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Biomedical subjects

H Kitagawa

Publications and source records attributed to H Kitagawa.

At least 505 records · Page 28Linked to original sources
PubMed1985

Pharmacologic studies of the central action of zopiclone: effects on locomotor activity and brain monoamines in rats.

To investigate the effects of zopiclone on the central nervous system, we examined the effects of zopiclone on brain monoamines such as dopamine (DA), noradrenaline (NA) and serotonin (5-HT) and their metabolites such as homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA), as well as locomotor activity in comparison with those of nitrazepam and flurazepam. Zopiclone in a dose of 10 mg/kg (p.o.) significantly reduced it (p less than 0.01) in 30 min and the reduced locomotor activity persisted until 180 min. The reducing effect on locomotor activity by zopiclone was similar to that of nitrazepam and more potent than flurazepam. The effects of zopiclone on brain monoamines (MA) were examined. No significant changes in DA, NA and 5-HT were observed, but HVA and 5-HIAA were reduced. A fluorescent-histochemical study conducted simultaneously revealed almost the same results as the biochemical test results. From the facts that zopiclone inhibited locomotor activity in rats, and inhibited brain DA and 5-HT turnover, the mechanism of action of zopiclone in brain MA neurons seems to be similar to that of benzodiazepine derivatives.

Animals↗
PubMed1985

Pharmacologic studies of central actions of zopiclone: influence on brain monoamines in rats under stressful condition.

In order to investigate the central action of zopiclone, the rat brain was divided into 8 regions and the changes in monoamines (MA) in each region were examined. The effect of zopiclone on stress was also examined from changes in brain monoamines under electro-footshock stress load in comparison with that of nitrazepam and flurazepam. The animals were decapitated at 1 h after administration of zopiclone, nitrazepam and flurazepam at each dose of 1 and 10 mg/kg (p.o.). No changes in MA at each region of the brain were noted, but the metabolite, homovanillic acid (HVA) was reduced at the cortex, hippocampus, hypothalamus and cerebellum. 5-hydroxyindoleacetic acid (5-HIAA) was reduced at the amygdala. Noradrenaline (NA) turnover accelerated by electro-footshock stress load was inhibited by zopiclone. From the results of this experiment, it was found that the effects of zopiclone on brain MA were similar to those of nitrazepam and flurazepam: inhibition of 5-HT turnover at the amygdala was common to these three compounds. This result suggests that zopiclone has similar pharmacological properties to benzodiazepines as an antianxiety agent.

Amygdala↗
PubMed1985

Effect of repeated administration of monomethyl-aminoantipyrine on the activities of gamma-glutamyltranspeptidase and microsomal drug metabolizing enzymes in rat liver.

The effects of consecutive administration of 4-monomethylaminoantipyrine, a metabolite of aminopyrine, on the gamma-glutamyltranspeptidase activities of liver, kidney, urine and serum were investigated in rats. On day 5 after repeated treatment, a pronounced increase of gamma-glutamyltranspeptidase activity was seen in the liver homogenate as well as in the hepatic microsomes. Furthermore, simultaneous administration of 4-monomethylaminoantipyrine with phenobarbital increased to the same degree as compared with the single administration of aminopyrine. However, no change in gamma-glutamyltranspeptidase activity was observed in kidney, urine, serum and hepatic cytosolic fractions. Under the same experimental condition, the contents of cytochrome P-450 and b5, NADPH cytochrome c reductase, the activities of aminopyrine N-demethylase and aniline hydroxylase were also enhanced.

Aminopyrine↗
PubMed1985

Simultaneous purification and properties of dehydropeptidase-I and aminopeptidase-M from rat kidney.

