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N Haga

Publications and source records attributed to N Haga.

At least 19 recordsLinked to original sources
PubMed1995

Stimulatory mechanism of EM523-induced contractions in postprandial stomach of conscious dogs.

BACKGROUND & AIMS: EM523, a motilin agonist, is intended to be used as a gastroprokinetic during the postprandial period, but the mechanism(s) by which EM523 stimulates postprandial contractions in the stomach has not been studied before. The aim of this study was to examine the mechanism of contraction-stimulating activity by EM523 in fed dogs. METHODS: Contractile activity in the gastric antrum of 5 dogs was monitored using a long-term implanted force transducer and measured by integrating the area under the curve. Test materials were continuously infused or injected intravenously. RESULTS: EM523 (1-30 micrograms/kg) induced a dose-dependent increase in fed-type contractions. EM523-induced contractile activity was partially inhibited by atropine, hexamethonium, dopamine, 5-hydroxytryptamine 3 (5-HT3) receptor antagonist, and substance P antagonist. Atropine-resistant and EM523-induced contractions were further inhibited by 5-HT3 receptor antagonist and substance P antagonist, and the combined use of the two antagonists completely eliminated the atropine-resistant and EM523-induced contractions. CONCLUSIONS: EM523-induced contractions in the fed stomach are quite different from phase III contractions in the fasted state and are mediated partially through the cholinergic pathway. The noncholinergic pathway involves 5-HT3 and neurokinin 1 receptors.

Animals↗
PubMed1995

Kinetics and mechanism of photocycloaddition of deoxyuridines to 2,3-dimethyl-2-butene.

The mechanism of photocycloaddition of 2'-deoxyuridine (1a) and thymidine (1b) to 2,3-dimethyl-2-butene (Bu) in acetonitrile by UV irradiation has been studied. The reciprocal quantum yield for the cycloaddition increased linearly with reciprocal concentrations of Bu in acetonitrile to give limiting quantum yields at infinite concentration of Bu as 0.030 and 0.0096 for 1a and 1b, respectively. This shows that the cycloaddition proceeds in a two-step mechanism between the triplet state of 1 and Bu through biradical intermediates. Addition of cis-1,3-pentadiene quenched the reaction obeying the Stern-Volmer equation. The above quenching experiments and laser transient spectroscopy revealed that the triplet state of 1a reacts with Bu with much larger rate constant (1.3-1.6 x 10(9) M-1 s-1) than that of 1b (4-5 x 10(7) M-1 s-1) reflecting larger steric hindrance exerted in the reaction of 1b than that of 1a.

Alkenes↗
PubMed1995

[A case of localized fibrous tumor of the pleura with bloody pleural effusion].

A 25-year-old female came to our hospital with the chief complaint of right dorsal pain. On her initial chest X-ray, the tumor (5 x 3 cm) was recognized in the right lower lung field. The tumor grew rapidly during the three month period between the initial X-ray taken on her first visit and her getting admitted in the hospital. A preoperative diagnosis was done by percutaneous aspiration biopsy. Initial diagnosis of spindle cell tumor was made. Partial resection of right lower lobe with chest wall resection was carried out. There were about 500 ml of bloody pleural effusion. Macroscopically, the tumor was encapsulated, measuring 8.0 x 6.0 x 5.0 cm. The cross section was of a yellowish brown solid tumor. The histological diagnosis was of a low grade malignant fibrous mesothelioma. Only 14 cases of localized mesothelioma with pleural effusion including our case have been reported in Japan. She is still alive nine months after surgery. This patient should be carefully followed for the recurrence of the disease.

Adult↗
PubMed1994

Inhibition of phase III activity by acid in canine stomach.

