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Biomedical subjects

M Uchida

Publications and source records attributed to M Uchida.

At least 55 records · Page 3Linked to original sources
PubMed2001

Alterations of nitric oxide and monoamines in the brain of the EL mouse treated with phenobarbital and zonisamide.

The effects of phenobarbital (PB; doses, 5, 10, and 25 mg/kg, intraperitoneally (i.p.)) and zonisamide (ZNS; doses, 30, 75, and 150 mg/kg, i.p.) on nitric oxide (NO) production, and those of coadministration of PB (5 mg/kg, i.p.) and ZNS (75 mg/kg, i.p.) on monoamines in the brain of the seizure-susceptible EL mouse were investigated. Nitric oxide production was obtained by measuring the combined level of nitrite plus nitrate (NOx). Zonisamide and PB dose-dependently suppressed the seizure of the EL mouse, and coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) induced a greater degree of seizure suppression than treatment with ZNS or PB alone. Although PB (5 mg/kg) had no effect on brain NOx levels, ZNS (150 mg/kg) and coadministration of ZNS (75 mg/kg) and PB (5 mg/kg) decreased NOx levels significantly. Phenobarbital (5 mg/kg) did not influence monoamines, while coadministration of PB (5 mg/kg) and ZNS (75 mg/kg) decreased dihydroxyphenylacetic acid and increased 5-HT concentrations. The effect of the coadministration of two drugs on monoamines were similar to that of ZNS alone. These results suggest that one of the anticonvulsant effects of coadministration of PB and ZNS may be caused by changes in NOx levels.

Animals↗
PubMed2001

Influences of caffeine to nitric oxide production and zonisamide concentration in the brain of seizure-susceptible EL mice.

To investigate changes of nitric oxide (NO) productions and zonisamide (ZNS) concentrations in the brain of seizure-susceptible EL mice given caffeine orally, mice were given caffeine (600 microg/mL) solution ad libitum as a drinking fluid for 1-3 weeks. Nitric oxide production in the brain was determined by measuring levels of nitrite plus nitrate (NOx). The brain NOx levels of mice treated with caffeine for 3 weeks were significantly higher than the control. Seizures in mice treated with caffeine for 2 and 3 weeks were not suppressed by ZNS at a dose of 75 mg/kg. Serum ZNS concentrations of mice with caffeine intake for 1-3 weeks were higher than in untreated mice. Conversely, brain ZNS concentrations of mice with caffeine intake for the same periods were significantly lower than in untreated mice. These results suggested that caffeine influenced brain NO production and ZNS concentrations in the seizure susceptibility of EL mice.

Animals↗
PubMed2001

The effects of alpha-human atrial natriuretic peptide and milrinone on pial vessels during blood-brain barrier disruption in rabbits.

UNLABELLED: The effects of alpha-human atrial natriuretic peptide (HANP) and milrinone on cerebral pial vessels, especially during blood-brain barrier (BBB) disruption, are not clear. We studied topical HANP (10(-14), 10(-12), and 10(-10) M) or milrinone (10(-7), 10(-5), and 10(-3) M), and IV HANP (0.1, 0.2, and 1.0 microg. kg(-1). min(-1)) or milrinone (0.5, 5.0, and 20.0 microg. kg(-1). min(-1)) with or without hyperosmolar BBB disruption, using a rabbit cranial window preparation. At 10(-12) and 10(-10) M topical HANP produced significant arteriolar (16%, 20%, respectively), but no venular dilation. Topical milrinone (10(-3) M) produced significant arteriolar and venular dilation (21%, 8%, respectively). IV HANP produced no arteriolar or venular changes at any dose except during BBB disruption, when it caused a significant arteriolar (16%, 16%, and 17%, respectively), but no venular dilation. In contrast, IV milrinone caused small but significant arteriolar and venular dilation without BBB disruption (arterioles, 6%, 7% and 8%, respectively; venules, 6% at 20.0 microg. kg(-1). min(-1)). During BBB disruption, these responses to milrinone were similar. Although HANP and milrinone each have a direct vasodilator effect on arterioles, their systemic administration at clinical doses could induce different effects. BBB disruptive conditions could increase the response of pial vessels to systemically administered HANP. IMPLICATIONS: Although alpha-human atrial natriuretic peptide (HANP) and milrinone each have a direct vasodilator effect on cerebral pial arterioles, their systemic administration at clinical doses could have different effects and blood-brain-barrier disruptive conditions could alter the response of pial vessels to HANP, but not to milrinone.

