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Biomedical subjects

K Ishihara

Publications and source records attributed to K Ishihara.

At least 253 records · Page 14Linked to original sources

Inhibition by gamma-aminobutyric acid system activation of epileptic seizures in spontaneously epileptic rats.

The effects of muscimol, a gamma-aminobutyric acid (GABA)A-receptor agonist, and aminooxy-acetic acid (AOAA), an inhibitor of GABA-converting enzyme, on tonic and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) were investigated to elucidate whether GABAergic function operates normally in these animals. Muscimol at doses of 1 and 3 mg/kg (i.p.) induced high-voltage slow waves in the cortical and hippocampal EEG of SER, although the behavioral observation suggested inhibition of absence-like seizures. Similar high-voltage slow waves were also observed in the cortical and hippocampal EEG of normal rats with muscimol (1 and 3 mg/kg). Tonic convulsions in SER were dose-dependently inhibited by muscimol. AOAA (3 and 10 mg/kg, i.v.) inhibited both tonic and absence-like seizures in SER, although there were no obvious changes in EEG pattern. The inhibitory effects of AOAA on tonic convulsions appeared more slowly and lasted longer than those on absence-like seizures. Cerebral, hippocampal and cerebellar GABA levels were significantly higher in SER than the normal Kyo:Wistar and zitter rat (zi/zi), which were both the parent strains. These findings suggest that GABA receptors and GABAergic neurons are functional in SER and that the GABA system is involved in the inhibition of both seizures.

4-Aminobutyrate Transaminase↗

Protection against glutamate neurotoxicity in retinal cultures by acidic conditions.

We evaluated the effects of extracellular acidic conditions on glutamate-induced death in cultured retinal neurons. Primary retinal cultures, obtained from 3- to 5-day-old Wistar rats, were estimated to be consisted of mainly amacrine cells (90%) together with a small population of horizontal (8%) and ganglion cells (2%). We examined the effects of acidic pH (pH 6.0 to 7.0) on glutamate neurotoxicity by monitoring the delayed death of retinal neurons induced by brief (10 min) exposure to 1 mM glutamate followed by a 24-hr incubation. The glutamate-induced delayed death of cultured retinal neurons was attenuated with an acidic pH between 6.0 and 7.0. Furthermore, whole-cell patch-clamp recordings were taken from retinal neurons to examine the effects of acidic pH on N-methyl-D-aspartate (NMDA) or kainate receptor-mediated currents. NMDA- and kainate-induced currents were suppressed at pH 6.0 to 7.0 and pH 6.0 to 6.5, respectively. The acidity of the medium protected the retinal neurons from glutamate-induced delayed death, probably by inhibiting NMDA and/or kainate receptor activation.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Inhibition of icosanoid production in MC/9 mouse mast cells by n-3 polyunsaturated fatty acids isolated from edible marine algae.

The effects of two polyunsaturated fatty acids, 18:4n-3 and 16:4n-3 purified from the marine algae, Undaria pinnatifida and Ulva pertusa, on icosanoid production in MC/9 mouse mast cells were assessed. Both fatty acids suppressed the production of leukotriene B4 (LTB4), leukotriene C4 (LTC4), and 5-hydroxyeicosatetraenoic acid (5-HETE). The order of the suppressive activity for the two marine algae-derived fatty acids and three other common polyunsaturated fatty acids was as follows; 22:6n-3 = 18:4n-3 = 18:3n-3 > 20:5n-3 = 16:4n-3 for LTB4; 22:6n-3 = 18:4n-3 = 18:3n-3 > 16:4n-3 > 20:5n-3 (no suppression) for LTC4; 22:6n-3 = 18:4n-3 > 18:3n-3 > 20:5n-3 = 16:4n-3 for 5-HETE.

Animals↗

Inhibition by a capsaicin antagonist (capsazepine) of capsaicin-induced swimming capacity increase in mice.

We investigated the endurance swimming capacity of mice injected with CAP antagonist (capsazepine). The increase of endurance swimming capacity by the administration of CAP was significantly suppressed by the injection of capsazepine. At the same time, serum adrenaline secretion, which was induced by CAP, was depressed by capsazepine. These findings suggested that the increase in endurance swimming capacity by CAP was mediated by the CAP receptor.

