A selective and extremely potent antagonist of the neurokinin-1 receptor.

Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking.

Synthesis of deuterium-labeled 16 alpha,19-dihydroxy C19 steroids as internal standards for gas chromatography-mass spectrometry.

[2 beta,7,7,16 beta-2H4]16 alpha,19-Dihydroxyandrost-4-ene-3,17-dione (14) and [7,7,16 beta-2H3]3 beta,16 alpha,19-trihydroxyandrost-5-en-17-one (16), with high isotopic purity, respectively, were synthesized from unlabeled 3 beta-(tert-butyldimethylsiloxy)-androst-5-ene-17 beta-yl acetate (1). The deuterium introduction at C-7 was carried out by reductive deoxygenation of the 7-keto compound 3 with dichloroaluminum deuteride and that at C-2 beta and/or C-16 beta by controlled alkaline hydrolysis of 16-bromo-17-ketone 11 or 12 with NaOD in D2O and pyridine. [7,7-2H2]3 beta-Hydroxyandrost-5-en-17-one (6), obtained from compound 1 by a five-step sequence, was converted to compound 14 or 16 by an eight-step or seven-step sequence, respectively.

Structural identification of an epitope of antigenic factor 5 in mannans of Candida albicans NIH B-792 (serotype B) and J-1012 (serotype A) as beta-1,2-linked oligomannosyl residues.

In previous articles, we reported the presence of phosphate-bound beta-1,2-linked oligomannosyl residues in the mannans of strains of Candida albicans serotypes A and B and Candida stellatoidea. To identify the antigenic factor corresponding to this type of oligomannosyl residue, a relationship between chemical structure and antigenic specificity in the mannans of C. albicans NIH B-792 (serotype B, B-strain) and C.

The relationship of putrescine incorporation to transferrin uptake by reticulocytes.

We previously reported that putrescine incorporation occurred during transferrin uptake by rat reticulocytes (1). Both the putrescine incorporation and transferrin uptake were enhanced by the presence of Ca2+ and A23187. Furthermore, putrescine dose-dependently increased the transferrin uptake.

Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium.

The effect of selenium administered acutely or chronically on the hepatic microsomal drug-metabolizing system has been investigated in mice. After 72 h following acute administration of selenium (7.5 mg/kg, i.

Inhibition of hepatic drug biotransformation by carrageenan-induced inflammation in the rat: effect of sex hormone alterations.

Following in vivo treatment with carrageenan, sex-related differences in alteration of hepatic drug metabolism were found in the rat. In adult male rats, marked decreases were observed in hepatic 9000 x g supernatant cytochrome P-450 content and in the biotransformation of hexobarbital, aminopyrine, ethylmorphine, and meperidine. Hexobarbital hypnosis was significantly prolonged by carrageenan treatment in intact and testectomized animals as compared to their respective controls.

[Effects of selenium on the serum glucose and insulin levels in diabetic rats].

We investigated the effects of selenium (Se) on the serum glucose and insulin levels in rats with diabetes induced by streptozotocin (STZ, 75 mg/kg, i.p.) and pancreatectomized rats.

Structure of the D-mannan of the pathogenic yeast, Candida stellatoidea ATCC 20408 (type II) strain, in comparison with that of C. stellatoidea ATCC 36232 (type I) strain.

Acid treatment of the cell-wall D-mannas of Candida stellatoidea strains ATCC 36232 (Type I, A3 strain) and ATCC 20408 (Type II, A2 strain) gave (1----2)-linked beta-D-manno-oligosaccharides (dp 2-5), whereas treatment with alkali gave the (1----2)-linked alpha-D-mannobiose. Conventional acetolysis of the acid- and alkali-treated D-mannan of the A3 strain gave oligosaccharides consisting of (1----2)- and (1----3)-linked alpha-D-mannopyranose residues, similar to those of Candida albicans serotype B strain. Mild acetolysis of the acid- and alkali-treated D-mannan of the A2 strain gave higher oligosaccharides that were digested by the Arthrobacter GJM-1 strain exo-alpha-D-mannosidase.

