Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：岡山大学教師教育開発センター  

子どもの多様な健康課題に対応して，学校における安全・安心な環境の確保や子どもの心身の健康を守り，はぐくむことのできる体制構築が求められる今日，教育実習等においては，実習生を学校保健に対する関心・理解を高め，子どもの健康・安全な学校生活を考慮した教育活動を展開できる教員として育成することが重要となる。そこで，教育実習等の機会に附属学校園養護教諭が，学校保健活動を遂行できる教員養成を目的とした講義・演習を実施した。その結果，実習生は学校保健に対する認識を高めることができた。附属学校園養護教諭が教員養成に積極的に参画することは，学校保健活動を遂行できる教員養成に果たす役割が大きいといえる。

DOI： 10.18926/CTED/53243

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：岡山大学大学院教育学研究科  

この研究では，小学校の通学区域を国勢調査結果や住民基本台帳データのうち小学校の通学区域（学区）別に編纂されているものを用いてそれらの類型化を試み，その結果を地図上に表現した。そのような類型が生じる背景にある人口学的な性質を考察し，学校ごとに濃淡がある児童生徒の種々の健康課題について，日常生活における背景を考察するためのツールとしての可能性に言及した。

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本学校保健学会  

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Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：岡山大学環境管理センター  

Nowadays,we experience severe hot climate during summer.Ambient temperature and wet bulb globe temperature (WBGT) in our gymnasium designed for dance lessons exceeded exposure limits of both school health and industrial health. Such environment was our direct concern for risk of heat related disorders among students, guests and staffs using the facility. The building was old, and heat insulation seemed to be insufficient compared to recent standards for the building of the same kind. Introduction of a new air conditioning system to the facility was supposed to be avoided according to energy conservation policy. We considered that applying high-albedo paint to the roof would reflex the solar infrared irradiation and block the heat influx, thus lowering the ambient temperature inside the gymnasium. The renovation of the roof resulted in improved ambient temperature and WBGT. We concluded that application of high-albedo paint might be a useful technique to control high ambient temperature in similar buildings and to reduce risk of heat related disorders.

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Language：Japanese   Publisher：日本養護教諭教育学会  

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (bulletin of university, research institution)   Publisher：岡山大学大学院教育学研究科  

熱中症予防対策に使用する目的で,湿球黒球温度を自動的に連続して測定･記録できる簡便な装置を試作した｡この装置を本学グラウンドに設置し,2008年夏季の暑熱環境の測定を行った結果に若干の考察を加えて報告した。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

In the present study, we examined the dynamic of school-health-based parasite control and the related socio-economic influences. This is an ecological study based on data from 46 prefectures in Japan. The exponential decay of Ascaris lumbricoides prevalence was calculated by iterative least-squares method. Pearson's correlation and multiple linear regression model analysis were performed to assess the associations between the prevalence of Ascaris lumbricoides in Japanese school children and socio-economic variables such as the prefecture income per capita, the percentage of primary industry, the population density per 1 km2, the diffusion rate of population under water supply, and the percentage of upper secondary school enrollment. The results indicated that the parasite carrier rate was higher in younger students. The half-life of Ascaris lumbricoides prevalence was approximately 3 years with significant variation among prefectures. Multiple regression analyses showed that the decrease of infection in elementary and lower secondary school children had a significant positive association with primary industry and a significant negative association with prefecture income per capita. The school-health-based parasite intervention differs by prefecture and has changed over time according to the respective prefectural stage of economic development.

DOI： 10.18926/AMO/30970

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Authorship：Lead author   Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：厚生統計協会  

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：厚生統計協会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

The morbidity of diabetes mellitus is increasing gradually in Japanese populations. It is important to clarify the risk factors of diabetes in Japanese populations in order to take adequate measures against the increasing morbidity of diabetes. In order to evaluate the link between past and concurrent obesity and diabetes in middle-aged Japanese men, we conducted a worksite-based historical cohort study in Okayama, Japan in 1999. Annual health examination data of middle-aged male workers in a worksite were collected. The relative risks of past and concurrent obesity for developing diabetes were calculated. Subjects with a past history of obesity at between 40 and 50 years of age had a significantly higher risk of developing diabetes by age 55 than did subjects in the normal weight group. These results suggest that, in order to prevent diabetes in middle-aged Japanese men, health guidance for normal weight maintenance should be provided not only for middle-aged men, but also for men under age 40.

