フランス株式会社法と会社契約理論-株式会社における物的要素と人的要素についての一考察-

早大学位記番号:新7651早稲田大

Enantioselective disposition of clenbuterol in rats

Clenbuterol is a long-acting β2-adrenoceptor agonist and bronchodilator that is used for the treatment of asthma, but the desired activities reside almost exclusively in the (-)-R-enantiomer. This study examined enantioselectivity in the disposition of clenbuterol following administration of clenbuterol racemate to rats. Concentrations of clenbuterol enantiomers in plasma, urine and bile were determined by LC-MS/MS assay with a Chirobiotic T column. This method was confirmed to show high sensitivity, specificity and precision, and clenbuterol enantiomers in 0.1ml volumes of plasma were precisely quantified at concentrations as low as 0.25ng/ml. The pharmacokinetic profiles of clenbuterol enantiomers following intravenous and intraduodenal administration of clenbuterol racemate (2mg/kg) in rats were significantly different. The distribution volume of (-)-R-clenbuterol (9.17l/kg) was significantly higher than that of (+)-S-clenbuterol (4.14l/kg). The total body clearance of (-)-R-clenbuterol (13.5ml/min/kg) was significantly higher than that of the (+)-S-enantiomer (11.5ml/min/kg). An in situ absorption study in jejunal loops showed no difference in the residual amount between the (-)-R- and (+)-S-enantiomers. Urinary clearance was the same for the two enantiomers, but biliary excretion of (-)-R-clenbuterol was higher than that of the (+)-S-enantiomer. The fractions of free (non-protein-bound) (-)-R- and (+)-S-clenbuterol in rat plasma were 48.8% and 33.1%, respectively. These results indicated that there are differences in the distribution and excretion of the clenbuterol enantiomers, and these may be predominantly due to enantioselective protein binding. © 2013 John Wiley & Sons, Ltd.発行後1年より全文公

Forebrain Ptf1a Is Required for Sexual Differentiation of the Brain

The mammalian brain undergoes sexual differentiation by gonadal hormones during the perinatal critical period. However, the machinery at earlier stages has not been well studied. We found that Ptf1a is expressed in certain neuroepithelial cells and immature neurons around the third ventricle that give rise to various neurons in several hypothalamic nuclei. We show that conditional Ptf1a-deficient mice (Ptf1a cKO) exhibit abnormalities in sex-biased behaviors and reproductive organs in both sexes. Gonadal hormone administration to gonadectomized animals revealed that the abnormal behavior is caused by disorganized sexual development of the knockout brain. Accordingly, expression of sex-biased genes was severely altered in the cKO hypothalamus. In particular, Kiss1, important for sexual differentiation of the brain, was drastically reduced in the cKO hypothalamus, which may contribute to the observed phenotypes in the Ptf1a cKO. These findings suggest that forebrain Ptf1a is one of the earliest regulators for sexual differentiation of the brain

Gastrointestinal failure in intensive care: a retrospective clinical study in three different intensive care units in Germany and Estonia

BACKGROUND: While gastrointestinal problems are common in ICU patients with multiple organ failure, gastrointestinal failure has not been given the consideration other organ systems receive. The aim of this study was to evaluate the incidence of gastrointestinal failure (GIF), to identify its risk factors, and to determine its association with ICU mortality. METHODS: A retrospective analysis of adult patients (n = 2588) admitted to three different ICUs (two ICUs at the university hospital Charité-Universitätsmedizin Berlin, Germany and one at Tartu University Clinics, Estonia) during the year 2002 was performed. Data recorded in a computerized database were used in Berlin. In Tartu, the data documented in the patients' charts was retrospectively transferred into a similar database. GIF was defined as documented gastrointestinal problems (food intolerance, gastrointestinal haemorrhage, and/or ileus) in the patient data at any period of their ICU stay. ICU mortality, length of stay, and duration of mechanical ventilation were assessed as outcome parameters. RESULTS: GIF was identified in 252 patients (9.7% of all patients). Only 20% of GIF patients were identifiable at admission. GIF was related to significantly higher mortality (43.7% vs. 5.3% in patients without GIF), as well as prolonged length of ICU stay (10 vs. 2 days) and mechanical ventilation (8 vs. 1 day), p < 0.001, respectively. Patients' profile (emergency surgical or medical), APACHE II and SOFA scores and the use of catecholamines at admission were identified as independent risk factors for the development of GIF. Development of GIF during ICU stay was an independent predictor for death. CONCLUSION: Gastrointestinal failure represents a relevant clinical problem accompanied by an increased mortality, longer ICU stay and mechanical ventilation

メバカリ ・ テバカリ ニ ヨル ショクヒン ジュウリョウ スイソク ニ カンスル ケンキュウ

食品重量を的確に推測することは、栄養士にとって献立作成や栄養教育などの業務に必要な能力である。本研究では学年別に食品重量推測の比較を行った。対象者は本学食物栄養学専攻12B 生37 名、13B 生33 名、14B 生21 名、計91 名。調査方法は日常の食事で一般的によく食材として使用される10 種類の食品(きゅうり、じゃがいも、たまご、たまねぎ、トマト、にんじん、バナナ、ほうれん草、りんご、ロールパン)の重量を目ばかり・手ばかりにより推測させた。目ばかり・手ばかりの推測重量と実際重量から誤差率を算出し分析した。結果から12B 生、13B 生の学年比較では、1年半の専門授業を学習している2年生のほうが誤差率が低かった。13B 生、14B 生の学年比較では、1年半の専門授業を学習している2年生より半年間しか専門授業を学習していない1年生のほうが誤差率が低かった。昨年度の学年比較では2年生のほうが1年生よりよい結果がみられたが、今年度では逆転している結果となった。このことから、学年ごとの結果を比較することは、あまり意味がなくむしろ、その学年ごとに経時的にみて成績が上がっていることが大切であると感じた。また、14B 生の誤差率が低いことについては、14B 生からの試みとして各自スケール(デジタル台ばかり)を持たせ、常に食品の重さを量るよう指導しているため、その効果が現れたと考える。今後は食品の目ばかり・手ばかりの機会を増やし、日常から食品の慨量を意識させ、重量感覚を得られるような教育方法を考えていきたい