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M Kagoshima

Publications and source records attributed to M Kagoshima.

54 records · Page 3Linked to original sources
PubMed1991

Effect of Y-20811, a long-lasting thromboxane A2 synthetase inhibitor, on antigen-induced airway hyperresponsiveness in guinea pigs.

Effect of Y-20811 on airway hyperresponsiveness was studied in sensitized guinea pigs. Airway hyperresponsiveness to acetylcholine (ACh) reached maximum 7 h after antigen challenge in guinea pigs sensitized actively. Y-20811 (0.3-3 mg/kg) administered orally 3 h prior to challenge inhibited this airway hyperresponsiveness in a dose-dependent manner. Y-20811 (3 mg/kg) administered orally 4 h after antigen challenge also decreased the airway hyperresponsiveness. On the other hand, Y-20811 did not affect the bronchoconstriction induced by ACh, serotonin and histamine in nonsensitized guinea pigs. The number of eosinophils in bronchoalveolar lavage fluid in the guinea pig reached the peak 7 h after antigen challenge. Y-20811 had a tendency to decrease the number of total cells, macrophages and eosinophils in a dose-dependent manner. These results suggest that Y-20811 suppress the asthmatic mechanism which causes antigen-induced airway hyperresponsiveness.

Acetylcholine↗
PubMed1991

[Effects of Y-20811, a specific thromboxane A2 synthetase inhibitor, on chemical mediator-induced bronchoconstriction in guinea pigs].

We investigated the effects of Y-20811 on chemical mediator-induced bronchoconstriction and the release of chemical mediators into lung perfusion fluid during arachidonic acid (AA)-induced bronchoconstriction in guinea pigs. Y-20811 (0.01-1 mg/kg, i.v.), like acetylsalicylic acid or indomethacin, dose-dependently suppressed arachidonic acid- and LTD4-induced bronchoconstriction, and it (1 mg/kg, i.v.) also inhibited PAF-induced bronchoconstriction in guinea pigs. However, at a dose of 1 mg/kg, i.v., it was inactive against the bronchoconstriction induced by histamine, serotonin and acetylcholine in guinea pigs. Y-20811 (0.3-10 mg/kg) administered orally also prevented the LTD4-induced bronchoconstriction in a dose-dependent manner. This protective effect of Y-20811 (10 mg/kg, p.o.) persisted for at least 24 hr. Y-20811 (10 mg/kg, p.o.) also inhibited antigen-induced bronchoconstriction in guinea pigs passively sensitized with anti-ovalbumin guinea pig serum and pretreated with mepyramine. In the perfused and ventilated guinea pig lungs, Y-20811 inhibited AA-induced bronchoconstriction, decreased the release of TXA2 (estimated as TXB2) and increased the release of PGE2 into the perfused lung fluid, significantly (TXB2 and PGE2 were measured by HPLC). Therefore, Y-20811 suppressed various stimulant-induced bronchoconstrictions through the decrease of TXA2 production and the increase of PGE2 production. Thus, Y-20811 should prove useful as an anti-asthmatic drug.

Animals↗
PubMed1991

[Effects of 3-hydroxymethyl-2-methylimidazo [2, 1-b] benzothiazole (NIK-228) on gastric acid secretion and various experimental peptic ulcers in rats].

We examined the antisecretory and antiulcer activities of NIK-228 in rats. Male Wistar rats (200 to 250 g) were used under 24 to 48 hr fasted (without water) conditions. NIK-228 and famotidine were administered orally 1 hr before pylorus ligation, stress or each ulceration inducer. Both NIK-228 (10 to 100 mg/kg) and famotidine (0.3 to 3 mg/kg) dose-dependently inhibited gastric secretion in pylorus ligated rats. Water-immersion stress-, indomethacin- or pylorus ligation (Shay)-induced gastric ulcers were dose-dependently inhibited by NIK-228 (10 to 100 mg/kg), but only water-immersion stress and indomethacin induced ulcers were dose-dependently inhibited by famotidine (0.03 to 3 mg/kg). Ethanol- and 0.6 N HCl-induced gastric lesions were remarkably inhibited by NIK-228 (ED50 = 2.7 and 5.6 mg/kg), but tended to be inhibited also by famotidine (0.3 to 3 mg/kg). Cysteamine-induced duodenal ulcer was inhibited significantly by NIK-228 (30, 100 mg/kg) or famotidine (3 mg/kg). NIK-228 may produce its antiulcer effects via antisecretory and cytoprotective effects. These results suggest that NIK-228 has antisecretory and antiulcer activities.

