Biomedical subjects

T Fukuda

Publications and source records attributed to T Fukuda.

At least 703 records · Page 39Linked to original sources

PubMed1991

Effect of alpha-chloralose on disposition and pharmacological action of orally administered chlorzoxazone in rats.

The pharmacodynamic behavior of orally administered chlorzoxazone (CZX) was studied in rats. From the time course of CZX plasma concentration data under alpha-chloralose (80 mg/kg, i.p.) anesthesia, it was found that CZX obeyed a one-compartment model with first-order absorption. The pharmacological response intensity of CZX on the crossed extensor reflex was closely related to the plasma concentration data via Hill's equation under alpha-chloralose (80 mg/kg) anesthesia, but not at a 150 mg/kg dose. The influence of alpha-chloralose at the latter dose on CZX pharmacokinetics and pharmacodynamics appeared to be due to the pharmacodynamic interaction of alpha-chloralose and CZX, thus suggesting that the pharmacokinetic and pharmacodynamic concept proposed by Smolen was not applicable to CZX's behavior at such a dose in rats. Under alpha-chloralose (80 mg/kg) anesthesia, the biophase compartment was determined to be identical to the central compartment using our proposed model. On the basis of the effect of anesthetics on drug behavior, one may select an appropriate anesthetic dose to evaluate the relationship between the plasma levels and the onset and duration of the drug action. At the higher dose of alpha-chloralose (150 mg/kg), the free fraction of CZX was increased and a possible enhancement in CZX action was suggested.

Administration, Oral↗

PubMed1991

Phenolic constituents of licorice. III. Structures of glicoricone and licofuranone, and inhibitory effects of licorice constituents on monoamine oxidase.

Two new phenolic compounds, glicoricone (3) and licofuranone (4), were isolated from a species of licorice brought from the northwestern region of China, and their structures were assigned. Among the twelve licorice constituents examined for the inhibition of monoamine oxidase (MAO), six compounds, 3, 4, genistein (6), licopyranocoumarin (7), licocoumarone (14) and glycyrrhisoflavone (15), inhibited the enzyme with the IC50 (concentration required for 50% inhibition of the enzyme activity) values of 6.0 x 10(-5)-1.4 x 10(-4) M. Glycyrrhizin (1) also inhibited MAO with the IC50 value of 1.6 x 10(-4) M.

Animals↗

PubMed1991

[Phenolic constituents of licorice. IV. Correlation of phenolic constituents and licorice specimens from various sources, and inhibitory effects of licorice extracts on xanthine oxidase and monoamine oxidase].

The roots and/or rhizomes of Glychyrrhiza uralensis, G. glabra and G. inflata, and commercial licorice specimens from various regions or countries were analyzed by high-performance liquid chromatography (HPLC), and classified into three types based on their phenolic constituents. i) Type A: The roots and rhizomes of G. uralensis, commercial licorice specimens from northwestern region of China (Seihoku-kanzo) and from northeastern region of China (Tohoku-kanzo) in Japanese markets, and also several licorice specimens from Chinese markets. They contain licopyranocoumarin (6), glycycoumarin (7) and/or licocoumarone (8), which were not found in G. glabra and G. inflata. ii) Type B: The root and rhizome of G. glabra, and the licorice specimens imported from the Soviet Union and Afghanistan. They contain glabridin (9) and glabrene (10), which were not found in the samples of the other two Glycyrrhiza species. A root sample of Glycyrrhiza species from Turkey also contains 9 and 10. iii) Type C: The root sample of G. inflata. They contain licochalcones A (11) and B (12), which were not found in the samples of the other two Glycyrrhiza species. Commercial licorice specimens obtained in Japan, which were imported from Sinkiang of China (Shinkyo-kanzo), and some licorice specimens obtained from Chinese markets, have also been found to contain 11 and 12. The phenolics 6-12, characteristic constituents of types A, B or C, were not found in a specimen of cortex-free licorice from a Japanese market (kawasari-kanzo). Extracts of some licorice specimens of types A and B, and all of the licorice specimens of type C inhibited 40-56% of the xanthine oxidase activity at the concentration of 30 micrograms/ml. Extracts of some licorice specimens of types A and B also showed inhibitory effects on monoamine oxidase (44-64% inhibition, at the concentration of 30 micrograms/ml), which were slightly weaker than that of harmane hydrochloride.

