PubMed Health⌕ Search

Biomedical subjects

T Terawaki

Publications and source records attributed to T Terawaki.

At least 19 recordsLinked to original sources
PubMed1995

[Inhibitory effects of prostaglandin E1.alpha-cyclodextrin (PGE1.CD) on dimethylnitrosamine-induced acute liver damage in rats].

The effects of PGE1.CD on dimethylnitrosamine (DMN)-induced acute liver damage with intravascular coagulation in rats were biochemically and histopathologically investigated. PGE1.CD was administered i.v. from 30 min before to 24 hr after DMN-intoxication (pretreatment) and from 30 min after or from 4 hr after to 24 hr after DMN-intoxication (post-treatment). Pretreatment with PGE1.CD (0.2-2 micrograms/kg/min) dose-dependently suppressed the decrease of platelet counts and the elevation of blood biochemical parameters (PT, HPT, GOT, GPT, LDH, LAP, T-Bil) caused by DMN-intoxication. PGE1.CD (0.5 microgram/kg/min and over) significantly suppressed the DMN-induced histopathological changes (occurrence of hemorrhage and necrosis). Post-treatment with PGE1.CD (2 micrograms/kg/min) also suppressed the liver damage. Furthermore, pretreatment with PGE1.CD (2 micrograms/kg/min) not only suppressed the disruption of hepatocytes, but also prevented the damages of sinusoidal endothelial cells and lysosomal membrane, and it reduced the increase of lipid peroxidation. PGE1.CD (1 microgram/kg/min and over) significantly suppressed the decrease of hepatic tissue blood flow caused by DMN-intoxication. These results demonstrate that PGE1.CD has therapeutically efficacy against DMN-induced acute liver damage in rats; Therefore, it will be clinically useful for the treatment of severe hepatitis such as fulminant hepatitis with intravascular coagulation in the sinusoid.

Acute Disease↗
PubMed1993

Effect of a peptide leukotriene receptor antagonist, ONO-1078, on guinea-pig models of asthma.

Peptide leukotrienes have been suggested to play an important role in bronchial asthma. As antigen-induced bronchoconstrictions, airway hyperreactivity, and pulmonary eosinophil accumulation are characteristics of the pathology of asthma, we investigated the effect of a peptide leukotriene receptor antagonist, ONO-1078, on these responses using guinea-pig models of asthma. Oral administration of ONO-1078 (3 mg/kg) significantly inhibited slow-reacting substance of anaphylaxis-mediated bronchoconstriction induced by i.v. administered ovalbumin. ONO-1078 (30-100 mg/kg), when administered orally both 1 h before and 4 h after ovalbumin challenge, significantly reduced immediate- and late-phase asthmatic responses, with peak responses occurring immediately and 5-11 h after challenge with inhaled ovalbumin. Oral administration of ONO-1078 significantly reduced the airway hyperreactivity (10-30 mg/kg) and the pulmonary eosinophil accumulation (30-100 mg/kg) observed 4 and 24 h after ovalbumin challenge, respectively. These results suggest that ONO-1078 may be of therapeutic use for bronchial asthma.

Acetylcholine↗
PubMed1993

Inhibitory effect of a peptide leukotriene antagonist ONO-1078 on LTD4- and antigen-induced thromboxane B2 production in guinea pig lungs.

The effect of a peptide leukotriene receptor antagonist ONO-1078 on the production of thromboxane (Tx) B2 induced by leukotriene (LT) D4 and antigen challenge was examined in guinea pig lungs. LTD4 (1-1,000 nM) induced a concentration-dependent production of TxB2 in non-sensitized guinea pig lungs and ovalbumin challenge (0.01-100 micrograms/ml) produced TxB2 and peptide leukotrienes in a concentration-dependent manner in ovalbumin-sensitized guinea pig lungs. ONO-1078 inhibited LTD4 (100 nM)-induced TxB2 production with the IC50 value of 0.24 microM. Furthermore, ONO-1078 inhibited antigen (10 micrograms/ml)-induced TxB2 production with the IC50 value of 0.14 microM without effect on the production of peptide leukotrienes. These results suggest that ONO-1078 may prevent the antigen-induced production of TxB2 through the blockade of the activation of receptors by endogenously generated peptide leukotrienes.

Animals↗
PubMed1992

Effect of a peptide leukotriene antagonist, ONO-1078 on antigen-induced airway microvascular leakage in actively sensitized guinea pigs.

We examined the effect of ONO-1078, a peptide leukotriene antagonist, on antigen-induced airway microvascular leakage in ovalbumin-sensitized guinea pigs. When guinea pigs were pretreated with mepyramine, ovalbumin challenge increased vascular permeability to Evans blue dye in trachea, main bronchi and intrapulmonary airways. Oral administration of ONO-1078 significantly reduced microvascular leakage in intrapulmonary airways at doses more than 3 mg/kg, but not in trachea. Moreover, oral administration of ONO-1078 significantly reduced SRS-A mediated microvascular leakage into all airway tissues and was more effective in intrapulmonary airways at 3 mg/kg. Simultaneously, ONO-1078 also inhibited SRS-A mediated bronchoconstriction. On the other hand, azelastine (10 mg/kg, p.o.), an anti-asthma agent, failed to inhibit microvascular leakage into the airways. These results suggest that peptide leukotrienes may be important mediators of airway microvascular leakage, and that the inhibitory effect of ONO-1078 on antigen-induced airway microvascular leakage in addition to the blockade of bronchoconstriction may have therapeutic implications for bronchial asthma.

