Japanese Economic Growth during the Edo Period

During the Edo period, Japanese production of silver declined drastically. Japan could not export silver in order to import cotton, sugar, raw silk and tea from China. Japan was forced to carry out import-substitution. Because Japan adopted seclusion policy and did not produce big ship, it used small ships for coastal trade, which contributed to the growth of national economy. Japanese economic growth during the Edo period was indeed Smithian, but it formed the base of economic development in Meiji period

Signal transduction of reactive oxygen species and mitogen-activated protein kinases in cardiovascular disease

Reactive oxygen species (ROS), generated by reduction-oxidation (redox) reactions, have been recognized as important chemical mediators that regulate signal transduction. It has been reported that increase in ROS generation may relate to a risk for cardiovascular diseases such as atherosclerosis, angina pectoris, and myocardial infarction. Therefore, understanding the ROS-generating biological processes and ROS-induced intracellular signaling will be informative to gain insights into the pathogenesis of these diseases. In this review, we focus on the sources and reactions of ROS in the cardiovascular system and the role of mitogen-activated protein (MAP) kinase pathway in redox-mediated signal transduction. Clinical implications of ROS and MAP kinase are then described to provide insight into the pathogenesis of various redox-sensitive cardiovascular diseases. The pathways responsible for ROS generation in the cardiovascular system may provide novel therapeutic targets

ヤクリ サヨウ カラ ミタ ケンコウ ショクヒン

The several biologically active substances in foods were isolated as chemical compounds and each isolated chemical compound has been used as a drug in clinic. It is very difficult to make as harp distinction between drug and a chemical compound in functional food. At present, many functional food products with health claims are available in the local market. Since there is no distinct regulatory framework for functional foods, they are regulated as foods.However, some of these may have potentially disastrous side-effects and evaluation system of so-called health food is not established. We proposed that an isolated chemical compound in functional food, which has a pharmacological active effects, must handle as a drug and should be evaluated carefully in terms of its effectiveness and toxicity

Albuminuria and Serum Tumor Necrosis Factor Receptor Levels in Patients with Type 2 Diabetes on SGLT2 Inhibitors : A Prospective Study

Introduction: Large-scale clinical trials of sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrate proteinuria-reducing effects in diabetic kidney disease, even after treatment with renin–angiotensin inhibitors. The precise mechanism for this favorable effect remains unclear. This prospective open-label single-arm study investigated factors associated with a reduction in proteinuria after SGLT2i administration. Methods: Patients with type 2 diabetes (T2DM) who had glycated hemoglobin (HbA1c) levels ≥ 6.5% despite dietary and/or oral hypoglycemic monotherapy were recruited and administered the recommended daily dose of SGLT2i for 4 months. Dual primary outcomes were changes in the urine albumin-to-creatinine ratio (uACR) and urine liver-type fatty acid-binding protein (L-FABP)-to-creatinine ratio (uL-FABPCR) at month 4 from baseline. Changes in kidney injury, inflammation, and oxidative stress biomarkers were investigated as secondary endpoints to examine the effects of this treatment on the kidney. The correlation between renal outcomes and clinical indicators, including circulating tumor necrosis factor receptors (TNFR) 1 and 2, was evaluated using univariate and multivariate analyses. Results: Participants (n = 123) had a mean age of 64.1 years (SD 13.4), with 50.4% being male. The median BMI was 25.8 kg/m2 (interquartile range (IQR) 23.1–28.9), and the median HbA1c level was 7.3% (IQR 6.9–8.3). After SGLT2i administration, the uACR declined from 19.2 mg/gCr (IQR 7.1–48.7) to 13.3 mg/gCr (IQR 7.5–31.6), whereas the uL-FABPCR was not influenced. In univariate analysis, the change in log-transformed uACR due to SGLT2i administration showed a positive correlation with the change in serum TNFR1 level (R = 0.244, p < 0.01). Multivariate regression analysis, including confounding factors, showed that the changes in serum TNFR1 level were independently associated with the changes in the log-transformed uACR (independent t = 2.102, p < 0.05). Conclusion: After the 4-month SGLT2i administration, decreased albuminuria level was associated with decreased serum TNFR level in patients with T2DM

チュートリアル キョウイク ノ カイゼン ニ カンスル ケンキュウ : チュートリアル キョウイク ドウニュウ ノ タメ ノ ガクセイ ワークショップ ノ シコウ ト ソノ セイカ

