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Biomedical subjects

S Terao

Publications and source records attributed to S Terao.

At least 73 records · Page 4Linked to original sources
PubMed1989

A novel anti-asthmatic quinone derivative, AA-2414 with a potent antagonistic activity against a variety of spasmogenic prostanoids.

The anti-asthmatic activity of AA-2414 [(+/-)-7-(3,5,6-trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptano ic acid] has been studied in vivo and in vitro. Experimental allergic asthma was inhibited by orally administered AA-2414 in a dose-dependent manner. AA-2414, 0.08-1.25 mg/kg (p.o.), inhibited the bronchconstriction in guinea pigs induced by a prostaglandin endoperoxide analogue (U-46619), leukotriene D4 (LTD4), and platelet activating factor (PAF) with a long duration of action. The compound did not inhibit histamine-induced bronchoconstriction. AA-2414 reduced the induction of pulmonary inflation caused by LTD4 aerosol inhalation. AA-2414 competitively inhibited the contractile response to U-46619 in guinea pig tracheal and parenchymal strips and dog saphenous vein strips with pA2 values of 7.69, 8.29 and 6.79, respectively. Furthermore, the contractile responses of guinea pig tracheal strip to PGD2, 9 alpha, 11 beta-PGF2 and PGF2 alpha were inhibited with pA2 values of 7.20, 7.79 and 5.71, respectively. These results suggest that AA-2414, a quinone derivative, is a novel, potent and orally active antagonist of a variety of spasmogenic prostanoids.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Quinones. 4. Novel eicosanoid antagonists: synthesis and pharmacological evaluation.

A new series of omega-phenyl-omega-quinonylalkanoic acids and related compounds was synthesized. The compounds were tested for their inhibitory effects on U-44069-induced contraction of the rabbit aorta. (+/- )-7-(3,5,6-Trimethyl-1,4-benzoquinon-2-yl)-7-phenylheptanoic acid (4d) (AA-2414) with pA2 value of 8.28 was one of the most potent compounds. Compound 4d inhibited U-46619-induced contraction of the guinea pig lung (pA2 = 8.29) and U-44069-induced aggregation of the guinea pig platelet (IC50 = 3.5 x 10(-7) M). Compound 4d displaced the binding of [3H]U-46619 to guinea pig platelets (IC50 = 7.4 x 10(-9) M). Compound 4d also showed very potent inhibitory effects with an MED of 0.3 mg/kg (po) on U-46619-, LTD4-, PAF-, or IgG1-induced bronchoconstriction in guinea pigs. The enantiomers of 4d were prepared. The R-(+) isomer 8a was active in both in vitro and in vivo tests, but the S-(-) isomer 8b was much less active. We concluded that the antiasthmatic effects of 4d were based mainly on the TXA2 receptor antagonistic action. In addition, compound 4d showed potent inhibitory effects on PGD2-, PGF2 alpha-, and 11-epi-PGF2 alpha-induced contraction of the guinea pig tracheal strips. The diverse inhibitory effects might be expressed in terms of eicosanoid-antagonistic activity.

Animals↗
PubMed1989

[Loss of spinal anterior horn cells in X-linked recessive bulbospinal muscular atrophy--a morphometric study of lower motoneuron loss].

A morphometric analysis was performed to study three-dimensional distribution of the anterior horn cells in the L1 segmens from four cases of X-linked bulbospinal muscular atrophy (X-BSMA) and three age-matched controls. At autopsy, the L4 spinal segment was removed and fixed in 4% paraformaldehyde in PBS at pH 7.4, then embedded in paraffin. Serial sections of 10 microns in thickness from the rostral end of L4 segment were obtained. Every tenth section was stained with Klüver-Barrera method. The anterior spinal horn in this study was designated as the gray matter anterior to the line from the central spinal canal perpendicular to the ventral spinal fissure. The diameter of the remaining neurons with obvious nucleolus in the anterior horn was measured with TGZ-3 particle size analyzer (Zeiss) on the 205 time-magnified picture, and their location was schematically plotted on a montage of the ventral horn. Neuronal loss was more marked in X-BSMA than in amyotrophic lateral sclerosis (ALS) and Shy-Drager syndrome (SDS). In X-BSMA, the loss was most prominent in cells with large-size, and in those located in the lateral and medial vental nuclei (lamina IX after Rexed's classification). Small or intermediate cells located in the area of inner-medial portion of the ventral horn (lamina VII & VIII after Rexed's classification) were also significantly depleted. In some cases, the loss of small neuron was more marked than SDS.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Acquired idiopathic generalized anhidrosis: a distinctive clinical syndrome.

The present study concerns a 28-year-old Japanese man with acquired generalized anhidrosis. The patient's ability to perspire was investigated in an artificial climate room maintained at 40 degrees C and 40% humidity. Although the body temperature rose to 38 degrees C, the patient did not sweat. Neither did sweating occur when the patient was given an intradermal injection of pilocarpine or nicotine. The serum IgE level was elevated. Atrophy and degeneration of the sweat glands, as well as infiltration by lymphocytes and mast cells around the sweat glands, were observed in skin biopsies. Anhidrosis in this patient was suggested to be the result of reduced function of the sweat glands themselves with possible underlying immune-mediated basis.

