The Design Method of Axial Flow Runners Focusing on Axial Flow Velocity Uniformization and Its Application to an Ultra-Small Axial Flow Hydraulic Turbine

We proposed a portable and ultra-small axial flow hydraulic turbine that can generate electric power comparatively easily using the low head of open channels such as existing pipe conduits or small rivers. In addition, we proposed a simple design method for axial flow runners in combination with the conventional one-dimensional design method and the design method of axial flow velocity uniformization, with the support of three-dimensional flow analysis. Applying our design method to the runner of an ultra-small axial flow hydraulic turbine, the performance and internal flow of the designed runner were investigated using CFD analysis and experiment (performance test and PIV measurement). As a result, the runners designed with our design method were significantly improved in turbine efficiency compared to the original runner. Specifically, in the experiment, a new design of the runner achieved a turbine efficiency of 0.768. This reason was that the axial component of absolute velocity of the new design of the runner was relatively uniform at the runner outlet in comparison with that of the original runner, and as a result, the negative rotational flow was improved. Thus, the validity of our design method has been verified

Changes in Blood Pressure after the First Dose of Calcitonin (Elcatonin)

We had found previously that calcitonin treatment (elcatonin once a week for 10 weeks) results in significant decreases in blood pressure. The aim of the present study was to determine whether these effects were due to a cumulative effect of elcatonin or could be elicited by treatment with a single dose. To this end, we recruited 62 patients (eight men, 54 women; mean age 83 years; range 67-101 years) with a chief complaint of lower back pain to the present study and examined changes in blood pressure following administration of the first dose of elcatonin. All subjects in the study had been hospitalized either at our institution or an affiliated hospital. After acute phase symptoms had settled, subjects received 1 U (1mL), i.m., elcatonin S20. Blood pressure was measured the day before the first scheduled treatment and on the day of treatment. Both systolic and diastolic blood pressure decreased from 2 h after administration, and dropped significantly 4 and 6 h after administration. Therefore, elcatonin decreased blood pressure without first having to be accumulated in the body. There are several possible explanations for the results, including effects mediated by changes in concentrations of calcitonin gene-related peptide and calcium ions, as well as involvement of the parasympathetic nervous system. In conclusion, calcitonin inhibits bone resorption and pain, lowers blood pressure, and is easy to use in elderly patients who exhibit age-related increases in blood pressure

Efficacy and safety of luseogliflozin added to various oral antidiabetic drugs in Japanese patients with type 2 diabetes mellitus

Introduction: Two studies were carried out to investigate the efficacy and safety of luseogliflozin added to existing oral antidiabetic drugs (OADs) in Japanese type 2 diabetic patients inadequately controlled with OAD monotherapy. Materials and Methods: In the trial involving add‐on to sulfonylureas (study 03‐1), patients were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for a 24‐week double‐blind period, followed by a 28‐week open‐label period. In the open‐label trial involving add‐on to other OADs; that is, biguanides, dipeptidyl peptidase‐4 inhibitors, thiazolidinediones, glinides and α‐glucosidase inhibitors (study 03‐2), patients received luseogliflozin for 52 weeks. Results: In study 03‐1, luseogliflozin significantly decreased glycated hemoglobin at the end of the 24‐week double‐blind period compared with the placebo (–0.88%, P < 0.001), and glycated hemoglobin reduction from baseline at week 52 was –0.63%. In study 03‐2, luseogliflozin added to other OADs significantly decreased glycated hemoglobin from baseline at week 52 (–0.52 to –0.68%, P < 0.001 for all OADs). Bodyweight reduction was observed in all add‐on therapies, even with agents associated with weight gain, such as sulfonylureas and thiazolidinediones. Most adverse events were mild in severity. When added to a sulfonylurea, incidences of hypoglycemia during the double‐blind period were 8.7% and 4.2% for luseogliflozin and placebo, respectively, but no major hypoglycemic episodes occurred. The frequency and incidences of adverse events of special interest for sodium glucose cotransporter 2 inhibitors and adverse events associated with combined OADs were acceptable. Conclusions: Add‐on therapies of luseogliflozin to existing OADs improved glycemic control, reduced bodyweight and were well tolerated in Japanese type 2 diabetic patients. These trials were registered with the Japan Pharmaceutical Information Center (add on to sulfonylurea: JapicCTI‐111507; add on to other OADs: JapicCTI‐111508)

Development of improved method to identify and analyze lung fibrocytes with flow cytometry in a reporter mouse strain

