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Biomedical subjects

T Hidaka

Publications and source records attributed to T Hidaka.

At least 253 records · Page 14Linked to original sources

N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agent: effects on cardiac conduction.

Effects of N-(2,6-dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165) on cardiac conduction were studied in anesthetized, anesthetized open-chest and conscious dogs and rabbit Langendorff hearts following either intravenous (i.v.) bolus injection and continuous infusion or intraarterial injection. SUN 1165 at antiarrhythmic doses (or concentrations), prolonged PQ interval in dogs inherently showing broad QRS complex without affecting QRS duration, but prolonged both PQ interval and QRS duration in dogs showing narrow QRS complex, in a dose-dependent manner. At higher doses (or plasma concentrations), SUN 1165 caused a marked prolongation of PQ interval together with QRS duration and subsequently, in most cases, elicited conduction block within the atrial muscle as evidenced by disappearance of P wave. SUN 1165 caused the dose-related prolongations of atrio-ventricular conduction time and intra-atrial conduction time, and at the highest dose it blocked conduction within the atrial muscle in some cases. In the rabbit Langendorff hearts, SUN 1165 tended to prolong intraatrial and His-Purkinje-ventricular conduction time in preference to atrio-ventricular one. At higher concentrations, SUN 1165 produced conduction block in the Purkinje-ventricular system. These results suggest that SUN 1165, at the antiarrhythmic doses (or plasma concentrations), causes a delay of cardiac conduction by acting on the atrial muscle and His-Purkinje-ventricular system without affecting conduction through A-V node region, and at higher doses (or concentrations) produces conduction block by acting again on the atrial muscle or on His-Purkinje-ventricular system without impairing conduction in the A-V node.

Animals↗

Cell-to-cell contact in primary embryonic induction: effects of lectin on electrical coupling and neural induction.

The effects of lectin (concanavalin A; ConA) on the electrical coupling between inducing chorda-mesoderm and reacting ectoderm cells, and the realization of neural induction were investigated. The electrical coupling between cells of the chorda-mesoderm of the late gastrula (stage 13b) and the competent ectoderm or Con-A-treated ectoderm of the early gastrula (stage 12a) was measured. Neural induction was tested with ectoderm explants which had been combined with the inducing chorda-mesoderm for 1, 3 and 6 h. Electrical coupling was observed after 3 h. By 6 h, the coupling ratio had recovered to the same level as that between the homogeneous germ-layer cells. However, the electrical coupling did not recover in the combinant with Con-A-treated ectoderm. This suggests that Con-A disturbs close cell contact between the ectoderm and chorda-mesoderm cells. Neural induction was realized in the ectoderm which was combined with chorda-mesoderm for more than 3 h; this occurred parallel to the recovery of electrical coupling. In contrast, Con-A treatment (50 micrograms/ml) of the competent ectoderm for 30 min prevented neural induction. After 3 h of contact, the neural induction of Con-A-treated ectoderm was only one-third of that of the control ectoderm. The present study suggests that cellular contact between the inducing mesoderm and the ectoderm target cells plays an important role in the realization of neural induction.

Animals↗

Morphometric analysis of human neuromuscular junction in different ages.

Application of morphometric analysis to the study of neuromuscular junction is helpful to the quantitative approach of ultrastructural changes. In this study, twelve autopsied subjects of different ages were examined on the ultrastructure of neuromuscular junctions using morphometric analysis. The postsynaptic area and postsynaptic membrane length were significantly greater in adults than in infants. The results indicate that the number and/or depth of the secondary synaptic clefts of adults are greater than those of infants. In the aged subjects, presynaptic membrane length and postsynaptic membrane density showed a significant decrease. The latter observations were thought to be the results of regressive changes of pre-and postsynaptic structure with aging. The variations of each structural element were also studied. The large variations were found in the postsynaptic area, postsynaptic membrane length, and membrane length ratio of adults and aged group. On the other hand, variations in postsynaptic membrane density were small in all age groups. The importance of the knowledge of these age related changes and variations in the studies of neuromuscular junction was discussed.

Adult↗

Pharmacological properties of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolacto ne (KME-4), and its inhibitory effects on prostaglandin synthetase and 5-lipoxygenase.

