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Biomedical subjects

T Satake

Publications and source records attributed to T Satake.

At least 181 records · Page 10Linked to original sources
PubMed1986

Mechanism of rat lung microsomal dysfunction induced by oxygen breathing in relation to the effect of alpha-tocopherol.

The toxic effect of high oxygen concentrations on the lung was investigated together with the effect of alpha-tocopherol (Juvela). Rats were exposed to 80, 60 or 40% oxygen for 2, 4 or 8 days with or without alpha-tocopherol treatment. The composition of fatty acids in microsomal phospholipids was determined by high-performance liquid chromatography. Microsomal electron transport activity and the levels of lipoperoxides in lung microsomes were determined by measuring the specific activity of NADPH (reduced nicotinamide adenine dinucleotide phosphate)-cytochrome c reductase and by spectrophotometry, respectively. Exposure to 80 or 60% oxygen induced significant decreases in the contents of arachidonic and docosahexaenoic acids, and also reduced microsomal electron transport activity. The level of lipoperoxides was elevated on the 2nd day of exposure to 80 or 60% oxygen, however, it returned to normal thereafter. On the other hand, exposure to 40% oxygen affected none of these parameters. Treatment with alpha-tocopherol prevented the changes in those fatty acids and microsomal function up to 2 days with exposure to 80% oxygen and up to 4 days with exposure to 60% oxygen. However, microsomal dysfunction and reductions of arachidonic and docosahexaenoic acids contents were observed after the 4th day of exposure to 80% oxygen or the 8th day of exposure to 60% oxygen irrespective of alpha-tocopherol administration. On the contrary, alpha-tocopherol administration prevented an elevation of the level of lipoperoxides. These results suggest that lung microsomal dysfunction induced by over 60% oxygen breathing is ascribed to the alteration of fatty acids composition in microsomal phospholipids and that alpha-tocopherol has a protective effect in the early phase.

Animals↗
PubMed1986

Pharmacokinetics of theophylline in beagle dogs and asthmatic patients after multiple oral doses of sustained-release theophylline tablet formulation.

The bioavailability and pharmacokinetics of theophylline after a single intravenous administration of theophylline and multiple oral administration of a sustained-release theophylline tablet formation were studied in dogs. In addition, the pharmacokinetics of theophylline after multiple oral doses of the drug was also studied in asthmatic patients. In the intravenous administration of theophylline (5 mg/kg) to dogs, the theophylline half-life was 4.0 +/- 0.2 h. The apparent volume of distribution (Vd) and plasma theophylline clearance (CL) were 0.734 +/- 0.019 l/kg and 126.7 +/- 3.4 ml/kg/h, respectively. In the multiple oral doses of the drug in amounts ranging from 7.52 to 9.09 mg/kg, the Vd and CL were 0.765 +/- 0.021 l/kg and 111.0 +/- 2.4 ml/kg/h, respectively. The mean oral absorption rate constant (ka) was calculated to be 0.355 +/- 0.035 h-1 and the mean elimination rate constant (kel) was 0.146 +/- 0.007 h-1. The absolute bioavailability of the drug calculated by a computer fitting method was 1.08 +/- 0.07. The result suggests that the drug has complete absorption. On the other hand, the pharmacokinetic parameters in the asthmatic patients were 0.337 +/- 0.055 l/kg for the Vd, 32.55 +/- 3.48 ml/kg/h for the CL, 0.222 +/- 0.058 h-1 for the ka and 0.105 +/- 0.016 h-1 for the kel, respectively. This study indicated that the dog may be useful to predict bioavailability of a sustained-release theophylline tablet formulation in humans. However, it showed that there are differences between dogs and humans in the pharmacokinetic parameters.

Administration, Oral↗
PubMed1986

The effect of coenzyme Q10 against the attack of phospholipase to myocardial membrane.