Very few phase III activity of the interdigestive migrating contractions (phase III) occurs in the stomach of fasted duodenal ulcer patients. But the mechanism is not well understood. In this study, we studied the effect of gastric and duodenal acidification on the spontaneous phase III activity in the upper gastrointestinal tract of conscious dogs. Gastric and duodenal motor activity in 5 conscious dogs was monitored by means of chronically implanted force transducers. Intragastric pH changes were measured by placing a pH glass electrode in the gastric antrum. Intragastric and intraduodenal acidification was achieved by i.v. infusion of histamine, and by intragastric and intraduodenal instillation of acidic solutions of different pHs. The plasma motilin concentrations were measured by radioimmunoassay. Histamine (40 micrograms/kg/h) inhibited spontaneous phase III activity, but the histamine-induced inhibition was completely prevented by pretreatment with famotidine, a potent histamine H2 receptor antagonist (0.3 mg/kg, i.v.). Intragastric acidification at pH 1.0 strongly inhibited spontaneous phase III activity, but an acidic solution at pH 2.0 had no effect in inhibiting phase III activity. Intraduodenal acidification at pH 1.0 also inhibited spontaneous phase III activity. Histamine injection and gastric and duodenal acidification at pH 1.0 strongly suppressed motilin release. It is concluded that gastric and duodenal acidification at pH 1.0 inhibits the occurrence of the spontaneous phase III activity, and the suppression of endogenous release of motilin due to gastric and duodenal acidification at pH 1.0 is involved in this inhibitory mechanism.

Animals↗
PubMed1994

Inhibition of phase III activity by acidifying stomach in vagally denervated and innervated dogs with gastric pouches.

BACKGROUND/AIMS: Intragastric acidification at pH 1.0 strongly inhibits phase III contractions in the dog, but this mechanism is not well known. We studied the mechanism in conscious dogs. METHODS: Vagally denervated and innervated gastric pouch dogs were prepared. Force transducers were chronically implanted on the serosa of the pouch, main stomach, and mid-duodenum. The pH of the perfusate was monitored. RESULTS: Administration of histamine (40 micrograms.kg-1.h-1 intravenously [i.v.]) and instillation of acidic saline at pH 1.0, but not pH 2.0, into the main stomach strongly inhibited the motilin-induced (0.1 microgram/kg i.v.) phase III activity in the main stomach and the innervated pouch but did not influence contractions in the extrinsically denervated pouch. Famotidine completely reversed the histamine-induced inhibition of phase III in the main stomach and Pavlov pouch. Acidification of the pouch itself or duodenum at pH 1.0 did not affect contractions in the main stomach and pouch of either type. CONCLUSIONS: The mechanism of inhibition of motilin-induced phase III activity by acid in the stomach involves the intact vagovagal reflex, but sympathetic participation is not completely ruled out. The inhibition of motilin-induced phase III activity may originate in the antral mucosa of the stomach.

Acids↗
PubMed1994

Vagovagal inhibition of motilin-induced phase III contractions by antral acidification in dog stomach.

Gastric acidification at pH 1.0 strongly inhibits the spontaneously occurring and motilin-induced phase III contractions in canine and human stomach. In this study, we examined inhibition by gastric acidification in dogs following gastrojejunostomy, truncal vagotomy, and antrectomy. As a result, gastric acidification with 0.1 N HCl solution at pH 1.0 for 30 min at a rate of 1.0 ml/min significantly inhibited motilin-induced phase III activity to 23.5 +/- 5.9% of the control in the normal intact dogs and to 17.2 +/- 3.4% in the gastrojejunostomized dogs. In the antrectomized dogs, gastric acidification did not significantly inhibit the action of motilin (81.7 +/- 10%), but, in the vagotomized dogs, gastric acidification inhibited the action of motilin to 72.0 +/- 4.9%; the inhibition was much weaker than in the intact and gastrojejunostomized dogs but was significant. The duodenal acidification had no effect at all on the action of motilin (94.6 +/- 12.5%) in the gastrojejunostomized dogs. These findings strongly suggest the existence of a vagovagal reflex in the inhibition of motilin-induced phase III contractions by gastric antral acidification, although the involvement of sympathetic regulation cannot be completely ruled out.

