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Biomedical subjects

Y Kataoka

Publications and source records attributed to Y Kataoka.

At least 91 records · Page 5Linked to original sources

Capillary electrophoresis for therapeutic drug monitoring of antiepileptics.

We examined the use of capillary electrophoresis for therapeutic drug monitoring of antiepileptic drugs. Micellar electrokinetic capillary chromatography (MEKC) with a diode array detector simultaneously determined concentrations of zonisamide, a new type of antiepileptic drug, and phenobarbital, phenytoin and carbamazepine, typical antiepileptic drugs, in human serum. Zonisamide levels in human serum obtained by MEKC correlated well with levels obtained by high-performance liquid chromatography. The serum levels of phenobarbital, phenytoin and carbamazepine determined by MEKC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MEKC for intra- and inter-day assays were appropriate. This MEKC method could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs, especially in patients treated with a combination of zonisamide and other antiepileptic drugs. MEKC may be an attractive method for therapeutic drug monitoring, because of its specificity of separation, automation of procedure, ease of method development, low cost, small aqueous buffer amounts, speed of analysis, small injection volume and high environment-directed performance.

Anticonvulsants↗

Quality evaluation by capillary electrophoresis of amphotericin B injection after filtration through various membrane filters.

The determination of amphotericin B, an antifungal agent, was developed using micellar electrokinetic capillary chromatography (MEKC) with a diode array detector. Repeatability and intermediate precision of MEKC analysis were acceptable. A high correlation was found between amphotericin B levels in pharmaceutical solutions obtained by MEKC and those by high-performance liquid chromatography (HPLC) (r = 0.994). This MEKC method is therefore useful for the determination of amphotericin B. The concentration of amphotericin B did not significantly change after filtration through polyethersulfone (PES, 0.2 microm) and polyvinylidene difluoride (PVDF, 0.45 microm) membrane filters. When the Fungizone injection was filtered through PES (0.2 microm) and added to 5% dextrose for injection (500 mL), particulate matters larger than 10 microm decreased by 64% to a level under the standard defined by United States Pharmacopoeia (USP XXIII). PVDF filtration (0.45 microm) did not have this effect. Our results suggest that filtration of Fungizone injection through PES (0.2 microm) membrane filters is recommended for the preparation of intravenous amphotericin B fluid.

Amphotericin B↗

Pasteurella multocida infection in the chicken embryo.

Pasteurella multocida infection in embryonated chicken eggs was studied by chorio-allantoic membrane inoculation. Strain differences were demonstrated in terms of lesion severity and time to death, especially during the first 24 h post-inoculation. A strain of low virulence gave a clear dose response but more virulent strains did not. Comparable results were obtained by infecting 6-week-old chickens. The main lesions in inoculated embryos appeared as severe vascular involvement of the entire embryo and feather tracts, thickening of the chorio-allantoic membrane, and enlargement and congestion of the yolk sac. The bacteria were demonstrated by transmission electron microscopy, either extracellularly or multiplying intracellularly in hepatocytes, heart tissue, and in the hyperplastic layer of the chorio-allantoic membrane, with resulting damage to the cellular organelles, and severe tissue changes.

Allantois↗

Impaired motor coordination in mice lacking prion protein.

1. Prion protein (PrPC) is a host-encoded glycoprotein constitutively expressed on the neuronal cell surface. Accumulation of its protease-resistant isoform is closely related to pathologic changes and prion propagation in the brain tissue of a series of prion diseases. However, the physiological role of PrPC remains to be elucidated. 2. After long-term observation, we noted impaired motor coordination and loss of cerebellar Purkinje cells in the aged mice homozygous for a disrupted PrP gene, a finding which strongly suggests that PrPC plays a role in the long-term survival of Purkinje cells. 3. We also describe the resistance of the PrP null mice to the prion, indicating the requirement of PrPC for both the development of prion diseases and the prion propagation.