This study was designed to clarify the biochemical and electrophysiological influences of phospholipase (PLase) A2 and PLase C on canine myocardial membrane and to investigate the effect of coenzyme Q10 (CoQ10) against the action of these enzymes. Nine different species of free fatty acids (FFA), i.e., lauric, myristic, palmitic, palmitoleic, stearic, oleic, linoleic, arachidonic and docosahexaenoic acids were detected in myocardial membrane preparations by a high performance liquid chromatography. Incubation of the membrane with PLase A2 increased all of the unsaturated FFA, but not the saturated FFA. Incubation with PLase C increased all of the detected FFA. While PLase A2 and PLase C induced deleterious effects on myocardial membrane potentials, such as decreasing in the resting potential and in the magnitude of action potential, and shortening of the action potential duration. Premedication with CoQ10 significantly prevented all of these biochemical and electrophysiological changes induced by the action of PLases, suggesting that CoQ10 exerts a protective effect on myocardial membrane against the attack of PLases.

Animals↗
PubMed1985

Effects of orally administered glandular kallikrein on urinary kallikrein and prostaglandin excretion, plasma immunoreactive prostanoids and platelet aggregation in essential hypertension.

The effects of orally administered glandular kallikrein on urinary kallikrein, aldosterone and prostaglandin E (PGE) excretion, plasma renin activity (PRA), immunoreactive 6-keto PGF1 alpha and thromboxane B2 concentrations and platelet aggregation were studied in 12 patients with essential hypertension (EH). After a 2-week control period, each patient was given orally 450 KU/day of hog glandular kallikrein for 8 weeks. Urinary kallikrein, aldosterone and PGE excretion, and plasma 6-keto PGF1 alpha and thromboxane B2 concentrations were measured by radioimmunoassay. Platelet aggregation was measured by the addition of ADP, collagen or ristocetin with an aggregometer. Urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration were significantly decreased in patients with EH. There were no significant differences in PRA, urinary aldosterone excretion and plasma thromboxane B2 concentrations between control subjects and patients with EH. There was a significant decrease in blood pressure in patients with EH coinciding with significant increases of urinary kallikrein and PGE excretion and plasma immunoreactive 6-keto PGF1 alpha concentration after administration of glandular kallikrein. There was also a significant inhibition of platelet aggregation induced by collagen in these patients. Thus, a suppression of the kallikrein-kinin-prostaglandin system in patients with EH was found, and a decrease in blood pressure with an increment of urinary kallikrein, PGE excretion, plasma immunoreactive 6-keto PGF1 alpha and inhibition of platelet aggregation in vivo by the administration of glandular kallikrein.

6-Ketoprostaglandin F1 alpha↗
PubMed1985

Late estimation of myocardial infarct size by total creatine kinase nomogram.

We studied the possibility of enzymatic estimation of myocardial infarct size in patients late (between days 2 and 6) after the onset of acute myocardial infarction (AMI), in whom estimation of infarct size was difficult by analysis of time-activity curves of serum creatine kinase (CK) because of the lack of the enzymatic information during the initial 48 hours. Serial determinations of serum enzymes were performed in 32 patients within 6 hours after the onset of AMI and significantly close correlations were observed between cumulative total CK release and the cardiac fraction of lactate dehydrogenase isoenzyme (LDH1) activities from day 2 to day 6 after the onset of AMI (r = 0.863 to 0.870; p less than 0.001). We developed a nomogram to estimate cumulative total CK release by serum LDH1 activities obtained between days 2 and 6 after AMI and evaluated the reliability of the nomogram. Cumulative total CK release obtained from serial serum CK activities correlated closely with total CK release obtained from the nomogram in the second group of patients with AMI (r = 0.923 to 0.946; n = 24; p less than 0.001). Our total CK nomogram requiring few blood samples was useful in late estimation of infarct size in patients who were admitted to the hospital between days 2 and 6 after the onset of AMI.

Aged↗
PubMed1985

Some properties of calcium-induced contraction in the isolated human and guinea-pig tracheal smooth muscle.

