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1.
ANAS SUBARNAS TAKESHI TADANO YOSHITERU OSHIMA KENSUKE KISARA YASUSHI OHIZUMI 《The Journal of pharmacy and pharmacology》1993,45(6):545-550
Abstract— Effects of β-amyrin palmitate isolated from the leaves of Lobelia inflata were studied on the central nervous system of mice and were compared with those of antidepressant drugs, mianserin and imipramine. In the forced swimming test, β-amyrin palmitate, like mianserin and imipramine, reduced the duration of immobility of mice significantly in a dose-dependent manner (5, 10 and 20 mg kg?1). β-Amyrin palmitate (5, 10 and 20 mg kg?1) or mianserin (5, 10 and 20 mg kg?1) elicited a dose-related reduction in locomotor activity of mice and antagonized locomotor stimulation induced by methamphetamine. In contrast, imipramine (5, 10 and 20 mg kg?1) increased locomotor activity and potentiated methamphet-amine-induced hyperactivity. β-Amyrin palmitate showed no effect on reserpine-induced hypothermia, whilst mianserin (10 mg kg?1) and imipramine (10 and 20 mg kg?1) antagonized the reserpine-induced effect. Unlike imipramine, β-amyrin palmitate and mianserin did not affect haloperidol-induced catalepsy, tetrabenazine-induced ptosis and apomorphine-induced stereotypy. β-Amyrin palmitate and imipramine had no effects on the head-twitch response induced by 5-hydroxytryptophan, whereas mianserin (5, 10 and 20 mg kg?1) decreased it in a dose-dependent manner. A potentiating effect of β-amyrin palmitate (5, 10 and 20 mg kg?1) on narcosis induced by sodium pentobarbitone was stronger than that of imipramine (10, 20 and 40 mg kg?1) but weaker than that of mianserin (2·5, 5 and 10 mg kg?1). These results suggest that β-amyrin palmitate has similar properties in some respects to mianserin and might possess a sedative action. We suggest that β-amyrin palmitate has antidepressant activity with a mianserin-like profile of action. 相似文献
2.
KATSUHIRO HAYASHI TOSHIMASA OCHIAI YOSHIHIRO ISHINODA TAKESHI OKAMOTO TOSHIHIRO MARUYAMA KAZUNORI TSUDA HIROHITO TSUBOUCHI 《Journal of gastroenterology and hepatology》1997,12(3):249-256
The importance of oxygen in maintaining the functional integrity of hepatocytes has been well established in a variety of experimental models, such as in vivo , perfused liver and isolated hepatocytes. However, one of the shortcomings of these systems is their short life span. Therefore, we have examined the effects of long-term hypoxia on cellular adenine nucleotide content and cellular functions, such as albumin production, urea production and DNA synthesis, in adult rat hepatocytes in primary culture. Hepatocytes were cultured at a density of 11 × 104 and 5 × 104 cells/0.18 mL per cm2 for the study of albumin and urea production and DNA synthesis, respectively, at various oxygen tensions (20, 12, 8 and 5%) for 24 h. Cellular ATP content in cultured hepatocytes in hypoxia gradually declined, corresponding to the decrease in oxygen tension, and the cellular ATP level at 5% oxygen was approximately 20% of that at 20% oxygen. Albumin production also decreased in parallel with the decrease in cellular ATP content in cultured hepatocytes in hypoxia. However, even when cellular ATP content gradually declined corresponding with the decrease in oxygen tension in cultured hepatocytes in hypoxia, such as at 8 or 5% oxygen, urea production remained at a high level; in contrast, DNA synthesis was completely suppressed. These results suggest that the cellular ATP content decreases in cultured hepatocytes during long-term hypoxia in relation to oxygen tension and that the relationship between decreased ATP levels and liver function in cultured hepatocytes during hypoxia differs for albumin production, urea production and DNA synthesis. 相似文献
3.
