.

关键词： Alcohol Fatty liver disease Obesity Diabetes Metabolic syndrome

Evaluating the Effects of Crystallinity on Drug Release Behaviour in Itraconazole- or Miconazole-Loaded PLGA Microparticles Prepared Using a Co-Grinding Method

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Pharmacology & Pharmacy 2023年第9期14卷 348-362页

作者： Kazuhiro Matsuura Honami kojima Miyako Yoshida Takahiro Uchida Formulation Technology Research Laboratories Daiichi Sankyo Co. Ltd. Hiratsuka Japan Faculty of Pharmaceutical Science Mukogawa Women’s University Nishinomiya Japan

This study aimed to prepare and characterize itraconazole (ITCZ)- or miconazole (MCZ)-loaded poly (lactide-co-glycolide) (PLGA) microparticles (MP) using a co-grinding method with ball milling, which is a solvent-free and convenient procedure. PLGA MP was prepared by grinding for 60 min, and the fixed theoretical drug loading was set at 9.1% and 16.7% for both drugs. The obtained loading efficiency for both drugs was estimated to be approximately 100%. The average diameters of the drug-loaded PLGA MP were approximately 20 - 35 μm. Powder X-ray diffraction (PXRD) or differential scanning calorimetry (DSC) confirmed amorphization of ITCZ and MCZ in ITCZ- or MCZ-loaded PLGA MP in all formulations. The drug release percentage from 9.1%-loaded ITCZ-PLGA7505 MP at 24 h was almost 50%, which was higher than that of ITCZ powder. The drug release percentage from MCZ-loaded PLGA7505 MP at 4 h was over 80%, which was higher than that of MCZ powder. This enhancement of release rate is caused by the amorphization of ITCZ or MCZ in the PLGA matrix. MCZ-loaded PLGA7510 MP showed a sustained release profile up to 24 h, suggesting that MCZ exists in an amorphous form in the PLGA matrix;however, the release rate declined owing to the large molecular weight of PLGA. Therefore, the release enhancement of antifungal drugs loaded on PLGA MP could be achieved by their amorphization using a co-grinding method with ball milling.

关键词： Co-Grinding Method Ball Milling Poly (Lactide-co-Glycolide) Itraconazole Miconazole Amorphization

Nonalcoholic fatty liver disease is a novel predictor of cardiovascular disease

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World Journal of Gastroenterology 2007年第10期13卷 1579-1584页

作者： Masahide Hamaguchi Takao kojima Noriyuki Takeda Chisato Nagata Jun Takeda Hiroshi Sarui Yutaka Kawahito Naohisa Yoshida Atsushi Suetsugu Takahiro Kato Junichi Okuda Kazunori Ida Toshikazu Yoshikawa Inflammation and Immunology Graduate School of Medical ScienceKyoto Prefectural University of MedicineJapan Department of Gastroenterology Murakami Memorial HospitalAsahi UniversityJapan Department of Endocrinology and Metabolism Murakami Memorial HospitalAsahi UniversityJapan Department of Epidemiology & Preventive Medicine Graduate School of MedicineGifu UniversityJapan Department of Diabetes and Endocrinology Division of Molecule and StructureGraduate School of MedicineGifu UniversityJapan

AIM:To clarify whether nonalcoholic fatty liver disease(NAFLD)increases the risk of cardiovascular ***:We carried out a prospective observational study with a total of 1637 apparently healthy Japanese men and women who were recruited from a health check-up *** was diagnosed by abdominal *** metabolic syndrome(MS)was defined according to the modified National Cholesterol Education Program(NCEP)ATP Ⅲ *** years after the baseline evaluations,the incidence of cardiovascular disease was assessed by a self-administered ***:Among 1221 participants available for outcome analyses,the incidence of cardiovascular disease was higher in 231 subjects with NAFLD at baseline(5 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage)than 990 subjects without NAFLD(3 coronary heart disease,6 ischemic stroke,and 1 cerebral hemorrhage).Multivariate analyses indicated that NAFLD was a predictor of cardiovascular disease independent of conventional risk factors(odds ratio 4.12,95% CI,1.58 to 10.75,P = 0.004).MS was alsoindependently associated with cardiovascular *** simultaneous inclusion of NAFLD and MS in a multivariate model revealed that NAFLD but not MS retained a statistically significant correlation with cardiovascular ***:Although both of them were predictors of cardiovascular disease,NAFLD but not MS retained a statistically significant correlation with cardiovascular disease in a multivariate *** is a strong predictor of cardiovascular disease and may play a central role in the cardiovascular risk of MS.

