Search PubMed⌕ Search

Biomedical subjects

S Murata

Publications and source records attributed to S Murata.

At least 271 records · Page 15Linked to original sources

Gastric motility and emptying in health and after vagotomy and after gastric resection.

By observing the relation of the three emptying curves on the whole stomach, proximal and the antral area, we could clarify the distinction of the emptying curves for the stomach forms in healthy subjects, and the gastric emptying motility and the movement of gastric contents were also clarified. Based on these results, the emptying curves on SPV and segmental gastrectomy were studied. From these results, we concluded that the emptying of SPV was similer to that of the healthy subjects when pyloroplasty was applied to SPV. On the segmental gastrectomy, we could make it clear that when pyloromyotomy was applied to the segmental gastrectomy, early rapid emptying did not occur, either. In addition to these results, we would like to emphasize the necessity for describing three curves on the whole stomach area, the proximal area and the antral area for the analysis of gastric emptying and motility.

Gastrectomy↗

Dexamethasone suppression test in autistic children.

A dexamethasone suppression test (DST) was carried out on autistic and other handicapped children to investigate the function of the hypothalamo-pituitary adrenal axis (HPA-axis). The subjects were 19 autistic children consisting of 11 relatively well-developed and eight poorly-developed children. The control groups were 26 normal volunteers, 19 patients with schizophrenia and 15 children with mental retardation (MR) or minimal brain dysfunction (MBD). The DST procedures followed the Carroll method. As a result, all of the normal volunteers and 19 schizophrenic patients showed normal response (suppressor). Nine of the 11 well-developed autistic children exhibited suppressor, while all of the poorly-developed children showed an abnormal response (non-suppressor). Nine of the 10 children with MR and all of the five children with MBD were suppressor. These results suggest that there might be a dysfunction in the HPA-axis of the poorly-developed autistic children.

Adolescent↗

A novel method to predict the elimination half-lives and the renal excretion mechanisms of cephalosporins.

A novel method was proposed to predict the elimination half-lives of cephalosporins from plasma protein binding (unbound fraction, f) and fraction of the dose excreted into urine (f*) on the basis of the following four assumptions. 1) The drug is only distributed to the extracellular fluid, 2) the bound fraction of the drug in plasma is independent of the plasma drug concentration, 3) the binding protein of the drug is albumin, 4) the unbound drug in plasma is excreted by the glomerular filtration and the contribution of active secretion and reabsorption is negligible. The VSS's and t1/2 beta's of MT-141, one of cephalosporins, in rabbits, dogs and healthy human subjects were well predicted, whereas in rats, the prediction of the both values was failed. The t1/2 beta's of various cephalosporins in healthy subjects were calculated from f and f*, in reasonably good agreement with the observed ones, except for some cephalosporins which have been reported to be secreted actively in the renal tubules. Thus, the comparison of the calculated t1/2 beta's with the observed ones makes it possible to presume the renal excretion mechanism. Moreover, this method will be applicable to other drugs which satisfy the above four assumptions.

Animals↗

Cardiovascular effects of a new positive inotropic agent, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]-ethanol (TA-064) in the anesthetized dog and isolated guinea pig heart.

The positive inotropic effect of TA-064, (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, was studied in the anesthetized dog and isolated guinea pig heart. An intravenous administration of TA-064 dose-dependently increased the cardiac contractile force with little effect on blood pressure in dogs. The positive inotropic activity of TA-064 was 1/100 that of isoproterenol and similar to that of dobutamine. This effect of TA-064 was stereospecific, and it was blocked by practolol. Thus TA-064 has beta 1-adrenoceptor agonistic action. The positive inotropic effect of TA-064 was more pronounced than the positive chronotropic effect, compared with those of isoproterenol. Similar effect of TA-064 was observed in the reserpinized dog and in the isolated perfused heart of the guinea pig as well. TA-064 administered intraduodenally at a dose of 0.1 mg/kg increased contractile force by 120% of the control, and the effect lasted for more than 150 min. TA-064 given in the femoral artery demonstrated a very weak vasodilating effect on the artery. TA-064 is an orally active, positive inotropic agent. The selective positive inotropic action of TA-064 may result from its beta 1-adrenoceptor agonistic property.