DOI： 10.18926/AMO/31704

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC OCCUPATIONAL HEALTH  

Organic solvents generally depress the central nervous system (CNS), similarly to volatile anesthetics. The precise mechanism of their action on the CNS, however, is not fully understood, and remains to be clarified. This study is focused on how inhaled m-xylene distributes in the brain, and whether region specific change in GABA A receptor binding takes place due to the exposure. To conduct this study, we first developed a simple exposure system suitable for inhalation experiments with small animals. Using this system, six-week-old male Sprague-Dawley rats were exposed to m-xylene vapor (2000 ppm) 4 h/d, for 5 consecutive days. At the end of the exposure, m-xylene levels in four different regions of the brain were measured by head-space gas chromatography. Also 14 mum-thick frozen sections of the brain were made, and [S-35] t-butylbicyclophosphorothionate (TBPS) binding autoradiography was performed. Uneven distribution of m-xylene in the brain was observed. The concentration in the cerebellum (976+/-93.4 mug/g tissue) was the highest, while that in the cerebral cortex (467+/-43.6 mug/g tissue) was the lowest. [S-35]TBPS binding was significantly greater in the molecular layer of the cerebellum (control: 12.6+/-0.64, m-xylene 16.0+/-1.34 fmol/mg tissue). These results suggest that m-xylene is distributed unevenly in the rat brain, and acute exposure to m-xylene at a high concentration alters [S-35]TBPS binding, which may reflect changes in GABA A receptor characteristics.

DOI： 10.1539/joh.44.69

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Recent animal studies regarding phencyclidine (PCP), which induces psychotic symptoms in humans, have suggested that g-roup II metabotropic glutamate receptors (mGluRs) represent a novel target for the treatment of PCP psychosis. In the present study, we used in situ hybridization to investigate the gene expressions of the mGluR 1-5 subtypes following single and repeated administration of PCP in rats. A single administration Of PCP (7.5mg/kg, i.p.,) resulted in a significant decrease in the mGluR5 inRNA expression of group I inGluR in the subcortical regions (thalamus (-15%), central gray (-23%), inferior colliculus (-23%), and nucleus accumbens (-10%)) and hippocampal formation (CA1 (-14%), CA2 (-15%), CA3 (-18%), and dentate gyrus (-18%)). After repeated PCP administration for 14 days,, the mGluR2 inRNA expression of group II inGluR in the anterior cingulate cortex (-23%) and the mGluR4 mRNA expression of group III mGluR in the cortical regions (parietal (-11%), temporal (-13%) and entorhinal cortices (-18%)), the caudate putamen (-12%), thalamus (-17%), and subiculum (-25%) were significantly decreased. These results indicate that PCP affects not only group II mGluR but also group I and III of mGluR, and it is of particular interest that mGluR2 subtype is involved in a development of behavioral abnormality following repeated PCP administration. Single and repeated administrations of PCP independently regulate the expression of mGluR subtypes of mRNA in the brain. [Neuropsychopharmacology 25:173-184,2001] (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc.

DOI： 10.1016/S0893-133X(00)00250-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

The effects of intermittent intraperitoneal (i.p.) administration of cocaine (20 mg/kg) on GABA(A)-benzodiazepine (BZD) receptors labeled by t-[S-35]butylbicyclophosphorothionate (TBPS), and on several types of mRNA subunits were investigated in rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. Phosphor screen imaging with high sensitivity and a wide linear range of response was utilized for imaging analysis. There was a significant decrease in the level of alpha 1, alpha 6, beta 2, beta 3, and gamma 2 subunits mRNA, with no alteration of [S-35]TBPS binding in any regions in the brain of rats at 1 h following a single injection of cocaine. In chronically treated animals, the mean scores of stereotyped behavior were increased with the number of injections, The level of beta 3 subunit mRNA was decreased in the cortices and caudate putamen, at 24 h after a final injection of chronic administrations for 14 days. In the withdrawal from cocaine, the frontal cortex and hippocampal complexes showed a significant increase in [S-35]TBPS binding and alpha 1 and beta 3 subunit mRNA in the rats 1 week after a cessation of chronic administration of cocaine; These findings suggest that the disruption of GABA(A)-BZD receptor formation is closely involved in the development of cocaine-related behavioral disturbances. Further studies on the physiological functions on GABA(A)-BZD receptor complex will be necessary for an explanation of the precise mechanisms underlying the acute effects, development of hypersensitization, and withdrawal state of cocaine. (C) 2000 Wiley-Liss, Inc.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER-VERLAG  

DOI： 10.1007/s001280000170

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

We investigated the time-course effects of a single administration of cocaine (20 mg/kg) on GABA(A) receptor binding labeled by t- [35S]butylbicyclophophorothionate (TBPS) and on several types of GABA(A) receptor subunit mRNAs in the rat brain by in vitro quantitative receptor autoradiography and in situ hybridization. The levels of α1, β2, and β3 subunit mRNAs in several brain regions such as the cortex, cerebellum, and striatum were significantly decreased within 1 h, while β3 subunit mRNA was increased in the dentate gyrus. All of these changes were transient, occurring within 1 h after the injection of cocaine. In the cortex and cerebellum, the reduction in α1 subunit mRNA was followed by a significant decrease in [35S]TBPS receptor binding, which occurred 4 h after cocaine injection. These findings suggest that acute cocaine administration discretely regulates GABA(A) receptor subunit mRNA levels in several brain regions through a change in transcription or turnover rates of subunit mRNAs, which may be closely related to cocaine-induced behavioral abnormalities. (C) 2000 Elsevier Science B.V.

