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Predictors of kidney tubular dysfunction induced by adefovir treatment for chronic hepatitis B

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World Journal of Gastroenterology 2015年第7期21卷 2116-2123页

作者： Motohiro Shimizu Norihiro Furusyo Hiroaki Ikezaki Eiichi Ogawa Takeo hayashi Takeshi Ihara Yuji Harada Kazuhiro Toyoda Masayuki Murata jun hayashi Department of General Internal Medicine Kyushu University Hospital Kyushu General Internal Medicine Center Haradoi Hospital

AIM:To investigate the predictors of proximal kidney tubular dysfunction(PKTD)induced by adefovir dipivoxil(ADV)treatment for chronic hepatitis ***:Seventy-nine patients(age at the evaluation of PKTD:56.9±10.7 years)with chronic hepatitis B undergoing long-term oral antiviral nucleos(t)ide analogue treatment were consecutively *** was defined by the presence of at least two of the following five abnormalities:phosphate diabetes,nondiabetic glucosuria,metabolic acidosis,β2-microglobulinuria,or renal *** single-nucleotide polymorphisms(SNPs)in the SLC22A6 gene encoding human organic anion transporter 1(h OAT1)and ABCC2 encoding multidrug resistance protein 2(MRP2)were analyzed using the Taq Man Allelic Discrimination Demonstration ***:Nine(30.0%)of the 30 ADV-treated patients were diagnosed with PKTD,while no patients without ADV developed PKTD(P<0.001).Three patients with ADV were diagnosed with symptomatic *** the patients who took ADV,those with PKTD were of higher age at initiation,had significantly longer treatment duration,and had a significantly lower body mass index than those without *** incidence of PKTD dramatically increased after 96 mo from the start of ADV *** contrast,the SNPs were not correlated with *** regression analysis extracted older age at initiation(OR=5.0,95%CI:1.1-23.4;P=0.040)and longer treatment duration(OR=3.2,95%CI:1.2-8.6;P=0.020)as significant factors associated with ***:Our results suggest that the tubular function of the kidney of older patients undergoing longterm ADV treatment should be carefully evaluated.

关键词： Adefovir dipivoxil Proximal kidney tubular dysfunc

Continuous monitoring of char surface activity toward benzene

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Carbon Resources Conversion 2019年第1期2卷 43-50页

作者： Cheolyong Choi Kentaro Shima Shinji Kudo Koyo Norinaga Xiangpeng Gao jun-ichiro hayashi Interdisciplinary Graduate School of Engineering Sciences Kyushu University6-1Kasuga KoenKasuga 816-8580Japan Institute for Materials and Engineering Chemistry Kyushu University6-1Kasuga KoenKasuga 816-8580Japan Department of Materials Science and Engineering School of EngineeringNagoya UniversityNagoya 464-8601Japan Discipline of Electrical Engineering Energy and PhysicsSchool of Engineering and Information TechnologyMurdoch University90 South StreetMurdochWA 6150Australia Transdisciplinary Research and Education Center of Green Technology Kyushu University6-1Kasuga KoenKasuga 816-8580Japan

Kinetics of thermal decomposition of benzene on lignite-derived char was investigated at 900℃ by applying a new method to continuously monitor the char surface *** vapor was continuously forced to pass through a micro fixed bed of char with residence time as short as 7.6 ms,and then detected continuously by a flame-ionization *** showed the presence of two different types of char surfaces;consumptive Type I surface and non-consumptive(sustainable)Type II *** I surface of a partially CO_(2)-gasified char had an capacity of carbon deposit from benzene over 20 wt%-char and an initial activity(represented by a first-order rate constant)as high as 160 s−*** of them decreased with increasing carbon deposit due to consumption of micropores accessible to benzene,and finally became zero leaving Type II surface that had a very stable activity with rate constant of 4 s−*** chars without gasification had capacities of Type I surfaces smaller by two orders of magnitude than the partially gasified char,while the Type II surfaces had activities similar to that of the partially gasified *** was found that Type II surface converted benzene into not only carbon deposit but also diaromatics and even greater *** of the greater aromatics was unknown because they were deposited onto the reactor wall immediately after passing through the char bed.