The pharmacological effects of a new anti-inflammatory compound, alpha-(3,5-di-tert-butyl-4-hydroxybenzylidene)-gamma-butyrolactone (KME-4), and its inhibitory effects on arachidonate prostaglandin synthetase and 5-lipoxygenase activities were examined. KME-4 showed anti-inflammatory activity. It was less active than indomethacin, but more active than naproxen and ibuprofen in carrageenin-induced paw edema in rats; and it was less active than indomethacin, equipotent as naproxen, but more active than ibuprofen in granuloma formation in rats. The ulcerogenic activity of KME-4 was weaker than indomethacin and naproxen, but stronger than ibuprofen in starved rats. The ratio of UD50 stomach to ED30 carrageenin edema or to ED25 granuloma for KME-4 showed higher values than those of the reference drugs. KME-4 showed antipyretic activity in yeast-induced fever in rats. It also inhibited platelet aggregation induced by arachidonic acid and protected rabbits from arachidonic acid-induced death. Furthermore, KME-4 was found to be equipotent in inhibiting both prostaglandin synthetase and 5-lipoxygenase activities of rat basophilic leukemia cells, unlike indomethacin, naproxen and ibuprofen. It also inhibited the prostaglandin synthetase activity of bovine seminal vesicle. The present findings indicate that KME-4 may be a new type of anti-inflammatory drug with dual prostaglandin synthetase and 5-lipoxygenase inhibition.

4-Butyrolactone↗

[DNA-RNA cytofluorometry for a primary cancer of the stomach and choledochus].

We standardized DNA-RNA cytofluorometry with AO stain using a NIKON SPM-RFI-D instrument for cell smears. We applied this technique in a 72-year-old woman with primary double cancer of the stomach and choledochus. We first suspected malignancy of the choledochus and examined the desquamated cells in the bile cytofluorometrically to obtain by X-Y plotting the irregularly increased polyploid cells with a high percentage of cells in S phase. These polyploid cells and S phase cells were found to have an increased RNA content. Before operation, the presence of another malignancy of the stomach was also ascertained. The surgical specimens were diagnosed histopathologically as well differentiated, tubular adenocarcinoma of the stomach and moderately differentiated, tubular adenocarcinoma of the choledochus. By cytofluorometric analysis similar results were obtained, i.e., polyploidization with increase of S phase cells. Based on these results, we concluded that our method is useful for the diagnosis of alimentary tract malignancy, and that the criteria of malignancy appear to be unusual polyploidization with increased fractions of S phase cells.

Adenocarcinoma↗

[Pharmacological effects of brovanexine hydrochloride (BR-222) on the respiratory tract system, particularly on the respiratory tract fluid, mucociliary transport and cough].

Pharmacological effects of brovanexine hydrochloride (BR-222), a new expectorant, on the respiratory tract system was studied in comparison with that of bromhexine hydrochloride. 1. When doses ranging from 5 to 40 mg/kg of BR-222 were given orally (p.o.) or intraduodenally (i.d.) to rats, rabbits and dogs, it caused a significant increase in the output volume of respiratory tract fluid (RTF). It was almost as potent as bromhexine, but its pattern of increasing RTF was different from that of bromhexine. The increase in the serous ingredient of RTF after BR-222 administration seemed to be more remarkable than that after bromhexine treatment, though both drugs had no influences on the component ratio of glucose or protein in the RTF of dogs. 2. BR-222 at 10 and 20 mg/kg (i.d.) showed a tendency to reduce the viscosity of RTF in anesthetized dogs and so did bromhexine. A dose of 10 mg/kg (i.d.) of BR-222 also showed a tendency to reduce the viscosity of sputum obtained from the SO2-exposed rabbits. 3. A dose of 6 mg/kg (i.m.) of BR-222 caused a significant increase in the mucociliary transport rate in unanesthetized pigeons; in contrast with this, bromhexine caused a slight decrease. 4. Both drugs given orally showed no antitussive effects when examined by the "coughing dog" method.

Animals↗

Arachidonate metabolism in bovine gallbladder muscle.