Adrenergic beta-Agonists↗

Therapeutic efficacy of a new cephamycin, MT-141, in compromised mice.

The antibacterial activity of MT-141 against Escherichia coli and Proteus morganii in compromised mice was investigated and compared with that of latamoxef, cefmetazole and cefoxitin. The bactericidal activity of MT-141 in short-term contact with E. coli and P. morganii was markedly enhanced when combined with mouse serum, and the activity of MT-141 was greater than the activities of the three reference drugs. The antibacterial activities of MT-141 in the liver, spleen and kidney of neutropenic and Sarcoma 180 tumor-bearing mice infected with E. coli and P. morganii were superior to the activities of the reference drugs. MT-141 was more potent than cefmetazole and cefoxitin, and similar to latamoxef in potency against systemic P. morganii infection in Sarcoma 180 tumor-bearing mice.

Animals↗

[The mutagenicity evaluation of MT-141, a new cephamycin].

Mutagenicity of MT-141, a new cephamycin, was evaluated by in vitro and in vivo assays. MT-141 did not induce mutations of the test strains, Escherichia coli WP2 (uvr A) and Salmonella typhimurium TA1535, TA1537, TA1538, TA100 and TA98, with and without metabolic activation in vitro. In bone marrow micronucleus assay with male mice, MT-141 showed no induction of micronucleated polychromatic erythrocyte at 6 hours and 30 hours after administration. In addition MT-141 was found not to cause any dominant lethal effects on male mice for 8 weeks after administration.

Animals↗

[Distribution, metabolism and excretion of 14C-MT-141 in rats. I. Distribution, metabolism and excretion after single intravenous administration in male rats].

The distribution, metabolism and excretion of the radioactivity were studied in male rats after the bolus intravenous administration of 14C-MT-141. The biological half-lives obtained from the blood concentration-time curve were 0.43 hour for the data in the first 4 hours and 16.5 hours for the data from 6 hours to 24 hours after the intravenous administration of 14C-MT-141. The radioactivity was excreted mainly into urine, and the cumulative urinary and fecal excretion of the radioactivity were 75.2% and 24.1% of the dose, respectively, within 120 hours after the intravenous administration of 14C-MT-141. The cumulative biliary excretion of the radioactivity was 18% of the dose within 48 hours after the intravenous administration, and 35% of the radioactivity excreted into bile (about 6% of the dose) was reabsorbed from the intestine. The highest concentration of the radioactivity was observed in the kidneys, and also the relatively high concentrations were observed in the liver, plasma and intestine, while the concentrations in the brain, fat and muscle were low. Within 24 hours after the intravenous administration of 14C-MT-141, the radioactivity in the highly distributed organs or tissues was decreased to less than 3% of the values at 5 minutes after the intravenous administration. A small amount of N-acetyl-MT-141 was found in urine and feces as a metabolite.

Animals↗

[Distribution, metabolism and excretion of 14C-MT-141 in rats. II. Distribution and excretion after multiple intravenous administration in male rats and after single intravenous administration in female rats].

The distribution and tissue accumulation of the radioactivity were studied in male rats after the multiple intravenous administration of 14C-MT-141. The distribution and the placental transfer were also studied using pregnant rats or lactating rats after the single intravenous administration of 14C-MT-141. The radioactive concentration in the fetus was low and the radioactivity was distributed almost uniformly through the fetus body. The peak time of the milk level was 2 hours after the administration and the radioactivity in milk decreased gradually thereafter. The milk levels decreased more slowly than the blood levels did. The blood level after the last dose administered daily for 7 days tended to decrease more slowly, when compared with the single administration. However the blood concentration at 48 hours after the last administration was less than 3 times as high as that after the single administration.

Animals↗

[Pharmacological studies on a new cephamycin, MT-141. (2) Its effect on preparations of neuromuscular junction, smooth muscle organs and gastro-intestinal system].

