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S Aonuma

Publications and source records attributed to S Aonuma.

At least 55 records · Page 3Linked to original sources

Studies on pharmacological activation of human serum IgG by chemical modification and active subfragments. II. Inhibitory effects of carboxamide-methylated L chain from human serum IgG on various ulcer models and its inhibition mechanism.

In view of the strong inhibitory effects of the carboxamide-methylated L chain (Fr. I-L) from human IgG on gastric ulceration and juice secretion, we carried out various experiments to clarify the mechanism of its action and obtained the following results. Fr. I-L inhibited the gastric ulceration induced by phenylbutazone or aspirin in rats, but no appreciable effect was observed on stress or acetic acid ulceration. The distribution of 14C-labelled Fr. I-L increased particularly in the stomach mucous membrane of rats after the intravenous or intraperitoneal administration. The hexosamine content in the gastric mucous membrane, reduced by the treatment with phenylbutazone, aspirin or pylorus-ligation, was recovered by the administration of Fr. I-L to an intact level. The high total of hexosamine levels found in the gastric juice after aspirin treatment or pylorus-ligation were decreased by the injection of Fr. I-L or cimetidine. The histochemical observation revealed that the concomitant administration of Fr. I-L with phenylbutazone or aspirin prevented the abolishment of Hematoxylin-Eosin, Periodic Acid Schiff and Alcian Blue staining polysaccharides from the stomach epithelial cells.

Animals↗

Inhibitory effects of unsaturated fatty acids of trans-2-C10:1 to trans-2-C16:1 several C18:n and C20:n on gastric secretion and experimental ulceration in rats.

Among various unsaturated fatty acids which were examined in this experiment, trans-2-tridecenoic acid was found to be a potent inhibitor on gastric secretion in rats (i.p. or i.d.). Therefore, the effects of trans-2-tridecenoic acid on several experimental ulcerations in rats were examined. At the dose of 10 mg/kg, trans-2-tridecenoic acid significantly decreased the ulcer index in pylorus-ligated rats; aspirin-, phenylbutazone-, histamine- and stress-induced ulcerations were also significantly inhibited at the dose of 25 mg/kg. Finally, effects of trans-2-tridecenoic acid on hexosamine and sialic acid contents in the gastric mucous were examined. In intact or phenylbutazone-induced ulcerated rats, trans-2-tridecenoic acid increased the sialic acid levels in the gastric mucous at the dose of 25 mg/kg. The decreased hexosamine content in the gastric mucous by phenylbutazone treatment was recovered by the administration of trans-2-tridecenoic acid.

Animals↗

Studies on aspirin derivatives with very little side effect. IV. Inhibitory effect of aspirin-isopropylantipyrine (AIA) on several experimental thromboses.

The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with potent platelet anti-aggregant activity, on several experimental thromboses was evaluated and compared with that of aspirin. AIA (50 mg/kg, s.c.) as well as aspirin (50 mg/kg, s.c.) significantly inhibited thrombus formation in extracorporeal shunt model of rats. AIA (50 mg/kg, s.c.) significantly shortened the duration of apnea and respiratory distress induced by a rapid injection of adenosine 5'-diphosphate in rats, while aspirin (50 mg/kg, s.c.) did not. Inhibitory effect of AIA (50 mg/kg, s.c.) on arachidonic acid-induced mortality in mice was less than that of aspirin (50 mg/kg, s.c.). AIA and aspirin (10 mg/kg/d X 10, s.c.) had no effect on laurate-induced arterial occlusive disease in rats. AIA (200 microM) showed weak and reversible inhibition of prostaglandin I2 generation in isolated rat aorta strip, while aspirin (200 microM) showed irreversible inhibition. AIA (50 and 200 microM inhibited Ca2+-, K+- or norepinephrine-induced contraction on isolated rat aorta strip. AIA (200 microM) had no effect on malondialdehyde formation, cyclic AMP level and adenylate cyclase activity in rat platelets. AIA (100 microM) inhibited arachidonic acid-induced contraction on rat fundus strip by about 50%, while aspirin (100 microM) did not. These results strongly suggest that anti-thrombotic activity of AIA was originated at least from its anti-aggregant effect on platelets, differing from aspirin.

Adenosine Diphosphate↗

Inhibitory effects of alkylated Bence-Jones protein, k-type light chain, from urine of a patient with macroglobulinemia on gastric juice secretion and ulceration in rats.

Bence-Jones protein (BJP) was isolate from the urine of a patient with macroglobulinemia by salting out the ammonium sulfate, followed by chromatography on DEAE-cellulose column and gel filtration. This native BJP was identified as k-type light chain by immunoelectrophoresis and the native light chain showed almost no activity of inhibiting the gastric ulceration in pylorus-ligated rats. In contrast, reduction of the disulfide bond by 2-mercaptoethanol and alkylation of the thiol by iodoacetate in this native light chain resulted in significant inhibition of the gastric ulceration. The alkylated light chain also showed a significant inhibition of gastric juice secretion in pylorus-ligated rats.

