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Biomedical subjects

Y Ukai

Publications and source records attributed to Y Ukai.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Lactitol suppresses the disturbance of consciousness caused by experimentally induced hepatic encephalopathy in rats: an EEG study].

Electroencephalographic (EEG) studies were conducted to demonstrate the ameliorating effects of lactitol and its reference drug lactulose on the disturbance of consciousness caused by severe hepatic encephalopathy in rats permanently implanted with cortical electrodes. A novel experimental animal model of combined-type human hepatic encephalopathy was prepared by portacaval shunting followed by a single treatment with dimethylnitrosamine (30 mg/kg, i.p.). Lactitol or lactulose was orally administered twice a day for seven days and once on the morning of the eighth day. Ammonium acetate (500 mg/kg) was injected into the cecum 4 hr after the final administration of the drug. In control animals not treated with either drug, but in which hepatic encephalopathy had been induced, ammonium acetate induced a comatose state defined by a loss of the righting reflex accompanied by slowing or flattening of the cortical EEG. In control animals, significant increases in delta (1-3 Hz)-activity and significant decreases in beta (13-25 Hz)-activity during coma were detected by means of EEG power spectral analysis. Lactitol at doses of 3 g/kg/day or higher or lactulose at 6 g/kg/day significantly suppressed these EEG changes. Both drugs also suppressed in a dose-dependent manner the loss of the righting reflex. Lactitol may therefore be useful for ameliorating the disturbance of consciousness in patients with hepatic encephalopathy.

Animals↗
PubMed1995

[Ameliorating effect of lactitol on experimental hepatic encephalopathy in Eck fistula dogs].

Eck fistula (portacaval shunted) dogs were prepared for use as an experimental model of chronic hepatic encephalopathy. The effect of lactitol on hepatic encephalopathy was investigated by observing the behavior, electroencephalograms (EEGs) and visually evoked potentials (VEPs) of the experimental dogs. Lactitol was administered intragastrically once a day for 12 weeks from the third week after the portacaval-shunt operation and the behavior, EEGs and VEPs of the dogs were observed every two weeks. Dogs not given lactitol became sluggish, then apparently blind, and eventually fell into a coma, over a period of several weeks after the operation. Some dogs died. The EEGs revealed low-voltage slow waves and, at a later stage, displayed flattening in some dogs. The VEPs displayed prolonged latency of both the positive and the negative component as well as an increased amplitude. Lactitol at 1 or 3 g/kg/day suppressed the behavioral symptoms and the changes in the EEGs and the VEPs. These results suggest that lactitol may be useful for the treatment of various nervous symptoms in patients with hepatic encephalopathy accompanied by hyperammonemia.

Animals↗
PubMed1994

NS-3, a TRH analog, reverses repeated ECS-induced deficits in water maze performance in the rat.

Rats given five consecutive daily electroconvulsive shock (ECS) treatments and trained to run in the Morris water maze, starting three days posttreatment, showed deficits in learning and memory functions. Treatment before each training session with the thyrotropin-releasing hormone (TRH) analog NS-3 [(CG-3703), (3R),(6R)-6-methyl-5-oxo-3-thiomorphorinyl-l-histidyl-l-prolinamid e tetrahydrate] reversed these behavioral deficits. The possible use of TRH and its analogs as therapeutic treatment for the cognitive dysfunctions resulting from electroconvulsive shock treatment for depression and the possible involvement of central cholinergic systems in the cognitive dysfunctions are discussed.

Animals↗
PubMed1994

Change in genetic variance under selection in a self-fertilizing population.

