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Biomedical subjects

T Satake

Publications and source records attributed to T Satake.

At least 109 records · Page 6Linked to original sources
PubMed1988

Neutrophil-derived epoxide, 9,10-epoxy-12-octadecenoate, induces pulmonary edema.

We have observed that neutrophils biosynthesize linoleate epoxide, 9,10-epoxy-12-octadecenoate, and have named it leukotoxin because of its cytotoxic effect. In this experiment, the effect of leukotoxin on the lung was investigated. Acute effect of leukotoxin: Using Wistar rats, leukotoxin (100 mumol/kg) was injected intravenously for the leukotoxin group, and linoleate (100 mumol/kg) for the linoleate group. Physiological saline was injected as the control. Ten min after injection, rats were divided into 3 groups: (1) lungs were isolated, and lung wet weight, and dry weight were measured; (2) lung lavages were performed, and albumin concentration and activity of angiotensin converting enzyme (ACE) were measured; (3) morphological changes were studied by light and electron microscope. After administration of leukotoxin, lung wet weight/body weight ratios and dry weight/wet weight ratios were increased. Albumin concentration and ACE activity in lung lavages were also increased. Pulmonary edema was also confirmed by light microscopic findings. Alveolar epithelial cell damage and endothelium damage were also observed. Linoleate had no significant effect on these biochemical parameters and morphological findings. Subacute effect of leukotoxin: Twelve hr after administration of leukotoxin (50 mumol/kg) or linoleate (50 mumol/kg), the same studies were performed as in the acute experiments. Immediately after administration of leukotoxin, no significant effect was observed. However, 12 hr later similar changes were observed as in the acute experiments. Linoleate did not show any significant effect 12 hr after injection. These results indicate that leukotoxin biosynthesized by neutrophils might be closely related to the genesis of inflammatory edema.

Animals↗
PubMed1988

A calmodulin antagonist (W-7) and a protein kinase C inhibitor (H-7) have no effect on atrial natriuretic peptide release induced by atrial stretch.

The role of intracellular signals in the regulation of atrial natriuretic peptide (ANP) release was investigated using isolated rat left atria. Dibutyryl cyclic AMP and dibutyryl cyclic GMP had no effect on ANP release. Arginine vasopressin and phenylephrine, both of which activate the polyphosphoinositide system and consequently both the diacylglycerol-protein kinase C system and the Ca2+-Ca2+ receptor system, stimulated ANP release dose-dependently. The ANP release stimulated by phenylephrine was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), a calmodulin antagonist, and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7), a protein kinase C inhibitor. Atrial stretch stimulated ANP release, but the release was not inhibited by W-7 or H-7. These results suggest that the mechanism responsible for phenylephrine-induced ANP release differs from that for stretch-induced ANP release.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1988

The effects of lipoxygenase inhibitor and peptidoleukotriene antagonist on myocardial injury in a canine coronary occlusion-reperfusion model.

UNLABELLED: We studied effects of lipoxygenase inhibitor (AA-861) and peptidoleukotriene antagonist (ONO-1078) on infarct size, polymorphonuclear leukocyte (PMNs) infiltration, gross myocardial hemorrhage and ventricular arrhythmias in canine coronary occlusion (2 hr)-reperfusion (5 hr) model. Infarct size (IS) and risk area (RA) were determined by dual staining technique. Thirty minutes before coronary occlusion dogs were randomly assigned to one of the following three groups: lipoxygenase inhibitor group (n = 11) receiving AA-861 3 mg/kg i.v., peptidoleukotriene antagonist group (n = 11) receiving continuous intravenous infusion of ONO-1078 1 micrograms/kg/min and vehicle control group (n = 15). Both AA-861 and ONO-1078 reduced infarct size [AA-861: 21.8 +/- 1.3% of RA (mean +/- SEM), ONO-1078: 22.5 +/- 4.4% vs CONTROL: 54.0 +/- 6.4%, p less than 0.01 and p less than 0.01, respectively] and area of gross myocardial hemorrhage (AA-861: 5.1 +/- 2.4% of IS, ONO-1078: 5.2 +/- 2.5% vs CONTROL: 22.3 +/- 3.9%, p less than 0.01 and p less than 0.01, respectively). Both drugs also decreased frequency of ventricular premature contractions both during occlusion and during reperfusion, and that of ventricular tachycardia during reperfusion. AA-861 inhibited PMNs recruitment into infarcted area. However, ONO-1078 had no significant influence on degree of PMNs infiltration. These results suggest that lipoxygenase products, especially peptidoleukotrienes (LTC4, D4 and E4) may play important roles in the pathogenesis of myocardial ischemic and reperfusion injuries.