DOI： 10.1016/S0169-328X(00)00166-2

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DOI： 10.1007/s001289900573

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier Ltd  

The effect of hyperbaric oxygenation on arginine metabolism was investigated. Rats were exposed to oxygen at 3 atmospheres absolute for 2 h. Under these conditions, lipid peroxidation and activation of the anti-oxidant system were observed. Levels of thiobarbiturate reactive substances and carbon-centered radicals were increased in the cerebral cortex, while superoxide dismutase activity was also increased in the mitochondrial and cytosolic fraction of cerebrocortical homogenates. This suggested that the increase of both Mn and Cu,Zn-superoxide dismutase activities was probably an early compensatory reaction to oxidative stress. Levels of arginine as well as its metabolite, guanidinoacetic acid, were increased in the cerebral cortex. This increase seemed to be, at least in part, explained by a decrease in the arginase activity in the same region. Moreover, arginase activity in the brain showed heterogeneous distribution. Arginine: glycine amidinotransferase activity was decreased in the pons-medulla oblongata. The observed effects of hyperbaric oxygenation seem to favor nitric oxide generation.

DOI： 10.1016/0197-0186(95)00119-0

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Barbiturates are central nervous system depressants that are used as sedatives, hypnotics, anesthetics and anticonvulsants. However, prolonged use of the drugs produces physical dependence, and the drugs have a high abuse liability. The gamma-aminobutyric acid, (GABA(A)) receptor is one of barbiturates' main sites of action, and therefore it is thought to play a pivotal role in the development of tolerance to and dependence on barbiturates. Recent advances in the study of the GABA(A) receptor/chloride channel complex allow us to examine possible mechanisms that underlie barbiturate tolerance/dependence in a new light. In this minireview, we mainly focus on molecular and cellular aspects of the action of barbiturates and the possible mechanisms that contribute to development of tolerance to and dependence on barbiturates.

DOI： 10.1016/0024-3205(96)00199-3

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In order to study the chronic effects of pentobarbital, a positive GABAA receptor modulator, on the inverse agonist binding of the benzodiazepine site, binding of [3H]Ro15-4513 and levels of GABAA receptor alpha 6-subunit mRNA were investigated in the brains of pentobarbital-tolerant/dependent animals, using receptor autoradiography and in situ hybridization histochemistry in consecutive brain sections. Pentobarbital was administered to rats either 60 mg/kg, i.p., once, for acute treatment, or 300 micrograms/10 microliters/h i.c.v. continuously for 6 days via osmotic minipumps to render rats tolerant to pentobarbital. Rats assigned to the dependent group were sacrificed 24 h after discontinuance of pentobarbital infusion, while those assigned to the tolerant group were sacrificed at the end of infusion. The alpha 6 subunit mRNA was increased in the tolerant group only. Diazepam-insensitive [3H]Ro15-4513 binding was increased in the cerebellar granule layer of pentobarbital-tolerant and -dependent rats. No alterations in these parameters were observed in acutely treated animals. These data suggest that chronic pentobarbital treatment induced expression of alpha 6-subunit mRNA. This was in contrast to alpha 1- and gamma 2-subunit mRNA, which in tolerant animals are unchanged, but for which withdrawal triggers a surge in levels. Because the alpha 6-subunit is a major component of the diazepam-insensitive [3H]Ro15-4513 binding site, the increased diazepam-insensitive [3H]Ro15-4513 binding implied de novo synthesis of the receptor subunit protein.

DOI： 10.1002/(SICI)1098-2396(199602)22:2<106::AID-SYN3>3.0.CO;2-H

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A new technique of image acquisition for quantitative receptor autoradiography and in situ hybridization histochemistry was developed using storage phosphor screen imaging. This method was at least 4-5 times faster than conventional film densitometry. Two of the advantages of the phosphor screen method are high sensitivity and wide linear range of response. Other aspects of this method were compared with those of conventional densitometry. Use of storage phosphor screen imaging will allow greatly increased speed of pharmacological screening procedures that utilize quantitative autoradiography.