Two peptidases, dehydropeptidase-I and aminopeptidase-M were solubilized from rat kidney microsomes by treatment with papain and separated by DE-52 ion exchange chromatography. Each enzyme was further purified by Sephacryl S-300 gel filtration and affinity chromatography on Con-A Sepharose. Purified dehydropeptidase-I and aminopeptidase-M were homogeneous by SDS-polyacrylamide gel electrophoresis, and their molecular weights were estimated by gel filtration to be 148,000 and 240,000, respectively; both being homodimer, with a 78,000 subunit for the former and a 120,000 subunit for the latter. Both dehydropeptidase-I and aminopeptidase-M were capable of hydrolyzing L-leucyl-L-leucine with a Km valve of 1.1 mM and 1.7 mM, respectively, although the hydrolyzing activity of aminopeptidase-M was much higher than that of dehydropeptidase-I. Aminopeptidase-M was inhibited by bestatin, and dehydropeptidase-I was significantly inhibited by cilastatin. Dehydropeptidase-I catalyzed the conversion of leukotriene D4 to E4 and the hydrolysis of L-cystinyl-bis-glycine, but aminopeptidase-M did not to any appreciable extent. The physiological significance of dehydropeptidase-I was pointed out and discussed.

Aminopeptidases↗
PubMed1985

Effects of atropine and pirenzepine on healing of gastric ulcer induced by mucosal excision in rats.

We studied the effects of atropine and pirenzepine on acid secretion induced by electrical vagal stimulation (EVS) and on healing of gastric ulcers after mucosal excision in rats. Both atropine (50, 125, and 250 micrograms/kg/hr) and pirenzepine (2.5, 5.0, and 12.5 mg/kg/hr), administered intraperitoneally, inhibited vagally stimulated acid secretion in a dose-dependent manner. Pirenzepine given at a rate of 0.25 mg/kg/hr had no effect on the acid secretory response to EVS. Either atropine (125 micrograms/kg/hr) or pirenzepine (2.5 mg/kg/hr) given for one week caused an inhibition of approximately 80% in acid secretory response to EVS. The antisecretory dosage of pirenzepine caused a significant reduction in the surface area of the ulcer by the seventh postoperative day, whereas neither the antisecretory dosage of atropine nor the nonantisecretory dosage of pirenzepine significantly affected the size of the ulcer. We conclude that an antisecretory dosage of pirenzepine accelerates the healing of gastric ulcers produced in rats.

Animals↗
PubMed1985

Embryotoxic effects of EGTA-induced hypocalcemic condition on cultured rat embryos.

EGTA-treated rat serum was added to the culture medium and tested the toxic effect of EGTA on development of embryo using 11.5-day-old embryo in vitro. Exposure of the embryo to the medium treated with 25 micrograms/ml of EGTA for 2 or 24 hours caused a variety of teratogenic effects such as tail and hind limb bud deformities and facial anomalies (cleft lip). At a higher concentration of EGTA (50 micrograms/ml), damage of yolk sac (shrinkage type), developmental anomalies and dead fetuses were frequently observed. Embryonic growth and differentiation were only moderately affected under any experimental conditions. Calcium levels in EGTA-treated culture medium at doses of 25 and 50 micrograms/ml were significantly reduced as compared to the non-treated medium. These results suggested that the teratogenic action of EGTA is closely related to the decrease of calcium level in the medium.

Abnormalities, Drug-Induced↗
PubMed1985

[Therapeutic effect of sequential doses of methotrexate (MTX) and 5-fluorouracil (5-FU) in advanced gastric cancer: comparison of intermediate-dose MTX with high-dose MTX].

Twenty-one patients were treated with sequential doses of MTX and 5-FU so as to be classified by MTX dosage into an intermediate MTX-dose group and a high MTX-dose group. In the intermediate-dose MTX group, the drug was given at a dosage of 100 mg/m2 intravenously (i.v.) and followed 1 hour later by 5-FU at 800 mg/m2 i.v. (dripping for 1 hour); the drugs were recycled every 1 week. In the high-dose MTX group, the drug was administered at a dose of 1.5 g/m2 i.v. (dripping for 2 hours) and followed 1 hour later by 5-FU at 1.5 g/m2 i.v. (dripping for 2 hours); the drugs were recycled every 2-3 weeks. Average MTX concentrations in serum at the start of 5-FU administration were 1.69 X 10(-5) and 1.33 X 10(-4) mol/l/h in the intermediate and high-dose MTX groups, respectively. Six (50%) of 12 patients adequately treated with intermediate-dose MTX had a partial response (PR), and one (14.3%) of 7 evaluable patients treated with high-dose MTX had a PR. Major toxicity included diarrhea (33.3%) in the intermediate-dose MTX group and hair loss (71.4%) in the high-dose MTX group. Hematological toxicity was mild in MTX group: six (50%) of 12 patients had a granulocyte count nadir less than 1,000/microliters and one (8.3%) of 12 patients had a platelet count nadir less than 10(5)/microliters in the intermediate-dose MTX group. Five (71.4%) of 7 patients had a granulocyte nadir less than 1,000/microliters and two (28.6%) of 7 patients had a platelet count nadir less than 10(5)/microliters in the high-dose MTX group.