Cytotoxin and urease activities of Helicobacter pylori isolates from Japanese patients with atrophic gastritis or duodenal ulcer 总被引:1,自引:0,他引:1
HAJIME MURAKITA MASAMICHI HIRAI SHIGEJI ITO TAKESHI AZUMA TAKUJI KATO YOSHIHIRO KOHLI MASARU KURIYAMA 《Journal of gastroenterology and hepatology》1996,11(9):819-824
The vacuolating cytotoxin and urease secreted by Helicobacter pylori are thought to be virulent factors. Because vacuolation is potentiated by the presence of ammonium ion, which is produced by urease in vitro, it is of interest to examine whether cytotoxin and urease work reciprocally in the development of atrophic gastritis or duodenal ulcer. In the present study, patients (all H. pyloripositive) were divided into four groups: mild atrophic gastritis (group 1; nine patients), severe atrophic gastritis (group 2; 36 patients), duodenal ulcer with mild atrophic gastritis (group 3; 19 patients) and duodenal ulcer with severe atrophic gastritis (group 4; 12 patients). Cytotoxin production and urease activity of H. pylori isolated from these patients were analysed. Cytotoxin production was observed in four of nine (44.4%), 28 of 36 (77.8%), 11 of 19 (57.9%) and eight of 12 (66.7%) isolates from groups 1, 2, 3 and 4, respectively. Cytotoxin-producing H. pylori isolates were found significantly more in patients with severe atrophy than in patients with mild atrophy (P= 0.048). The mean of relative activity of cytotoxin in H. pylori isolate was 1. 6. ± 2. 3, 7. 9. ± 7. 4, 5. 8. ± 6. 0 and 9. 0 ± 9. 1 in groups 1, 2, 3 and 4, respectively. Helicobacter pylori isolates from severe atrophy or duodenal ulcer patients in groups 2 or 4 possessed significantly higher activity than those from non-ulcer patients in group 1 (P= 0.017 and 0.030, respectively). The mean of urease activity was 8. 6 ± 4. 6, 10. 0 ± 5. 9, 10. 0 ± 8. 5 and 11. 2 ± 7. 7 IU/mg in groups 1, 2, 3 and 4, respectively. These differences indicated no statistical significance. In each H. pylori isolate, the production of cytotoxin and urease were independent, which indicated that there was no reciprocal effect between them in vivo. Thus, cytotoxin-producing H. pylori isolates were more prevalent in patients with severe atrophic gastritis and the cytotoxin activities of H. pylori isolates from the patients with severe atrophic gastritis or duodenal ulcer were much higher than those from the patients with mild atrophic gastritis, which suggested that vacuolating cytotoxin may be a disease-inducing factor. 相似文献
4.
J. SVEDENHAG J. HENRIKSSON A. JUHLIN-DANNFELT K. ASANO 《Acta physiologica (Oxford, England)》1984,120(1):77-86
The effect of chronic β-adrenergic blockade on central circulatory adaptations to physical training was investigated. 16 healthy sedentary males (20–31 yrs) trained on cycle ergometers 40 min/day, 4 days a week for 8 weeks at a work load that during the last 5 weeks corresponded to 75% of the pretraining VO2 max. In a single blind way, 8 subjects were during the training period treated with the β-adrenergic receptor blocker propranolol (160 mg/day), while the remaining 8 received placebo tablets. Pretraining tests were performed before the start of medication and posttraining tests were performed 6 days after the last day of training and medication. The training program resulted in a similar increase (8%) in VO2 max in both groups (p<0.01). The resting heart rate (-4 beats/min; p<0.05) as well as the exercise heart rate at a moderate work load (120 W: -11 beats/min; p<0.01) decreased with training, and no significant difference was seen between the 2 groups. At a high work load (180 W), however, the heart rate decreased significantly more with training in the placebo group as compared with the β-blockade group (-19 vs.-7 beats/min; p<0.05). The oxygen pulse (VO2/HR) increased in both groups at 120 W (+6%; p<0.01). At 180 W the oxygen pulse increased only in the placebo group (+8%; p<0.05). The estimated stroke volume at 120 and 180 W, as determined by impedance cardiography, did not change significantly with training although there was a tendency towards an increase in the placebo group only. The resting left ventricular wall thickness and diameter, as determined by echocardiography, did not change significantly with training in either group.—In conclusion, the present study indicates that a moderate degree of β-adrenergic blockade does not prevent or impair the training-induced increase in the maximal oxygen uptake. During submaximal work, however, the circulatory adaptation may be less apparent if training has been performed during partial blockade of the sympathoadrenal system. 相似文献
5.