Animals↗
PubMed1988

The dissociation constant of verapamil estimated from its effect on Ca concentration-tension curves in guinea-pig tracheal muscle.

Concentration-tension curves for calcium ions (Ca2+) were studied in indomethacin-treated guinea-pig tracheal muscle in the presence of different concentrations of carbachol in media containing 5.9 mM K+ or 40 mM K+. The effect of verapamil was investigated taking into account the steepness (the Hill coefficient) of the Ca2+ curve. When carbachol (1 microM) was added to 40 mM K+ solution, the Ca2+ concentration to produce half maximum tension (EC50) was reduced from 0.2 mM to 0.08 mM and the Hill coefficient was increased from 1.4 to 2.0, respectively. In the presence of carbachol (1 microM), the Ca2+ concentration-tension curve was not much influenced by increasing the K+ concentration from 5.9 to 40 mM K+. Verapamil (0.5 microM) shifted the Ca2+ concentration-tension curve to the right in a parallel manner under all experimental conditions, the shift being greater with curves having a smaller Hill coefficient. The dissociation constant of verapamil was not altered by carbachol when estimated from the shift of the curve if the Hill coefficient is taken into consideration. It is concluded that the relatively low susceptibility of carbachol-induced contractions to verapamil in the presence of 40 mM K+, compared with these produced by K+ alone, is not due to a decreased verapamil affinity but to improved Ca(2+)-response coupling.

Animals↗
PubMed1988

Cardiovascular effects of leukotoxin (9, 10-epoxy-12-octadecenoate) and free fatty acids in dogs.

Leukotoxin (9,10-epoxy-12-octadecenoate) biosynthesised from linoleate by neutrophils is highly toxic to cellular function. Its cardiovascular effects were studied in dogs together with the effects of various fatty acids. Aortic flow, left ventricular peak dP.dt-1, and aortic pressure were measured in 60 anaesthetised dogs, which were divided into 10 groups of six animals each--namely, control group (10 ml of physiological saline), three leukotoxin groups (5, 10, and 50 mg.kg-1), two linoleic acid groups (10 and 50 mg.kg-1), two oleic acid groups (10 and 50 mg.kg-1), and two stearic acid groups (10 and 50 mg.kg-1). Leukotoxin injected intravenously depressed cardiac function in a dose dependent manner. Administration of leukotoxin 5 mg.kg-1 showed no significant cardiotoxic effect. However, 10 mg.kg-1 of leukotoxin significantly decreased aortic flow from 0.74(0.04) to 0.40(0.07) litre.min-1 (mean(SEM], left ventricular peak dP.dt-1 from 2040(205) to 1140(217) mmHg.s-1, and aortic pressure from 106(7.1)/67(6.3) to 75(9.2)/48(6.5) mmHg 5 min after injection. Dogs given leukotoxin 50 mg.kg-1 showed more pronounced cardiodepressive effects; aortic flow was decreased to 0.19(0.06), left ventricular dP.dt-1 to 560(134), and aortic pressure to 72(15.1)/41(10.6) 5 min after injection. All dogs in this group were dead within 45 min. Administration of 10 mg.kg-1 of linoleic acid, oleic acid, or stearic acid caused no significant haemodynamic changes. Administration of linoleic acid 50 mg.kg-1 had cardiotoxic effects, but the effect was less than that of leukotoxin. Since leukotoxin appears to be a potent cardiodepressive agent it may be an important factor in the development of heart failure observed in patients with severe burns.

Animals↗
PubMed1988

Prostaglandin I2 analogue and propranolol prevent ischaemia induced mitochondrial dysfunction through the stabilisation of lysosomal membranes.