Administration, Oral↗
PubMed1991

[Evaluation of HCl-induced gastric mucosal lesions using a computer image processing system].

Oral administration of HCl (0.2 N, 0.4 N, 0.6 N, 0.8 N) solution produced congestive or hemorrhagic gastric mucosal lesions in rats. Lesion areas were differentiated into two areas (i.e., brown area and black area) macroscopically. Then, fine observations were performed on two areas using a computer image processing system (CIPS) and histological techniques. Cell necrosis from the mucosal surface to the middle mucosal layer were observed in the brown area, and gastric mucosal necrosis that reached to a deeper layer were observed in the black area. These results indicate that histological degree of lesion may be reflected in the macroscopic changes. Concerning the concentration of HCl, over 0.4 N HCl solution induced mucosal lesions, but HCl solution (0.4 N HCl) only produced a brown area. Maximum changes in the mucosal surface were observed at 30 min to 1 hr by 0.6 N HCl and at 15 to 30 min by 0.8 N HCl. Therefore, the best condition for evaluating the preventive effects of anti-ulcer agents is 30 min after treatment by 0.6 N HCl solution and 15-30 min after treatment by 0.8 N HCl solution. These results suggest that this technique may provide both quantitative and qualitative information on histological changes.

Animals↗
PubMed1991

[Effects of NIK-228 on gastric acid secretion in rats using the congo red sprayed method].

We have reported the antiulcer activities of a new compound that we named NIK-228 (3-hydroxy-methyl-2-methylimidazo [2, 1-b] benzothiazole). In the present report, we studied the antisecretory effects of NIK-228 on basal and stimulated gastric acid secretion using the Congo red sprayed method. Male Wistar rats (200 to 250 g) were used after 24 hr of fasting (without water). NIK-228, atropine and cimetidine were administered orally or intravenously 1 hr before operation for Congo red spraying. NIK-228 (100 mg/kg, p.o.), atropine (5 mg/kg p.o.) and cimetidine (100 mg/kg, p.o.) all inhibited basal gastric acid secretion. Oral administration of NIK-228 and atropine inhibited gastrin, 2-deoxy-D-glucose (2-DG) and bethanechol-induced acid secretion, but didn't inhibit histamine-induced acid secretion. Cimetidine inhibited all of histamine, gastrin, 2-DG and bethanechol-induced acid secretion. In vagotomized rats, oral and intravenous administration of atropine both inhibited bethanechol-induced acid secretion, but NIK-228 was not inhibited. These results suggested that antisecretory effects of NIK-228 were caused by the central vagal systems.

Animals↗
PubMed1990

Mechanism of nasal absorption of drugs. III: Nasal absorption of leucine enkephalin.

