MDPI Acta Medica Okayama 2079-9721 12 11 2024 The Change in Public Perception and Knowledge Acquisition Methods of Chronic Kidney Disease Among General Population in Okayama Prefecture, Japan 268 EN Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hitoshi Sugiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Okayama University Naoki Kashihara Kawasaki Geriatric Medical Center Hirofumi Makino Okayama University Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences CKD public education plays a very important role in effective chronic kidney disease (CKD) countermeasure. We have been conducting CKD public education programs in Okayama Prefecture since 2007. Here, we aimed to examine the actual status of CKD perceptance and changes in CKD perceptance due to these education programs. The study was conducted on individuals who underwent health checkups at 12 medical institutions across five medical regions in Okayama Prefecture between 1 October and 30 November in 2015, 2019, and 2023. The results showed that overall CKD perceptance has improved over time (perceptance of "CKD" 4% to 7%, "chronic kidney disease" 27% to 34%, 2015 vs. 2023). "Chronic kidney disease" was more commonly recognized than "CKD", and the elderly were more aware of the disease than younger people. The CKD perceptance improved across all age groups. However, the rate of CKD perceptance is still low, especially among young people. Previously, newspapers were the second most common resource of information about CKD after television. However, the Internet has recently replaced newspapers as the second most common source of information, especially among younger people. Understanding of the exact diagnosis of CKD also remains insufficient. It is necessary to continue more effective CKD public education programs through more intelligible terminology and information sources that match the demographics of target population. No potential conflict of interest relevant to this article was reported.

Elsevier BV Acta Medica Okayama 0085-2538 106 5 2024 A randomized, open-label, clinical trial examined the effects of canagliflozin on albuminuria and eGFR decline using an individual pre-intervention eGFR slope 972 984 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J.L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Kota Sakamoto Center for Innovative Clinical Medicine, Okayama University Hospital Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Hiromi Kuramoto Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Demonstrating drug efficacy in slowing kidney disease progression requires large clinical trials when targeting participants with an early stage of chronic kidney disease (CKD). In this randomized, parallel-group, open-labeled trial (CANPIONE study), we assessed the effect of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin using the individual’s change in estimated glomerular filtration rate (eGFR) slope before (pre-intervention slope) and during treatment (chronic slope). We randomly assigned (1:1) participants with type 2 diabetes, urinary albumin-to-creatinine ratio (UACR) of 50 to under 300 mg/g, and an eGFR of at least 45 ml/min/1.73m2 to receive canagliflozin or guideline-recommended treatment except for SGLT2 inhibitors (control). The first and second primary outcomes were the geometric mean percentage change from baseline in UACR and the change in eGFR slope, respectively. Of 98 randomized participants, 96 received at least one study treatment. The least-squares mean change from baseline in log-transformed geometric mean UACR was significantly greater in the canagliflozin group than the control group (between group-difference, −30.8% (95% confidence interval −42.6 to −16.8). The between-group difference (canagliflozin group – control group) of change in eGFR slope (chronic – pre-intervention) was 4.4 (1.6 to 7.3) ml/min/1.73 m2 per year, which was more pronounced in participants with faster eGFR decline. In summary, canagliflozin reduced albuminuria and the participant-specific natural course of eGFR decline in participants with type 2 diabetes and microalbuminuria. Thus, the CANPIONE study suggests that the within-individual change in eGFR slope may be a novel approach to determine the kidney protective potential of new therapies in early stages of CKD. No potential conflict of interest relevant to this article was reported.

BMJ Publishing Group Acta Medica Okayama 2052-4897 12 3 2024 Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3) e004237 EN Asami Ueno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Yasuhiro Onishi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Koki Mise Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Yamaguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ayaka Kanno Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Ichiro Nojima Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Chigusa Higuchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Haruhito A. Uchida Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kenichi Shikata Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Satoshi Miyamoto Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Jun Eguchi Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Akihiro Katayama Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Mayu Watanabe Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Tatsuaki Nakato Department of Internal Medicine, Okayama Saiseikai General Hospital Atsuhito Tone Department of Internal Medicine, Okayama Saiseikai General Hospital Sanae Teshigawara Okayama Saiseikai General Hospital Takashi Matsuoka Department of Diabetic Medicine, Kurashiki Central Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Kazutoshi Murakami Department of Diabetic Medicine, Kurashiki Central Hospital Ikki Shimizu Sakakibara Heart Institute of Okayama Katsuhito Miyashita Japanese Red Cross Okayama Hospital Shinichiro Ando Okayama City General Medical Center Tomokazu Nunoue Nunoue Clinic Jun Wada Okayama University Graduate School of Medicine Dentistry and Pharmaceutical Sciences Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 136 1 2024 第38回日本糖尿病合併症学会開催報告 39 40 EN Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital No potential conflict of interest relevant to this article was reported.

