鈴木 敦詞

Osteoporosis patients with chronic kidney disease (CKD) are becoming common in our superaging society. Renal dysfunction causes phosphorus accumulation in the circulating plasma and leads to the development of CKD-mineral bone disorder (MBD). We have previously reported that type III Pi transporter-overexpressing transgenic (Pit-1 TG) rats manifest phosphate (Pi)-dependent podocyte injury. In the present study, we explored the effect of risedronate on Pi-induced podocyte injury in vivo. Pit-1 TG rats and wild-type rats at 5 weeks old were divided into a risedronate-treated group and an untreated group. We subcutaneously administered 5 μg/kg body weight of risedronate or saline twice a week during the experimental period. Risedronate did not alter serum creatinine levels at 5, 8, and 12 weeks of age. However, electron microscopy images showed that thickening of the glomerular basement membrane was improved in the risedronate treatment group. Furthermore, immunostaining for podocyte injury markers revealed that both desmin- and connexin43-positive areas were smaller in the risedronate-treated group than in the untreated group, suggesting that bisphosphonates could rescue Pi-induced podocyte injury. In conclusion, our findings suggest that risedronate could maintain glomerular barrier function by rescuing Pi-induced podocyte injury.

Summary: The Fracture Liaison Service (FLS) Consensus Meeting endorsed by the International Osteoporosis Foundation (IOF), Asian Federation of Osteoporosis Societies (AFOS), and Asia Pacific Osteoporosis Foundation (APOF) was hosted by the Taiwanese Osteoporosis Association on October 14, 2017. International and domestic experts reviewed the 13 Best Practice Framework (BPF) standards and concluded that all standards were generally applicable in the Asia-Pacific region and needed only minor modifications to fit the healthcare settings in the region. Purpose: To review and generate consensus on best practices of fracture liaison service (FLS) in the Asia-Pacific (AP) region. Methods: In October 2017, the Taiwanese Osteoporosis Association (TOA) invited experts from the AP region (n = 23), the Capture the Fracture Steering Committee (n = 2), and the USA (n = 1) to join the AP region FLS Consensus Meeting in Taipei. After two rounds of consensus generation, the recommendations on the 13 Best Practice Framework (BPF) standards were reported and reviewed by the attendees. Experts unable to attend the on-site meeting reviewed the draft, made suggestions, and approved the final version. Results: Because the number of FLSs in the region is rapidly increasing, experts agreed that it was timely to establish consensus on benchmark quality standards for FLSs in the region. They also agreed that the 13 BPF standards and the 3 levels of standards were generally applicable, but that some clarifications were necessary. They suggested, for example, that patient and family education be incorporated into the current standards and that communication with the public to promote FLSs be increased. Conclusions: The consensus on the 13 BPF standards reviewed in this meeting was that they were generally applicable and required only a few advanced clarifications to increase the quality of FLSs in the region.

Purpose: This study aimed to evaluate the feasibility and safety of intracorporeal anastomosis with Billroth I, Billroth II, or Roux-en-Y reconstructions in totally laparoscopic distal gastrectomy. Materials and Methods: A single-institution, retrospective, cohort study including 553 patients was conducted. Intracorporeal isosceles right triangle-shaped anastomosis without slack and torsion was created using linear staplers. Billroth I was primarily used. Surgical outcomes and perioperative nutritional status were assessed. Results: Morbidity was 11.5%. Postoperative early complications related to anastomosis occurred in 13 patients (2.4%). Operative time and reconstruction type (Billroth I vs. others) were the only significant independent risk factors determining postoperative early and late complications, respectively. No difference was observed in postoperative changes in nutritional status across the groups, although Billroth II increased reflux esophagitis requiring medication. Conclusions: Intracorporeal isosceles right triangle-shaped anastomosis using linear staplers in totally laparoscopic distal gastrectomy, in combination with our selection algorithm for type of reconstruction, is feasible and safe.

This paper describes a technology for predicting the aggravation of diabetic nephropathy from electronic health record (EHR). For the prediction, we used features extracted from event sequence of lab tests in EHR with a stacked convolutional autoencoder which can extract both local and global temporal information. The extracted features can be interpreted as similarities to a small number of typical sequences of lab tests, that may help us to understand the disease courses and to provide detailed health guidance. In our experiments on real-world EHRs, we confirmed that our approach performed better than baseline methods and that the extracted features were promising for understanding the disease.