Chromatography, High Pressure Liquid↗

PubMed1991

[Effects of Y-20811, a specific thromboxane A2 synthetase inhibitor, on chemical mediator-induced bronchoconstriction in guinea pigs].

We investigated the effects of Y-20811 on chemical mediator-induced bronchoconstriction and the release of chemical mediators into lung perfusion fluid during arachidonic acid (AA)-induced bronchoconstriction in guinea pigs. Y-20811 (0.01-1 mg/kg, i.v.), like acetylsalicylic acid or indomethacin, dose-dependently suppressed arachidonic acid- and LTD4-induced bronchoconstriction, and it (1 mg/kg, i.v.) also inhibited PAF-induced bronchoconstriction in guinea pigs. However, at a dose of 1 mg/kg, i.v., it was inactive against the bronchoconstriction induced by histamine, serotonin and acetylcholine in guinea pigs. Y-20811 (0.3-10 mg/kg) administered orally also prevented the LTD4-induced bronchoconstriction in a dose-dependent manner. This protective effect of Y-20811 (10 mg/kg, p.o.) persisted for at least 24 hr. Y-20811 (10 mg/kg, p.o.) also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti-ovalbumin guinea pig serum and pretreated with mepyramine. In the perfused and ventilated guinea pig lungs, Y-20811 inhibited AA-induced bronchoconstriction, decreased the release of TXA2 (estimated as TXB2) and increased the release of PGE2 into the perfused lung fluid, significantly (TXB2 and PGE2 were measured by HPLC). Therefore, Y-20811 suppressed various stimulant-induced bronchoconstrictions through the decrease of TXA2 production and the increase of PGE2 production. Thus, Y-20811 should prove useful as an anti-asthmatic drug.

Animals↗

PubMed1991

[Inhibition by Y-25130 of the von Bezold-Jarisch effect evoked by 5-HT or 2-methyl-5-HT in anesthetized rats].

Effect of Y-25130 on 5-hydroxytryptamine3 (5-HT3) receptors was investigated using the von Bezold-Jarisch effect (BJE) in anesthetized rats. Intravenous or intraduodenal administration of Y-25130 antagonized the BJE evoked by 5-HT and its effect was over 100 times more potent than that of metoclopramide. Y-25130 also completely blocked the BJE induced by 2-methyl-5-HT, a selective 5-HT3 receptor agonist. The BJE induced by 5-HT was not antagonized by spiperone, ketanserin, phenoxybenzamine, yohimbine and haloperidol, but antagonized by atropine. Atropine inhibited the bradycardia caused by electrical stimulation of the vagus nerve, but Y-25130 had no inhibitory effect. These results indicate that Y-25130 possesses a potent and selective 5-HT3 receptor antagonistic property.

Anesthesia↗

PubMed1991

Mechanisms of veratramine-induced 5-HT syndrome in mice.

Regional monoamine assays revealed that during veratramine-induced myoclonic movements, the contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the cerebral cortex were reduced with a slight increase in dopamine metabolites in the midbrain and brainstem. A similar tendency to decrease 5-HT and 5-HIAA contents was observed in the hypothalamus and hippocampus without increase in the contents of dopamine and its metabolites. Norepinephrine levels were not modified in any brain region at any time after the administration of the veratrum alkaloid. It was found that the veratramine evoked 3H-5-HT release from the frontal cortical slices was Ca+(+)-independent and persistent, and it continued approximately 20 min after the 2-min exposure to veratramine. The uptake of 3H-5-HT into the frontal cortical slices was inhibited competitively by veratramine. These results suggest that veratramine is both a releaser and uptake inhibitor of 5-HT and that the veratramine-induced involuntary movements may be mediated by serotonergic hyperfunction.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effect of concanavalin A on intracellular calcium concentration in single blood platelets.

Mobilization of Ca++ was estimated in single rabbit blood platelets with digital imaging microscopy. Concanavalin A (Con A) caused a rapid initial increase in intracellular concentration of Ca++ ([Ca++]i) with a latent time of about 20 sec, followed by a sustained increase in [Ca++]i. This effect of Con A was antagonized by alpha-methyl-D-mannose, which already was shown to antagonize the inhibitory effect of Con A on 5-HT transport, indicating that this effect of Con A was also derived from its binding to cell surface glycoproteins. The presence of EGTA in the medium did not affect the initial rise, but inhibited the latter phase of sustained rise. Thus, Con A induced elevation of [Ca++]i was suggested to consist of two different processes: mobilization of Ca++ from the intracellular storage sites and successive Ca++ influx through Ca++ channels. The effect of Con A on the 5-HT transport was tested in the presence of EGTA, a condition where no Ca++ influx occurs. The results indicate that Con A induced inhibition of 5-HT transport was not influenced by EGTA in the medium. It is suggested that the effect of Con A on 5-HT transport might be exerted through the Ca++ mobilization from its intracellular storage sites.

