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Biomedical subjects

Y Masuda

Publications and source records attributed to Y Masuda.

At least 757 records · Page 42Linked to original sources
PubMed1986

Biopharmaceutical studies on hydantoin derivatives. V. Pharmacokinetics and pharmacodynamics of 5,5-diphenylhydantoin and 1-benzenesulfonyl-5,5-diphenylhydantoin.

Disposition of 1-benzenesulfonyl-5,5-diphenylhydantoin (II) having a potent anti-inflammatory activity was compared with that of 5,5-diphenylhydantoin (I), an antiepileptic drug, in order to elucidate whether the pharmacodynamic difference between them can be explained by their physicochemical and pharmacokinetic properties. After oral administration of I-14C to rats, radioactivity was distributed in all tissues including the brain, whereas after II-14C administration, the concentrations of radioactivity in most tissues were lower than those in plasma. The results were consistent with the finding obtained by whole-body autoradiography which revealed that after oral administration of II-14C to rats, radioactivity was not transferred into brain but was significantly transferred into inflamed tissues. Brain/plasma concentration ratio of I was about 1.3, whereas that of II was about 0.05. Plasma protein binding of I having pKa value of 8.30 was about 88%, whereas that of II having pKa value of 4.89 was about 99%. The changes in physicochemical properties due to introduction of a benzenesulfonyl group into the hydantoin ring may be responsible for the difference in the disposition between I and II. When II was cerebroventricularly administered to mice, it showed a potent anti-convulsant activity against maximal electroshock seizure, the activity being comparable to that for I. This indicates that the earlier failure to demonstrate the activity of II in a routine screening test for antiepileptic drugs was due to the inability of II to penetrate the blood-brain barrier and to achieve effective concentration in the brain. II was found to inhibit the biosynthesis of prostaglandin. These findings along with the physicochemical properties suggest that although II does not fall structurally under any category of anti-inflammatory drugs the mechanism of action may be similar to that for non-steroidal acidic anti-inflammatory drugs.

Administration, Oral↗
PubMed1986

The mode of enhanced enteral absorption of macromolecules by lipid-surfactant mixed micelles. I.

The enhancement of absorption of water soluble macromolecules by lipid-surfactant mixed micelles (MM) was performed in two in vitro experimental systems using rat large intestine, which were isolated epithelial cells containing transcellular route alone and everted sac involving trans- and paracellular routes. Four kinds of fluorescein isothiocyanate-labelled dextrans (FDs) having different average molecular weights (9K-70K) were used as models of water soluble macromolecules. In the absence of MM, very poor transport of FDs was observed in both isolated epithelial cells and everted sac experiments. Linoleic acid-polyoxyethylated (60 mol) hydrogenated castor oil (HCO60) MM enhanced the transport of FDs in both systems, especially for smaller size FDs. This promotive effect by MM decreased with an increase in molecular weight of FDs in both systems. Although enhanced transport of the largest FD (molecular weight, 70K) by MM was clearly demonstrated in the everted sac, the enhanced transport of the same FD in the isolated cells was negligible. These results suggest the possibility of participation of paracellular route as well as transcellular route in the enhancing effect of MM on the large intestinal absorption of water soluble macromolecules.

Animals↗
PubMed1986

The effects of diethyldithiocarbamate on the hepatotoxic action and antitumor activity of N-methylformamide in mice.

The oral administration of diethyldithiocarbamate (DTC) prevented hepatic necrosis induced by N-methylformamide (NMF) in ddY-strain mice, in more susceptible BALB/c mice and in diethylmaleate-treated mice in which NMP-hepatotoxicity was potentiated, as evidenced by suppression of increases of plasma glutamic pyruvic transaminase activity and liver calcium content or by histological observations. Early depletion of liver glutathione following NMF administration was also prevented by DTC. DTC markedly delayed the in vivo metabolism of NMF as indicated by a prolonged retention of plasma and liver NMF levels and an enhancement of urinary excretion of NMF. These observations support a bioactivation mechanism for NMF hepatotoxicity, and the hepatoprotective action of DTC may be due to an inhibition of the metabolic activation of NMF. Hepatotoxic manifestations after repeated administration of NMF also tended to be ameliorated by simultaneous treatment with DTC. Cotreatment with DTC, however, decreased the antitumor activity of NMF against Ehrlich ascites tumors, and Sarcoma 180. This also implies the involvement of a bioactivation mechanism in the antitumor action of NMF, but further studies are necessary to confirm this point. The possible therapeutic value of DTC as a hepatoprotector may be diminished by the suppression of the antitumor activity of NMF.

Animals↗
PubMed1986

Normal development of the middle ear in the mouse: a light microscopic study of serial sections.