Additional risk stratification may provide more aggressive and focalized preventive treatment to high-risk hypertensive patients according to the Japanese hypertension guidelines. We prospectively investigated the predictive value of high-sensitivity troponin I (hsTnI), both independently and in combination with N-terminal pro-B-type natriuretic peptide (NT-proBNP), for incident heart failure (HF) in high-risk hypertensive patients with preserved left ventricular ejection fraction (LVEF). Baseline hsTnI and NT-proBNP levels and echocardiography data were obtained for 493 Japanese hypertensive outpatients (mean age, 68.5 years) with LVEF ae<yen> 50%, no symptomatic HF, and at least one of the following comorbidities: stage 3-4 chronic kidney disease, diabetes mellitus, and stable coronary artery disease. During a mean follow-up period of 86.1 months, 44 HF admissions occurred, including 31 for HF with preserved ejection fraction (HFpEF) and 13 for HF with reduced ejection fraction (HFrEF; LVEF < 50%). Both hsTnI (p < 0.01) and NT-proBNP (p < 0.005) levels were significant independent predictors of HF admission. Furthermore, when the patients were stratified into 4 groups according to increased hsTnI (ae<yen>highest tertile value of 10.6 pg/ml) and/or increased NT-proBNP (ae<yen>highest tertile value of 239.7 pg/ml), the adjusted relative risks for patients with increased levels of both biomarkers versus neither biomarker were 13.5 for HF admission (p < 0.0001), 9.45 for HFpEF (p = 0.0009), and 23.2 for HFrEF (p = 0.003). Finally, the combined use of hsTnI and NT-proBNP enhanced the C-index (p < 0.05), net reclassification improvement (p = 0.0001), and integrated discrimination improvement (p < 0.05) to a greater extent than that of any single biomarker. The combination of hsTnI and NT-proBNP, which are individually independently predictive of HF admission, could improve predictions of incident HF in high-risk hypertensive patients but could not predict future HF phenotypes.

Increased intracellular cyclic AMP (cAMP) in renal tubular epithelia accelerates the progression of polycystic kidney disease (PKD). Thus, decreasing cAMP levels by an adenylyl cyclase inhibitory G protein activator is considered to be an effective approach in ameliorating PKD. In fact, pasireotide (PAS) was effective in reducing disease progression in animal models of PKD. However, hyperglycemia caused by the administration of PAS is an adverse effect in its clinical use. Whereas, co-administration of octreotide (OCT) with PAS did not increase serum glucose in normal rats. In the current study, we examined the efficacy of combined treatment with OCT and PAS in PCK rats, an autosomal recessive PKD model. Four-week-old PCK males were treated with the long-acting release type of OCT, PAS, or a combination of both (OCT/PAS) for 12 weeks. After termination, serum and renal tissue were used for analyses. Kidney weight, kidney weight per body weight, renal cyst area, renal Ki67 expression, and serum urea nitrogen were significantly decreased either in the PAS or OCT/PAS group, compared with vehicle. Renal tissue cAMP content was significantly decreased by PAS or OCT/PAS treatment, but not OCT, compared with vehicle. As a marker of cellular mTOR signaling activity, renal phospho-S6 kinase expression was significantly decreased by OCT/PAS treatment compared with vehicle, OCT, or PAS. Serum glucose was significantly increased by PAS administration, whereas no difference was shown between vehicle and OCT/PAS, possibly because serum glucagon was decreased either by the treatment of OCT alone or co-application of OCT/PAS. In conclusion, since serum glucose levels are increased by the use of PAS, its combination with OCT may reduce the risk of hyperglycemia associated with PAS monotherapy against PKD progression.

<p>  A 34-year-old woman with type 1 diabetes on hemodialysis was admitted to our hospital for simultaneous pancreas kidney transplantation received from her father. She had suffered from type 1 diabetes mellitus since age 13, and had complained of serious atonic gastroenteropathy and orthostatic hypotension. After the transplantation, she became free from hemodialysis and insulin injection. At the same time, her gastrointestinal symptoms disappeared. However, she still had orthostatic hypotension, which was improved by taking fludrocortisone. Two months after the transplantation, orthostatic hypotension with marked polyuria became obvious. By hypertonic saline challenge test, she was diagnosed as partial central diabetes insipidus. Although treatment with desmopressin was necessary for 5 months, she became free from medication afterwards. Diabetes insipidus seems to be a rare but could be an important complication after simultaneous pancreas kidney transplantation and/or or kidney transplantation.</p>

