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N Haga

Publications and source records attributed to N Haga.

At least 19 recordsLinked to original sources
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↗
PubMed1985

Aldosterone antagonists. 1. Synthesis and biological activities of 11 beta,18-epoxypregnane derivatives.

Several steroid derivatives having the 11 beta,18-epoxypregnane skeleton, 7, 8, 19, 20, 21, and 31, were synthesized to evaluate their antialdosterone activity. Among them, 3-(9 alpha-fluoro-17 beta-hydroxy-3-oxoandrost-4-en-17 alpha-yl)propionic acid gamma-lactone (31) possessed fairly strong binding affinity for the cytoplasmic mineralocorticoid receptor of rat kidney and exhibited good aldosterone antagonist activity in an in vivo assay. However, its agonistic nature cannot be ignored. The properties of 31 as an aldosterone antagonist were enhanced by its very low to negligible binding affinity for the androgen, progestin, estrogen, and glucocorticoid receptors.

Animals↗
PubMed1985

Effect of NCO-700, an inhibitor of protease, on myocardial pH decreased by coronary occlusion in dogs.

During myocardial ischemia in dogs effects of NCO-700, a protease inhibitor on myocardial pH, were investigated. Ischemia was produced for 90 min by partial occlusion of the left anterior descending coronary artery (LAD). Myocardial pH was measured by a micro glass pH electrode inserted in the subendocardium of the LAD area. Before partial occlusion, myocardial pH was 7.50-7.67. It decreased by 0.65 to 0.86 pH units after partial occlusion. NCO-700 was injected intravenously after 30 min partial occlusion. At a dose of 5 or 20 mg/kg NCO-700 increased myocardial pH, which had been decreased by LAD partial occlusion, by 0.26 or 0.31 pH units, respectively. In the nonischemic myocardium pH increased only 0.03 units. Drug-induced restoration of myocardial [H+] was then calculated. At a dose of 5 or 20 mg/kg NCO-700 restored myocardial [H+], which had been increased by partial occlusion. However, NCO-700 did not attenuate the ischemia-induced elevation of ST segment of the surface electrocardiogram. These observations demonstrate that NCO-700 attenuates myocardial pH depressed by partial occlusion of LAD.

Animals↗
PubMed1985

Effect of cinpropazide on ischemic myocardial acidosis in dogs.

In dogs anesthetized with pentobarbital, the left anterior descending coronary artery (LAD) was occluded by an occluder so that the LAD flow could be set to about half the original flow (partial occlusion). Partial occlusion of the LAD continued for 90 min, and myocardial pH decreased by 0.71 pH unit 30 min after the start of partial occlusion. Cinpropazide, a coronary vasodilator, was injected intravenously 30 min after partial occlusion. Cinpropazide at the dose of 1 mg/kg, which increased LAD flow insignificantly in the nonischemic normal heart, attenuated the myocardial pH that has been reduced by partial occlusion, with a slight reduction in diastolic blood pressure. Restoration of myocardial [H+] 60 min after the injection of cinpropazide was 75.3%, and that of saline solution was 29.5%, indicating that cinpropazide restored the myocardial [H+] by 45.8% during ischemia. The effect of cinpropazide to increase myocardial pH was not observed in the dog with nonischemic heart, however. It is concluded that cinpropazide attenuates myocardial acidosis during ischemia.

Acidosis↗