关键词： Carbon deposition Aromatics Tar Char Kinetics Pyrolysis Gasification

Long-term effects of lamivudine treatment in Japanese chronic hepatitis B patients

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World Journal of Gastroenterology 2011年第24期17卷 2945-2952页

作者： Masayuki Murata Norihiro Furusyo Mami Unno Eiichi Ogawa Kazuhiro Toyoda Hiroaki Taniai Hachiro Ohnishi jun hayashi Department of General Internal Medicine Kyushu University Hospital Department of Environmental Medicine and Infectious Disease Faculty of Medical SciencesKyushu University

AIM： To analyze the association between the emergence of tyrosine-methionine-asparatate-asparatate （YMDD） mutants （reverse transcription; rtM204I/V） and deterioration of liver function during long-term lamivudine treatment of Japanese patients with chronic hepatitis B virus （HBV） infection. METHODS： The data of 61 consecutive Japanese pa- tients with chronic hepatitis B who underwent continu- ous lamivudine treatment for more than 24 mo and had a virological response were analyzed. Analysis of YMDD mutants was done by real-time polymerase chain reaction with LightCycler probe hybridization assay for up to 90 mo （mean, 50.8 too; range, 24-90 too）.RESULTS： A mixed mutant-type （YMDD ＋ tyrosine-iso- leucine-asparatate-asparatate： YIDD or tyrosine-valineasparatate-asparatate： YVDD） or a mutant-type （YIDD or YVDD） were found in 57.4% of 61 patients at i year, 78.7% of 61 patients at 2 years, 79.6% of 49 patients at 3 years, 70.5% of 34 patients at 4 years, 68.4% of 19 patients at 5 years, 57.1% of 14 patients at 6 years, and 33.3% of 6 patients at 7 years. Of the 61 patients, 56 （92%） had mixed mutant- or a mutant-type. Only 5 （8%） had no mutants at each observation point. Vi- rological breakthrough was found in 26 （46.4%） of 56 patients with YMDD mutants, 20 of whom had a hepa- titis flare-up： the remaining 30 （53.6%） had neither a virological breakthrough nor a flare-up. All 20 patients who developed a hepatitis flare-up had a biochemical and virological response after adefovir was added to the lamivudine treatment. CONCLUSION： Our results suggest that it is possible to continue lamivudine treatment, even after the emergence of YMDD mutants, up to the time that the patients develop a hepatitis flare-up.

关键词： Tyrosine-methionine-asparatate-asparatatemutant Hepatitis B virus Lamivudine Drug resistance

Effect of SiO_(2)on loss of catalysis of inherent metallic species in CO_(2)gasification of coke from lignite

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Carbon Resources Conversion 2019年第1期2卷 13-22页

作者： Cheolyong Choi U.P.M.Ashik Shinji Kudo Kazuya Uebo Koyo Norinaga jun-ichiro hayashi Interdisciplinary Graduate School of Engineering Sciences Kyushu University6-1Kasuga KoenKasuga 816-8580Japan Institute for Materials Chemistry and Engineering Kyushu University6-1Kasuga KoenKasuga 816-8580Japan Process Research Laboratories Nippon Steel&Sumitomo Metal Corporation20-1ShintomiFuttsu 293-8511Japan Department of Materials Science and Engineering School of EngineeringNagoya UniversityNagoyaAichi 464-8601Japan Transdisciplinary Research and Education Center of Green Technology Kyushu University6-1Kasuga KoenKasuga 816-8580Japan

Inherent metallic species retained by coal char or coke,such as Na and Ca,behave as catalysts in *** char/coke normally contains inherent SiO_(2),which can react with the inherent catalysts to form silicates,resulting in catalyst deactivation over the range of pyrolysis,carbonization and gasification,and thereby reducing the char/coke *** present authors simulated the inherent catalyst deactivation experimentally by blending a Victorian lignite with SiO_(2),briquetting the SiO_(2)/lignite blend,carbonizing the briquette,and then gasifying the coke with CO_(2).The kinetic analysis of the gasification employed a comprehensive model,which assumed progress in parallel of non-catalytic and catalytic *** model quantitatively described the measured kinetics of the coke gasification with different SiO_(2)contents over a range of coke conversion up to 99.9%.The kinetic analysis revealed that the SiO_(2)deactivated substantial and entire portions of the most active catalyst and its precursor,respectively,before the gasification(i.e.,during the carbonization).The catalyst deactivation also occurred during the gasification,but mainly following a self-deactivation mechanism that involved no silicates formation.