Informa UK Limited Acta Medica Okayama 0163-5581 76 6 2024 Perioperative and Postoperative Continuous Nutritional Counseling Improves Quality of Life of Gastric Cancer Patient Undergoing Gastrectomy 476 485 EN Shunya Hanzawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoru Kikuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shinji Kuroda Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ryohei Shoji Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Hajime Kashima Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yuki Matsumi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Ayako Takahashi Clinical Nutrition, Okayama University Hospital Yoshihiko Kakiuchi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kosei Takagi Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Tanabe Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuhiro Noma Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shunsuke Kagawa Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Clinical Nutrition, Okayama University Hospital Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Post-gastrectomy syndrome (PGS) and body weight loss (BWL) decrease quality of life (QOL) and survival of the patient undergoing gastrectomy. We have introduced perioperative and post-discharge continuous nutritional counseling (CNC) to prevent BWL and improve QOL after gastrectomy. In the present study, we evaluated the effect of CNC on QOL using the Post-gastrectomy Syndrome Assessment Scale-45 (PGSAS-45). Eighty-three patients with gastric cancer (GC) who underwent curative gastrectomy between March 2018 and July 2019 were retrospectively analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 45) or CNC (CNC group, n = 38) after gastrectomy. QOL at 12 months after gastrectomy was compared between the two groups. In QOL assessment, change in body weight (−7.98% vs. −12.77%, p = 0.0057), ingested amount of food per meal (7.00 vs. 6.07, p = 0.042) and ability for working (1.89 vs. 2.36, p = 0.049) were significantly better in CNC group than control group. Multiple regression analysis showed that CNC was a significantly beneficial factor for abdominal pain subscale (p = 0.028), diarrhea subscale (p = 0.047), ingested amount of food per meal (p = 0.012), Ability for working (p = 0.031) and dissatisfaction at the meal (p = 0.047). Perioperative and postoperative CNC could improve QOL in the patient undergoing gastrectomy in addition to preventing postoperative BWL. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 13 7 2022 Reduction in the magnitude of serum potassium elevation in combination therapy with esaxerenone (CS‐3150) and sodium–glucose cotransporter 2 inhibitor in patients with diabetic kidney disease: Subanalysis of two phase III studies 1190 1202 EN Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Sadayoshi Ito Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, Tohoku University School of Medicine Naoki Kashihara Department of Nephrology and Hypertension, Kawasaki Medical School Masaomi Nangaku Division of Nephrology and Endocrinology, Graduate School of Medicine, The University of Tokyo Takashi Wada Department of Nephrology and Laboratory Medicine, Kanazawa University Yasuyuki Okuda Department of Nephrology and Laboratory Medicine, Kanazawa University Tomoko Sawanobori Clinical Development Department, Daiichi Sankyo Co., Ltd. Kotaro Sugimoto Primary Medical Science Department, Daiichi Sankyo Co., Ltd. Aims/Introduction: We evaluated the effect of co-administration of esaxerenone and a sodium–glucose cotransporter 2 (SGLT2) inhibitor on the magnitude of serum potassium elevation in Japanese patients with diabetic kidney disease. Materials and Methods: We carried out a prespecified subanalysis of data from two phase III studies: a multicenter, randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes and microalbuminuria (J308); and a multicenter, single-arm, open-label trial in patients with type 2 diabetes and macroalbuminuria (J309). Changes in serum potassium levels during the studies and other measures were evaluated according to SGLT2 inhibitor use. Results: In both studies, time-course changes in serum potassium levels, and incidence rates of serum potassium elevation were lower in patients with co-administration of SGLT2 inhibitor in both the placebo and esaxerenone groups than those without the inhibitor. In contrast, time-course changes and mean percentage changes from baseline in urinary albumin-to-creatinine ratio, the proportion of patients with albuminuria remission and time-course changes in blood pressure did not change with or without SGLT2 inhibitor, whereas the albumin-to-creatinine ratio and blood pressure were reduced with esaxerenone. The blood glucose-lowering effect of SGLT2 inhibitor was not affected by esaxerenone. Conclusions: In Japanese patients with type 2 diabetes and albuminuria treated with esaxerenone, concomitant use of SGLT2 inhibitor reduced the magnitude of serum potassium elevation without any change of its antihypertensive and albuminuria-suppressing effects. Co-administration of esaxerenone and SGLT2 inhibitor might be a beneficial treatment option for patients with diabetic kidney disease. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 1462-8902 24 8 2022 Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study 1429 1438 EN Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hiddo J. L. Heerspink Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Dick de Zeeuw Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen Masao Toyoda Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine Daisuke Suzuki Suzuki Diadetes Clinic Takashi Hatanaka Department of Diabetes and Endocrinology, National Hospital Organization Fukuyama Medical Center Tohru Nakamura Diabetes Internal Medicine, Sumitomo Besshi Hospital Shinji Kamei Department of Diabetic Medicine, Kurashiki Central Hospital Satoshi Murao Department of Diabetes and Endocrinology, Takamatsu Hospital Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Shinichiro Ando Department of Internal Medicine Diabetic Center, Okayama City Hospital Hiroaki Akai Division of Diabetes and Metabolism, Faculty of Medicine, Tohoku Medical and Pharmaceutical University Yasushi Takahashi Department of Diabetes, Ochiai General Hospital Daisuke Koya Department of Diabetology and Endocrinology, Kanazawa Medical University Munehiro Kitada Department of Diabetology and Endocrinology, Kanazawa Medical University Hisashi Sugano Department of Diabetes and Endocrinology, Kochi Health Sciences Center Tomokazu Nunoue Nunoue Clinic Akihiko Nakamura Internal Medicine, Osafune Clinic, Setouchi Motofumi Sasaki Department of Diabetes and Endocrinology, Matsue City Hospital Tatsuaki Nakatou Diabetes Center, Okayama Saiseikai General Hospital Kei Fujimoto Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, The Jikei University Kashiwa Hospital Daiji Kawanami Department of Endocrinology and Diabetes Mellitus, Fukuoka University School of Medicine Takashi Wada Department of Nephrology and Laboratory Medicine, Graduate School of Medical Sciences, Kanazawa University Nobuyuki Miyatake Department of Hygiene, Faculty of Medicine, Kagawa University Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital the CANPIONE study Investigators Aim: To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria. Methods: The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope. Results: A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g. Conclusions: The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 14 2 2022 Suramin prevents the development of diabetic kidney disease by inhibiting NLRP3 inflammasome activation in KK-Ay mice 205 220 EN Kaori Oda Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Kodera Osafune Clinic Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Aims/Introduction Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasomes produce IL-18 upon being activated by various stimuli via the P2 receptors. Previously, we showed that serum and urine IL-18 levels are positively associated with albuminuria in patients with type 2 diabetes, indicating the involvement of inflammasome activation in the pathogenesis of diabetic kidney disease (DKD). In the present study, we investigated whether the administration of suramin, a nonselective antagonist of the P2 receptors, protects diabetic KK.Cg-A(y)/TaJcl (KK-Ay) mice against DKD progression. Materials and Methods Suramin or saline was administered i.p. to KK-Ay and C57BL/6J mice once every 2 weeks for a period of 8 weeks. Mouse mesangial cells (MMCs) were stimulated with ATP in the presence or absence of suramin. Results Suramin treatment significantly suppressed the increase in the urinary albumin-to-creatinine ratio, glomerular hypertrophy, mesangial matrix expansion, and glomerular fibrosis in KK-Ay mice. Suramin also suppressed the upregulation of NLRP3 inflammasome-related genes and proteins in the renal cortex of KK-Ay mice. P2X4 and P2X7 receptors were significantly upregulated in the isolated glomeruli of KK-Ay mice and mainly distributed in the glomerular mesangial cells of KK-Ay mice. Although neither ATP nor suramin affected NLRP3 expression in MMCs, suramin inhibited ATP-induced NLRP3 complex formation and the downstream expression of caspase-1 and IL-18 in MMCs. Conclusions These results suggest that the NLRP3 inflammasome is activated in a diabetic kidney and that inhibition of the NLRP3 inflammasome with suramin protects against the progression of early stage DKD. No potential conflict of interest relevant to this article was reported.