Animals↗
PubMed1994

Inhibition of motilin-induced phase III contractions by pentagastrin in Heidenhain pouch dogs.

We compared the inhibitory effects of histamine and pentagastrin (PG) on motilin-induced upper gastrointestinal phase III activity in conscious dogs that had surgically prepared Heidenhain pouchs (HP). Contractile activity was measured by means of chronically implanted force transducers, and changes in pH of the perfusate through the HP were monitored simultaneously. Intravenous infusion of PG (4 micrograms/kg-hr) inhibited motilin-induced phase III activity both in the main stomach and in the HP, whereas histamine (40 micrograms/kg-hr) inhibited activity only in the main stomach. Famotidine (0.3 mg/kg, i.v., the dose that completely inhibited gastric acid secretion by PG or histamine) blocked the inhibition of phase III activity induced by histamine but did not affect PG-induced inhibition. L-364,718 (1 mg/kg, i.v.), which had no effect on the PG-induced decrease in the pH of the perfusate lowered by PG, reversed the inhibition of phase III activity by PG in the HP but not in the main stomach. However, L-364,718, when combined with famotidine, potently reversed the PG-induced inhibition of phase III activity both in the main stomach and in the HP. These results show that the inhibitory effect of PG on motilin-induced phase III activity is brought about by two distinctive mechanisms, gastric acid and the cholecystokinin receptors-dependent mechanism, whereas the histamine-induced inhibition is mediated only by gastric acid. In the vagally denervated HP, however, gastric acid is not involved in an inhibitory effect of PG.

Animals↗
PubMed1992

A novel class of platelet activating factor (PAF) antagonists. I. Synthesis and structure-activity studies on PAF-sulfonamide isosteres.

New platelet activating factor (PAF) antagonists, 3 were synthesized by replacing the charged phosphate and trimethylammonium moieties with sulfonamide and heterocyclic quaternary ammonium functionalities, respectively (PAF-sulfonamide isosteres). Darmstoff phosphatidic acid analogues of this class (Darmstoff-sulfonamide isosteres), 6 were also synthesized. The activity of these compounds as PAF antagonists was evaluated from their in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma. Among the compounds tested, some of the 2-methoxypropane derivatives with an octadecylcarbamoyloxy or octadecylcarbamoylthio side chain at the 1-position and a propylsulfonamide function bearing a terminal polar substituent such as a quaternary quinolinium or substituted quinolinium group at the 3-position were found to be the most potent (IC50 = 0.3-0.6 microM).

Animals↗
PubMed1992

A novel class of platelet activating factor (PAF) antagonists. II. Modification of the 2-position of the glycerol backbone of PAF-sulfonamide isosteres.

In a continuing effort to obtain more potent platelet activating factor (PAF) antagonists, we tried to synthesize a series of PAF-sulfonamide isosteres in which the substituent at the 2-position was modified to an acetoxy equivalent other than the methoxy group. These modifications produced highly active PAF antagonists. Compound 3-[2-(5-methyl-2H-tetrazol-2-yl)-3-(octadecylcarbamoyloxy) propylaminosulfonyl]propylquinolinium iodide (52) showed the most potent activity in the in vitro inhibitory effect on PAF-induced platelet aggregation in rabbit platelet-rich plasma (IC50 = 125 nM) and also in the in vivo protective effect on PAF-induced lethality in mice, with prolonged duration of action. Optically active enantiomers of this compound were synthesized and the (S)-(-)-isomer (IC50 = 87 nM) was found to be three times more potent that the (R)-(+)-isomer (IC50 = 289 nM), clearly exemplifying the enantioselectivity in the PAF-antagonist action of this novel compound.

Animals↗
PubMed1990

Synthesis of thromboxane receptor antagonists with bicyclo[3.1.0]hexane ring systems.

