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Bicarbonate Attenuates Irinotecan-Induced Cytotoxicity through Regulation of Both Extracellular and Intracellular <i>pHs</i>in Intestine Cell Line

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Journal of Cancer Therapy 2013年第5期4卷 944-952页

作者： Teruo Miyazaki Tadashi Ikegami yoshiaki nagai Amy Nguyen Yasushi Matsuzaki Kunihiko Kobayashi Susan Ceryak Department of Biochemistry and Molecular Biology The George Washington University Washington DC USA Department of Internal Medicine Division of Gastroenterology and Hepatology Tokyo Medical University Ibaraki Medical Center Ami Ibaraki Japan Department of Pharmacology The George Washington University Washington DC USA Department of Respiratory Medicine Saitama International Medical Center Saitama Medical University Hidaka Saitama Japan Joint Research Center Tokyo Medical University Ibaraki Medical Center Ami Ibaraki Japan

The anti-cancer therapy of irinotecan (CPT-11) is often limited due to severe late-onset diarrhea. Because the higher toxic form of CPT-11/its active metabolite (SN-38) is produced at acidification, the usefulness of oral sodium bicarbonate treatment against the CPT-11/SN-38-induced intestinal injuries and diarrhea has been confirmed. However, the roles of bicarbonate have been suggested to affect not only intestinal pH environment but also intracellular pH and CPT-11/SN-38 dynamics. The present study proposed to clarify the hypothesis in CPT-11/SN-38-exposed colon cell line in various pH conditions adjusted by bicarbonate. HT29 cell pre-exposed to ~1.0 μM SN-38 lactone or carboxylate forms was incubated at different pH adjusted by either bicarbonate or HCl/NaOH. The degrees of SN-38-induced cell injury depended on the higher proportion of the toxic form (lactone) of SN-38 rather than mere pH condition of medium. Apoptosis and cell injury induced by SN-38 were significantly inhibited by bicarbonate in a dose-dependent manner. Intercellular pH acidification induced by SN-38 was significantly prevented by 30 mM bicarbonate. Cell cytotoxicity of SN-38 depended on not only extracellular but also intracellular pH that converts the SN-38 form, while the intracellular acidification was prevented by bicarbonate. The multiple regulations of bicarbonate on both exracellular and intracellular pH would be essential mechanism against intestinal cell injury by CPT-11/SN-38.

关键词： Bicarbonate SN-38 CPT-11 pHi Anti-Cancer Drug Intestine

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SPERA Hydrogen System^(TM)by LOHC-MCH Method for Massive Hydrogen Storage and Transportation

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Journal of Environmental Science and Engineering(A) 2024年第2期13卷 50-60页

作者： Yoshimi Okada Kaji Naohiro Osamu Ikeda Kenichi Imagawa Hironori Kawai Masashi nagai Yasuhiro Inoue Frontier Business Division Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan Hydrogen Business Department Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan R&D Center Chiyoda Corporation3-13 Moriya-cho Kanagawa-kuYokohama 2208765Japan Technology Development Department Chiyoda Corporation4-6-2 Minatomirai Nishi-kuYokohama 2208765Japan

Expanding the hydrogen energy utilization is essential for decarbonization,and the commercialization of hydrogen energy carrier systems that can“store”and“transport”hydrogen in a large scale is necessary.The organic chemical hydride method incorporates hydrogen atoms into the molecular structure of a LOHC(Liquid Organic Hydrogen Carrier)to store and transport hydrogen in a liquid state under normal temperature and pressure,and is a highly safe method with low business risk.Chiyoda has been developing the technology since 2002,completed a pilot demonstration in 2014 and named it the SPERA Hydrogen^(TM) System,and successfully completed an international supply chain demonstration that transports hydrogen from Brunei to Japan in a large scale in 2020,moving to the commercialization stage.Currently,Chiyoda is conducting feasibility studies with a number of domestic and foreign companies with the aim of commercializing the system as soon as possible.In this paper,outline,features,development status and our efforts in commercialization of SPERA HydrogenTM System are introduced.