Development of the ear, especially the middle ear, was studied histologically in ddN and CF mice. Primordia of the 3 ossicles and the otic capsule appeared on day 12 of pregnancy. The stapedial primordium was observed as a mass of mesenchymal cells lateral to the primordium of the otic capsule, attaching to the medial part of the facial nerve. On day 13, the stapedial primordium continued to develop with the Reichert's cartilage. On day 14, the malleus and incus were differentiated. On day 15, the 3 ossicles were mostly completed in shape, and the stapedial footplate had a bilaminar structure at this stage. This structure appeared to correspond to the lamina stapedialis in the developing human stapes.

Animals↗
PubMed1986

[Diagnosis of mitral valve prolapse by X-ray CT and MRI].

To evaluate the usefulness of enhanced X-ray CT and gating magnetic resonance imaging (MRI) for diagnosing mitral valve prolapse, three patients with this abnormality and several controls were examined by these two methods. The mitral valve was not recognized by X-ray CT except a few cases with thickened mitral valve. However, MRI could demonstrate clearly the mitral leaflets and annulus in many subjects. In transverse MR imaging of the subjects without valvular disease, the closed mitral valve showed V-shaped appearance in the left ventricle during systole. In a patient with marked mitral valve prolapse, MRI revealed buckling of the posterior mitral leaflet into the left atrium, and in two other patients with mild mitral valve prolapse, MRI demonstrated displacement of coaptation of the anterior leaflet toward the left atrium. These results suggest MRI is a useful method for diagnosing mitral valve prolapse.

Echocardiography↗
PubMed1986

[Pericardial defect: roles of the pericardium on kinetoanatomic changes of the heart influenced by patients' postures].

To elucidate the physioanatomic roles of the pericardium, the alterations in gross anatomy and cardiac motion induced by posture were examined by two-dimensional echocardiography in seven patients with total absence of the left pericardium. Ten healthy subjects were served as controls. The heart was located deeper within the chest at end-diastole in patients with pericardial defect than in healthy subjects, especially in the left lateral decubitus position. With progression of systole, the cardiac apex swung anteriorly with the cardiac base as the fulcrum, and the heart approximated the normal position at end-systole. The deeper the position of the center of the cross-section of the left ventricular cavity at end-diastole, the more exaggerated the swinging motion in systole. The deep location of the heart in end-diastole is considered to result from release from pericardial support, and the systolic tonus of the cardiac muscle restores the apex to nearly normal position. The characteristic swinging motion of the heart and its alterations dependent of posture seemed the signs suggestive of total absence of the pericardium. The shape of the short-axis view of the left ventricular cavity was nearly circular throughout the cardiac cycle. Therefore, paradoxical motion of the ventricular septum observed on M-mode echocardiography in pericardial defect results from the anterior shift of the entire heart overcoming the proper motion of the interventricular septum. The left ventricular dimension become enlarged according to the postural change from the right to left lateral decubitus positions regardless of the presence or absence of the pericardium. The right ventricular cavity became enlarged in the left lateral decubitus position in patients with pericardial defect. The elevation of hydrostatic pressure due to postural change was considered excessive due to the absence of the pericardium. In the left lateral decubitus position, systolic excursions of the mitral and tricuspid rings became more prominent in healthy subjects, whereas these excursions, particularly of the tricuspid ring, were reduced in patients with pericardial defect. Depressed tricuspid ring motion was also observed in the right lateral position in cases with pericardial defects. The reduced excursion of the tricuspid, ring and the right ventricular dilatation may affect systemic venous return to the right atrium.

Adult↗
PubMed1986

[A case of malignant meningioma with subcutaneous infiltration of the scalp].

A case of malignant meningioma in a 78-year-old man is reported. It was found as a subcutaneous tumor of the scalp, following which some neurological symptoms were clinically noted. The tumor showed infiltrative growth and was located from the subcutaneous tissue to the meninges through the skull. Histologically, it was composed predominantly of spindle, epithelioid and bizarre tumor cells, but a whorl formation was also detected in a restricted area. The histogenesis of the present case and the relationship between the histopathological findings and clinical behavior of malignant meningioma are also discussed.

Aged↗
PubMed1985

Increased anticonvulsant effect of phenobarbital with age in mice--a possible pharmacological index for brain aging.

We have recently reported that the anticonvulsant effect of phenytoin increases with age in mice (1). Since some of the mechanisms of anticonvulsant action of phenytoin and phenobarbital may be different, the present study sought to determine whether a similar increase with age in the anticonvulsant effect of phenobarbital could also be observed. The anticonvulsant effect of phenobarbital was examined in BDF1 female mice of different ages (6, 12, 24 and 30 months old) using the abolition of the tonic hindlimb extensor component of maximal electro-shock seizure as the index. The minimal effective concentration (MEC) values of phenobarbital in plasma and brain were significantly lower in aged (24 and 30 month old) mice compared with the respective values in the youngest animal group (6 month old). Series using nearly two-fold different intensities of electroshock (30 and 55 mA) showed almost identical MEC values in 24 month-old mice. It was concluded that the brain of aged mice is more sensitive to phenobarbital, as it is to phenytoin.