Animals↗

Effect of roxatidine bismuth citrate (MX1) against acetylsalicylic acid- and indomethacin-induced gastric mucosal damage in rats.

We have studied the effect of the newly synthesized agent, roxatidine bismuth citrate (N-[3-(3-(1-piperidinyl-methyl)phenoxy)propyl]-hydroxyacetamide-2- hydroxypropane-1,2,3-tricarboxylate-bismuth(3+) complex), code name MX1, against acetylsalicylic acid (ASA)- and indomethacin-induced gastric mucosal damage in rats. Effects of MX1 (12.5, 50, 125, 184, 250 mg/kg) were compared to the effects of equimolar doses of roxatidine and bismuth subcitrate. Effect of MX1 (10(-6) M) on mucin biosynthesis measured by [3H] glucosamine incorporation in rat gastric corpus has been determined. MX1-pretreatment dose-dependently decreased the mean ulcer number and length in all doses used in an extent similar to that of roxatidine and more pronounced in comparison with bismuth subcitrate. The morphometrical results have been confirmed histomorphologically. The biosynthesis of mucin was found to be significantly enhanced after MX1 addition. The results of the present study suggest that MX1 has a gastroprotective effect against ASA- and indomethacin-induced ulcers which might be due both to its H2-blocking and mucus-stimulating activity.

Animals↗

Dynamics of serum immunoglobulin G avidity for Porphyromonas gingivalis in adult periodontitis.

The purpose of this study was to examine avidity of immunoglobulin G (IgG) antibody for surface antigens of Porphyromonas gingivalis in sera from patients with adult periodontitis. The antigens used were whole cell antigens, lipopolysaccharides (LPS), and fimbriae of non-invasive P. gingivalis ATCC 33277 and invasive 16-1. Serum IgG titers for the P. gingivalis antigens were measured by enzyme-linked immunosorbent assay (ELISA) before and after periodontal initial preparation. IgG avidity was measured by diethylamine dissociation ELISA. IgG titers for the whole cell antigens of 16-1, LPS, and the fimbria antigens from both P. gingivalis strains were significantly higher in the patient group than those in the control group, whereas values for avidities were significantly lower in patient sera. Although we found a statistically significant decrease in the IgG titers of patients following initial preparation, avidities against the fimbria antigen of invasive 16-1 strain increased. The present study showed that IgG antibodies elicited in patients were different in their ability to respond to invasive P. gingivalis 16-1 and to non-invasive 33277. The patient sera with high IgG titers demonstrated low values for avidity, suggesting that IgG responses in patients play a limited role in colonization inhibition or elimination of P. gingivalis. The data indicate that periodontally healthy individuals may have highly functional antibodies which may protect against P. gingivalis colonization. Our findings suggest that the ability to produce functional antibodies in the patient group is lower than that in the periodontally healthy group, but the functional antibodies can be induced by the initial preparation.

Adult↗

Application of a 3D display system for biplane cerebral angiography.

To improve the total safety for the biplane cerebral angiographic examination, we have developed a new three dimensional (3D) display system. By applying this system, shortening the examination time and reducing the risk of infection and embolization were achieved. We added just one graphic-workstation for 3D reconstruction to an ordinary biplane digital-cine-angiography system. This system can process the images of angiogram extempore in a short time and display the run of arterial vessels to the examiner. Biplane images were taken from the digital-cine-angiography system into the workstation through a video display. Three dimensional positions were calculated and displayed on a CRT monitor. It took from 15 to 45 seconds for the calculation. This system could display instantly the run of arterial vessels from any angle by using the computer mouse. Our system doesn't disturb the examination, but helps us to understand the run of the arterial vessels. This system was useful in cases where the arteries wound their way around or over-lapped each other.

Algorithms↗

Anion gap acidosis.