Leakage of lysosomal enzymes is associated with irreversible cellular damage. To determine the effect of prostaglandin I2 analogue and propranolol on the ischaemic myocardium in relation to changes in lysosomal integrity 26 anaesthetised mongrel dogs were divided into three treatment groups and subjected to 2 h coronary occlusion. In the control group (n = 12) physiological saline was infused throughout the experiment. In the prostaglandin I2 analogue group (n = 7) the prostaglandin I2 analogue, OP-41483-alpha-CD;5(E)-6-Deoxa-6,9 alpha-methylene-15-cyclopentyl-16,17,18,19,20-pentanor-PGI2. alpha-cyclodextrin clathrate (5 ng.kg-1.min-1) was infused from 25 min before occlusion until the end of the experiment. In the propranolol group (n = 7) propranolol (0.3 mg.kg-1) was injected for 10 min 25 min before occlusion. Two hours after occlusion mitochondria were prepared from both ischaemic and non-ischaemic areas in each group and their function measured polarographically with succinate as substrate. Fractionation of myocardial tissue from both non-ischaemic and ischaemic areas was performed and the activities of lysosomal enzymes (N-acetyl-beta-glucosaminidase; beta-glucuronidase) were measured. In the control group, mitochondrial function in the ischaemic area was reduced compared with that from the non-ischaemic area. The activities of both lysosomal enzymes were increased significantly in the supernatant fraction obtained from the ischaemic area compared with those for the supernatant from the non-ischaemic area. The administration of prostaglandin I2 analogue or propranolol not only prevented the leakage of lysosomal enzymes but also maintained mitochondrial function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Sustained diacylglycerol formation in norepinephrine-stimulated rat heart is associated with alpha 1-adrenergic receptor.

We measured the amount of 1,2-diacylglycerol (DG) in rat hearts using thin-layer chromatography and a flame ionization detection technique, since 1,2-DG is thought to play a central role in the metabolism of phosphoinositide hydrolysis. In response to exogenous norepinephrine, a significant increase in 1,2-DG content in the myocardium was observed over 10-60 min, achieving an 80% increase over unstimulated controls at 60 min. On the other hand, the cholesterol content and six species of phospholipids were not significantly affected. In order to elucidate the mechanism of 1,2-DG accumulation elicited by norepinephrine, alpha- and beta-adrenergic antagonists were given. Pretreatment with phentolamine and prazosin, but not propranolol, inhibited the norepinephrine-induced 1,2-DG accumulation. Yohimbine appeared to have a partially inhibitory effect. These results suggest that myocardial norepinephrine-related 1,2-DG formation, which is likely to activate protein kinase C, is associated with alpha-adrenergic receptors, especially alpha 1-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1988

Cytologic features of ascites in malignant fibrous histiocytoma of the colon.

The cytologic features of ascitic fluid in a case of malignant fibrous histiocytoma (MFH) of the colon are described. At autopsy, two solid tumor masses were found around the ascending and transverse colon, accompanied by about 3,000 ml of ascites. Tumor cells had infiltrated diffusely into the outer layers of almost all of the gastrointestinal wall, simulating peritonitis carcinomatosa. Cytologic examination of the ascites revealed various kinds of tumor cells; short spindle-like cells, multinucleated giant cells, and round cells with an invaginated nuclear margin, forming small clusters. These cytologic findings were considered to be very useful in the diagnosis of MFH, especially in cytologic examinations of ascites.

Ascitic Fluid↗
PubMed1988

Effect of dietary salt and cholesterol loading on vascular adrenergic receptors.

