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Biomedical subjects

K Shuto

Publications and source records attributed to K Shuto.

At least 109 records · Page 6Linked to original sources
PubMed1982

Effect of N-acetyl-L-glutamine aluminum complex (KW-110), an antiulcer agent, on the non-steroidal anti-inflammatory drug-induced exacerbation of gastric ulcer in rats.

Gastric ulcer induced by the injection of acetic acid (0.025 ml of 20%) into the gastric wall of rats was healed considerably 5 days after the injection of acetic acid. Non-steroidal anti-inflammatory drugs (NSAID) such as aspirin, indomethacin, and phenylbutazone were given consecutively for 5 days, and they exacerbated the ulcer and enlarged the ulcer area. Aspirin caused exacerbation when it was given for the initial 5 days of the ulcer healing process. Phenylbutazone caused exacerbation by the administration for 5 days at the middle stage of the ulcer healing process. In contrast, indomethacin caused exacerbation not only when it was given for the initial 5 days but also when it was given for the middle 5 days. The effect of the antiulcer agent N-acetyl-L-glutamine aluminum complex (KW-110) on the exacerbation was studied. KW-110 at an oral dose of 500 mg/kg inhibited remarkably the exacerbation induced by all of the NSAID used. The development of gastric lesions induced by these NSAID was also prevented by KW-110. Further study was carried out with regard to the influences of KW-110 on the pharmacological properties of NSAID. The results showed no influences of KW-110 on the antiedematous and antipyretic actions of the NSAID.

Aluminum↗
PubMed1982

[Pharmacological studies on oxatomide (KW-4354): (1) Effect on passive cutaneous anaphylaxis (PCA)].

The present experiment was an attempt to clarify the pharmacological properties of oxatomide. Oxatomide administered i.v. was found to be as active as disodium cromoglycate (DSCG) in inhibiting the IgE-mediated 48 hr homologous PCA in rats. In contrast to DSCG, oxatomide was also effective when administered p.o. Oxatomide inhibited the IgG-mediated 4 hr heterologous PCA in guinea pigs. However, DSCG did not prevent this reaction. In an attempt to determine at what stage in the PCA reaction oxatomide was effective, the experiment was performed utilizing a double sensitization technique with two different IgE antibodies, anti-dinitrophenylated-ascaris extract and anti-egg albumin. When the same antigen was challenged twice in sequence, the second antigen challenge did not produce the PCA regardless of the presence or absence of oxatomide at the initial antigen challenge. However, the presence of oxatomide during the period of the first challenge preserved completely the PCA responsiveness of the tissue to the second challenge with the other antigen. Similar results were obtained with DSCG. These results suggest that oxatomide may not impair the antigen-antibody combination, but it probably prevents the release of chemical mediators in a manner similar to DSCG.

Adrenalectomy↗
PubMed1982

[Pharmacological studies on oxatomide (KW-4354): (2) Effect on the experimental models of the type 1-type 4 allergic reactions].

The present experiment was performed to examine the effects of oxatomide on the four types of allergic reactions classified by Cooms and Gell. 1) type 1: Oxatomide administered p.o. showed inhibitory effects on the 48 hr homologous passive cutaneous anaphylaxis in rats and the passive anaphylactic bronchoconstriction in guinea pigs. 2) type 2: Oxatomide showed few effects on the complement-dependent cytolysis of sheep red blood cells, the Forssman shock in guinea pigs, and the reversed cutaneous anaphylaxis and the swelling of the footpad induced by rabbit antiserum against rat serum in rats. 3) type 3: Oxatomide alleviated the symptoms during the early stage of the active Arthus reaction in guinea pigs, but the drug did not inhibit the symptoms during the later stage of the reaction. 4) type 4: Oxatomide did not exert an inhibitory effect on the delayed-type hypersensitivity responses to picryl chloride and to sheep red blood cells in mice. These results indicate that oxatomide selectively suppress the type 1 allergic reaction.

Animals↗
PubMed1982

[Pharmacological actions of oxatomide (KW-4354). 3. Actions on experimental asthma and Schultz-Dale reaction].