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Authorship：Last author   Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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Language：Japanese   Publisher：(一社)日本衛生学会  

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The increase in lipid peroxide levels in mice brain following Fe 3+ administration was about 50% of that when 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was administered. This may be due to excessive oxidation by Fe3+, and was supported by the decrease in activities of antioxidant enzymes, such as superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX), Na+,K+-ATPase activity and membrane fluidity after Fe3+ administration. Relatively low-dose X-ray irradiation (0.5 Gy) inhibited lipid peroxidation associated with Fe 3+ administration and restored the decreased activities of the above antioxidant enzymes and Na+K+-ATPase, and membrane fluidity to the levels in the non-Fe3+-administered group. In the purine metabolism system, uric acid decreased after Fe3+ administration, which may be due to transient impairment of the system for production of uric acid from xanthine by excessive oxidation by Fe3+. However, 0.5 Gy irradiation inhibited this decrease in uric acid, increasing its level to that in the non Fe3+-administrated group. This may be due to factors such as rapid recovery of the activities of the above antioxidant enzymes and Na+,K+-ATPase, and membrane fluidity after 0.5 Gy irradiation. In addition, since no changes were observed in xanthine and uric acid, increased inosine and hypoxanthine may have advanced to a salvage pathway leading to not xanthine but inosine 5′-monophosphate (IMP).

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：厚生統計協会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS INC  

The solubility of benzo(a)pyrene (BaP) in water is small, and measured total BaP concentration (t-BaP) in fresh water is the sum of BaP dissolved in water (d-BaP) and BaP adsorbed to suspended solids (p-BaP). We have collected fresh water samples in a lake and rivers in Okayama Prefecture, Japan, and measured both d-BaP and p-BaP in each sample. The blue rayon method or solid-liquid extraction was used for extraction of BaP in water or in suspended solids, respectively. The measurement of BaP was done using high-performance liquid chromatography according to our previously reported method. The present data indicate that p-BaP was about 1.5 to 5 times higher than d-BaP. In general, the amount of suspended solids in each sample did not show a correlation to p-BaP. These results suggest that BaP adsorbed to suspended solids must be taken into account when assessment of t-BaP is done in any given fresh water sample. (C) 2000 by John Wiley & Sons, Inc.

DOI： 10.1002/1522-7278(2000)15:5<500::AID-TOX19>3.0.CO;2-E

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Recent biochemical observations have suggested the abnormalities in the gamma-amino-butyric acid (GABA)ergic system in schizophrenic brains. In the present study, we investigated the subunits gene expressions and ligand binding of the GABA(A) receptor following acute and chronic administration of phencyclidine (PCP), which induces schizophrenia-like symptoms, in rats using in situ hybridization and in vitro quantitative autoradiography. PCF i.p. administration at a daily dose of 7.5 mg/kg resulted in a significant decrease in expression of alpha 1 subunit mRNA in cerebral cortices (cingulate (-13%) and temporal cortex (-6%)) and hippocampal formation (CA1 (-11%), CA2 (-10%), CA3 (-11%) and dentate gyrus (-1.2%)) 1 h after a single treatment. In the repeated PCP administrations for 14 days, the expression of beta 2 mRNA in the cerebellum (-10%) and of beta 3 mRNA in the cerebral cortices (cingulate (-12%), parietal (-16%) and temporal cortex (-16%), caudate putamen (-18%), inferior colliculus (-18%), and cerebellum (-15%) were significantly decreased. In addition, [S-35] t-butylbicyclophosphorothionate (TBPS) binding was also reduced in layer IV of the frontoparietal cortex (-14%), inferior colliculus (-17%), and cerebellum (-12%) following chronic PCP treatment, while no changes were observed following acute PCP treatment. These results indicate that single and repeated administrations of PCP independently regulate the expression of GABA(A)/benzodiazepine (BZD) receptor subunits mRNA and its receptor binding in the brain. Synapse 38:51-60, 2000. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/1098-2396(200010)38:1<51::AID-SYN6>3.0.CO;2-A

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ELSEVIER SCIENCE BV  

The effects of single and repeated administration of cocaine on mRNA subunits of glutamate receptors were investigated in the rat brain by in situ hybridization. A significantly increased level of NMDAR1 subunits mRNA in the hippocampus was seen 1hr after a single injection of cocaine. Repeatedly treated-rats showed a decreased level of NMDAR1 subunit mRNA in the cortices, striatum, nucleus accumbens and ventral pallidum, and an increased level in the dentate gyrus 24 hrs after a final injection of chronic administration. During cocaine withdraw al, thecortes, striatum, hippocampus and cerebellum showed a significantly decreased level of NMDAR1 and mGluR5 subnuit mRNAs. These findings suggest that a reduction in glutamate receptor subunit mRNA level may reflect a compensatory don:regulation related to enhanced glumate transmission during sensitized and withdrawal state.