We studied the effects of the cyclooxygenase inhibitors, indomethacin and aspirin, the leukotriene antagonist, FPL 55712 and the Ca antagonist, verapamil on basal tone and Ca-induced contractions in the human and guinea-pig tracheal muscle. Indomethacin and aspirin usually increased spontaneous tone or Ca-induced contractions in human strips, while consistently decreased tension development in the guinea-pig muscle. FPL 55712 strongly reduced contractions in the human, whereas it had a very weak effect on the guinea-pig muscle. Verapamil had a small inhibitory effect in the human trachea, either at 5.9 or 40 mM K, but markedly suppressed Ca-induced contractions of guinea-pig trachea in 40 mM K and had little effect on contractions in 5.9 mM K in this tissue. It is concluded that active tone in the two different tracheal muscles were controlled by different processes; that different arachidonate by-products may exert an effect on basal tone in the two different muscles; and that different plasma membrane Ca channels may be operative under basal conditions in the different muscles.

Aged↗
PubMed1985

Effects of high K on relaxation produced by drugs in the guinea-pig tracheal muscle.

In the guinea-pig tracheal smooth muscle, effects of various relaxants were compared in normal (5.9 mM) and excess (40 mM) K media. The relaxing effect of calcium-channel blockers, nifedipine and verapamil (group I) was potentiated by increasing the external K concentration. The effect of the drugs which are supposed to increase intracellular cyclic AMP, such as isoprenaline, forskolin, isobutylmethylxanthine, theophylline, dibutyryl cyclic AMP (group II) was moderately reduced by excess K. Nitroprusside, 8-bromo-cyclic GMP and sodium nitrite (group III) are generally considered to increase intracellular cyclic GMP and their effect was markedly reduced by excess K. When the tension development was made the same at 5.9 mM K and 40 mM K by adjusting the Ca concentration, the relaxing effect was similar and independent of the K concentration both for group II and group III drugs. It seems that the group II drugs can better overcome a large influx of Ca than group III drugs.

Animals↗
PubMed1985

The effect of Coenzyme Q10 on reperfusion injury in canine myocardium.

The mechanism of mitochondrial damage during reperfusion injury of ischemic myocardium was studied using mongrel dogs in vivo and isolated mitochondria in vitro. Seventy-seven adult dogs were divided into three groups: the control group (n = 38), the Coenzyme Q10 (CoQ10)-5 mg group (n = 24), and the CoQ10-15 mg group (n = 15). In the control group, the left anterior descending coronary artery (LAD) of the dog was occluded for 15 min followed by 5 min of reperfusion after 40 min of premedication with physiological saline. In both CoQ10 groups, 5 mg/kg or 15 mg/kg of CoQ10 was infused intravenously for 20 min and then physiological saline was administered for 20 min before 15 min occlusion of the LAD. Subsequently, reperfusion was allowed for 5 min. Each group was further divided into two subgroups depending on the presence (arrhythmia group) or the absence (non-arrhythmia group) of ventricular arrhythmias. Immediately after 15 min occlusion, myocardial samples were taken from the normal and reperfused areas to measure CoQ10 content of myocardium. Heart mitochondria were prepared after 5 min of reperfusion from both areas. Arrhythmias appeared in 12 of 38 dogs in the control group (32%), two of 24 dogs in the CoQ10-5 mg group (8%) and none of 15 dogs in the CoQ10-15 mg group (0%). Premedication with CoQ10 increased tissue CoQ10 content in a dose-dependent manner. In the CoQ10-5 mg group, the increase in CoQ10 content of dogs with reperfusion arrhythmias was relatively less than that of dogs without reperfusion arrhythmias. In each group, mitochondrial function was decreased in the arrhythmia group compared to that of the non-arrhythmia group. The increase in free fatty acid (FFA) content and the decrease in phospholipid content were also observed in mitochondria from the reperfused area of each arrhythmia group. The increase in FFA and mitochondrial dysfunction were induced by the incubation of mitochondria in vitro with phospholipase (PLase) A2 or PLase C, and protected by the addition of CoQ10. These results suggest that PLase plays an important role in the development of mitochondrial damage associated with reperfusion.

Animals↗
PubMed1985

Effects of verapamil on the contractions of guinea-pig tracheal muscle induced by Ca, Sr and Ba.