The nasal absorption of a model peptide, leucine enkephalin (LE), was studied in rats using an in situ technique in which 4 mL of perfusion solution was circulated. Leucine enkephalin (LE) was found to undergo hydrolysis to its major metabolite des-tyrosine leucine enkephalin (DTLE). The addition of 1% sodium glycocholate (SGC) to the perfusion solution resulted in an increase in the overall rate of disappearance of LE and a decrease in the rate of formation of DTLE. When LE was added to nasal washings (i.e., Ringer's buffer that was precirculated through the nasal cavity to extract enzymes), LE was found to form DTLE. When SGC or puromycin was added to the nasal washings prior to the addition of LE, the rate of conversion of LE to DTLE was significantly reduced, suggesting that these two agents can inhibit peptidase enzyme activity in the nasal cavity. Since the volume of the solution has been shown to influence the kinetics of absorption of drugs administered nasally, a new experimental technique, the in vivo-in situ technique, which utilizes small volumes of solution and simulates realistic use of nose drops, was employed to further examine the mechanism of absorption and hydrolysis of LE in rats. Leucine enkephalin (LE) dissolved in 100 microL of Ringer's buffer was placed in the isolated nasal cavities of rats. The disappearance of LE and the appearance of DTLE were followed by rinsing the nasal cavity with fresh buffer. Disappearance of LE was always accompanied by appearance of DTLE, and the fraction of LE converted to DTLE decreased as the concentration of LE increased, suggesting a saturable enzymatic process.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1990

Mechanism of nasal absorption of drugs. IV: Plasma levels of radioactivity following intranasal administration of [3H]leucine enkephalin.

To study the factors influencing nasal absorption of a model pentapeptide, plasma levels of total radioactivity were determined following the administration of [3H]tyr-leucine enkephalin to rats intravenously, intranasally alone, and intranasally in the presence of puromycin. The major pathway for transport of radioactivity into the blood from the nasal cavity appeared to be hydrolysis of [3H]tyr-leucine enkephalin to [3H]L-tyrosine, followed by absorption of [3H]L-tyrosine. When puromycin was added to the nasal solution in concentrations at which the in vitro hydrolysis of leucine enkephalin was completely inhibited, the appearance of radioactivity in the plasma was slowed, but plasma concentrations of radioactivity eventually reached levels comparable to those observed in the absence of puromycin. In view of the inhibitory effect of puromycin on the hydrolysis of leucine enkephalin, it was assumed that a significant fraction of the [3H]tyr-leucine enkephalin was absorbed intact in the presence of this substance. However, an assay method for intact leucine enkephalin in plasma is needed to confirm these preliminary observations.

Administration, Intranasal↗
PubMed1989

[N-isopropyl I-123 p-iodoamphetamine single photon emission computed tomography of herpes simplex encephalitis].

Two patients with herpes simplex encephalitis were studied with N-Isopropyl I-123 p-Iodoamphetamine (IMP) single photon emission computed tomography (IMP-SPECT) and X-ray computed tomography (CT). In both cases the affected temporal lobes showed an increased IMP uptake. In case 1, the initial increased IMP uptake decreased as symptoms and CT findings improved. In case 2, the increased IMP uptake was shown at the time of symptoms progressed, while CT had no abnormal findings. IMP uptake is sensitive for its demonstration of inflammatory processes of herpes simplex encephalitis.

Aged↗
PubMed1989

Neuroanatomical substrates regulating rat conflict behavior evidenced by brain lesioning.

The present study was designed to clarify neural circuits involved in the mediation of behavioral suppression using the Vogel type conflict procedure in rats. Among the brain nuclei inclusive of neuroanatomical substrates of behavioral suppression, lesioning of the central amygdala, mammillary body or frontal cortex led to a significant increase in the punished drinking responses. Lesion of the septum also tended to increase these responses. These results show the key role of these brain areas in mediation of behavioral suppression such as conflict behavior.

Amygdala↗
PubMed1989

The measurement of gastric mucus using a computer image processing system.

The measurement of gastric mucus, and the effects of aspirin and some antiulcer drugs on the content or components of gastric mucus were investigated in normal rats by using a newly devised computer image processing system. The present method enabled us to separate mucus components into PAS positive mucus (PAS+), and AB positive mucus (AB+), and to measure the amount of each mucus. Aspirin induced significant decreases in both PAS+ and AB+, teprenone increased the total amount of gastric mucus (PAS+ plus AB+), secretin tended to increase AB+, and cimetidine and omeprazole caused no remarkable changes on mucus secretion. These changes in gastric mucus could be observed on both microscopic observation and with the computer image processing system. The results indicate that the computer image processing system is very useful for the measurement of gastric mucus.