A radiometric assay method for aromatase activity using [1 beta-3H]16 alpha-hydroxyandrostenedione.

[1 beta-3H]16 alpha-Hydroxyandrostenedione (16 alpha-OHA) (715 mCi/mmol) was prepared from commercially available [1 beta-3H]androstenedione (A) by the microbiological method with Streptomyces roseochromogenes and its structure and purity were determined by chromatographic and reverse isotope dilution methods. When [1 beta-3H]16 alpha-OHA was incubated with human placental microsomes and reduced nicotinamide adenine dinucleotide phosphate (NADPH), 3H2O-release into the medium was dependent upon protein concentration and incubation time. An apparent Km and Vmax of the microsomal aromatase for the [1 beta-3H]substrate were 650 nM and 34 pmol/min/mg protein, respectively.

Naloxone-reversible effect of spantide on the spinally mediated behavioural response induced by neurokinin-2 and -3 receptor agonists.

[D-Arg1, D-Trp7,9, Leu11]-substance P (spantide) was tested for antagonism against the licking, biting and scratching response induced by various neurokinin (NK) receptor agonists and bombesin (Bom) in mice. When co-administered with substance P (SP) intrathecally, spantide reduced the SP-induced behavioural responses in a dose-dependent manner. The duration of this antagonistic effect was approximately 30 min.

Sequential nuclear magnetic resonance assignment of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of the pathogenic yeast Candida albicans NIH B-792 strain.

The H-1 and H-2 signals of beta-1,2-linked mannooligosaccharides isolated from the phosphomannan of Candida albicans NIH B-792 strain by mild acid hydrolysis were assigned by a sequential NMR assignment method that combines two-dimensional 1H-1H correlated spectroscopy (COSY) and two-dimensional nuclear Overhauser enhancement and exchange spectroscopy (NOESY). The results indicated that the H-1 and H-2 of each beta-1,2-linked mannopyranose unit show largely different signals compared with those of the alpha-linked ones and that the correlation between linkages and signals could not be explained by a conventional additivity rule. Furthermore, a regular proportional downfield shift of the H-1 signal was observed in the order of the mannose unit from the reducing terminal except those of the reducing and nonreducing terminal positions.

Sustained release of 5-fluorouracil from oil/water emulsions.

Release profile of 5-fluorouracil (5-FU) from O/W emulsion and bone marrow toxicity of 5-FU to mice were compared with those of an aqueous solution of 5-FU. 5-FU emulsion had lower bone marrow toxicity and a slower drug release rate than the 5-FU aqueous solution which exhibited high bone marrow toxicity and fast drug release rate. A correlation between the rate of drug release and bone marrow toxicity was suggested.

Structural study of a cell wall mannan-protein complex of the pathogenic yeast Candida glabrata IFO 0622 strain.

We conducted a structural analysis of the cell wall mannan-protein complex (mannan) isolated from a pathogenic yeast, Candida glabrata IFO 0622 strain. The chemical structure of mannobiose released from this mannan by treatment with 10 mM HCl at 100 degrees C for 1 h was identified as Manp beta 1-2Man. The treatment of this mannan with 100 mM NaOH at 25 degrees C for 18 h gave a mixture of alpha-1,2- and alpha-1,3-linked oligosaccharides, from tetraose to biose, and mannose.

[Determination of synephrine in oriental pharmaceutical decoctions containing Aurantii nobilis pericarpium by ion-pair high-performance liquid chromatography].

A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of synephrine in oriental pharmaceutical decoctions containing Aurantii Nobilis Pericarpium. An ODS column and a mixture of water, acetonitrile, sodium dodecyl sulfate and phosphoric acid (65:35:0.5:0.

Evidence for oligomannosyl residues containing both beta-1,2 and alpha-1,2 linkages as a serotype A-specific epitope(s) in mannans of Candida albicans.

