Biomedical subjects

S Otsubo

Publications and source records attributed to S Otsubo.

17 recordsLinked to original sources

PubMed1991

[An operated case report of pulmonary aspergillosis by sapprophytic infection of Aspergillus candidus in congenital bronchial cyst of right lower lobe].

Aspergillosis is a mycotic disease caused by a variety of species of the dimorphic fungus aspergillosis, especially aspergillus fumigatus. But the report of pulmonary aspergillosis by aspergillus candidus is very rare. We experienced a surgical case of pulmonary aspergillosis caused by aspergillus candidus. The patient is a 18-year-old girl. Eleven years ago, she had suffered from pneumonia of rt. lower lobe, there after she often has suffered from cough and fever every year. In 1986, chest x-ray photography shows a small cavity in rt. lower lobe. In 1989, it becomes a big cavity of 8 X 8 cm in diameter with niveau. She has cough and bloody sputum of 100-150 ml daily. We have cultured aspergillus candidus from sputum, bloody pus obtained by percutaneous aspiration needle lung biopsy of the cavity and bloody pus in the cavity which was resected on March 3, 1989. But the pathological investigation could not demonstrate any fungus ball or fungus body of aspergillus candidus.

Adolescent↗

PubMed1988

[Effect of the nonsteroidal anti-inflammatory drug 480156-S on hepatic drug-metabolizing activity and pharmacological action of diazepam and pentobarbital in rats].

Effect of the nonsteroidal anti-inflammatory drug 480156-S on liver drug-metabolizing activity was studied in rats, and its effect was compared with that of cimetidine. Cytochrome P-450-dependent 7-alkoxycoumarin O-dealkylase activity was not affected by a single administration of 480156-S, but the activity, especially the O-demethylase but not the O-depropylase, was suppressed dose-dependently by multiple administrations. Pretreatment of rats with phenobarbital caused a diminution of the inhibitory action of 480156-S. Treatment of rats with cimetidine resulted in a marked decrease in the activity, although it recovered 24 hr later. After the pretreatment of animals with 480156-S or reference drugs, the pharmacological action of diazepam was determined using muscle relaxation and inhibitions of electroshock-induced convulsion and pentetrazole-induced clonic convulsion as the indicators. Prolonged pharmacological activity of diazepam was observed when liver drug-metabolizing activity was lowered by the pretreatment. On the other hand, pentobarbital-induced anesthesia was prolonged by the pretreatment of rats with cimetidine, but the anesthesia was not modified by the administration of 480156-S. These results suggest the inhibitory action of 480156-S on a specific form(s) of P-450 isozyme.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1987

Effects of beta-lactam antibiotics on the acetaldehyde-metabolizing system in germ-free rats.

Effects of several beta-lactam antibiotics on the acetaldehyde-metabolizing system were studied using germ-free rats. Administration of cefamandole (CMD) to the rats caused a decrease in liver mitochondrial low Km aldehyde dehydrogenase activity and an increase in blood acetaldehyde level during ethanol metabolism, similar to the case in conventional rats. Oral administration of CMD produced a pronounced increase in blood acetaldehyde level compared to the subcutaneous administration of the antibiotic. When the animals were given various beta-lactam antibiotics subcutaneously, only the antibiotics having an N-methyltetrazolylthiomethyl group at the 3-position of the cephalosporin nucleus exhibited the disulfiram-like effects on the acetaldehyde-metabolizing system. The results indicate that intestinal bacteria do no participate in the development of the disulfiram-like reaction of several beta-lactam antibiotics.

Acetaldehyde↗

PubMed1987

Pharmacokinetics of latamoxef and N-methyltetrazolethiol in rats associated with the development of disulfiram-like effects.

