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Hyperglycemia is a significant prognostic factor of hepatocellular carcinoma after curative therapy

World Journal of Gastroenterology 2013年第2期19卷 249-257页

作者： Takanori Hosokawa Masayuki Kurosaki Kaoru Tsuchiya Shuya Matsuda Masaru Muraoka Yuichiro suzuki Nobuharu Tamaki Yutaka Yasui Toru Nakata Takashi Nishimura shoko suzuki Ken Ueda Hiroyuki Nakanishi Jun Itakura Yuka Takahashi Namiki Izumi Division of Gastroenterology and Hepatology Musashino Red Cross HospitalTokyo 180-8610Japan

AIM:To evaluate whether metabolic factors are related to distant recurrence of hepatocellular carcinoma(HCC) and survival after curative ***:This retrospective study included 344 patients whose HCC was treated curatively by radiofrequency ablation(RFA) *** mean age was 67.6 years and the mean observation period was 4.04 *** etiological background of liver disease was hepatitis B virus infection in 30,hepatitis C virus infection in 278,excessive alcohol drinking in 9,and other in 27 *** Child-Pugh classification grade was A(n = 307) or B(n = 37).The number of HCC nodules was one in 260,two in 61,and three in 23 *** surveillance of HCC recurrence after curative therapy with RFA,patients were radiologically evaluated every 3 *** associated with distant recurrence of HCC or survival were ***:Inadequate maintenance of blood glucose in diabetic patients was associated with higher incidence of distant *** 1-,2-,and 3-year recurrence rates were significantly higher in diabetic patients with inadequate maintenance of blood glucose compared with the others:50.6% vs 26.8%,83.5% vs 54.4%,and 93.8% vs 73.0%,respectively(P = 0.0001).Inadequate maintenance of blood glucose was an independent predictor of distant recurrence [adjusted relative risk 1.97(95%CI,1.33-2.91),(P = 0.0007)] after adjustment for other risk factors,such as number of HCC nodules [2.03(95%CI,1.51-2.73),P < 0.0001] and initial level of serum alpha fetoprotein(AFP) [1.43(95%CI,1.04-1.97),P = 0.028].Obesity was not an independent predictor of *** incidence of distant recurrence did not differ between diabetic patients with adequate maintenance of blood glucose and non-diabetic *** 232 patients who had HCC recurrence,138 had a second *** 1-,2-,and 3-year rates of second recurrence were significantly higher in diabetic patients with inadequate maintenance of blood glucose than in the others:9.0% vs 5.9%,53.1

关键词： Hyperglycemia Hepatocellular carcinoma Recurrence Radio frequency ablation Survival

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Perfect Solvent- and Catalyst-Free Syntheses of Imine Derivatives Using the Pressure Reduction Technique

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Green and Sustainable Chemistry 2019年第4期9卷 105-118页

作者： shoko suzuki Hiroyuki Ito Shinji Ishizuka Risehiro Nonaka Motoyoshi Noike Takeshi Kodama Kenji Funaki Mizuho Taguchi Taisei Kagaya Sayaka Sato Guillaume Redler Yasuo Yokoyama Faculty of Education Kyoto University of Education Kyoto Japan Department of Chemical and Biological Engineering National Institute of Technology Akita College Akita Japan Environment Systems Engineering Course National Institute of Technology Akita College Akita Japan Department of Applied Chemistry National Institute of Technology Akita College Akita Japan Science et Génie des Matériaux IUT Blois Blois France.

In the field of organic syntheses, the development of environmentally friendly methods based on the concept of green chemistry has been always required. In response to this requirement, we reported solvent- and catalyst-free syntheses of imines using the pressure reduction technique as a key technology. We found that this reaction proceeded very rapidly in the initial stage, but its rate decreased with the passage of time. It was also found that the reaction of benzaldehyde with aniline had a specificity that the phase transition occurred. In this method, the desired imines could be obtained in good to excellent yields, but target compounds had to be given by purifications using organic solvents. Therefore, we tried to develop the perfect synthetic method of imine derivatives without organic or inorganic solvents. We selected two methods and took them into this investigation. One was exactly mixing (1:1, substance ratio) aldehydes and amines and the other was employing lower pressure (>0.1 mmHg, previous method: 1.0 mmHg) at the pressure reducing technique. When this improved synthetic method was performed, it was revealed that pure target imines were obtained in excellent yields without any purification.