关键词： Nonalcoholic fatty liver disease Metabolic syndrome Coronary heart disease Cardiovascular disease Risk factors

Interferon augments the anti-fibrotic activity of an angiotensin-converting enzyme inhibitor in patients with refractory chronic hepatitis C

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World Journal of Gastroenterology 2006年第42期12卷 6786-6791页

作者： Hitoshi Yoshiji Ryuichi Noguchi Hideyuki kojima Yasuhide Ikenaka Mitsuteru Kitade Kosuke Kaji Masahito Uemura Junichi Yamao Masao Fujimoto Masaharu Yamazaki Masahisa Toyohara Akira Mitoro Hiroshi Fukui Third Department of Internal Medicine Nara Medical University Nara Japan

AIM： To evaluate the effect of combination treatment with the interferon （IFN） and angiotensin-converting enzyme inhibitor （ACE-Ⅰ） on several fibrotic indices in patients with refractory chronic hepatitis C （CHC）. METHODS： Perindopril （an ACE-Ⅰ; 4 mg/d） and/or natural IFN （3 MU/L; 3 times a week） were administered for 12 mo to refractory CHC patients, and several indices of serum fibrosis markers were analyzed. RESULTS： ACE-Ⅰ decreased the serum fibrosis markers, whereas single treatment with IFN did not exert these inhibitory effects. However, IFN significantly augmented the effects of ACE-Ⅰ, and the combination treatment exerted the most potent inhibitory effects. The serum levels of alanine transaminase and HCV-RNA were not significantly different between the groups, whereas the plasma level of transforming growth factor-β was significantly attenuated almost in parallel with suppression of the serum fibrosis markers. CONCLUSION： The combination therapy of an ACE-Ⅰand IFN may have a diverse effect on disease progression in patients with CHC refractory to IFN therapy through its anti-fibrotic effect.

关键词： Interferon Angiotensin-converting enzyme inhibitor Liver fibrosis Chronic hepatitis C Transforming growth factor-β

Assessment of Biofouling Using Leaching Rate of Antifouling Agents and Bioluminescent Assay

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Journal of Shipping and Ocean Engineering 2014年第7期4卷 214-224页

作者： Ryuji kojima Shoko Imai Toshiaki Shibata Koichi Ueda National Maritime Research Institute Tokyo 1810004 Japan National Institute for Minamata Disease Kumamoto 8670008 Japan

The authors investigated the leaching rate of antifouling agents from marine paint using an instrument that allows direct measurement from the flat bottom of ship hulls shortly after dry dock. A similar procedure was also used for painted flat panels that were immersed in the ocean. The relationship between leaching rate and fouling condition was considered by quantifying the amount of ATP （adenosine triphosphate） on the surface of immersed flat panel using fluorescence spectroscopy. The leaching rate results from ship hulls showed good agreement with the value by reporting of leaching rate of antifouling agents. The fluorescence spectroscopy results showed that the amount of ATP on the surface of the panel increased over time as the leaching rate fell, which implies an inverse relationship between leaching rate and fouling index. Fluorescence spectroscopy was also seen to be a simple method for evaluating the relationship between biofouling indexes and leaching rate.

关键词： Antifouling agent biofouling leaching rate biomass ATP fluorescence spectroscopy.

Deterioration of Water Ballast Tank Coating Systems by Active Substances in Ballast Water Management Systems

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Journal of Shipping and Ocean Engineering 2014年第9期4卷 229-235页

作者： Ryuji kojima Michiaki Ikai Toshiaki Shibata Koichi Ueda Department of Marine Environment and Engine Systems National Mazitime Research Institute Tokyo 1810004 Japan

Sodium hypochlorite and ozone are the principal active substances and usually employed in ballast water management systems. In the present study, the authors focus on the effect of these active substances to the maaix polymer of coating. In order to obtain such information, the authors investigated the penetration of active substances to the polymer from cross section of specimens introduced by SAICAS （surface and interracial cutting analysis system）, followed by FT-IR-ATR （Fourier transform infrared and attenuated total reflectance） spectroscopy analysis from Z direction of cross section. The corrosion test of coating panels by these active substances （control as artificial seawater） has been conducted for 120 days. The results show that the depth profile of each active substance is around few dozens of micrometers from coating surface. The criteria of corrosion test cannot be determined by these results due to lacking in actual corrosion data immersed for 15 years under active substances. However, the authors evaluated the effect on ballast tank coating systems by active substances using analytical methods of SAICAS and FT-IR-ATR spectroscopy.