Springer Science and Business Media LLC Acta Medica Okayama 1068-9265 30 2 2022 Effect of Patient-Participation Continuous Nutritional Counseling in Gastric Cancer Patients who Underwent Gastrectomy 1110 1118 EN Nobuo Takata Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Satoru Kikuchi Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shinji Kuroda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Shunsuke Tanabe Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Naoaki Maeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kazuhiro Noma Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Ayako Takahashi Department of Clinical Nutrition, Okayama University Hospital Yuzo Umeda Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Kenichi Shikata Department of Clinical Nutrition, Okayama University Hospital, Okayama, Japan Center for Innovative Clinical Medicine, Okayama University Hospital Kazuhide Ozaki Department of Gastroenterological Surgery, Kochi Health Sciences Center Toshiyoshi Fujiwara Department of Gastroenterological Surgery, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine Background. Body weight loss (BWL) and skeletal muscle loss (SML) are inevitable after gastrectomy for gastric cancer (GC) and can decrease patients’ quality of life (QOL) and survival. Objective. The aim of this retrospective study was to evaluate the effect of perioperative and post-discharge patient participation in continuous nutritional counseling (CNC) on post-gastrectomy BWL and SML. Methods. Ninety-three patients with GC who underwent curative gastrectomy between March 2018 and July 2019 were analyzed. Patients received either pre-discharge nutritional counseling alone (control group, n = 49) or patient-participation CNC (CNC group, n = 44) after gastrectomy. Differences between percentage BWL (%BWL), percentage SML (%SML), and nutrition-related blood parameters between the preoperative values and those at 12 months after surgery were compared between the groups. Results. Compared with the control group, %BWL was significantly lower in the CNC group at 1 month (−6.2 ± 2.5% vs. −7.9 ± 3.3%, p = 0.005), 6 months (−7.8 ± 6.6% vs. −12.3 ± 6.4%, p = 0.001) and 12 months (−7.9 ± 7.6% vs. −13.2 ± 8.2%, p = 0.002), and %SML was significantly lower in the CNC group at 12 months (−5.3 ± 10.3% vs. −12.8 ± 12%, p = 0.002). Regarding nutrition-related blood parameters, change in total cholesterol was significantly lower in the CNC group than the control group at 12 months after surgery (p = 0.02). Multivariate analysis identified no CNC as an independent risk factor for severe BWL (p = 0.001) and SML (p = 0.006) at 12 months after surgery. Conclusions. Following gastrectomy, patient-participation CNC prevented postoperative BWL and SML after surgery. These results support the induction of such a CNC program in these patients. No potential conflict of interest relevant to this article was reported.

MDPI Acta Medica Okayama 2218-273X 12 8 2022 Edaravone Attenuated Angiotensin II-Induced Atherosclerosis and Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice 1117 EN Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Tetsuharu Takatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Venkateswaran Subramanian Saha Cardiovascular Research Center, University of Kentucky Alan Daugherty Saha Cardiovascular Research Center, University of Kentucky Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Faculty of Medicine, Dentistry and Pharmaceutical Sciences Background: The aim of the study was to define whether edaravone, a free-radical scavenger, influenced angiotensin II (AngII)-induced atherosclerosis and abdominal aortic aneurysms (AAAs) formation. Methods: Male apolipoprotein E-deficient mice (8-12 weeks old) were fed with a normal diet for 5 weeks. Either edaravone (10 mg/kg/day) or vehicle was injected intraperitoneally for 5 weeks. After 1 week of injections, mice were infused subcutaneously with either AngII (1000 ng/kg/min, n = 16-17 per group) or saline (n = 5 per group) by osmotic minipumps for 4 weeks. Results: AngII increased systolic blood pressure equivalently in mice administered with either edaravone or saline. Edaravone had no effect on plasma total cholesterol concentrations and body weights. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas and en face atherosclerosis but was significantly attenuated by edaravone administration. Edaravone also reduced the incidence of AngII-induced AAAs. In addition, edaravone diminished AngII-induced aortic MMP-2 activation. Quantitative RT-PCR revealed that edaravone ameliorated mRNA abundance of aortic MCP-1 and IL-1 beta. Immunostaining demonstrated that edaravone attenuated oxidative stress and macrophage accumulation in the aorta. Furthermore, edaravone administration suppressed thioglycolate-induced mice peritoneal macrophages (MPMs) accumulation and mRNA abundance of MCP-1 in MPMs in male apolipoprotein E-deficient mice. In vitro, edaravone reduced LPS-induced mRNA abundance of MCP-1 in MPMs. Conclusions: Edaravone attenuated AngII-induced AAAs and atherosclerosis in male apolipoprotein E-deficient mice via anti-oxidative action and anti-inflammatory effect. No potential conflict of interest relevant to this article was reported.

Hindawi Ltd. Acta Medica Okayama 2314-6745 2022 2022 The Association of Postprandial Triglyceride Variability with Renal Dysfunction and Microalbuminuria in Patients with Type 2 Diabetic Mellitus: A Retrospective and Observational Study 3157841 EN Natsumi Matsuoka-Uchiyama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Academic Field of Medicine, Dentistry and Pharmaceutical Sciences Shugo Okamoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Yasuhiro Onishi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Katsuyoshi Katayama Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Mariko Tsuchida-Nishiwaki Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Hidemi Takeuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Rika Takemoto Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Ryoko Umebayashi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Naoko Kurooka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Tsuji Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Hirofumi Nakajima Nakashima Hospital Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Academic Field of Medicine, Dentistry, and Pharmaceutical Sciences Objective. We examined whether or not day-to-day variations in lipid profiles, especially triglyceride (TG) variability, were associated with the exacerbation of diabetic kidney disease. Methods. We conducted a retrospective and observational study. First, 527 patients with type 2 diabetes mellitus (DM) who had had their estimated glomerular filtration rate (eGFR) checked every 6 months since 2012 for over 5 years were registered. Variability in postprandial TG was determined using the standard deviation (SD), SD adjusted (Adj-SD) for the number of measurements, and maximum minus minimum difference (MMD) during the first three years of follow-up. The endpoint was a & GE;40% decline from baseline in the eGFR, initiation of dialysis or death. Next, 181 patients who had no micro- or macroalbuminuria in February 2013 were selected from among the 527 patients for an analysis. The endpoint was the incidence of microalbuminuria, initiation of dialysis, or death. Results. Among the 527 participants, 110 reached a & GE;40% decline from baseline in the eGFR or death. The renal survival was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0073, 0.0059, and 0.0195, respectively). A lower SD, lower Adj-SD, and lower MMD were significantly associated with the renal survival in the adjusted model (hazard ratio, 1.62, 1.66, 1.59; 95% confidence intervals, 1.05-2.53, 1.08-2.58, 1.04-2.47, respectively). Next, among 181 participants, 108 developed microalbuminuria or death. The nonincidence of microalbuminuria was lower in the higher-SD, higher-Adj-SD, and higher-MMD groups than in the lower-SD, lower-Adj-SD, and lower-MMD groups, respectively (log-rank test p=0.0241, 0.0352, and 0.0474, respectively). Conclusions. Postprandial TG variability is a novel risk factor for eGFR decline and the incidence of microalbuminuria in patients with type 2 DM. No potential conflict of interest relevant to this article was reported.