The results for pharmacological experiments of MT-141 were as follows; Twitch tension of gastrocnemius muscle evoked by the stimulation of sciatic nerve was slightly reduced with 400 mg/kg MT-141 i.v. and upper doses. As the change was very small, however, it seems that MT-141 has no neuromuscular junction blocking action. Although MT-141 did not show any effects on most of isolated smooth muscle organs, only isolated tracheal muscle was somewhat relaxed with 10(-3) g/ml MT-141. The spontaneous motility of smooth muscle in situ was temporarily increased with 800 mg/kg MT-141 i.v. and upper doses. Two hundred mg/kg MT-141 showed no effect on the value of blood sugar and functions of kidney and liver. Any hemolysis did not appear even in the highest dose of 200 mg/kg MT-141 used in this experiment. From the present results and previous report (Krebe, M. et al., Jap. J. Antibiotics, in press), it seems that MT-141 is promised to be a highly safe and useful antibiotic agent in clinical use.

Anesthetics, Local↗

Analysis of bile acids by micro high-performance liquid chromatography with postcolumn enzyme reaction and fluorometric detection.

Free and conjugated bile acids in human sera were analyzed by micro high-performance liquid chromatography with detection by an immobilized hydroxysteroid dehydrogenase postcolumn reaction and a spectrofluorometer. Bile acids could be effectively collected on a precolumn, 10 X 0.2 mm I.D., packed with silica-ODS (octadecylsilane), by passing a dilute phosphate solution of a serum through it. The detection limit was 0.13-0.28 pmole for a single-to-noise ratio of 2. An amount of 0.1 ml of serum was enough for analysing each bile acid in it.

3-Hydroxysteroid Dehydrogenases↗

Purification and fluorometric assay of proteinase A from yeast.

Proteinase A was purified from commercial baker's yeast to homogeneity by using affinity chromatography. Simple and sensitive fluorometric assay procedures were developed for this enzyme, where Suc-Arg-Pro-Phe-His-Leu-Leu-Val-Tyr-4-methylcoumaryl-7-amide and dimethylcasein were used as synthetic substrate and protein substrate, respectively. Proteinase A cleaved the former substrate at the Leu-Val bond. The extent of the cleavage was monitored by measuring the amount of fluorescent 7-amino-4-methylcoumarine produced by the successive cleavage with an auxiliary enzyme, aminopeptidase M, or by measuring the fluorescence generated by the reaction of newly formed amino groups with fluorescamine. In the assay with the latter substrate, the amounts of newly formed amino groups were measured by the reaction with fluorescamine. The optimal pH of the reaction was 5.0 to 5.5. The methods were applied to the study of the effects of denaturing agents on the activity of proteinase A.

Aspartic Acid Endopeptidases↗

[Experimental study on the action mechanism of a new bronchodilator agent, BB-1502].

The action mechanism of the bronchodilator activity of BB-1502 was studied in comparison with aminophylline. Orally administered BB-1502 did not inhibit passive cutaneous anaphylaxis in rats, an immediate allergic reaction of Type I, but strongly protected the same antigen-mediated anaphylactic asthma by the intraduodenal route, the activity being approximately 13 times more potent than that of aminophylline. BB-1502 also inhibited IgG-mediated anaphylactic asthma in guinea pigs by the oral route. Both IgE- and IgG-mediated histamine releases from rat lung were similarly inhibited by BB-1502, the potency being 2--3 times that of aminophylline. Disodium cromoglycate showed specific inhibition of the IgE-mediated reaction. BB-1502 and aminophylline showed nonspecific inhibition of the spasms of guinea pig ileum elicited by histamine, acetylcholine and BaCl2. Both compounds inhibited cyclic AMP and cyclic GMP phosphodiesterases (PDEs) derived from guinea pig organs. BB-1502 specifically inhibited the cyclic AMP PDE of lung and brain origins, while aminophylline showed no such specificity. The results of the present study suggested that the bronchodilator and anti-asthmatic actions of BB-1502 might, at least in part, be due to the regulation of cyclic nucleotide PDEs.

3',5'-Cyclic-AMP Phosphodiesterases↗