Animals↗

Direct and continuous electrochemical measurement of noradrenaline-induced nitric oxide production in C6 glioma cells.

1. Nitric oxide (NO) production in C6 glioma cells was directly monitored in real time by electrochemical detection with a NO-specific biosensor. 2. We present here the first direct evidence that noradrenaline elicits long-lasting NO production in C6 cells pretreated with lipopolysaccharide and interferon-gamma, an effect blocked by NG-monomethyl-L-arginine, a NO synthase inhibitor. 3. This direct electrochemical measurement of glia-derived NO should facilitate our understanding of the kinetics of glial signaling in glia-glia and glia-neuron networks in the brain.

Animals↗

Enhancement of replication of genetically engineered herpes simplex viruses by ionizing radiation: a new paradigm for destruction of therapeutically intractable tumors.

Human U-87 malignant glioma xenografts in mice were exposed to ionizing radiation, inoculated with a herpes simplex virus 1 mutant R3616 lacking both copies of the gamma 34.5 gene, or received both virus and radiation. Dual treatment caused a significantly greater reduction in volume or total regression of tumors than either radiation or infection alone. The significantly enhanced oncolytic effects of the combined treatment correlate with two-to five-fold enhanced replication in irradiated tumor cells than in tumors receiving virus only. In addition, in situ hybridization with viral DNA probes showed that infected tumor cells were the dominant landscape of irradiated tumors and much less apparent in the nonirradiated tumors administered this virus.

Animals↗

Biochemical and serological examination of beta-hemolytic streptococci isolated from slaughtered pigs.

A total of 170 beta-hemolytic streptococci isolated from lesions in slaughtered pigs during 1988 to 1995 were identified by biochemical and serological examinations. Of these, 132 strains (77.6%) were Streptococcus (S.) dysgalactiae and 38 strains (22.4%) were S. porcinus. The largest serological group of streptococci was group C (78 strains, 45.9%), followed by group L (43 strains, 25.3%), group U (14 strains, 8.2%), group G (11 strains, 6.5%), group E (5 strains, 2.9%), and group P (5 strains, 2.9%). Most of isolates from endocarditis (61 strains) and arthritis (25 strains) were group C S. dysgalactiae, but about 33.3% of the isolates from lymphadenitis were group L S. dysgalactiae (28 strains), followed by group C (14 strains, 16.7%), group U S. porcinus (14 strains, 14.3%), and group G (10 strains, 11.9%).

Abattoirs↗

[The relationship between respiratory function and the change in end-tidal nitrous oxide concentration].

The aim of the present study is to clarify the relationship between respiratory function and the rate of change in alveolar anesthetic concentration. We measured the concentration of end-tidal nitrous oxide (N2O) when 50% N2O was administered to 15 patients of ASA I possessing normal respiratory function during the course of propofol-100% oxygen anesthesia. All patients were ventilated at a rate of 8-10 ml.kg-1 x 8 times per minute using a conventional anesthetic ventilator with semi-closed circuit and 4 l.min-1 inflow of fresh gas. Arterial CO2 partial pressure was maintained at 36.2 +/- 1.8 mmHg and no significant circulatory change was observed while N2O was administered. The rate of increase of end-tidal N2O concentration in poor FEV1.0/FVC% group was significantly slower than that in high FEV1.0/FVC% group, while there was no relation between %VC and the end-tidal N2O concentration change. Since N2O is an inhaled anesthetic, it is well considered that the effect of FEV1.0/FVC% may be observed in other inhaled anesthetic although the magnitude of the effect may vary. The present result suggests that respiratory function, especially FEV1.0/FVC%, is an important factor affecting the rate of change in alveolar anesthetic concentration and, in lower FEV1.0/FVC% group, it takes more time to achieve the intended alveolar concentration.

Aged↗

Application of high-performance thin-layer chromatography for the detection of organophosphorus insecticides in human serum after acute poisoning.

