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Biomedical subjects

K Kihira

Publications and source records attributed to K Kihira.

108 records · Page 6Linked to original sources
PubMed1983

Synthesis of four diastereoisomers at carbons 24 and 25 of 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid, intermediates of bile acid biosynthesis.

The synthesis of four stereoisomers at C-24 and C-25 of 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid is described. Pyridium chlorochromate oxidation of 3 alpha,7 alpha,12 alpha-triacetoxy-5 beta-cholan-24-ol (II) prepared from cholic acid (I) afforded 3 alpha,7 alpha,12 alpha-triacetoxy-5 beta-cholan-24-al (III) which was converted to a mixture of the four stereoisomers (IV-VII) by a Reformatsky reaction with ethyl DL-alpha-bromopropionate followed by alkaline hydrolysis. Separation of these isomers (IV-VII) was achieved by silica gel column chromatography, and subsequent reversed-phase partition column chromatography. The configurations at C-24 were elucidated by conversion of each isomer into (24R)- or (24S)-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol (XII or XI) by Kolbe electric coupling, the C-24 configurations of which were determined by modified Horeau's method and 13C-nuclear magnetic resonance spectroscopy. The stereochemistries at C-25 were deduced by comparison of IV-VII with the products of the hydroboration followed by oxidation with alkaline hydrogen peroxide of (24E)-3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholest-24-en-26-oic acid (XIII).

Bile Acids and Salts↗
PubMed1981

Metabolism of bile alcohols, 24-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one, in rats.

24-Nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,25-tetrol and 3 alpha,7 alpha,12 alpha-trihydroxy-26,27-dinor-5 beta-cholestan-24-one were administered intraperitoneally to bile fistula rats, and the metabolites excreted in the bile were analyzed. No formation of bile acids from these bile alcohols was observed. 7 alpha,12 alpha,25-Trihydroxy-24-nor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid was identified as the only biliary metabolite of the 24-nor-5 beta-cholestanetetrol. The major metabolite of the trihydroxy-26,27-dinor-5 beta-cholestanone was 7 alpha,12 alpha-dihydroxy-24-oxo-26,27-dinor-5 beta-cholestane-3 alpha-O-(beta-D-glucopyranosid)uronic acid, and the minor metabolite was the glucurono conjugate of 26,27-dinor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24 beta-tetrol. The results indicated that in rat liver these C25- and C26-bile alcohols, in contrast to C27-bile alcohols, were not converted into bile acids, and that the glucuronide production became necessary for hepatic elimination of the accumulated bile alcohols.

Animals↗
PubMed1981

Intestinal absorption of bile alcohols.

The absorption of bile alcohols by rat small intestine was studied using in vivo and in vitro preparations. In bile duct cannulated rats, intraduodenal administered bile alcohols were certainly absorbed and excreted in the bile, although the absorption was not so efficient as for bile acids. The absorption during a 24 h period for free bile alcohol, bile alcohol 3-sulfate, and bile alcohol 3-glucuronide was 60%, 31%, and 30% of the dose, respectively, compared with 98% for taurocholate. In situ recirculation experiments demonstrated the linear relationship between perfusate concentration and intestinal absorption for unconjugated and 3-sulfated bile alcohols. Everted gut sacs of rat ileum actively transported a bile alcohol possessing a sulfuric acid ester group on the side chain. However, free bile alcohol, bile alcohol 3-sulfate, and bile alcohol 3-glucuronide were not transported. These results indicate that bile alcohols having no negative charge on the side chain are absorbed by passive diffusion and not by active transport.

Animals↗
PubMed1981

Synthesis of (22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids and structure of haemulcholic acid, a unique bile acid isolated from fish bile.

(22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids were synthesized, starting from chenodeoxycholic acid, in order to establish the chemical structure of haemulcholic acid, which has been found in certain fish as the major bile component. Oxidative decarboxylation of diformoxylated chenodeoxycholic acid with lead tetraacetate yielded 24-nor-5 beta-chol-22-ene-3 alpha, 7 alpha-diol, which was hydroxylated to form a mixture of (22R and 22S)-24-nor-5 beta-cholane-3 alpha, 7 alpha, 22,23-tetrols. Lead tetraacetate oxidation of the mixture yielded 3 alpha, 7 alpha-dihydroxy-23,24-dinor-5 beta-cholan-22-a1. A Reformatsky reaction of the dihydroxydinorcholanal with bromoacetate resulted in the formation of a mixture of (22R and 22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acids. The bile acids epimeric at C-22 were resolved by silica gel column chromatography, and their configurations of C-22 were assigned by a modification of Horeau's method and 13C-nuclear magnetic resonance spectroscopy. By direct comparison with synthetic bile acids, the naturally occurring haemulcholic acid was shown to be (22S)-3 alpha, 7 alpha, 22-trihydroxy-5 beta-cholan-24-oic acid.