ELSEVIER Acta Medica Okayama 0022-2275 48 4 2007 The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis 768 781 EN Masako Tabuchi Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Katsumi Inoue Department of Pathology, Kokura Memorial Hospital Hitomi Usui-Kataoka Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kazuko Kobayashi Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Misako Teramoto Department of Pathology, Kokura Memorial Hospital Koji Takasugi Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenichi Shikata Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Masahiro Yamamura Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Ando Department of Cardiology, Kokura Memorial Hospital Keiichiro Nishida Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Junko Kasahara Department of Internal Medicine, Okayama Central Hospital Noriaki Kume Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Luis R. Lopez Corgenix, Inc. Kazuaki Mitsudo Department of Cardiovascular Medicine, Kurashiki Central Hospital Masakiyo Nobuyoshi Department of Cardiology, Kokura Memorial Hospital Tatsuji Yasuda Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Toru Kita Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine Hirofumi Makino Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Eiji Matsuura Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences C-reactive protein (CRP) is one of the strongest independent predictors of cardiovascular disease. We have previously reported that oxidized LDL (oxLDL) interacts with beta 2-glycoprotein I (beta 2GPI), implicating oxLDL/P2GPI complexes as putative autoantigens in autoimmune-mediated atherosclerotic vascular disease. In this study, we investigated the interaction of CRP with oxLDL/beta 2GPI complexes and its association with atherosclerosis in patients with diabetes mellitus (DM). CRP/oxLDL/R2GPI complexes were predominantly found in sera of DM patients with atherosclerosis. In contrast, noncomplexed CRP isoforms were present in sera of patients with acute/chronic inflammation, i.e., various pyrogenic diseases, rheumatoid arthritis (RA), and DM. Immunohistochemistry staining colocalized CRP and beta 2GPI together with oxLDL in carotid artery plaques but not in synovial tissue from RA patients, strongly suggesting that complex formation occurs during the development of adierosclerosis. Serum levels of CRP correlated with soluble forms of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and oxLDL/beta 2GPI complexes correlated with total cholesterol and hemoglobin Al c. Thus, the generation of CRP/oxLDL/beta 2GPI complexes seems to be associated with arterial inflammation, hyperglycemia, and hypercholesterolemia. CRP/oxLDL/R2GPI complexes can be distinguished from pyrogenic noncomplexed CRP isoforms and may represent a more specific and predictive marker for atherosclerosis. No potential conflict of interest relevant to this article was reported.

Frontiers Media SA Acta Medica Okayama 2297-055X 8 2021 Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2) 668059 EN Koki Mise Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mariko Imamura Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Satoshi Yamaguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Mayu Watanabe Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Chigusa Higuchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Akihiro Katayama Diabetes Center, Okayama University Hospital Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kazuyuki Hida Department of Diabetology and Metabolism, National Hospital Organization Okayama Medical Center Tatsuaki Nakato Okayama Saiseikai General Hospital Atsuhito Tone Okayama Saiseikai General Hospital Sanae Teshigawara Okayama Saiseikai General Hospital Takashi Matsuoka Kurashiki Central Hospital Shinji Kamei Kurashiki Central Hospital Kazutoshi Murakami Kurashiki Central Hospital Ikki Shimizu The Sakakibara Heart Institute of Okayama Katsuhiro Miyashita Japanese Red Cross Okayama Hospital Shinichiro Ando Okayama City General Medical Center Tomokazu Nunoue Nunoue Clinic Michihiro Yoshida Center for Innovative Clinical Medicine, Okayama University Hospital Masao Yamada GlycoTechnica Ltd. Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 11 2 2020 Prevalence of albuminuria and renal dysfunction, and related clinical factors in Japanese patients with diabetes: The Japan Diabetes Complication and its Prevention prospective study 5 325 332 EN Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Ryo Kodera The Japan Diabetes Society Kazunori Utsunomiya The Japan Diabetes Society Daisuke Koya The Japan Diabetes Society Rimei Nishimura The Japan Diabetes Society Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Naoko Tajima The Japan Diabetes Society the JDCP study group Aims/Introduction To clarify the prevalence of albuminuria and renal dysfunction, and related factors in Japanese patients with diabetes, we analyzed the baseline data of the Japan Diabetes Complication and its Prevention prospective study. Materials and Methods We used the data of 355 patients with type 1 diabetes and 5,194 patients with type 2 diabetes to evaluate the prevalence of albuminuria and renal dysfunction, and related factors. A binomial logistic regression analysis was used to investigate independent contributing factors for estimated glomerular filtration rate <60 mL/min/1.73 m2 or albuminuria. Results The prevalence of microalbuminuria and macroalbuminuria was 15.2% (54/355) and 3.1% (11/355) in type 1 diabetes patients, and 25.0% (1,298/5,194) and 5.1% (265/5,194) in type 2 diabetes patients, respectively. The proportion of renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2) was 9.9% (35/355) in type 1 diabetes patients, and 15.3% (797/5,194) in type 2 diabetes patients. The proportion of patients with renal dysfunction with normoalbuminuria was 7.3% (26/355) for type 1 diabetes patients, and 9.0% (467/5,194) for type 2 diabetes patients. The factors related to albuminuria in type 2 diabetes patients were glycated hemoglobin, hypertension, age, duration of diabetes, body mass index and estimated glomerular filtration rate. In contrast, factors to related renal dysfunction were age, duration of diabetes, dyslipidemia, hypertension, body mass index, male sex and albuminuria. Conclusions We showed the recent prevalence of albuminuria and renal dysfunction, and related factors in Japanese type 1 and type 2 diabetes patients using the baseline data of the Japan Diabetes Complication and its Prevention prospective study. The current results suggest that renal disease in patients with type 2 diabetes is heterogeneous, and different mechanisms might be involved in albuminuria and deterioration of renal function. No potential conflict of interest relevant to this article was reported.