Thromboxane A2 receptor antagonists 11a, 15a, 26a, 30a, 34a, 36a, 46a, 52a, 61a, 72a, and 82a, which contain 6-oxabicyclo[3.1.0]hexane, 6-thiabicyclo[3.1.0]hexane, bicyclo[3.1.0]hexane, or 6,6-dimethylbicyclo[3.1.0]hexane ring systems with heptenoic and (phenylsulfonyl)amino side chains, and their corresponding sodium salts and methyl esters were synthesized. This study then examined the inhibitory effects of their sodium salts for the platelet aggregation induced by arachidonic acid with rabbit platelet-rich plasma and platelet aggregation induced by collagen with rat washed platelets.

Animals↗
PubMed1988

Method for evaluating mutagenicity of water. I. A new method of preparing samples for mutagenicity test.

A sample preparation method for a convenient and quantitative mutagenicity test of water was developed using two new superior resinous adsorbents. One, CSP800, is a small particle size and highly porous polystyrene resin, and the other, CHPA25, is a small particle size and highly porous anion-exchange resin. CSP800 adsorbed more nonionic compounds from water than conventional resins, and CHPA25 adsorbed anionic compounds not adsorbed by conventional resins. Sample water (10 l) at pH 5 was fed at 550 ml h-1 into two columns in series, one containing 5 ml of CSP800 and the other 2 ml of CHPA25. The adsorbed substances were subsequently desorbed by DMSO from CSP800 and by 4 N NaNO3 from CHPA25, at 10 ml h-1. Various organic substances, which were measured by different indices such as total trihalomethanes (THM), total organic halogen (TOX) and the absorbence at 260 nm, could be recovered by this method much more efficiently and conveniently than by conventional methods.

Chromatography, Ion Exchange↗
PubMed1988

Method for evaluating mutagenicity of water. II. Conditions for applying new sample preparation method to the Ames test.

Conditions for the application of a new sample preparation method developed in a previous study using the small particle size and highly porous polystyrene and anion-exchange resins CSP800 and CHPA25 were investigated. The desorbing solvents DMSO and 4 N NaNO3 (0.5 ml), corresponding to 11 of water sample, could be dosed on a plate for the mutagenicity test, the Ames test. It was confirmed that trace impurities from the resins were not mutagenic. The mutagenicity of several drinking water samples was determined by this new method and evaluated quantitatively by converting to the concentrations of the standard mutagens, 4-nitroquinoline-1-oxide and 2-aminoanthracene, without S9 and with S9 respectively. Furthermore, the mutagenicity of the nonionic pollutants adsorbed on CSP800 and that of the anionic pollutants adsorbed on CHPA25 could be evaluated separately.

Dose-Response Relationship, Drug↗
PubMed1987

Aldosterone antagonists. 2. Synthesis and biological activities of 11,12-dehydropregnane derivatives.

Several steroid derivatives having the delta 11-pregnane skeleton with a 17-gamma-spirolactone function were synthesized to evaluate their antialdosterone activity and to elucidate the relation between their binding affinity to mineralocorticoid receptor (MR) and their mineralo- and/or antimineralocorticoid activity. Although many of the synthesized compounds showed strong binding affinity for the MR and aldosterone agonist activity, 3-(17 beta-hydroxy-3-oxoandrosta-1,4,6,11-tetraen-17 alpha-yl)propionic acid gamma-lactone exhibited good aldosterone antagonist activity in an in vivo assay. Its in vivo antiandrogenic activity was also found to be relatively weak.

Adrenalectomy↗
PubMed1986

Attenuation by isosorbide dinitrate of coronary occlusion-induced acidosis in the dog myocardium.