Although an anion gap at less than 20 mEq/L rarely has a defined etiology, significant elevations in the anion gap almost always signify presence of an acidosis that can be easily identified. Anion gap acidoses can be divided into those caused by lactate accumulation, ketoacid production, toxin/drugs, and uremia. Lactic acidoses caused by decreased oxygen delivery or defective oxygen utilization are associated with high mortality. The treatment of lactic acidosis is controversial. The use of bicarbonate to increase pH is rarely successful and, by generating PCO2, may worsen outcome. Ketoacidosis is usually secondary to diabetes or alcohol. Treatment is aimed at turning off ketogenesis and repairing fluid and electrolyte abnormalities. Methanol, ethylene glycol, and salicylates are responsible for the majority of toxin-induced anion gap acidoses. Both methanol and ethylene glycol are associated with severe acidoses and elevated osmolar gaps. Treatment of both is alcohol infusion to decrease formation of toxic metabolites and dialyses to remove toxins. Salicylate toxicity usually is associated with a mild metabolic acidosis and a respiratory alkalosis. Uremia is associated with a mild acidosis secondary to decreased ammonia secretion and an anion gap caused by the retention of unmeasured anions. A decrease in anion gap is caused by numerous mechanisms and thus has little clinical utility.

Acid-Base Equilibrium↗

[A comparison of a 3 day course with a 2 week course of oral prednisolone in patients with chronic asthma].

To investigate an appropriate duration of short course of a oral prednisolone (PSL), we compare the results of a 3 day course of PSL (3D) with those of a 2 week course of PSL (2W) in 20 patients with chronic asthma. All subjects had been inhaling beclomethasone dipropionate (BDP, mean daily dose: 1325 micrograms), and had been self-monitoring their peak expiratory flow rate (PEF) for at least 6 months. Mean +/- SE of the best PSL-induced PEF in 2W (2W-best) was not different from that in 3D (397 +/- 29 and 356 +/- 23 L/min, respectively, p = 0.26). Mean weekly morning PEF/2W-best before and 1, 2, 3 and 4 weeks after PSL was 60, 76, 80, 76 and 76% in 2W, and 63, 73, 67, 67 and 65% in 3D, respectively. Both changes over the course of time were significant. The frequency of emergency room visits and/or unscheduled hospital visits was not significantly different between 2W and 3D. However, both the frequency of use of inhaled beta 2 agonists and the symptom score significantly decreased only in 2W. Seven patients (35%) did not need additional oral PSL during the 4-week period after initiating 3D, and among these patients, emergency room visits and/or unscheduled hospital visits were completely controlled. In conclusion, although the effect of 3D was inferior than that of 2W, it was a sufficient duration in 35% of the patients, and thus, may be appropriate as a initial duration of rescue course of oral steroids.

Administration, Oral↗

Ethanol reduces spontaneous firing and potentiates GABA-induced currents in acutely dissociated rat medial vestibular nucleus neurons.

Effects of ethanol on acutely dissociated medial vestibular nucleus (MVN) neurons were examined using whole-cell patch clamp technique to elucidate the mechanism underling the inhibitory effects of this drug on the neurons observed in in vivo studies. Dissociated MVN neurons obtained from male Wistar rats were superfused with extracellular solution continuously at a flow rate of 1-3 ml/min. Whole-cell patch clamp recording was performed according to standard procedures. GABA was applied by pressure from a pipette placed near the neuron recorded. Ethanol was applied via pipette by pressure or through bath perfusion. Acutely dissociated MVN neurons regularly showed spontaneous firing. Under current-clamp conditions, bath application of ethanol at 0.1% caused hyperpolarization and reduced spontaneous firing in MVN neurons, while 0.1% ethanol did not affect spontaneous firing. Pulse application of higher concentrations of ethanol (0.1-1%) caused similar hyperpolarization. Under voltage-clamp conditions at a holding potential of -30 mV, GABA induced outward currents in a concentration-dependent manner. GABA-induced currents were potentiated in the presence of 0.01% ethanol. These results indicate that high concentrations of ethanol (0.1-1%) directly induce inhibition of spontaneous firing and low concentrations (0.01%) enhance GABA-induced inhibition in the MVN neurons.

Action Potentials↗

Protective effect of a prostaglandin I2 analog, TEI-7165, on ischemic neuronal damage in gerbils.