Alkylation↗

Studies on aspirin derivatives with very little side effects. III. Absorption, distribution, excretion and metabolism of tritium-labeled aspirin-isopropylantipyrine (AIA) in rats.

The absorption, distribution, excretion, metabolism and protein binding of orally administered tritium-labeled aspirin-isopropylantipyrine (AIA) were demonstrated in rats. 3H-AIA having 0.1 micro Ci/mg of specific activity and 93.2% of radiochemical purity was prepared by the Wilzbach's method. When 3H-AIA was administered orally to rats, about 20% of the given 3H was absorbed from gastro-intestinal tracts in 30 min and about 50% in 3 h, 72% of the dose was excreted in the feces and urine during 5 d, and 10% was excreted in the bile in 24 h. The highest accumulation of 3H in most organs was found in one to three hr after oral administration and 3H was concentrated in the liver. THe major metabolites excreted in urine within 24 h after administration were salicylic acid-isopropylantipyrine (SIA) sulfate (57.7%) and SIA glucuronide (30.5%). The amount of free SIA excreted in urine was 1.2%. The carboxylamide bond of AIA was never cleaved in vivo to give salicylic acid and 3-aminomethylisopropylantipyrine. About 58% of 3H in blood 1 h after the administration was found with serum protein.

Animals↗

Increase of anti-ulcerogenic activity by reduction and alkylation of disulfide bonds of a globulin fraction from bovine serum.

Bovine serum was subjected to ammonium sulfate fractionation, and subsequently chromatographed on DEAE-cellulose column to obtain a globulin protein having a weak anti-ulcerogenic activity, Fr.II-A. Agar immunoelectrophoresis and immunodiffusion using rabbit antiserum against bovine IgG revealed that Fr.II-A from bovine serum shared antigenic determinant with bovine IgG. Furthermore, Fr.II-A showed a single band on polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. By reducing and alkylating the disulfide bonds by 2-mercaptoethanol and iodoacetic acid, Fr.II-A was separated into two subfragments in the same manner as in the case of immunoglobulin to produce Fr.L (molecular weight; 24000) and Fr.H (molecular weight; 50000). Fr.L showed anti-ulcerogenic activity up to about ten times greater than that of original Fr.II-A, but in the case of Fr.H, the activity increased approximately several times. Fr.L showed significant activity in preventing ulcer formation and gastric juice secretion in pylorus-ligated rats, and was also effective in reducing index of the phenylbutazone-induced ulcer.

Alkylation↗

Studies of heart. XXI. Amino acid sequence of antiarrhythmic peptide (AAP) isolated from atria.

The amino acid sequence of an atrial peptide, AAP, that improves the rhythmicity of cultured myocardial cell clusters, was established as Gly-Pro-4Hyp-Gly-Ala-Gly. This was accomplished by the sequence analyses with dansyl-Edman degradation and carboxypeptidase Y digestion on the isolated native peptide. The hexapeptide and its several constituent peptides were synthesized by using dicyclohexylcarbodiimide as a condensing agent. Synthetic AAP was found to be chemically and biologically indistinguishable from the native one. In a structure-activity correlation of AAP, it was recognized that the whole molecule of this peptide was essential for its antiarrhythmic activity and its promoting effect on spreading phenomenon of myocardial cells in culture.

Amino Acid Sequence↗

Capacitation inducing activity of serum albumin in fertilization of mouse ova in vitro.

The role of serum albumin in in vitro fertilization of mouse ova was studied relating to the fertilization inhibitory activity of Zn2+. The time required for mouse sperm capacitation was dependent on the concentration of serum albumin which was added to the medium. The majority of Zn2+ added to the medium was shown to be bound to serum albumin (95% out of 200 microM) by means of equilibrium dialysis. Furthermore, it was suggested that the serum albumin was necessary for the initiation of the sperm capacitation process by the periodic observation of sperm penetration through zona pellucida.

Animals↗

Studies on aspirin derivatives with very little side effect. II. Potent platelet anti-aggregant activity and no mutagenicity of aspirin-isopropylantipyrine (AIA).