Animals↗
PubMed1980

Bile acids and bile alcohols of bullfrog.

Gallbladder bile of the bullfrog, Rana cetesbeiana was found to contain a number of minor bile acids and bile alcohols in unconjugated forms. The following bile acids and bile alcohols were identified by combined gas-liquid chromatography-mass spectrometry: cholic acid, allocholic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-5 alpha-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-24-methyl-5 beta-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 alpha-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestan-26-oic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 alpha-cholestan-27-oic acid, 3 alpha,7 alpha,12 alpha,26-tetrahydroxy-5 beta-cholestan-27-oic acid, 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 alpha-cholestan-24-one, and 3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one. These minor constituents of the bile may represent intermediates in the biosynthetic pathway of bile acids and bile alcohols in the bullfrog.

Animals↗
PubMed1980

Bile salts of frogs: a new higher bile acid, 3 alpha, 7 alpha, 12 alpha, 26-tetrahydroxy-5 beta-cholestanoic acid from the bile Rana plancyi.

Bile salts of ten species of frogs of the family Ranidae were examined by means of thin-layer chromatography, gas-liquid chromatography, and gas-liquid chromatography-mass spectrometry. Their major bile alcohols were ranol, cyprinol, or bufol. Four species of frogs contained lesser amounts of higher bile acids, and in two species C24 bile acids were present. A higher bile acid that has not been previously described was detected in Rana plancyi. On the basis of the spectral data and the direct comparison with a synthetic sample, the chemical structure of the new bile acid was established to be 3 alpha, 7 alpha, 12 alpha, 26-tetrahydroxy-5 beta-cholestanoic acid.

Animals↗
PubMed1979

Reverse cross-coupling in the synthesis 3 alpha, 7 alpha-dihydroxy-5 beta-cholestanoic acid.

The present report describes the characterization of (24R and 24S)-27-nor-24-methyl-3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acids obtained in considerable amounts during the synthesis of (25RS)-3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid by the electrolytic coupling of chenodeoxycholic acid and the half ester of methylsuccinic acid. The mixture of 24R and 24S diastereomers was resolved by analytical and preparative thin-layer chromatography and characterized by gas-liquid chromatography, proton magnetic resonance, and molecular rotation differences. For reference, the model compound, 27-nor-3 alpha, 7 alpha-dihydroxy-5 beta-cholestan-26-oic acid, was synthesized by electrolytic coupling of chenodeoxycholic acid and the half ester of succinic acid.

Cholestanols↗
PubMed1978

Metabolism of (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid in guinea pigs.

[7beta-3H]-(24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids and [7beta-3H]-27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid (C27 and C26 bile acids having the same nuclear configuration as cheno-deoxycholic acid and its precursor, 3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic-acid) were synthesized and administered intraperitoneally to bile fistula guinea pigs. The biliary bile acids formed were hydrolyzed and analyzed by thin layer chromatography, and the metabolites were identified by the inverse isotope dilution method. The results showed that both (24R and 24S)-27-nor-24-methyl-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acids were not metabolized by the liver and were excreted unchanged as their taurine and glycine conjugates whereas 27-nor-3alpha,7alpha-dihydroxy-5beta-cholestan-26-oic acid was converted to chenodeoxycholic acid.

Animals↗
PubMed1976

New bile alcohols - synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols.

The synthesis of (22R)- and (22S)-5beta-cholestane-3alpha,7alpha,12alpha,22,25-pentols is described. Bisnorcholyl aldehyde was prepared from cholic acid and converted into the cholestane-pentols by a Grignard reaction with 3-methyl-3-(tetrahydropyran-2-yloxy)-butynylmagnesium bromide followed by hydrogenation and acid hydrolysis. One of the synthetic pentols, the 22R-isomer was identical with a metabolite of 5beta-cholestane-3alpha,7alpha,25-triol formed in the rabbit.

Animals↗
PubMed1976

Identification of (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentol in cerebrotendinous xanthomatosis.

The synthesis of (23R)- and (23S)-5beta-cholestane-3alpha, 7alpha, 12alpha, 23, 25-pentols is described. Norcholyl aldehyde was converted into the cholestanepentols by a Reformatsky reaction with ethyl bromoacetate followed by a Grignard reaction with methylmagnesium iodide. One of the synthetic pentols, the 23S epimer was identical with a bile alcohol isolated from patients with cerebrotendinous xanthomatosis.

Brain Diseases↗
PubMedDate not supplied

Synthesis of alpha,beta-unsaturated C24 bile acids.