Animals↗

PubMed1991

Endothelial cells stimulate proliferation of human thyroid epithelial cells.

The present study was undertaken to investigate cellular interactions between human thyroid epithelial cells (thyrocytes) and endothelial cells. Normal thyrocytes were cultured with either mitomycin C-treated endothelial cells or mitomycin C-treated human foreskin fibroblasts. The proliferative responses of thyrocytes were markedly stimulated by endothelial cells, but not by skin fibroblasts. The proliferative response of the thyrocytes obtained from patients with Graves' disease were similar to that of normal thyrocytes. Furthermore, the cell number of thyrocytes in endothelial cell-thyrocyte co-culture was markedly increased as compared with that in thyrocytes alone. The culture medium of endothelial cells only partly had any effect in the endothelial cell-thyrocyte co-culture experiment. Indomethacin, a cyclooxygenase inhibitor, did not increase the endothelial cells-induced thyrocyte proliferation. Furthermore, the increased proliferative response of thyrocytes stimulated by endothelial cells was not suppressed by heparin. These results suggest that endothelial cells increase thyrocyte proliferation, and that cell contact or extracellular matrix production by endothelial cells may play an important role in the proliferation of thyrocytes.

Cell Count↗

PubMed1991

Clonazepam serum levels in epileptic patients determined simply and rapidly by high-performance liquid chromatography using a solid-phase extraction column.

We studied the use of high-performance liquid chromatography (HPLC), using a solid phase extraction column (Bond Elut cartridge column), for the simple, rapid and sensitive determination of serum clonazepam levels in epileptic patients. Extracted aliquots were analyzed by HPLC, using a reverse phase ODS column (mu-Bondapak C18). The analytical mean recovery of clonazepam added to the blank serum averaged 99.9%. The detection limit was as high as approximately 2 ng/ml in the serum. The reproducibilities were 2.3-8.6 CV % in the within-day assay and 6.5 CV % in the between-day assay, indicating that the analysis method was effective in the determination of clonazepam serum levels. Accordingly, we suggest that the present method, using a solid phase extraction column, may be useful for the routine monitoring of clonazepam serum levels in epileptic patients.

Chromatography, High Pressure Liquid↗

PubMed1991

[Effects of anti-asthmatic drugs on human eosinophil chemotaxis].

To evaluate the acute effects of anti-asthmatic drugs in vitro, we examined the modulation of various anti-asthmatic drugs in therapeutic concentrations on PAF-induced human eosinophil chemotaxis. Aminophylline (20 micrograms/ml) and Isoproterenol (10 nM) inhibited PAF (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas no inhibitory effects were observed by Dexamethasone (0.1 microM), Tranilast, Ketotifen or Azelastine. Aminophylline (20 micrograms/ml) also inhibited LTB4 (3 X 10(-8) M)-induced eosinophil chemotaxis nearly 30%, whereas it did not inhibit chemotaxis induced by zymosan (5 mg/ml)-activated serum. These results indicate that anti-asthmatic drugs except for aminophylline and isoproterenol, when used acutely in therapeutic concentrations, have no striking inhibitory effects on PAF-induced eosinophil chemotaxis. These results further suggest the possibility that there are different mechanisms in eosinophil chemotaxis induced by PAF, LTB4 or by C5a.

Aminophylline↗

PubMed1991

[A case of thyrotoxicosis with prolonged muscle cramp and hypocalcemia after treatment with methimazole].

We report a case of thyrotoxicosis with prolonged post-treatment muscle cramp and hypocalcemia. A 36 year-old woman with hyperthyroidism was treated with Methimazole (MMI). As plasma levels of T4 and T3 were normalized, hypocalcemia was noted and severe cramp of skeletal muscle appeared so that the patient was unable to walk. The cramp was gradually relieved as the levels of thyroid hormones re-increased by discontinuance of MMI, and recurred as the hormone levels were normalized by readministration of MMI. The plasma levels of free calcium ion was positively correlated with those of thyroid hormones, and the muscle cramp was worsened with lowering of the calcium level. Serum examination also revealed vitamin D-deficiency, which was probably due to an unbalanced diet of the patient. A therapeutic trial with 1 alpha-vitamin D3 and calcium lactate in addition to MMI improved both thyrotoxicosis and muscle cramp. These findings suggested that hypocalcemia due to vitamin D-deficiency was involved in the exceptionally prolonged muscle cramp associated with the treatment of hypothyroidism in this patient.