关键词： Coke Lignite Reactivity CO_(2)gasification Inherent metallic species Catalyst Deactivation SiO_(2)

Pre-treatment role of inosine triphosphate pyrophosphatase polymorphism for predicting anemia in Egyptian hepatitis C virus patients

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World Journal of Gastroenterology 2013年第9期19卷 1387-1395页

作者： Walaa H Ahmed Norihiro Furusyo Saad Zaky Abeer Sharaf Eldin Hany Aboalam Eiichi Ogawa Masayuki Murata jun hayashi Department of Environmental Medicine and Infectious Diseases Kyushu University Hospital Fukuoka 812-8582 Japan Department of General Internal Medicine Kyushu University Hospital Fukuoka 812-8582 Japan Department of Tropical Medicine and Gastroenterology Assiut University Hospital Assuit 71515 Egypt National Center for Treatment of Chronic Hepatitis C Ministry of Health Assiut 71329 Egypt

AIM: To investigate and clarify, for the first time, the role of inosine triphosphate pyrophosphatase (ITPA ) polymorphism in Egyptian chronic hepatitis C virus (HCV) ***:The human genomic DNA of all patients was extracted from peripheral blood cells in order to determine the single nucleotide polymorphism (SNP) of ITPA (rs1127354). SNP genotyping was performed by real time polymerase chain reaction (PCR, ABI TaqMan allelic discrimination kit) for 102 treatment-naive Egyptian patients with chronic HCV. All patients had no evidence of cardiovascular or renal diseases. They received a combination treatment of pegylated interferon α (PEG-IFNα) as a weekly subcutaneous dose plus an oral weight-adjusted dose of ribavirin (RBV). The majority received PEG-IFNα2a (70.6%) while 29.4% received PEG-IFNα2b. The planned duration of treatment was 24-48 wk according to the viral kinetics throughout the course of treatment. Pre-treatment liver biopsy was done for each patient for evaluation of fibrosis stage and liver disease activity. The basal viral load level was detected quantitatively by real time PCR while viral load throughout the treatment course was performed qualitatively by COBAS TaqMan assay. RESULTS: Ninety-three patients (91.2%) had ITPA SNP CC genotype and 9 (8.8%) had non-CC genotype (CA and AA). The percentage of hemoglobin (Hb) decline was higher for CC patients than for non-CC patients, particularly at weeks 4 and 8 (P=0.047 and 0.034, respectively). During the first 12 wk of treatment, CC patients had significantly more Hb decline > 3 g/dL than non-CC patients: 64.5% vs 22.2% at weeks 8 and 12, respectively, (P=0.024 and 0.038). Reduction of the amount of the planned RBV dose was significantly higher for CC patients than non-CC patients during the first 12 wk (18% ± 12.1% vs 8.5% ± 10.2%, P=0.021). The percentage of CC patients with RBV dose reduction was significantly greater than that of non-CC patients (77.4% vs 44.4%, P=0.044). Multivariate anal

关键词： Anemia Dose reduction Hepatitis C Inosine triphosphate Ribavirin Rs1127354

Pegylated interferon α-2b plus ribavirin for older patients with chronic hepatitis C

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World Journal of Gastroenterology 2010年第35期16卷 4400-4409页

作者： Mosaburo Kainuma Norihiro Furusyo Eiji Kajiwara Kazuhiro Takahashi Hideyuki Nomura Yuichi Tanabe Takeaki Satoh Toshihiro Maruyama Makoto Nakamuta Kazuhiro Kotoh Koichi Azuma junya Shimono Shinji Shimoda jun hayashi Department of General Internal Medicine Kyushu University Hospital Department of Internal Medicine Nippon Steel Yawata Memorial Hospital Department of Medicine Hamanomachi Hospital The Center for Liver Disease Shin-Kokura Hospital Department of Medicine Fukuoka City HospitalYoshiduka-honmachi Center for Liver Disease National Hospital Organization Kokura Medical Center Department of Medicine Kitakyushu Municipal Medical Center Department of Gastroenterology Kyushu Medical CenterNational Hospital Organization Department of Medicine and Bioregulatory Science Graduate School of Medical ScienceKyushu University Department of Medicine and Clinical Science Graduate School of Medical SciencesKyushu University Saiseikai Yahata General Hospital Harunomachi Department of Medicine and Biosystemic Science Graduate School of Medical ScienceKyushu University

