Hypotaurine is an Energy-Saving Hepatoprotective Compound against Ischemia-Reperfusion Injury of the Rat Liver

Metabolome analyses assisted by capillary electrophoresis-mass spectrometry (CE-MS) have allowed us to systematically grasp changes in small molecular metabolites under disease conditions. We applied CE-MS to mine out biomarkers in hepatic ischemia-reperfusion. Rat livers were exposed to ischemia by clamping of the portal inlet followed by reperfusion. Metabolomic profiling revealed that l contents of taurine in liver and plasma were significantly increased. Of interest is an elevation of hypotaurine, collectively suggesting significance of hypotaurine/taurine in post-ischemic responses. Considering the anti-oxidative capacity of hypotaurine, we examined if supplementation of the compound or its precursor amino acids could affect hepatocellular viability and contents of taurine in liver and plasma. Administration of hypotaurine, N-acetylcysteine or methionine upon reperfusion comparablly attenuated the post-ischemic hepatocellular injury but with different metabolomic profiling among groups: rats treated with methionine or N-acetylcysteine but not those treated with hypotaurine, exhibited significant elevation of hepatic lactate generation without notable recovery of the energy charge. Furthermore, the group treated with hypotaurine exhibited elevation of the plasma taurine, suggesting that the exogenously administered compound was utilized as an antioxidant. These results suggest that taurine serves as a surrogate marker for ischemia-reperfusion indicating effectiveness of hypotaurine as an energy-saving hepatoprotective amino acid

Functional localization and effective connectivity of cortical theta and alpha oscillatory activity during an attention task

Objectives: The aim of this paper is to investigate cortical electric neuronal activity as an indicator of brain function, in a mental arithmetic task that requires sustained attention, as compared to the resting state condition. The two questions of interest are the cortical localization of different oscillatory activities, and the directional effective flow of oscillatory activity between regions of interest, in the task condition compared to resting state. In particular, theta and alpha activity are of interest here, due to their important role in attention processing. Methods: We adapted mental arithmetic as an attention ask in this study. Eyes closed 61-channel EEG was recorded in 14 participants during resting and in a mental arithmetic task (“serial sevens subtraction”). Functional localization and connectivity analyses were based on cortical signals of electric neuronal activity estimated with sLORETA (standardized low resolution electromagnetic tomography). Functional localization was based on the comparison of the cortical distributions of the generators of oscillatory activity between task and resting conditions. Assessment of effective connectivity was based on the iCoh (isolated effective coherence) method, which provides an appropriate frequency decomposition of the directional flow of oscillatory activity between brain regions. Nine regions of interest comprising nodes from the dorsal and ventral attention networks were selected for the connectivity analysis. Results: Cortical spectral density distribution comparing task minus rest showed significant activity increase in medial prefrontal areas and decreased activity in left parietal lobe for the theta band, and decreased activity in parietal-occipital regions for the alpha1 band. At a global level, connections among right hemispheric nodes were predominantly decreased during the task condition, while connections among left hemispheric nodes were predominantly increased. At more detailed level, decreased flow from right inferior frontal gyrus to anterior cingulate cortex for theta, and low and high alpha oscillations, and increased feedback (bidirectional flow) between left superior temporal gyrus and left inferior frontal gyrus, were observed during the arithmetic task. Conclusions: Task related medial prefrontal increase in theta oscillations possibly corresponds to frontal midline theta, while parietal decreased alpha1 activity indicates the active role of this region in the numerical task. Task related decrease of intracortical right hemispheric connectivity support the notion that these nodes need to disengage from one another in order to not interfere with the ongoing numerical processing. The bidirectional feedback between left frontal-temporal-parietal regions in the arithmetic task is very likely to be related to attention network working memory function. Significance: The methods of analysis and the results presented here will hopefully contribute to clarify the roles of the different EEG oscillations during sustained attention, both in terms of their functional localization and in terms of how they integrate brain function by supporting information flow between different cortical regions. The methodology presented here might be clinically relevant in evaluating abnormal attention function

Dynamic 13C Flux Analysis Captures the Reorganization of Adipocyte Glucose Metabolism in Response to Insulin.

Cellular metabolism is dynamic, but quantifying non-steady metabolic fluxes by stable isotope tracers presents unique computational challenges. Here, we developed an efficient 13C-tracer dynamic metabolic flux analysis (13C-DMFA) framework for modeling central carbon fluxes that vary over time. We used B-splines to generalize the flux parameterization system and to improve the stability of the optimization algorithm. As proof of concept, we investigated how 3T3-L1 cultured adipocytes acutely metabolize glucose in response to insulin. Insulin rapidly stimulates glucose uptake, but intracellular pathways responded with differing speeds and magnitudes. Fluxes in lower glycolysis increased faster than those in upper glycolysis. Glycolysis fluxes rose disproportionally larger and faster than the tricarboxylic acid cycle, with lactate a primary glucose end product. The uncovered array of flux dynamics suggests that glucose catabolism is additionally regulated beyond uptake to help shunt glucose into appropriate pathways. This work demonstrates the value of using dynamic intracellular fluxes to understand metabolic function and pathway regulation