Adult↗
PubMed1988

Studies on scavengers of active oxygen species. 1. Synthesis and biological activity of 2-O-alkylascorbic acids.

A novel series of 2-O-alkylascorbic acids (5a-u) was synthesized, and their scavenging activities against active oxygen species as well as their suppressive effects on the arrhythmias in rat heart ischemia-reperfusion models were evaluated. Some 2-O-alkylascorbic acids (5e-1) exhibited potent inhibiting activities against lipid peroxidation in rat brain homogenates and in alleviating effects in the ischemia-reperfusion models. Studies on the structure-activity relationship demonstrated that a free 3-enolic hydroxyl group and the longer alkyl chains substituted on the 2-hydroxyl group of ascorbic acid were beneficial for the biological and pharmacological activities. 2-O-Octadecylascorbic acid (5k, CV-3611), one of the most potent and promising compounds, markedly inhibited lipid peroxidation (IC50 = 4.3 X 10(-6) M) and alleviated myocardial lesions induced by ischemia-reperfusion at an oral dose of 1 mg/kg in rats.

Animals↗
PubMed1987

Leukotriene A4 hydrolase in the human lung. Inactivation of the enzyme with leukotriene A4 isomers.

Leukotriene A4 hydrolase from the human lung was purified to apparent homogeneity. The molecular weight (68,000-71,000), the amino acid composition, and the N-terminal amino acid sequence were similar to those of the human neutrophil enzyme but different from those of human erythrocyte enzyme. The lung enzyme was inactivated by its substrate, leukotriene A4. To elucidate the substrate and the inactivator specificity of this enzyme, we synthesized various geometric and positional isomers of leukotriene A4. 14,15-Leukotriene A4, leukotriene A4 methyl ester, and geometric isomers of leukotriene A4 could not serve as substrates, but they inactivated the enzyme. On the other hand, styrene oxide and (5S)-trans-5,6-oxide-8,10,14-cis-12-trans-eicosatetraenoic acid neither served as substrates nor inactivated the enzyme. These results indicate that whereas allylic epoxide structures of arachidonic acids are responsible for inactivation of the enzyme, the free carboxylic acid, 5,6-oxide, and the tetraene structure with the 7,9-trans-11,14-cis configuration are required as a substrate for leukotriene A4 hydrolase.

Arachidonic Acids↗
PubMed1987

[A case of amebic liver abscess rupturing into the stomach].

A forty-eight year-old man complained of upper abdominal pain and diarrhea with mucinous bloody stool. He had not been abroad. Except high fever, anemia, leukocytosis and elevated rate of erythrocyte sedimentation, laboratory findings were not abnormal. Gastrofiberscopy showed the protrusion of gastric mucosa with a hollow on its surface in the angle. Abdominal CT scan and echogram revealed an abscess in the right hepatic lobe and an abscess in the left lobe. Ulceration and small protrusion of the rectal mucosa were found by romanoscopy. Stool examinations could not reveal amebas, but serological test for amebiasis by the Ouchterlony method showed positive. Under the diagnosis of the perforation into the stomach of amebic liver abscess, he was treated with Metronidazole and tetracycline. But, as a diffuse shadow appeared in the right thoracic cavity on the chest x-ray films with bloody sputa, perforation of amebic liver abscess to the right thoracic cavity was suspected. Laparotomy showed the communication of the abscess to gastric lumen. The post operative course was uneventful. We reported a case with the rare complication of amebic liver abscess.

Humans↗
PubMed1986

Spectral studies on structure-activity relationships of thromboxane synthase inhibitors.

Thromboxane A2 synthase is a cytochrome P450-type enzyme and its interaction with imidazole or pyridine-based inhibitors could be studied by absolute and difference spectroscopy with the solubilized as well as the purified enzyme. Nitrogenous bases shift the 418-nm Soret absorption by 4-6 nm to the red and among them the best inhibitors of enzyme activity showed a stoichiometric binding to the enzyme. The structural and energetic prerequisites for such high binding affinities were primarily the liganding of the basic nitrogen to the hemin but also the attachment of a hydrophobic carboxylic side chain to the active site at an about 1 nm distance from the nitrogen. In addition, the side chain seemed to be oriented almost parallel to the plane of the heme. If this geometry was changed, a decrease in affinity was observed and if the ligand binding was sterically hindered, a spectral shift to a five-coordinated complex absorbing at 390 nm occurred. This is best explained by the displacement of an endogenous oxygen ligand, presumably water, from the sixth coordination position of the heme. From these results it can be concluded that the inhibitors mimic the binding of prostaglandin H2 (PGH2) with its carboxylic group at the carboxyl side chain and the endoperoxide oxygen atom at C9 as previously reported. The methyl side chain of PGH2 does not seem to play a role in the formation of the enzyme-substrate complex.