MOTOYOSHI NOMIZU TAKANORI IWAKI TAKEYOSHI YAMASHITA YOSHIMASA INAGAKI KATSUHIKO ASANO MIKI AKAMATSU TOSHIO FUJITA 《Chemical biology & drug design》1993,42(3):216-226
One hundred Suc-X-Y-Ala-pNA peptides (SUC: succinyl, pNA: p-nitroanilide, X, Y: Gly, Ala, Val, Leu, Ile, Phe, Pro, x-aminobutyric acid, norvaline, norleucine) were synthesized and their reaction constants with porcine pancreatic elastase (Km, Kcat and Kcat/Km) were determined. These reaction constants were quantitatively analyzed using the Free–Wilson/Fujita–Ban method. The contribution of amino acid side chains to the reaction constants Km, Kcat and Kcat/Km), expressed logarithmically, was found to be additive. On the other hand, 19 elastase inhibitors of the general formula CF3CO-X-Y-Ala-pNA (X,Y: ten amino acids) were synthesized, and their inhibition constants were compared with the Michaelis constant for the corresponding substrates and analyzed using free-energy-related substituent constants. In the analysis of amino acid side chains in the Y position, the Ki value of the inhibitor was generally correlated to the Km value of the substrate, which corresponded to the inhibitor, thus confirming the validity of the equation This study may serve as a prototypical approach to unraveling structure–activity relationships of peptide substrates and inhibitors of medicinal or agricultural importance. 相似文献
6.
Differences in the Mode of Lethality Produced through Intravenous and Oral Administration of Organophosphorus Insecticides in Rats 总被引:2,自引:0,他引:2
TAKAHASHI HIROAKI; KOJIMA TAKESHI; IKEDA TAKANORI; TSUDA SHUJI; SHIRASU YASUHIKO 《Toxicological sciences》1991,16(3):459-468
Differences in the Mode of Lethality Produced through Intravenousand Oral Administration of Organophosphorus Insecticides inRats. TAKAHASHI, H., KOJIMA, T., IKEDA, T., TSUDA, S. and SHIRASU,Y. (1991). Fundam. Appl. Toxicol. 16, 459468. This studywas undertaken to investigate the possibility that mechanismsother than cholinesterase (ChE) inhibition account for the acutetoxicity of organophosphorus insecticide. Both the PO type insecticide(direct ChE inhibitors: chlorfenvinphos and dichlorvos) andthe PS type insecticide (indirect ChE inhibitors: diazinon andfenthion) were employed. Rats treated with lethal doses of intravenousand oral PO type insecticides and oral PS type insecticidesexhibited typical signs of anti-ChE poisoning along with markedinhibition of brain and erythrocyte ChE activity. In contrast,rats given lethal doses of intravenous PS type insecticidesexhibited tonic convulsions and opisthotonos, with only slightinhibition of ChE activities. When PO type insecticides wereintravenously administered to anesthetized and conscious rats,animals exhibited typical anti-ChE poisoning signs in cardiorespiration:hypertension and apnea which were antagonized by atropine. Afteradministration of lethal doses of PO type insecticides, breathingdisappeared before the cessation of heart beats. Rats receivinglethal doses of intravenous PS type insecticides did not showhypertension, but exhibited transient cessation of breathingand heart beats. Breathing was observed after the disappearanceof heart beats. The electroencephalogram (EEG) was characterizedby spike and wave complexes. The EEG and cardiorespiratory changeswere not antagonized by atropine. It was concluded that lethalityfollowing intravenous PS type insecticides may be independentof ChE inhibition. 相似文献
7.