关键词： Ozone sodium hypochlorite SAICAS FT-IR-ATR epoxy resin PSPC ballast water management systems.

Influence of NUDT15 variants on hematological pictures of patients with inflammatory bowel disease treated with thiopurines

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World Journal of Gastroenterology 2018年第4期24卷 511-518页

作者： Yuichiro kojima Yosuke Hirotsu Wataru Omata Makoto Sugimori Shinya Takaoka Hiroshi Ashizawa Keiko Nakagomi Dai Yoshimura Kenji Hosoda Yoji Suzuki Hitoshi Mochizuki Masao Omata Department of Gastroenterology Yamanashi Prefectural Central Hospital Genome Analysis Center Yamanashi Prefectural Central Hospital Department of Dermatologic Oncology National Cancer Institute Division of Gastroenterology Department of Medicine Yokohama City University Graduate School of Medicine Department of Gastroenterology Genome Analysis Center Yamanashi Prefectural Central Hospital

AIM The single nucleotide polymorphism(SNP) c.415C>T in exon 3 of NUDT15 affects thiopurine-induced leukopenia in Asian patients with Crohn's disease. Meanwhile, three additional genetic variants of NUDT15 were reported in patients with acute lymphoblastic leukemia. We evaluated the effects of these additional genetic variants of NUDT15 in patients with inflammatory bowel disease(IBD) treated with *** Ninety-six Japanese patients with IBD were enrolled. Genotyping for the NUDT15 and TPMT genes was performed using Custom Taq Man SNP genotyping assays or Sanger sequencing. The changes in white blood cell(WBC) count, mean corpuscular volume(MCV), platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT, and ESR were *** Genetic variants of exon 1 and exon 3 of NUDT15 were identified in 24 of 96 patients(25.0%). C.52G > A and c.36_37 insG GAGTC in exon 1 were found in three patients each. All three patients with c.36_37 insG GAGTC in exon 1 were heterozygotes of ***139 Cys in exon 3. Eighteen patients had ***139 Cys in exon 3 alone. The WBC count gradually decreased after initiation of thiopurine treatment in the mutated cases(n = 24), and was significantly lower at 6, 8, 10, and 16 wk(P = 0.0271, 0.0037, 0.0051, and 0.0185, respectively). The WBC counts were also evaluated in patients with and without prednisolone treatment. In the patients with prednisolone treatment, the WBC count tended to show a greater decrease in the mutated cases, with significant differences at 8 and 10 wk(P = 0.012 and 0.029, respectively). In the patients without prednisolone treatment, the WBC count was significantly lower at 2, 4, 8, and 14 wk in mutated cases(P = 0.0196, 0.0182, 0.0237 and 0.0241, respectively). MCV increased after starting thiopurine treatment in the mutated cases, and was significantly higher at 10 wk(P = 0.0085). Platelet count, hemoglobin, CRP, amylase, albumin, AST, ALT and ESR did not differ significantly between the wildtype and

关键词： Inflammatory bowel disease NUDT15 Leukopenia Mean corpuscular volume Japanese

Influence of Ozone Injection on Corrosion Behavior of Steel in Water Ballast Tank

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Journal of Shipping and Ocean Engineering 2014年第11期4卷 327-337页

作者： Ryuji kojima Michiaki Ikai Jinsun Liao Yoichi Mori Department of Marine Environment and Engine Systems National Maritime Research Institute Tokyo 1810004 Japan Technology Development Division Kurimoto Ltd. Osaka 5590021 Japan

Ozone is the principal active substances and usually employed in ballast water management systems. In the present study, the corrosion protective effect of ozone was conducted by immersion test and electrochemical techniques. It was found that corrosion protective effect was revealed in the range of 2.0 to 2.7 ppm of ozone concentration in seawater. The ratio of the rust area of specimen became 20% in that concentration region. The rusted area is strongly influenced by the ozone concentration and the flow rate determined by FEM （finite element method）. Ozone has a good influence for ballast tanks, i.e., ozone can delay the rust of ballast tanks, provided that the suitable concentration of ozone is selected. In this case, ozone may stop the corrosion at the defects, if a part of the paint in ballast tank is peeled off. However, ozone may also promote the corrosion of steel when the ozone concentration is very high, e.g., 10 ppm. Attention should be paid to the ozone concentration, if we use ozone as an active substance for ballast water management systems.

关键词： Ozone corrosion protective effect water ballast tank coating film electrochemical measurement FEM analysis.

Production of smooth muscle "SH1 null" myosin by site-directed mutagenesis

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Production of smooth muscle "SH1 null" myosin by site-direct...