In this study we show how the genetic variance of a quantitative trait changes in a self-fertilizing population under repeated cycles of truncation selection, with the analysis based on the infinitesimal model in which it is assumed that the trait is determined by an infinite number of unlinked loci without epistasis. The genetic variance is reduced not as a consequence of the genotypic frequency change but due to the build-up of linkage disequilibrium under truncation selection in this model. We assume that the order of the genotypic contribution from each locus is n-1/2, where n is the number of loci involved, and investigate the change in linkage disequilibrium resulting from selection and self-fertilization using genotypic frequency dynamics in order to analyze the change in the genetic variance. Our analysis gives recurrence relations of genetic variance among the succeeding generations for the three cases of gene action, i.e., purely additive action, pure dominance without additive effect and the presence of both additive effect and dominance, respectively. Numerical examples are also given as a check on the recurrence formulas.

Fertilization↗
PubMed1994

The analeptic effect of methamphetamine in pentobarbital-narcotized rats is mediated via a dopaminergic-cholinergic mechanism.

Methamphetamine (MAP) administered in doses of 0.5 to 5 mg/kg i.p. to rats anesthetized with pentobarbital produced a shortening of the duration of loss of righting reflex. This analeptic effect of MAP was blocked by atropine but not by atropine methylbromide, indicating the central cholinergic nature of the response. This effect was also blocked by the D1 and D2 dopamine antagonists SCH 23390 (0.2 mg/kg) and raclopride (2 mg/kg), respectively. Pentobarbital decreased sodium-dependent high-affinity choline uptake (HACU) in frontal cortex and hippocampus as measured in synaptosomes from treated rats. MAP given to pentobarbital-narcotized rats restored HACU activity to nonanesthetized levels, but this restorative effect of MAP was blocked by SCH 23390 or raclopride. These data suggest that in addition to a cholinergic mechanism, the analeptic effect of MAP involves the dopamine system. alpha-Methyl-p-tyrosine, but not reserpine, pretreatment completely blocked the MAP analeptic response. In reserpinzed rats, MAP produced a markedly enhanced analeptic response. Studies of the effects of repeated administration of MAP on its analeptic activity were also undertaken in view of the well known sensitization to the locomotor and stereotypic effects of the amphetamines that occur with repeated intermittent administration. Rats pretreated daily with MAP (5 mg/kg) for 5 or 12 days showed neither tolerance nor sensitization to the analeptic effect of subsequent MAP administrations. 3H-quinuclidinyl benzilate-binding studies also showed no changes in muscarinic binding characteristics of membranes prepared from cortex or hippocampus of rats pretreated chronically with MAP. These and our earlier studies suggest that the analeptic effect of MAP is mediated via a dopaminergic-cholinergic mechanism.

Animals↗
PubMed1994

Effect of NS-3, a thyrotropin-releasing hormone analog, on in vivo acetylcholine release in rat brain: regional differences and its sites of action.

The effects of thyrotropin-releasing hormone (TRH) and its analog, NS-3 [CG-3703: (3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl- prolinamide tetrahydrate], on acetylcholine (ACh) release were examined in the rat brain by using in vivo microdialysis, and possible sites of action of NS-3 were subsequently examined. Both NS-3 (0.1 and 0.3 mg/kg i.v.) and TRH (3 mg/kg i.v.) produced an increase in the ACh release from the cerebral cortex and hippocampus but not from the striatum, although the action of NS-3 was much longer in duration than that of TRH. The ACh-releasing action of NS-3 was more marked in the hippocampus than in the cerebral cortex. Application of NS-3 (0.1-10 microM) via a dialysis probe into the nucleus basalis Meynert but not into the cortex caused a rapid and significant increase in cortical ACh release. Similarly, hippocampal ACh release was elevated by NS-3 (1 microM) perfused into the medial septum-diagonal band but not into the hippocampus. These findings suggest that NS-3 produces regionally specific enhancement of ACh release in the rat brain, and such effects of NS-3 are far more potent and longer in duration than those of TRH. In addition, the nucleus basalis Meynert and medial septum-diagonal band may be the respective sites of action of NS-3 in enhancing cortical and hippocampal ACh release.