Adult↗
PubMed1985

Effects of adrenalectomy on gonadal hormone-induced changes in hepatic microsomal carboxylesterase activities in rats.

Hepatic microsomal carboxylesterase (E.C. 3.1.1.1) showed a different capacity for the hydrolysis of various substrates in rats. Adrenalectomy in castrated male rats slightly decreased the activities towards p-nitrophenyl-acetate and malathion. The magnitude of testosterone-induced changes in the hydrolase activities by liver microsomes in adrenalectomized-castrated male rats was markedly decreased castrated male rats. However, when 5 alpha-dihydrotestosterone was administered to adrenalectomized-castrated male rats, malathion and p-nitrophenylacetate hydrolase activities were significantly increased. But in all cases, isocarboxazid and acetanilide hydrolase activities were not affected by physiological states. These results suggest that hepatic microsomal carboxylesterases may be, at least in part, regulated by adrenal gland and gonadal hormones which exert different effects on the several isozymes of carboxylesterases.

Adrenalectomy↗
PubMed1985

[Study on placental blood flow in late pregnancy by intravenous 99mTc method].

A method for the continuous recording of uteroplacental blood flow (PBF) in late pregnancies by using 99mTc-albumin has been described. The PBF curve of toxemia of pregnancy has been plotted to indicate small artery spasm in proving ischemic necrosis of placenta. In the PBF of placental insufficiency evidenced by the values for urinary E3, an unfavorable build-up and a delayed build-up time were observed. The pathologic diagnosis showed condensation, fusion and necrosis of villi. In the PBF in which a intrauterine fetal death (IUFD) was caused by placental factors, a sudden change in the PBF was observed showing the presence of an ischemia. In the PBF of pregnancy with diabetes, a large wave pattern change was observed indicating a decrease in the PBF. The pathologic diagnosis showed the fusion, hyalinization and necrosis of villi. The PBF wave patterns were classified into four kinds: normal pattern, angio-spasm pattern, delayed build-up pattern, circulation pattern. It has become clear that these abnormal wave patterns are frequently observed in toxemia of pregnancy, placental insufficiency and pregnancy with diabetes.

Female↗
PubMed1985

Increase in anti-carboxylesterase action of organophosphorothioates by nicotinamide adenine dinucleotide (NAD) in vitro.

The purpose of the present study was to investigate the relationship between chemical structure of organophosphorus insecticides and potentiation of anti-carboxylesterase (CEase) action of these insecticides by NAD in vitro (NAD-effect). Experiments using with three organophosphorothioates having ethoxy group except for diazinon exhibited greater NAD-effect than those having methoxy ones such as methylparathion and fenitrothion. In contrast, none of five organophosphates tested showed NAD-effect. And, 3-acetylpyridine adenine dinucleotide (Ac-py AD) among four derivertives of NAD was also found to have NAD-effect. These results suggested that P = S group in the molecule of organophosphorus insecticides was needed to occur NAD-effect. In addition, the extent of NAD-effect using acetylcholinesterase (AChE) was lesser than that of CEase, therefore, a higher susceptibility of liver microsomal CEase to organophosphorus insecticides may be explained, at least inpart, by NAD-effect.

Animals↗
PubMed1985

Inhibition of sympathetic nervous system by mexiletine, an antiarrhythmic agent, and its antagonism against ouabain.