Adult↗

PubMed1991

Detection of Leu-19 (CD56) antigen on human thyroid epithelial cells by an immunohistochemical method.

The Leu-19 (CD56) antigen, which is recognized by anti-Leu-19 and NKH-1 monoclonal antibody, is a 200,000-220,000 molecular weight (MW) glycoprotein that is expressed predominantly on human natural killer (NK) cells that mediate major histocompatibility complex (MHC)-unrestricted cytotoxicity. However, cross-reactivity of this antibody has been observed in lung cancer, and in muscle and neural tissues. In the present study, we used the immunoperoxidase technique to examine the expression of Leu-19 antigen in human thyroid epithelial cells. In normal thyroid tissues (n = 4), thyroid tissues from Graves' patients (n = 7) and benign thyroid tumours (n = 7), thyroid epithelial cells expressed Leu-19 antigen in all cases. In thyroid papillary carcinoma (n = 6) there was no expression in four cases. This staining pattern of anti-Leu-19 antibody is similar to that of anti-thyroid peroxidase antibody. These findings implicate that the expression of Leu-19 antigen is closely related to the differentiation of thyroid epithelial cells.

Antigens, CD↗

PubMed1991

[Eosinophil cationic protein in patients with bronchial asthma].

To evaluate the role of eosinophils in the pathogenesis of bronchial asthma, we measured eosinophil cationic protein (ECP), one of the eosinophil granule proteins. Serum ECP levels were measured by radioimmunoassay in asthmatic (n = 59) and non-asthmatic (n = 47) patients. Preliminary study showed that ECP levels were time-dependently increased in the blood samples until 3 hr. Based on the findings, we determined to measure serum ECP levels at 30 min after blood sampling. Serum ECP levels and blood eosinophil counts in asthmatic patients were significantly higher than those in non-asthmatic patients (p less than 0.01). There was also a positive correlation between serum ECP levels and blood eosinophil counts in patients with asthma (r = 0.46, p less than 0.001). No significant difference was observed in either serum ECP levels or blood eosinophil counts in asthmatic patients classified by clinical type and severity. Blood eosinophil counts in patients with asthma attacks were significantly greater than in those in remission (p less than 0.05), but no significant difference was observed in serum ECP levels between these groups, suggesting an enhanced elimination of ECP during attack. Serum alpha-2 macroglobulins, which bind to ECP and may function as scavengers for ECP, were not significantly different in these group. These results suggest that serum ECP levels may not be a direct indicator of eosinophil activation or degranulation in the pathogenesis of asthma.

Adult↗

PubMed1991

Prevention of posttransfusional non-A, non-B hepatitis by a screening test for hepatitis C virus antibody of donor bloods.

The preventive effect on posttransfusional non-A, non-B hepatitis (PTH) of screening out HCV-Ab positive blood and the prevalence of HCV-Ab-positive donor blood were examined. The incidence of HCV-Ab-positivity in donor blood A was 0.9% and that in donor blood B was 1.35%. The mean ALT and guanase levels were 11.5 +/- 5.8 and 0.58 +/- 0.24 IU/l in HCV-Ab negative blood and 17.3 +/- 7.9 and 0.84 +/- 0.23 IU/l in HCV-Ab-positive blood. Both levels were significantly higher in HCV-Ab-positive blood. These differences were considered to be nonspecific, but there may be some relationship between the levels of ALT and guanase in donor blood and the HCV carrier status. After adoption the screening test for HCV-Ab positive blood, there was no case of a definite diagnosis of PTH, although 4 patients (6.6%) suspected of developing PTH. So, the incidence of PTH was clearly lower than the lowest incidence before adoption of this test. Therefore, we conclude that screening for HCV-Ab in donor blood should be routinely used for prevention of PTH.

Blood Donors↗

PubMed1991

A simple test for mothball component differentiation using water and a saturated solution of table salt: its utilization for poison information service.