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：ELSEVIER SCIENCE BV  

To investigate the effects of phencyclidine (PCP) on N-methyl-d-aspartate (NMDA) receptors, we examined the effects of both single and repeated administrations of PCP on the NMDA receptor subunits in rat brain using in situ hybridization. Intraperitoneal (i.p.) administration of a daily dose of 7.5mg/kg PCP resulted in significantly decreased in expression of NMDAR2A subunit mRNA in the cingulate cortex Ih after a single administration. Repeated PCP administrations for 14 days resulted in significantly decreased the expression of NMDAR1(-) mRNA in the nucleus accumbens and piriform cortex. These results suggest that region-specific decreases of NMDA receptor subunits may represent a compensatory response to enhanced glutamate availability in the limbic region.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS INC  

Blue rayon, an adsorbent selective to compounds having three or more fused rings, for detecting benzo(a)pyrene and measuring mutagenicity was used in Lake Baikal (Russia), Asahi River, Sasagase River, and Lake Kojima (Okayama, Japan). One gram of blue rayon was immersed in 1 L of water in a bottle, and manually shaken for 30 min. The blue rayon was recovered and transported to the laboratory where the analyses for benzo(a)pyrene and the mutagenicity assay were performed. The recovered benzo(a)pyrene from the water sample ranged from 0.13 to 0.65 ng/L for take Baikal and from 0.13 to 1.41 ng/L for the rivers and the lake in Okayama. Six samples out of 11 from Lake Baikal showed positive but weak mutagenicity. No mutagenicity was found in the samples from the rivers and the lake in Okayama. The present method allows easy sampling at remote sites because there is no need for transporting voluminous water samples to the place where analysis is performed. (C) 1999 by John Wiley & Sons, Inc.

DOI： 10.1002/(SICI)1522-7278(199905)14:2<279::AID-TOX9>3.0.CO;2-P

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We examined changes in benzodiazepine binding sites labeled by [3H]flunitrazepam in five nuclei of the thalamus, the central medial, central lateral, intermediodorsal, ventroposterior, and laterodorsal nuclei, in rats made tolerant to and dependent on pentobarbital. Animals were made tolerant by intracerebroventricular infusion with pentobarbital (300 μg (10 μl)-1 h-1 for six days) through pre-implanted cannulae. Pentobarbital dependence was assessed 24 h after abrupt withdrawal from pentobarbital. Pentobarbital-tolerant rats showed no significant change in [3H]flunitrazepam binding sites (B(max) and K(d)) in any nucleus examined in the thalamus. In the rats made dependent on pentobarbital, significant increases in the B(max) of [3H]flunitrazepam binding without changes in K(d) were noted in central medial and central lateral nuclei. GABAergic (γ-aminobutyric acid) neurons in the ventrobasal nucleus and in nuclei in the midline group are important in seizure regulation and arousal. These findings suggest that alterations of benzodiazepine receptors in certain nuclei of thalami are involved in the physiological changes induced by pentobarbital dependence. There were no changes in the binding parameters for [3H]flunitrazepam in pentobarbital-tolerant rats. Copyright (C) 1998 Elsevier Science B.V.

DOI： 10.1016/S0014-2999(98)00447-6

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We have proposed a time-weighted measurement using blue rayon that selectively adsorbs and concentrates polycyclic aromatic hydrocarbons (PAH), e.g. benzo(a)pyrene (BaP). Though the method was demonstrated to be a convenient way to monitor PAH, the amount adsorbed to the blue rayon depends on the intensity of water stream and the level of PAH. The intensity of water stream was measured by 'plaster ball' method, while TWA of PAH in water was measured by a portable sampler using solid phase extraction cartridge. A level of BaP measured by the original blue rayon technique was corrected in this way by the water stream intensity, which correlated well with the TWA of BaP measured by the portable sampler. The improved blue rayon hanging method was applied to several field sites in the Seto Inland Sea of Japan. TWA of BaP ranged from 0.08 to 3.78 ng l-1. These results showed the possibility that the method could be used to evaluate pollution in aquatic environment.

DOI： 10.1016/S0141-1136(97)00063-9

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The pharmacological characteristics and the regional distribution of [3H]3-OH-PCP (1-[1(3-hydroxyphenyl)-cyclohexyl)piperidine) binding were investigated in rat brain by quantitative autoradiography. Kinetic analysis of [3H]3-OH-PCP binding revealed fast and slow components, in the association and dissociation studies. The regional distribution of binding closely corresponded to those of binding sites labeled by [3H]N-[1-(2-thienyl)-cyclohexyl]3,4-piperidine (TCP) and [3H](+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten- 5,10-imine maleate (MK 801). High densities of [3H]3-OH-PCP binding sites were found in the stratum radiatum and oriens of field CA1 in the hippocampus and in the outer layers of cerebral cortices. In contrast, low levels of binding were seen in the brain stem and the granular cell layer of the cerebellum. [3H]3-OH-PCP binding was strongly inhibited by MK 801 and 3-OH-PCP, while the potency of (+)-SKF 10047 in inhibiting [3H]3-OH-PCP binding was less in the cerebral cortex and hippocampus. The antagonists for the glutamate, glycine and polyamine recognition sites at the NMDA/PCP receptor complex displaced [3H]3-OH-PCP binding sites with a potency similar to that of [3H]MK 801. These findings suggest that the [3H]3-OH-PCP binding site is similar or identical to the PCP binding site labeled by [3H]TCP and [3H]MK 801.