The effects of mexiletine on the sympathetic nervous system and the antiarrhythmic action were studied and compared with those of lidocaine. In isolated blood vessels, mexiletine inhibited the contractile responses to nicotine, tyramine and electrical transmural stimulation, but did not affect the contractile responses to exogenous norepinephrine and KCl. Lidocaine also inhibited the contractile responses to nicotine and electrical transmural stimulation, but such an inhibitory activity was weaker than that of mexiletine. Lidocaine did not affect the contraction induced by tyramine and enhanced significantly contractile responses to exogenous norepinephrine and KCl. Mexiletine and lidocaine inhibited the release of 3H-norepinephrine from the isolated rabbit pulmonary artery induced by transmural electrical stimulation. Mexiletine increased the dose of ouabain required for the occurrence of arrhythmia and cardiac arrest. These effects of mexiletine did not occur after reserpine. Though lidocaine increased the dose of ouabain required for cardiac arrest, the development of arrhythmia was not prevented. The increase in the dose of ouabain required for cardiac arrest induced by lidocaine was not affected by reserpine. On the other hand, mexiletine and lidocaine prevented the epinephrine-induced arrhythmia. These results suggested that the antagonism of mexiletine against ouabain may be due not only to the previously reported quinidine-like direct action on the myocardium, but also partially to the inhibitory action on releasing norepinephrine from the sympathetic nerve terminals.

Animals↗
PubMed1984

Purification and properties of cytochrome P-450 from untreated monkey liver microsomes.

Untreated monkey liver cytochrome P-450 (monkey P-450) has been purified to a specific content of 14.9 n mole/mg protein. The purified preparation was apparently homogeneous and the minimum molecular weight was estimated to be 50,000 by SDS-PAGE. Absolute spectrum of the oxidized form showed peaks at 565, 535 and 417 nm. The monkey P-450 was active in the mixed function oxidation of benzphetamine, aminopyrine, ethylmorphine, aniline and 7-ethoxycoumarin in the presence of rat liver NADPH-cytochrome P-450 reductase and DLPC. Anti monkey P-450 IgG could not inhibit rat P-450s (PB P-450, MC P-448(1) and MC P-448(2] catalyzed 7-ethoxycoumarin O-deethylation activities.

Animals↗
PubMed1984

Antitussive effect of RU-20201--central and peripheral actions.

The antitussive effect of the new compound 1, 2, 3, 4a, 9b-hexahydro-8, 9b-dimethyl-4-[3-(4-methyl-piperazine-1-yl) propionamide] dibenzofuran-3-one dihydrochloride (RU-20201) was investigated in dogs and guinea pigs, including its sites of action. The antitussive effect of RU-20201 was about 1/10 as potent as that of codeine phosphate in dogs with the puncture electrode-induced cough (PEC) method and about 1/12 and 1/4 as potent as that of codeine phosphate in guinea pigs with the PEC and chemical stimulation methods, respectively. When RU-20201 was administered in a dose range of 1 to 10 mg into the vertebral artery toward the brain in lightly anesthetized dogs, no antitussive effect was observed against the coughing elicited by electrical stimulation of the central cut end of the superior laryngeal nerve. However, a stimulative effect on respiration, especially on respiratory rate occurred. The peripheral effect of RU-20201 on the cough was investigated using the in situ upper trachea perfusion preparation which allows a direct drug administration to the local site around the tracheal mucosa, this site being electrically stimulated to induce coughing. A close i.a. infusion of RU-20201 in doses of 1 and 3 mg/min into the tracheal vascular bed for 5 min inhibited the cough response elicited by mucosal stimulation. The above findings suggest that RU-20201 has a significant antitussive activity, the site of action being probably, at least, at the cough receptor level.

Animals↗
PubMed1984

Potentiation of EPN-induced inhibition of liver microsomal carboxylesterase by addition of liver cytosol from 6-aminonicotinamide-treated, starved rats.

Addition of liver cytosol from 16 hr-starved rats treated with 6-aminonicotinamide to rat liver microsomes caused potentiation of the anti-carboxylesterase action of ethyl-p-nitrophenyl phenylphosphonothioate (EPN). This was not found when liver cytosol from non-pretreated rats after 16 hr-starvation was used. This potentiation of EPN-induced inhibition of carboxylesterase may be, at least in part, explained by the fact that treatment of rats with 6-aminonicotinamide resulted in a significant increase in NADPH level in liver cytosol which, in turn, stimulated formation of an EPN oxygen analog, a potent inhibitor of carboxylesterase, through cytochrome P-450-coupled monooxygenase.

6-Aminonicotinamide↗