Animals↗
PubMed2001

The differential effects of stereoisomers of ropivacaine and bupivacaine on cerebral pial arterioles in dogs.

UNLABELLED: We investigated whether the stereoisomers of ropivacaine and bupivacaine exert differential effects on the cerebral microcirculation. Pentobarbital-anesthetized dogs (n = 16) were prepared for measurement of cerebral pial vessel diameters by using a closed cranial window preparation. We administered three different concentrations (10(-7), 10(-5), and 10(-3) M) of each of three drug solutions [R(+), racemic, and S(-) forms of ropivacaine (n = 8) or bupivacaine (n = 8)] under the window in a randomized manner and measured cerebral pial arteriolar diameters. Various physiologic data were obtained before and after topical application of each test solution. All three forms of ropivacaine constricted cerebral pial arterioles, each in a concentration-dependent manner. The rank order for degree of vasoconstriction was S(-) ropivacaine > racemic ropivacaine > R(+) ropivacaine. In contrast, R(+) and racemic bupivacaine dilated, but S(-) bupivacaine constricted, cerebral pial arterioles, each in a concentration-dependent manner. We could find no difference in vascular reactivity to these drugs between large (> or = microm) and small (<100 microm) arterioles. Topical application of these drugs induced no changes in mean blood pressure or heart rate. The observed differences in the microvascular alterations induced by the stereoisomers of ropivacaine and bupivacaine suggest that the vasoactive effects of these drugs on cerebral arterioles could, at least in part, depend on their chirality. IMPLICATIONS: The differential effects of the stereoisomers of ropivacaine and bupivacaine on cerebral pial vessels could, at least in part, depend on their chirality.

Amides↗
PubMed2001

Antidepressant effects of apocynum venetum leaves in a forced swimming test.

An extract of the leaves of Apocynum venetum L. (Apocynaceae) markedly shortened the immobility time of male rats in a forced swimming test (FST) in a dose range of 30-125 mg/kg, indicating a possible antidepressant activity. This effect was comparable to that of the tricyclic antidepressant imipramine (20 mg/kg). Neither imipramine (20 mg/kg) nor the Apocynum extract in various doses (30, 60, 125 mg/kg) produced any overt behavioural change or motor dysfunction in the open field test. This result confirms the assumption that the antidepressant effect of an Apocynum extract in the FST is specific. Further, it can be speculated that this effect might be related to hyperoside and isoquercitrin which are major flavonoids in the extract.

Animals↗
PubMed2001

Studies on new platelet aggregation inhibitors 1. Synthesis of 7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives.

A series of 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-ones were prepared and tested for platelet aggregation inhibitory effect, cardiotonic activity and chronotropic activity. These compounds appeared to show selective inhibitory activity against platelet aggregation. Among them, 6-(4-ethoxycarbonylpiperidino)-7-nitro-3,4-dihydroquinoline-2(1H)-one (22f) showed the most potent inhibitory activity and high selectivity. A divergent synthetic route to 6-cyclic aliphatic amino-7-nitro-3,4-dihydroquinoline-2(1H)-one derivatives has also been investigated.

Acetylation↗
PubMed2001

Nitric oxide donating compounds inhibit HCl-induced gastric mucosal lesions mainly via prostaglandin.

Prostaglandin (PG) and nitric oxide (NO) have been known to inhibit the lesion formation induced by necrotic agents. However, no clear correlation between PG and NO has been shown in the gastroprotective action against necrotic agent-induced gastric mucosal lesions in rats. Thus, the present study was performed to clarify this correlation. Gastric mucosal lesions were induced by the oral administration of 0.6 M HCl in rats. 16,16-Dimethyl PGE2 (0.3-3 microg/kg, p.o.; dim-PGE2), sodium nitrite (0.3 and 1 mg/kg, s.c.) and sodium nitroprusside (30 and 100 microg/kg, i.v.; SNP) dose-dependently inhibited the lesion formation. Orally administered sodium nitrite or SNP (3 mg/kg) also significantly inhibited the lesion formation. The gastroprotective action by dim-PGE2 was not affected by the pre-treatment with N(G)-nitro-L-arginine methylester (10 mg/kg, i.v.). The gastroprotective effect by sodium nitrite or SNP was markedly attenuated by the pre-treatment with indomethacin (10 mg/kg, s.c.). These findings suggest that NO donating compounds inhibit the HCl-induced mucosal lesions mainly through prostaglandin, but dim-PGE2 directly inhibits the lesions without involvement of NO in rats.