In dogs anaesthetized with pentobarbitone, the thorax was opened and myocardial pH measured continuously by the use of a glass pH electrode inserted in the left ventricular wall. The left anterior descending coronary artery (LAD) was partially occluded so that the LAD flow could be reduced to a half or one-third of the original flow (partial occlusion). LAD partial occlusion was continued for 90 min, drug or saline being infused for the last 60 min of this period. LAD occlusion decreased myocardial pH significantly by 0.41 to 0.67 pH units, and increased ST segment of the surface electrocardiogram from 11.7 to 12.1 mV. In dogs with non-ischaemic normal hearts, isosorbide dinitrate (ISDN; 1 mg kg-1) did not change markedly either the LAD flow, myocardial pH or heart rate, whereas it decreased myocardial contractile force (determined by a strain gauge arch) slightly and both the systolic and diastolic blood pressure markedly. In dogs with partial LAD occlusion, ISDN (1 mg kg-1) increased myocardial pH significantly and decreased blood pressure, but did not change ST segment elevation in an epicardial lead. These results indicate that ISDN attenuates ischaemia-induced acidosis without attenuating ischaemia-induced ST elevation in the dog myocardium.

Acidosis↗
PubMed1986

Microinjection of immaturin rejuvenates sexual activity of old Paramecium.

The sexual activity of aged Paramecium that underwent about 700 fissions after conjugation was remarkably decreased. Microinjection of a soluble cytoplasmic fraction prepared from young immature cells (about 20 fissions after conjugation) restored the sexual activity of the aged cells to that of presenescent mature cells. The factor responsible for the recovery of the sexual activity was shown to have the same characteristics as immaturin in terms of molecular size and net charge. Rejuvenation of sexual activity lasted up to 20 fissions after microinjection. However, cell division rate or fertility after self-conjugation was not increased by the microinjection. Our finding indicates that the decrease in sexual activity caused by aging was not due to defects in the genes for mating substances but to a decrease in the activity of a soluble protein responsible for the expression of mating activity. This is the first description of the restoration of a senescent defect by microinjection of young cytoplasmic components into Paramecium.

Animals↗
PubMed1986

Relationships of the molecular structure of aldosterone derivatives with their binding affinity for mineralocorticoid receptor.

The molecular structures of 19-nor-11-deoxycorticosterone (III) and 21-hydroxypregna-4,11-diene-3,20-dione (IV) were determined by X-ray crystallographic analysis and the factors affecting the binding affinities for the mineralocorticoid receptor were examined with six aldosterone derivatives (I-VI) containing these two compounds. The most important factor was found to be the steric one; affinity increased with increasing flatness of the structure. The electronic factor may be a minor influence although a good relationship was found between the affinity and the 13C-NMR chemical shift of the C(5) atom. The factor playing no role in the binding is the hydrophobic one.

Aldosterone↗
PubMed1986

Effect of dilazep on decrease in myocardial pH during ischemia in dogs.

The present study was undertaken in order to examine whether dilazep (1,4-bis-[3-(3,4,5-trimethoxybenzoyloxy)propyl]perhydro-1, 4-diazepine dihydrochloride monohydrate) attenuates myocardial acidosis induced by coronary artery occlusion in dogs. In dogs with nonischemic normal heart, dilazep (300 or 500 micrograms/kg i.v.) increased blood flow in the left anterior descending coronary artery (LAD) with a decrease in heart rate and diastolic blood pressure. In other dogs, LAD flow was reduced by an occluder by 57 to 68% (partial occlusion) for 90 min. Partial occlusion for 30 min decreased myocardial pH by 0.67 to 0.87 pH units, increased ST segment of the surface electrocardiogram, and decreased regional myocardial contractile force. Dilazep was injected i.v. 30 min after partial occlusion. The decrease in myocardial pH induced by partial occlusion was attenuated by the injection of 300 micrograms/kg of dilazep insignificantly and by that of 500 micrograms/kg of dilazep significantly. Restoration of myocardial [H+] induced by dilazep was calculated from the myocardial pH data. Dilazep (500 micrograms/kg) restored myocardial [H+] induced by partial occlusion by 56.7%, and saline solution restored it by 27.4% 60 min after the drug injection, the actual restoration induced by dilazep being 29.3%. Dilazep, however, did not restore the ST segment elevation and contractile force decrease. It is concluded that dilazep attenuates myocardial acidosis during ischemia.

Animals↗