The leukocyte populations of periparturient dairy cows were analyzed after administration of active egg white/Clostridium butyricum Miyairi additive. Sixty-eight Holstein milking cows were divided into 3 groups. Group A was administered active egg white product (AEWP)/Clostridium butyricum Miyairi (Miyairi ) additive (n=23). Group B was administered Miyairi only (n=23), and Group C was the control group (n=22). The challenged groups were administered 100 g of AEWP + Miyairi , or Miyairi alone, daily for 60 days from 1 month before until 1 month after paturition. Blood samples were collected from all groups three times (1 month before, 1 week after and 1 month after parturition) for analysis of the peripheral leukocyte population. The results showed significantly higher numbers of CD4⁺ cells in Group A compared with Group C 1 week after paturition. AEWP/Miyairi additive may enhance the number of CD4⁺ T cells in periparturient dairy cows.

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Effects of R(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N, N-diethylamino)ethoxy]ethanol hydrochloride (T-) on normobaric hypoxia, histotoxic anoxia by KCN and complete ischemia by decapitation were investigated in mice. T- (30-100 mg/kg, p.o.) showed a significant and dose-dependent prolongation of the survival time in all of the models studied. Bifemelane (100-300 mg/kg, p.o.) was also protective against all the models. Tacrine was protective against hypoxia but had no effect on anoxia and ischemia. Imipramine was protective against anoxia, but shortened the survival time of hypoxic mice. It had no effect on ischemia. The anti-hypoxic effect of T- was completely inhibited by pretreatment with scopolamine (1 mg/kg, i.p.), while the anti-anoxic effect was partially inhibited. Its effect on the ischemia was not affected by scopolamine. Hypoxia decreased the cerebral contents of ATP, phosphocreatine and glucose and increased the contents of lactate in mice. T- had no effect on these changes. Bifemelane prolonged pentobarbital-induced sleeping time in mice with the doses inducing anti-anoxic action, but T- did not. These results suggest that the activation of the CNS cholinergic system is involved as one of the mechanisms for the anti-anoxic action of T-.

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The effects of (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-), a cognitive enhancer, on sodium nitroprusside (SNP)-induced cytotoxicity were examined in cultured rat astrocytes. Treatment with 100 μM SNP for 72 h decreased cell viability and mitochondrial function assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenil tetrazolium bromide (MTT) reduction activity, mitochondrial transmembrane potential, and intracellular ATP level. T- at 100 μM prevented SNP-induced mitochondrial dysfunction and cell injury. Furthermore, T- increased MTT reduction activity without affecting cell proliferation in astrocytes. These results suggest that T- has a protective effect against SNP-mediated toxicity via improvement of mitochondrial dysfunction in astrocytes.

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The present study examines the effect of the cognition enhancer (1R)-1-benzo[b]thiophen-5-yl-2-[2-(diethylamino)ethoxy]ethan-1-ol hydrochloride (T-) on neuronal injury induced by serum deprivation or amyloid-β protein (Aβ). T- protected partially against neuronal injury induced by serum deprivation or Aβ in cultured cortical neurons. T- did not affect the phosphorylation of extracellular signal-regulated kinase (ERK) in cortical neurons and SH-SY5Y cells. These results suggest that T- has a protective effect in neuronal injury models and the effect is not mediated by an ERK signal pathway.

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Previously, we reported that(R)−(−)−1−(benzo[b]thiophen−5−yl)−2−[2−(N, N−diethylamino)ethoxy]ethanol hydrochloride(T−), a novel putative cognitive enhancer, stimulated noradrenaline(NA)release from rat cerebral cortical slices.In this study, we investigated the effects of T− compared to other secretagogues on NA release from PC12 cells.Addition of as little as 10 μM T− stimulated [³H]NA release in a dose−dependent and an extracellular Ca²⁺−independent manner from PC12 cells.Ten micromolar ionomycin−, 300 μM adenosine−5′−O−(γ−thiotriphosphate)− and 10 μM forskolin−induced extracellular Ca²⁺−dependent [³H]−NA release was further enhanced by 30 μM T−.Cytosolic synaptophysin and 25−kDa synaptosome−associated protein immunoreactivity was increased by addition of T− in a dose−dependent manner.Interestingly, increases in synaptic vesicle−related proteins triggered by T− had a 4−min lag time and were completely dependent on extracellular CaCl₂.These findings suggest that T− stimulates NA release from PC12 cells in a Ca²⁺−independent manner.T− also induced the translocation of synaptic vesicles in a Ca²⁺−dependent manner.