DOI： 10.1016/0014-2999(96)00382-2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

The effects of continuous administration of pentobarbital on the benzodiazepine receptor labeled by [3H]flunitrazepam were investigated. Animals were made tolerant to pentobarbital by intracerebroventricular (i.c.v.) infusion with pentobarbital (300 μg/10 μl/h) for 6 days through pre-implanted cannulae connected to osmotic mini-pumps. The dependent rats were assessed 24 h after cessation of pentobarbital infusion. Changes in [3H]flunitrazepam binding were examined in 37 brain regions at a concentration of [3H]flunitrazepam of 1 nM. In subsequent saturation studies, the binding parameters B(max) and K(D) were also investigated in 17 brain regions, most of which showed significant changes in [3H]flunitrazepam binding in experiments using a fixed concentration of radioligand. The pentobarbital-tolerant rats showed a significant increase in B(max) with an increase in K(D) for [3H]flunitrazepam in the ventroposterior nucleus of thalamus. In the dependent rats, a significant increase in B(max) for [3H]flunitrazepam binding, without a change in K(D), was observed in all layers of the frontal cortex, the caudate-putamen, olfactory tubercle, and some nuclei in thalamus, compared to those in the control. Increased [3H]flunitrazepam binding in the molecular layer of the olfactory bulb, the ventral pallidum, and the cerebellum of the pentobarbital dependent rats at a fixed concentration of [3H]flunitrazepam was also observed. There was no significant change in [3H]flunitrazepam binding in the hippocampus and several nuclei of the brain stem. These findings suggest that benzodiazepine receptors are closely involved in the development of tolerance to and dependence on pentobarbital. Further studies on changes in γ-aminobutyric acid (GABA)A receptor subunit mRNA or the effects of pentobarbital on GABA(A) receptor phosphorylation would be necessary for an explanation of the precise mechanisms underlying the development of tolerance to and dependence on pentobarbital.

DOI： 10.1016/0014-2999(95)00595-1

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

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Language：English   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Binding of a novel radioligand, [H-3]3-OH-PCP (1-(1(3-hydroxyphenyl)cyclohexyl)piperidine), to N-methyl-D-aspartate (NMDA) receptor-coupled and -uncoupled PCP sites was investigated in the rat brain. The highest densities of [H-3]3-OH-PCP binding were observed in the hippocampal formation, notably in the stratum radiatum and oriens of CA1 region, and dentate gyrus, There were relatively high levels of binding in the olfactory system, superficial layer of cortices, the amygdala and the thalamus. In contrast, lower levels of binding were found in the globus pallidus, cerebellum, and brain stem, except for the superior colliculus. These findings demonstrate that [H-3]3-OH-PCP binds to discrete regions within the rat brain, Its distribution is consistent with autoradiographic localization of [H-3]TCP and [H-3]MK-801 binding sites in the rat brain, suggesting that [H-3]3-OH-PCP binds to NMDA/PCP ion-channel complexes in preference to sigma sites.

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Language：English   Publishing type：Research paper (scientific journal)  

Changes in benzodiazepine binding sites labeled by [3H]flunitrazepan (FNZ) in twenty discrete brain regions of rats made tolerant to and dependent upon pentobarbital were examined. Animals were rendered tolerant by intracerebroventricular (i.c.v.) infusion with pentobarbital (300 micrograms/ 10 microliters/ hr for six days) through pre-implanted cannulae connected to osmotic mini-pumps. The pentobarbital dependence was assessed 24 hr after abrupt withdrawal from pentobarbital. In the tolerant rats, a significant increase in [3H]FNZ binding sites was found in layer IV of frontal cortex and the molecular layer of olfactory bulb. [3H]FNZ binding sites in the pentobarbital dependent rats were significantly increased in layers I-III and V-VI of frontal cortex, caudate-putamen, olfactory tubercle, globus pallidus and ventral pallidum, in addition to those observed in the tolerant group. There was, however, no significant difference in the hippocampus and several regions in the hindbrain in either pentobarbital-treated group. Taken together with characteristics of subtypes of benzodiazepine receptors and changes in GABA-benzodiazepine receptor complexes elucidated in our previous studies, these findings suggest that both types of benzodiazepine receptors are involved in the development of pentobarbital intoxication mediated by GABAA receptors.