The Preclinical Safety Evaluation of Human Monoclonal Antibody against Cytomegalovirus 总被引:1,自引:0,他引:1
MATSUZAWA KEIKO; KOYAMA TAMOTSU; SUGAWARA SHIGEKI; IKEGAWA SUNAO; ASANO SATOSHI; SASAKI SATOSHI; TOMIYAMA TAKAMI; KASAHARA YOSHINORI; OKAMIYA YOSHIAKI; INOUE KYOKO; OHTA TOMOHIRO; MAKITA TOKUTARO 《Toxicological sciences》1992,19(1):26-32
The human monoclonal antibody against cytomegalovinis (Mab C23)was examined pharmacokinetically and toxicologically as partof the preclinical studies prior to approval for human use.Rats given repeated intravenous administrations of Mab C23 producedno antibodies against Mab C23 and maintained a blood Mab C23level in a dose-dependent manner. However, pregnant rabbitsproduced antibodies against Mab C23. The half-life of Mab C23in plasma was 15.9 days in rats, which was similar to that ofnormal human serum -globulin (NHSG). Neither behavioral effectsnor circulatory disturbance was found in mice, rats, and dogseven after a single intravenous injection of 100 or 200 mg/kg,which corresponds to 50 or 100 times the intended clinical dosage.The repeated doses of 2, 10, or 20 mg/kg of Mab C23 on six occasionswith 1- or 2-week intervals elicited a transient decrease inleukocyte counts in rats given 10 or 20 mg/kg, but no adverseeffects in cynomolgus monkeys. Mab C23 did not cause any reproductiveor developmental toxicity when administered to rats and rabbitsat dose levels of 20 mg/kg or less. However, pregnant animalsshowed lower plasma levels of Mab C23 than non-pregnant animals.The chromosomal aberration test disclosed no clastogenicityin human lymphocytes. An immunostaining for Mab C23 revealedno localizations in several tissues of cynomolgus monkeys givenintravenous doses of Mab C23. The preclinical safety evaluationin animals other than rabbits, which produced no antibodiesagainst Mab C23, showed that the behavior of Mab C23 is pharmacokineticallysimilar to that of NHSG and is as safe as NHSG, which has longbeen used as a biological agent. However, because there wasa difference in blood levels of Mab C23 between pregnant andnonpregnant animals, its clinical administration to pregnantpatients should differ from that to non-pregnant patients. 相似文献
8.
HISAKI MAKIMOTO M.D. Ph.D. IKUTARO NAKAJIMA M.D. KOJI MIYAMOTO M.D. YUKO YAMADA M.D. HIDEO OKAMURA M.D. TAKASHI NODA M.D. Ph.D. TAKESHI AIBA M.D. Ph.D. SHIRO KAMAKURA M.D. Ph.D. KENGO KUSANO M.D. Ph.D. WATARU SHIMIZU M.D. Ph.D. KAZUHIRO SATOMI M.D. Ph.D. 《Pacing and clinical electrophysiology : PACE》2015,38(5):630-640
9.
10.
Shunsuke TAKENAKA Yoshitaka ASANO Jun SHINODA Yuichi NOMURA Shingo YONEZAWA Kazuhiro MIWA Hirohito YANO Toru IWAMA 《Neurologia medico-chirurgica》2014,54(4):280-289
The aim of this study is to assess the different metabolic activities characteristic of glioma recurrence and radiation necrosis (RN) and to explore the diagnostic accuracy for differentiation of the two conditions using 11C-methionine (MET), 11C-choline (CHO), and 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET). Fifty patients with lesions suggestive of recurrent glioma by magnetic resonance imaging (MRI) underwent MET, CHO, and FDG-PET. All patients who had previously been treated with radiotherapy for malignant glioma were subjected to open surgery and pathological diagnosis (17 recurrent grade 3- gliomas (Gr.3s) comprising 7 anaplastic astrocytomas (AAs) and 10 anaplastic oligodendrogliomas (AOs), 17 recurrent glioblastomas (Gr.4s), and 16 RNs). We measured the PET/Gd volume ratio, the PET/Gd overlap ratio, and the lesion/normal brain uptake ratio (L/N ratio) and determined the optimal index of each PET scan. The PET/Gd volume ratio and the PET/Gd overlap ratio for RN were significantly lower than those of glioma recurrence only with MET-PET (P < 0.05). The L/N ratio of RN was significantly lower than that of Gr.4 with all PET imaging (P < 0.001) and was significantly lower than that of Gr.3, especially for AO, only with MET-PET images (P < 0.005). Receiver operating characteristic (ROC) analysis showed that the area under the curve of MET, CHO, and FDG was 92.5, 81.4, and 77.4, respectively. MET L/N ratio of greater than 2.51 provided the best sensitivity and specificity for establishing glioma recurrence (91.2% and 87.5%, respectively). These results demonstrated that MET-PET was superior to both CHO and FDG-PET for diagnostic accuracy in distinguishing glioma recurrence from RN. 相似文献