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Previously, we reported that (R)-(-)-1-(benzo[b]thiophen-5-yl)-2-[2-(N, N-diethylamino)-ethoxy]ethanol hydrochloride (T-), a novel cognitive enhancer, stimulated noradrenaline (NA) release from rat cerebral cortical slices. In this study, we investigated the effects of T- on NA uptake and release, compared to the effects of desipramine, a blocker of the NA carrier on the plasma membrane. Both T- and desipramine caused dose-dependent inhibition of [³H]NA uptake into the slices. Addition of 3 mM T- stimulated [³H]NA release from the prelabeled slices even in the presence of 10 μM desipramine, which inhibited NA uptake completely. Tyramine, which accelerates NA carrier-mediated release, also stimulated [³H]NA release, and tyramine-stimulated release was inhibited by desipramine. These findings indicated that T--stimulated NA release was not mediated by 1) inhibition of reuptake or 2) reverse transport mediated by NA carriers. Reserpine, which interacts with the intracellular vesicular transport system, increased [³H]NA efflux from slices. High K⁺-, not T--, stimulated [³H]NA release was shifted upward by reserpine. These findings suggest that T- evokes NA release by a mechanism similar to that induced by reserpine. T- might act as a cognitive enhancer via neurotransmitter release in the brain.

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1. Two intermediary products of heme decomposition in the system of dicyanhematin-ascorbic acid-hydrogen peroxide were isolated. They were designated tentatively as - and 618-heme from their spectroscopic properties.
2. The millimolar extinction coefficients of dicyanhemochromes and dipyridine hemochromes derived from - and 618-heme purely isolated were determined as =14.73, ε⁵⁸⁰_mM=1 7.2, ε⁶¹⁸_mM=10.02, and ε⁶⁰⁸_mM=9.48.
3. By detachment of iron from these two hemes, - and 618-porphyrin were prepared and purified. Absorption maxima of -porphyrin dimethylester in 20 per cent HC1 solution were at 624, 573 and (520)mμ. Those of 618-porphyrin dimethylester were at (690), 643, and (540)mμ. In chloroform solution, -porphyrin showed its maxima at 640, 586, 554 and 514 mμ, while 618-porphyrin at 658, 605, 570 and 525mμ.
The spectroscopical properties of these two products and their de-rivatives are summarized in Table I.
4. No biliverdin nor its precursor could be obtained from -heme nor 618-heme in the system of their pyridine-hemochrome-ascorbic acid-hydrogen peroxide.
5. In the present reaction, -heme has been proved to be the immediate precursor of 618-heme.
The present work was aided in part by the grant of Scientific Research Fund of the Ministry of Education for which the authors wish to thank.

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生菌性整腸剤の効果に対する作用機序解明並びに実験的評価を目的として, 各種腸管病原菌と酪酸菌MIYAIRI 株を混合培養し, 経時的に菌数の増減を測定した. 腸管病原菌はいずれも患者由来株を使用し, 37℃ 嫌気培養を行った.
混合培養において酪酸菌は, コレラ菌・ナグビブリオ・アエロモナス・赤痢菌の発育を強く抑制した. 酪酸菌は主として消化管下部において発芽増殖するので赤痢菌との関連を更に追求し, 次のような結果を得た. (1) 赤痢菌をBHIbrothで嫌気培養すると培養終了時に培地のpHは5.2程度まで下がったが, 菌は順調に発育した. (2) 酪酸菌と混合培養するとpHは5.6程度で留まったが, 赤痢菌の発育は強く抑制された. (3) 酪酸菌24時間培養液はpH5.5前後であり, この上清中で赤痢菌は全く増殖できなかった. (4) この上清をNaOHでpH7.2に調製すると赤痢菌は新鮮培地におけると同様に増殖した. (5) 培養中のpHを6.0以上に維持させるため燐酸緩衝液を加えたBHIbrothでも混合培養によって赤痢菌の増殖は抑制された. この様な結果から, 酪酸菌による赤痢菌の発育抑制は, 培地のpH, 代謝産物など単一の要因によるものではなく, その両者及び酪酸菌そのものの存在が作用しあっているものと考えられた.