We developed a rapid and simple method for identifying 25 commonly used organophosphorus insecticides in human serum using high-performance thin-layer chromatography (HPTLC). These organophosphates were separated on plates with three different developing systems within 6-18 min and detected by means of ultraviolet radiation and coloring reactions with 4-(4-nitrobenzyl)pyridine-tetraethylenepentamine reagent (NT reagent) or palladium chloride reagent (PdCl2 reagent). Each organophosphate was accurately identified by means of the R(F) x 100 value and the spot color in three systems. The detection limits of dichlorvos, fenitrothion, malathion, methidathion, parathion and trichlorfon in serum by the liquid-liquid extraction method were 1.1, 0.12, 0.12, 0.05, 0.6 and 0.1 microg/ml, respectively. These sensitivities may be sufficient to detect those organophosphates in patient serum after acute poisoning.

Chromatography, High Pressure Liquid↗

Propofol produces anticonflict action by inhibiting 5-HT release in rat dorsal hippocampus.

We examined the effect of propofol, an injectable anesthetic agent on conflict behavior in a Vogel type conflict test and on release of serotonin (5-hydroxytryptamine, 5-HT) in the dorsal hippocampus using an in vivo microdialysis method in rats. Propofol (20 and 40 mg/kg, i.p.) dose-dependently suppressed elevated 5-HT release normally seen in a conflict situation and concomitantly attenuated conflict behavior. These findings suggest that propofol exerts an antianxiety action by inhibiting 5-HT neuronal activity in the dorsal hippocampus.

Anesthetics, Intravenous↗

A postsynaptic excitatory amino acid transporter with chloride conductance functionally regulated by neuronal activity in cerebellar Purkinje cells.

Excitatory amino acid (EAA) neurotransmitters induce postsynaptic depolarization by activating receptor-mediated cation conductances, a process known to underlie changes in synaptic efficacy. Using a patch-clamp method, we demonstrate here an EAA-dependent postsynaptic anion conductance mediated by EAA transporters present on cerebellar Purkinje cell bodies and dendrites in culture. This transporter-mediated current was modulated by neuronal activity: it exhibited facilitation for >20 min after transient depolarization accompanied by Ca2+ influx. Evidence is presented suggesting that the transporter facilitation is mediated by arachidonate release after Ca2+-dependent activation of phospholipase A2, which exists in Purkinje cells. This postsynaptic reuptake system may represent a novel modulatory mechanism of synaptic transmission as well as prevent neuronal excitotoxicity.

Animals↗

Micellar electrokinetic capillary chromatography for therapeutic drug monitoring of zonisamide.

The simultaneous determination of zonisamide, a new type of antiepileptic drug, and the typical antiepileptic drugs phenobarbital, phenytoin and carbamazepine in human serum was developed using micellar electrokinetic capillary chromatography (MECC) with a diode array detector. A high correlation was revealed between the zonisamide levels in human serum obtained by MECC and those obtained by high-performance liquid chromatography (r=0.981). The serum levels of phenobarbital, phenytoin and carbamazepine determined by MECC were almost equal to those obtained by fluorescence polarization immunoassay. The reproducibility of separation and quantification with MECC analysis was appropriate for the intra- and inter-day assay coefficients. Therefore, the MECC method established here could provide a simple and efficient therapeutic drug monitoring method for antiepileptic drugs in patients, especially those treated with a combination of zonisamide and other antiepileptic drugs.

Anticonvulsants↗

Expression of endothelin receptors and nitric oxide synthase in the brain of stroke-prone spontaneously hypertensive rats with cerebral apoplexy.