Thyroid storm is an endocrine emergency which is characterized by multiple organ failure due to severe thyrotoxicosis, often associated with triggering illnesses. Early suspicion, prompt diagnosis and intensive treatment will improve survival in thyroid storm patients. Because of its rarity and high mortality, prospective intervention studies for the treatment of thyroid storm are difficult to carry out. We, the Japan Thyroid Association and Japan Endocrine Society taskforce committee, previously developed new diagnostic criteria and conducted nationwide surveys for thyroid storm in Japan. Detailed analyses of clinical data from 356 patients revealed that the mortality in Japan was still high (∼11%) and that multiple organ failure and acute heart failure were common causes of death. In addition, multimodal treatment with antithyroid drugs, inorganic iodide, corticosteroids and beta-adrenergic antagonists has been suggested to improve mortality of these patients. Based on the evidence obtained by nationwide surveys and additional literature searches, we herein established clinical guidelines for the management of thyroid storm. The present guideline includes 15 recommendations for the treatment of thyrotoxicosis and organ failure in the central nervous system, cardiovascular system, and hepato-gastrointestinal tract, admission criteria for the intensive care unit, and prognostic evaluation. We also proposed preventive approaches to thyroid storm, roles of definitive therapy, and future prospective trial plans for the treatment of thyroid storm. We hope that this guideline will be useful for many physicians all over the world as well as in Japan in the management of thyroid storm and the improvement of its outcome.

OBJECTIVE: Thyroid storm (TS) is a life-threatening endocrine emergency. This study aimed to achieve a better understanding of the management of TS by analyzing therapeutic modalities and prognoses reported by nationwide surveys performed in Japan. DESIGN, PATIENTS AND MEASUREMENTS: Retrospective analyses were performed on clinical parameters, outcomes, and treatments in 356 TS patients. RESULTS: Patient disease severities assessed via Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores significantly correlated with mortality. Free triiodothyronine (FT3) and the FT3/free thyroxine (FT4) ratio inversely correlated with disease severity. Methimazole (MMI) was used in the majority of patients (78·1%), and there were no significant differences in mortality or disease severity between those treated with MMI and those receiving propylthiouracil (PTU). Patients who received inorganic iodide (KI) demonstrated higher disease severity but no change in mortality compared to those who did not. Patients treated with corticosteroids (CSs) demonstrated significantly higher disease severity and mortality than those who were not. Disease severity in patients treated with intravenous administration of beta-adrenergic antagonists (AAs) was significantly higher than those treated with oral preparations, although no significant difference in mortality was observed between these groups. In addition, mortality was significantly higher in patients treated with non-selective beta-AAs as compared with other types of beta-AAs. CONCLUSION: In Japan, MMI was preferentially used in TS and showed no disadvantages compared to PTU. In severe TS, multimodal treatment, including administration of antithyroid drugs, KI, CSs and selective beta1 -AAs may be preferable to improve outcomes.

Objective: Traditional Japanese food appears to be healthy but contains a small amount of milk products. Type 2 diabetes (T2DM) patients commonly reduce their energy intake to control their blood glucose levels. However, nutritional guidance for diabetes does not emphasize calcium (Ca) consumption. The aim of this study is to estimate the nutritional status of Ca and other nutrients, which affect bone and Ca metabolism, in T2DM patients. Methods: This observational study was conducted with Japanese T2DM patients (n = 96 M/F = 50/46 age: 61.6 � 10.1 years). We estimated nutrient intake using a simple food frequency questionnaire. Results: Median total energy intake was 1750 kcal/day (1440-1970). Their median daily intake of Ca, vitamin D, and vitamin K was 451 mg (336-560), 10.2 μg (8.5-12), and 206 μg (84-261), respectively. Only 17.7% of the study subjects were found to take more than 600 mg/day of Ca. Protein and salt intake was 78 (64-90) and 10.6 (9.3-12.2) g/day, respectively. Male subjects had more salt, less Ca and vitamin K than female. Daily Ca intake was positively associated with total energy, protein, and lipid intake but not with carbohydrates. Vitamin D intake correlated only with protein intake. Conclusion: The daily Ca intake of Japanese T2DM patients appears to be insufficient and could depend on protein and lipid intake. Additionally, these patients should have specific recommendations to ensure sufficient intake of Ca with protein and lipid during energy restriction.