16,16-Dimethylprostaglandin E2↗
PubMed2001

Enhancement of phenylephrine-induced contraction in the isolated rat aorta with endothelium by H2O-extract from an Oriental medicinal plant Leonuri herba.

Leonuri herba (I-mu-ts'ao, the Chinese motherwort) is an ancient Chinese traditional herb. Although the pharmacological effects of extracts of Leonuri herba have been shown in platelets and uteri, the effect on the vascular system has not been determined. In the present study, we investigated the effects of extracts of Leonuri herba on the contraction of the isolated rat aorta. Although the H20-extract (0.3-3 mg/ml) by itself showed a limited effect, the extract enhanced phenylephrine-induced contraction of the aorta with endothelium, but not without endothelium. The H20-extract, like N(G)-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase), significantly inhibited the relaxation induced by acetylcholine in the aorta with endothelium. The inhibitory effect of H20-extract on the relaxation decreased by co-addition with 1 mM L-arginine. The vasoconstrictive effect of H20-extract was not due to leonurine, which is a constituent in Leonuri herba and shows uterotonic activity. Intravenous injection of the H20-extract (1.5 mg/kg) to rats caused an increase in blood pressure for 5 min, like L-NAME (1.35 mg/kg). These findings suggest that there is a component(s) in Leonuri herba, which shows a vasoconstrictive activity in rat aorta in vitro and in vivo and has similar pharmacological profile to that of L-NAME.

Animals↗
PubMed2001

Transcriptional induction of matrix metalloproteinase-13 (collagenase-3) by 1alpha,25-dihydroxyvitamin D3 in mouse osteoblastic MC3T3-E1 cells.

The removal of unmineralized matrix from the bone surface is essential for the initiation of osteoclastic bone resorption because osteoclasts cannot attach to the unmineralized osteoid. Matrix metalloproteinases (MMPs) are known to digest bone matrix. We recently reported that among the MMPs expressed in mouse osteoblastic cells, MMP-13 (collagenase-3) was the one most predominantly up-regulated by bone resorbing factors including 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)2D3]. In this study, we examined the mechanism of regulation of MMP-13 expression by 1alpha,25(OH)2D3 in mouse osteoblastic MC3T3-E1 cells. 1Alpha,25(OH)2D3 increased steady-state messenger RNA (mRNA) and protein levels of MMP-13. De novo protein synthesis was essential for the induction because cycloheximide (CHX) decreased the effect of 1alpha,25(OH)2D3 on the MMP-13 mRNA level. 1Alpha,25(OH)2D3 did not alter the decay of MMP-13 mRNA in transcriptionally arrested MC3T3-E1 cells; however, it increased the MMP-13 heterogeneous nuclear RNA (hnRNA) level and MMP-13 transcriptional rate. The binding activity of nuclear extracts to the AP-1 binding site, but not to the Cbfa1 binding site, in the MMP-13 promoter region was up-regulated by 1alpha,25(OH)2D3, suggesting the mediation of AP-1 in this transcriptional induction. To determine the contribution of MMPs to bone resorption by 1alpha,25(OH)2D3, the inhibitory effect of BB94, an MMP inhibitor, on resorbed pit formation by mouse crude osteoclastic cells was examined on either an uncoated or collagen-coated dentine slice. BB94 did not prevent resorbed pit formation on uncoated dentine whereas it did on collagen-coated dentine. We therefore propose that the transcriptional induction of MMP-13 in osteoblastic cells may contribute to the degradation of unmineralized matrix on the bone surface as an early step of bone resorption by 1alpha,25(OH)2D3.

3T3 Cells↗
PubMed2001

Simultaneous detection of cholyl adenylate and coenzyme A thioester utilizing liquid chromatography/electrospray ionization mass spectrometry.