关键词： Hydrogen carrier LOHC Methylcyclohexane MCH toluene

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Diffuse large B-cell lymphoma successfully treated with amplified natural killer therapy alone: A case report

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World Journal of Clinical Cases 2023年第30期11卷 7432-7439页

作者： Kenjiro nagai Syo nagai Yuji Okubo Keisuke Teshigawara Department of Internal Medicine Medical Corporation Ebino Centro ClinicEbino 889-4304Japan Department of Internal Medicine Higashinotoin ClinicKyoto 604-8175Japan

BACKGROUND The prognosis of patients with advanced diffuse large B-cell lymphoma(DLBCL)is poor,with a 5-year survival rate of approximately 50%.The mainstay of treatment is multidrug combination chemotherapy,which has been associated with serious side effects.Amplified natural killer(ANK)cell therapy amplifies and activates natural killer(NK)cells to attack only malignant tumors.As ANK cells attack programmed death ligand 1(PD-L1)-positive tumor cells,ANK therapy is considered effective against adult T-cell lymphoma and malignant lymphoma.CASE SUMMARY Herein,we report a case of an older patient with advanced DLBCL who was successfully treated with ANK immunotherapy.A 91-year-old female visited our hospital with sudden swelling of the right axillary lymph node in April 2022.The patient was diagnosed with stage II disease,given the absence of splenic involvement or contralateral lymphadenopathy.ANK therapy was administered.Six rounds of lymphocyte sampling were performed on July 28,2022.To reduce the occurrence of side effects,the six samples were diluted by half to obtain 12 samples.Cultured NK cells were administered twice weekly.The treatment efficacy was evaluated by performing computed tomography and serological tests every 1 or 2 mo.The treatment suppressed lesion growth,and the antitumor effect persisted for several months.The patient experienced mild side effects.PD-L1 immunostaining was positive,indicating that the treatment was highly effective.CONCLUSION ANK therapy can be used as a first-line treatment for malignant lymphoma;the PD-L1 positivity rate can predict treatment efficacy.

关键词： Diffuse large B-cell lymphoma Natural killer cells Immunostaining Hodgkin's lymphoma Older adult Case report

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Optimal consumption–investment under partial information in conditionally log-Gaussian models

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Probability, Uncertainty and Quantitative Risk 2023年第1期8卷 95-120页

作者： Hideo nagai MMDS Osaka UniversityToyonaka 560-8531OsakaJapan

Certain Merton type consumption−investment problems under partial information are reduced to the ones of full information and within the framework of a complete market model.Then,specializing to conditionally log−Gaussian diffusion models,concrete analysis about the optimal values and optimal strategies is performed by using analytical tools like Feynman−Kac formula,or HJB equations.The explicit solutions to the related forward-backward equations are also given.

关键词： Optimal consumption-investment problem Conditionally log−Gaussian models HJB equations Feynman−Kac formula Forward-backward equations

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Relationship between arterial stiffness and cognitive function in outpatients with dementia and mild cognitive impairment compared with community residents without dementia

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Journal of Geriatric Cardiology 2022年第8期19卷 594-602页

作者： Ai Hirasawa Kumiko nagai Taiki Miyazawa Hitomi Koshiba Mami Tamada Shigeki Shibata Koichi Kozaki Department of Health and Welfare Faculty of Health SciencesKyorin UniversityTokyoJapan Department of Geriatric Medicine Faculty of MedicineKyorin UniversityTokyoJapan Department of Health and Sports Science Faculty of WellnessShigakkan UniversityAichiJapan

BACKGROUND It is unclear whether the dementia patients with Alzheimer’s disease(AD)and vascular dementia(VaD)and mixed dementia(MIX,including AD and VaD)would have more developed arterial stiffness as compared with local residents without dementia.The aim of this study was to assess arterial stiffness and cognitive function in different types of dementia pa-tients[AD,VaD,MIX and mild cognitive impairment(MCI)]and community residents without dementia.METHODS This was a single-center,cross-sectional observational study.We studied a cohort of 600 elderly outpatients with a complaint of memory loss,who were divided into four groups(AD,VaD,MIX and MCI).In addition,they were compared with 55 age-matched local residents without dementia(Controls).We assessed arterial stiffness by brachial-ankle pulse wave velocity(baPWV)and the global cognitive function by the Mini-Mental State Examination(MMSE).RESULTS The baPWV was higher in AD,VaD and MIX than in MCI and in Controls(P<0.05).The baPWV was higher in MCI than in Controls(P=0.021),while MMSE were compatible between them(P=0.119).The higher baPWV predicted the presence of AD,VaD,MIX and MCI with the odds ratio of 6.46,8.74,6.16 and 6.19,respectively.In contrast,there were no difference in baPWV among three different types of dementia(P=0.191).The linear relationship between baPWV and MMSE was observed in the elderly with MMSE≥23(R=0.452,P=0.033),while it was not in dementia patients(MMSE<23).CONCLUSIONS The findings suggest that MCI and dementia patients have stiffer arteries as compared with age-matched local residents,although global cognitive function may be comparable between MCI and the local residents.