BackgroundA total of 26 pancreas transplants from brain dead donors, including 21 simultaneous pancreas and kidney (SPK) transplantation procedures, have been performed at Fujita Health University Hospital since the new pancreas transplant program was initiated in August 2012. The objective of this study is to investigate the outcomes of pancreatic transplantation in our facility in first 3 years of the program. MethodsThe background characteristics of the donors and the outcomes of 26 pancreas transplant recipients were analyzed. ResultsThe mean age of the recipients was 44.0years, and all recipients had a long-term history of diabetes (mean: 30.2years). In the SPK cases, the patients also had a long history of hemodialysis (mean: 6.3years). Although the average donor age was 41.0years and more than half of the donors were marginal donors (defined according to Kapur's criteria and Troppmann's criteria), the patient survival and pancreatic graft survival rates were 100% and 91.7%, respectively. Unfortunately, two recipients experienced graft failure due to graft thrombosis, which resulted in graft loss. ConclusionsThe new pancreas transplant program at Fujita Health University has provided excellent outcomes for patients with type 1 diabetes.

Pancreatic graft thrombosis is the primary cause of non-immunologic graft loss, with an incidence ranging from 5% to 15%. Therefore, developing a screening test to detect graft thrombosis after pancreatic transplantation is important. We created a screening test to assess graft thrombosis after pancreatic transplantation using contrast-enhanced ultrasonography (CEUS) with Sonazoid. A total of seven patients were examined using CEUS after undergoing pancreatic transplantation. All patients were observed to have a clear blood flow in the splenic vein in the pancreatic graft, while only one of the seven patients exhibited a blood flow in the horizontal portion of the splenic vein on Doppler ultrasonography performed immediately after pancreatic transplantation. CEUS with Sonazoid demonstrated the blood flow in the splenic vein and parenchyma of the pancreatic graft in detail, in spite of the slow and lateral blood flow in the splenic vein of the pancreatic graft immediately after transplantation.<br>Evaluation of tissue blood flow in pancreatic graft using &Delta;Tp(V-P) calculated by time intensity curve as shown by CEUS correlates with endocrine function of pancreatic graft 1 month after transplantation. These findings suggest that CEUS should become one of the novel and useful examination for pancreas transplantation.

Autoimmune thyroid diseases (AITDs), including Graves' diseases (GD) and Hashimoto's thyroiditis (HT), are the most common autoimmune diseases, and are mainly mediated by T cells that produce cytokines and chemokines in abnormal amounts. Few reports have described the circulating chemokines active in AITDs. Recently, we used a new multiplex immunobead assay to simultaneously measure cytolcines and chemokines in small volume serum samples from patients with AITDs. We measured 23 selected serum chemokines in patients with GD (n=45) or HT (n=26), and healthy controls (n=9). GD patients were further classified as either untreated, intractable, or in remission, while HT patients were classified as either hypothyroid or euthyroid. Of the 23 serum chemokines assayed, only the serum level of IP-10 (CXCL10/interferon-gamma-inducible protein 10) was elevated, depending on disease activity, in GD or HT compared with healthy controls. However, the serum level of IP-10 was also increased in both untreated GD patients and hypothyroid HT patients, suggesting that levels of this cytokine may not be affected by disease specificity. In conclusion, autoimmune inflammation in patients with AITD is closely related to the level of the serum chemokine, IP-10. Therefore, IP-10 might be a good biomarker for tissue inflammation in the thyroid, but not a useful biomarker for predicting disease specific activity, the progression of AITDs, or responsiveness to treatment because of its independence from thyroid function or disease specificity.

骨粗鬆症の有病率の高まりを受けて、合併する慢性疾患治療薬の骨代謝への影響が注目されている。抗糖尿病薬であるチアゾリジン薬がその代表である。さらに降圧薬、脂質異常症治療薬、選択的セロトニン再取り込み阻害薬、抗けいれん薬、ループ利尿薬、プロトンポンプ阻害薬など骨代謝と関連する薬剤は多岐にわたる。糖質コルチコイドに関しては国際的にもガイドラインが定められているが、ステロイド以外の薬剤の骨代謝への影響にはまとまったガイドラインはない。高齢者の健康寿命延伸をはかる上で、他疾患の薬剤からの骨への作用は無視し得ない検討課題となってきている。(著者抄録)