Aging↗
PubMed1985

Age related increased threshold for electroshock seizure in BDF1 mice.

The thresholds for inducing the minimal and maximal electroshock seizures were examined in relation to age in BDF1 mice of both sexes. The 50 percent effective intensities for the maximal electroshock seizure (tonic hindlimb extensor component) were lowest in the youngest age groups (6-month-old) for both male (10.68 mA) and female (9.18 mA) animals. The threshold increased with age and became significantly higher at 24 months (14.00 mA, 12.70 mA for male and female mice respectively). There was also a further increase in threshold at 30 months for both sexes. Similarly, the threshold for inducing the minimal seizure also increased with age but the differences in mean threshold levels between the youngest and oldest groups were much smaller in comparison to the maximal seizure. It was concluded that the threshold for inducing electroshock seizures significantly increases with age in mice of both sexes.

Age Factors↗
PubMed1985

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in mice by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Hepatic aryl hydrocarbon hydroxylase (AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofurans (PCDFs), 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in four inbred strains of mice with different phenotypes of Ah locus, i.e., AHH-responsive strains: C57BL/6N and AKR/Ms Qdj, and AHH-nonresponsive strains: DBA/2Cr Slc and Qdj; DDD. Eight individual PCDF isomers or TCDD were administered IP in doses of 30 micrograms/kg; HCB was given in a dose of 120 micrograms/kg. In AHH-nonresponsive strains of mice, only TCDD significantly induced hepatic AHH activity, while in AHH-responsive strains, 2,3,7,8-tetrachlorodibenzofuran(2,3,7,8-TCDF), 1,2,3,7,8-pentachlorodibenzofuran(1,2,3,7,8-PCDF), 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), and TCDD significantly enhanced the enzyme activity, and the induced AHH activities with the three PCDF isomers were about 30-65% of those of TCDD. These results indicate that AHH responsiveness in mice segregates with the induction of AHH activity by PCDF isomers and may also segregate with the toxic potency of the isomers; i.e., toxic potencies of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF in AHH-responsive strains of mice may be much greater than those in AHH-nonresponsive strains of mice. Taking into account both the potent AHH inducibility and the high bioaccumulation of 2,3,7,8-TCDF, 1,2,3,7,8-PCDF, and 2,3,4,7,8-PCDF, these three PCDF isomers should be given greater attention with regard to environmental contamination.

Animals↗
PubMed1985

Genetically mediated induction of aryl hydrocarbon hydroxylase activity in human lymphoblastoid cells by polychlorinated dibenzofuran isomers and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Aryl hydrocarbon hydroxylase(AHH)-inducing potency of toxic polychlorinated aromatic hydrocarbons such as polychlorinated dibenzofuran (PCDF) isomers, 3,4,5,3',4',5'-hexachlorobiphenyl (HCB) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was investigated in human lymphoblastoid cell lines with different AHH inducibility for 3-methylcholanthrene (3-MC) obtained from healthy subjects. Each of the cell lines was treated with eight individual PCDF isomers, TCDD, and HCB at doses of 1.9-15 ng/ml of culture medium, 1.9-7.5 ng/ml and 95 ng/ml, respectively. Lymphoblastoid cell lines were arbitrarily classified into three groups based on their AHH inducibilities with 3-MC (2.5 microM); low (3-MC/control = I less than 3), middle (3 less than or equal to I less than 6) and high (I greater than or equal to 6). Degrees of the enzyme inducibilities of the organochlorine compounds proportionally increased with those for 3-MC. AHH inducibilities with 2,3,4,7,8-pentachlorodibenzofuran(2,3,4,7,8-PCDF), 1,2,3,4,6,7-hexachlorodibenzofuran(1,2,3,4,6,7-HCDF) and 1,2,3,4,7,8-hexachlorodibenzofuran(1,2,3,4,7,8-HCDF) were comparable to those of TCDD at doses of 7.5 ng/ml, and about twice as high as those of 2,3,7,8-tetrachlorodibenzofuran (TCDF), at the same dose, HCB, at a dose of 95 ng/ml, did not induce enzyme activity. The experimental evidence indicated that AHH inducibility by the organochlorine compounds reflected the genetic susceptibility of the cells to the phenomenon of induction, and PCDF isomers found at relatively high concentrations in tissues of mammals exerted the highest values of AHH induction.

