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Biomedical subjects

K Miyano

Publications and source records attributed to K Miyano.

103 records · Page 6Linked to original sources
PubMed1976

A novel metabolic pathway in the metabolism of 5-(4'-chloro-n-butyl)picolinic acid.

The metabolism of 5-(4'-chloro-n-butyl)picolinic acid, which inhibits dopamine beta-hydroxylase and exhibits an antihypertensive effect, has been studied by gas chromatography mass spectrometry, utilising characteristic reaction products after derivatization. In rat urine five metabolities were identified by mass spectral analysis. It is found that four were elongated by a C2 unit in the carboxyl group at the 2-position on the pyridine ring and accounted for approximately 50% of the radioactivity in the 24 hour urine. The facts show that the metabolic pathway corresponding to the chain elongation of fatty acids is the major route of metabolism for this drug in the rat. Furthermore, this pathway would be confirmed in man, rabbit, guinea pig and mouse.

Animals↗
PubMedDate not supplied

The determination of a new inhalational anaesthetic, sevoflurane, using an internal standard, xenon, by gas chromatography/mass spectrometry/selected ion monitoring.

A novel determination method for a new inhalation anaesthetic, sevoflurane, in a closed circuit in the presence of carbon dioxide absorbents is investigated using gas chromatography/selected ion monitoring with xenon as an internal standard. The decrease rate of sevoflurane with soda lime was 0.22% +/- 0.158/h (mean +/- SD), while that with baralyme was 0.57% +/- 0.115/h (mean +/- SD).

Anesthesia, Inhalation↗
PubMedDate not supplied

Metabolic pathway of Propionibacterium growing with oxygen: enzymes, 13C NMR analysis, and its application for vitamin B12 production with periodic fermentation.

The metabolic pathway of Propionibacterium grown under an aerobic condition is still not clear so far. In this work, cell growth, organic acid formation, vitamin B12 synthesis, and enzyme activities were determined in different aerobic cultivation systems. It was found that the propionate, which is accumulated during anaerobic cultivation, was completely decomposed when the cultivation was shifted to an aerobic condition. Moreover, pyruvate was formed in accordance with the decomposition of the propionate. Besides, more acetate was produced and a large amount of malate was formed during the aerobic cultivation. Such phenomena could be repeatedly observed in a periodic cultivation in which the dissolved oxygen concentration was alternatively controlled at 0 or 1 ppm. Enzyme analysis indicates that the regulation of organic acid formation depends on which molecule, i.e., oxygen or fumarate, serves as an electron acceptor in the respiratory chain reactions. No tricarboxylic acid cycle was found to exist in this species grown under an aerobic condition. It is evident that the randomizing pathway worked in a reversed direction in the presence of oxygen, through which the propionate is oxidized to pyruvate. The 13C NMR spectral analysis confirmed this observation.

Aerobiosis↗
PubMedDate not supplied

Anti-HIV-1 activity of myo-inositol hexaphosphoric acid (IP6) and myo-inositol hexasulfate(IS6).

It is known that polysulfates have some anti-HIV-1 activity. We investigated the anti-HIV-1 activity of myo-inositol hexaphosphoric acid (IP6) and myo-inositol hexasulfate(IS6), low molecular weight carbohydrates. IP6 and IS6 inhibited the replication of HIV-1 in a T cell line as well as that of a freshly isolated strain in peripheral blood mononuclear cells. Neither substance inhibited HIV-1-induced giant cell formation, but addition of IS6 when infecting cells with HIV-1 inhibited the replication of HIV-1. Neither substance inhibited HIV-1 reverse transcriptase activity in vitro and no influence on late stage replication was noted. Although the mechanisms of IP6 and IS6 action remain unclear, it can be speculated that they act on HIV-1 early replicative stage. Although it is not possible to develop IP6 and IS6 themselves as anti-AIDS drugs, studies of these anti-HIV agents might be expected to provide seed for eventual production of superior drugs for AIDS treatment.

Anti-HIV Agents↗
PubMedDate not supplied

Preparation of four optical isomers of hydroxylated hexobarbital and activities of 3-hydroxyhexobarbital dehydrogenase from guinea pig and rabbit liver.

The preparation of four optical isomers of 3'-hydroxyhexobarbital [5-(3'-hydroxy-1'-cyclohexen-1'-yl)-1,5-dimethylbarbituric acid] is described. The absolute configuration of the four isomers were assigned as (3'S, 5 R) and (3'R, 5R) for alpha- and beta-isomers from (R)-(--)-hexobarbital, respectively. Some of these isomeric 3'-hydroxyhexobarbitals, which are formed in the reaction of hexobarbital with liver microsomal mono-oxygenase, are oxidized to 3'-oxohexobarbital [5-(3'-oxo-1'-cyclohexen-1'-yl)-1,5-dimethylbarbituric acid] by dehydrogenase localized in the soluble fraction of liver homogenates. Comparison of activities among the four isomers for 3-hydroxyhexobarbital dehydrogenase was made by use of enzymes from guinea pig and rabbit liver. It became evident that either enzyme had a quite different activity towards each optical isomer, and the configuration of the 3'-position of hydroxyhexobarbital was an important factor affecting the reactivity of enzyme; isomers with 3'S-configuration were preferentially dehydrogenated to enantiomers with 3'R-configuration. Both enzymes had the highest activity towards (3'S, 5R)-3'-(--)-hydroxy-(--)-hexobarbital, irrespective of their having specificity towards different types of substrates.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Stereoselective formation of glucuronides in metabolism of hexobarbital enantiomers in vivo: isolation and quantitation of glucuronides in rabbit urine.

An improved column-chromatographic method was described for isolation and purification on preparative scale of a glucuronide from urine of rabbits administered (RS)-hexobarbital. The analytically pure preparation obtained was found to be a mixture of two glucuronides of diastereomeric 3'-hydroxyhexobarbitals. Rates of hydrolysis of the glucuronides were dependent on the enzyme preparations used as well as on the configuration of the substrate. For quantitative determination, the glucuronides were hydrolyzed completely by beta-glucuronidases from either Escherichia coli or abalone entrails under the conditions used. In vivo studies on the metabolism of (R)-(-)- and (S)-(+)-hexobarbital in the rabbit showed that the glucuronides excreted in 24-hr urine accounted for about 30% of the dose of each enantiomer, and that conjugation of the hydroxy isomers with glucuronic acid was so stereoselective that the isomers with S-configuration at the 3'-position were preferentially conjugated. There were almost no differences in the urinary metabolite profile between normal an PB-treated rabbits; however, a noticeable change was observed in recovery of unchanged (S)-hexobarbital after phenobarbital treatment.

Animals↗
PubMedDate not supplied

Thymic lesions in chicken infected with infectious bursal disease virus.

Thymic lesions were investigated in specific-pathogen-free chickens infected with the highly virulent HPS-2 strain or virulent reference GBF-1 strain of infectious bursal disease virus (IBDV). Both viruses induced follicular lymphoid necrosis and depletion in the bursa, as well as thymic lesions. However, cortical lymphocyte condensation and depletion in the thymus were more prominent in the HPS-2 group than in the GBF-1 group. Electronmicroscopically, alterations of cortical lymphocytes were characterized by nuclear disintegration resembling apoptosis. Immunohistologically, the virus-antigen-positive epithelial reticular cells in the medulla were more extensive in the HPS-2 group. These results suggest that HPS-2 IBDV persists in the thymic medulla and that cortical lymphocyte depletion is caused by virus-induced apoptosis.

Animals↗