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Biomedical subjects

T Akao

Publications and source records attributed to T Akao.

At least 73 records · Page 4Linked to original sources

Inhibitory effect of glycine on ethanol absorption from gastrointestinal tract.

The oral administration of glycine remarkably decreased the blood ethanol level in mice which had ingested ethanol, and a large amount of ethanol was retained in their stomachs. These effects were observed by the oral administration of glycine previous to the ethanol ingestion, and depended on the dose of glycine. An intravenous injection of glycine did not affect the ethanol absorption at all. These findings indicate that glycine suppresses the rate of ethanol absorption from the gastrointestinal tract. Glycylglycine, glycylglycylglycine and alanine showed the same effects, but glucose did not. However, ethanol absorption from the ligated stomach of mouse was inhibited not only by glycine but also by glucose. On the other hand, the rate of ejecting a pigment from the stomach to the small intestine was lowered by glycine, but not by glucose. Thus, glycine lowers the gastric emptying rate, resulting in the suppression of ethanol absorption from the gastrointestinal tract.

Administration, Oral↗

Intestinal bacterial hydrolysis is indispensable to absorption of 18 beta-glycyrrhetic acid after oral administration of glycyrrhizin in rats.

Gnotobiote rats were prepared by infecting germ-free rats with Eubacterium sp. strain GLH, a human intestinal bacterium capable of hydrolysing glycyrrhizin to 18 beta-glycyrrhetic acid. Their faeces and caecal contents showed glycyrrhizin-hydrolysing activities (31.7 and 31.3 pmol min-1 (mg protein)-1, respectively) similar to those (81.0 and 39.9 pmol min-1 (mg protein)-1, respectively) of conventional rats, although there was no detectable activity in germ-free rats. When glycyrrhizin (100 mg kg-1) was orally administered to conventional, germ-free and gnotobiote rats, no glycyrrhizin could be detected in plasma 4 or 17 h after the administration, using EIA and HPLC assays. Plasma 18 beta-glycyrrhetic acid was not detected 4 or 17 h after the administration of glycyrrhizin to germ-free rats nor could this compound be detected in caecal contents or in the faeces. However, 18 beta-glycyrrhetic acid (0.6-2.6 nmol mL-1) was detected in plasma of the conventional and the gnotobiote rats 4 and 17 h after the administration, and the caecal contents after 4 h and the cumulative faeces up to 17 h of the conventional and the gnotobiote rats contained considerable amounts of 18 beta-glycyrrhetic acid. These findings indicate that orally administered glycyrrhizin is poorly absorbed from the gut, but is hydrolysed to 18 beta-glycyrrhetic acid by intestinal bacteria such as E. sp. strain GLH, and the resulting 18 beta-glycyrrhetic acid is absorbed.

Administration, Oral↗

Isolation of a human intestinal anaerobe, Bifidobacterium sp. strain SEN, capable of hydrolyzing sennosides to sennidins.

A strictly anaerobic bacterium capable of metabolizing sennosides was isolated from human feces and identified as Bifidobacterium sp., named strain SEN. The bacterium hydrolyzed sennosides A and B to sennidins A and B via sennidin A and B 8-monoglucosides, respectively. Among nine species of Bifidobacterium having beta-glucosidase activity, only Bifidobacterium dentium and B. adolescentis metabolized sennoside B to sennidin B, suggesting that the sennoside-metabolizing bacteria produce a novel type of beta-glucosidase capable of hydrolyzing sennosides to sennidins.

Anthracenes↗

Enzymic studies on the animal and intestinal bacterial metabolism of geniposide.

