Branched Chain Amino Acids Promote ATP Production Via Translocation of Glucose Transporters

Purpose: We have previously shown that maintenance of ATP levels is a promising strategy for preventing neuronal cell death, and that branched chain amino acids (BCAAs) enhanced cellular ATP levels in cultured cells and antagonized cell death. BCAAs attenuated photoreceptor degeneration and retinal ganglion cell death in rodent models of retinal degeneration or glaucoma. This study aimed to elucidate the mechanisms through which BCAAs enhance ATP production. Methods: Intracellular ATP concentration was measured in HeLa cells under glycolysis and citric acid cycle inhibited conditions. Next, glucose uptake was quantified in HeLa cells and in 661W retinal photoreceptor-derived cells under glycolysis inhibition, endoplasmic reticulum stress, and glucose transporters (GLUTs) inhibited conditions, by measuring the fluorescence of fluorescently labeled deoxy-glucose analog using flow cytometry. Then, the intracellular behavior of GLUT1 and GLUT3 were observed in HeLa or 661W cells transfected with enhanced green fluorescent protein-GLUTs. Results: BCAAs recovered intracellular ATP levels during glycolysis inhibition and during citric acid cycle inhibition. BCAAs significantly increased glucose uptake and recovered decreased glucose uptake induced by endoplasmic reticulum stress or glycolysis inhibition. However, BCAAs were unable to increase intracellular ATP levels or glucose uptake when GLUTs were inhibited. Fluorescence microscopy revealed that supplementation of BCAAs enhanced the translocation of GLUTs proteins to the plasma membrane over time. Conclusions: BCAAs increase ATP production by promoting glucose uptake through promotion of glucose transporters translocation to the plasma membrane. These results may help expand the clinical application of BCAAs in retinal neurodegenerative diseases, such as glaucoma and retinal degeneration

コウリュウ ト タイワ オ トオシタ ガクナイ ノ レンケイ オ カンガエル : イブンカ コウリュウ ノ タイケン カラ ナニ オ マナブ ノカ ト ニホン ジジョウ IV ノ レンケイ

2011年後期より現在（2012年後期）まで徳島大学共通教育にて開講している「日本事情IV」と「異文化交流の体験から何を学ぶのか」の二つの授業を教師の連携によって実施した。留学生と日本人学生（社会人も含む）の協同学習（Peer learning）を実施するにあたって、互いの目的とその達成を確認しながら授業デザインを振り返り、この取り組みとその意義を確認することが可能となった。言い換えれば両者の協同学習を進めるための教師の協働を評価する試みである。教師の連携による授業の実施には、従来とは違った方法や内容の工夫等が、またそれぞれの学習者に対する目標の確認とそれらが達成されたかの検証が必要となった。この授業に関わった学生らの評価と教師の評価をもとに、今大学において必要とされる教育とは何か、そしてそれを具現化する内容とその方法を考えたものである。同時にFD活動として、教師の協働に対する示唆も行いたい。（本稿では2011年後期の実施内容を分析及び考察する。

Relationship between hemoglobin A1c and cardiovascular disease in mild-to-moderate hypercholesterolemic Japanese individuals: subanalysis of a large-scale randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although the ADA/EASD/IDF International Expert Committee recommends using hemoglobin A1c (HbA1c) to define diabetes, the relation between HbA1c and cardiovascular disease (CVD) has not been thoroughly investigated. We analyzed this relation using clinical data on Japanese individuals with hypercholesterolemia.</p> <p>Methods</p> <p>In the large-scale MEGA Study 7832 patients aged 40 to 70 years old with mild-to-moderate hypercholesterolemia without CVD were randomized to diet alone or diet plus pravastatin and followed for >5 years. In the present subanalysis of that study a total of 4002 patients with baseline and follow-up HbA1c data were stratified according to having an average HbA1c during the first year of follow-up <6.0%, 6.0%-<6.5%, or ≥6.5% and their subsequent 5-year incidence rates of CVD compared according to sex, low-density lipoprotein cholesterol (LDL-C), and treatment arm.</p> <p>Results</p> <p>Overall, risk of CVD was significantly 2.4 times higher in individuals with HbA1c ≥6.5% versus <6.0%. A similar relation was noted in men and women (hazard ratio [HR], 2.1; p <0.01 and HR, 3.0; p <0.01, respectively) and was regardless of treatment arm (diet alone group: HR, 2.2; p <0.001; diet plus pravastatin group: HR, 1.8; p = 0.02). Spline curves showed a continuous risk increase according to HbA1c level in all subpopulations studied.</p> <p>Conclusions</p> <p>In hypercholesterolemic individuals the risk of CVD increases linearly with HbA1c level. This significant contribution by elevated HbA1c to increased CVD is independent of pravastatin therapy, and thus requires appropriate HbA1c management in addition to lipids reduction.</p