To evaluate the effects of salt and cholesterol intake on vascular responses to catecholamines, alpha 1- and beta-adrenergic receptor densities were determined in control, cholesterol-loaded, salt-loaded with desoxycorticosterone acetate (DOCA) and furosemide-loaded male rabbits, using [3H]-prazosin and (-)-[125I]-cyanopindolol as ligands, respectively. In the aortic membrane, the density of alpha 1-adrenergic receptors (Bmax = 120 +/- 14 fmol/mg protein, Kd = 0.48 +/- 0.05 nM) was higher than that of beta-adrenergic receptors (Bmax = 10.5 +/- 1.7 fmol/mg protein, Kd = 47.1 +/- 8.6 pM). Salt loading and depletion did not alter the density or affinity of either the alpha 1- or beta-adrenergic receptors. By contrast, cholesterol loading significantly decreased alpha 1-adrenergic receptor affinity to a Kd value of 0.81 +/- 0.11 nM from the control level of 0.48 +/- 0.05 and increased the beta-adrenergic receptor density to a Bmax of 18.7 +/- 1.9 fmol/mg protein from the control level of 10.5 +/- 1.7. These results showed that the density of alpha 1-adrenergic receptors was higher than that of beta-adrenergic receptors in the rabbit aortic membrane preparation, and suggested that the sensitivity of aortic membrane to catecholamines was changed by cholesterol loading.

Animals↗
PubMed1988

Mechanism responsible for alterations in numbers of autonomic nerve receptors in experimental asthma.

This study was designed to elucidate the mechanism responsible for alterations in the numbers of autonomic nerve receptors in experimental asthma. In the in vivo experiment, guinea pigs sensitized by exposure to aerosol of 2% ovalbumin for 7-8 min for 10 successive days were used as the experimental asthma group. The control group was exposed to saline. Beta-, alpha-1-adrenergic and muscarinic acetylcholine receptors in lung membranes were studied by direct binding techniques using l-3H-dihydroalprenolol, 3H-bunazosin and l-3H-quinuclidinyl benzilate, respectively. The experimental asthma group showed a 33% decrease in the number of beta-adrenergic receptors, a 37% increase in the number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors compared with the control group. The endogenous phospholipase activity was determined by high-performance liquid chromatography using tridecanoyl phosphatidylcholine as a substrate. The phospholipase activity in lung membranes in the experimental asthma group was elevated by 50% compared with that in the control group. Lung membrane phospholipid composition was analyzed by thin-layer chromatography with a flame ionization detector. In the experimental asthma group, the amounts of phosphatidylcholine and phosphatidylethanolamine decreased significantly compared with those in the control group. In the in vitro experiment after pretreatment of lung membranes with phospholipase A2, a decreased number of beta-adrenergic receptors, an increased number of alpha-1-adrenergic receptors and no change in the number of muscarinic acetylcholine receptors were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Concerning the assays for autonomic nerve receptors. Effects of incubation temperature and time on alterations in the number of receptors.

Alterations in autonomic nerve receptors play an important role in various pathological conditions, including bronchial asthma. Nevertheless, receptor assay conditions such as incubation temperature and incubation time are not consistent among various investigators. This study was designed to clarify the effects of incubation temperature and time on alterations in the number of autonomic nerve receptors. Guinea pig lung membranes were divided into five groups which were incubated under different incubation temperatures and over different incubation times. After incubation, the following experiments were performed. Beta-, alpha-1-adrenergic, and muscarinic acetylcholine receptor assays were performed by direct binding technique using L-3H-dihydroalprenolol, 3H-bunazosin, and L-3H-quinuclidinyl benzilate, respectively. Elevation of incubation temperature and prolongation of incubation time caused a significant decrease in the number of beta-adrenergic receptors and an increase in the number of alpha-1-adrenergic receptors. The number of muscarinic acetylcholine receptors did not change significantly in spite of changes in incubation temperature and time. Adenylate cyclase activity was measured by following the synthesis of cyclic adenosine monophosphate from nonradioactive adenosine triphosphate. Isoproterenol-stimulated adenylate cyclase activity decreased significantly in correspondence with the elevation of incubation temperature and prolongation of the incubation time. Contents of free fatty acids in lung membranes were measured by high-performance liquid chromatography. Free fatty acid contents increased significantly in accordance with elevation of incubation temperature and prolongation of incubation time which reflected on the degradation of membrane phospholipids.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases↗
PubMed1988

Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome.

Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS.

Animals↗
PubMed1988

Structure-activity relationship in N3-alkyl-xanthine derivatives.