关键词： arterial impairment stiffness

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Chiral hierarchical structure of bone minerals

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Nano Research 2022年第2期15卷 1295-1302页

作者： Chao Zhou Xueliang Zhang Jing Ai Ting Ji Masaya nagai Yingying Duan Shunai Che Lu Han School of Chemistry and Chemical Engineering State Key Laboratory of Composite MaterialsShanghai Key Laboratory for Molecular Engineering of Chiral DrugsShanghai Jiao Tong University800 Dongchuan RoadShanghai 200240China School of Chemical Science and Engineering Tongji University1239 Siping RoadShanghai 200092 China Graduate School of Engineering Science Osaka University1-3 MachikaneyamaToyonakaOsaka 5608531Japan

Chirality is an indispensable integral of biological system.As an important part of organisms,chiral organic structure of bone has been extensively investigated.However,the chirality of bone minerals is unclear and not fully determined.Here,we report nine levels of fractal-like chirality of bone minerals by combining electron microscopic and spectrometric characterizations.The primary helically twisted acicular apatite crystals inside collagen fibrils and between fibrils merge laterally to form secondary helical subplatelets.The chiral arrangement of several subplatelets forms tertiary spiral mineral platelets.Further coherent stepwise stacking of mineral platelets with collagen fibrils leads to quaternary to ninth levels,which reconciled the previous conflicting models.The optical activities in the UV-visible,infrared and terahertz regions demonstrated chirality from atomic to macroscopic scales based on circularly selective absorption and Bragg resonance at different levels of chirality.Our findings provide new insight into the structural integrity of bone,osteology,forensic medicine and archaeology and inspire the design of novel biomaterials.

关键词： chiral hierarchical structure fractal-like chirality chirality of organisms bone bone minerals

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Efficacy of ripasudil in reducing intraocular pressure and medication score for ocular hypertension with inflammation and corticosteroid

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International Journal of Ophthalmology(English edition) 2023年第6期16卷 904-908页

作者： Ryoji Yanai Sho-Hei Uchi Masaaki Kobayashi Tomohiko nagai Shinichiro Teranishi Makiko Wakuta Kazuhiro Kimura Department of Ophthalmology Yamaguchi University Graduate School of MedicineYamaguchi 755-8505Japan

·AIM:To investigate the efficacy of ripasudil,a Rho kinase inhibitor,in reducing intraocular pressure(IOP)and medication scores of anti-glaucoma drugs in patients with ocular hypertension with inflammation and corticosteroid.·METHODS:The study included 11 patients diagnosed with ocular hypertension with inflammation and corticosteroid,all of whom were prescribed ripasudil eye drops and followed up for at least 2y after the initiation of treatment.IOP was measured using a non-contact tonometer before enrollment and at each follow-up visit.The medication score of glaucoma eye drops was calculated for each patient.·RESULTS:The mean IOP(26.4±2.9 mm Hg before treatment)significantly decreased after ripasudil therapy(13.7±3.3 mm Hg at 3mo)and remained stable in the low-teens during the 2-year follow-up period(P<0.0001).A significant decrease in the medication score was observed at 12mo or later after the initiation of ripasudil therapy(P<0.05).Both baseline medication scores and glaucomatous optic disc change rates were significantly higher in the five eyes that required glaucoma surgery during the 2-year observation period than the 10 eyes that did not require surgery.·CONCLUSION:Our results demonstrate the efficacy of ripasudil,in reducing IOP and the medication score over a 2-year treatment period in patients with ocular hypertension with inflammation and corticosteroid.Our findings also suggest that ripasudil could reduce the IOP in uveitic glaucoma patients with both lower baseline medication score and lower glaucomatous optic disc change rate.

关键词： KEYWORDS:intraocular pressure medication score uveitis glaucoma Rho kinase inhibitor

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An old uterine rupture repaired 2 months postpartum using laparoscopy aided by hysteroscopy: A case report

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第4期5卷 153-157页

作者： Yuichiro Kizaki Kouki Samejima Shigetaka Matsunaga Tomonori nagai Yasushi Takai Department of Obstetrics and Gynecology Saitama Medical CenterSaitama Medical UniversitySaitama Ken 350-8550Japan

With an incidence of 0.005%,unscarred uterine rupture is extremely rare.It is difficult to diagnose uterine rupture because of the absence of characteristic clinical symptoms.Here,we report a rare case of a 31-year-old woman with a uterine rupture that was accurately diagnosed and repaired by laparoscopy and hysteroscopy on postpartum day 69.The patient recovered uneventfully and was discharged on postoperative day 4.Three months after surgery,pelvic magnetic resonance imaging was performed,which confirmed wound repair.In women with a stable condition,laparoscopy with hysteroscopy could be an alternative choice for the diagnosis and treatment of suspected uterine rupture;however,more substantial studies are needed to confirm this surgical approach.