キョウセイ シャカイ オ ササエル キョウヨウ キョウイク ノ カノウセイ I : パフォーマティブ ラーニング オ ドウニュウ スル

2011年度後期より現在（2014年度後期）まで徳島大学共通教育の「日本事情I・II（留学生対象科目）」と「異文化交流から学ぶグローバル化（前期）/異文化交流の体験から何を学ぶのか（後期）」の二つの授業を教師の連携によって実施している。教師の協働から留学生と日本人学生（社会人も含む）の協同学習を考え、大学という教育機関でのこのような取組みの必要性を「交流と対話を通した学内の連携を考える（2012）」にて考察した。活動を続ける上で、学生の協同学習及び主体的に取り組むというアクティブラーニングを模索しながら、2013年度後期からは演劇的アプローチを取り入れ、すなわちこれまでのスピーチによるプレゼンテーション活動に加えて最終課題を聴衆に向けて発表するパフォーマンス型の活動を取り入れた。インプロヴィゼーションによる準備活動から最終課題にいたるまでの経緯とともにパフォーマティブ・ラーニングを軸とした新たな教養教育の可能性を考えるものである。（本稿は2014年度前期の内容を対象とする。

Involvement of endothelins in neuroprotection of valosin-containing protein modulators against retinal ganglion cell damage

We have previously shown that Kyoto University Substances (KUSs), valosin-containing protein (VCP) modulators, suppress cell death in retinal ganglion cells of glaucoma mouse models through alterations of various genes expressions. In this study, among the genes whose expression in retinal ganglion cells was altered by KUS treatment in the N-methyl-D-aspartic acid (NMDA) injury model, we focused on two genes, endothelin-1 (Edn1) and endothelin receptor type B (Ednrb), whose expression was up-regulated by NMDA and down-regulated by KUS treatment. First, we confirmed that the expression of Edn1 and Ednrb was upregulated by NMDA and suppressed by KUS administration in mice retinae. Next, to clarify the influence of KUSs on cell viability in relation to the endothelin signaling, cell viability was examined with or without antagonists or agonists of endothelin and with or without KUS in 661W retinal cells under stress conditions. KUS showed a significant protective effect under glucose-free conditions and tunicamycin-induced stress. This protective effect was partially attenuated in the presence of an endothelin antagonist or agonist under glucose-free conditions. These results suggest that KUSs protect cells partially by suppressing the upregulated endothelin signaling under stress conditions

Detection Sensitivity of Retinitis Pigmentosa Progression Using Static Perimetry and Optical Coherence Tomography

Purpose: To compare the detection sensitivities of the progression of retinitis pigmentosa (RP) by automated perimetry to obtain the mean deviation (MD) and total point score and by optical coherence tomography (OCT) to determine the residual ellipsoid zone (EZ) length and thickness of retinal layers. Methods: Twenty-two eyes of 22 patients with RP who underwent annual automated perimetry (Humphrey Field Analyzer 10-2) and OCT examinations during the same period more than four times were included. Disease progression was evaluated using linear regression analysis with the least-squares method. The disease progression speed and interinspection fluctuations for the different examinations were compared using standardized values. The progression detection ability factor, defined as the average of the least squares divided by the square of annual change, was used to compare the sensitivities of the examinations for detecting the progression of RP. Results: EZ length showed a high correlation with MD (R = 0.87; P = 1.12E-07) at baseline. Disease progression was detected more frequently using EZ length (12/22 eyes) than using MD (3/22 eyes; P = 0.004) or central retinal thickness (1/11 eyes; P = 0.012). Linear regression using standardized values showed that the EZ length had the fastest annual change, with the smallest least absolute values. EZ length was more sensitive for detecting RP progression than MD, total point score, visual acuity, or central retinal thickness. Conclusions: EZ measurement was sensitive for detecting RP progression, and the results of this study indicate that EZ length is appropriate for end points in clinical trials. Translational Relevance: The study provides a basis for conducting future clinical trials

Expansion of retinal nerve fiber bundle narrowing in glaucoma: An adaptive optics scanning laser ophthalmoscopy study

Purpose: To investigate longitudinal changes in the retinal nerve fiber bundle in eyes with primary open angle glaucoma using adaptive optics scanning laser ophthalmoscopy. Methods: A prospective observational case series. Fourteen eyes from 12 patients with primary open angle glaucoma that exhibited retinal nerve fiber layer defects on fundus photography were imaged with adaptive optics scanning laser ophthalmoscopy over time. Results: The expansion of retinal nerve fiber bundle narrowing was observed on adaptive optics scanning laser ophthalmoscopy in 8 eyes (57.1%) over a period of 1.44 ± 0.42 years. Retinal nerve fiber bundle narrowing expanded horizontally in 2 eyes and vertically in 6 eyes. In 3 eyes, changes in the retinal nerve fiber layer were only detectable on adaptive optics scanning laser ophthalmoscopy images. Conclusions and Importance: The expansion of retinal nerve fiber bundle narrowing was observed using adaptive optics scanning laser ophthalmoscopy. Accordingly, this tool may be a useful tool for detecting glaucoma-related changes in retinal nerve fibers in a short time