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Biomedical subjects

H Yuki

Publications and source records attributed to H Yuki.

At least 55 records · Page 3Linked to original sources
PubMed1991

Pharmacologic profile of (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride (YM060), a potent and selective 5-hydroxytryptamine3 receptor antagonist, and its enantiomer in the isolated tissue.

(R)-5-[(1-Methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride (YM060) is a structurally novel, extremely potent, and highly selective serotonin (5HT)3 receptor antagonist. Its 5HT3 receptor blocking properties were compared with those of its enantiomer (S-form), granisetron and ondansetron, in the isolated distal colon of the guinea pig. YM060 competitively antagonized 5HT- and 2-methyl-5HT-induced contraction of the colon, with pA2 values of 8.71 +/- 0.09 (n = 12) and 8.69 +/- 0.06 (n = 9), respectively. Its antagonistic activity was approximately 200, 5 and 50 times more potent than those of the S-form (pA2 = 6.33 +/- 0.06, n = 9 against 5HT; 6.47 +/- 0.1, n = 9 against 2-methyl-5HT), granisetron (pA2 = 8.03 +/- 0.07, n = 9; 8.02 +/- 0.04, n = 9), and ondansetron (pA2 = 7.02 +/- 0.08, n = 9; 6.98 +/- 0.02, n = 9), respectively. Each pA2 value was constant and the isomeric activity ratio (R-form/S-form) was constant irrespective of the agonist used, suggesting that each drug acted on the same 5HT3 receptor. YM060 failed to antagonize contractions induced by 5HT in the saphenous vein of the dog (5HT1-like receptor) or in the aorta of the rabbit (5HT2 receptor. YM060 has a low affinity for alpha-1 (rabbit aorta; pA2 = 5.08 +/- 0.07, n = 8) and alpha-2 (guinea pig ileum; pA2 = 5.61 +/- 0.09, n = 11) adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serotonin (5-HT)3 receptor blocking activities of YM060, a novel 4,5,6,7-tetrahydrobenzimidazole derivative, and its enantiomer in anesthetized rats.

YM060 [(R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimida zol e hydrochloride], is structurally independent of other 5-HT3 receptor antagonists. We investigated in vivo 5-HT3 receptor blocking activity of YM060 and compared results with those of its enantiomer (S-form), ondansetron (GR38032F), granisetron (BRL43694), ICS205-930 [(3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester], LY277359 [endo-5-chloro-2,3-dihydro-2,2-dimethyl-N-(8-methyl-8-azabicyclo[3.2.1] oct-3-yl)-7-benzofuran-carboxamide-(Z)-2-butenedioate (1:1)], Y25130 [(+-)-N-(1-azabicyclo[2.2.2]oct-3-yl)-6-chloro-4-methyl-3-oxo-3,4- dihydro-2H-1,4-benzoxazine-8-carboxamide hydrochloride] and zacopride [(R,S)4-amino-N-[1-azabicyclo (2.2.2)oct-3-yl]-5-chloro-2-methoxybenzamide(E)-2-butenedioat e]. YM060 injected i.v. dose-dependently inhibited the reduction in heart rate induced by 5-HT (30 micrograms/kg i.v.) in rats (von Bezold-Jarisch reflex) with an ED50 value of 0.036 (0.031-0.041) micrograms/kg (n = 3-5). Based on these values, YM060 was 53, 18, 23, 16, 11 and 4 times as potent as ondansetron, granisetron, ICS205-930, LY277359, Y25130 and zacopride, respectively. The S-form of YM060 also inhibited 5-HT-induced bradycardia, but with a potency approximately 250 times less than that of YM060 (R-form). YM060 dosed p.o. also inhibited 5-HT-induced bradycardia with an ED50 value of 0.59 (0.44-0.80) micrograms/kg (n = 3-5), indicating the drug to be 387, 66, 97, 6 and 16 times more potent than ondansetron, granisetron, ICS205-930, LY277359 and Y25130, respectively, but 2 times less potent than zacopride. Bioavailability of YM060 based on the p.o.-to-i.v. ED50 ratio (p.o./i.v. = 16) was lower than those of zacopride (2) and LY277359 (6), similar to that of Y25130 (22) and better than those of ondansetron (109), granisetron (60) and ICS205-930 (71).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

Fluorometric determination of carnitine in serum with immobilized carnitine dehydrogenase and diaphorase.

A fluorometric flow-injection method for determining carnitine with use of immobilized enzymes carnitine dehydrogenase (EC 1.1.1.108) and diaphorase (EC 1.8.1.4) was developed and applied to the assay of carnitine in serum of patients treated with valproic acid. After fractionation and hydrolysis of carnitines in serum samples by perchloric acid and potassium hydroxide, liberated carnitine was converted to resorufin by immobilized carnitine dehydrogenase and diaphorase in the presence of beta-NAD+ (1.0 mmol/L), resazurin (12.5 mumol/L), and Tris acetate (0.6 mol/L, pH 9.0) at 37 degrees C. The fluorescence intensity of resorufin was monitored at lambda Ex 560 nm and lambda Em 580 nm. The calibration curve was linear for carnitine amounts from 0.1 to 1.0 nmol. Quantitative analytical recovery and satisfactory within- and between-run imprecision of carnitine in each carnitine fraction were obtained. Interference by bilirubin, serum albumin, and hemoglobin was negligible. Carnitine deficiencies were detected in about 20% of the valproic acid-treated patients (n = 198). The present method should be useful for monitoring carnitine deficiencies in clinical laboratories.

Alcohol Oxidoreductases↗
PubMed1990

[Postoperative pancreatitis following thoracoabdominal aortic aneurysmectomy--a case report].