The present experiment was carried out to elucidate the effectiveness of oxatomide for prophylaxis in the bronchial anaphylaxis and Schultz-Dale response. 1) Oxatomide administered i.v. was found to be as active as disodium cromoglycate (DSCG) in inhibiting IgE-mediated active anaphylactic bronchoconstrictions in rats. In contrast to DSCG, oxatomide was effective when administered p.o. 2) Passive anaphylactic broncho-constrictions in guinea pigs mediated IgG-like rabbit antibody against egg albumin was also prevented dose-dependently by treatment with oxatomide given p.o. and i.v., but not by DSCG. 3) Oxatomide and DSCG inhibited passive anaphylactic bronchoconstrictions in guinea pigs mediated by IgE-like antibody against BPO X BGG. 4) The anaphylactic reaction of the isolated guinea pig ileum, the so-called Schultz-Dale reaction, showed a bi-phasic response: a short, rapid contraction followed by a partial relaxation and a slow contractile response. Oxatomide significantly depressed both the rapid first contraction and the slow sustained one. 5) Oxatomide administered after the development of antigen-induced contraction of isolated guinea pig trachea resulted in relaxation. These results suggest that oxatomide may be effective for the treatment of allergic bronchial asthma.

Animals↗
PubMed1982

[Pharmacological studies on oxatomide: (4) Effect on the histamine release from isolated rat peritoneal exudate cells (PEC) and lung slices].

The present study was carried out to evaluate the inhibitory effect of oxatomide and disodium cromoglycate (DSCG) on the histamine release from rat PEC and lung slices induced by antigen-antibody reaction, concanavalin A, compound 48/80 and A-23187. Oxatomide in the range of 1 microM to 10 microM inhibited the allergic histamine release from rat PEC and lung slices induced by antigen-antibody reaction in the presence of phosphatidyl-L-serine (PS). Although the inhibitory action of oxatomide was significant even at a concentration of 1 microM, the action did not increase with an increase in concentration of the drug. DSCG showed a concentration-dependent inhibition on the allergic histamine release from rat PEC and lung slices in the range of 10 microM to 100 microM. The histamine release from rat PEC induced by the combined treatment of concanavalin A and PS was inhibited by oxatomide (0.1 to 10 microM) and DSCG (10 to 100 microM). Oxatomide (up to 10 microM) showed no effect on the histamine release induced by compound 48/80, while DSCG in the range of 10 microM to 100 microM showed a concentration dependent inhibition of the release. Oxatomide at a concentration of 10 microM showed a significant inhibition on the histamine release induced by the calcium ionophore A-23187. On the other hand, DSCG had no effect on this reaction. Oxatomide at high concentrations did not stimulate the histamine release by itself.

Animals↗
PubMed1982

[Effects of (E)-1-[bis (4-fluorophenyl)methyl]-4-(3-phenyl-2-propenyl) piperazine dihydrochloride(flunarizine) on cerebral circulation].

Effects of flunarizine (0.3-3 mg/kg, i.v.) on cerebral circulation were compared with those of cinnarizine (0.3-3 mg/kg, i.v.) and papaverine (0.1-1 mg/kg, i.v.) in anaesthetized dogs and cats. In dogs any of the three drugs caused a dose-related increase in vertebral, common carotid, and femoral arterial blood flow, while a transient decrease in renal blood flow was seen. In particular, the vasodilatation caused by flunarizine and cinnarizine was much more marked in the vertebral vascular beds as compared to the other ones. Flunarizine (10 and 30 mg/kg, intraduodenally) caused a greater and more prolonged increase in the vertebral blood flow than cinnarizine and papaverine did when they were used in the same doses. Concerning the local circulation in cats, flunarizine and cinnarizine produced a marked flow increase in the cerebellar cortex, and apparent blood flow and pO2 increases in the cerebral cortex with no observable concomitant changes in arterial blood pO2 and pCO2; but a slight decrease in hippocampal blood flow without any consistent effect in hypothalamic blood flow. In this study, flunarizine was shown to have a more prolonged pharmacological activity on the responses of the cerebral circulation than equal doses of cinnarizine or papaverine.

Animals↗
PubMed1982

[Effects of flunarizine on nystagmus and cochlear blood flow].

The effects of flunarizine (1.25-5 mg/kg, i.v.), a cerebral vasodilator, on nystagmus were compared with those of cinnarizine (2.5-5 mg/kg, i.v.) and diphenidol (2.5-5 mg/kg, i.v.) in rabbits. Flunarizine produced significant decrease in the beat number and duration of caloric-induced nystagmus. On the other hand, cinnarizine and diphenidol decreased the beat number, but hardly shortened the duration. In the same way, these three drugs suppressed the amplitude of the corneocortical potential induced by optokinetic stimulation. However, flunarizine up to 5 mg/kg had no effect on central nystagmus induced by unilateral stimulation to the lateral geniculate body. Flunarizine (0.312-1.25 mg/kg, i.v.), cinnarizine (0.625-2.5 mg/kg, i.v.) and diphenidol (0.625-2.5 mg/kg, i.v.) markedly increased the blood flow in the radiating arteriole of cochlea in the anaesthetized guinea pig. The duration of their increasing activities was in the following order: flunarizine greater than or equal to cinnarizine greater than diphenidol. From these results, it is suggested that the suppression of nystagmus by flunarizine may be at least partly due to the favorable effect on microcirculation in the vestibular organ.