关键词： Solvent-Free Catalyst-Free Neat Reaction Pressure Reduction Technique Imine

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Environmentally Friendly Syntheses of Imines Applying the Pressure Reduction Technique: Reaction Cases of Less Reactive Amines and Studies by Computational Chemistry

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Green and Sustainable Chemistry 2020年第1期10卷 1-17页

作者： shoko suzuki Hiroyuki Ito Motoyoshi Noike Shinji Ishizuka Risehiro Nonaka Kenji Funaki Takeshi Kodama Shujiro Sakaki Tomomichi Nishino Mina Ito Toranosuke Takahasi Yasuo Yokoyama Faculty of Education Kyoto University of Education Kyoto Japan Department of Chemical and Biological Engineering National Institute of Technology Akita College Akita Japan Institute of Natural Medicine University of Toyama Toyama Japan Department of Applied Chemistry National Institute of Technology Akita College Akita Japan

Recently, the development of environmentally friendly syntheses of imine derivatives, which were attracting great attention for their reactivity and structure in various fields, progressed rapidly because the concept of green chemistry had deeply penetrated into society. In our previous work, we had reported new synthetic methods of imine derivatives using some active amines under solvent- and catalyst-free reaction conditions. This synthetic reaction proceeded smoothly and target compounds were obtained in excellent yields. In this system, when less reactive amines were used as substrates, the synthetic reaction was not finished in the short reaction time, and the corresponding compounds were given in moderate yields. In order to solve this point, we tried to improve the reaction conditions of this method. Through this improvement, it was found that pure target compounds could be obtained in excellent yields by using 1.1 equivalents of less reactive amines to aldehydes and extending the reaction time compared with our previous work. In this paper, we will introduce the detail of this study, and also report the result of the investigation of the reaction property by computational chemistry.

关键词： Solvent-Free Catalyst-Free Pressure Reduction Technique Imine Computational Chemistry

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Efficient Solvent- and Catalyst-Free Syntheses of Imine Derivatives Applying the Pressure Reduction Technique: Remarkable Change of the Reaction Rate with the Phase Transition

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Green and Sustainable Chemistry 2018年第2期8卷 167-179页

作者： shoko suzuki Shujiro Sakaki Shinji Ishizuka Tomomichi Nishino Hiroyuki Ito Risehiro Nonaka Motoyoshi Noike Takeshi Kodama Hajime Nozaka Tsuneyuki Sato Hitoshi Agematsu Koichi Maruyama Shun Oyamada Takashi Kuroishi Kazuma Sasaki Kei Yagawa Mami Yoshioka Yasuo Yokoyama Faculty of Education Kyoto University of Education Kyoto Japan Department of Chemical and Biological Engineering National Institute of Technology Akita College Akita Japan Environment Systems Engineering Course National Institute of Technology Akita College Akita Japan Department of Applied Chemistry National Institute of Technology Akita College Akita Japan

Because imines could be used as convenient starting materials in various fields, the development of an easy synthetic method of imine was strongly desired. In response to this demand, we thought that it would be an effective synthesis method if an aldehyde and an amine could be reacted to give an imine in good yield under solvent- and catalyst-free conditions. In fact, we tried the reaction of benzaldehyde with various amines under solvent- and catalyst-free conditions followed by removal of water that was produced in the reaction system by a vacuum pump, and desired imines could be obtained in good yields. Observation of this reaction using a nuclear magnetic resonance spectrometer revealed that the reaction rate was extremely fast at the initial stage but slowed over time. However, the reaction of benzaldehyde with aniline differed greatly, and the reaction rate dramatically improved in 47 - 48 minutes after the start of the reaction. At this time, we found that the reaction system underwent a phase transition from the liquid phase to the solid phase.

关键词： Solvent-Free Catalyst-Free Pressure Reduction Technique Imine Reaction Rate Phase Transition

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Species differences in regulation of renal proximal tubule transport by certain molecules

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World Journal of Nephrology 2015年第2期4卷 307-312页

作者： George Seki Motonobu Nakamura Masashi suzuki Nobuhiko Satoh shoko Horita Department of Internal Medicine Faculty of MedicineUniversity of Tokyo

Renal proximal tubules （PTs） play important roles in the regulation of acid/base, plasma volume and blood pressure. Recent studies suggest that there are substantial species differences in the regulation of PT transport. For example, thiazolidinediones （TZDs） are widely used for the treatment of type 2 diabetes mellitus, but the use of TZDs is associated with fluid overload. In addition to the transcriptional enhancement of sodium transport in distal nephrons, TZDs rapidly stimulate PT sodium transport via a non-genomic mechanism depending onperoxisome proliferator activated receptor g/Src/epidermal growth factor receptor （EGFR）/MEK/ERK. In mouse PTs, however, TZDs fail to stimulate PT transport probably due to constitutive activation of Src/EGFR/ERK pathway. This unique activation of Src/ERK may also affect the effect of high concentrations of insulin on mouse PT transport. On the other hand, the effect of angiotensin Ⅱ （Ang Ⅱ） on PT transport is known to be biphasic in rabbits, rats, and mice. However, Ang Ⅱ induces a concentration-dependent, monophasic transport stimulation in human PTs. The contrasting responses to nitric oxide/guanosine 3’,5’-cyclic monophosphate pathway may largely explain these different effects of Ang Ⅱ on PT transport. In this review, we focus on the recent fndings on the species differences in the regulation of PT transport, which may help understand the species-specific mechanisms underlying edema formation and/or hypertension occurrence.