Structure-activity studies were carried out to compare the relaxant effects of various xanthine derivatives synthesized by substitution of the alkyl groups of the N3 position in the xanthine molecule. We evaluated the relaxant effects and the inhibitory activities on c-AMP phosphodiesterase (PDE) in tracheal smooth muscle isolated from guinea pigs. A comparative study on their pharmacokinetic characteristics was also carried out in rabbits. Dose-dependent relaxant effects were observed, and the relaxant effect of propylxanthine was nearly equal to the effects of butyl- and isobutylxanthines. Based on the estimation of the Ki values for PDE inhibition, it was found that butylxanthine is a potent inhibitor of PDE. There was good correlation between the alkyl chain length and the Ki value of these derivatives. The results showed that the alkyl chain length plays an important role in the inhibition of PDE. There were no significant differences in the volume of distribution, although the half-life showed significant differences. It is likely that the half-lives of these derivatives are affected by their chain lengths. The present study indicated that butylxanthine may be a new candidate as a bronchodilator. However, clinical studies have to be carried out to compare its efficacy and adverse effects with those of existing bronchodilators such as theophylline.

Animals↗
PubMed1988

Alteration of 1,2-diacylglycerol content in myocardium from diabetic rats.

1,2-Diacylglycerol has been proposed to be a secondary messenger; therefore, in this study we evaluated the amount of 1,2-diacylglycerol in heart tissue from streptozocin-induced diabetic rats and examined the effect of insulin treatment on 1,2-diacylglycerol content. Diabetic rats had lower body and ventricular weights and higher ratios of ventricular to body weight, all of which shifted toward normal values after 4 wk of untreated diabetes followed by 4 wk of insulin treatment. The contents of major phospholipids were significantly depressed in the diabetic rat hearts. In contrast, the triglyceride and cholesterol contents in the myocardium were increased by streptozocin injection and completely normalized by insulin treatment, and glucose levels returned to normal. The 1,2-diacylglycerol content in the myocardium was also significantly elevated in the diabetic rats compared with age-matched controls. Moreover, the 1,2-diacylglycerol content was significantly higher in rats with 4 wk of diabetes than in those with 8 wk of diabetes. Insulin treatment in the diabetic rats, however, did not produce any decrease in 1,2-diacylglycerol content. The results of this study suggest that the development of cardiomyopathy induced by streptozocin injection is associated with a high 1,2-diacylglycerol level, which may result in the activation of protein kinase C. Insulin is one of the agonists that generates 1,2-diacylglycerol in myocytes; however, the relationship between the sustained 1,2-diacylglycerol level and the normalization of diabetes by insulin administration is unclear.

Animals↗
PubMed1988

Comparative studies on interaction between theophylline and quinolones.

A comparative study of the pharmacokinetic and metabolic interactions between theophylline and a newly developed quinolone, T-3262, was carried out under steady-state conditions in seven healthy male volunteers, using enoxacin as the reference drug. A sustained-release theophylline formulation (200 mg twice daily) was given as monotherapy and coadministered with T-3262 (150 mg three times a day) or enoxacin (200 mg three times a day). The total and free concentrations of theophylline in the plasma and the excreted concentration of theophylline and its metabolites in the urine were measured by a high-performance liquid chromatography method. The mean steady-state plasma theophylline concentration significantly increased by approximately 1.5-fold and threefold after coadministration of T-3262 and enoxacin, respectively. In both cases, a significant decrease in the total body clearance was found for T-3262 (34%) and enoxacin (63%), but the plasma protein binding of theophylline remained unchanged. There was a significant increase in urinary theophylline and a decrease in urinary 3-methylxanthine after coadministration of T-3262 or enoxacin. The degree of change in the steady-state plasma theophylline concentration as a result of coadministration of T-3262 was small compared to that of enoxacin. A decrease in the total body clearance in the case of coadministration of a quinolone probably resulted from inhibition of the 1-demethylation metabolic pathway.

Adult↗
PubMed1988

Migration of neutrophils in experimental asthma.

Ovalbumin (OA) aerosol exposure caused an increase in phospholipase (PLase) activity in guinea pig lung membranes and in leukotriene B4 (LTB4) in lung lavages with subsequent neutrophil influx into lung lavages. These results suggest that activation of PLase after exposure to OA aerosol triggers an increase in LTB4 synthesis resulting in neutrophil influx into the airways.

Animals↗