Animals↗
PubMed1981

Proteinase inhibitors suppress the formation of granulation tissue in the carrageenin-induced inflammation in rats.

Effect of proteinase inhibitors on the carrageenin-induced inflammation was studied. The formation of granulation tissue was markedly inhibited by a single injection of epsilon-amino-n-caproic acid n-hexyl ester (EACA hexyl ester, 300 mg/kg) into the carrageenin-airpouch immediately after carrageenin injection, whereas repeated injections of the inhibitor starting at 12 hr, 24 hr and 48 hr after carrageenin injection were less effective, slightly effective and ineffective, respectively. A dose-dependent inhibition of both the formation of granulation tissue and the migration of polymorphonuclear leukocytes (PMNs) into the inflammatory locus was found by a single injection of EACA hexyl ester into the carrageenin-airpouch immediately after carrageenin injection. Similarly, a single injection of L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK, 50 mg/kg) and N-alpha-p-tosyl-L-lysine chloromethyl ketone (TLCK, 30 mg/kg) inhibited both the formation of granulation tissue and the migration of PMNs into the inflammatory locus. These results suggest that serine proteinase inhibitors such as EACA hexyl ester, TPCK and TLCK exert their anti-inflammatory actions by interfering with the initial inflammatory reactions including the migration of PMNs into inflammatory locus after carrageenin injection.

Aminocaproic Acid↗
PubMed1981

Cellular origin of cathepsin B in carrageenin-induced granuloma tissues in rats.

Cathepsin B isolated from carrageenin-induced granuloma tissue was separated into two peaks (one large and one small) on CM-cellulose column chromatography. The cathepsin B activities from the peritoneal macrophages and polymorphonuclear leukocytes were eluted at the positions identical to those of the larger (P-D and the smaller (P-II) peaks, respectively. Similarly, the cathepsin B activities in the P-I and P-II fractions from granuloma tissue corresponded to those from macrophages and leukocytes, respectively, in isoelectric focusing in polyacrylamide gel. Both the cathepsin B activities were completely inhibited by iodoacetamide and leupeptin, but phenylmethanesulfonyl fluoride and o-phenanthroline were ineffective. The molecular weight of the cathepsin B of the cellular origin and granuloma tissue was approximately 24,000 by gel filtration. The pI value of cathepsin B in the P-I and P-II fractions from granuloma tissue was 5.09 and 5.18, respectively. These results strongly suggest that two types of cathepsin B in granuloma tissue may be different in cellular origin and may be isozymes.

Animals↗
PubMed1980

Antagonism of KW-5338 (domperidone) against emesis and depression of intestinal motility induced by L-DOPA.

KW-5338 (domperidone), a new dopamine antagonist, is considered to be an agent to cross the blood-brain barrier with difficulty. The antagonistic activities of KW-5338 against L-DOPA were investigated, KW-5338 showed a strong anti-emetic action against L-DOPA induced emesis in beagle dogs (ED50=0.056 mg/kg (p.o.)) and restored the L-DOPA induced depression of intestinal motility to some extent, while it did not antagonize anti-tremorine activities of L-DOPA and trihexyphenidyl in mice. These results suggest that KW-5338 prevents side effects of L-DOPA such as nausea, vomiting and constipation, without reduction in therapeutic effects of L-DOPA in Parkinson's disease.

Animals↗
PubMed1980

Effects of KW-5338 (domperidone) on gastric motility.

The effects of KW-5338 (domperidone) on gastric motility were studied by the balloon method in pentobarbital anesthetized mongrel dogs. KW-5338 was found to enhance the antrum motility. Its enhancement pattern showed the following characteristics: (1) The tonus was not affected, (2) the contraction pressure increased, (3) the frequency of contraction decreased slightly, and (4) the enhancement was long lasting. Metoclopramide showed strong but short enhancement of antrum motility. KW-5338 augmented also the gastric body motility, although the enhancement pattern was different from that in the antrum: (1) The action did not last so long, and (2) an increase in tonus was observed. The augmentation of the gastric motility by KW-5338 was observed even after vagotomy and splanchnicotomy, but it was weaker and shorter than in the intact state. THe KW-5338 induced augmentation was diminished by tetrodotoxin treatment. The gastric relaxation response to dopamine was blocked by KW-5338. These results show that KW-5338 activates the gastric motility not only by central mechanism but also by stimulation to intramural neurons. The dopamine blocking activity of KW-5338 might play some role in the enhancement of gastric motility.

Animals↗