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Biomedical subjects

T Satake

Publications and source records attributed to T Satake.

At least 145 records · Page 8Linked to original sources
PubMed1987

Acetylcholine and norepinephrine concentrations in the heart of spontaneously hypertensive rats: a parasympathetic role in hypertension.

To determine the role of the parasympathetic system in the development of essential hypertension, the concentrations of acetylcholine (ACh) as a parasympathetic marker and norepinephrine (NE) as a sympathetic marker were measured simultaneously in the heart of spontaneously hypertensive rats (SHR) at 4, 10 and 27 weeks of age, and in age-matched control Wistar-Kyoto rats (WKY). ACh was measured using a highly sensitive and specific high performance liquid chromatography-electrochemical detection (HPLC-ECD) attached to a newly developed immobilized fixed enzyme column system. NE was measured by conventional HPLC-ECD. The ACh concentration decreased in the order right atrium (RA) greater than left atrium (LA) greater than right ventricle (RV) greater than interventricular septum (IVS) greater than left ventricle (LV) in both SHR and WKY of all age groups, and NE showed an almost identical pattern. The concentration of ACh tended to increase and that of NE to decrease with age in both strains. The concentrations of ACh in the heart were significantly different in the two strains, with the levels being consistently higher in the SHR strain regardless of age, although differences were most significant at 10 weeks. The mean concentrations of NE were higher in SHR than in WKY, but the differences between the two strains were significant only in the RV and IVS. The functional meanings of a given tissue concentration of a neurotransmitter are still controversial. However, the increase in SHR heart ACh concentration, in parallel with the development of hypertension, may reflect the augmented parasympathetic activity counteracting or compensating for the augmented sympathetic drive in the early stage of hypertension.

Acetylcholine↗
PubMed1987

Comparative studies on the combined cytotoxic effect of forskolin with mitomycin C and responsiveness to forskolin in rat ascites hepatoma AH66 cells and AH66F cells.

The combined cytotoxic effect of forskolin with mitomycin C (MMC) was investigated using two cell lines, AH66 and AH66F. Forskolin significantly enhanced the cytotoxicity of MMC and increased the uptake of MMC and the intracellular adenosine 3',5'-cyclic monophosphate (cyclic AMP) level in AH66 cells but similar results were not obtained with AH66F cells. Dibutyryl cyclic AMP enhanced the effect and uptake of MMC in both cell lines. These results confirm that elevated cyclic AMP in the cells increases the cellular uptake of MMC and enhances the cytotoxicity of MMC as reported in our previous papers. Therefore, forskolin may be suitable for antitumor combination therapy. On the other hand, the functional components associated with the cyclic AMP generating system were thought to be present in membranes of both AH66 cells and AH66F cells from results that showed that cholera toxin, islet-activating protein and prostaglandin E1 increased the level of cyclic AMP in both cells. The elevation of cyclic AMP by these adenylate cyclase activators in AH66 cells was augmented by forskolin. However, the cyclic AMP level in AH66F cells was scarcely affected by forskolin and the elevation of cyclic AMP by the activators was inhibited by this diterpene. From these results, it appears that the AH66F cell line may be useful for the elucidation of the action mechanism of forskolin and of the transmission system from hormone receptors to adenylate cyclase.

Animals↗
PubMed1987

Multiform combination effects of smooth muscle relaxants with antitumor agents in rat ascites hepatoma AH66 cells.

At non-cytotoxic concentrations, actions of smooth muscle relaxants except for the action of isoproterenol (IPN) on the effect of vinblastine (VBL) and mitomycin C (MMC) in rat ascites hepatoma AH66 cells resistant to these antitumor agents clearly separated into two groups. IPN hardly influenced the effects of both VBL and MMC. Although verapamil, a calcium-antagonist, and W-7, a calmodulin inhibitor, enhanced the growth-inhibitory effect and uptake of VBL by inhibiting the VBL efflux, these drugs did not influence the effect and uptake of MMC. In contrast, forskolin, an adenylate cyclase activator, db-cAMP, a cAMP analog, and theophylline, a cyclic nucleotide phosphodiesterase inhibitor, potentiated the effect of MMC, but did not influence the effect of VBL. The combination effect of forskolin and db-cAMP might be elucidated from the increase of inward transport of MMC through the action of the intracellular cAMP elevated by these drugs. Theophylline, however, only slightly increased both intracellular cAMP level and MMC uptake into the cells, similar to the action of IPN. We thought that the combination effect of theophylline was effected through its other activity of repair inhibition against AH66 cells, which are resistant to MMC due to their high capacity to repair impaired DNA. Thus, the smooth muscle relaxants used in this study enhanced the growth-inhibitory effect of a distinct antitumor agent through their individual activity against tumor cells.

Animals↗
PubMed1987

Effects of a selective thromboxane synthetase inhibitor (OKY-046) in patients with coronary artery disease during exercise.