Thoracoabdominal aortic aneurysmectomy with a temporary bypass from left axillary to right common iliac artery was successfully performed in a 57 year-old-female with an aneurysm involving celiac, superior mesenteric and renal arteries. An elevation of serum amylase level with a peak value on 7 POD was observed and ultrasonography revealed acute pancreatitis resulting from seventy minutes ischemia of celiac artery during the procedure. The patient was treated conservatively and discharged. It seems to be important to prevent pancreatic ischemia in thoracoabdominal aortic aneurysmectomy as well as to maintain renal and hepatic circulation.

Acute Disease↗
PubMed1989

Determination of inorganic phosphate by flow injection method with immobilized enzymes and chemiluminescence detection.

A flow injection method with chemiluminescence detection has been developed for the enzymatic determination of inorganic phosphate. Purine nucleoside phosphorylase, xanthine oxidase, and urate oxidase were immobilized on controlled-pore glass beads. Hydrogen peroxide released by the enzymatic reactions of phosphate and inosine in carrier buffer was detected by the luminol-microperoxidase system in a flow cell. The calibration graph was linear over the range of 5 to 250 pmol, and reproducibility was 1.75% at 10 pmol. The detection limit was 500 fmol of phosphate in 50 microliters of sample injected. The phosphate content in deoxyribonucleic acid was measured by this method.

Animals↗
PubMed1989

Effects of anticholinergic bronchodilators on mucociliary transport and airway secretion.

The effects of atropine, ipratropium and oxitropium on the mucociliary clearance were studied in pigeons and rabbits. The normal mucociliary transport (MCT) in pigeons was inhibited after the treatment by any of the three drugs at concentrations of 10(-4) to 10(-3) g/ml. These three drugs markedly inhibited eserine-induced MCT acceleration at a lower concentration than ACh-induced acceleration. The normal airway secretion was inhibited only by atropine in rabbits. The results indicate that neither oxitropium nor ipratropium depress the normal mucociliary clearance, but atropine may depress it under some conditions. Additionally, we suggest that these anticholinergic drugs might selectively affect the mucociliary transport modulated by endogenous ACh.

Acetylcholine↗
PubMed1989

Automated determination of drugs in serum by column-switching high-performance liquid chromatography. IV. Separation of tricyclic and tetracyclic antidepressants and their metabolites.

We describe automated column-switching high-performance liquid chromatography for determining nine tricyclic and tetracyclic antidepressants (TCAs) and their metabolites in human serum. TSKgel ODS-80TM and TSKprecolumn PW (Tosoh Co., Tokyo) are used in the analytical column and the precolumn, respectively. A 200-microL serum sample is directly injected onto the precolumn. After washing the serum proteins from the precolumn with potassium phosphate buffer, the precolumn connection is switched to introduce the retained substances onto the analytical column. The drugs are then eluted within 30 min with an acetonitrile/potassium phosphate buffer mixture containing sodium 1-heptanesulfonate. The analytical recoveries (95-104%), reproducibilities (within-run CV less than 3%), and detection limits (10 micrograms/L) indicate that this HPLC system is suited for therapeutic drug monitoring. Correlations were good between the TCA concentrations in serum and administered dose (r = 0.713, n = 41), and between 10-hydroxynortriptyline and nortriptyline in serum (r = 0.691, n = 24).

Amitriptyline↗
PubMed1988

Synergistic effect of lymphokines and lipopolysaccharides on macrophage chemiluminescence. Appearance of spontaneous chemiluminescence and its correlation with cytotoxicity.

A new type of chemiluminescence (CL) was observed in thioglycolate-elicited ICR mouse peritoneal macrophages which had been incubated for 24 h in medium containing lymphokines (LK) and lipopolysaccharides (LPS), and then exposed to a CL reagent solution containing luminol and phorbol myristate acetate (PMA). The new CL, which was clearly distinguishable from PMA-induced CL, appeared immediately after the addition of the CL reagent solution, reaching a maximal level at about 30 s, and disappeared rapidly. We have called the new CL 'spontaneous CL', since it appeared spontaneously without PMA triggering. When the macrophages were incubated with LK in the presence of 10 ng/ml of LPS, the spontaneous CL began to appear after about 4 h incubation, the maximal level being reached at about 12 h, after which it decreased gradually on further incubation. After 48 h, it could not be observed at all. The spontaneous CL could be observed only in macrophages simultaneously treated with LK and LPS, as in the case of cytotoxicity. The correlation between spontaneous CL and cytotoxicity was suggested by the following; they showed a similar dose dependency to LK, and neither of them could be induced in aged macrophages which had been incubated in vitro for 1 day before exposure to LK and LPS. These results suggest that spontaneous CL measurement could possibly replace the cytotoxicity test as a simple method for the determination of macrophage activating factor.

Animals↗
PubMed1986

A simple and rapid method for the determination of macrophage activating factor involving a new type of apparatus suitable for the measurement of macrophage chemiluminescence.

A simple and rapid method for the determination of macrophage activating factor is described. A new type of apparatus suitable for the measurement of macrophage chemiluminescence was devised, and the effect of lymphokines on macrophage activities was studied by measuring phorbol myristate acetate-induced luminol-dependent chemiluminescence. An outstanding feature of the new apparatus is that the plastic dish used for the cell culture can be used as the vessel for the chemiluminescence reaction. When thioglycollate-elicited ICR mouse peritoneal macrophages were incubated with lymphokines, their ability to generate chemiluminescence increased rapidly, reaching a maximal level at about 4 h, and then it progressively decreased to the control level at 8 h. Although this increasing effect of lymphokines on macrophage chemiluminescence was short-lived, it could be seen at a relatively low concentration, at which lymphokine-mediated cytotoxic activity of macrophages was not observed.

Animals↗