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The catalyst temperature was adjusted by changing the position of catalyst bed in the column reactor tube for the preparation of carbon nanotubes (CNTs) from methane using the microwave plasma technique. The maximum value of the carbon yield (80%) was obtained for a catalyst temperature of 794 K. CNTs grew at temperatures as low as K with this method. CNTs prepared at temperatures above 794 K were cylindrical and that of those prepared at K were herringbone type.

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Animal gastrointestinal tracts are populated by highly diverse and complex microbiotas. The gut microbiota influences the bioavailability of dietary components and is closely associated with physiological processes in the host. Clostridium butyricum reportedly improves growth performance and affects the gut microbiota and immune functions in post-weaning piglets. However, the effects of C. butyricum on finishing pigs remain unclear. Therefore, we herein investigated the effects of C. butyricum MIYAIRI

(CBM) on the gut microbiota of finishing pigs. 16S rRNA gene sequencing was performed using fecal samples and ileal, cecal, and colonic contents collected after slaughtering. The α-diversity of the small intestinal microbiota was lower than that of the large intestinal microbiota, whereas β-diversity showed different patterns depending on sample collection sites. The administration of CBM did not significantly affect the α- or β-diversity of the microbiotas of fecal and intestinal content samples regardless of the collection site. However, a linear discriminant ana­lysis Effect Size revealed that the relative abundance of Lactobacillaceae at the family level, Bifidobacterium at the order level, and Lactobacillus ruminis and Bifidobacterium pseudolongum at the species level were higher in the fecal samples and cecal and colonic contents of the treatment group than in those of the control group. Therefore, the administration of CBM to finishing pigs affected the composition of the gut microbiota and increased the abundance of bacteria that are beneficial to the host. These results provide important insights into the effects of probiotic administration on relatively stable gut microbial ecosystems.

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This study reports on the clinical application of gene therapy and oral administration of T- for laryngeal paralysis. The therapeutic effects of gene therapy in rat laryngeal paralysis studies have been demonstrated. Now, the development of a safe gene delivery system is the essential issue for realizing clinical application. Currently, we are investigating two gene delivery systems, Sendai virus vector and electroporation, for possible clinical use. Sendai virus (SeV), a negative strand RNA virus has no known pathogenicity to humans, and its strict cytoplasmic life cycle in mammalian cells may guarantee substantial safety for human gene therapy. We scrutinized the applicability and efficacy of Sev vectors expressing either LacZ or IGF-I in gene transfer into skeletal muscle tissue. Seven days after the intramuscular injection of LacZ/SeV, a large number of X-gal labeled myofibers were observed in the leg muscle of a rat. The introduction of IGF-I/SeV showed a significant increase in regenerating and split myofibers indicative of hypertrophy, and also an increase in the total number of myofibers. We also investigated the applicability of electroporation for gene transfer into rabbit laryngeal muscle tissue, using plasmid DNA expressing GEP. The laryngeal muscle were injected with the plasmid DNA and electric pulses were delivered. Five days after gene transfer, a large number of muscle fibers expressing GEP were observed. These results indicate that either SeV or electroporation may be used as a gene delivery system for human gene therapy for laryngeal paralysis. In addition to gene therapy, we are investigating whether orally administered T-, a neuroprotective agent, can be applied as a novel drug therapy for laryngeal paralysis. T- showed neuroprotective effects in a rat vagal nerve avulsion model as well as improvement in neurofunction in a rat recurrent nerve-injured model. These results support the applicability of T- for the treatment of laryngeal paralysis.