Introduction Fibrocytes are emerging myeloid-derived circulating cells that can migrate into damaged tissues and usually contribute to their repair. Key features of fibrocytes include the expression myeloid markers, production of extracellular matrix proteins, and secretion of various humoral factors that activate resident fibroblasts; they also have the potential to differentiate into fibroblasts. However, no specific surface markers have been identified to identify fibrocytes in vivo. One reason could be that the method used to detect fibrocytes requires intracellular collagen staining. Methods In the present study, to establish an improved method for the detection of lung fibrocytes and to analyze viable fibrocytes, we used collagen I(α)2-green fluorescent protein (Col-GFP) reporter mice, which had undergone the intratracheal instillation of bleomycin (BLM). Results Using flow cytometry to gate out cells with autofluorescence, we clearly found that CD45+ GFP+ cells resided in the lungs of Col-GFP mice at a steady state and these cells increased after BLM injury, peaking at Day 14. These cells expressed not only known cell surface markers of fibrocytes, but also some novel markers, in addition to a low level of collagen I in comparison to CD45− GFP+ cells. Conclusion Our findings suggest that the improved method can be a useful for the detection of pure lung fibrocytes and allows us to further analyze the characteristics of viable fibrocytes

Long-term efficacy and safety of canagliflozin in combination with insulin in Japanese patients with type 2 diabetes mellitus

Aim: The aim of this study was to assess the long-term efficacy and safety of canagliflozin as add-on therapy in Japanese patients with type 2 diabetes mellitus who had inadequate glycaemic control with insulin. Materials and methods: The study comprised a 16-week, double-blind period in which patients were randomized to either placebo (P; N = 70) or canagliflozin (100 mg, CAN; N = 76), followed by a 36-week open-label period in which all patients received canagliflozin. The efficacy endpoints included the change in HbA1c from baseline to end of treatment. The safety endpoints were adverse events, hypoglycaemic events, and laboratory test values. Results: The changes from baseline (mean ± standard deviation, last observation carried forward) in the P/CAN and CAN/CAN groups, respectively, were −1.09% ± 0.85% and −0.88% ± 0.86% for HbA1c, −1.40% ± 2.54% and −2.14% ± 2.75% for body weight, and 7.84% ± 14.37% and 8.91% ± 10.80% for HOMA2-%B (all, P < .001). Adverse events occurred in 85.1% of the P/CAN group and 92.0% of the CAN/CAN group. Hypoglycaemic events occurred in 43.3% and 54.7%, respectively. All hypoglycaemic events were mild in severity and insulin dose reduction decreased the incidence rate of hypoglycaemic events. Post-hoc ordinal logistic modelling/logistic modelling showed that lower serum C-peptide at Week 0 was a risk factor for hypoglycaemia in both the P and CAN groups in the double-blind period as well as in the canagliflozin all-treatment period. Conclusions: This study demonstrates the long-term efficacy and safety of canagliflozin combined with insulin in Japanese patients

切除不能進行胃癌に対する化学療法有効例の治癒形態の検討

大学院医学系研究

Pulmonary Macrophages Attenuate Hypoxic Pulmonary Vasoconstriction via beta(3)AR/iNOS Pathway in Rats Exposed to Chronic Intermittent Hypoxia

Chronic intermittent hypoxia (IH) induces activation of the sympathoadrenal system, which plays a pivotal role in attenuating hypoxic pulmonary vasoconstriction (HPV) via central beta(1)-adrenergic receptors (AR) (brain) and peripheral beta(2)AR (pulmonary arteries). Prolonged hypercatecholemia has been shown to upregulate beta(3)AR. However, the relationship between IH and beta(3)AR in the modification of HPV is unknown. It has been observed that chronic stimulation of beta(3)AR upregulates inducible nitric oxide synthase (iNOS) in cardiomyocytes and that IH exposure causes expression of iNOS in RAW264.7 macrophages. iNOS has been shown to have the ability to dilate pulmonary vessels. Hence, we hypothesized that chronic IH activates beta(3)AR/iNOS signaling in pulmonary macrophages, leading to the promotion of NO secretion and attenuated HPV. Sprague-Dawley rats were exposed to IH (3-min periods of 4-21% O-2) for 8 h/d for 6 weeks. The urinary catecholamine concentrations of IH rats were high compared with those of controls, indicating activation of the sympathoadrenal system following chronic IH. Interestingly, chronic IH induced the migration of circulating monocytes into the lungs and the predominant increase in the number of proinflammatory pulmonary macrophages. In these macrophages, both beta(3)AR and iNOS were upregulated and stimulation of the beta(3)AR/iNOS pathway in vitro caused them to promote NO secretion. Furthermore, in vivo synchrotron radiation microangiography showed that HPV was significantly attenuated in IH rats and the attenuated HPV was fully restored by blockade of beta(3)AR/iNOS pathway or depletion of pulmonary macrophages. These results suggest that circulating monocyte-derived pulmonary macrophages attenuate HPV via activation of beta(3)AR/iNOS signaling in chronic IH