The disulfiram-like effect of beta-lactam antibiotics, having an N-methyltetrazolethiol (NMTT) as a 3'-position substituent of the cephalosporin nucleus, was determined in rats using latamoxef (LMOX) as a model. Intravenous and subcutaneous administrations of these antibiotics caused a decrease in the low Km aldehyde dehydrogenase (ALDH) activity in liver mitochondria and an increase in blood acetaldehyde level during ethanol metabolism, as in the case of disulfiram. When the antibiotic was administered intravenously to biliary fistula rats, the blood acetaldehyde level did not increase. On the other hand, oral administration of antibiotic to normal and biliary fistula rats caused pronounced development of disulfiram-like effects in both animals. When LMOX was injected to normal rats, the rapid and slow eliminations of LMOX and NMTT, respectively, were observed from blood and liver. After oral administration of LMOX, NMTT remained in the blood and liver for a long time with higher concentrations, although LMOX could not be detected in the body. With biliary fistula rats, intravenous injection of LMOX led to rapid urinary excretion of both LMOX and NMTT. These results indicate that the development of disulfiram-like effects of NMTT-containing antibiotics is closely related to the pharmacokinetic profile of NMTT released from its parent drugs.

Acetaldehyde↗

PubMed1987

Effects of beta-lactam antibiotics and N-methyltetrazolethiol on the alcohol-metabolizing system in rats.

The disulfiram-like effect of various beta-lactam antibiotics containing N-methyltetrazolethiol (NMTT) on the alcohol-metabolizing system was studied using rats. Their administration caused decreased activities in low Km aldehyde dehydrogenase (ALDH) and acetaldehyde oxidation in the liver, with marked depression from several hours to 2 days after the treatment. Blood acetaldehyde level increased markedly when ethanol was administered 18-24 hr after pretreatment with antibiotics. A similar time course change in the effect was obtained when disulfiram was administered. The following results obtained in the present study indicate that the disulfiram-like effect associated with these antibiotics was not mediated by the whole molecular structures of these drugs: Firstly, the antibiotics were eliminated rapidly from the plasma and liver, and the disulfiram-like effect was followed by a disappearance of the drugs. Secondly, the concentration of antibiotics required to inhibit mitochondrial low Km ALDH activity in vitro was very high compared with their liver concentration. Thirdly, rapid onset of disulfiram-like effects occurred after administration of NMTT itself, and a pronounced elevation of blood acetaldehyde level was observed when ethanol was administered 3-5 hr after the NMTT injection. Fourthly, almost the same amounts of NMTT were released in the body after the intravenous administration of various NMTT-containing antibiotics, as judged by the urinary excretion. These results suggest that the disulfiram-like effect of beta-lactam antibiotics is mediated by NMTT released from them.

Acetaldehyde↗

PubMed1987

Effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics on ethanol elimination in rats.

The in vivo effects of alcohol-metabolizing enzyme inhibitors and beta-lactam antibiotics upon the ethanol elimination rate were examined in rats. Intravenous administration of ethanol caused a dose-dependent increase in blood ethanol level, and the ethanol elimination could be well described by a two compartment model. Pretreatment of rats with enzyme inhibitors caused a marked decrease in the ethanol elimination rate associated with the depression of the enzyme activities. Fasting of the animals caused a decrease in the ethanol elimination rate per animal associated with a decrease in the liver weight. However, no alteration was evident when the rate was expressed as the rate per g of liver. When animals were pretreated with a high dose of N-methyltetrazolethiol (NMTT)- containing beta-lactam antibiotics or NMTT itself, which causes a disulfiram-like reaction, the ethanol elimination rate per animal was depressed concomitant with an increase in the blood acetaldehyde level. The ethanol elimination rate in these animals showed lower values even when expressed as the rate per g liver. On the other hand, administration of cephems without NMTT, which cause no disulfiram-like reaction, led to a slight decline in the elimination rate per animal, although no alteration was detected when the rate was expressed as the rate per g liver. The findings indicated that the ethanol elimination in vivo per animal is regulated by the total capacity of the alcohol-metabolizing enzyme activities in the whole liver.

Acetaldehyde↗

PubMed1986

A comparative study on the effects of disulfiram and beta-lactam antibiotics on the acetaldehyde-metabolizing system in rats.