The effect of a new aspirin derivative, aspirin-isopropylantipyrine (AIA), with very little gastric ulcerogenic activity and very slight acute toxicity and with analgesic, antipyretic anti-inflammatory, and platelet aggregation inhibitory activities was evaluated in vitro and ex vivo and compared with those of aspirin and isopropylantipyrine (IA). In vitro, AIA, aspirin and IA (50-200 microM) caused concentration-dependent inhibition of collagen-induced aggregation in rabbit platelets although AIA was several-fold more active than the others Arachidonic acid-induced aggregation was inhibited by all three agents (200 microM) in the following magnitude; IA greater than aspirin greater than AIA. Three agents did not influence primary ADP-induced aggregation. The in vitro effects on the release-inducing aggregants were confirmed by ex vivo experiments in rats. These demonstrated that AIA and aspirin (50 mg/kg) exhibited almost identical inhibitory potencies in the extent and the rate of collagen-induced aggregation 4 h after subcutaneous injection. AIA was still effective 24 h after administration as well as aspirin. IA was less effective, differing from the results in vitro. AIA had no effect on plasmin activity and blood flow through the common carotid artery. AIA (1 mM) maintained spreading and beating of myocardial cells in a serum-free culture. As special toxicity trials on AIA mutagenecity tests were made by the Rec-assay with Bacillus subtilis, by the plate culture with Escherichia coli, and by the Ames system with Salmonella typhimurium. AIA was found to have no mutagenic effect under any of those methods and to have no effect on the mutagenic action of 3, 4-benzopyrene under the liver microsome test using the Ames system.

Animals↗

Effects of branched chain fatty acids of iso-C12:0 to iso-C16:0 on gastric secretion and experimental ulceration in rats.

We examined the inhibitory activities of branched-chain fatty acids of iso-C12:0 to iso-C16:0 on gastric secretion in rats. Consequently, iso-C13:0 and iso-C15:0 were found to have strong inhibitory activities on gastric secretion in rats. In the case of intraduodenal administration, iso-C15:0 also showed a significant inhibition of gastric juice secretion. Therefore, the effects of iso-C13:0 and iso-C15:0 on ulceration in pylorus-ligated rats and aspirin-induced ulcer were examined. At the doses of 10 and 25 mg/kg, iso-C13:0 and iso-C15:0 significantly decreased the ulcer index in pylorus-ligated rats, and aspirin-induced ulcer was also significantly inhibited at the doses of 25 and 50 mg/kg. Finally, effect of iso-C15:0 on pepsin, Mg++-ATPase and carbonic anhydrase, which are considered to play an important role in the mechanism of gastric juice secretion, was examined in vitro, centering around iso-C15:0 which showed a marked effect in gastric juice secretion inhibitory and anti-ulcerogenic activities. Iso-C15:0 showed inhibitory activity on pepsin and Mg++-ATPase, but entirely no activity on inhibiting carbonic anhydrase.

Adenosine Triphosphatases↗

Zinc effects on mouse spermatozoa and in-vitro fertilization.

The fertilizing ability of mouse epididymal and capacitated spermatozoa was tested by mixing with normal or zona-free ova. In the presence of Zn2+, the epididymal spermatozoa failed not only to penetrate the zona pellucida but also to fuse with zone-free ova, while no effect was observed on capacitated spermatozoa. Zn2+ also inhibited fertilization with spermatozoa preincubated in Ca2+-free medium. However, shortly after the addition of Ca2+ to the preincubated spermatozoa, Zn2+ lost its fertilization inhibitory activity.

Animals↗

Effect of normal C10:0-C20:0 fatty acids and their related compounds on gastric secretion and experimental ulceration in rats.

Fatty acids of C10:0, C12:0, C13:0, C14:0 and C16:0 significantly inhibited the amount of gastric juice, total acid output, and total peptic activity, but fatty acids of C17:0-C20:0 entirely failed to show significant inhibitory activity. Only the methyl ester of C14:0 showed significant inhibition of these parameters at the dose of 100 mg/kg, while at the dose of 200 mg/kg, methyl esters of fatty acids of fatty acids of C10:0, C12:0, C14:0, and C16:0 significantly inhibited these three parameters. alpha-Monoglyceride of C14:0 significantly inhibited the amount of gastric juice at the dose of 100 mg/kg, while alpha-monoglycerides of C10:0, C12:0', C13:0, C14:0, and C16:0 significantly inhibited the amount of gastric juice, total acid output, and total peptic activity at the dose of 200 mg/kg. In the case of intraduodenal administration, myristic acid also showed significant inhibition of these parameters at 100 and 200 mg/kg doses. The dose-activity correlation in gastric secretion inhibitory activity was examined with myristic acid and this activity was found to increase with increasing dose of the acid administered. Myristic acid significantly decreased the ulcer index in aspirin-induced ulcer, it was entirely ineffective in preventing histamine-induced ulcer. Finally, inhibitory effect of myristic acid on pepsin and histidine decarboxylase was examined in vitro and it was found that myristic acid inhibited peptic activity, but it had almost no effect of inhibiting the histidine decarboxylase activity.

Animals↗