チュートリアル教育は、少人数グループにチューターが付いて学生の自主的な学習を指導・促進す る学習方法である。徳島大学医学部医学科では2001 年から導入して、3 年生の9 月から4 年生12 月まで の47 週間行なっている。2004 年度で4 年目を迎えるが、学生が教員に学習課題を少なめに出して早く終 了する傾向もみられ始めた。われわれは、こうした傾向を憂い、グループ学習の楽しさを体験させてから チュートリアル学習を開始する方が、好ましい学習態度を形成できるのではないかと考え、3 年生の7 月 に従来の2 時間程度の説明会以外に4 時間かけて「沖縄旅行計画」を作る学生ワークショップを行なった。 この結果、前年度の学生よりも、このチュートリアル学習に対する好感度・有用感などが高くなり、グル ープ学習時間も増加して、この導入プログラムの有効性を示唆した。New curriculum of the school of medicine, the University of Tokushima included 47-week PBL-tutorial hybrid program started in 2001.To improve their learning skill and attitude, and to introduce a new learning style of PBL-tutorial to students smoothly, we held a half day student workshop. The content of workshop is of making tour plans for a family who had relationship problems among family members. Twelve groups with eight students respectively competed and evaluated each other, and all students enjoyed working as groups. The efficacy of this introductory program was evaluated with questionnaire and their study time of group learning between this year and last year students. Impression and feeling of usefulness toward PBL-tutorial was improved, and time of group study increased this year. Results suggested usefulness of this introductory program. We will continue the evaluation of this program

Possible role of bradykinin on stimulus-secretion coupling in adrenal chromaffin cells

Nonapeptide bradykinin is known to be a central nervous system neurotrans-mitter and to play a role in regulation of neuronal function. However, few details are known of the function of its peptide on stimulus-secretion coupling in neuronal cells. In this article, the role of bradykinin on catecholamine biosynthesis, secretion and Ca2+movement in adrenal chromaffin cells as a model for catecholamine-containing neurons are examined. Bradykinin receptors are classified as B1 and B2 receptor subtypes. These receptors are present on the adrenal chromaffin cell membrane. Bradykinin increases the influx of Ca2+ and the turnover of phosphoinositide through the stimulation of bradykinin B2 receptor. The secretion of catecholamine from the cells is initiated by the raise of [Ca2+]i. An increase in [Ca2+]i and production of diacylglycerol stimulate the activation of calcium-dependent protein kinases. These kinases stimulate the activation of tyrosine hydroxylase, a rate-limiting enzyme in the biosynthesis of catecholamine. Otherwise, bradykinin increases Ca2+ efflux from the cells through the stimulation of the bradykinin-B2 receptor. This action may be explained by an extracellular Na+-dependent mechanism, probably through acceleration of Na+/Ca2+ exchange. It is interesting that bradykinin, which stimulates the biosynthesis and secretion of catecholamine in adrenal chromaffin cells, plays a role in the termination of calcium-signal transduction through the stimu-lation of Ca2+ efflux from the cells

ヒト サイタイ ジョウミャク ナイヒ サイボウ HUVEC ニオケル Lysophosphatidylcholine LPC シゲキ ニヨル VEGF レセプター ノ トランス アクチベーション

One of the major lipid components of oxidized low density lipoprotein, lysophosphatidylcholine （LPC） is involved in numerous biological processes as a bioactive lipid molecule and has been shown to be involved in the progression of atherosclerosis. As counter-ligands, G２A and GPR４ were identified with high binding affinity for LPC that are belonging to orphan G-protein-coupled receptors （GPCRs） at plasma membranes. Although several GPCR ligands transactivate receptor tyrosine kinases （RTKs）, such as epidermal growth factor receptor, transactivation of RTK by LPC has not yet been reported. Here we observed for the first time that LPC treatment induces tyrosyl phosphorylation of vascular endothelial growth factor （VEGF） receptor２ （fetal liver kinase-１／kinase-insert domain-containing receptor, Flk-１／KDR） in human umbilical vein endothelial cells （HUVEC）. VEGF receptor tyrosine kinase inhibitors, SU１４９８ and VTKi inhibited Flk-１／KDR transactivation by LPC. Furthermore, we examined the effect of the Src family kinases inhibitors, Herbimycin A and PP２ on LPC-induced Flk-１／KDR transactivation. Herbimycin A and PP２ inhibited Flk-１／KDR transactivation in HUVEC, suggesting that c-Src is involved in LPC-induced Flk-１／KDR transactivation. Kinase-inactive （KI） Src transfection also inhibited LPC-induced Flk-１／KDR transactivation. In addition, LPC activated extracellular signal-regulated kinase１／２ and Akt, which are downstream effectors of Flk-１／KDR, and these were inhibited by SU１４９８，VTKi, Herbimycin A, PP２ and KI Src transfection in HUVEC. LPC-mediated HUVEC proliferation was shown to be secondary to transactivation because it was suppressed by SU１４９８，VTKi, Herbimycin A, PP２and KI Src transfection. It is concluded that c-Src-mediated Flk-１／KDR transactivation by LPC may have important implications for the progression of atherosclerosis