We previously showed that aripiprazole increases intracellular NADPH and glucose-6-phosphate dehydrogenase mRNA in PC12 cells. Aripiprazole presumably activates a system that concurrently detoxifies reactive oxygen species and replenishes NADPH. Nrf2, a master transcriptional regulator of redox homeostasis genes, also activates the pentose phosphate pathway, including NADPH production. Therefore, our aim was to determine whether aripiprazole activates Nrf2 in PC12 cells. Aripiprazole increased mRNA expression of Nrf2-dependent genes (NAD(P)H-quinone oxidoreductase-1, Nqo1; heme oxygenase-1, HO1; and glutamate-cysteine ligase catalytic subunit) and protein expression of Nqo1 and HO1 in these cells (p &lt; 0.05). To maintain increased Nrf2 activity, it is necessary to inhibit Nrf2 degradation; this is done by causing Nrf2 to dissociate from Keap1 or beta-TrCP. However, in aripiprazole-treated cells, the relative amount of Nrf2 anchored to Keap1 or beta-TrCP was unaffected and Nrf2 in the nuclear fraction decreased (p &lt; 0.05). Aripiprazole did not affect phosphorylation of Nrf2 at Ser40 and decreased the relative amount of acetylated Nrf2 (p &lt; 0.05). The increase in Nqo1 and HO1 in aripiprazole-treated cells cannot be explained by the canonical Nrf2-degrading pathways. Further experiments are needed to determine the biochemical mechanisms underlying the aripiprazole-induced increase in these enzymes.

Urinary liver-type fatty acid-binding protein (L-FABP) reflects the degree of stress in proximal tubules of the kidney. We examined the level of L-FABP in type-2 diabetes mellitus (T2DM) patients with chronic kidney disease (CKD) stage G1 and G2, and its relationship with cardiac markers and electrocardiographic (ECG) abnormalities. T2DM patients whose estimated glomerular filtration rate (eGFR) was &gt;= 60 mL/min/1.73 m(2) were recruited [n = 276 (165 males), mean age 64 years]. The median level of urinary L-FABP was 6.6 mu g/gCr. Urinary L-FABP showed significant correlation with urinary albumin-to-creatinine ratio (ACR) (r = 0.51, p &lt; 0.0001). Median (25th-75th percentile) eGFR was 82 (72-95) mL/min/1.73 m(2). We divided patients into four subgroups (group 1, L-FABP &lt;= 8.4 mu g/gCr and ACR &lt;= 30 mg/gCr; group 2, L-FABP &lt;= 8.4 mu g/gCr and ACR &gt;30 mg/gCr; group 3, L-FABP &gt;8.4 mu g/gCr and ACR &lt;= 30 mg/gCr; group 4, L-FABP &gt;8.4 mu g/gCr and ACR &gt;30 mg/gCr). Compared with group 1, group 4 was significantly higher in systolic blood pressure, and eGFR using standardized serum cystatin C, high-sensitivity troponin T, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Group 4 had significantly higher level of NT-proBNP than group 3. Groups 2, 3 and 4 showed more ECG abnormalities than group 1. These findings suggest that simultaneous measurement of urinary L-FABP and ACR should be useful to assess cardiovascular damage reflecting on the elevation of cardiac markers and ECG abnormalities in T2DM with CKD G1 and G2.

骨粗鬆症リエゾンサービスは、骨折予防におけるケアギャップを埋めるために日本骨粗鬆症学会により展開されつつある事業である。海外のFracture Liaison Serviceが骨折の二次予防を主たる目的としているのに対し、本サービスでは骨検診推進を含めた一次予防ならびに地域での啓発活動まで視野に入れた包括的取り組みである。骨粗鬆症マネージャー資格を取得したメディカルスタッフを本サービスの担い手とすることで、サービスの質の担保と統一性をはかっている。第1回資格試験に合格した骨粗鬆症マネージャーが、平成27年(2015年)4月より活動を開始する。(著者抄録)