Animals↗
PubMed1989

[Secondary degeneration of substantia nigra following massive basal ganglia infarction].

Two autopsied cases of massive unilateral cerebral infarction due to occlusion of the middle cerebral artery (MCA) were reported with special reference to presence of the secondary degeneration of the substantia nigra. Case 1 was a 70-year-old male who suddenly suffered from left hemiplegia 3 years and 2 months prior to death. CT scan showed massive infarction involving basal ganglia and fronto-parietal white matter on the right side. Some parkinsonian features such as oily face and rigidity of limbs were noted during the course. At autopsy, the proximal portion of rt MCA was found occluded and the right substantia nigra was found depigmented. Case 2 was a 71 year-old male who suddenly became hemiplegic 4 years prior to death. CT scan revealed a low density area in the corona radiata of the right cerebral hemisphere. On carotid antiography, complete obstruction of the horizontal portion of right MCA at its distal end was observed, which was confirmed at autopsy. Histologically, the right substant a nigra in case 1 showed marked neuronal loss with gliosis as well as presence of many extracellular melanin pigments. These changes were more prominent in its medial portion where chromatolytic neurons were occasionally seen. The adjacent fronto-pontine tract and pyramidal tract showed secondary degeneration. The left substantia nigra appeared normal. In case 2, the substantia nigra on both sides appeared normal. The whole right cerebral peduncle, on the other hand, showed diffuse myelin pallor.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1984

[Effects of some drugs on plasma uric acid in rats--actions of catecholamines and beta-blocking agents].

Effects of catecholamines on plasma uric acid and allantoin levels were studied in oxonate-treated rats and non-treated rats. 1) In non-treated rats, epinephrine, isoproterenol and phenylephrine, which were injected intravenously, clearly increased plasma uric acid and allantoin, and norepinephrine had only a slight effect. The orders of potency to increase plasma uric acid and allantoin were epinephrine greater than isoproterenol greater than phenylephrine greater than norepinephrine. Beta-adrenoceptor agonists also increased plasma uric acid and allantoin in non-treated rats. The order of potency to increase plasma uric acid was isoproterenol salbutamol trimetoquinol greater than terbutaline, and that of potency to increase plasma allantoin was isoproterenol salbutamol greater than or equal to trimetoquinol greater than terbutaline. 2) In oxonate-treated rats, the four beta-adrenoceptor agonists (50 micrograms/kg, i.v.) markedly potentiated the hyperuricemic effect of oxonate. These effects of beta-adrenoceptor agonists were inhibited by propranolol (2.0 mg/kg. i.v.). In addition, the effect of isoproterenol was inhibited by butoxamine (1.0 mg/kg, i.v.), but not by atenolol (1.0 mg/kg, i.v.). These results suggest that hyperuricemia induced by catecholamines is closely related to beta 2-adrenoceptor action.

Adrenergic beta-Antagonists↗
PubMed1982

[Changes of gastric mucosal vessels in reserpine-induced ulcer (author's transl)].

The gastric microvascular changes in reserpine (RES 6 mg/kg s.c.)-induced ulcer in Wistar male rats were studied. Two kinds of water paints were injected through the superior mesenteric vein and celiac artery. Excised stomachs were frozen instantly by cooled methanol (-70 degrees C) and were put into methylsalicylate after 24 hr in order to make transparent preparations. RES caused constriction of the vein from the middle layer till the muscularis mucosae and congestion with ischemia in the gastric mucosa after 1 hr. Even after 3 hr, these vascular changes remained and were accompanied by erosion. After 6 and 9 hr, the erosion became more severe, while ischemia was no longer found and the vessels were rather dilated. These lesions initiated from the fundic-antral border area in the lesser curvature and gradually extended to the greater curvature. The early changes up to 3 hr were inhibited by phentolamine, isoproterenol, C6, metiamide and methysergide, but not by carbachol, atropine, vagotomy and propranolol. Atropine, vagotomy, isoproterenol, propranolol and C6 inhibited erosion in the late stage. Phentolamine, carbachol, diphenhydramine, metiamide and methysergide were not effective. From these results and the gastric movement caused by RES, it is suggested that the vascular changes of the early stage in RES-induced ulcer are due not only to the autonomic nervous system but also to the endogenous biogenic amines, and the erosions in the late stage depend on the hypermotility of the stomach rather than on the hypersecretion of the stomach.