Acetylcholine↗
PubMed1994

Enhancement of noradrenaline release from rat frontal cortex by thyrotropin releasing hormone and its analog, (3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L-prolinami de, as studied by intracerebral microdialysis.

The effects of thyrotropin-releasing hormone (TRH) and NS-3 [CG-3703: (3R,6R)-6-methyl-5-oxo-3-thiomorpholinylcarbonyl-L-histidyl-L- prolinamide], a metabolically stable analog of TRH, on the extracellular concentration of noradrenaline (NA) in the frontal cortex of urethane anesthetized rats were examined by using intracerebral microdialysis coupled with high-performance liquid chromatography with electrochemical detection. NS-3 (0.1 and 0.3 mg/kg i.v.) produced a significant increase in NA release. This effect reached to its peak 20 to 40 min (174% of basal level) after NS-3 (0.3 mg/kg) injection and exhibited a duration of 80 min. TRH (10 mg/kg i.v.) also significantly increased NA concentrations to the same extent as that produced by 0.3 mg/kg of NS-3, although the effect of TRH was transient. Blockade of NA reuptake by perfusion with desipramine (10(-7) M) caused a gradual increase in extracellular NA concentration. NS-3 at 0.3 mg/kg (i.v.) produced a significant elevation of NA concentrations after desipramine perfusion. When NS-3 (10(-6) and 10(-5) M) was perfused to the frontal cortex through the dialysis probe for 1 hr, no significant change in cortical NA concentration was observed. In contrast, perfusion of NS-3 (10(-5) M) through the dialysis probe implanted into the locus ceruleus induced a significant increase in the cortical NA release. These results suggest that NS-3 is far more active than TRH in facilitating cortical NA release and that the locus ceruleus is one of sites of action of this drug.

Animals↗
PubMed1990

[Pharmacological studies of celiprolol: II. Alpha 2-Adrenoceptor blocking effects of a cardioselective beta-blocker, celiprolol].

alpha-Adrenoceptor blocking effects of the cardioselective beta-blocker celiprolol were tested. 1. Celiprolol antagonized the contractions induced by UK-14304, but not those by phenylephrine, in isolated rat tail arteries with a pA2 value of 4.95. 2. In the isolated rat vas deferens, twitch contractions elicited by the transmural electrical stimulation (TS) were almost blocked by TTX (10(-7) M). Clonidine inhibited the TTX-sensitive contraction in a concentration-dependent manner. Celiprolol produced little effect on the inhibitory effects of clonidine. The concentration-inhibition curve of clonidine was shifted to the right by yohimbine (10(-8) M), but not by prazosin (10(-8) M). 3. Although celiprolol slightly increased the 3H-efflux to TS from the [3H]-norepinephrine-loaded rat vas deferens, the increment was not significant. Yohimbine (10(-7) M) significantly increased the 3H-efflux. TTX (10(-7) M) and bretylium (3 x 10(-5) M) blocked the 3H-efflux. 4. In the spinal rat treated with propranolol (3 mg/kg, i.v.) and prazosin (0.1 mg/kg, i.v.), celiprolol (30 and 100 mg/kg, i.v.) and yohimbine (0.1-1 mg/kg, i.v.) inhibited the pressor response to clonidine. 5. These results indicate that celiprolol may have a weak alpha 2-blocking effect which was more effective on postsynaptic alpha 2-receptors than presynaptic ones.

Adrenergic alpha-Antagonists↗
PubMed1990

[Effect of zirconium on immunological reactions of T cells and macrophages in mice].