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Language：English   Publishing type：Research paper (scientific journal)  

We previously found that low-dose X-ray irradiation or radon (weak α-ray) inhalation increases SOD activities and reduces lipid peroxide levels in various organs of 7-week-old rats or rabbit. In this study, we examined how the changes of SOD activity, lipid peroxide level, and membrane fluidity of the cerebral cortex in aged male Wistar rats (65 and 91 weeks old) were affected by low-dose X-ray irradiation (100 cGy or under) compared with those in 7-week-old rats, to elucidate the mechanism of aging inhibition. The following results were obtained: Although radiation sensitivity was observed to decreases with age, low-dose irradiation changed the Mn-SOD activity, lipid peroxide level, and membrane protein fluidity parameter of the cerebral cortex in the aged rats to be closer to those in the youth. These finding suggest that the increased SOD activity induced by low-dose irradiation enhances biomembrane functions, and that the decrease of lipid peroxide level enhances the membrane protein fluidity. © 1994.

DOI： 10.1016/0891-5849(94)90132-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PHYSIOL CHEM PHYSICS MED NMR  

This study examines the influence of low dose X-irradiation on the structure and transport function of cell membranes of rat cerebral cortex. We found that unlike high dose irradiation which promotes membrane damage, low dose irradiation stimulates the SH group of membrane proteins and enhances the ability to control the membrane transport mechanism as reflected by an increase in Na+, K+-ATPase activity. The concentration of cysteine (Cys) significantly increased at 25-100 cGy and the concentration of cystine (Cys-Cys) significantly decreased at 25 cGy. It showed no dose dependent changes in tyrosine (Tyr), phenylalanine (Phe) and glycine (Gly). Similarly phospholipid and cholesterol levels were unchanged. Na+, K+-ATPase activities significantly decreased at 100 cGy or higher but significantly increased at doses of 25 and 50 cGy.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kluwer Academic Publishers-Plenum Publishers  

It is reported that CNS hemorrhage causes membrane dysfunction and may exacerbate this damage as a result of secondary ischemia or hypoxia. Since hyperbaric oxygenation improves oxygen metabolism, it may reduce this membrane damage. The present study was conducted to reveal whether hyperbaric oxygenation influences membrane alteration after hemorrhage. Thirty minutes after subarachnoid hemorrhage induction, rats were treated with hyperbaric oxygenation 2 ATA for 1 hour. Rats were decapitated 2 hours after subarachnoid hemorrhage induction. Na+, K(+)-ATPase activity measurement and spin-label studies were performed on crude synaptosomal membranes. Subarachnoid hemorrhage decreased Na+, K(+)-ATPase activity. Spin label studies showed that hydrophobic portions of near the membrane surface became more rigid and the mobility of the membrane protein labeled sulfhydryl groups decreased after subarachnoid hemorrhage. Hyperbaric oxygenation significantly ameliorated most of the subarachnoid hemorrhage induced alterations. We conclude that hyperbaric oxygenation may be a beneficial treatment for acute subarachnoid hemorrhage.

DOI： 10.1007/BF00966765

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Authorship：Lead author   Language：Japanese   Publisher：Okayama Medical Association  

Lipid peroxidation, free radical contents, antioxidant activity, guanididno compound metabolism and changes in amino acid contents in rat brain were studied to clarify the effect of a clinically relevant dose of hyperbaric oxygen (HBO). Seven-week-old rats were exposed to HBO at 3 atmosphere absolute for 2 hours. An increase in thiobarbituric acid reactive substances and carbon centered radicals was observed after exposure. Superoxide dismutaselike activity also increased. The measurement of guanidino compounds revealed a significant rise in arginine and guanidinoacetic acid (GAA) levels. Since arginase activity decreased while there was no significant alteration in arginine: glycine-amidinotransferase activity, these changes in enzyme activities seem to cause the increase of arginine and GAA levels. In relation to guanidino compound metabolism, the amino acid contents were determined. An increase in glutamine and taurine levels were observed and these seemed to favor the defense mechanism. These data suggested that ongoing lipid peroxidation in the brain was caused by HBO, and that the defense mechanism against the oxidative stress was activated in response.

DOI： 10.4044/joma1947.105.3-4_291

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kluwer Academic Publishers-Plenum Publishers  

The effects of 2-guanidinoethanol (GEt) on the release of monoamines and on the activity of their degrading enzymes were studied in order to investigate why 3,4-dihydroxyphenylacetic acid (DOPAC) increased to a much greater extent than homovanillic acid (HVA) after GEt injection into rat brain. In differential pulse voltammograms recorded using an electrochemically treated carbon fiber electrode, two distinct oxidation peaks, one at 130mV (DOPAC peak) and the other at 300 mV (5-hydroxyindoleacetic acid (5-HIAA) peak), were observed. In the hippocampus, the DOPAC peak increased markedly compared to the peak height recorded prior to the intracerebroventricular injection of GEt (6μmol). Although the DOPAC peak height increased to 350% 4 hours after GEt injection, the 5-HIAA peak showed no change. In the striatum, the DOPAC peak increased to 150% 3 hours after GEt injection. Serial changes in the extracellular levels of DOPAC, HVA, and 5-HIAA were monitored in the striatum after GEt injection, using an in vivo brain micro-dialysis technique. Although the DOPAC levels strated to increase 80 minutes after GEt injection, HVA and 5-HIAA levels showed no change. On the other hand, monoamineoxidase, which metabolizes dopamine to DOPAC, was not activated and catechol-0-methyltransferase, which metabolizes DOPAC to HVA, were not inhibited by 5 mM of GEt in vitro. These data suggested that GEt increased the release of dopamine, but not of serotonin, and that GEt might restrict the DOPAC transport system. © 1992 Plenum Publishing Corporation.