Animals↗
PubMed1982

[Gastric movements and reserpine-induced ulcer in rats].

Changes of gastric movements and ulcerogenic mechanisms in reserpine (6 mg/kg s.c.)-induced ulcer were studied in Wistar male rats weighing 180 to 220 g after fasting for about 20 hr. Under anesthesia with Nembutal (30 mg/kg i.p.), rats were fixed on their backs. The abdomen was incised and the stomach was exposed. Gastric movements of the fundic glandular area of greater curvature (A), the fundic-antral area of lesser curvature (B), and the neighboring area of pylorus (C) were recorded electromyographically after placing a small bipolar electrode of 1 mm distance on each area. Spontaneously, many higher amplitudes were found in area B and less found in area A. In area C, there were the least number of spikes and the lowest amplitudes. These gastric movements were inhibited until 1 hr after reserpine followed by a gradual increase in spikes and higher amplitudes. This increase was long-lasting and most marked in area B. Increased gastric movements due to reserpine were completely inhibited by atropine and vagotomy, moderately inhibited by hexamethonium and diphenhydramine, and only weakly inhibited by l-phenylephrine, l-isoproterenol, phentolamine, propranolol, metiamide, and methysergide. In reserpine-induced ulcer, ischemia occurred most markedly in area A, but erosions initiated from area B as reported previously. In area B, the gastric movements were most active, and the erosions were inhibited by the drugs which suppress gastric movements. These results suggest that reserpine-induced ulcer is due not only to the ischemia in the earlier stage, but also to the long-lasting hypermotility in the later stage.

Animals↗
PubMedDate not supplied

How signaling pathways interact with gene transcription.

Activation of inflammatory cells by extracellular stimuli such as cytokines, viruses, allergens or oxidants lead to stimulation of intracellular amplifying signalling pathways. These activation pathways lead to enhanced inflammatory gene expression through activation of transcription factors such as nuclear factor kappa B (NF-kappa B). Upon activation, NF-kappa B translocates to the nucleus where it binds specific sites in the promoter regions of responsive genes in a time-dependent manner. This leads to the alterations in the structure of the surrounding DNA/chromatin complex resulting in local unwinding of DNA. Changes in chromatin structure occur as a result of recruitment of large, essentially pre-formed, complexes that contain chromatin remodelling factors and histone acetyltransferases (HATs) such as CREB binding protein (CBP). Acetylations of histones are regulated by HATs whose activity is controlled by a number of factors including phosphorylation. Phosphorylation of HATs by signalling pathways, differentiate themselves from those controlling specific transcription factor activation and result in enhanced transcriptional activity as a result of cross-talk between signalling pathways at the level of chromatin modifications.

Acetylation↗
PubMedDate not supplied

Effect of a potent PAF antagonist, Y-24180, on an allergen-induced late asthmatic response in guinea-pigs.

The effect of Y-24180, a potent and specific PAF antagonist, on the antigen-induced late asthmatic response in guinea-pigs was investigated. We used an asthmatic guinea-pig model which had a high incidence of dual-phase reaction and high reproducibility. Y-24180 (1 mg/kg, p.o.) had a significant inhibitory effect on the late asthmatic response and eosinophil infiltration in bronchoalveolar lavage fluid. These results suggest that PAF may play, at least partially, an important role in the development of the late asthmatic response. Thus, Y-24180 may be useful for the treatment of asthma.

Allergens↗