Background Nutritional status affects clinical outcomes in patients with chronic renal failure. Glucose intolerance, dyslipidemia, obesity, hypertension, and a calcium-phosphorus-vitamin D imbalance are the major nutritional and metabolic problems that occur in posttransplant patients. In this study, we assessed the daily intake in long-term renal transplant recipients to determine whether they have sufficient nutrients based on the Japanese nutrition recommendations (recommended dietary allowances [RDA] in Japan 2010). Subjects and Methods Thirty-one renal allograft recipients followed for &gt 10 years (median, 16.3) were recruited. The median serum creatinine level was 1.2 g/dL (95% CI, 0.6-3.4). We estimated the intake of nutrients, including protein and salt, using a simple food frequency questionnaire. Results The median body mass index was 20.1 kg/m2. The median total energy intake was 1566 kcal/d (95% CI, 892-2556). The daily intake of protein and salt was 65.1 and 9.1 g/d, respectively. The calcium, iron, vitamin D, and vitamin K intakes were 423 mg, 7.0 mg/d, 9.7 μg/d, and 197 μg/d, respectively. Patients with dyslipidemia displayed greater amounts of lipid and calcium than those with normal lipid levels. Discussion Our findings suggest that long-term renal transplant recipients in Japan seem to restrict caloric intake, while maintaining appropriate intake of protein, lipids, carbohydrates, and vitamins A, D, and K. However, daily calcium and iron intake were insufficient salt intake was greater than the recommended dietary allowances in all subjects. In patients with dyslipidemia, calcium intake was lower than those in patients without dyslipidemia, although their intake of lipids was also lower than those without dyslipidemia. Conclusion Nutritional guidance beginning during the early posttransplant phase helps to foster a healthy body mass index and nutritional balances for long-term renal transplant recipients. However, greater salt restriction was needed, and additional nutritional guidance aiming to prevent osteoporosis seems to be considered.

Objectives: According to our previous work, aripiprazole exerted a protective effect on hydrogen peroxide (H2O2)-treated PC12 cells; haloperidol did not. Because aripiprazole has distinct affinities to a set of neurotransmitter receptor subtypes, this study aimed to clarify which subtype is responsible for rescuing cells from 0.25 mM H2O2 exposure.Methods: A set of compounds, which are more specific to each subset of G-protein coupled receptors, wereexamined for their ability to mimic the pharmacological effects of aripiprazole or haloperidol, including their Ki values.The viability of PC12 cells cultured with test compounds with or without H2O2 was assessed using WST-8 reagent.Results: Results from in vitro studies using PC12 cells showed that agonism at serotonin 5-HT2C-receptors based on the antagonism against 5-HT2B-receptors played a significant role in resistingH2O2-induced cell death. However, the use of a specific 5-HT2B-receptor agonist instead of a 5-HT2B-receptor antagonist completely negated the effect of a specific 5-HT2C-receptor agonist. Furthermore, unlike the dopamine D1-receptor specific antagonist, none of the agonists of dopamine D2-, D3-, and D4-receptors ameliorated the cytopathic effects of H2O2.Conclusion: Antagonism at 5-HT2B-receptors is fundamental for the protection of PC12 cells against the cytopathiceffects caused by 0.25 mM H2O2. However, the role of negatively regulated cyclic adenosine monophosphate in this phenomenon requires further investigation.

Background. Under a revision to the law in 2010, the number of pancreas transplantations from brain-dead donors has been increasing in Japan. We started a new Pancreatic Transplant Program at Fujita Health University Hospital in September 2012. Methods. A total of 11 cases of pancreas transplantation from brain-dead donors performed at Fujita Health University Hospital were analyzed in terms of the background characteristics of the donors and recipients and the outcomes. Results. The mean age of the recipients was 45.2 years, and all recipients had a long-term history of diabetes (mean: 32.5 years). In the simultaneous pancreas and kidney transplantation (SPK) cases, the patients also had a long history of hemodialysis (mean: 8.0 years). Although the average donor age was 42.5 years, 90% of the donors were marginal donors, defined according to the following factors: (1) &gt; 45 years old, (2) death from cardiovascular disease, (3) episodes of cardiac arrest, (4) use of high doses of catecholamines. The pancreatic graft survival rate was 100%, although 1 patient required a small amount of insulin to maintain euglycemia. In addition, the kidney graft survival rate was also 100% in the SPK cases. Conclusions. The new Pancreatic Transplant Program at Fujita Health University has provided excellent outcomes for type 1 diabetic patients.