All 651 cases of mothball ingestion received by a poison information center were studied. At each time of inquiry, the staff member asked the caller to test whether the mothball floated or sank in water and a saturated solution of table salt. With the results of the test the staff member identified the mothball ingredient. Though most of the callers were housewives with little knowledge of medicine, the differentiations were each completed within 5 min. Later, gas chromatographic analyses revealed that no errors in differentiations had been made. Our method proved a quick preliminary test for mothball component differentiation in poison information service.

Animals↗

PubMed1991

Production of platelet-activating factor in slugs.

The land slug, Incilaria bilineata, was shown to contain a large amount of 1-O-alkyl-2-acyl (long chain)-sn-glycero-3-phosphocholine, which accounts for as much as 47% of the choline glycerophospholipid fraction. Since this unique either phospholipid has been regarded as a stored precursor form of platelet-activating factor (PAF) in mammalian inflammatory cells, we examined the possibility of the presence of PAF in this animal. We obtained the evidence for the occurrence of significant amounts of PAF in two species of slugs, Incilaria bilineta and Incilaria fruhstorferi. Gas chromatography-mass spectrometry analysis revealed that the alkyl fatty chain of PAF principally consists of 16:0. We confirmed the presence of both enzyme activities catalyzing the formation of PAF, one for the remodeling pathway and the other for the de novo pathway. We also found the occurrence of other enzyme activities involved in PAF metabolism: acetylhydrolase activity which inactivates PAF and phospholipase A2 activity toward alkylacylglycerophosphocholine. However, we failed to detect cofactor-independent transacylation activity in this animal. The amounts of PAF in slugs were markedly increased when slugs were administered several treatments which are considered to induce shock, such as the injection of dimethyl sulfoxide or injuries. These results suggest that PAF is produced and may have certain physiological and pathological roles in the land slug, as in the case of mammals.

Acetyltransferases↗

PubMed1991

[Serum beta 2-microglobulin as a index of the initiation of dialysis therapy for diabetic patients with chronic renal failure].

This study was designed whether serum beta 2-microglobulin is good index for the initiation of dialysis therapy in diabetic patients with chronic renal failure. Serum creatinine (S. Cr), beta 2-microglobulin (S. beta 2-MG) and guanidinoacetic acid (S. GAA) were measured in dialyzed or undialyzed diabetic patients with chronic renal failure in comparison with non diabetic patients. 28.6% of diabetic patients showed S. Cr below 8.0 mg/dl at the initiation of dialysis therapy although all of non diabetic patients showed it over 8.0 mg/dl. On the other hand, there was no significant difference in S. beta 2-MG between diabetic and non diabetic patients, and all patients of the two groups showed S. beta 2-MG over 12.0 mg/l. In non diabetic patients whose S. Cr was below 8.0 mg/dl, undialyzed patients had a significant correlation between S. Cr and S. beta 2-MG (r = 0.840, P less than 0.01), and all non diabetic patients showed relatively high value of S. Cr as compared with that of beta 2-MG at the initiation of dialysis therapy. Undialyzed diabetic patients whose S. Cr was below 8.0 mg/dl also revealed a close correlation between serum creatinine and beta 2-MG (r = 0.864, P less than 0.01), but dialyzed diabetic patients showed different correlation between S. Cr and S. beta 2-MG from it of non diabetic patients and S. Cr was underestimated as compared with S. beta 2-MG. Undialyzed diabetic patients showed significant lower values of S. Cr and S. GAA of non diabetic patients whose S. beta 2-MG were almost same as diabetics.(ABSTRACT TRUNCATED AT 250 WORDS)

Creatinine↗

PubMed1991

[Eosinophil activation in acute asthma attacks evaluated by electronmicroscopic findings of eosinophils and the concentration of eosinophil cationic protein in sputum].

We evaluated the activation of eosinophils in the airways of patients with acute asthma attacks by measuring the concentration of sputum eosinophil cationic protein (ECP) and changes in the electron densities of the eosinophil specific granules in sputum. In six hospitalized patients with asthmatic attacks, sputum samples were collected for seven consecutive days after admission and were used for the evaluation of eosinophil activation. The concentration of sputum ECP, the incidence of changes in the electron densities of eosinophil specific granules and the severity of asthma attacks were highest on the day of admission and decreased in association with each other after treatment. A significant correlation was found between the concentration of sputum ECP and the incidence of changes in the electron densities of eosinophil specific granules. These findings suggest that the eosinophils in the airways are markedly activated and degranulated in asthma attacks.

Adult↗