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弘前盆地浪岡町付近の大釈迦層からこけ虫化石を得たので報告する。9属11種を識別し記載した。古環境, 地史については, 従来の貝類, 腕足類化石の研究結果と何ら矛盾しない結論に達した。

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The influences of inert gas additives on the oscillation characteristics at 7, and 4, 924Å in the He-Zn hollow cathode laser were investigated using an improved laser tube. An increase in laser power at 7, Å has been observed at higher than normal optimum zinc vapor pressure, when xenon of nearly 1% to the optimum helium pressure (about 13 torr) is mixed. In view of the various spectroscopic examination, it is infered that the increase in laser output power at 7, Å is due to the enhancement of population density in the laser upper level (5p²P⁰_3/2) by Penning-type collision with enhanced He(n=3, 4) atom density, through some processes such as the second-kind collisions between the Xe(1s₅) metastable and zinc ground-state atoms and collisions between the Zn(4p³P⁰_{0, 2}) and He(2³S) metastable atoms. Also, it is to be considered that the decrease in threshold current at 4, 924 Å with the addition of krypton, especially in the relatively low zinc vapor pressure region, is attributable to an increase in zinc vapor density by the sputtering action of krypton ions.

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This paper deals with the recycling of bearing steel grinding swarf by high-density consolidation. The grinding swarf was compacted at the pressing pressure from 98 to MPa. The maximum density of 5.41 g/cm³ was obtained at the pressing pressure of MPa. Metal recovery rate that is one of the most important factors in metal recycling depended on the density of the grinding swarf briquet. The metal recovery rate of about 90% was obtained at the density of 4.8 g/cm³. Chemical compositions of original bearing steel (SUJ 2) and recycled metals obtained from melting of grinding swarf briquets in air and Ar were evaluated.

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6頭の乳牛を3頭ずつ,2つのグループ(A,B)に分け,グループーAの乳牛に対しては1日1頭当たり豆腐粕15kg,グルテン5kg,市販濃厚飼料1kg,麸1kg,砕麦1kgを80日間給与した.一方,グループーBの乳牛に対しては上記飼料にClostridium butyricum MIYAIRI の乾燥菌体粉朱(4.7×10⁹/g)1.5g,炭酸カルシュウム25gを混ぜて給与した.給餌前の第1胃ジュースを採取し,ジュースの中の乳酸桿菌と大腸菌群の菌数を定期的に調べた.その結果,グループ-Bの乳牛において乳酸桿菌は試験開始後有意に増加し,大腸菌群数は減少する傾向が認められた、なお,第1胃内でのCl.butyricum MIYAIRI の菌数も試験開始後増加の傾向を示したが,下痢等の病状は全く認められず,第1胃内での揮発姓脂肪酸と乳酸の含量が一定になる傾向を示した.さらに,グループ-Bの乳牛から得られた牛乳中にはCl. butyricum MIYAIRI は全く検出されず,またその牛乳を用いてゴーダタイプのチーズを製造した場合,熟成率や熟成中のスターター乳酸菌の変動は対照チーズの場合と変わらなかった.
以上より,Cl. butyricum MIYAIRI の乳牛に対する給与は第1胃内での菌叢の改善に効果のあることが明らかとなった.

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The title compound (T-) has been evaluated for its ameliorating effect on memory impairment generated by cerebral embolization and by a basal forebrain (BF) lesion in male Wistar rats. The memory and learning deficits induced by injection of carbon-microspheres into the internal carotid artery were significantly improved by T- at oral dose of 3-10 mg/kg, as determined by an active avoidance response assay, whereas the reference drugs (tacrine, idebenone and indeloxazine) proved almost inactive in the same assay procedure. As far as the embolization was concerned, a significant decrease in cerebral acetylcholine and monoamines was observed. The effect on the memory impairment caused by an electrolytic lesion of the BF was assessed by a passive avoidance task. T- exhibited a bell-shaped dose-response curve and was most active at 1 mg/kg (oral dose), while tacrine showed equal activity at 10 mg/kg.

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