The effects of zirconium (Zr) on T cells and macrophages in mice were studied in vitro using the indexes of immunological reactions, mitogenesis of C3H/HeJ mouse thymocytes induced by PHA and the production of interleukin-1 of C3H/He mouse intraperitoneal macrophages (MIL-1). The mitogenesis of thymocytes induced by PHA when stimulated with Zr solutions at various concentrations or culture supernatants of macrophages stimulated with LPS and Zr, or Zr alone, ware as shown below. 1. The mitogenesis of thymocytes by PHA was enhanced in the presence of Zr at 0.625-2.5 microM, and suppressed in the presence of Zr at 5-10 microM in culture 2. This reaction was enhanced by the addition of supernatants of macrophages stimulated with LPS and Zr. The most activation by LPS and Zr was shown at concentrations of 0.625-1.25 microM in culture, and the degree activated corresponding to 12.5-25 I.U. of MIL-1. 3. On the other hand, this reaction was inhibited by addition of supernatants of macrophages stimulated with Zr alone. From these results, it is suggested that Zr serves various functions such as an activator or inhibitor of T-cell mitogenesis by PHA, and that this may depend upon the Zr concentration in culture. In regard to the effect of Zr on MIL-1 production, Zr may activate this reaction by LPS, and Zr alone may induce MIL-1 production from macrophages.

Animals↗
PubMed1989

Enhancement of phosphatidylinositol turnover and cyclic nucleotide accumulation by chronic anethole trithione treatment in rat submaxillary glands.

The effect of chronic treatment with anethole trithione (ANTT) on the phosphatidylinositol (PI) turnover and cyclic (c)AMP and cGMP accumulation in rat submaxillary glands (SMG) has been compared with the effect of chronic treatment with atropine and a cholinesterase inhibitor, diisopropylfluorophosphate (dyflos, DFP). Experiments were performed 24, 48 and 24 h after the last dose of ANTT, atropine and dyflos, respectively. ANTT and atropine enhanced carbachol-stimulated [32P] incorporation into phosphatidic acid in the SMG slices, while dyflos showed no effect. Pilocarpine-stimulated in-vivo incorporation of [3H]myoinositol into inositol phosphates was significantly enhanced by ANTT, but not by atropine or by dyflos. Phospholipase C-dependent hydrolysis of phosphatidylinositol 4,5-bisphosphate was significantly enhanced by ANTT and atropine, but not by dyflos. Pilocarpine-stimulated in-vivo accumulation of cAMP and cGMP was enhanced by ANTT and atropine, but dyflos reduced cAMP accumulation without affecting cGMP accumulation. The enhancement of PI turnover and cyclic nucleotide accumulation seems to contribute to the development of supersensitivity of the salivary gland caused by chronic treatment with ANTT and atropine, while reduction of cAMP accumulation may be responsible for the subsensitivity caused by dyflos.

Anethole Trithione↗
PubMed1989

[Immunotoxicity of cobalt and nickel--experimental study on cytotoxicity of immuno-sensitive metals].

The effects of cobalt (Co) and nickel (Ni) on the humoral immune response were studied by two indexes of specific IgM antibody production against sheep red blood cells (SRBC) and polyclonal IgG antibody production in the spleens of mice intraperitoneally injected with cobalt chloride or nickel chloride. An experiment for the effect of both metals on specific IgM production was carried out by measuring IgM plaque-forming cells in the spleens of mice intraperitoneally injected with both metal salts using 1/10, 1/100 or 1/200 of LD50 for i.p. injection three times every other day and were immunized with SRBC on the day of the last injection of each metal salt. The other experiment for the effect of both metals on polyclonal IgG production was done by measuring, on days +3 or +6 in relation to the last injection of metal salts, polyclonal IgG-forming cells in the spleens of mice injected with both metal salts using 1/10 or 1/100 of LD50 for i.p. injection three times every other day by the reverse plaque-forming method. The following results may be drawn from this study: 1. Co may cause changes in the homeostasis of humoral immune response even more than affecting the immune system with immunotoxicity as antigenicity. 2. On the other hand, Ni may have antigenicity even more than an acting as immunomodulator influencing the immune system.

Adjuvants, Immunologic↗
PubMed1989

[A case of secretory carcinoma of the breast in a elderly Japanese woman].