Nature Research Acta Medica Okayama 2045-2322 10 1 2020 Dysfunction of CD8+PD-1+T cells in type 2 diabetes caused by the impairment of metabolism-immune axis 14928 EN Ichiro Nojima Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Shingo Eikawa Department of Hematology/Oncology, Hess Cancer Institute, Icahn School of Medicine At Mount Sinai Nahoko Tomonobu Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Yoshiko Hada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Nobuo Kajitani Department of Internal Medicine, Diabetes Center, Okayama City Hospital Sanae Teshigawara Diabetes Center, Okayama S Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Atsuhito Tone Diabetes Center, Okayama Saiseikai General Hospital Haruhito A. Uchida Department of Chronic Kidney Disease and Cardiovascular Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Heiichiro Udono Department of Immunology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Jun Wada Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences The metabolic changes and dysfunction in CD8+T cells may be involved in tumor progression and susceptibility to virus infection in type 2 diabetes (T2D). In C57BL/6JJcl mice fed with high fat-high sucrose chow (HFS), multifunctionality of CD8+splenic and tumor-infiltrating lymphocytes (TILs) was impaired and associated with enhanced tumor growth, which were inhibited by metformin. In CD8+splenic T cells from the HFS mice, glycolysis/basal respiration ratio was significantly reduced and reversed by metformin. In the patients with T2D (DM), multifunctionality of circulating CD8+PD-1+T cells stimulated with PMA/ionomycin as well as with HLA-A*24:02 CMV peptide was dampened, while metformin recovered multifunctionality. Both glycolysis and basal respiration were reduced in DM, and glycolysis was increased by metformin. The disturbance of the link between metabolism and immune function in CD8+PD-1+T cells in T2D was proved by recovery of antigen-specific and non-specific cytokine production via metformin-mediated increase in glycolytic activity. No potential conflict of interest relevant to this article was reported.

Wiley Acta Medica Okayama 2040-1116 12 2 2020 Randomized trial of an intensified, multifactorial intervention in patients with advanced‐stage diabetic kidney disease: Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) 207 216 EN Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Masakazu Haneda Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University Toshiharu Ninomiya Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University Daisuke Koya Department of Diabetology & Endocrinology, Kanazawa Medical University Yoshiki Suzuki Health Administration Center, Niigata University Daisuke Suzuki Suzuki Diabetes Clinic Hitoshi Ishida Research Center for Health Care, Nagahama City Hospital Hiroaki Akai Division of Metabolism and Diabetes, Tohoku Medical and Pharmaceutical University Yasuhiko Tomino Division of Nephrology, Department of Internal Medicine, Juntendo University Faculty of Medicine Takashi Uzu Division of Nephrology, Department of Medicine, Nippon Life Hospital Motonobu Nishimura Department of Diabetes and Endocrinology, National Hospital Organization Chiba‐East National Hospital Shiro Maeda Department of Advanced Genomic and Laboratory Medicine, Graduate School of Medicine, University of the Ryukyus Daisuke Ogawa Okayama Diabetes and Neurology Clinic Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Hirofumi Makino Okayama University the Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) collaborative group Aims/Introduction We evaluated the efficacy of multifactorial intensive treatment (IT) on renal outcomes in patients with type 2 diabetes and advanced‐stage diabetic kidney disease (DKD). Materials and Methods The Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT‐Japan) is a multicenter, open‐label, randomized controlled trial with a 5‐year follow‐up period. We randomly assigned 164 patients with advanced‐stage diabetic kidney disease (urinary albumin‐to‐creatinine ratio ≥300 mg/g creatinine, serum creatinine level 1.2–2.5 mg/dL in men and 1.0–2.5 mg/dL in women) to receive either IT or conventional treatment. The primary composite outcome was end‐stage kidney failure, doubling of serum creatinine or death from any cause, which was assessed in the intention‐to‐treat population. Results The IT tended to reduce the risk of primary end‐points as compared with conventional treatment, but the difference between treatment groups did not reach the statistically significant level (hazard ratio 0.69, 95% confidence interval 0.43–1.11; P = 0.13). Meanwhile, the decrease in serum low‐density lipoprotein cholesterol level and the use of statin were significantly associated with the decrease in primary outcome (hazard ratio 1.14; 95% confidence interval 1.05–1.23, P < 0.001 and hazard ratio 0.53, 95% confidence interval 0.28–0.998, P < 0.05, respectively). The incidence of adverse events was not different between treatment groups. Conclusions The risk of kidney events tended to decrease by IT, although it was not statistically significant. Lipid control using statin was associated with a lower risk of adverse kidney events. Further follow‐up study might show the effect of IT in patients with advanced diabetic kidney disease. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 2190-1678 11 2 2019 The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study 97 104 EN Akihiro Katayama Diabetes Center, Okayama University Hospital Atsuhito Tone Diabetes Center, Okayama Saiseikai General Hospital Mayu Watanabe Department of Primary Care and Medical Education, Okayama University Sanae Teshigawara Diabetes Center, Okayama Saiseikai General Hospital Satoshi Miyamoto Center for Innovative Clinical Medicine, Okayama University Hospital Jun Eguchi Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Atsuko Nakatsuka Okayama Univ, Dept Med & Clin Sci, Grad Sch Med Dent & Pharmaceut Sci Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital Jun Wada Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Aims/introduction The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. Materials and methods We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. Results The area under the curve (AUC) of hypoglycemia of < 70 mg/dL was lowered from 0.42 ± 0.43 mg/dL day to 0.18 ± 0.18 mg/dL day (P = 0.012). Correspondingly, the duration of severe hypoglycemia (< 54 mg/dL) was reduced significantly from 15.3 ± 21.7 min/day to 4.8 ± 6.9 min/day (P = 0.019). The duration of hypoglycemia was reduced, but the reduction was not significant. Regarding the AUC for hyperglycemia > 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. Conclusions The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 128 2 2016 中央西日本臨床研究コンソーシアム 121 123 EN Kenichi Shikata Center for Innovative Clinical Medicine, Okayama University Hospital 10.18926/54461 No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 68 4 2014 Factors Associated with Remission and/or Regression of Microalbuminuria in Type 2 Diabetes Mellitus 235 241 EN Tetsuichiro Ono Kenichi Shikata Mikako Obika Nobuyuki