Aryl Hydrocarbon Hydroxylases↗
PubMed1985

A giant tumor thrombus in the right atrium clearly detected by 111In-oxine labeled platelet scintigraphy.

A 54-year-old man was admitted to hospital with a 3-month history of progressive dyspnea with coughing. A giant right atrial mass, originating from a hepatocellular carcinoma, was visualized by computed tomography, and digital subtraction angiography. The volume of the right atrial mass was increasing rapidly. It was therefore essential to determine whether this giant mass was a tumor thrombus or a multiplication of the hepatocellular carcinoma. 111In-oxine labeled platelet scintigraphy revealed active accumulation in the right atrium caused by the presence of active platelet deposition, and slight accumulation in the lung fields probably due to embolic showers originating from the tumor thrombus in the right atrium. This is the first case report showing that 111In-oxine labeled platelet scintigraphy can aid in confirming the nature of a giant tumor thrombus in the right atrium and can clarify the pathogenesis of the respiratory symptoms.

Blood Platelets↗
PubMed1985

Normal ventricles in chronic schizophrenics.

The computed tomography (CT) scans of 46 chronic schizophrenic patients and 46 controls were studied using ventricular-brain ratio. Ewans' index, and cella media index. None of the indices used revealed significant differences between the patient and the control groups.

Adult↗
PubMed1985

Responses of the atrial myocardium to cardiac sympathetic nerve stimulation.

The cardiac responses to sympathetic nerve stimulation were measured in open-chest, anesthetized dogs before and after infusions of cocaine, which were given to inhibit the neuronal uptake of norepinephrine. Cocaine did not augment the inotropic or chronotropic responses, but it did retard their decay after cessation of sympathetic stimulation. Before cocaine, the half-times for decay of the chronotropic, atrial inotropic, and ventricular inotropic responses were 28.4 +/- 2.2, 29.8 +/- 2.7, and 22.1 +/- 1.9 (+/- SE) s, respectively. After cocaine, however, the half-times were significantly greater (147 +/- 12.0, 51.4 +/- 3.9, and 32.9 +/- 2.5 s, respectively). The cocaine-induced prolongation of the decay time in a given cardiac tissue is a measure of the relative efficacy of neuronal uptake as a mechanism for dissipating the neurally released norepinephrine. Our data indicate, therefore, that among the various cardiac tissues that we studied, the neuronal uptake mechanism is least effective in the ventricular myocardium, somewhat more effective in the atrial myocardium, and most effective in the sinoatrial nodal region.

Animals↗
PubMed1985

Heart rate modulates the disposition of neurally released norepinephrine in cardiac tissues.

We determined the effect of heart rate on the disposition of neurally released norepinephrine from the cardiac tissues in open-chest, anesthetized dogs with complete atrioventricular block. After injecting desipramine to block the neuronal uptake of norepinephrine, we stimulated the cardiac sympathetic nerves supramaximally for about 3 minutes at a mean frequency of 2.7 Hz. In one series of experiments, we allowed coronary sinus blood flow to change spontaneously in response to cardiac pacing and sympathetic stimulation. The mean coronary sinus blood flows just before cessation of sympathetic stimulation were 67.4 +/- 4.2 (SE) and 37.4 +/- 2.7 ml/min during pacing at a high (150/min) and a low (60/min) frequency, respectively. The mean norepinephrine overflow into the coronary sinus blood during steady state sympathetic stimulation was 45.0 +/- 14.2% greater during high frequency pacing than during low frequency pacing. After cessation of neural stimulation, the norepinephrine overflow decayed more rapidly during high frequency pacing than during low frequency pacing. This difference in decay rates was mainly ascribable to the difference in coronary blood flows. In a second series of experiments, we adjusted the coronary sinus blood flow during sympathetic stimulation so that the flows were not significantly different during pacing at the two frequencies. During the initial 30-second period, after cessation of sympathetic stimulation, the mean decrements of norepinephrine overflow were 95.9 +/- 21.4 and 59.2 +/- 17.3 ng/min at the high- and low-pacing frequencies, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Platelet activating factor analogues: lack of correlation between their activities to produce hypotension and endothelium-mediated vasodilation.

Hypotensive activities of 11 synthetic derivatives of platelet activating factor (PAF) were examined and compared with their activities to produce endothelium-related relaxation of isolated rat thoracic aorta. The derivatives showed variety of hypotensive activities; some of the derivatives were more potent than natural PAF and some were virtually inactive compared to PAF. However, all of the compounds tested exhibited exactly the same activities to produce endothelium-related vasodilation. These results confirmed our previous view that the PAF-induced hypotension is not solely due to the endothelium-related vascular relaxation observed in vitro.

Acetylcholine↗