Geniposide, a main iridoid glucoside of Gardenia fruit, is transformed to genipin, a genuine choleretic, in vivo in rats (Aburada et al., J. Pharmacobio-Dyn., 1, 81 (1978)). As geniposide was not hydrolyzed to any metabolite by rat liver homogenate, which has beta-D-glucosidase and esterase activities, beta-D-glucosidases in intestinal bacteria seem to be required for an exhibition of its choleretic action. The crude extract of Eubacterium sp. A-44, a human intestinal anaerobe, hydrolyzed geniposide, but that of Ruminococcus sp. PO1-3, another human anaerobe, did not, though both extracts had beta-D-glucosidase activities for p-nitrophenyl beta-D-glucopyranoside. Only one of three beta-D-glucosidases from E. sp. A-44 and none of two from R. sp. PO1-3 hydrolyzed geniposide to genipin. However, carboxylesterases from E. sp. A-44 and pig liver were unable to hydrolyze geniposide to geniposidic acid, but hydrolyzed genipin to an aglycone of geniposidic acid, indicating that geniposide is first hydrolyzed to genipin by beta-D-glucosidases and subsequently to the aglycone of geniposidic acid by esterases. Thus, when geniposide is orally administered, genipin seems to be effectively produced in the intestine and then absorbed to act as a genuine choleretic.

Animals↗

Design of a new cationic amphiphile with efficient DNA-transfection ability.

Several double-chain ammonium amphiphiles were designed to have physicochemical properties, such as membrane fluidity and aggregate morphology, suitable for DNA transfection, according to our previous results (1, 2). Potency of the amphiphiles during the transfer of plasmid DNA into COS cells was examined. Of the amphiphiles tested, O,O'-ditetradecanolyl-N-(trimethylammonio acetyl)diethanolamine chloride (14Dea2) had the highest transfection activity. Optimal conditions for transfection of COS cells by 14Dea2 were also determined.

Animals↗

Cleavages of the O- and C-glucosyl bonds of anthrone and 10,10'-bianthrone derivatives by human intestinal bacteria.

A strictly anaerobic bacterium, Bifidobacterium sp. SEN, capable of hydrolyzing the O-glucosyl of sennosides was isolated from human feces. The bacterium stepwisely hydrolyzed sennoside B to sennidin B through sennidin-8-monoglucoside in PYF medium but not in GAM broth. Addition of D-glucose to PYF medium resulted in loss of the hydrolyzing activity in culture but addition of D-fructose did not affect the activity. Coculture of this bacterium with Peptostreptococcus intermedius led to rapid accumulation of rhein anthrone in the medium. Similarly, a bacterium, Eubacterium sp. BAR, capable of cleaving the C-glucosyl of barbaloin was isolated from human feces. This bacterium grew in PYF medium containing barbaloin and produced enzyme(s) that cleave(s) the C-glucosyl. The induction of the enzymes was completely inhibited in the presence of D-glucose. Nojirimycin inhibited the enzyme activity induced by barbaloin but it did not inhibit the bacterial growth in the presence of D-glucose.

Aloe↗

L-gulono-gamma-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver.

A methylguanidine-synthesizing enzyme localized in rat liver microsomes produces methylguanidine via the intermediates creatone A and creatone B from the substrate, creatol, a substance produced from creatinine mainly by reaction with hydroxyl radicals. This enzyme has been identified as L-gulono-gamma-lactone oxidase (EC 1.1.3.8). However, no corresponding activity was found in extracts from human livers.

Amino Acid Sequence↗

Purification of methylguanidine synthase from the rat kidney.

Methylguanidine (MG)-synthesizing enzyme was purified from rat kidney lysosomes and peroxisomes. The enzyme was a flavoprotein with a molecular weight of about 37,000 and oxidized creatol to produce MG. The present results suggest that the reaction mechanism of this enzyme is different from that of L-gulono-gamma-lactone oxidase (EC 1.1.3.8) isolated from rat liver microsomes.

Amino Acid Sequence↗

[Malignant fibrous histiocytoma of the spermatic cord: a case report].