AIM:To analyze the efficacy and safety of a combination therapy of pegylated interferon(PEG-IFN) α-2b plus ribavirin(RBV) in older Japanese patients(65 years or older) infected with hepatitis C virus(HCV).METHODS:This multicenter study included 938 patients with HCV genotype 1 who received 1.5 μg/kg per week PEG-IFN α-2b plus RBV 600-1000 mg/d for 48 wk and 313 HCV genotype 2 patients who received this treatment for 24 ***:At 24 wk after the end of combination therapy,the overall sustained virological response(SVR) for genotypes 1 and 2 were 40.7% and 79.6%,*** SVR rate decreased signif icantly with age in each genotype,and was markedly reduced in genotype 1(P<0.001).Moreover,the SVR was significantly higher in patients with genotype 1 who were less than 65 years(47.3% of 685) than in those 65 years or older(22.9% of 253)(P<0.001) and was higher in patients with genotype 2 who were less than 65 years(82.9% of 252) than in those 65 years or older(65.6% of 61)(P=0.004).When patients received a dosage at least 80% or more of the target dosage of PEG-IFN α-2b and 60% or more of the target dosage of RBV,the SVR rate significantly increased to 66.5% in patients less than 65 years and to 45.2% in those 65 years or older(P<0.001).Adverse effects resulted in treatment discontinuation more often in patients with genotype 1(14.4%) than in patients with genotype 2(7.3%),especially by patients 65 years or older(24.1%).CONCLUSION:PEG-IFN α-2b plus RBV treatment was effective in chronic hepatitis C patients 65 years or older who completed treatment with at least the minimum acceptable treatment dosage.

关键词： Hepatitis C virus Gerontology Pegylated interferon Ribavirin

Long-term lamivudine treatment for chronic,hepatitis B in Japanese patients:A project of Kyushu University Liver Disease Study

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World Journal of Gastroenterology 2006年第4期12卷 561-567页

作者： Norihiro Furusyo Hiroaki Takeoka Kazuhiro Toyoda Masayuki Murata Yuichi Tanabe Eiji Kajiwara junya Shimono Akihide Masumoto Toshihiro Maruyama Hideyuki Nomura Makoto Nakamuta Kazuhiro Takahashi Shinji Shimoda Koichi Azuma Hironori Sakai jun hayashi Department of General Medicine Kyushu University Hospital Department of Environmental Medicine and Infectious Diseases Graduate School of Medical Sciences. Kyushu University Fukuoka Japan Department of Medicine Fukuoka City HospitalFukuoka Japan Department of Internal Medicine Nippon SteelYawata Memorial Hospital Kitakyushu Japan Department of Medicine Yahata SaiseikaiHospital Kitakyushu Japan Department of Clinical Research NationalHospital Organization Kokura Hospital Kitakyushu Japan Department of Medicine KitakyushuMunicipal Medical Center Kitakyushu Japan Department of Internal Medicine ShinKokura Hospital Kitakyushu Japan Department of Medicine and Bioregulatory Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine HamanomachiHospital Fukuoka Japan Department of Medicine and Biosystemic Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Medicine and Clinical Science Graduate School of Medical Sciences Kyushu University Fukuoka Japan Department of Gastroenterology National Hospital Organization Kyushu Medical Center Fukuoka Japan

AIM： To determine the efficacy of long-term lamivudine treatment of a large number of Japanese patients with chronic hepatitis B. METHODS： In this retrospective, multi-center trial, 318 Japanese patients with chronic hepatitis B received 100 mg of lamivudine daily for up to 36 （median 21） mo. Virological response was a decline to a serum HBV DNA level less than 3.7 log copies/mL. Virological breakthrough was defined as the reappearance of a serum HBV DNA level to more than 10-fold the minimum during treatment. RESULTS： Lamivudine produced virological response in 86.8% of the 318 patients at 6 mo, in 80.2% of 252 patients at 12 mo, in 69.2% of 133 patients at 24 mo, and in 53.6% of 28 patients at 36 mo. Forward stepwise logistic regression analysis showed an HBV DNA level less than 6.8 log copies/mL （P〈 0.0001）, HBeAg negativity （P〈 0.0001）, a platelet count of 100×10^9/L or more （P= 0.0162） at baseline, and a decline of the HBV DNA level of more than 3.2 log copies/mL as compared with the baseline level at 3 mo after the start of treatment （P= 0.0003） to be significantly associated with virological response. Among patients with a virological response, virological breakthrough was seen in 5.3% of 19 patients who responded virologically at 1 mo, in 20.7% of 203 patients at 3 mo, in 27.5% of 51 patients at 6 mo, in 33.3% of 12 patients at 9 mo, and in 100% of 3 patients at ≥15 mo. A virological breakthrough was found significantly more often in patients with delayed virological response. CONCLUSION： Lamivudine treatment could suppress serum HBV DNA in most of the tested Japanese patients. Long-term efficacy might be seen in patients without HBeAg at baseline, in the absence of cirrhosis, and in patients with a decline in HBV DNA level soon after the start of treatment.