Synthesis of the alpha,beta-unsaturated analogues of cholic acid, deoxycholic acid, chenodeoxycholic acid, and ursodeoxycholic acid is described. Each common bile acid was converted to the corresponding C22 aldehyde which was then converted to the delta 22 bile acid by Wittig reaction with methyl (triphenylphosphoranylidene)acetate. The synthetic unsaturated bile acids were characterized by thin-layer chromatography, gas-liquid chromatography, and mass spectrometry.

Bile Acids and Salts↗
PubMedDate not supplied

Bile acid profiles in bile, urine, and feces of a patient with cerebrotendinous xanthomatosis.

Bile acid profiles of bile, urine, and feces obtained from a patient with cerebrotendinous xanthomatosis on the same day have been analyzed by gas-liquid chromatography-mass spectrometry after fractionation into groups by mode of conjugation by an ion-exchange chromatography. The predominant biliary bile acid was cholic acid conjugated with glycine and taurine. Lesser amounts of the amino acid conjugates of chenodeoxycholic acid, ursodeoxycholic acid, 7-ketodeoxycholic acid, allocholic acid, and deoxycholic acid, and of unconjugated norcholic acid and allonorcholic acid were also present in the bile. The major fecal bile acid was 7-epicholic acid. Relatively large amounts of bile acids were excreted in the urine. Unconjugated 7-epicholic acid, norcholic acid, allonorcholic acid, and cholic acid predominated. The bile acid profiles of the patient were different from those of normal subjects and should be useful for the diagnosis.

Bile↗
PubMedDate not supplied

Metabolism of C26 bile alcohols in the bullfrog, Rana catesbeiana.

Metabolism of C26 bile alcohols in the bullfrog, Rana catesbeiana, was studied. [24-14C]-24-Dehydro-26-deoxy-5 beta-ranol (3 alpha,7 alpha,12 alpha-trihydroxy-27-nor-5 beta-cholestan-24-one) was chemically synthesized from [24-14C]cholic acid and incubated with bullfrog liver homogenate fortified with NADPH. 24-Dehydro-26-deoxy-5 beta-ranol was shown to be converted into both 26-deoxy-5 beta-ranol and 24-epi-26-deoxy-5 beta-ranol [(24S)- and (24R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24-tetrols] in addition to 5 beta-ranol [(24R)-27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26-pentol], which is the major bile alcohol of the bullfrog. [24-3H]-26-Deoxy-5 beta-ranol and [24-3H]-24-epi-26-deoxy-5 beta-ranol were prepared from 24-dehydro-26-deoxy-5 beta-ranol by reduction with sodium [3H] borohydride and administered respectively to two each of four bullfrogs by intraperitoneal injection. After 24 h, labeled 5 beta-ranol was isolated from the bile of the bullfrogs that received [24-3H]-26-deoxy-5 beta-ranol. In contrast little if any radioactivity could be detected in 5 beta-ranol or its 24-epimer after administration of [24-3H]-24-epi-26-deoxy-5 beta-ranol.

Acetylcysteine↗
PubMedDate not supplied

Identification of bile alcohols in serum from healthy humans.

Bile alcohol glucuronides present in human serum were isolated by ion exchange chromatography on piperidino-hydroxypropyl Sephadex LH-20. Following hydrolysis with beta-glucuronidase, the bile alcohols were analyzed by a combination of gas-liquid chromatography and mass spectrometry. Bile alcohols identified were 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, 27-nor-5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25-pentol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,26-pentol, 5 beta-cholestane-3 alpha,7 alpha,12 alpha,25,26-pentol, and 5 beta-cholestane-3 alpha,7 alpha,12 alpha,24,25,26-hexol. The bile alcohol composition in serum was similar to that in urine but not to that in bile. The concentration of total bile alcohols in serum was 59.5 +/- 24.6 micrograms/L.

Adult↗
PubMedDate not supplied

Daily cost of ophthalmic solutions for treating glaucoma in Japan.

PURPOSE: We conducted a study of the daily cost of various ophthalmic solutions used in Japan for treating glaucoma: beta-adrenergic blockers (11 products), epinephrine (3), cholinergics (3), prostaglandins (2), and carbonic anhydrase inhibitors (2). METHODS: The total number of drops in one bottle of each solution was counted drop by drop. The cost per drop was calculated by dividing the government-controlled standard prices by the total number of drops in one bottle. The daily cost of therapy was calculated by multiplying the cost per drop by the number of drops typically used per day. RESULTS: The average cost of each preparation was calculated based on the prices and the daily usage. The daily cost of the beta-adrenergic blockers studied ranged widely, from $0.43 to $1.04. CONCLUSIONS: These data may be useful in selecting ophthalmic products for glaucoma therapy in Japan.

Adrenergic Agonists↗