Analysis of Variance↗
PubMed1992

In vivo pharmacologic profile of ONO-1078: a potent, selective and orally active peptide leukotriene (LT) antagonist.

We investigated the in vivo antagonistic activity of ONO-1078 against peptide leukotrienes (LTs) in guinea pigs. ONO-1078, when administered p.o. (0.3-3 mg/kg), caused a dose-dependent reduction of LTC4-, LTD4- and LTE4-induced bronchoconstriction, LTD4-induced airway microvascular leakage and LTD4-induced increase in cutaneous vascular permeability. When administered intravenously, ONO-1078 (3-30 micrograms/kg) inhibited these responses approximately 200-600 fold more potently than FPL55712. When guinea pigs were treated with indomethacin to examine the antagonism of ONO-1078 on the direct action against peptide LTs, intravenous (3-30 micrograms/kg) and oral (0.3-3 mg/kg) administration of ONO-1078 also inhibited LTC4- and LTD4-induced bronchoconstriction, and its activity was approximately 300-500 fold more potent than that of FPL55712. ONO-1078 (10 mg/kg, i.v.) had no inhibitory effect on bronchoconstrictions induced by histamine, acetylcholine, serotonin, arachidonic acid, LTB4, prostaglandin (PG) F2 alpha, PGD2, 9 alpha, 11 beta-PGF2, a stable thromboxane A2 mimetic agent and platelet activating factor. Furthermore, oral administration of ONO-1078 (1-10 mg/kg) inhibited slow-reacting substance of anaphylaxis mediated bronchoconstriction induced by antigen in a dose-dependent manner. These results indicate that ONO-1078 is an extremely potent, selective and orally active peptide LT antagonist and that oral administration of ONO-1078 antagonizes not only exogenously administered peptide LTs but also endogenous peptide LTs.

Animals↗
PubMed1992

In vitro antagonism of ONO-1078, a newly developed anti-asthma agent, against peptide leukotrienes in isolated guinea pig tissues.

We evaluated the antagonist activity of ONO-1078 against peptide leukotrienes (LTs) by a radioligand binding assay and functional experiments in guinea pigs. In the radioligand binding assay, ONO-1078 inhibited [3H]LTD4 and [3H]LTE4 bindings to lung membranes (Ki = 0.99 and 0.63 nM, respectively) and was 2,000- to 3,000-fold more potent than FPL55712. Antagonism of ONO-1078 against [3H]LTC4 binding (Ki = 5640 nM) was approximately twofold more potent than that of FPL55712. The antagonism of ONO-1078 against [3H]LTD4 binding was competitive. In functional experiments, ONO-1078 showed competitive antagonism against the LTC4- and LTD4-induced contractions of guinea pig trachea and lung parenchymal strips with a pA2 range of 7.70 to 10.71 and was approximately 400- to 3,300-fold more potent than FPL55712. Interestingly, in the presence of an inhibitor of the bioconversion of LTC4 to LTD4, ONO-1078 also antagonized the LTC4-induced contraction of guinea pig trachea (pA2 = 7.78). ONO-1078 significantly reversed the LTD4-induced prolonged contraction without effect on the KCl- and BaCl2-induced contractions of guinea pig trachea. Furthermore, ONO-1078 antagonized the antigen-induced SRS-A mediated contraction of guinea pig trachea. On the other hand, ONO-1078 showed no antagonism against histamine, acetylcholine, 5-hydroxytryptamine, prostaglandin D2 and U-46619. In addition, ONO-1078 showed little or no effect on the activities of cyclooxygenase, 5-lipoxygenase and thromboxane synthetase. These in vitro studies indicate that ONO-1078 is a highly potent, selective and competitive antagonist of peptide leukotrienes that acts with higher affinity at LTD4 and LTE4 receptors than LTC4 receptors.

Animals↗
PubMed1988

Effect of a prostacyclin analog OP-2507 on acute ischemic cerebral edema in cats.

We evaluated the inhibitory activity of a novel prostacyclin analog, OP-2507 (15-cis-(4-n-propylcyclohexyl)-16,17,18,19,20-pentanor-9-deo xy-6,9 alpha- nitriloprostaglandin F1 methyl ester) on the brain edema induced by occlusion of the middle cerebral artery in cats. Middle cerebral artery occlusion for 4h caused a decrease of regional cerebral blood flow. The specific gravity of the cerebral cortex measured 4h after the middle cerebral artery occlusion as an index of cerebral edema showed a significant reduction. Intravenous infusion of OP-2507 at infusion rates of 10 and 50 ng/kg per min was started 30 min before the middle cerebral artery occlusion and was continued for 4.5 h. While OP-2507 did not affect the blood pressure, heart rate and regional cerebral blood flow before and after the middle cerebral artery occlusion, the reduction of the specific gravity of cerebral cortex was significantly prevented by OP-2507 treatment at both doses. Prostacyclin prevented the reduction of the specific gravity only at the higher dose of 50 ng/kg per min. The present results indicate the potential usefulness of OP-2507 in acute ischemic cerebral disorders.