Several beta-lactam antibiotics, especially those containing N-methyltetrazolylthiomethyl groups at the 3-position of the cephalosporin nucleus, affect the alcohol-metabolizing system in rats. These effects were compared those with disulfiram, well-known as a potent inhibitor of aldehyde dehydrogenase (ALDH). Both disulfiram and antibiotics containing the N-methyltetrazolylthiomethyl group inhibited both mitochondrial low Km ALDH and acetaldehyde oxidation in rat livers. The high Km ALDH and alcohol dehydrogenase activities in livers were not affected by these treatments. When ethanol was given to rats pretreated with disulfiram or these antibiotics, the blood acetaldehyde concentration increased markedly concomitant with a decrease in activity of the low Km ALDH. Administration of N-methyltetrazolethiol alone suppressed the low Km enzyme activity and also increased the blood acetaldehyde level; both effects were pronounced and observed several hours after administration. beta-Lactam antibiotics without N-methyltetrazolethiol in their molecule did not affect the liver mitochondrial enzyme activity or the blood acetaldehyde level.

Acetaldehyde↗

PubMed1983

Liver microsomal cytochrome P-450-dependent O-dealkylation reaction in various animals.

Liver microsomal O-dealkylation activity was determined using O-methyl, O-ethyl and O-propyl derivatives of p-nitrophenol, 7-hydroxycoumarin (umbelliferon) and 7-hydroxyphenoxazone (resorufin) as substrates. Microsomal O-dealkylation activities of p-nitrophenol and 7-hydroxycoumarin O-alkyl derivatives were of similar levels, but the activities of 7-hydroxyphenoxazone O-alkyl derivatives were very low compared with those of other substrates. Pretreatment of rats with beta-naphthoflavone resulted in the preferential increase of O-deethylation and O-depropylation activities regardless of the ring structure of the substrates, and the ratio of O-deethylation and O-depropylation activities to that of O-demethylation increased markedly. On the other hand, the O-dealkylase activity of all substrates increased generally upon pretreatment of the rats with phenobarbital, but the ratio of O-deethylase or O-depropylase activity to that of O-demethylase in the pretreated rats was not very different from that of the untreated animals. Hexobarbital inhibited competitively the O-dealkylation activity in control and phenobarbital-pretreated rat microsomes. On the other hand, the O-dealkylase activity in microsomes obtained from beta-naphthoflavone-pretreated rats was inhibited remarkably by alpha-naphthoflavone, but not in microsomes prepared from untreated and phenobarbital-pretreated rats. Based on these results, this report discusses the relationship between the alteration of O-dealkylation activity and the composition change of cytochrome P-450 in microsomal membrane. Species differences in the substrate specificity of the O-dealkylation reaction and in the responsiveness of the animals to typical inducers were also observed using liver microsomes obtained from several animals under various conditions.

Animals↗

PubMed1983

Biotransformation of coumarin derivatives. (2). Oxidative metabolism of 7-alkoxycoumarin by microsomal enzymes and a simple assay procedure for 7-alkoxycoumarin O-dealkylase.

The in vitro biotransformation of 7-alkoxycoumarin by rat liver microsomes was studied to develop a simple and accurate assay procedure for 7-alkoxycoumarin O-dealkylase. 7-Alkoxycoumarin was converted to the O-dealkylated metabolite, 7-hydroxycoumarin, by aerobic incubation of the parent compound with microsomes and NADPH, but the decreased amount of 7-alkoxycoumarin in the reaction mixture was several times higher than that of the 7-hydroxycoumarin produced during the incubation. The thin-layer chromatogram of the ether extractable metabolites in the reaction mixture showed the existence of several fluorescent metabolites including 7-hydroxycoumarin. Fluorescent properties of the parent compound, 7-alkoxycoumarin, and most of the metabolites differed from that of 7-hydroxycoumarin, but the reaction cofactor, NADPH, showed similar properties. Treatment of the reaction mixture with perchloric acid resulted in conversion of NADPH to the non-fluorescent form without any effect upon the fluorescent properties of 7-hydroxycoumarin and its related compounds. Based on these properties, an improved and simple in vitro fluorometric assay of the O-dealkylation of 7-alkoxycoumarin was developed. The method is applicable to routine determination of O-dealkylase activity in both isolated microsomes and whole homogenate. Species differences in the substrate specificity of the O-dealkylation reaction and in the responsiveness of animals to the inducer were observed even with use of the liver homogenate obtained from untreated and phenobarbital- or beta-naphthoflavone-pretreated animals, similar to what was observed with the microsomal system.

7-Alkoxycoumarin O-Dealkylase↗

PubMed1971