关键词： Hysteroscopy Laparoscopic surgery Uterine rupture Postpartum hemorrhage Uterine preservation

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Factors associated with surgical-site infection after total laparoscopic hysterectomy

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Laparoscopic, Endoscopic and Robotic Surgery 2022年第4期5卷 131-135页

作者： Kosuke Shigematsu Koki Samejima Yuichirou Kizaki Shigetaka Matsunaga Tomonori nagai Yasushi Takai Department of Obstetrics and Gynecology Saitama Medical CenterSaitama Medical UniversitySaitama 350-8550Japan

Objective:In recent years,minimally invasive surgery has been emphasized in gynecological surgery,and total laparoscopic hysterectomy has been increasingly reported.In this retrospective single-center study,the main objective was to identify risk factors for the development of surgical-site infection(SSI)after total laparoscopic hysterectomy.The secondary objective was to investigate the efficacy of transvaginal drainage as a treatment for SSI.Methods:This retrospective study investigated 377 patients who underwent total laparoscopic hysterectomy in the Department of Obstetrics and Gynecology at the Saitama Medical Center,Saitama Medical University,Japan between January 1,2015 and December 31,2019.Patients were divided into the SSI group and non-SSI group based on whether they suffered from SSI.The data of preoperative,intraoperative,and postoperative risk factors for SSI were collected and analyzed.Results:Of the 377 patients who underwent total laparoscopic hysterectomy,21 patients were in the SSI group and 356 patients were in the non-SSI group.After the comparison between the two groups and the multivariate analysis,only the C-reactive protein level on postoperative day 3(OR¼1.556,95%CI:1.233 e1.964,p7.6 mg/dL on postoperative day 3 could detect the SSI onset early.In the SSI group,the hospital stay was longer for patients with transvaginal drainage than for patients without(17.40±3.21 d vs.10.90±2.39 d,p¼0.0027).However,none required reoperation.Conclusions:Patients with a high postoperative C-reactive protein level may be experiencing SSI,and ultrasonography and other imaging procedures should be performed immediately.If a vaginal abscess is confirmed on imaging,transvaginal drainage should be performed early,which may prevent reoperation.

关键词： Hysterectomy Laparoscopic surgery Surgical-site infection

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Biological efficacy of perpendicular type-I collagen protruded from TiO_(2)-nanotubes

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International Journal of Oral Science 2020年第4期12卷 346-355页

作者： Chia-Yu Chen David M.Kim Cliff Lee John Da Silva Shigemi nagai Toshiki Nojiri Masazumi nagai Department of Oral Medicine Infection and ImmunityHarvard School of Dental Medicine188 Longwood AvenueBostonMAUSA Department of Restorative Dentistry and Biomaterials Sciences Harvard School of Dental Medicine188 Longwood AvenueBostonMAUSA Department of Prosthodontics and Oral Implantology School of Dental MedicineIwate Medical University19-1 UchimaruMoriokaIwateJapan

The aim of this study was to evaluate the biological efficacy of a unique perpendicular protrusion of type-I collagen(Col-I)from TiO2 nanotubes(NT-EPF surface).We hypothesized that the NT-EPF surface would play bifunctional roles in stimulating plateletmediated fibroblast recruitment and anchoring fibroblast-derived Col-I to form a perpendicular collagen assembly,mimicking the connective tissue attachment around natural teeth for the long-term maintenance of dental implants.Ti surface modification was accomplished in two steps.First,TiO2 nanotubes(NT)array was fabricated via anodization.Diameters and depths of NTs were controlled by applied voltage and duration.Subsequently,an electrophoretic fusion(EPF)method was applied to fuse Col-I into nanotube arrays in a perpendicular fashion.Surface wettability was assessed by contact angle measurement.The bioactivity of modified TiO2 surfaces was evaluated in terms of NIH3T3 fibroblast attachment,platelet activation,and collagen extension.Early attachment,aggregation,and activation of platelets as well as release of platelet-related growth factors were demonstrated on NTEPF surfaces.Platelet-mediated NIH3T3 cells migration toward NT-EPF was significantly increased and the attached cells showed a typical fibrous morphology with elongated spindle shape.A direct linkage between pseudopod-like processes of fibroblasts to NTEPF surfaces was observed.Furthermore,the engineered EPF collagen protrusion linked with cell-derived collagen in a perpendicular fashion.Within the limitation of this in vitro study,the TiO2 nanotube with perpendicular Col-I surface(NT-EPF)promoted better cell attachment,induced a strong platelet activation which suggested the ability to create a more robust soft tissue seal.

关键词： activation linkage sized

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