A case of malignant fibrous histiocytoma of the spermatic cord is reported. A 44-year-old man was admitted because of a painless, gradually enlarging mass in the left scrotum. Local tumor excision and subsequent radical inguinal orchidectomy was performed. The histological diagnosis was malignant fibrous histiocytoma. There were no signs of recurrence or metastasis 8 months after the operation. Malignant fibrous histiocytoma in the spermatic cord is rare. We reviewed 34 previously reported cases. The rate of local recurrence and distant metastasis are 34.5% and 17.2%, respectively.

Adult↗

A development of computerized laminate veneer restoration system.

The fabrication of laminate veneer requires many complicated procedures and skills to obtain good accuracy and shape. Thus, the use of CAD/CAM is subjected to in laminate veneer fabrication in order to reduce complication and time consuming. In this study, CAD/CAM system of laminate veneer fabrication was developed. The system consisted of laser displacement meter, computer-controlled scanning machine and personal computer. This system is able to measure tooth shape with three dimension, design and manufacture laminate veneer shells of ABS resin with satisfied accuracy and shape.

Computer-Aided Design↗

Purification and characterization of a peptide essential for formation of streptolysin S by Streptococcus pyogenes.

Peptides in a pronase digest of bovine serum albumin were required for streptolysin S formation by Streptococcus pyogenes besides maltose and a carrier (the oligonucleotide fraction obtained by treatment of Saccharomyces cerevisiae RNA with RNase A). A peptide essential for streptolysin S formation was purified to homogeneity from a pronase digest of bovine serum albumin by Sephadex G-25 column chromatography, and anion-exchange, reverse-phase, and gel filtration high-performance liquid chromatography. The purified peptide was divided into more than two peptides by HCOOOH oxidation and was composed of four residues of cysteine, three of leucine, and one each of aspartic acid and glutamic acid. Leucine and cysteine were detected as amino-terminal residues, and leucine and glutamic acid were detected as carboxyl-terminal residues, suggesting that two or three peptides are linked by a disulfide bond(s). A disulfide bond structure in the peptide seemed to be required for streptolysin S formation.

Amino Acid Sequence↗

Inhibitory effects of glycyrrhetic acid and its related compounds on 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol.

Glycyrrhetic acid (GA), aglycone of glycyrrhizin (GL), inhibited potently (I50 = 7 x 10(-6) M) and non-competitively the activity of NAD(P)+-linked 3 alpha-hydroxysteroid dehydrogenase of rat liver cytosol. The inhibition was slightly weaker than that of indomethacin, a potent anti-inflammatory agent, but stronger than that of dexamethasone, another anti-inflammatory agent. GL, GA monoglucuronide, and 3-epi-glycyrrhetic acid also inhibited this enzyme activity, but did so less effectively (I50 = 5-8 x 10(-5) M). Carbenoxolone (GA 3-hemisuccinate) and 3-keto-glycyrrhetic acid showed potent inhibitory effects similar to GA, and 18 alpha-GA showed the most powerful inhibition of the activity.

3-Hydroxysteroid Dehydrogenases↗

Inhibitory effects of glycyrrhetic acid derivatives on 11 beta- and 3 alpha-hydroxysteroid dehydrogenases of rat liver.

Glycyrrhetic acid (GA), an aglycone of glycyrrhizin (GL), is a potent inhibitor of 11 beta- and 3 alpha-hydroxysteroid dehydrogenases. 11 beta-Hydroxysteroid dehydrogenase activity of rat liver microsomes was potently inhibited by GA, 3-deoxyglycyrrhetic acid (3-deoxyGA), 3-ketoglycyrrhetic acid (3-ketoGA), 3-epiglycyrrhetic acid (3-epiGA) and 11-deoxoglycyrrhetic acid (11-deoxoGA), with I50 values of 2-4 x 10(-7) M. However, 18 alpha-stereoisomers (I50 = 3-7 x 10(-6) M) of GA, 3-deoxyGA and 11-deoxoGA were one tenth less inhibitory on the enzyme activity than the corresponding 18 beta-isomers. On the other hand, 18 alpha-stereoisomers of GA, 3-deoxyGA and 11-deoxoGA inhibited 3 alpha-hydroxysteroid dehydrogenase activity of rat liver cytosol more potently than the corresponding 18 beta-isomers. I50 values of 18 alpha- and 18 beta-isomers were 2 and 7 x 10(-6) M, respectively, in the case of GA, 8 and 20 x 10(-6) M in 3-deoxyGA, 3 and 20 x 10(-6) M in 11-deoxoGA. These results indicate that the 18 beta-conformation of oleanane is important for the inhibition of 11 beta-hydroxysteroid dehydrogenase but on the contrary the 18 alpha-conformation is important for the inhibition of 3 alpha-hydroxysteroid dehydrogenase.