关键词： Renal proximal tubule Thiazolidinediones Peroxisome proliferator activated receptor g Insulin Angiotensin Ⅱ Nitric oxide

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The Effects of Insulin Resistance and Inflammation on Renal Proximal Tubule Sodium Transport and Hypertension

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Open Journal of Endocrine and Metabolic Diseases 2013年第5期3卷 34-41页

作者： shoko Horita Motonobu Nakamura Masashi suzuki Hideomi Yamada George Seki Department of Internal Medicine The University of Tokyo Hospital Tokyo Japan

Insulin resistance, closely linked to inflammation, is recognized as a key factor in the onset and aggravation of diabetes, cardio-renal syndrome, hypertension, and obesity. In the renal proximal tubule, insulin resistance may increase renal sodium reabsorption, leading to hypertension, edema and sometimes heart failure. Recently some anti-diabetic agents have been shown to have effects on the transporters in renal proximal tubule. Because renal proximal tubule mediates about 70% of sodium reabsorption, it is quite important to clarify the function of renal proximal tubule under insulin resistance and inflammation.

关键词： Insulin Inflammation TNF-α Proximal Tubule Insulin Resistance PPARγ Thiazolidinediones

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Functional coupling of V-ATPase and CLC-5

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World Journal of Nephrology 2017年第1期6卷 14-20页

作者： Nobuhiko Satoh Masashi suzuki Motonobu Nakamura Atsushi suzuki shoko Horita George Seki Kyoji Moriya Department of Internal Medicine Faculty of Medicinethe University of Tokyo Hospital Department of Endocrinology and Nephrology Yaizu City Hospital Department of Infection Control and Prevention the University of Tokyo Hospital

Dent’s disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl-/H＋ antiporter chloride channel 5 （CLC-5）, which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H＋-ATPase （V-ATPase）. Initially identified as a member of the CLC family of Cl- channels, CLC-5 was presumed to provide Cl shunt into the endosomal lumen to dissipate H＋ accumulation by V-ATPase, thereby facilitating efficient endosomal acidification. However, recent findings showing that CLC-5 is in fact not a Cl- channel but a 2Cl-/H＋ antiporter challenged this classical shunt model, leading to a renewed and intense debate on its physiological roles. Cl- accumulation via CLC-5 is predicted to play a critical role in endocytosis, as illustrated in mice carrying an artifcial Cl- channel mutation E211A that developed defective endocytosis but normal endo-somal acidification. Conversely, a recent functional analysis of a newly identifed disease-causing Cl- channel mutation E211Q in a patient with typical Dent’s disease confrmed the functional coupling between V-ATPase and CLC-5 in endosomal acidifcation, lending support to the classical shunt model. In this editorial, we will address the current recognition of the physiological role of CLC-5 with a specific focus on the functional coupling of V-ATPase and CLC-5.

关键词： V-ATPase CLC-5 Endocytosis Endosomal acidifcation Dent’s disease Gating glutamate E211Q

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The acid-base regulation by renal proximal tubule

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Open Journal of Molecular and Integrative Physiology 2013年第4期3卷 186-193页

作者： shoko Horita Osamu Yamazaki Motonobu Nakamura Hideomi Yamada Masashi suzuki George Seki Department of Internal Medicine The University of Tokyo Hospital Tokyo Japan

The kidney plays quite an important role in the regulation of acid-base homeostasis. The dysfunction of renal acid-base regulation causes diseases such as developmental disorder, bone malformation, calcification of eye and brain, etc. In the kidney, this regulation is performed, to a considerable part, in the proximal tubule of the nephron. In the luminal side the key player is sodium-proton exchanger type 3 (NHE3), whereas sodium-bicarbonate cotransporter (NBCe1) plays the critical role in the basolateral side. In the cytoplasm there is carbonic anhydrase type 2 (CAII) that intermediates the conversion of CO2/ . Interestingly, in human, mutations have been found in NBCe1 and CAII but not in NHE3 so far. Mutations of NBCe1 lead to severe proximal renal tubular acidosis (pRTA) and other systemic manifestations. In animal model studies, however, the relative contribution of NHE3 to proximal tubule functions remains controversial. Recently, V-ATPase with renal specific subunits is suggested to have some roles in the regulation of proximal tubule functions. In this review, we will discuss the regulation of acid-base transport in the proximal tubule and the updates.