关键词： Hepatitis B virus Lamivudine HBeAg Cirrhosis

Interferon alpha plus ribavirin combination treatment of Japanese chronic hepatitis C patients with HCV genotype 2:A project of the Kyushu University Liver Disease Study Group

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World Journal of Gastroenterology 2006年第5期12卷 784-790页

作者： Norihiro Furusyo Masaki Katoh Yuichi Tanabe Eiji Kajiwara Toshihiro Maruyama junya Shimono Hironori Sakai Makoto Nakamuta Hideyuki Nomura Akihide Masumoto Shinji Shimoda Kazuhiro Takahashi Koichi Azuma jun hayashi Kyushu University Liver Disease Study Group Department of General Medicine Kyushu University HospitalFukuokaJapan Department of Medicine Fukuoka City HospitalFukuokaJapan Department of Internal Medicine Nippon Steel Yawata Memorial HospitalKitakyushuJapan Department of Medicine Kitakyushu Municipal Medical CenterKitakyushuJapan Department of Medicine Yahata Saiseikai HospitalKitakyushuJapan Department of Gastroenterology National Hospital Organization Kyushu Medical CenterFukuokaJapan Department of Medicine and Bioregulatory Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Internal Medicine ShinKokura HospitalKitakyushuJapan Department of Clinical Research National Hospital OrganizationKokura HospitalKitakyushuJapan Department of Medicine and Biosystemic Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan Department of Medicine Hamanomachi HospitalFukuokaJapan Department of Medicine and Clinical Science Graduate School of Medical SciencesKyushu UniversityFukuokaJapan

AIM： To determine the efficacy of an interferon alpha and ribavirin combination treatment for Japanese patients infected with hepatitis C virus （HCV） of genotype 2, a multi-center study was retrospectively analyzed. METHODS： In total, 173 patients with HCV genotype 2 started to receive interferon-alpha subcutaneously thrice a week and 600-800 mg of ribavirin daily for 24 wk. RESULTS： The overall sustained virological response （SVR）, defined as undetectable HCV RNA in serum, 24 wk after the end of treatment, was remarkably high by 84.4%, （146/173） by an intention-to-treat analysis. A significant difference in SVR was found between patients with and without the discontinuation of ribavirin （46.9% vs 92.9 %）, but no difference was found between those with and without a dose reduction of ribavirin. A significant difference in SVR was also found between patients with less than 16 wk and patients with 16 or more weeks of ribavirin treatment （34.8 % vs 92.0 %）. CONCLUSION： The 24-wk interferon and ribavirin treatment is highly effective for Japanese patients with HCV genotype 2. The significant predictor of SVR is continuation of the ribavirin treatment for up to 16

关键词： Hepatitis C virus Interferon Ribavirin Genotype 2

Decomposition of Toluene as a Biomass Tar through Partial Combustion

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Journal of Energy and Power Engineering 2012年第6期6卷 869-877页

作者： Noriaki Nakatsuka Yasushi Imoto jun hayashi Miki Taniguchi Kenichi Sasauchi Mayumi Matsuda Fumiteru Akamatsu Department of Mechanical Engineering Osaka University Osaka 5650871 Japan Environmental Engineering Department Chugai Ro Co. Ltd. Osaka 5928331 Japan Gas Chromatograph Department J-Science Lab. Co. Ltd. Kyoto 6018144 Japan

One way for reducing tar is oxidative and thermal cracking by partial combustion of the biomass producer gas in the gas reformer. Cracking and polymerization of the tar occur simultaneously at the proximity of inverse diffusion flame. Experimental study has been performed to clarify the effect of hydrogen concentration on soot formation and the growth of polycyclic aromatic hydrocarbons. In the present study, hydrogen concentration is controlled by the small amount of hydrogen addition to the oxidizer. The main results are as follows. Soot formation is suppressed by the small amount of hydrogen addition. The suppression of soot formation is caused by higher concentration of hydrogen. Carbon yield increases by hydrogen addition since carbon content in the undetectable components by the integrated gas chromatograph decreases. In addition, the increase in carbon yield is caused mainly by the increase in carbon monoxide stemmed from reforming of high-boiling components.

关键词： Biomass tar inverse diffusion flame PAHs soot formation.