Background. Despite recent progress of immunosuppressive therapy with newly developed agents, long-term pancreatic graft survival after pancreas transplantation still remains low. Therefore, precise assessment of beta-cell function after pancreas transplantation is necessary. Methods. Pancreatic beta-cell secretory activity was measured by means of the peripheral plasma fasting serum C-peptide (CPR) response to 1 mg of glucagon intravenously in 23 patients after pancreas transplantation. The utility of Delta CPR after injection was compared with other indices that reflect insulin secretion. Results. When we performed the test, 6 patients still needed insulin injection after the transplantation. Mean CPR before and after glucagon intravenously were 1.9 +/- 0.98 ng/mL and 4.6 +/- 2.29 ng/mL, respectively. Fasting serum CPR, secretory unit of islet in transplantation (SUIT) index, and Delta CPR after glucagon injection were significantly different between insulin users and nonusers. During follow-up (501 228 days), 3 patients could stop using insulin, and their increase of CPR (1.8 +/- 0.5 ng/mL) was significantly higher than that in continuous insulin users (0.3 +/- 0.3 ng/mL). Conclusion. Fasting CPR, SUIT index, and Delta CPR after glucagon injection could reflect beta-cell function for post-pancreas transplant patients, and glucagon stimulation test could give us additional information to predict insulin-free treatment.

Uptake of Pi at the cellular membrane is essential for the maintenance of cell viability. However, phosphate overload is also stressful for cells and can result in cellular damage. In the present study, we investigated the effects of the transgenic overexpression of type III Pi transporter Pit-1 to explore the role of extracellular Pi in glomerular sclerosis during chronic renal disease. Pit-1 transgenic (TG) rats showed progressive proteinuria associated with hypoalbuminemia and dyslipidemia. Ultrastructural analysis of TG rat kidney by transmission electron microscopy showed a diffuse effacement of the foot processes of podocytes and a thickening of the glomerular basement membrane, which were progressively exhibited since 8 wk after birth. TG rats died at 32 wk of age due to cachexia. At this time, more thickening of the glomerular basement membrane and segmental sclerosis were observed in glom-eruli of the TG rats. Immunohistochemical examination using anti-connexin 43 and anti-desmin antibodies suggested the progressive injury of podocytes in TG rats. TG rats showed higher Pi uptake in podocytes than wild-type rats, especially under low Pi concentration. When 8-wk-old wild-type and TG rats were fed a 0.6% normal phosphate (NP) or 1.2% phosphate (HP) diet for 12 wk, HP diet-treated TG rats showed more progressive proteinuria and higher serum creatinine levels than NP diet-treated TG rats. In conclusion, our findings suggest that overexpression of Pit-1 in rats induces phosphate-dependent podocyte injury and damage to the glomerular barrier, which result in the progression of glomerular sclerosis in the kidney.© 2011 by the American Physiological Society.© 2011 by the American Physiological Society.

妊娠30週以降の後期妊婦20例を対象に、冬季に血清25(OH)D値と骨関連因子を測定し、あわせて関連について検討した。その結果、冬季においては血清25(OH)D値が20ng/ml未満の相対的ビタミンD欠乏症が疑われる妊婦は18例と多かった。しかし、血清25(OH)D値と血清iPTH値、血清BAP値、血清NTX値との間にはいずれも相関は示されなかった。また、周産期合併症との関連も示されなかった。

Context and objective: Arterial stimulation and venous sampling (ASVS) is an important technique for localizing insulinoma. The principle behind ASVS is that insulin secretion is promoted from insulinoma cells by the injection of calcium into the insulinoma-feeding artery. However, the mechanism for ASVS-induced insulin secretion remains unclear. Both insulnoma and familial hypocalciuric hypercalcemia (FHH) are rare diseases. This study reports on a case in which both of these diseases occur concurrently. Design and patient: The patient with FHH also suffered from insulinoma. We reasoned that insulin secretion for ASVS is dependent on the calcium-sensing receptor (CaSR). ASVS was performed on this patient. The expression of the CaSR protein and corresponding mRNA were confirmed. Results: No significant changes in the plasma levels of insulin and C-peptide were observed during ASVS. The patient was clinically diagnosed as having FHH. We confirmed that a mutation in the CaSR gene was present in the genomic DNA of this patient and that there were no mutations in the multiple endocrine neoplasia type I gene. In addition, expression of both CaSR mRNA and CaSR protein was confirmed in the insulinoma samples. Conclusion: These results suggest that the CaSR gene is involved in ASVS-induced insulin secretion.