Endothelin (ET) receptors, ET-1-like immunoreactivity and nitric oxide synthase (NOS) were examined in the brain of stroke-prone spontaneously hypertensive rats (SHRSPs) with cerebral apoplexy. Our receptor autoradiographic method with 125I-ET-1 and unlabeled selective ligands for ET receptors revealed de novo expressions of ET(A) and ET(B) receptors in areas of neural lesions with cerebrovascular damage in SHRSPs. Immunohistochemical staining for ET-1 showed clear ET-1-like immunoreactivity in areas with highly expressed ET receptors. Histochemical studies on astrocytes and microglia suggested that these glial cells, aggregating in lesions, may carry ET receptors, ET-1-like immunoreactivity. Furthermore, NOS detected histochemically using an NADPH-diaphorase staining method was rich on glial cells in damaged areas of the brain in SHRSPs with cerebral apoplexy. Our data suggest the pathophysiological significance of glial ET(A) and ET(B) receptors, ET-1 and NOS in neural lesions of SHRSPs.

Animals↗

Repeated interferon-alpha administration inhibits dopaminergic neural activity in the mouse brain.

In vivo effects of single and repeated interferon-alpha administrations on the dynamics of noradrenaline, dopamine and 5-hydroxytryptamine were investigated in the mouse brain. Single interferon-alpha administration (15, 30 and 60 X 10(6) U/kg i.p.) had no significant effect on the levels of monoamines and their metabolites or monoamine turnover. When interferon-alpha (15 X 10(6) U/kg i.p.) was administered once a day for 5 days, however, both dopamine and 3,4-dihydroxyphenylacetic acid levels were significantly decreased and alpha-methyl-p-tyrosine-induced dopamine depletion was significantly suppressed. These results suggest that repeated interferon-alpha administration inhibits dopaminergic neural activity. This inhibitory action of interferon-alpha in dopamine neurons may be involved in adverse central effects, such as parkinsonism and depression with suicidal potential.

Animals↗

Endothelin receptors in kainic acid-induced neural lesions of rat brain.

Seven days after an intracerebroventricular injection of 0.8 microgram kainic acid, a time of neural tissue-repair after damage, we applied our receptor autoradiographic method to examine changes in the endothelin receptors in kainic acid-induced neural lesions of the rat brain. There were belt-shaped areas with the de novo expressed [125I]endothelin-1 binding sites in the damaged hippocampus CA1, CA3, and CA4 subfields. We also noted a homogeneous zone with a low binding-density, the area sandwiched by the belt-shaped areas. In a "remote" area corresponding anatomically to the deep soma layer of the piriform cortex plus lateral parts of amygdaloid complex we noted a well-defined area with "punched hole-figure" of low density [125I]endothelin-1 binding sites. The lesion was surrounded by areas rich in binding sites. The de novo expressed [125I]endothelin-1 binding sites were characterized endothelin B receptor. Microglia were present in the area with "punched hole-figure" and in the hippocampus pyramidal cell layer with neuronal death. In contrast to microglia, astrocytes were rich with hypertrophia in kainic acid-induced neural lesions anatomically corresponding to areas with the de novo endothelin B receptor. Taken together with the present observations of microscopic evidence of cellular distribution, we suggest that the de novo expressed endothelin B receptor was carried by astrocytes aggregating in neural lesions. In light of our findings, the possibility that astrocytes can be activated by the endothelin B receptor in response to neural tissue repair after damage to neurons would have to be considered.

Animals↗

Prion protein is necessary for latent learning and long-term memory retention.

1. The cellular prion protein, designated PrPc, is a key molecule in the prion diseases but its physiological function remains unknown. To elucidate whether PrPc plays some role in the central nervous system, we established a line of mice in which the PrP gene had been disrupted and subsequently conducted long-term observations. 2. Performance in latent learning and passive avoidance was evaluated using water-finding and step-through tests, respectively. 3. PrP-/- mice showed impaired performance in the water-finding test, indicating a disturbance in latent learning, at 23 weeks of age. In the step-through test, although the PrP-/- mice showed normal learning ability and short-term memory retention, they evidenced a significant disturbance in long-term memory retention. 4. These results indicate that PrPc is needed for certain types of learning and memory and that the loss of function of this protein may contribute to the pathogenesis of prion diseases.

Animals↗