In order to identify the branches containing both beta-1,2 and alpha-1,2 linkages as the serotype A-specific epitope(s) in the mannans of Candida albicans, serotype A strains with oligosaccharides constituting the beta-1,2 linkage, the alpha-1,2 linkage, and both the beta-1,2 and the alpha-1,2 linkages were prepared from the mannans of C. albicans serotype A strains (NIH A-207 and J-1012) and tested for their inhibitory effects in the precipitin and slide agglutination assays. The results indicated that two oligosaccharides containing both beta-1,2 and alpha-1,2 linkages, Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man and Manp beta 1-2Manp beta 1-2Manp alpha 1-2Manp alpha 1-2Manp alpha 1-2Man, served as epitopes participating in the serotype A specificity of C.

Effect of retinoic acid on liver transglutaminase activity and carbon tetrachloride-induced liver damage in mice.

Transglutaminase (TGase) activity in the cytosol fraction of the mouse liver increased following intraperitoneal injection of retinoic acid. Retinoic acid inhibited the carbon tetrachloride-induced increase in serum alanine transaminase activity. These findings suggest that TGase is involved in the effect of retinoic acid on carbon tetrachloride-induced liver damage.

Effect of carrageenan-induced inflammation on the induction of hepatic microsomal enzymes by phenobarbital and benzo[a]pyrene in male rats.

The inhibitory effect of carrageenan-induced inflammation was examined by utilizing rats treated with inducers of this drug metabolizing system. Animals were given sodium phenobarbital (PB, 80 mg/kg, i.p.

[Determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma by ion-pair high-performance liquid chromatography].

A simple method using ion-pair high-performance liquid chromatography was established for the rapid and precise determination of sennoside A in oriental pharmaceutical decoctions containing Rhei Rhizoma. This method was compared with other two methods, i.e.

Structural study of cell wall mannan of a Candida albicans (serotype A) strain.

The structure of the mannan of Candida albicans NIH A-207 strain (serotype A) was investigated by adopting mild acetolysis followed by enzymolysis with an Arthrobacter GJM-1 exo-alpha-mannosidase. The resultant oligosaccharides, from pentaose to octaose (where manp = D-mannopyranose), were identified as manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)- manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp and manp beta (1----2)manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, respectively. Analyses of alpha-linked oligosaccharides obtained by acetolysis under conventional conditions gave the same oligosaccharides, from biose to heptaose, as those obtained from the mannans of C.

Epidermal growth factor stimulates the release of GDP induced by isoproterenol from isolated liver membrane.

Epidermal growth factor (EGF) stimulated the release of GDP induced by isoproterenol from isolated liver membrane. This GDP release was not induced by EGF only. The stimulatory effect of EGF was dependent on the presence of Mg2+.

Comparison of opioid properties between D-Arg-containing dipeptides and tetrapeptides.

Since the D-Arg-containing dipeptides, H-Tyr-D-Arg-OMe (TDA) and H-Tyr(Et)-D-Arg-OMe, and D-Arg2-substituted dermorphin N-terminal tetrapeptide analogues, H-Tyr-D-Arg-Phe-Gly-OEt (TDAPG) and H-Tyr(Et)-D-Arg-Phe-Gly-OEt gave different pharmacological responses in vivo, opioid interaction and structure-activity relationships have been investigated in vitro. In the isolated guinea-pig ileum assay, the tetrapeptides were potently inhibitory, their activity markedly exceeding that of the dipeptides. In particular, the first tetrapeptide had twice the activity of morphine, while the potency of the dipeptides was less than one twentieth that of morphine.

Application of 67Ga for the estimation of reticulocyte production.

In order to estimate the production of reticulocytes, which have a larger number of transferrin receptors than erythrocytes, we used 67Ga which is exclusively bound to transferrin in the blood. The pattern of uptake of 67Ga by reticulocytes was quite similar to the time course of transglutaminase activity which might be involved in receptor-mediated endocytosis. The preinjection of Fe3+ decreased the uptake of 67Ga by reticulocytes.