It has been proposed that acyl adenylate is first formed during activation of the carboxy group into the acyl CoA thioester, an intermediate in the formation of amino acid conjugates. Acyl CoA synthetases may be responsible for this acyl adenylate formation. Recently, we hypothesized the preferential formation of cholic acid adenylate, a major bile acid, preceding production of the corresponding CoA thioester in incubations with rat liver microsomal fractions. To verify this biosynthetic mechanism, monitoring of the incubation mixture of acyl adenylate together with both substrate and acyl CoA thioester is needed. We have developed a detection method for the simultaneous detection of these cholic acid derivatives utilizing liquid chromatography/electrospray ionization mass spectrometry. The CoA thioester of cholic acid forms a chelation complex with the divalent cations remaining on the silica gel packed into the analytical column. Both the addition of a chelating agent, such as EDTA, to the mobile phase and an adjustment of the mobile phase pH to a weak alkaline effectively removed such chelate formation, producing a sharp CoA thioester peak. For a simultaneous mass spectrometric analysis of cholic acid, the corresponding adenylate and CoA thioester, the combined use of a 300 A particle diameter ODS column and 20 mM ammonium acetate buffer (pH 9.0)/2-propanol/acetonitrile as the mobile phase have been proved to be preferable. To avoid any degradation of the chemically unstable adenylate produced in the incubation, we employed a direct injection of the sample onto a preconcentration column. The obtained results indicated a high sensitivity of this method.

Adenosine Monophosphate↗
PubMed2001

CAM-cytarabine, aclarubicin plus macrophage colony-stimulating factor in the treatment of acute myelogenous leukemia with trilineage dysplasia: usefulness of in vitro apoptosis in leukemic cells.

A 67-year-old woman was treated for acute myelogenous leukemia with trilineage dysplasia (AML-TLD) by combination chemotherapy with cytarabine, aclarubicin plus macrophage colony-stimulating factor (M-CSF) (referred to as CAM therapy). Complete remission was achieved after two courses of CAM therapy. After coculture of her bone marrow mononuclear cells with M-CSF in vitro, differentiation of leukemic cells into macrophages with apoptotis was observed. This case confirms an earlier report that an effect of M-CSF inducible by differentiation with apoptotic phenomena, against human leukemic cells was shown both in vitro and in vivo when achieving complete remission.

Aged↗
PubMed2001

Long-term follow-up of asymptomatic patients with major artery occlusion: rate of symptomatic change and evaluation of cerebral hemodynamics.

BACKGROUND AND PURPOSE: The natural history of asymptomatic major cerebral artery occlusive disease is unclear. Rate of symptomatic change, appearance of new lesions on MR images, and cerebral hemodynamics were analyzed for patients with asymptomatic major cerebral artery occlusion. METHODS: This prospective study included asymptomatic patients who had occlusive disease between 1992 and 1995. MR imaging and MR angiography were used to detect internal carotid artery (ICA) or middle cerebral artery (MCA) occlusion in 3965 neurologically asymptomatic patients and for follow-up of affected patients for 67 to 105 months (mean, 79 months). Regional cerebral blood flow and cerebrovascular reserve capacity were examined by xenon-enhanced CT at rest and after the administration of acetazolamide, respectively. RESULTS: Eighteen patients had MCA occlusion and 17 had ICA occlusion. During the follow-up period, five patients became symptomatic (four with MCA occlusion and one with ICA occlusion), with no significant difference (P = .332) in the rate of symptomatic change. Among these five patients, new infarction occurred on the ipsilateral side in three patients, contralateral side in one, and bilateral sides in one. New stenotic or occlusive changes occurred in three patients. The patients were divided into groups: group A, without new lesions on MR images (n = 23), and group B, with new lesions (n = 12). There was no significant difference in regional cerebral blood flow value between groups A and B in the whole hemisphere, anterior cerebral artery territory, or MCA territory. There was a significant difference in cerebrovascular reserve capacity between groups A and B between the affected side (P = .00051 and P = .00068, respectively) and the contralateral side (P = .00101 and P = .00115, respectively) for the whole hemisphere and MCA territory, and the difference was more severe on the affected side in both regions. CONCLUSION: These pilot data suggest that asymptomatic MCA occlusion has a worse prognosis than does ICA occlusion. Silent events are common bilaterally. This may be because of hemodynamic factors or perhaps MCA occlusion is a marker for a more progressive type of atherosclerosis. A prospective study involving assessment of hemodynamics and baseline stroke risk factors in patients with MCA occlusion is indicated.

Aged↗
PubMed2001

[Contrivance for frozen section diagnosis of early minute lung cancer during operation].