TTC-909 (Clinprost), a chemically stable PGI2 analog, isocarbacyclin methyl ester (TEI-9090 or Clinprost) incorporated in lipid microspheres, when administered intravenously after brain ischemia, prevents ischemic neuronal damage possibly by modulating cerebral blood flow and platelet aggregation. However, the possibility exists that TEI-7165, which is the free acid form and a central metabolite of TEI-9090, has direct neurotrophic action in vivo, since TEI-7165 has been shown to block neuronal voltage-dependent Ca2+ channels in vitro, and a novel prostacyclin receptor showing high affinity with TEI-7165 has been detected in a variety of brain regions including the hippocampus. In the present study, we infused TEI-7165 for 7 days into the lateral ventricle of gerbils starting 2 h before or just after 3-min forebrain ischemia. TEI-7165 infusion prevented significantly the ischemia-induced shortening of response latency time as revealed by a step-down passive avoidance task. Subsequent light and electron microscopic examinations showed that pyramidal neurons in the hippocampal CA1 region, as well as synapses within the strata moleculare, radiatum and oriens of the region, were significantly more numerous in gerbils infused with TEI-7165 than in those receiving vehicle infusion. TEI-7165 infusion did not affect hippocampal blood flow or temperature. These findings, together with the previously depicted accumulation of centrally administered [3H]TEI-7165 around hippocampal neurons, suggest that TEI-7165 has a direct neuroprotective action in brain ischemia.

Animals↗

Reduction of surface-induced platelet activation on phospholipid polymer.

omega-Methacryloyloxyalkyl phosphorylcholine (MA-PC) polymers which have been synthesized with attention to the surface structure of a biomembrane show excellent blood compatibility, i.e., resistance to protein adsorption and blood cell adhesion. To clarify the stability of platelets in contact with the MAPC polymer surfaces, cytoplasmic free calcium concentration ([Ca2+],) in the platelets was measured. A platelet suspension was passed through a column packed with various polymer beads after treatment with plasma, and the [Ca2+]i in the platelets eluted from the column was measured. The [Ca2+]i in contact with the MAPC polymers, i.e., poly[2-methacryloyloxyethyl phosphorylcholine-co-nbutyl methacrylate (BMA)] (PMEB) and poly(6-methacryloyloxyhexyl phosphorylcholine-co-BMA) (PMHB), was less than that in contact with poly(BMA). However, poly(10-methacryloyloxydecyl phosphorylcholine-co-BMA) (PMDB) was not effective in suppressing the increase in [Ca2+]i, and thus was at the same level as in the poly(BMA). This result indicated that platelets in contact with PMEB or PMHB were less activated compared with those in contact with PMDB and poly(BMA). Moreover, the state of the platelets adhered to these polymer surfaces, both morphologically and immunologically, was examined. Scanning electron microscopic observation of the polymer surface after contact with a platelet suspension revealed that many platelets adhered and changed their shape on the poly(BMA). The numbers of adhetent platelets were reduced on all MAPC polymer surface. The relative amount of alpha-granule membrane glycoprotein (GMP-140) which appears on the cell membrane by activation of platelets on the PMEB surfaces was less than that on poly(BMA) and poly(2-hydroxyethyl methacrylate). These results suggest that PMEB and PMHB suppressed not only platelet adhesion but also activation of the platelets in contact with these surface.

Animals↗

Stabilization of Liposomes Attached to Polymer Surfaces Having Phosphorylcholine Groups