DOI： 10.1007/BF00968014

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Association for Laboratory Animal Science  

The spontaneously epileptic rat (SER; &lt;I&gt;zi/zi&lt;/I&gt;, &lt;I&gt;tm/tm&lt;/I&gt;) is the double mutant obtained by mating the tremor rat (TRM; &lt;I&gt;tm/tm&lt;/I&gt;) with the zitter rat (ZI; &lt;I&gt;zi/zi&lt;/I&gt;), exhibits tonic convulsions and absencelike seizures without external stimulation, and has marked vacuolation and hypomyelination in the brain. Vacuole formation is seen widely in the brain of TRM rat as same as SER. As free radical and its related materials may possibly participate to form vacuole in the brain of SER and TRM rats, free radicals (&amp;sdot;C, &amp;sdot;OH, &amp;sdot;H), TBARS level, SOD activity and content of fatty acids were investigated.&lt;BR&gt;During maturation, free radicals and Cu, Zn-SOD activities in the brain of SER did not change, but TBARS levels in cerebellum and pons-medulla oblongata increased. On the other hand, in pons-medulla oblongata of TRM rats, Cu, Zn-SOD activity and &amp;sdot;OH radical increased during maturation. In the same region of the 24-week-old TRM rats, TBARS level increased and the content of arachidonic acid (C&lt;SUB&gt;22: 4&lt;/SUB&gt;) decreased significantly compared with those in WTC rats. These results suggest that vacuole formation may be caused by lipid peroxidation of membrane.

DOI： 10.1538/expanim1992.8.27

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Language：Japanese   Publisher：産業医学振興財団  

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00003804404

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Language：Japanese   Publisher：日本教育大学協会第二常置委員会  

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00002552646

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00002552764

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/sangyoeisei.KJ00003948042

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/sangyoeisei.KJ00003948202

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Language：Japanese   Publisher：Japan Society for Occupational Health  

DOI： 10.1539/joh.44.69

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Language：Japanese  

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00002552570

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The acute effects of systemic administration of the anti-obesity agent sibutramine on extracellular dopamine (DA) in the nucleus accumbens of freely moving rats were studied using in vivo microdialysis and compared with the actions of phentermine and d-amphetamine at doses 1x and 3x their respective 2 h ED50 values to reduce food intake in rats. At the lower dose, sibutramine did not elevate extracellular DA concentrations; however, at the higher dose (6.0 mg kg-1, i.p.) it caused a modest and prolonged increase in extraneuronal DA. A maximal rise was observed at 60 min post-sibutramine treatment (+231% compared to controls) with DA levels remaining elevated for up to 160 min post treatment. In contrast, phentermine and d-amphetamine significantly enhanced DA efflux at both the lower and higher doses. These elevations of DA levels were significantly greater than that seen with the corresponding dose of sibutramine over 0-80 min post treatment. Maximal rises in DA levels resulting from the higher dose of each drug were +733% (phentermine, 3.9 mg kg-1, i.p.) and +603% (d-amphetamine, 1.5 mg kg-1, i.p.) compared to controls 40 min post treatment. The highest doses of phentermine and d-amphetamine increased rat locomotor activity up to 100 min and 160 min post treatment, respectively, whereas the equivalent sibutramine dose had no effect. These findings therefore suggest that dopaminergic reward mechanisms are not involved in the reduction of food intake by sibutramine. Furthermore, they are consistent with the view that sibutramine lacks abuse potential. (C) 2000 Wiley-Liss, Inc.

DOI： 10.1002/1098-2396(200011)38:2<167::AID-SYN8>3.0.CO;2-W

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Language：Japanese  

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Language：Japanese   Publisher：日本環境変異原学会  

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Language：Japanese   Publisher：公益社団法人 日本産業衛生学会  

DOI： 10.1539/sangyoeisei.KJ00002552198

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Language：Japanese  

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Language：English   Publisher：the Japan Radiation Research Society  

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Other Link： https://projects.repo.nii.ac.jp/?action=repository_uri&item_id=233943

Language：Japanese   Publisher：公益社団法人 日本実験動物学会  

DOI： 10.1538/expanim1992.9.49

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Country：Japan

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