Animals↗
PubMed1986

Effects of sensitization of hemolytic streptococcal M-protein fraction on embryonic heart in the rat.

After sensitization by M-protein fraction (MP) of hemolytic streptococci for two generations, Wistar rats were injected with 9 ml/kg of MP on day 9 of gestation (plug day = day 0). The incidence of malformations was about 12% whether anti-MP antibody was positive or not in the maternal sera. The primary malformations were ventricular septal defect, anophthalmia, and microphthalmia. Light microscopic study revealed no myocarditis nor endocarditis in either the maternal or fetal heart. No antinuclear antibody was detected in the maternal sera by the fluorescent antibody technique. No complete heart block was found in the fetus by electrocardiogram. These results were similar to previous findings using a single injection of MP, and therefore further demonstration that the principal factor in the teratogenesis induced by MP administration in the rat is not an inflammation in the fetal organs caused by an autoimmune mechanism but rather yolk sac dysfunction.

Animals↗
PubMed1986

[Receptive relaxation of the canine stomach].

Receptive relaxation of the stomach by feeding was studied in 5 conscious dogs by means of chronically implanted force transducers on the gastric body and antrum. It was found that only the gastric body but not antrum relaxed by feeding, and magnitude of the relaxation of the gastric body was linearly related to the volume (5, 10 and 20 g/kg) of test meals, given once or in multiple times. Secondly, in the study of pharmacological blockers, it was found that atropine, hexamethonium and phentolamine significantly inhibited relaxation, while naloxone and proglumide significantly suppressed relaxation in 3 dogs. Propranolol and domperidone did not influence on receptive relaxation. It is concluded that receptive relaxation of the stomach is mainly mediated through a cholinergic reflex, however, involvement of neurotransmitters other than acetlycholine is suggested in the regulation of receptive relaxation.

Afferent Pathways↗
PubMed1985

The effects of M-protein fraction of hemolytic streptococci on embryonic heart in the rat.

Wistar rats were administered M-protein fraction (MP) of group A type 12 hemolytic streptococci on day 9 of gestation. When 9 mg/kg of MP was injected, the incidence of malformations was 11.8%, and the incidence of cardiovascular malformations was 7.9%. The main malformations were ventricular septal defect, microphthalmia, and hydrocephaly. Light and electron microscopic studies revealed no myocarditis nor endocarditis in either the maternal or fetal heart. Fluorescent antibody technique demonstrated no immunological cross-reaction between MP and rat heart tissue. The results suggest that MP is slightly teratogenic in the rat.

Abnormalities, Drug-Induced↗
PubMed1984

Circulating immune complexes and granulocytes chemotaxis in Kawasaki disease.

Serum immunoglobulin levels, complement titers, circulating immune complex levels, and chemotaxis of granulocytes were evaluated in 32 patients with Kawasaki disease with or without coronary aneurysm. The group of patients with coronary aneurysm showed relatively higher levels of IgG. Regardless of the presence of coronary aneurysm, the level of IgE in the acute phase was higher than that in the convalescent phase. The level of immune complexes was higher in the group of patients with coronary aneurysm (p less than 0.05). There was a low negative correlation between immune complexes and CH50. The chemotaxis of the patients with coronary aneurysm was significantly impaired (p less than 0.01).

Aneurysm↗
PubMed1983

Association of ectodermal dysplasia, ectrodactyly, and macular dystrophy: the EEM syndrome.

We report five patients with ectodermal dysplasia, ectrodactyly associated with syndactyly or cleft hand or both, and, in addition, macular dystrophy which was presumed to be progressive, in an isolated population on a remote island in Japan. The heredity of this syndrome was thought to be autosomal recessive. Three cases have been reported so far with a combination of the same abnormalities. The parents in these cases were consanguineous.

Adolescent↗
PubMed1982

Circulating immune complexes in rheumatic fever.

We measured the circulating immune complex levels in patients with rheumatic fever using the following three methods: the C1q binding test, the conglutinin binding test and Raji cell radioimmunoassay. Thirty-four samples from 21 patients with rheumatic fever were examined, and circulating immune complexes were detected in 47.6% of the patients by one or more of these methods. Especially by the C1q binding test, the sera obtained in the acute phase were found to contain the circulating immune complexes with higher frequency than those obtained in the post-acute phase. Therefore, the C1q binding test was more likely to be useful in the acute phase of this disease. The present study suggests that the circulating immune complexes are related to the pathogenesis of rheumatic fever.

Adolescent↗