The adsorption state of liposomes on a polymer surface containing a phosphorylcholine group, that is, omega-methacryloyloxyalkyl phosphorylcholine (MAPC) polymer, was evaluated using a quartz crystal microbalance and an atomic force microscope. After a quartz crystal resonator coated with the MAPC polymer or poly[2-hydroxyethyl methacrylate (HEMA)] was equilibrated with distilled water, the quartz crystal was contacted with a dipalmitoylphosphatidylcholine (DPPC) liposomal suspension. The resonance frequency change during liposome adsorption on the poly(HEMA)-coated resonator was larger than that on the MAPC polymer-coated resonator. The temperature response based on the phase transition of adsorbed DPPC liposomes, that is, the liquid crystalline state to gel state, on the MAPC polymer-coated resonator was more sensitive than that on the poly(HEMA)-coated resonator. Moreover, when the DPPC liposomes adsorbed on the polymer surfaces were disintegrated with a nonionic surfactant, it took longer for the frequency to return to the initial value of the poly(HEMA)-coated resonator than to that of the MAPC polymer-coated resonator. According to atomic force microscopic observation of the polymer surface after treatment with the liposomal suspension, the DPPC liposomes adsorbed on the MAPC polymers maintained their spherical shape well. We conclude that DPPC liposomes adsorbed on the poly(HEMA) surface can penetrate a hydrated layer and its ordered structure. On the other hand, DPPC liposomes may adsorb to the MAPC polymer surface without change in their original structure. Copyright 1997Academic Press

Journal Article↗

Oral bacteria inhibit Helicobacter pylori growth.

Various oral bacterial species were found to inhibit the growth of Helicobacter pylori strains. The growth inhibitory activities of most of these oral bacteria were adversely affected by heating at 80 degrees C for 60 min or by protease treatment, indicating that these bacteria produce bacteriocin-like inhibitory proteins against H. pylori strains. The antagonistic effects of oral bacteria against H. pylori may restrain colonization by this organism in the oral cavity.

Adult↗

Enhanced strength in cemented stem fixation using adhesive acrylic cement as a metal coating material.

One cause of aseptic loosening of cemented total hip arthroplasty is mechanical weakness at the interface between the metal stem and the cured bone cement. Adhesive acrylic bone cement containing 4-methacryloyloxyethyl trimellitate anhydride (4-META) was applied as a metal coating material to increase the strength of the cemented fixation. The 4-META cement has 2-3 times greater tensile bond strength to metals than does commercial acrylic bone cement. The shear strength of the coated metals fixed with bone cement was approximately 4 times greater in SUS-304 and 3 times greater in titanium (Ti) alloy than those of uncoated metals, and this strength did not decrease after 1 week's immersion in saline. The coating process using the 4-META cement can be performed at normal room temperature, so that metal stems for bone cement fixation could be coated during the course of an operation resulting in potentially improved results of total hip arthroplasty.

Biocompatible Materials↗

Examination of hydroxyapatite filled 4-META/MMA-TBB adhesive bone cement in vitro and in vivo environment.

Bone response to hydroxyapatite (HA) fillers in the cured-4-methacryloyloxye-thyl trimellitate anhydride (4-META)/methyl methacrylate (MMA)-tri-n-butyl borane (TBB) adhesive bone cement was examined mechanically and histologically. A two-component system, consisting of powder and liquid, was formulated. The liquid portion was 5% 4-META dissolved in MMA and TBB; the powder was composed of 50 wt% poly (MMA) (PMMA) and 50 wt% dense HA fillers. The results indicated that the tensile strength decreased with the increase of HA filler size. The bone-bonding behavior of the improved cement was examined by optical microscopy and scanning electron microscopy. Seventy-two implants in six dogs for up to 24 weeks showed 4-META cement filled with HA was stable in the cement-bone interface. Histologic examinations showed that the exposed HA particles at the surface of the cured cement were generally associated with intimate attachment to bone without fibrous tissue, as well as interdigitation of cement to bone. The results suggest the importance of HA fillers in inducing bone apposition that improves cement binding to bone for long-term stability, thereby complementing rapid initial bone fixation of the cement.

Animals↗

Cloning and sequence analysis of the fimbriae associated protein (fap) gene from Actinobacillus actinomycetemcomitans.

Fimbrial-associated protein, an attachment factor of Actinobacillus actinomycetemcomitans, was genetically analysed by cloning. The plasmid obtained was found to harbor a 1.7kb fragment which contained a 228bp open reading frame encoding 76 amino acids (7.970kDa). The fimbriae associated protein gene (fap) was strongly expressed in fimbriated A. actinomycetemcomitans 310a but not in non-fimbriated strains.

Aggregatibacter actinomycetemcomitans↗