[A study on the mechanism of the potentiating effects of glucocorticoids on the relaxing activity of isoproterenol in guinea-pig tracheal smooth muscle].
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Biomedical subjects
Publications and source records attributed to T Fukuda.
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The finding that taurine may possess an ability to inhibit development of tolerance to opioid peptides was demonstrated in the present study. Tolerance was produced in rats by five IVT administrations of DAME during 3 consecutive days. Pretreatment with taurine that had been injected IVT 10 min prior to every administration of DAME suppressed the development of tolerance to both the akinetic and analgetic effects of the peptide. In addition, taurine pretreatment inhibited the induction of hyperlocomotor activity which was observed in tolerant animals as the number of the DAME injections was increased. Tolerance to WDS effects also resulted from the repeated administration of the peptide. However, it could not be concluded from the present experimental condition that taurine affects development of tolerance to WDS, since the amino acid suppressed the induction of WDS from the first injection of DAME.
This study reports the presence of glycylprolyl dipeptidyl aminopeptidase in porcine pancreas, and its partial purification and some properties. Crude enzyme preparation was obtained by extraction from acetone-dried powder of the pancreas at pH 7.6. For solubilization of enzyme, freezing and thawing were carried out. Crude enzyme extract was fractionated with ammonium sulfate precipitation, gel filtration on Sephadex G-200 column and ion-exchange chromatography on DEAE-cellulose. Partially purified enzyme showed 2897-folds purification. The enzyme activity on polyacrylamide gel electrophoresis showed good agreement with a main protein band stained with Coomassie brilliant blue. Molecular weight of this enzyme from the pancreas was estimated to be 300000 by gel filtration on Sephacryl S-300 column. Optimum pH was between 8.5 and 9.0, and Km value for glycylproline-p-nitroanilide tosilate was 0.33 mM. This enzyme from the pancreas was a serine enzyme and was relatively stable to heat at 60 degrees C for 10 min.
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Effects of taurine on tolerance to [D-Ala2, Met5]enkephalinamide (DAME) were investigated in rats. Tolerance was produced by five intraventricular administrations of DAME (50 microgram) during 3 consecutive days. The magnitude of developed tolerance to DAME was not uniform for each behavioral parameter; tolerance to analgesia effects developed more intensively and rapidly from the repeated injections of the peptide than that to akinesia effects. Pretreatment with taurine (9.5 X 10(-2) M) which was injected in a volume of 10 microliter intraventricularly 10 min prior to every administration of DAME suppressed the development of tolerance to both analgesia and akinesia effects of this peptide, whereas pretreatment with L-leucine at the same concentration did not. Spontaneous locomotor activity was measured for 1 h after the 90-min behavioral observation period was completed. That activity increased with the number of the peptide injections. Taurine pretreatment inhibited the induction of 'hyper'-locomotor activity. These results support the view that taurine may possess an ability to inhibit development of tolerance to morphine-like peptides in rats.
The purpose of this study is to evaluate benign and/or malignant thyroid tumors with 201TI thyroid scan. We studied 76 cases of histologically verified thyroid tumors, all seen as cold nodules on the 123I thyroid scan. 201TI thyroid scan was performed 5-15 minutes (early scan) and 3-5 hours (delayed scan) after intravenous administration of 1.5-2.0 mCi of 201TI. In 35 (94.6%) of 36 malignant tumors (anaplastic carcinoma, six; papillary carcinoma 23; follicular carcinoma, five; epidermoid carcinoma, one; malignant lymphoma, 1) 201TI accumulated in the cold nodule of the 123I thyroid scan on both early and delayed scans. On the other hand, the delayed 201TI scan was negative in 35 out of 39 (89.7%) benign tumors. Employing early and delayed 201TI scans, we were able to differentiate most malignant thyroid tumors from those which were benign. False-negative and -positive cases are discussed.