We studied the levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), platelet aggregability, beta-thromboglobulin and platelet factor 4 in 30 coronary artery disease (CAD) patients and 21 normal subjects during exercise. During treadmill exercise, 13 of 30 CAD patients reported chest pain. We administered a selective thromboxane synthetase inhibitor (OKY-046) for 2 weeks to 10 CAD patients with exercise-induced chest pain and studied its effects. At rest, the plasma TXB2 levels and platelet aggregation were significantly lower in normal subjects than in CAD patients, and there was no difference between CAD patients with and without exercise-induced chest pain. On treadmill testing, plasma TXB2 levels and platelet aggregation increased significantly only in the CAD patients with exercise-induced chest pain. Plasma 6-keto-PGF1 alpha levels in normal subjects were significantly higher than those in CAD patients both at rest and during exercise. After administration of OKY-046, mean exercise time increased significantly from 7.5 to 8.6 min (p less than 0.001). Plasma TXB2 level and platelet aggregation decreased significantly after OKY-046 administration both at rest and during exercise. These results suggest that a marked increase in TXA2, with only a minimal change in PGI2, during exercise may contribute to exercise-induced myocardial ischemia, and that OKY-046 is useful in the treatment of CAD patients.

6-Ketoprostaglandin F1 alpha↗
PubMed1987

Effects of dibutyryl cyclic adenosine monophosphate and colforsin on mucociliary transport using frog palate.

For the determination of mucociliary transport, a method was developed to assess the mucociliary transport force (MCTF). Using this method, effects of isoprenaline (isoproterenol), theophylline, dibutyryl cyclic adenosine monophosphate (AMP) and colforsin on mucociliary transport were investigated for 15 min after the drug application. These agents induced a significant, dose-related increase in MCTF. Propranolol, a beta-adrenergic antagonist, inhibited the effect of isoprenaline, and 9-(tetrahydro-2-furyl)adenine, an inhibitor of adenylate cyclase, inhibited the effect of colforsin. These results indicated that mucociliary transport was stimulated by the agents which increased intracellular cyclic AMP level, and that intracellular cyclic AMP played an important role in the maintenance and/or regulation of mucociliary transport.

Animals↗
PubMed1987

Absorption of theophylline from a sustained-release theophylline tablet formulation, Theo-Dur.

The absorption kinetics of theophylline after single oral administration of a sustained-release theophylline tablet formulation, Theo-Dur, were studied in healthy volunteers. The pharmacokinetic parameters were estimated by utilizing a one-compartment model with zero-order or first-order absorption according to the procedure "Praxis". The release of theophylline from the formulation in the in vitro dissolution study was shown to be an apparent zero-order process. The in vivo studies demonstrated that the time required to reach maximum plasma concentration of theophylline was about 8 h. The mean residence time in vivo, MRT, was 18.6 h. The present study also showed that the formulation was good sustained-release properties with adequate bioavailability and that the in vitro sustained-release characteristic was confirmed to be reflected in the plasma concentration-time profile of theophylline in the in vivo. The computer-predicted concentrations of theophylline based on the zero-order absorption model fitted to the observed data points better than those based on the first-order absorption model. The regression curves obtained by nonlinear least squares method based on the first-order absorption model underestimate the maximum observed plasma concentrations of theophylline. There was a highly significant relationship between observed and calculated around the maximum plasma concentration data based on the zero-order absorption model. These results show that the drug absorption from the formulation is best described by an apparent zero-order rather than a first-order absorption model.

Absorption↗
PubMed1987

[Flomoxef treatment of patients with respiratory tract infections].

Flomoxef (FMOX, 6315-S) was administered to 22 patients with respiratory tract infections. The patients consisted of 13 patients with pneumonia, 7 with bronchitis, 1 with bronchiectasis and 1 with pyothorax. The drug was administered by intravenous injection or intravenous drip infusion twice a day with doses of 1 to 2 g and total doses ranged from 17 to 64 g. The following results were obtained. 1. Clinical responses to the therapy were excellent in 1 case, good in 10 cases, fair in 4 cases, poor in 4 cases and not determined in 3 cases. Efficacy ratio was 57.9%. 2. As for adverse reactions, exanthema in 1 patient and stomatitis and numbness of tongue in another patient were observed, but these symptoms improved with cessation of the therapy. Abnormal laboratory test values were observed in 5 cases. From these results it appears that FMOX is a valuable antimicrobial agent against patients with respiratory tract infections.

Aged↗
PubMed1986

Effects of kallidinogenase on urinary kallikrein excretion and plasma prostanoid concentrations in patients with essential hypertension.

The effects of kallidinogenase on urinary kallikrein excretion, plasma immunoreactive prostanoids and platelet aggregation were investigated in patients with essential hypertension. Urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration were significantly decreased in these patients. Significant decreases in blood pressure, as well as significant increases of urinary kallikrein excretion and plasma 6-keto PGF1 alpha concentration after kallidinogenase administration were also observed.

6-Ketoprostaglandin F1 alpha↗