We report a case of a secretory carcinoma of the breast in a 72-year-old woman with a long history of a left breast mass. Rapid growth and skin invasion of the tumor was noticed three months before a radical mastectomy was performed and a lung metastasis was found one month after the operation. A metastasis to the axillary nodes was noted in 6 of 9 resected specimens and a receptor assay of the estrogen and progesterone proved to be negative. This patient is the oldest case of a secretory carcinoma of the breast reported in Japan.

Adenocarcinoma↗
PubMed1988

Fitting of a binomial distribution to the number of chiasmata per bivalent.

Statistical tests on the distribution of the number of chiasmata per chromosome, collected from literatures, showed that they can be approximated by binomial distributions with one obligatory chiasma, i.e., B(N-1, p). N is proportional to the average number of chiasmata, while p is nearly constant for the species tested.

Analysis of Variance↗
PubMed1988

Pharmacological studies on anethole trithione.

Pharmacological studies on trithio-p-methoxy-phenylpropene (anethole trithione, ANTT, Felviten) were performed. ANTT at a dose of 100 mg/kg, p.o. lowered the increased serum transaminases GOT and GPT, and protected the liver from injuries caused by CCl4 in mice. In other studies in vivo, ANTT at a dose of 1000 mg/kg showed no effect on the central nervous system or the autonomic nervous system. In vitro experiments with smooth muscle preparations showed no significant effects of ANTT.

Anethole Trithione↗
PubMed1986

Effects of a new dihydropyridine calcium antagonist on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding.

The effects of methyl 2,6-dimethyl-4-(2-nitrophenyl)-5-(2-oxo-1,3,2-dioxaphosphorinan-2- yl)-1,4- dihydropyridine 3-carboxylate (DHP-218), a new dihydropyridine calcium antagonist, on vascular smooth muscles, cardiac muscles and [3H]-nitrendipine binding to the cardiac muscle and brain membranes were investigated in vitro. Vascular smooth muscles: Calcium-induced contraction of the rat aorta in high K+ solution was inhibited by DHP-218 with the pA2 value of 9.11. The IC50 value for the inhibitory effects of this compound in high K+-induced and phenylephrine-induced contraction was 6.3 nmol/l and 66 nmol/l, respectively. Vasodilatory effects of this drug on various blood vessels of rabbits contracted by high K+ appeared to a similar extent. The onset of the vasodilatory effect was very slow and the recovery rate of vasodilatory response after washout with the bathing solution containing high K+ or phenylephrine was also very slow. Cardiac muscles: Negative chronotropic and inotropic actions were observed at concentrations more than 30 and 100 nmol/l, respectively. Duration of the plateau phase of normal action potential was shortened and the amplitude and duration of slow action potential were reduced at concentrations more than 1 mumol/l. Very high vasculoselectivity was observed. Displacement of [3H]-nitrendipine binding: The pattern of displacement of [3H]-nitrendipine binding by DHP-218 was very similar to that of other 1,4-dihydropyridines but this compound was about 70 times less potent than nifedipine in [3H]-nitrendipine displacement capacity. These results indicate that DHP-218 has specific vasodilatory action due to calcium antagonism, but association and dissociation rates with tissue and receptors were different from those of nifedipine.

Action Potentials↗
PubMed1984

Chronic anethole trithione treatment enhances the salivary secretion and increases the muscarinic acetylcholine receptors in the rat submaxillary gland.

Chronic treatment with trithio-p-methoxyphenylpropene (anethole trithione; ANTT) increased the salivary secretion from the rat submaxillary gland induced by electrical stimulation of the parasympathetic nerve and by injection of pilocarpine. In parallel with the enhancement of the salivary secretion, the number of the muscarinic acetylcholine receptors was significantly increased. The increased number of receptors may be involved in the enhancement of the salivary secretion by ANTT treatment.

Anethole Trithione↗