When the bone scintigram reveals high diffuse skeletal activity, it may be misinterpreted as normal. Some authors have reported such scintigrams in articles entitled "Significance of absent or faint kidney sign on bone scan" and "False negative bone scintigram". Three cases with bone metastasis showing high diffuse skeletal activity are presented in this paper. The recognition of abnormally high diffuse skeletal activity on bone scintigrams is discussed. The exposure time of all three cases was short when compared with normal cases, when the bone image was taken with a preset count. Therefore, exposure time is very important for objective differentiation between the cases showing high diffuse skeletal activity and normal cases.
Clocapramine was introduced into clinical use as a successor to carpipramine which is designated as a "désinhibiteur' by Deniker et al. Pharmacological and biochemical studies were carried out in order to elucidate the central action of clocapramine. Antidopaminergic activity of clocapramine was more potent than that of carpipramine. Clocapramine did not show any imipramine-like action; on the other hand, carpipramine partially did. We discuss the correlation between the preclinical findings so far obtained and clinical disinhibitory activity.
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An attempt was made to eradicate respiratory diseases developed in about 1,000 mice of 19 congenic inbred strains which were maintained in a mouse breeding room. The contagious diseases with respiratory signs were found to be caused by mixed infections with Mycoplasma pulmonis and Sendai virus. The eradication of the diseases was mainly made by sanitary improvement in care of the mice such as intensive disinfection, culling some diseased mice and so on, instead of destroying all colonies. As the result, mycoplasma infection decreased gradually, resulting in a complete eradication about one and half years later and remarkable increases in litter size and weaning rate of mice were obtained. Sendai virus infection failed to be eradicated.
Pharmacokinetic analysis of the distribution and concentration of adriamycin (ADM) in mouse plasma and tissues was carried out by differentiating the unmetabolized form from metabolized ones using high-performance liquid chromatography after a single intravenous injection. Marked differences between ADM and total ADM equivalent values (total ADM values) or its metabolized forms were observed in the pharmacokinetic behavior in plasma and tissue distributions. The ratios of tissue per plasma for total ADM and for ADM values in the liver, kidney and heart showed a two-digit magnitude each time they were examined. Twenty four h later, the ratios for ADM values in the liver, kidney, heart and lung were at high levels; 43.1, 48.1, 57.9 and 45.5 times, respectively. Twenty min after injection the ratios for total ADM values in the spleen, lung and tumors were comparatively small, but 24 h later, the ratio had increased 36.5, 45.5 and 6.8 times respectively.
The excretion of AsS and total vitamin C into urine after oral administration of AsS to humans was investigated. When 10 mmol of AsS was administered to the subjects, the excretion of AsS into urine continued for 60 hr in males and 48 hr in females. The average amount excreted per hour was less than 5 mg. These results differed from those for AsA and DAsA orally administered to humans. The determination of vitamin C after oral administration of AsS to the subjects consisting of ten males and six females showed no vitamin C effect in humans, similarly to the case with the guinea pig and the rhesus monkey.
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2-(5-Ethylpyridin-2-yl)benzimidazole (KB-1043) is a new benzimidazole derivative with marked antiinflammatory, analgesic and antipyretic properties. KB-1043 possesses potent inhibitory activities on the acute inflammatory edema induced by chemical and physical irritants in the hind paw of rats, but almost ineffective (similar to tiaramide) against adjuvant-induced polyarthritis in the rat. The antagonistic effects of KB-1043 on increased vascular permeability are more potent than those of phenylbutazone, and the analgesic effects of KB-1043 on the pain induced by chemical and mechanical stimulations were nearly equal to, or slightly less potent than, those of tiaramide and phenylbutazone. The fevers induced by brewer's yeast and polysaccharide from Pseudomonas fluorescens (T.T.G.) were lowered by KB-1043. THe ulcerogenic activity of KB-1043 was weaker than those of tiaramide and phenylbutazone. The therapeutic index of KB-1043 therefore is superior to those of tiaramide and phenylbutazone.
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