Miyatake Ryo Kodera Daisyo Hirota Jun Wada Hitomi Kataoka Daisuke Ogawa Hirofumi Makino Original Article 10.18926/AMO/52789 The aim of this study was to clarify the factors associated with the remission and/or regression of microalbuminuria in Japanese patients with type 2 diabetes mellitus. We retrospectively analyzed the data of 130 patients with type 2 diabetes mellitus with microalbuminuria for 2-6 years (3.39±1.31 years). Remission was defined as improving from microalbuminuria to normoalbuminuria using the albumin/creatinine ratio (ACR), and regression of microalbuminuria was defined as a decrease in ACR of 50% or more from baseline. Progression of microalbuminuria was defined as progressing from microalbuminuria to overt proteinuria during the follow-up period. Among 130 patients with type 2 diabetes mellitus with microalbuminuria, 57 and 13 patients were defined as having remission and regression, respectively, while 26 patients progressed to overt proteinuria. Sex (female), higher HDL cholesterol and lower HbA1c were determinant factors associated with remission/regression of microalbuminuria by logistic regression analysis. Lower systolic blood pressure (SBP) was also correlated with remission/regression, but not at a significant level. These results suggest that proper control of blood glucose, BP and lipid profiles may be associated with remission and/or regression of type 2 diabetes mellitus with microalbuminuria in clinical practice. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 126 1 2014 糖尿病の腎臓においてcholecystokininはマクロファージに対する抗炎症作用を介した新規の保護効果を発揮する 1 6 EN Satoshi Miyamoto Kenichi Shikata Kyoko Miyasaka Shinichi Okada Motofumi Sasaki Ryo Kodera Daisho Hirota Nobuo Kajitani Tetsuharu Takatsuka Hitomi Kataoka Usui Shingo Nishishita Chikage Horiguchi Sato Akihiro Funakoshi Hisakazu Nishimori Haruhito Adam Uchida Daisuke Ogawa Hirofumi Makino No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 68 1 2014 Lifestyle Modification Is Associated with Improving Estimated Glomerular Filtration Rate (eGFR) and Proteinuria in Japanese with Proteinuria 43 46 EN Nobuyuki Miyatake Kenichi Shikata Hirofumi Makino Takeyuki Numata Short Communication 10.18926/AMO/52143 The link between lifestyle modification and changes in both proteinuria and estimated glomerular filtration rates (eGFRs) was evaluated in Japanese subjects with proteinuria who were not taking medications. We used data from 51 men (35.8±10.0 years) and 74 women (38.0±11.0 years) with proteinuria at baseline and a 1-year follow up. eGFR was defined by a new equation developed specifically for Japanese subjects. Subjects were given advice for dietary and lifestyle improvement at the initial appointment. At the 1-year follow up, eGFR was increased in both sexes, but not at significant levels. (men:p＝0.7709, women:p＝0.2180). Proteinuria was also improved in many subjects. A decrease in proteinuria may be associated with improving eGFR in Japanese. No potential conflict of interest relevant to this article was reported.

Springer Acta Medica Okayama 1342-1751 16 5 2012 Phenotypic change of macrophages in the progression of diabetic nephropathy; sialoadhesin-positive activated macrophages are increased in diabetic kidney 739 748 EN Ryo Nagase Nobuo Kajitani Kenichi Shikata Daisuke Ogawa Ryo Kodera Shinichi Okada Yuichi Kido Hirofumi Makino Inflammatory process is involved in pathogenesis of diabetic nephropathy, although the activation and phenotypic change of macrophages in diabetic kidney has remained unclear. Sialoadhesin is a macrophage adhesion molecule containing 17 extracellular immunoglobulin-like domains, and is an I-type lectin which binds to sialic acid ligands expressed on hematopoietic cells. The aim of this study is to clarify the activation and phenotypic change of macrophages in the progression of diabetic nephropathy. We examined the expression of surface markers for pan-macrophages, resident macrophages, sialoadhesin, major histocompatibility complex class II and alpha-smooth muscle actin in the glomeruli of diabetic rats using immunohistochemistry at 0, 1, 4, 12, and 24 weeks after induction of diabetes by streptozotocin. Expression of type IV collagen and the change of mesangial matrix area were also measured. The mechanism for up-regulated expression of sialoadhesin on macrophages was evaluated in vitro. The number of macrophages was increased in diabetic glomeruli at 1 month after induction of diabetes and the increased number was maintained until 6 months. On the other hand, sialoadhesin-positive macrophages were increased during the late stage of diabetes concomitantly with the increase of alpha-smooth muscle actin-positive mesangial cells, mesangial matrix area and type IV collagen. Gene expression of sialoadhesin was induced by stimulation with interleukin (IL)-1 beta and tumor necrosis factor-alpha but not with IL-4, transforming growth factor-beta and high glucose in cultured human macrophages. The present findings suggest that sialoadhesin-positive macrophages may contribute to the progression of diabetic nephropathy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 6 2011 Decreasing Abdominal Circumference Is Associated with Improving Estimated Glomerular Filtration Rate (eGFR) with Lifestyle Modification in Japanese Men: A Pilot Study 363 367 EN Nobuyuki Miyatake Kenichi Shikata Hirofumi Makino Takeyuki Numata Original Article 10.18926/AMO/47261 The link between changes in a subject's metabolic syndrome components and his estimated glomerular filtration rate (eGFR) was evaluated in healthy Japanese men. We used data from 120 Japanese men (45.5±8.4 years) with a 1-year follow up. eGFR was defined by a new equation developed for Japan. There were no significant differences in eGFR between men with and without metabolic syndrome components at baseline. Subjects were given advice for dietary and lifestyle improvement. At the 1-year follow up, almost all metabolic syndrome components were significantly improved. However, eGFR was significantly decreased. The changes in eGFR were weakly correlated with abdominal circumference (r＝－0.232, p＝0.0106). A decrease in abdominal circumference may be associated with improving eGFR in Japanese men. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 123 3 2011 生活習慣病治療のパラダイムシフト―慢性炎症を標的とした治療戦略― 197 206 EN Kenichi Shikata No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 4 2011 Involvement of MAPKs in ICAM-1 Expression in Glomerular Endothelial Cells in Diabetic Nephropathy 247 257 EN Naomi Watanabe Kenichi Shikata Yasushi Shikata Kei Sarai Kazuyoshi Omori Ryo Kodera Chikage Sato Jun Wada Hirofumi Makino Original Article 10.18926/AMO/46850 Inflammatory processes are involved in the pathogenesis of diabetic nephropathy. The aim of this study was to clarify the role of mitogen-activated protein kinase (MAPK) pathways for induction of intercellular adhesion molecule-1 (ICAM-1) expression in glomerular endothelial cells under diabetic conditions. We examined the expression of ICAM-1 in the kidneys of experimental diabetic rats. Human glomerular endothelial cells (GE cells) were exposed to normal glucose concentration, high glucose concentration (HG), or high mannitol concentration (HM), and then the expression of the ICAM-1 protein and the phosphorylation of the 3 subfamilies of mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. Next, to evaluate the involvement of MAPKs in HG- or HM-induced ICAM-1 expression, we preincubated GE cells with the inhibitors for ERK, p38 or JNK 1h prior to the application of glucose or mannitol. Expression of ICAM-1 was increased in the glomeruli of diabetic rats. Both HG and HM induced ICAM-1 expression and phosphorylation of ERK1/2, p38 and JNK in GE cells. Expression of ICAM-1 was significantly attenuated by inhibitors of ERK, p38 and JNK. We conclude that activation of ERK1/2, p38 and JNK cascades may be involved in ICAM-1 expression in glomerular endothelial cells under diabetic conditions. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 2 2011 Emphysematous Cystitis in a Patient with Type 2 Diabetes Mellitus 129 133 EN Noriko Toyota Daisuke Ogawa Keita Ishii Kyoji Hirata Jun Wada Kenichi Shikata Hirofumi Makino Case Report 10.18926/AMO/45272 A 62-year-old woman with a history of poorly controlled type 2 diabetes mellitus was admitted to our hospital with a 3-week history of mild fever, vomiting, and anorexia. Abdominal computed tomography (CT) showed bilateral hydronephrosis and gas accumulation in the urinary bladder wall and left ureter. Laboratory tests showed leukocytosis and elevated C-reactive protein level. Urine culture showed heavy growth of Escherichia coli. The final diagnosis was emphysematous cystitis. The patient was treated with systemic antibiotics and drainage using a urethral catheter. The clinical and radiographic findings resolved rapidly, and she was discharged from the hospital on day 28. Emphysematous cystitis is a relatively rare urinary tract infection associated with gas formation, and has the potential for a serious outcome if untreated. Early detection by imaging studies such as CT is important in providing prompt treatment and favorable clinical outcome. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 65 2 2011 The Macrophage Is a Key Factor in Renal Injuries Caused by Glomerular Hyperfiltration 81 89 EN Motofumi Sasaki Kenichi Shikata Shinichi Okada Satoshi Miyamoto Shingo Nishishita Hitomi Usui Kataoka Chikage Sato Jun Wada Daisuke Ogawa Hirofumi Makino Original Article 10.18926/AMO/45266 Glomerular hyperfiltration is a common pathway leading to glomerulosclerosis in various kinds of kidney diseases. The 5/6 renal ablation is an established experimental animal model for glomerular hyperfiltration. On the other hand, low-grade inflammation is also a common mechanism for the progression of kidney diseases including diabetic nephropathy and atherosclerosis. Here we analyzed the gene expression profile in the remnant kidney tissues of 5/6 nephrectomized mice using a DNA microarray system and compared it with that of sham-operated control mice. The 5/6 nephrectomized mice showed glomerular hypertrophy and an increase in the extracellular matrix in the glomeruli. DNA microarray analysis indicated the up-regulated expression of various kinds of genes related to the inflammatory process in remnant kidneys. We confirmed the up-regulated expression of platelet factor-4, and monocyte chemoattractant protein-1, 2, and 5 in remnant kidneys by RT-PCR. The current results suggest that the inflammatory process is involved in the progression of glomerulosclerosis and is a common pathway of the pathogenesis of kidney disease. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 64 5 2010 Decreasing Systolic Blood Pressure Is Associated with Improving Estimated Glomerular Filtration Rate (eGFR) with Lifestyle Modification in Japanese Healthy Women 339 343 EN Nobuyuki Miyatake Kenichi Shikata Hirofumi Makino Takeyuki Numata Short Communication 10.18926/AMO/40510 The link between changes in a subject's metabolic syndrome components and her estimated glomerular filtration rate (eGFR) was evaluated in healthy Japanese women. We used data for 53 Japanese women (46.0±10.9 years) with a 1-year follow up. eGFR was defined by a new equation developed for Japan. There were no significant relationships between eGFR and clinical parameters at baseline. Subjects were given advice for dietary and lifestyle improvement. At the 1-year follow up, eGFR was significantly increased. In addition, changes in eGFR were weakly correlated with systolic blood pressure(r＝－0.306, p＝0.0260). A decrease in systolic blood pressure may be associated with improving eGFR in Japanese women. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 64 3 2010 Relationship between Estimated Glomerular Filtration Rate (eGFR) and Metabolic Syndrome in Japanese 203 208 EN Nobuyuki Miyatake Kenichi Shikata Hirofumi Makino Takeyuki Numata Original Article 10.18926/AMO/40013 We investigated the link between renal function as evaluated by estimated glomerular filtration rate (eGFR) and metabolic syndrome in Japanese. A total of 11,711 Japanese subjects, aged 20-79 years, were recruited in a cross-sectional clinical investigation. From this group, we further investigated the data on 1,576 subjects. eGFR was calculated using serum creatinine (Cr), age and sex. The diagnosis of metabolic syndrome was based on the Japanese criteria. In the first analysis, 288 men (7.8%) and 498 women (6.2%) were diagnosed with reduced eGFR (<60ml/min). eGFR was not correlated with anthropometric, body composition parameters in either sex. In the second analysis, in subjects without medications, 132 men (20.8%) and 15 women (1.6%) were diagnosed with metabolic syndrome. eGFR was lower in men with abdominal obesity and in women with hypertension was than in those without. Among Japanese not taking medications, lower eGFR may be a characteristic of men with abdominal obesity and of women with hypertension. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 64 1 2010 Influencing Factors for Dietary Behaviors of Patients with Diabetic Nephropathy 39 47 EN Kazuko Sumiyoshi Chieko Kawata Kenichi Shikata Hirofumi Makino Original Article 10.18926/AMO/32856 The aim of this study was to clarify the factors influencing the dietary behavior of patients with diabetic nephropathy. One hundred twenty-two patients with type 2 diabetes were recruited from the outpatients of Okayama University Hospital in Okayama, Japan. We performed a cross-sectional study using a questionnaire including 206 items among 18 categories as follows:background factors, coping behavior (coping scale), degree of uncertainty in illness (uncertainty scale), and dietary behavior. The data were analyzed by correlation analysis, t-test, one-way analysis of variance, Pearson correlation analysis, and multiple regression analysis. We found that those patients with microalbuminuria alone tended to recognize more mild about their kidney status than those with macroalbuminuria and chronic renal failure. We also found that common factors influencing the dietary behavior of diabetic patients with and without nephropathy are as follows:1. coping with the problem (beta0.342, p0.01);2. anxiety about prognosis (beta0.344, p0.01);3. sex (beta0.234, p0.05);4. uncertainty regarding treatment (beta0.377, p0.01);5. negative coping (beta0.354, p0.01);and 6. employment status (beta0.367, p0.01). Coping and uncertainty in illness had a significant relation to positive support and lack of support. To maintain appropriate dietary behavior in diabetic patients, medical staff need to determine what the social supports are important for the patient, and also to ensure good communication among healthcare personnel as well as positive support for patients and families. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 46 6 1992 Mechanism of proteinuria in nephrotic syndrome. 483 487 EN Zensuke Ota Kenichi Shikata Kosuke Ota Article 10.18926/AMO/32632 We developed a "tissue negative staining method" to observe the molecular-level ultrastructure in situ in any portion of the ultrathin sections routinely prepared for electron microscopy. This method was used in electron microscopy of the glomerular basement membranes (GBM). The GBM in patients with nephrotic syndrome was discovered to possess a tunnel structure, designated as "nephrotic tunnel", with lumen large enough to allow free passage of protein molecules. This tunnel seemed to be involved in the etiology of nephrotic syndrome. This new method appears to be applicable to a variety of purposes in biological studies. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 47 4 1993 Ultrastructural changes of the glomerular basement membrane in diabetic nephropathy revealed by newly devised tissue negative staining method. 267 272 EN Kosuke Ota Zensuke Ota Kenichi Shikata Hirofumi Makino Article 10.18926/AMO/31556 In order to clarify the mechanism of proteinuria in diabetic nephropathy, ultrastructural changes of the glomerular basement membrane (GBM) in patients with diabetic nephropathy were examined by electron microscopy using our newly devised "tissue negative staining method". The normal human GBM showed a fine meshwork structure consisting of fibrils forming the small pores. The diameter of these pores was slightly smaller than that of human albumin molecules. The GBM in patients with diabetic nephropathy showed irregular thickening. At higher magnification, hitherto unknown cavities and tunnel structures, which were not seen in normal controls, were observed in the thickened GBM. In some portions, these cavities presented a honeycomb-like appearance. The diameters of the cavities and tunnels were far larger than the dimensions of albumin molecules. These enlarged structures are believed to allow serum protein molecules to pass through the GBM from the capillary lumen to the urinary space. These results suggest that the cause of massive proteinuria in diabetic nephropathy is the disruption of the size barrier of the GBM. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 48 3 1994 Changes in Plasma Concentrations of Vitronectin in Patients with Diabetic Nephropathy 137 142 EN Shigeru Morioka Hirofumi Makino Kenichi Shikata Zensuke Ota Article 10.18926/AMO/31126 To investigate the role of vitronectin in the progression of diabetic nephropathy, plasma concentrations of vitronectin were measured by enzyme-linked immunosorbent assay in patients with diabetes mellitus and compared with normal control subjects. In diabetic patients with normoalbuminuria and microalbuminuria, plasma concentrations of vitronectin were significantly higher than those of control subjects. Plasma concentrations of vitronectin in diabetic patients with chronic renal failure were significantly lower than those with normal renal function. There was a significant positive correlation between plasma concentration of vitronectin and blood platelet counts. In the early stage of diabetic nephropathy, vitronectin may be increased caused by synthesis from activated platelets. With progression of diabetic nephropathy, plasma vitronectin may be decreased because of accumulation in sclerotic glomeruli and arteriosclerotic lesions. In conclusion, the plasma concentration of vitronectin appears to be an important marker for the progression of diabetic nephropathy. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 43 6 1989 Human liver ferritin as a new tracer for studying glomerular permeability. 363 365 EN Zensuke Ota Isao Kumagai Kenichi Shikata Hirofumi Makino Article 10.18926/AMO/30866 Sprague-Dawley rats, 6 with aminonucleoside nephrosis and 6 controls, were intravenously injected with human liver ferritin isolated from post mortem liver, and their 24-h urine samples were examined for human ferritin by immunoradiometric assay. In rats with aminonucleoside nephrosis, the amount of excreted ferritin in urine was forty times greater than in control rats. Much more monomeric ferritin was excreted than that of polymeric ferritin. We are the first to have utilized human liver ferritin as a tracer to measure a minor amount of ferritin by a commercially available kit. Our present study seems to indicate a critical role for glomerular basement membrane as a size barrier. No potential conflict of interest relevant to this article was reported.

Okayama University Medical School Acta Medica Okayama 0386-300X 44 6 1990 Three-dimensional architecture of rat glomerular basement membrane by ultra-high resolution scanning electron microscopy. 333 335 EN Yasushi Yamasaki Hirofumi Makino Kazue Hironaka Yoshikazu Hayashi Kenichi Shikata Zensuke Ota Article 10.18926/AMO/30431 We demonstrated the ultrastructure of rat glomerular basement membrane (GBM) by ultra-high resolution scanning electron microscopy. GBM prepared by sonication methods and conductive-staining could be observed without metal coating at magnifications as high as 400,000 times. The GBM showed an irregular meshwork structure composed of various strands and pores. The width of the strands ranged from 6 to 15 nm, and the diameter of pores ranged from 6 to 50 nm. The present study confirmed our molecular sieve theory of the basement membrane. No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 117 1 2005 糖尿病性腎症の発症・進展における炎症機転の関与 9 15 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 118 3 2007 内臓脂肪組織に由来するセリンプロテアーゼ阻害剤：Vaspin の同定肥満状態でインスリン感受性を高める新規アディポサイトカイン 215 220 EN No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 120 2 2008 マクロファージスカベンジャー受容体（SR-A）は炎症を制御することにより糖尿病性腎症を抑制する 143 147 EN Hitomi Kataoka Kenichi Shikata Motofumi Sasaki Hirofumi Makino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 3 2008 糖尿病患者における血圧管理 311 313 EN Motofumi Sasaki Kenichi Shikata Hirofumi Makino No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 00301558 119 1 2007 糖尿病における血糖管理 75 77 EN Atsuhito Tone Kenichi Shikata Hirofumi Makino No potential conflict of interest relevant to this article was reported.

Acta Medica Okayama 1992 Ultrastructural　demonstration　of　field name="type"　Ⅳ　corlagen　meshwork　structure　of　the　glomerular　basement　membrance　　第1編　Hig　hresolution　three-dimensional　meshwork　structure　of　the　glomerular　basement　membrane　　第2編　Glomerular　basement　membrane　meshwork　structure　of　field name="type"　Ⅳ　collagen　after　SDS　and　mercaptoethanol　treatment EN No potential conflict of interest relevant to this article was reported.