Lactate production is a prioritized feature of adipocyte metabolism

Adipose tissue is essential for whole-body glucose homeostasis, with a primary role in lipid storage. It has been previously observed that lactate production is also an important metabolic feature of adipocytes, but its relationship to adipose and whole-body glucose disposal remains unclear. Therefore, using a combination of metabolic labeling techniques, here we closely examined lactate production of cultured and primary mammalian adipocytes. Insulin treatment increased glucose uptake and conversion to lactate, with the latter responding more to insulin than did other metabolic fates of glucose. However, lactate production did not just serve as a mechanism to dispose of excess glucose, because we also observed that lactate production in adipocytes did not solely depend on glucose availability and even occurred independently of glucose metabolism. This suggests that lactate production is prioritized in adipocytes. Furthermore, knocking down lactate dehydrogenase specifically in the fat body of Drosophila flies lowered circulating lactate and improved whole-body glucose disposal. These results emphasize that lactate production is an additional metabolic role of adipose tissue beyond lipid storage and release

MMMDB: Mouse Multiple Tissue Metabolome Database

The Mouse Multiple Tissue Metabolome Database (MMMDB) provides comprehensive and quantitative metabolomic information for multiple tissues from single mice. Manually curated databases that integrate literature-based individual metabolite information have been available so far. However, data sets on the absolute concentration of a single metabolite integrated from multiple resources are often difficult to be used when different metabolomic studies are compared because the relative balance of the multiple metabolite concentrations in the metabolic pathways as a snapshot of a dynamic system is more important than the absolute concentration of a single metabolite. We developed MMMDB by performing non-targeted analyses of cerebra, cerebella, thymus, spleen, lung, liver, kidney, heart, pancreas, testis and plasma using capillary electrophoresis time-of-flight mass spectrometry and detected 428 non-redundant features from which 219 metabolites were successfully identified. Quantified concentrations of the individual metabolites and the corresponding processed raw data; for example, the electropherograms and mass spectra with their annotations, such as isotope and fragment information, are stored in the database. MMMDB is designed to normalize users’ data, which can be submitted online and used to visualize overlaid electropherograms. Thus, MMMDB allows newly measured data to be compared with the other data in the database. MMMDB is available at: http://mmmdb.iab.keio.ac.jp

Insulin signaling requires glucose to promote lipid anabolism in adipocytes

Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride–glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo. Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism

言語聴覚療法におけるリスクマネジメントと養成校での教育

研究報告Original Paper医療現場におけるリスクマネジメントの重要性が認識され、多くの病院で医療事故防止のためのアプローチが試みられているが、言語聴覚士は資格制定からの日が浅く、養成校では言語聴覚療法そのものに関する教育のみに主眼が置かれ、医療安全に関する教育は十分とは言えない状況である。日本言語聴覚士協会の調査によれば、事故、ヒヤリハット、苦情、不満等を体験した回答者は83%に上り、事例の具体的記載内容では身体的危害に関するものが70%、患者との人間関係に関するものが27%であった。言語聴覚士にとってのリスクは、基本的な業務遂行上の問題、情報伝達・人間関係・守秘義務に関する問題、専門的臨床能力に関する問題、全般的な安全に関する問題に分類された。養成校におけるリスクマネジメント教育は、個々の専門科目のシラバスの改訂、臨床実習手引書の改訂と実習前教育、当該科目の新設によって改善が図られるべきである。As the importance of risk management in medical field has been emphasized these days, various kinds of approaches have been taken to help prevent medical incidents and accidents in many hospitals. It is only several years since the national law of the certification system of speech-language-hearing therapists was established, so education for those therapists at institutes tended to be focused on professional skill, not on medical safety. A survey organized by Japanese association of speech-language-hearing therapists showed that 83% of respondents had experienced accidents, incidents and complaints by their patients. 70% of specific instances of what they had experienced were concerned with physical damages and 27% of them were concerned with human relationships. The risk in speech-language-hearing therapy was assorted into four types of problems, 1) basic performance, 2) communication, human relationship and confidentiality, 3) professional ability and 4) general safety, which were then examined. We concluded that risk management education had to be improved by revising each syllabus of professional subjects, by amending each guidebook for clinical practice, by guiding students just before carrying out that practice and by setting up new subjects

「きこえとことばの相談室」報告

実践報告Practical report　言語聴覚学科は，学生に対する臨床教育を目的に，2009 年3 月に「きこえとことばの相談室」（以下:相談室）を開設した．2009 年3 月の開設から2014 年10 月末までの相談室の活動実績は，新規数：63名，継続数：53 名．総臨床件数612 件．臨床実数は，100 ～ 120 件で定着していた．開設当初の目的であった演習協力には至っていないが，教育活動，研究活動，臨床指導等に貢献している．今後は，言語聴覚療法の対象障害の拡大（失語症等），教育及び地域貢献の一環としての発展が望まれる．　In the Division of Speech-Language-Hearing Therapy, we established an outpatient counselingroom for hearing and language therapy in March of 2009 with the aim of providing clinical education for the students. From March 2009 to end of October 2014, the total numbers of counselings amounted 612 cases (63 new cases, 53 follow-up cases). The number of clinical cases was stable, between 100 and 120. Although it had little therapeutic impact, which was its original purpose, it has been contributing to education and research work. We expect it to expand to include disorders of speech-language-hearing therapy such as aphasia, etc., and as a part of the educational and regional contribution