We reported the technique of pathological diagnosis for minute lung cancer lesion of early stage during operation. Target lesion for our technique may be less than 1 cm in size and not be detected by palpation. Our technique may superior to usual method of frozen section of tissue specimen without fixation. At first, resected lung specimen was fixed by injection of 20% formalin solution subsequent warming by microwave oven for 40 seconds. Almost all lesions may be detected in proper thickness of specimen. Specimen was washed out and steeped in the 20% of sucrose solution for 30 to 60 seconds in order to avoid crystallization of water that was contained within lung specimen. Then thin sliced section of specimen was made by Cryostat in usual method. The minute cancer lesion was able to detect more easy than usual method of making frozen section of specimen. Formalin fixed and sucrose steeped frozen section may be able to evaluate the surgical margin from cancer exactly than the section made by non-fixed specimen.

Frozen Sections↗
PubMed2001

[Transdermal microparticle delivery by a supersonic-Helios gun system].

AIM: To investigate the effect of particle size and high speed flow of helium gas on the systemic absorption of indomethacin using a needle-less injection system. METHODS: Poly-L-lactic acid microspheres containing indomethacin was prepared by the o/w solvent evaporation technique. After anesthetizing the male hairless rat, microspheres filled in the tube cartridge was accelerated by a stream of helium gas at various velocity in the Helios gun system, and then was introduced to the abdominal skin. RESULTS: Introduction of indomethacin to the hairless rat skin was proportionally increased with enhancing the helium pressure (supersonic flow). Bioavailability and Cmax were also dependent on the helium pressure. CONCLUSION: This method can be used to deliver the powered drug and/or microparticulate systems into the skin tissues and the systemic circulation.

Administration, Cutaneous↗
PubMed2000

Poly(ADP-ribose) polymerase localizes to the centrosomes and chromosomes.

Poly(ADP-ribose) polymerase (PARP) takes part mainly in regulation of DNA repair, thereby maintaining genomic stability in the nucleus. However, what role PARP plays in mitotic cells is not known. Centrosomes play an important role in maintaining the fidelity of chromosome distribution during cell division. Loss of these functions might cause chromosomal instability and aneuploidy. p53 and BRCA1 were recently found to localize to the centrosome at mitosis. We found that PARP is localized to the centrosomes and the chromosomes at cell-division phase and interphase by indirect immunofluorescence. Furthermore, by analysis of isolated centrosomes PARP protein was found to associate with the centrosomes during mitosis. These data suggest that PARP may be involved in maintenance of chromosomal stability.

Cell Line↗
PubMed2000

Chlorination of harman and norharman with sodium hypochlorite and co-mutagenicity of the chlorinated products.

Harman and norharman are widely distributed in the environment and consequently contaminate in domestic waste-water. It has been reported that they have co-mutagenic activity in the presence of non- mutagenic aromatic amines such as aniline and o-toluidine with S9 mix. When these beta-carbolines were treated with sodium hypochiorite under mild conditions, chlorinated derivatives were produced. Among them, 6-chloroharman and 6-chloronorharman showed much more potent co-mutagenic activities than harman and norharman in the presence of o-toluidine toward Salmonella typhimurium TA98 with S9 mix. These results suggest that the chlorination of harman and norharman occurs during disinfection at the sewage plant to produce potent co-mutagens that contaminate river water.

Biotransformation↗
PubMed2000

Effects of combined administration of zonisamide and valproic acid or phenytoin to nitric oxide production, monoamines and zonisamide concentrations in the brain of seizure-susceptible EL mice.

This study was undertaken to elucidate the anticonvulsive effects of zonisamide (ZNS: 25, 50, and 75 mg/kg, intraperitoneal [i.p.]), which was coadministered with valproic acid (VPA: 25, 50, and 100 mg/kg, i.p.), or phenytoin (PHT: 10, 25, and 50 mg/kg, i.p.) to ZNS concentration, nitric oxide metabolites (NOx levels), and monoamines in the brain of the EL mouse, a strain highly susceptible to seizures. NOx levels were obtained from measuring of combined level of nitrite plus nitrate. Coadministration of ZNS with VPA or PHT suppressed convulsive seizures more effectively than with treatment of ZNS alone. Both serum and brain concentrations of ZNS tended to increase as the dose of VPA or PHT was increased. While coadministrations of ZNS (75 mg/kg) and VPA or PHT at any dose did not change brain and serum NOx levels, those altered brain monoamine contents. These results suggested that anticonvulsive effect of coadministrations of ZNS and VPA or PHT were caused by changes of monoamines rather than changes of NO metabolites.

Animals↗