关键词： PRTA NHE NBCe1 V-ATPase

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Bacteremia in hemodialysis patients

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World Journal of Nephrology 2016年第6期5卷 489-496页

作者： Masashi suzuki Nobuhiko Satoh Motonobu Nakamura shoko Horita George Seki Kyoji Moriya Department of Internal Medicine the University of Tokyo HospitalBunkyo-kuTokyo 113-0033Japan Department of Infection Control and Prevention the University of Tokyo HospitalBunkyo-kuTokyo 113-0033Japan Yaizu City Hospital YaizuShizuoka 425-8505Japan

Infection is a common complication and is the second leading cause of death in hemodialysis patients. The risk of bacteremia in hemodialysis patients is 26-fold higher than in the general population, and 1/2-3/4 of the causative organisms of bacteremia in hemodialysis patients are Gram-positive bacteria. The ratio of resistant bacteria in hemodialysis patients compared to the general population is unclear. Several reports have indicated that hemodialysis patients have a higher risk of methicillin-resistant Staphylococcus aureus infection. The most common site of infection causing bacteremia is internal prostheses; the use of a hemodialysis catheter is the most important risk factor for bacteremia. Although antibiotic lock of hemodialysis catheters and topical antibiotic ointment can reduce catheter-related blood stream infection(CRBSI), their use should be limited to necessary cases because of the emergence of resistant organisms. Systemic antibiotic administration and catheter removal is recommended for treating CRBSI, although a study indicated the advantages of antibiotic lock and guidewire exchange of catheters over systemic antibiotic therapy. An infection control bundle recommended by the Center for Disease Control and Prevention succeeded in reducing bacteremia in hemodialysis patients with either a catheter or arteriovenous fistula. Appropriate infection control can reduce bacteremia in hemodialysis patients.

关键词： Bacteremia Hemodialysis Blood stream infection Epidemiology Infection control

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Sitagliptin improves vascular endothelial function in Japanese type 2 diabetes patients without cardiovascular disease

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Journal of Diabetes Mellitus 2012年第3期2卷 338-345页

作者： Kazunari suzuki Kentaro Watanabe Tatsuya suzuki Motoshi Ouchi shoko Futami-Suda Yoshimasa Igari Hiroshi Nakano Kenzo Oba Department of Internal Medicine (Divisions of Cardiology Hepatology Geriatrics and Integrated Medicine) Nippon Medical School Tokyo Japan

We evaluated the effect of sitagliptin on vascular endothelial function in Japanese type 2 diabetes patients without cardiovascular disease. Subjects included 24 Japanese type 2 diabetes patients without cardiovascular disease. This study was a prospective, open-label, randomized clinical trial. We divided the study subjects into 2 groups: subjects who received sitagliptin 50 mg daily (sitagliptin group, n = 12) and subjects who did not receive sitagliptin (control group, n = 12). Brachial artery flow-mediated dilation (FMD) was measured after overnight fasting. Sitagliptin administration was initiated at 1 month after enrollment in study (baseline). FMD and level of biochemical variables in the sitagliptin and control groups were measured at baseline and 3 months from baseline (3 months). We evaluated the effect of sitagliptin on vascular endothelial function by measuring FMD. FMD at 3 months was significantly higher in the sitagliptin group than in the control group (5.36% ± 2.18% vs 3.41% ± 2.29%, P = 0.040), while FMD at baseline was not significantly different between the 2 groups. In addition, FMD of the sitagliptin group at 3 months was significantly higher than that at baseline (5.36% ± 2.18% vs 3.67% ± 2.30%, P = 0.004), while no significant differences were observed in the FMD of the control group during the study period. The change in the adiponectin from baseline to 3 months was significantly higher in the sitagliptin group than that in the control group (0.82 ± 2.18 μg/mL vs 0.01 ± 0.55 μg/mL, P = 0.039). Sitagliptin improves vascular endothelial function of the brachial artery in Japanese type 2 diabetes patients without cardiovascular disease. Furthermore, elevation of adiponectin may induce reduction of endothelial dysfunction in type 2 diabetes patients treated with sitagliptin.

关键词： Sitagliptin Endothelial Function Flow-Mediated Dilation Type 2 Diabetes Mellitus Adiponectin

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