11-beta-Hydroxysteroid Dehydrogenases↗

[Pseudosarcomatous fibromyxoid tumor of the urinary bladder: a case report].

A 41-year-old man was referred to our clinic for gross hematuria. Cystoscopy revealed a 6 x 5 x 5 cm wide-based tumor located at the dome of the bladder. Pathological diagnosis of the biopsy was pseudosarcomatous fibromyxoid tumor. Microscopically this tumor was composed of spindle cells and myxoid stroma, and immunohistochemical and ultrastructural studies showed benign characteristics of this tumor. Therefore partial cystectomy was performed. It is important to recognize the histological characteristics of this essentially benign condition so that total cystectomy can be avoided.

Adult↗

Metabolism of glycyrrhetic acid by rat liver microsomes--III. Male-specific glycyrrhetinate dehydrogenase.

Glycyrrhetinate (GA) dehydrogenase localized in microsomes of rat liver catalyses the oxidation and reverse reduction of 18 beta-glycyrrhetic acid (GA), an aglycone of glycyrrhizin and a main component of liquorice, to 3-keto-18 beta-glycyrrhetic acid (3-ketoGA). The enzyme activity was detected in microsomes of adult males, but not in those of adult females. It was not observed in infant males but appeared 6 weeks after birth, increased gradually and reached the maximum level at 12 weeks after birth, whereas it was not detected in the hepatic microsomes of females of any age. The administration of estradiol valerate to intact adult males decreased GA dehydrogenase activity remarkably. Castration of male rats also caused a marked reduction of the activity, but the administration of testosterone proprionate to these rats restored it to close to the normal level. On the other hand, ovariectomy of female rats did not bring the activity into existence, but the injection of testosterone proprionate to the ovariectomized rats brought it into a slight existence, in spite of no appearance of the activity by the treatment of testosterone proprionate to intact adult females. The sex-related difference in the activity in adults was eliminated by hypophysectomy of male and female rats, their microsomal activities after the operation being the same, 20-40% of the activity in intact males. Moreover, the administration of estradiol valerate to the hypophysectomized rats did not affect the activity. These results indicate that GA dehydrogenase is male-specific and regulated by sex-hormones through the pituitary.

3-Hydroxysteroid Dehydrogenases↗

Formation of nitrogen-containing metabolites from geniposide and gardenoside by human intestinal bacteria.

During the course of our studies on the metabolism of iridoid glycosides by human intestinal bacteria, we found that geniposide (1) and gardenoside (4) were transformed to new nitrogen-containing compounds, genipinine (3) and gardenine (6), respectively, along with the known aglycones. Although the amounts of new metabolites were somewhat lower than those of the aglycones, they were quantitatively analyzed by means of liquid chromatography/mass spectrometry (LC/MS). Of 25 strains of human intestinal bacteria, Peptostreptococcus anaerobius, Klebsiella pneumoniae, Fusobacterium nucleatum, and Bacteroides fragilis ssp. thetaotus produced appreciable amounts of 3, while a bacterial mixture of human feces produced 10 times or more higher amounts of 3, as compared to the individual strains.

Bacteria↗