Blood Platelets↗
PubMed1986

CV-4151--a potent, selective thromboxane A2 synthetase inhibitor.

(E)-7-Phenyl-7-(3-pyridyl)-6-heptenoic acid (CV-4151) inhibited horse platelet microsomal thromboxane (TX) A2 synthetase with an IC50 of 2.6 X 10(-8) M, but even at a high concentration of 10(-4) M it had little effect on cyclooxygenase, PGI2 synthetase and 5-lipoxygenase in in vitro enzymatic assays. CV-4151 did not affect PGI2 release from rat and rabbit aortic tissues in in vitro (10(-4) M) and ex vivo (10 and 100 mg/kg, p.o.) experiments, whereas aspirin (10(-4) M or 10 and 100 mg/kg, p.o.) markedly inhibited PGI2 release in these preparations. When given orally to rats and dogs, CV-4151 markedly inhibited blood TXA2 synthetase activity: the ID50 values (mg/kg, 2 hr later) were 0.05 in rats and 0.17 in dogs. The inhibitory effects at an oral dose of 1 mg/kg lasted more than 24 hr in both species; the inhibition was 41% in rats and 32% in dogs 24 hr after the administration. When injected i.v. to rats and dogs, CV-4151 caused inhibitory effects on TXA2 synthetase equipotent to those observed with the oral administration. In both species, CV-4151 given orally increased concentration of serum immunoreactive 6-keto-PGF1 alpha concomitant with a decrease of serum TXB2-8 concentration. CV-4151 was equipotent to OKY-1580 (IC50: 2.3 X 10 M), a well documented TXA2 synthetase inhibitor, in an in vitro TXA2 synthetase assay. However, CV-4151, given orally or i.v. to rats and dogs, was much more potent and longer acting in inhibition of blood TXA2 production than OKY-1580. Dazoxiben was less potent than these compounds in vitro. In rats, serial oral administration of CV-4151 (10 mg/kg) once daily for 14 days produced a constant and marked reduction of serum TXB2 concentration with concomitant increase of serum immunoreactive 6-keto-PGF1 alpha concentration. No rebound phenomenon in inhibition of TXA2 synthetase was observed after the dosing was stopped. These findings indicate that CV-4151 is a potent and long acting selective inhibitor of TXA2 synthetase and may reorient the metabolism of PG endoperoxides to PGI2.

Animals↗
PubMed1986

Role of leukotrienes in rat reversed passive Arthus pleurisy and the effect of AA-861, a 5-lipoxygenase inhibitor.

In studies of the role of leukotrienes in inflammatory reactions, the induction of rat reversed passive Arthus pleurisy (a type III allergic reaction) was employed. Increases of exudate volume, vascular permeability, and migration of inflammatory cells in the pleural cavity were observed. The vascular permeability was enhanced biphasically during 0-30 min (early response) and during 3-6 h (late response) after induction of the pleurisy. The infiltration of inflammatory cells, mainly polymorphonuclear leukocytes, into the cavity increased and reached a maximum 6 h after the pleurisy was induced. Leukotriene B4 (LTB4), 5-monohydroxyeicosatetraenoic acid (5-HETE), and slow-reacting substance of anaphylaxis (SRS-A), consisting of LTC4, LTD4 and LTE4, were detected in the exudate by reversed-phase high-performance liquid chromatography during the early response. The contents of LTC4 reached a maximum 10 min after the challenge, followed by a rapid decrease within 1 h. The rise and decay of LTC4 correlated with the increase in vascular permeability during the early phase. AA-861, a 5-lipoxygenase inhibitor, given intrapleurally inhibited the increase in vascular permeability, cell migration, and generation of leukotrienes during the early phase of the pleurisy. These results indicate that products of the 5-lipoxygenase pathway, such as LTC4 and LTB4, may play an important role as chemical mediators in the inflammatory reaction.

Animals↗
PubMed1986

The antiallergic agent amoxanox suppresses SRS-A generation by inhibiting lipoxygenase.

Amoxanox has potent antiallergic activity because it inhibits the release of chemical mediators such as histamine and leukotrienes. We studied the in vitro effect of amoxanox on arachidonic acid metabolism, including the lipoxygenase and cyclooxygenase pathways. Amoxanox inhibited calcium ionophore A23187-induced formation of 5-HETE, LTB4, SRS-A (LTC4, LTD4 and LTE4), and 12-HETE in rat peritoneal resident monocytes. These results indicate that amoxanox inhibits 5- and 12-lipoxygenases. The compound, however, did not affect the formation of TXB2 or 6-keto-PGF1 alpha in guinea pig lung fragments and PGE2 or PGF2 alpha in bovine seminal vesicles, suggesting that it did not inhibit cyclooxygenase. These results show that the antiallergic action of amoxanox is associated, at least in part, with the reduction of leukotrienes due to the inhibition of lipoxygenases.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