The prevention of osteoporotic fracture is an essential socioeconomical priority, especially in the developed countries including Japan. Estrogen, selective estrogen-receptor modulators (SERMs), and bisphosphonate are potent inhibitors of bone resorption; and they have clinical relevance to reduce osteoporotic fractures in postmenopausal women. However, we can prevent at most 50% of vertebral fractures with these agents. For the better compliance of aminobisphosphonate, the use of a daily bisphosphonate regimen is moving to a weekly or monthly bisphosphonate regimen. Both cathepsin K inhibitors and modulators of the RANK-RANKL system, which can reduce bone resorption, are the candidates for the future treatment of osteoporosis. As well as bone resorption, we need to increase bone formation to prevent osteoporotic fractures, particularly in elderly patients with low bone turnover. In the U.S., Europe, and Australia, they have already started intermittent parathyroid hormone injection and/or oral strontium ranelate to stimulate bone formation. We still need to discover new agents to reduce osteoporotic fractures for the better quality of life without fractures.

The level of leptin increases with obesity, whereas that of adiponectin decreases with obesity. It is reported that the ratio of leptin to adiponectin (L/A) is associated with insulin resistance. It is difficult to evaluate insulin resistance in diabetic patients who have a dysfunction of insulin secretion. The aim of this study was to examine whether the L/A ratio is a useful marker for insulin resistance in diabetic patients. We examined L/A in the serum of a total of 139 Japanese patients with type 2 diabetes mellitus (66 women and 73 men) and 7 healthy individuals recruited in our hospital. Changes in the levels of leptin and adiponectin were observed using the oral glucose tolerance test and a hyper- and euglycemic clamp test. Twenty-one patients with type 2 diabetes mellitus were observed for more than 6 months after treatment with pioglitazone, and 31 patients with type 2 diabetes mellitus were observed for more than 6 months after the treatment with metformin. The mean value of L/A in 139 Japanese patients with type 2 diabetes mellitus was 1.22 ± 1.41 (1.68 ± 1.76 in women, 0.81 ± 0.80 in men P = .0002). In the clamp tests, L/A correlated with glucose infusion rate (GIR) (r2 = 0.26, P = .0034). The correlation of L/A and GIR indicated a stronger correlation than either leptin (r2 = 0.144, P = .03) or adiponectin alone (r2 = 0.023, P = .41), or the homeostasis model assessment of insulin resistance (r2 = 0.103, P = .08). The average hemoglobin A1c (HbA1c) improved from 10.2% ± 1.2% to 9.2% ± 1.6% (P = .0037) in 6 months after treatment with pioglitazone. Our results indicate pioglitazone to be effective for HbA1c improvement in subjects with high L/A and low L/A. The average HbA1c improved from 9.2% ± 0.9% to 8.0% ± 1.2% (P = .0002) in 6 months after treatment with metformin. Our results indicate metformin to be effective for HbA1c improvement in subjects with a low L/A. In conclusion, we demonstrate that L/A is different between male and female subjects. The correlation of L/A and GIR by the euglycemic hyperinsulinemic clamp test suggests that L/A is a useful indicator for the choice of drug to treat diabetes mellitus. © 2008 Elsevier Inc. All rights reserved.

The metabolic syndrome is a common and complex disorder combining obesity, dyslipidemia, hypertension, and insulin resistance (IR). In the present study, we conducted the observational study in 126 non-diabetes Japanese male population, who visited our clinic for their routine medical check-up, about the relationship between IR indexes and parameters of metabolic syndrome. IR was assessed by both quantitative insulin check index (QUICKI) and homeostasis model assessment for IR (HOMA-IR). Body mass index, body fat content and blood pressure were related with QUICKI and HOMA-IR, but better association was observed with QUICKI. There was no significant association between age and IR indexes. In addition to the fasting plasma glucose (PG) and immunoreactive insulin (IRI) levels, the concentrations of PG and IRI at 30, 60 and 120 min during 75g oral glucose tolerance test were associated with HOMA-IR and QUICKI. Serum triglyceride concentration was associated with QUICKI and HOMA-IR, and serum HDL-cholesterol was related to QUICKI. On the contrary, none of serum total cholesterol, LDL-cholesterol or non-HDL cholesterol concentration was associated with IR indexes. These results suggest that IR was significantly related with the progress of metabolic syndrome even in non-diabetes Japanese male population. Early evaluation of IR by QUICKI would be expected to contribute to the prevention of cardiovascular event due to metabolic syndrome.