Incubation of (1-14C]arachidonic acid (AA) with homogenates of bovine gallbladder muscle generated a large amount of radioactive material having the chromatographic mobility of 6-keto-PGF1 alpha (stable product of PGI2) and smaller amounts of products that comigrated with PGF2 alpha PGE2. Formation of these products was inhibited by the cyclooxygenase inhibitor indomethacin. The major radioactive product identified by thin-layer chromatographic mobility and by gas chromatography - mass spectrometric analysis was found to be 6-keto-PGF1 alpha. The quantitative metabolic pattern of [1-14C]PGH2 was virtually identical to that of [1-14C]AA. Incubation of arachidonic acid with slices of bovine gallbladder muscle released labile anti-aggregatory material in the medium, which was inhibited by aspirin or 15-hydroperoxy-AA. These results indicate that bovine gallbladder muscle has a considerable enzymatic capacity to produce PGI2 from arachidonic acid.

Animals↗

Thromboxane formation from arachidonic acid and prostaglandin H2 in rabbit spleen.

Incubation of [1-14C]arachidonic acid (AA) and [1-14C]prostaglandin (PG)H2 with rabbit spleen homogenate and microsomes resulted in the formation of a substance with the chromatographic properties of thromboxane (Tx)B2. The radiolabeled material was indistinguishable from authentic TxB2 on TLC in three solvent systems and on radiometric gas chromatography. The generation of TxB2-like material from AA and PGH2 was not observed after boiling of the homogenate and microsomes, and was completely inhibited by imidazole (5 mM). The transformation of AA into the TxB2-like material was not observed during incubation in the presence of indomethacin (28 microM). These results indicate that TxB2 is the principal product of arachidonic acid metabolism by the homogenate or microsomes of rabbit spleen.

Animals↗

[Clinical application of latamoxef during the perinatal period].

Pharmacokinetic studies and clinical evaluations of latamoxef (LMOX) were carried out in perinatal mothers and infants. LMOX was promptly absorbed after intravenous injection and intravenous drip infusion in pregnant women, producing dose-related peak blood levels. Placental transference to the fetus was favorable. After intravenous injection and intravenous drip infusion of 1.0--2.0 g of LMOX, drug concentration of the cord blood, amniotic fluid and fetal blood exceeded MICs of the main pathogenic organisms. By administration of the dose of 1.0--2.0 g twice a day, it is possible to successfully prevent or treat uterine infections. LMOX was effective in the prophylaxis or therapy of perinatal infections. Moreover, newborn infants delivered from mothers receiving LMOX treatment having drug concentrations exceeded MICs of main pathogenic organisms however not remained more than 12 hours after birth, and did not exhibit any laboratory test abnormalities. The above results demonstrated that LMOX is a clinically useful antibiotic for the prophylaxis and treatment of perinatal infections.

Adult↗

[A measurement of 5-androstene-3 beta, 17 beta-diol in human serum (author's transl)].

A radioimmunoassay using specific antisera against 5-androstene-3 beta, 17 beta-diol-11 alpha-succinoyloxy-BSA was developed, and serum concentrations of 5-androstene-3 beta, 17 beta-diol (AD) in normal men and women (maternal vein during pregnancy and cord blood at delivery) were measured. The reliability of the method was assessed by means of the recovery rate (97-109%) and the co-efficient of variation of inter- and intra assay (10-14%). The concentrations in serum samples obtained from various sources were as follows (ng/ml of free steroid mean +/- SD): spermatic vein, 48.57 +/- 50.64, peripheral vein in men aged 57-84, 1.24 +/- 0.47; ovarian vein during follicular phase, 3.81 +/- 3.27, peripheral vein, 1.03 +/- 0.44; maternal vein at delivery, 3.03 +/- 0.77, umbilical artery, 6.58 +/- 3.00, umbilical vein, 6.32 +/- 2.82. Plasma AD levels in the spermatic and ovarian vein were significantly higher than in the peripheral vein, suggesting the gonadal secretion of this steroid. Maternal serum AD concentration increased as pregnancy advanced, and AD levels in cord blood at delivery were significantly higher than that in maternal blood. These results also indicate that AD is one of the products of the feto-placental unit.

Adult↗