A comparison was made of contractions produced by calcium (Ca), strontium (Sr) or barium (Ba) in guinea-pig tracheal smooth muscle after the preparation had been relaxed in Ca-free medium. Most of the experiments were carried out in the presence of indomethacin (5 microM) to inhibit endogenous prostaglandin synthesis. In 40 mM K+ solution, the Ca, Sr and Ba concentrations which produced 50% of maximum tension responses were 0.07 mM, 1 mM and 2 mM, respectively. Maximum tension of a similar size was produced by either 2.4 mM Ca, 9.6 mM Sr or 9.6 mM Ba. The Ca-induced contraction in 5.9 mM K solution, which is probably due to the presence of endogenous prostaglandins, was not significantly affected by verapamil. When the external K concentration was increased to 40 mM, the Ca-induced contraction became susceptible to inhibition by verapamil. Similarly, contractions induced by Sr and Ba in excess K solution were strongly suppressed by verapamil. In the presence of prostaglandin (PG) F2 alpha (1.4 microM) or carbachol (5 microM), Ca, Sr and Ba produced contractions in both the 5.9 mM K and 40 mM K solutions. Contractions produced by PGF2 alpha or carbachol in the presence of Ca were little affected by 10 microM verapamil, whereas those in the presence of Sr or Ba were strongly suppressed by verapamil in both the 5.9 and 40 mM K solutions. 4 A strong suppressant effect of verapamil on the K-induced contraction, but a weak effect on the drug-induced contraction, in the presence of Ca can be explained by assuming that verapamil blocks voltage-operated Ca channels, but not receptor-operated Ca channels. However, this theory cannot account for the effect of verapamil on drug-induced contractions in the presence of Sr or Ba. It may be that susceptibility to verapamil is determined by the relative affinity of'the divalent cations and verapamil for the Ca channels, both for voltage- and receptor-operated channels.

Animals↗
PubMed1985

The effects of phospholipase A2 on beta adrenoceptor function in isolated cardiac cells.

The role of phospholipids in the maintenance of beta-adrenoceptor function was investigated in isolated canine myocytes prepared from eight adult mongrel dogs by using collagenase. The characteristics of beta-adrenoceptors were assessed by determining the number and the affinity of receptors by a radioactive ligand binding assay using 125I-iodocyanopindolol. The increase in cyclic AMP content induced by isoproterenol or forskolin was also determined by radioimmunoassay with or without pretreatment with phospholipase (PLase) A2. The amount of free fatty acids released from isolated myocytes by PLase A2 was measured by high-performance liquid chromatography. PLase induced a significant decrease in the number of beta-adrenoceptors but did not affect their affinity. Although the isoproterenol-stimulated increase in cyclic AMP was significantly inhibited by the pretreatment with PLase A2, the forskolin-stimulated increase was not affected. Responsive accumulation of cyclic AMP to isoproterenol was much more impaired than the decrease in beta-adrenoceptor number. These results indicate that PLase A2 deteriorates the function of the adenylate cyclase system linked-beta-adrenoceptor, and suggest that PLase A2 affects both beta-adrenoceptors and the coupling of beta-adrenoceptors with adenylate cyclase.

Animals↗
PubMed1985

Type III procollagen N-terminal peptides in experimental pulmonary fibrosis and human respiratory diseases.

In order to detect the fibrotic response in lung-tissue, concentrations of type III procollagen N-terminal peptide (P-III-P) were examined in sera and bronchoalveolar lavage fluids from rabbits with bleomycin-induced pulmonary fibrosis, and in sera from patients with various respiratory diseases, using a radioimmunoassay method. In the bleomycin-induced pulmonary fibrosis, a significant (p less than or equal to 0.05) rise in P-III-P levels was observed in the lavage fluid at 7 days, and in the sera at 21 days after bleomycin treatment, with histological confirmation of pulmonary fibrosis. Many of the patients with pulmonary fibrotic changes had significantly elevated serum P-III-P level. In lung cancer patients, most of the post-radiation serum samples were found to have P-III-P levels greater than or equal to 18 ng/ml. These results suggest that the increase in P-III-P levels is the reflection of fibrotic changes in the lungs and that the clinical assessment of serum P-III-P level could be important in the early detection of pulmonary fibrosis.

Animals↗